United States
Environmental Protection
Agency
Prevention, Pesticides,
And Toxic Substances
(H7508W)
EPA738-S-93-014
September 1993
&EPA
Registration
Eligibility Decision (RED)
Thymol
Rfcycted/Recyclable
Printed on paper that contains
at least 50% recycled fiber
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United States
Environmental Protection
Agency
Office of Prevention, Pesticides
And Toxic Substances
(H-7508W)
EPA-738-F-93-010
September 1993
R.E.D. FACTS
Pesticide All pesticides sold or distributed in the United States must be registered by
Reregistration 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 risk to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this and
explains why in a Reregistration Eligibility Decision or RED. This fact
sheet summarizes the information in the RED for thymol.
Use Profile
Thymol is a constituent of oil of thyme, a naturally occurring mixture of
compounds in the plant Thymus vulgaris L., or thyme. Thymol is an
active ingredient in pesticide products registered for use as animal
repellents, fungicides/fungistats, medical disinfectants, tuberculocides, and
virucides. These products are used on a variety of indoor and outdoor
sites, to control target pests including animal pathogenic bacteria and fungi,
several viruses including HIV-I, and birds, squirrels, beavers, rats, mice,
dogs, cats and deer. Products are liquids applied by spray, mop, brush-on,
wipe-on dip, aerosol, immersion and spot treatment. Thymol also has
many non-pesticidal uses, including use in perfumes, food flavorings,
mouthwashes, pharmaceutical preparations and cosmetics.
Regulatory Thymol was initially registered as a pesticide in the United States in 1964
History f°r use ^ a repellent for domestic animals. Currently, five end-use (and no
manufacturing use) pesticide products containing the active ingredient
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thymol are registered. Thymol, thyme essential oil and thyme (spice) are
listed by the Food and Drug Administration (FDA) as foods for human
consumption, as well as food additives. They are considered Generally
Recognized as Safe or GRAS. (Please see 21 CFR 172.515, 182.10 and
182.20.)
Historically, certain thymol products and other liquid chemical germicides
have been regulated both by EPA as pesticides under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), and by FDA as
devices under the Federal Food, Drug, and Cosmetic Act (FFDCA). To
resolve the confusion and burden of dual regulation, EPA and FDA signed
a Memorandum of Understanding (MOU) on June 4, 1993, which clarifies
the future regulation of these germicides. The MOU divides liquid
chemical germicides used in conjunction with medical devices into two
categories: sterilants, which will be regulated by FDA as devices, and
general purpose disinfectants, which EPA will regulate as pesticides. Until
rulemaking is completed to permanently vest jurisdiction over these
categories, regulatory data need only be submitted to one Agency. For
thymol, the conditions of reregistration must be fulfilled and required data
must be submitted to EPA.
Human Health
Assessment
Thymol is among those pesticides for which EPA believes a broadly
reduced set of generic data requirements is appropriate for reregistration.
The Agency, therefore, has waived most generic data requirements for
thymol with the exception of studies that are considered essential, including
additional information about chemical purity, and product chemistry
studies. In evaluating thymol's potential risks to human health and the
environment, EPA relied on information commonly available in scientific
literature.
Thymol is a constituent of a mixture of organic compounds known to be
rapidly degraded in the environment to elemental compounds by normal
biological, physical and/or chemical processes that can reasonably be
expected to exist where the pesticide is applied. As a pesticide, thymol
repels vertebrate pests by a non-toxic mode of action, but is toxic to
microorganisms. EPA is not aware of any adverse effects of thymol to
humans or the environment when it is used in a manner prescribed by
product labeling. The Agency has no significant incident reports involving
thymol.
Toxicity data reported in available literature indicate that acute oral toxicity
for rats and guinea pigs corresponds to Toxicity Category m (Category I
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signals the highest degree of acute toxicity, and Category IV the lowest).
The Material Safety Data Sheet (MSDS) for technical grade thymol notes
that it is irritating to hupniS^^n exposed by inhalation, dermal or eye
contact. The dermal risk to humans f would be Toxicity Category IH.
Exposures and health risks to people using currently registered products are
expected to be relatively low. However, handling and use of the end-use
products could involve greater exposure by the dermal and inhalation
routes. Required product specific acute toxicity testing will enable the
Agency to design appropriate labeling to address these potential exposure
concerns.
The uses of thymol will result in negligible exposure of the environment
and nontarget organisms. EPA concludes that the use of thymol as an
active ingredient in currently-registered pesticide products should not result
in unreasonable adverse effects to human health or the environment.
Additional
Data Required
Although EPA has waived most generic studies for thymol, the Agency is
requiring information on the manufecturing process and additional
information about the characterization of the thymol used in the formulated
products. EPA also is requiring product-specific data, including product
chemistry, acute toxicity and efficacy studies, as well as revised
Confidential Statements of Formula and revised labeling, for reregistration.
Product Labeling The labels of all registered pesticide products containing thymol must
Changes Required comply with EPA's current pesticide labeling requirements.
Regulatory The use of currently registered pesticide products containing thymol in
Conclusion accordance with approved labeling will not pose unreasonable risks or
adverse effects to humans or the environment. Therefore, all uses of these
products are eligible for reregistration.
These thymol products will be reregistered once the required manufacturing
process information, physical and chemical properties data,
product-specific data, revised Confidential Statements of Formula and
revised labeling are received and accepted by EPA. Products containing
other active ingredients will be reregistered only when the other active
ingredients also are determined to be eligible for reregistration.
For More
Information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) for thymol during a 60-day time period, as announced in a
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Notice of Availability published in the Federal Register. To obtain a copy
of the RED 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), U.S. EPA,
Washington, DC 20460, telephone 703-305-5805.
Following the comment period, the thymol RED will be available from the
National Technical Information Service (NTTS), 5285 Port Royal Road,
Springfield, VA 22161, telephone 703-487-4650.
For more information about thymol or about EPA's pesticide reregistration
program, please contact the Special Review and Reregistration Division
(7508W), OPP, U.S. EPA, Washington, DC 20460, telephone 703-308-
8000.
For information about reregistration of individual repellent products
containing thymol, please contact Robert A. Forrest, Product Manager
Team 14, Registration Division (7505C), OPP, U.S. EPA, Washington,
DC 20460, telephone: 703-305-6600. For reregistration information on
individual antimicrobial products, please contact Ruth G. Douglas, Product
Manager Team 32, Registration Division (7505C), OPP, U.S. EPA,
Washington, DC 20460, telephone: 703-305-7964.
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REREGISTRATION ELIGIBILITY DECISION
Thymol
LISTC
CASE 3143
ENVIRONMENTAL-PROTECTION-AGENCY
OCTICE-OF-PESTTCIDE-PROGRAMS
SPECIAL-REVIEW-AND'REREGISTRATION-DIVISION
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TABLE OF CONTENTS
THYMOL REREGISTRATION ELIGIBILITY DECISION TEAM iii
GLOSSARY OF TERMS AND ABBREVIATIONS v
EXECUTIVE SUMMARY vii
I. INTRODUCTION 1
H. CASE OVERVIEW .... 2
A. Chemical Overview 2
B. Use Profile 3
C. Data Requirements . . . 4
D. Regulatory History 4
m. SCIENCE ASSESSMENT 5
A. Product Chemistry Assessment 5
B. Human Health And Environmental Assessment 5
IV. RISK MANAGEMENT AND REREGISTRATION ELIGIBILITY
DECISION 7
A. Determination of Reregistration Eligibility 7
1. Eligible and Ineligible Uses 8
B. Risk Management Decision 8
V. ACTIONS REQUIRED BY REGISTRANTS 9
A. Technical Grade Information 9
1. Generic Data Requirements 9
B. End-Use Products 9
1. Additional Product-Specific Data Requirements 9
2. Labeling Requirements for End-Use Products 10
C. Existing Stocks Information 10
VI. APPENDICES
Appendix A - Use Patterns Subject to Reregistration
Appendix B - Table of the Generic Data Requirements and Studies Used to Make the
Reregistration Decision
Appendix C - Citations Considered to be Part of the Data Base Supporting the
Reregistration of Wood Oils and Gums
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Appendix D - List of Available Related Documents
Appendix E - Pesticide Reregistration Handbook
Appendix F - Generic Data Call-In
Attachment A -
Attachment B -
Attachment C -
Attachment D -
Chemical Status Sheet
Generic DCI Response Forms (Form A) plus Instructions
Requirements Status and Registrants' Response Forms
(Form B) plus Instructions
List of all Registrant(s) sent this DCI
Appendix G - Product Specific Data Call-In
Attachment A -
Attachment B -
Attachment C -
Attachment D -
Attachment E -
Attachment F -
Attachment G -
Chemical Status Sheet
Product Specific DCI Response Forms (Form A) plus
Instructions
Requirements Status and Registrants' Response Forms
(Form B) plus Instructions
EPA Grouping of End Use Products for meeting Acute
Toxicology Data Requirements.
EPA Acceptance Criteria
List of all Registrant(s) sent this DCI
Cost Share/Data Compensation Forms
11
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IV
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THYMOL REREGISTRAHON ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Division
Hawa Herzi Biological Analysis Branch
Environmental Fate and Effects Division
William Schneider Science Analysis and Coordination Staff
Health Effects Division
Arliene M. Aikens
Flora Chow
Tom McClintock
Registration Division
Amelia Acierto
Ruth G. Douglas
Robert A. Forrest
Joanne Hayes
Daniel Peacock
Wallace Powell
Special Review and Reregistration Division
Kathy Davis
Kathleen Depukat
Office of General Counsel:
Kevin Lee
Office of Compliance Monitoring:
Phyllis Flaherty
Chemical Coordination Branch
Chemical Coordination Branch
Science Analysis Branch
Registration Support Branch
Antimicrobial Branch
Insecticide-Rodenticide Branch
Registration Support Branch
Insecticide-Rodenticide Branch
Antimicrobial Branch
Accelerated Reregistration Branch
Accelerated Reregistration Branch
111
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GLOSSARY OF TERMS AND ABBREVIATIONS
a.i. Active Ingredient
CAS Chemical Abstracts Service
CDC Center for Disease Control
CFR Code of Federal Regulations
CSF Confidential Statement of Formula
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
FFDCA Federal Food, Drug, and Cosmetic Act
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
GRAS Generally Recognized As Safe
HDT 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 or feed, e.g.,
mg/1 or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to
cause death in 50% of the test animals when administered by the route indicated
(oral, dermal). It is expressed as a weight of substance per unit weight of animal,
e.g., mg/kg.
LD10 Lethal Dose-low. Lowest Dose at which lethality occurs
LEL Lowest Effect Level
LOEL Lowest Observed Effect Level
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GLOSSARY OF TERMS AND ABBREVIATIONS (cent.)
mg/kg Milligrams per Kilograms of Body Weight
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRED Master Record Identification (number). EPA's system of recording and tracking
studies submitted.
MSDS Material Safety Data Sheets
N/A Not Applicable
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
ppm Parts Per Million
RED Reregistration Eligibility Decision Document
RfD Reference Dose
RS Registration Standard
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TC Toxic Concentration. The dose at which a substance produces a toxic effect.
TMRC Theoretical Maximum Residue Contribution.
USP United States Pharmacopeia
w/w Weight to Weight
VI
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EXECUTIVE SUMMARY
The U. S. Environmental Protection Agency (referred to as the "Agency" or "EPA") has
completed its reregistration assessment of the available information on the pesticide active
ingredient thymol. It has been determined that the currently registered uses will not cause
unreasonable risk to humans or the environment and the products registered for these uses are
eligible for reregistration.
Thymol is a constituent of oil of thyme, a naturally occurring mixture of compounds in
the plant Thymus vulgaris L., or thyme. Thymol, as used in pesticide products, may be applied
as an animal repellant, a fungicide/fungistat, a medical disinfectant, a tuberculocide, or a
virucide. The use sites include indoor residential, outdoor residential, indoor non-food, indoor
medical, and terrestrial non-food/outdoor residential. Application methods include spray, mop,
brush-on, wipe-on dip, aerosol, immersion and spot treatment.
All EPA registered thymol products are for non-food uses. Thymol, thyme essential oil
and thyme (spice) are Generally Recognized As Safe (GRAS) and are listed by the U.S. FDA
in Subchapter B-Food for human consumption (21 CFR §§ 172.515, 182.10 and 182.20).
Before reregistering the products containing thymol, the Agency is requiring that the
manufacturing process and additional information on the physical and chemical properties of the
extracted oil, product specific data, Confidential Statements of Formula (CSF) and revised
labeling be submitted within eight months of the issuance of this document. These data include
product chemistry, acute toxicity and efficacy testing for each registration. After reviewing
these data and revised labels and finding them acceptable in accordance with Section 3(c)(5) of
FIFRA, the Agency will reregister the single product containing only thymol. The remaining
four products cannot be reregistered until the Agency has determined that the other active
ingredients in those products are also eligible for reregistration.
Vll
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I.
INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (F1FRA) 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 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 thymol. The document consists of six sections. Section I is the
introduction. Section n describes thymol, its uses, data requirements and regulatory history.
Section HI discusses the human health and environmental assessment based on the data available
to the Agency. Section IV presents the reregistration decision for thymol. Section V discusses
the reregistration requirements for thymol. Finally, Section VI is the Appendices which support
this Reregistration Eligibility Decision Document. Additional details concerning the Agency's
review of applicable data are available on request.1
1EPA's reviews of data on the set of registered uses considered for FJPA's analysis may be
obtained from the OPP Public Docket, Field Operations Division (H7506C), Office of Pesticide
Programs, FJPA, Washington, DC 20460.
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H. CASE OVERVIEW
A. Chemical Overview
The following active ingredient is covered by this Reregistration Eligibility
Decision Document:
Common Name:
Case Number:
Chemical Name:
Synonyms:
Other Names:
CAS Registry No.:
Pesticide Chemical Code: 080402
Empirical Formula: ClftHMC
Molecular Formula:
Molecular Weight:
Trade Names:
Thymol
3143
5-Methyl-2-(l-methylethyl)phenol
5-methyl-2-isopropyl-l-phenol; l-methyl-3-hydroxy-
4-isopropylbenzene; isopropyl-meta-cresol
Thyme camphor
Thymic acid
89-83-8
(CH3)2CHC6H3(CH3)OH
150.21
Thymocide
Topps
Structural Formula:
OH
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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 thymol is in
Appendix A.
For Thymol:
Type of Pesticide: Animal repellant, fungicide/fungistat, medical disinfectant,
tuberculocide, virucide (antimicrobial)
Use Sites:
Target Pests:
Indoor Residential - bathroom premises/hard surfaces,
household/domestic dwellings - contents and indoor
premises, living/sleeping quarters
Outdoor Residential - fencerows/hedgerows,
household/domestic dwellings - outdoor premises,
refuse/solid waste containers (garbage cans)
Indoor Non-Food - commercial/institutional/uidustrial
premises/equipment
Indoor Medical - hospital critical items (surgical
instruments/pacemakers), hospital/medical institutions non-
conductive floors, critical premises (burn wards), patient
premises and other premises (human/veterinary)
Terrestrial Non-Food/Outdoor Residential - ornamental
and/or shade trees, ornamental herbaceous plants,
ornamental lawns and turf and ornamental woody shrubs
and vines
Animal pathogenic bacteria (G- and G+ vegetative),
Pseudomonas spp., Mycobacterium spp. (Tnhftrete hacilliV
animal pathogenic fungi (T. mentagrophytes). vaccinia
virus, Herpes simplex viruses I and H, Influenza A3 (H3N2
- Hong Kong) and Influenza A2 - Hong Kong, HTV-I
(Human Immunodeficiency Virus); birds, squirrels,
beavers, rats, mice, dogs, cats, and deer
Formulation Types
Registered:
Soluble concentrate/liquid, liquid-ready to use
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C. Data Requirements
The Agency has waived all generic data requirements except for manufacturing
information and the physical and chemical properties for this active ingredient. The
reason for this is described below in Section m. It has relied instead on general,
commonly available information about thymol. Appendix B includes all data
requirements identified by the Agency for currently registered uses needed to support
reregistration.
D. Regulatory History
Products containing thymol as an AI were originally registered in 1964 for use
as a repellent for domestic animals. These have included products to repel dogs, cats,
deer, beavers, rats, mice, birds, and tree squirrels. Subsequently, thymol-containing
pesticide products have been registered for use as an acaricide, fungicide/fungistat,
medical disinfectant, tuberculocide and virucide (antimicrobial). Currently, there are
five products containing thymol as the pesticide ingredient for use as animal repellents
or disinfectants. One product contains only the active ingredient thymol. The other four
products contain one or two additional active ingredients. The concentration of thymol
in these active products ranges from 0.027% to 13% (w/w). Thymol, thyme essential
oil and thyme (spice) are Generally Recognized As Safe (GRAS) and are listed by the
FDA in Subchapter B-Food for human consumption (21 CFR §§ 172.515, 182.10 and
182.20). Thymol is also used in perfumes, food flavorings, mouthwashes, disinfectants,
pharmaceutical preparations and cosmetics.
Historically, certain thymol products and certain other liquid chemical germicides
have been regulated both as pesticides under the Federal Insecticide, Fungicides and
Rodenticide Act (FIFRA) and as devices under the Federal Food, Drug and Cosmetic Act
(FFDCA). In an effort to resolve the confusion and burden of dual regulation, a
Memorandum of Understanding (MOU) was signed on June 4, 1993 between EPA and
the Food and Drug Administration (FDA). The objectives of the MOU are to (1)
stimulate both Agencies to undertake rulemaking to permanently vest exclusive
jurisdiction for certain categories of chemical germicides in each Agency and (2) serve
as interim guidance designed to minimize duplicative regulatory requirements between
the two Agencies until the rulemaking is complete.
The MOU separates the liquid chemical germicides into the following two
categories based on their use patterns and efficacy claims: (1) sterilants and (2) general
purpose disinfectants. Sterilants, under this agreement, refer to those chemical
germicides used to reprocess reusable critical and semicritical devices as defined by the
Centers for Disease Control (CDC). Critical devices are devices that are introduced
directly into the human body, either into or in contact with the bloodstream or normally
sterile areas of the body. Semicritical devices are those which contact intact mucous
membranes but which do not ordinarily penetrate the blood barrier or otherwise enter
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normally sterile areas of the body. , General disinfectants are defined as all remaining
types of public health liquid dhemicai genni6ides bearing non-sterilant claims for use on
non-critical surfaces.
The MOU outlines the future separate regulation of liquid chemical germicides
as either pesticides under FEFRA or devices under FFDCA by granting each Agency
primary jurisdiction over one of the two categories. All products which bear sterilant
label claims and can be used on critical or semicritical surfaces will be regulated by FDA
as devices. In addition, many sterilant products have claims which correspond to a high
level disinfectant use pattern. These claims will also be regulated by FDA for the
sterilant products. EPA will regulate the general purpose disinfectants.
Because the MOU does not change the statutory authority granted under FIFRA
and FFDCA, both Agencies will continue to have jurisdiction over all liquid chemical
germicides and will continue registration and premarket approval until rulemaking has
been completed. However, the MOU reduces the regulatory burden by stating that the
required data to support efficacy claims and product performance need only be submitted
and reviewed by the Agency with primary jurisdiction as defined above. In the case of
the thymol products, EPA has primary jurisdiction and the conditions of reregistration
must be fulfilled and required data submitted as presented in Appendices F and G.
A copy of the signed EPA/FDA MOU is attached as Appendix D.
m. SCIENCE ASSESSMENT
A. Product Chemistry Assessment
Thymol (5-methyl-2-isopropyl-l-phenol) is a constituent of oil of thyme, a
naturally occurring mixture of compounds in the plant Thymus vulgaris L., Monarda
punctata L., Ptychotic coptica. or it can be produced synthetically.
The assessment of the manufacturing process and the physical and chemical
properties are not complete. The Agency lacks generic product chemistry data on thymol
which may be available in the literature, including patent information. The Agency is
requiring registrants to provide manufacturing process information, and additional
physical and chemical properties data on the active ingredient thymol, as well as, the
Confidential Statement of Formula and labels (Appendix F) to confirm the chemical
properties and purity of source(s) of thymol usesd in registered products.
B. Human Health And Environmental Assessment
EPA has developed a target data base, set forth in the regulations (40 CFR Part
158) and the Agency's Reregistration Phase 2 Technical Guidance Document to be
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addressed for pesticide reregistration. These regulations and the guidance document
specify the necessary data based on factors including use sites, potential environmental
and human (dietary and occupational) exposures, product formulation types, and product
application methods. Due to the diverse nature and characteristics of pesticide products
and their uses subject to reregistration, the Agency also recognizes the necessity to
modify the data requirements for specific pesticides, including waiving certain data
requirements because such requirements are inappropriate or unnecessary for
reregistration.
The case specific approach to waiving individual data requirements has served to
identify the appropriate data requirement sets for pesticide products. Further, the Agency
believes there is a category of pesticide active ingredients for which a broadly reduced
set of data requirements are appropriate for reregistration. Specifically, products in this
category would be exempt from the generic data requirements for toxicology, human
exposure, ecological effects, and environmental fate on the active ingredient. The Agency
believes there are considerations which, when taken together, can form the basis for a
conclusion that such a reduction in data requirements is appropriate for a particular
pesticide active ingredient, while not compromising human health or environmental
safety.
There are, however, certain data requirements which are essential and not likely
to be waived. Basic product identity/chemistry information on the active ingredient and
formulated products is required for pesticides in this category so that the Agency has
reasonable certainty of the pesticide's identity and chemical and physical characteristics.
Also, product specific acute toxicology studies are required for the Agency to determine
appropriate product labeling for potential hazards to those who handle or apply such
products. However, these toxicology studies may also be waived if an assessment of the
product formulation, including the inert ingredients, indicates that such studies are
unnecessary to prescribe appropriate labeling. Efficacy studies may be required on
formulated products if those product labels specify a public health use.
In considering thymol for reregistration eligibility the Agency believes it is an
active ingredient that should be considered for this broad waiver of the generic data
requirements. The considerations that lead the Agency to this conclusion are presented
below.
Thymol is a component of many non-pesticidal consumer products currently
marketed in the United States. Thymol is listed as a food additive by the Food and Drug
Administration (21 CFR 172.515; synthetic flavoring substances and adjuvants). Thymol
is rapidly degraded in the environment to elemental constituents by normal biological,
physical, and/or chemical processes that can be reasonably expected to exist where the
pesticide is applied. As a pesticide, it repels vertebrate pests by a non-toxic mode of
action. The phenols of thymol are considered GRAS as set forth in 21 CRF 172.515
(synthetic flavoring substances and adjuvants). EPA is not aware of any adverse effects
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of the active ingredient to humans or thei enyironment in the literature when used in a
manner prescribed in end-use product labeling. There have been no significant incident
reports.
Thymol toxicity data reported in available literature cite acute oral LD50 values
as 980 mg/kg and 880 mg/kg for the rat,and guinea pig, respectively (Sax, 1984). The
acute oral toxicity reported for the rat and guinea pig, correspond to Toxicity Category
m. The Material Safety Data Sheet (MSDS) for the manufacture of technical grade
thymol cites human health effects as irritating when exposed by inhalation, dermal or eye
contact. The MSDS also estimates a human ingestion LD50 at two grams of the
synthetic thymol (99% w/w). Based upon an estimated thymol dermal toxicity LD50 of
greater than 2000 mg/kg, the dermal toxicity category would be Toxicity Category m.
Exposures and, therefore, health risks to people using currently registered
products are expected to be relatively low. The product specific acute toxicity testing
will indicate appropriate labeling to address potential exposure concerns.
No ecological or environmental data were submitted to support reregistration of
thymol. The Agency expects that there will be low exposure to the environment and to
nontarget organisms.
Based on these factors the Agency does not believe generic data are necessary to
determine whether the currently registered uses of this active ingredient pose
unreasonable risks to humans or the environment. Therefore, EPA is not requiring the
submission of additional generic data for the active ingredient thymol other than the
identity and physical and chemical properties. However, EPA is requiring the
submission of product specific data (chemistry, acute toxicity and efficacy) to
characterize the products and ensure their efficacy of public health uses. The Agency
believes that, based on the above factors, the registered uses of thymol do not pose
unreasonable risks to humans or the environment.
IV. RISK MANAGEMENT AND REREGISTRATION ELIGIBILITY DECISION
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of EDFJRA 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. As discussed above, the Agency has
determined that the set of generic requirements that would normally be applicable to
thymol are not necessary for the Agency to reach a decision on potential risks and
reregistration eligibility. Thymol meets the criteria in the Agency document entitled
"Guidance for Making Determinations to Reduce Data Requirements" (Appendix D).
The criteria thymol passed to become a reduced data RED are: (1) Thymol is recognized
as a significant component of a common human food; (2) Thymol is widely distributed
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in commerce and available to the general public throughout the U.S. for non-pesticidal
uses; (3) Thymol has no data submitted under Section 6(a)(2) of FIFRA; (4) The Agency
is not aware of any adverse effects of thymol when used in a manner prescribed in end-
use product labeling; (5) There have been no significant incident reports for thymol; (6)
There is no indication in the literature, as provided by the registant, that thymol poses
adverse effects in humans or to the environment when used in a manner prescribed in
end-use product labeling; (7) There is negligible human and environmental exposure to
thymol as a result of pesticidal use patterns, e.g., low use rate and frequency of
application, or product applied in confined or contained manner; and (8) Thymol can be
presumed non-persistent based on knowledge of its composition, e.g., organic material
known to be rapidly degraded in the environment to elemental constituents by normal
biological, physical, and/or chemical processes that can be reasonably expected to exist
where the thymol is applied. (See Appendix B).
The Agency has concluded from its review of this information that thymol can be
used without resulting in unreasonable adverse effects to human health and the
environment. The Agency, therefore, finds that all products containing thymol as an
active ingredient as the sole active ingredient are eligible for reregistration. The
reregistration of particular products is addressed in Section V of this document.
Although the Agency has found that all uses of thymol are eligible for
reregistration, it should be understood that the Agency may take appropriate regulatory
action, and/or require the submission of additional data to support the registration of
products containing thymol, 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. Eligible and Ineligible Uses
Based on its review of generic information for thymol, the Agency has
determined that products labeled for all uses of thymol are eligible for
reregistration. The Agency can reregister the single product containing only
thymol once the Agency has reviewed the data and labeling requested in this RED
and found them to be in accordance with section 3(c)(5) of FIFRA. Each of the
remaining four products can be reregistered when the Agency had determined its
eligibility for reregistration based on a review of generic data for the product's
other active ingredients and its compliance wilth section 3(c)(5).
B. Risk Management Decision
In consideration of the above information about thymol, the Agency finds no
reason to impose new risk reduction measures for currently registered uses. The Agency
will however, assess the need for product specific risk reduction measures upon receipt
of data that are being required under the Product Specific Data Call-in Notice appended
to this document.
8
-------
V. ACTIONS REQUIRED BY REGISTRANTS
This section specifies the data requirements and responses necessary for the reregistration
of both technical grade and end-use products. There are currently no manufactured use products
registered.
B.
Technical Grade Information
1. Generic Data Requirements
The generic data base supporting the reregistration of products containing
thymol for the eligible uses (Section n and Appendix A) has been reviewed and
determined to be incomplete. Registrants are required to submit the technical
chemistry data corresponding to Series 61 and Series 62 for the analysis and
certification of product ingredients. If the product is a USP grade, a copy of
USP analysis with citation of the analytical method used and certification would
satisfy the requirement for Series 62.
The Confidential Statement of Formula (CSF) must be supported by
analytical data. Registrants of end-use products using unregistered sources of
thymol are required to submit the data on the physical and chemical
characteristics of thymol from the Material Safety Data Sheet (MSDS) for the
product may be compiled by the registrant in the format required by the FIFRA
Accelerated Reregistration Phase 3 Technical Guidance, specifically PR Notice
86-5 to satisfy some of the requirements of Series 63. The generic data
requkements are listed in Appendix F, the Generic Data Call-in Notice.
End-Use Products
1. Additional Product-Specific Data Requirements
Based on consideration of the above information for the active ingredient
thymol, all currently registered uses of products containing thymol are eligible for
reregistration. Section 4(g)(2)B) of FIFRA calls for the Agency to obtain any
needed product specific data regarding the pesticide after a determination on the
active ingredient has been made. The product specific data requirements are
listed in Appendix G, the Product Specific Data Call-in Notice.
Previous data submissions must be reviewed to ensure that they meet
current EPA acceptance criteria (Appendix G; Attachment E) and if not, commit
-------
to conduct new studies. If it is believed that previously submitted data meet
current testing standards, then study MRID numbers should be cited according to
the instructions in the Requirement Status and Registrants' Responses Form
provided for each product.
It is the responsibility of the registrant(s) to ensure that their source
product is registered (i.e., not cancelled) and the registration numbers are current.
If the source product is unregistered, the registrant must provide the data base,
Series 61, 62 and 63 for that source product.
2. Labeling Requirements for End-Use Products
The labels and labeling of all products must comply with EPA's current
regulations and requirements as specified in 40 CFR §156.10 and described in the
Pesticide Reregistration Handbook.
C. Existing Stocks Information
Existing stocks may generally be distributed and products sold bearing old
labels/labeling for 26 months from the date of the issuances of this 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 thymol
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.
10
-------
VI.
APPENDICES
11
-------
-------
APPENDIX A
Table of Use Patterns Subject to Reregistration
13
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-------
APPENDIX B
Table of the Generic Data Requirements and
Studies Used to Make the Reregistration Decision
19
-------
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active
ingredients within the case anything covered by this Reregistration Eligibility Decision. It
contains generic data requirements that apply to anything 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
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this
column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRtD number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
21
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Thymol
REQUIREMENT
USE PATTERN
CITATION
PRODUCT CHEMISTRY
61-1 Chemical Identity
61-2a Start. Mat. & Mnfg. Process
61-2b Formation of Impurities
62-1 Preliminary Analysis
62-2 Certification of Limits
62-3 Analytical Method
63-2 Color
63-3 Physical State
63-4 Odor
63-5 Melting Point
63-6 Boiling Point
63-7 Density
63-8 Solubility
63-9 Vapor Pressure
63-10 Dissociation Constant
63-11 Octanol/Water Partition
63-12 pH
63-13 Stability
63-14 Oxidizmg/Reducing Action
63-15 Flammability
63-16 Explodability
63-17 Storage Stability
63-18 Viscosity
63-19 Miscibility
63-20 Corrosion Characteristics
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
REQUIRED
REQUIRED
REQUIRED
REQUIRED
REQUIRED
REQUIRED
SATISFIED1
SATISFIED1
SATISFIED1
SATISFIED1
SATISFIED1
SATISFIED1
REQUIRED
SATISFIED1
SATISFIED1
SATISFIED1
SATISFIED1
REQUIRED
REQUIRED
REQUIRED
REQUIRED
REQUIRED
REQUIRED
REQUIRED
REQUIRED
2 Data contained in a letter dated 3/12/92 from the source manufacturer
23
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Thymol
REQUIREMENT
USE PATTERN
CITATION
ECOLOGICAL EFFECTS
71-la Acute Avian Oral - Quail/Duck All
71-2a Avian Dietary - Quail All
71-2b Avian Dietary - Duck All
72-la Fish Toxicity Bluegill All
72-lc Fish Toxicity Rainbow Trout All
72-2a Invertebrate Toxicity All
122-la Seed Germination/Seedling Emergence All
122-lb Vegetative Vigor All
122-2 Aquatic Plant Growth All
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
TOXICOLOGY
81-1 Acute Oral Toxicity - Rat All
81-2 Acute Dermal Toxicity - Rabbit/Rat All
81-3 Acute Inhalation Toxicity - Rat All
81-4 Primary Eye Irritation - Rabbit All
81-5 Primary Dermal Irritation - Rabbit All
81-6 Dermal Sensitization - Guinea Pig All
84-2a Gene Mutation (Ames Test) All
84-2b Structural Chromosomal Aberration All
84-4 Other Genotoxic Effects All
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
24
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Thymol
REQUIREMENT
USE PATTERN
CITATION
ENVIRONMENTAL FATE
160-5 Chemical Identity
161-1 Hydrolysis
161-2 Photodegradation - Water
161-3 Photodegradation - Soil
162-1 Aerobic Soil Metabolism
162-2 Anaerobic Soil Metabolism
162-3 Anaerobic Aquatic Metabolism
163-1 Leaching/Adsorption/Desorption
164-1 Terrestrial Field Dissipation
165-1 Confined Rotational Crop
All
All
All
All
All
All
All
All
All
All
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
25
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APPENDIX C
THYMOL BIBLIOGRAPHY
Citations Considered to be Part of the Data Base
Supporting the Reregistration of
Thymol
27
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GUIDE TO APPENDIX C
CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere
in the Reregistration Eligibility Decision. Primary sources for studies in this
bibliography have been the body of data submitted to EPA and its predecessor agencies
in support of past regulatory decisions. Selections from other sources including the
published literature, in those instances where they have been considered, are included.
UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the
case of published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a distinct
title (or at least a single subject), can stand alone for purposes of review and can be
described with a conventional bibliographic citation. The Agency has also attempted to
unite basic documents and commentaries upon them, treating them as a single study.
roElSTHHCATION OF ENTRIES. The entries in this bibliography are sorted
numerically by Master Record Identifier, or "MRID number". This number is unique
to the citation, and should be used whenever a specific reference is required. It is not
related to the six-digit "Accession Number" which has been used to identify volumes of
submitted studies (see paragraph 4(d)(4) below for further explanation). In a few cases,
entries added to the bibliography late in the review may be preceded by a nine character
temporary identifier. These entries are listed after all MRID entries. This temporary
identifying number is also to be used whenever specific reference is needed.
FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic
conventions used reflect the standard of the American National Standards Institute
(ANSI), expanded to provide for certain special needs.
a. Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the
Agency has shown an identifiable laboratory or testing facility as the author.
When no author or laboratory could be identified, the Agency has shown the first
submitter as the author.
b. Document date. The date of the study is taken directly from the document.
When the date is followed by a question mark, the bibliographer has deduced the
date from the evidence contained in the document. When the date appears as
(19??), the Agency was unable to determine or estimate the date of the document.
29
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Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained
between square brackets.
Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following
elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received."
(2) Administrative number. The next element immediately following the
word "under" is the registration number, experimental use permit number,
petition number, or other administrative number associated with the
earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is
defaulted to the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the
trailing parentheses identifies the EPA accession number of the volume in
which the original submission of the study appears. The six-digit
accession number follows the symbol "CDL," which stands for "Company
Data Library." This accession number is in turn followed by an
alphabetic suffix which shows the relative position of the study within the
volume.
30
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REFERENCES
Code of Federal Regulations, Title 21, Part 172, Section 515, revised as of My 1, 1992.
Published by the Office of the Federal Register National Archives and Records Administration,
Washington, DC, U.S.A.
Code of Federal Regulations, Title 21, Part 182, Sections 10 and 20, revised as of July 1, 1992.
Published by the Offices of the Federal Register National Archives and Records Administration,
Washington, DC, U.S.A.
Gunether, E., The Essential Oils. Vol. PL. D. Van Nostrand Co., Inc.
Material Safety Data Sheets: 10/23/85, Ruger Chemical Co. Inc.
The Merck Index; An Encyclopedia of Chemicals, Drugs, and Biologicals. Windholz, Martha,
Ed. et al.. Tenth Edition. Published in 1983 by Merck and Company, Rahway, New Jersey,
U.S.A.
Sax, N. I., (1984), Dangerous Properties of Industrial Materials, Van Nostrand Reinhold Co.,
p. 2580.
31
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APPENDIX D
List of Available Related Documents
The following is a list of available documents related to thymol. Its purpose is to provide
a path to more detailed information if it is needed. These accompanying documents are part of
the Administrative Record for thymol and are included in the EPA's Office of Pesticide
Programs Public Docket.
1. Detailed Label Usage Information System (LUIS) Report
2. Thymol RED Fact Sheet
3. PR Notices 86-5 and 91-2 (included in these appendices). These notices pertain
to the correct submission of the data and label ingredient statements.
4. June 4, 1993 Memorandum of Understanding between FDA and EPA; Notice
regarding matters of mutual responsibility - Regulation of liquid chemical
germicides intended for use on medical devices (included hi these appendices).
33
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APPENDIX E
Pesticide Reregistration Handbook
PR Notices 86-5 and 91-2
Memorandum of Understanding Between FDA/EPA
35
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PESTICIDE REGISTRATION HANDBOOK
37
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PR Notice 86-5
39
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I
2
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
July 29, 1986
PR NOTICE 86-5
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
NOTICE TO PRODUCERS, FORMULATORS, DISTRIBUTORS
AND REGISTRANTS
Attention:
Subj ect:
Persons responsible for Federal registration of
pesticides.
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.
III. 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 dcite, 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
41
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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
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 compatible 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 costs 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 application
packages the data formatting requirements described herein.
OPP has also established a public docket which imposes
deadlines for inserting into 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 of all applicable
data requirements and an indication of how each is satisfied--the
statement of the method of support for 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
follows the index on the next page, and samples of some of the
requirements are attached. Except for the language of 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.
42
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- INDEX-
Text Example
Page Page
A.
B.
C.
D.
E.
F.
G.
A.
Organization of the Submittal Package 3
Transmittal Document .-;,. ,;".•'^M^l|>fc . i*->./.'!,;-..,••,, 4
:.v, :;'..*; ''';•'[<•>/>? tftfp;fl'|8p . "4W8^>* ®$'•*$••
Individual Studies . . . .. . .-. 4
C. 1 Special Considerations for Identifying Studies . . 5
Organization of each Study Volume 6
D. 1 Study Title Page 7
D. 2 Statement of Data Confidentiality Claims
(based on FIFRA §10 (d) (1)) 8
D. 3 Confidential Attachment 8
D. 4 Supplemental Statement of Data Confidentiality
Claims (other than those based on FIFRA §10(d)(1)) 8
D. 5 Good Laboratory Practice Compliance Statement . . 9
Reference to Previously Submitted Data 9
Physical Format Requirements & Number of Copies .... 9
Special Requirements for Submitting Data to the Docket 10
**************
Organization of Submittal Package
A "submittal package" consists of all studies submitted at
the same time for 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).
17
11
17
12
13
15
14
16
43
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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- -i.'§•';, a registration application,
petition, experimental use permit (EUP), §3 (c) (2) (B) data
call-in, §6(a)(2) submittal, or a special review; the transmittal
date; and a list of all individual studies included in the
package in the order of their appearance, showing (usually by
Guideline 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
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 petition 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
conventional bibliographic citation including author, date, and
title. Studies generally correspond in scope to a single Guide-
line requirement for supporting data, with some exceptions dis-
cussed in section C.I. Each study included in a submittal
package must be bound as a separate entity. (See comments on
binding 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., l 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.
44
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When a single study is extremely long, binding it in mul-
'tiple volumes 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.I Special Considerations fo'r^ Identifying- Studies
.'-3.1-
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 control 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
produced from unregistered source ingredients, should be bound as
a single study for each Guideline series (61, 62, and 63) for
conventional 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 would 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..
45
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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,
however, 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 commodities 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 laboratory Page 16
work subject to GLP require-
ments
For certain toxicology 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)
46
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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 content of 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 Identification. 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 on the title page elements a. through d. for the
previously submitted study, ailong 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 study. 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 document, identity on the title page all relevant facts of
publication, such as the journal title, volume, issue, inclusive
page numbers, and publication date.
47
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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
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 to 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
portion of a submitted study other than described by FIFRA §10(d)
(1)(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 of 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.
48
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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 to 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 should not be included in the transmit-
tal document, but should be incorporated 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 on one side only in
black ink, with high contrast and good resolution. Bindings for
individual studies must be secure, but easily removable to permit
disassembly for microfilming. Check with EPA for special
instructions before 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 proposed regulations 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.)
49
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G.
Special Requirements for Submitting Data to the Docket
Data submittal packages associated with a Registration Stan-
dard or Special Review must be provided in four copies, from 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".
V.
For Further Information
For further information contact John Carley, Chief,
Information Services Branch, Program Management and Support
Division, (703) 305-5240.
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 Good Laboratory Practice Statements
Attachment 7. Format Diagrams for Submittal Packages and Studies
50
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ATTACHMENT 1
ELEMENTS TO BE INCLUDED IN THEcTRANSMITTAL DOCUMENT*
1. Name and address of submitter .(or all joint submitters**)
+Smith Chemical Corporation
1234 West Smith Street
Cincinnati, OH 98765
-and-
Jones Chemical Company
5678 Wilson Blvd
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. Transmit tal. 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 joint 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:.
Company Name:.
Company Contact:
Name
Signature
Name
Phone
51
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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)
52
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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:
Title
Typed Name
Date:
Signature
2. Claim of confidentiality under FIFRA §10(d)(1)(A), (B), or
(C) .
STATEMENT OF DATA CONFIDENTIALITY CLAIMS
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:
Title
Typed Name
Date:
Signature
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
Methods 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.
53
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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 you claim
confidential treatment on 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.
• Enclose copies of any pertinent determinations of
confidentiality made by EPA, other Federal agencies, of
courts concerning this information.
• If you assert that disclosure of this information would
be likely to result in substantial harmful effects to
you, describe those harmful effects and explain why
they should be viewed as substantial.
• If you assert that the information 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.
54
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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 ;;6f:;;i:he fp.llowing words or phrase at the
indicated volume and page references.
DELETED WORDS OR PHRASE:
PAGE LINE REASON FOR THE DELETION
ono ftil trfol
6
12
100
14
25
19
Identity of Inert Ingredient
FIFRA REFERENCE
§10 (d) (1) (C)
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):
20.
Reproduce the deleted paragraph(s) here
PAGE LINES REASON FOR THE DELETION FIFRA REFERENCE
2-17 Description of the quality control process §10(d)(1)(C)
Example 3. (Confidential pages that have been deleted from the study)
CROSS REFERENCE NUMBER 7. This cross reference number noted on a place-
holder page is used in place of the following
whole pages at the indicated volume and page
references.
DELETED PAGE(S):' are attached immediately behind this page.
PAGE LINES REASON FOR THE DELETION FIFRA REFERENCE
20. 2-17 Description of the product manufacturing process §10(d)(1)(A)
55
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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
Study Director
Example 2.
This study does not meet the requirements of 40 CFR Part 160, and differs
in the following ways:
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
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ATTACHMENT 7.
FORMAT OF THE SUBMITTAL PACKAGE
LEGEND
Tranamittal Document.
Belated Administrative Materials
te.g.. Method of Support Statement, etc.)
Other materials about the subraittal
(e.g., summaries of groups of studies
to aid in their review).
Studies, submitted as unique
physical entities, according
to the format below.
FORMAT OP 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.
— 1 Supplemental Statement
I . of Confidentiality Claims,
P"J * When flagging requirements
are finalized.
Documents which must be submitted as
appropriate to meet established requirements
(
Documents submitted at submitter** option.
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PR Notice 91-2
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.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 policy 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(i). 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
of 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
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the active ingredient statement be as precise as possible
reflecting good 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
product composition because the nominal concentration would be
the amount of active ingredient typically found in the product.
It is important 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 concentration 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. Copies 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 provide certified limits
for each active, inert ingredient, impurities of toxicological
significance(i.e., upper limit(s) only) 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.
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IV. PRODUCTS THAT REQUIRE EFFICACY DATA. ..
All pesticides are•required to be efficacious. Therefore,
the certified lower limits may %fi.ofe :be lower then the minimum
level to achieve efficacy. This is extremely important for
products which are intended to control 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.
(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) above 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.
Ann* E. ££ndaay, Director
Registration Division (H-75Q5
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FDA/EPA MEMORANDUM OF UNDERSTANDING
Notice Regarding Matters of Mutual Responsibility -
Regulation of Liquid Chemical Germicides Intended
for Use on Medical Devices
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Memorandum of Understanding
Between
The Food and Drug Administration, Public Health Service,
Department of Health and Human Services
and
The Environmental Protection Agency
Notice Regarding Matters of Mutual Responsibility - Regulation of
Liquid Chemical Germicides Intended for Use on Medical Devices
I.
PURPOSE
This Memorandum of Understanding (MOU) between the Food and Drug
Administration (FDA) and the Environmental Protection Agency (EPA)
clarifies jurisdiction between the two agencies in the regulation
of certain liquid chemical germicides. These liquid chemical
germicides are devices under the Federal Food, Drug, and Cosmetic
Act (FD&C Act) and pesticides under the Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA). This MOU also embodies the
agreement of the two agencies to undertake certain rulemakings in
order to eliminate duplicative regulation of certain types of
liquid chemical germicides. This MOU includes the agencies' interim
agreement to simplify and coordinate their regulatory and
enforcement activities in shared areas of jurisdiction affecting
these types of products pending the conclusion of these
rulemakings.
II. STATUTORY AUTHORITIES
A. FDA Authorities
The FD&C Act grants FDA authority to regulate devices as defined in
21 U.S.C. §321(h). Under section 321 (h), the term "device" includes
an instrument, apparatus, implement, machine, contrivance, implant,
in vitro reagent, or other similar or related article, including
any component, part, or accessory that is intended to cure,
mitigate, treat, or prevent disease in man, or is intended to
affect the structure or any function of the body of man. Liquid
chemical germicides intended for use in conjunction with a variety
of articles that fit within the statutory definition of "device,"
such as operating instruments, medical examining tables, hospital
scales, and other hospital equipment, also fall within the
definition of "device", because they are considered accessories to
these devices.
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Unless liquid chemical gennicid§g,.used,;in conjunction with devices
were commercially distributed' prior to May 28, 1976,3
manufacturers of these products, under 21 U.S.C. §360(k) [section
510 (k) of the FD&C Act] are required to submit a premarket
notification to FDA before they market their products. Before these
products can be legally marketed, FDA must grant marketing
clearance by (1) issuance of an order in response to a section
510 (k) submission which exempts the device from the FD&C Act's
premarket approval requirements, or (2) approval of a premarket
approval application. In granting marketing clearance by issuance
of a section 510(k) order exempting a liquid chemical germicide
from premarket approval, FDA must find that the device is
"substantially equivalent," as the term is defined in 21 U.S.C.
§360c(i) (1) (A) , to a predicate device that does not require
premarket approval. Section 513 of the FD&C Act authorizes FDA to
exempt products from premarket notification requirements for which
there is a reasonable assurance of safety and effectiveness. At
present, no chemical germicides that are used with devices have
been exempted from premarket notification requirements.
In regulating liquid chemical germicides used with devices, FDA is
exercising its responsibilities under the FD&C Act for ensuring
that devices are safe and effective for their intended uses. The
FD&C Act provides enforcement authority to FDA to pursue regulatory
actions, including seizure, injunction, prosecution, and civil
penalties.
B. EPA Authorities
Liquid chemical germicides, including those regulated as devices,
are also under the authority of the EPA under FIFRA. Before a
pesticide product may be lawfully sold or distributed in commerce,
the product must be registered by EPA pursuant to FIFRA section 3,
or otherwise exempted from the requirements of FIFRA. A
registration is a license allowing a pesticide product to be sold
and distributed for specified uses in accordance with specified use
instructions, precautions, and other terms and conditions. Liquid
chemical sterilants are included among the various types of
antimicrobial products that are currently subject to FIFRA.
A pesticide product may be registered or remain registered only if
it meets the statutory standard for registration. Among other
things, a pesticide must perform its intended pesticidal function
without causing "unreasonable adverse effects on the environment"
(FIFRA section 3(c) (5)). "Unreasonable adverse effects on the
3
Devices marketed prior to May 28, 1976 are grandfathered from the FD&C Act's
premarket notification requirements. Neither FDA nor EPA are aware of any currently
marketed products that are exempt under this grandfather provision. Should any exist, they are
not covered by this Memorandum of Understanding.
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environment" is defined as "any unreasonable risk to man or the
environment, taking into account, the economic, social, and
environmental costs and benefits '""of the use of [the] pesticide"
(FIFRA section 2(bb)) .
The burden of demonstrating that a pesticide product satisfies the
statutory criteria for registration is at all times on the
proponents of initial or continued registration. FIFRA section 6
provides EPA with various regulatory tools that the Administrator
may use if it appears that the product no longer satisfies the
statutory criteria for registration. If appropriate, EPA _may
require modifications to the terms and conditions of registration,
such as deletion of particular uses or revisions to labeling, as an
alternative to regulatory outcomes such as cancellation,
suspension, or emergency suspension. FIFRA also provides
enforcement authority to EPA to pursue actions, including issuance
of stop sale, use, or removal orders when there is reason to
believe a pesticide is in violation of FIFRA. Additionally, EPA has
authority to seek the assessment of civil administrative penalties
as well as institute seizure and, criminal actions for violations of
FIFRA.
FIFRA section 25(b) authorizes the Administrator to exempt
pesticides from FIFRA through regulation if the Administrator
determines that the pesticide is "adequately regulated by another
Federal agency" or is "of a character which it is unnecessary to be
subject to this Act in order to carry out the purposes of this
Act."
III. REGULATORY RESPONSIBILITIES AND DEFINITIONS
For the purposes of this agreement, liquid chemical germicides that
are used in conjunction with medical devices are divided into two
product categories: (1) sterilants and (2) general purpose
disinfectants. Sterilants, for purposes of this agreement, means
those chemical germicides used to reprocess reusable critical and
semicritical devices2. Critical devices are devices that are
introduced directly into the human body, either into or in contact
with the bloodstream or normally sterile areas of the body. These
critical devices must be sterile. Semicritical devices are those
which contact intact mucous membranes but which do not ordinarily
penetrate the blood barrier or otherwise enter normally sterile
areas of the body. For these devices, sterilization is desirable
2 This definition is consistent with the definition of these terms used by the Centers for
Disease Control and Prevention (CDC). Block, S.S. 1991. Disinfection, Sterilization, and
Preservation. 4th Edition. Philadelphia, Lea & Febiger.
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but not mandatory. These devices must be subjected at least to a
high level disinfection3 process using a sterilant, but for a
shorter time than that required !:f or sterilization.
The second category of liquid chemical germicides are general
purpose disinfectants. General purpose disinfectants, for purposes
of this agreement, means those chemical germicides used to
reprocess noncritical devices and medical equipment surfaces4.
Noncritical devices and medical equipment surfaces must be
subjected to intermediate or low level disinfection5.
FDA's priority is to confirm the efficacy and safety of sterilants
used to reprocess critical and semicritical devices which pose the
greatest risk of disease transmission. This includes assuring that
they do not adversely affect device performance or pose a hazard to
the patient/user. Historically, EPA has assessed the effective
performance of all chemical germicides and addressed health and
safety issues their use.
The FD&C Act and FIFRA have overlapping regulatory schemes for
liquid chemical germicides used on devices. The objective of this
MOU is to minimize redundant regulation of these products by FDA
and EPA while assuring that the safety and efficacy requirements of
both statutes are met. This affects three areas: data requirements
for obtaining approval, procedures for obtaining approval, and
compliance.
In determining whether the FD&C Act's and FIFRA's statutory and
regulatory requirements are met, EPA and FDA will utilize the data
requirements and performance standards referenced in FDA's current
Guidance on the Content and Format of Premarket Notification
Submission for Liquid Chemical Germicides, FDA premarket
notification regulations at 21 CFR Part 807, Subpart E, EPA data
requirements regulations at 40 CFR Part 158, and EPA's Subdivision
G, Product Performance Guidelines.
Since the EPA registration requirements for general purpose
disinfectants parallel the requirements necessary to receive
marketing clearance for general purpose disinfectants under section
510 (k) of the FD&C Act, fulfillment of EPA's registration
3 "High level disinfectant" and "high level disinfection" are terms of are used by the public
health community. FDA recognizes "high level disinfectant" as a separate or subcategory of
sterilants. EPA does not register "high level disinfectants" as separate antimicrobial pesticides,
but instead may register uses of germicides that correspond with uses in FDA's "high level
disinfection" category.
4
This definition is consistent with the definition of the term used by CDC.
5 "Low and intermediate level disinfectants" are terms of art used by the public health
community. FDA recognizes "low and intermediate level disinfection" as subcategories of
general purpose disinfectants. EPA does not register low level and intermediate level
disinfectants, but has corresponding germicide classes.
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requirements fulfills FDA's section 510(k) requirements for those
products.
The EPA efficacy data requirements for liquid chemical sterilants,
including those with high level disinfectant uses, are fulfilled by
FDA's section 510(k) requirements or premarket approval
requirements. Therefore, premarket clearance by FDA fulfills
certain EPA registration requirements for liquid chemical
sterilants, insofar as efficacy and product performance are
concerned. FDA premarket clearance does not satisfy EPA's
chemistry, toxicology, and ecological effects requirements.
IV. AGREEMENT
The Administrator of the Environmental Protection Agency and the
Commissioner of the Food and Drug Administration agree that until
exemptions referred to in Section V occur, the following division
of responsibility will govern the activities of the agencies in the
regulation of liquid chemical germicides that are intended for use
on devices:
A. Regulatory Responsibilities
1. FDA will be primarily responsible for the premarket review of
safety and efficacy requirements for liquid chemical
germicides that are sterilants6 intended for use on critical
or semicritical devices. Examples of critical devices are
laparoscopes, surgical instruments, heart-lung oxygenators,
and transfer forceps. Examples of semicritical devices are
gastrointestinal endoscopes, endotracheal tubes, cystoscopes,
anesthesia breathing circuits, and vaginal specula. FDA will
also be primarily responsible for premarket review of contact
lens solutions.
EPA will be primarily responsible for premarket review of
liquid chemical germicides that are general purpose
disinfectants7 intended for use on devices other than critical
6 If a liquid chemical sterilant product has subordinate claims such as tuberculocidal or
virucidal, these claims also will be regulated by FDA.
7 Procedures described in Paragraph 4 only apply to liquid chemical germicide products that
do not contain any sterilant claims. If a liquid chemical germicide product contains both
sterilant and general purpose disinfectant claims, registration will proceed according to the
procedures described in Paragraph 3. If the registrant of a general purpose disinfectant product
registered by EPA subsequently applies for registration of a sterilant claim, registration of that
product must proceed under procedures described hi Paragraph 3 and the existing EPA
registration will become void upon FDA's clearance of the product.
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B.
1.
or semicritical devices. Examples of noncritical devices are
wheel chairs, medical beds, stands, certain operating room
surfaces, medical lamps, dental units, and stethoscopes.
FDA marketing clearance through the section 510(k) process or
approval through the premarket approval process of sterilants
will satisfy certain requirements for registration under FIFRA
Section 3. Upon submission to EPA by the applicant of an order
issued by FDA granting marketing clearance or approval for a
liquid chemical germicide that is a sterilant, EPA will
consider the efficacy data requirements for registration to be
satisfied, and will promptly determine whether the other
requirements for registration are satisfied.
EPA registration of liquid chemical germicides that are used
as disinfectants for devices, except sterilants, will satisfy
the criteria necessary to establish substantial equivalence as
defined in 21 U.S.C. §360c(i) (1) (A) . For this category of
liquid chemical germicides, submission by the manufacturer to
FDA of a copy of the EPA correspondence granting registration
will satisfy FDA's requirement for a premarket notification
under 21 U.S.C. §360 (k) . Upon receipt of this information from
the manufacturer of a liquid chemical germicide in this
category, FDA will issue an order finding the product
substantially equivalent to a predicate device that does not
require premarket approval. This order will allow the device
to be legally marketed without an approved FDA premarket
approval application.
As part of the EPA registration process, EPA will require
registrants of liquid chemical germicides, other than
sterilants that have received FDA premarketing clearance or
approval, to put the following statement on their product
labels:
"This product is not to be used on any surface or
instrument that (1) is introduced directly into the human
body, either into or in contact with the bloodstream or
normally sterile areas of the body, or (2) contacts
intact mucous membranes but which does not ordinarily
penetrate the blood barrier or otherwise enter normally
sterile areas of the body."
Compliance Responsibilities
FDA will be responsible for all sampling and all efficacy
testing of liquid chemical sterilants intended for use on
critical and semicritical devices and for instituting
appropriate enforcement and/or regulatory action against any
products that do not comply with the FD&C Act.
Upon request, EPA will provide FDA with copies of the latest
accepted labeling and the name and location of the production
site for each product FDA intends to sample.
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To the extent allowed under 21 U.S.C. § 331j, 21 U.S.C.
§360(j)(c), 42 U.S.C. §263g.(d) , 42 U.S.C. 263i(e), and 21
C.F.R. Part 20, FDA will gha±e all safety and efficacy test
results, labeling changes,x;and' upon EPA request, any other
information obtained during FDA enforcement/regulatory actions
relating to liquid chemical sterilants. EPA may use this
information to determine whether the registrant has complied
with FIFRA. On the basis of this information, EPA may
determine that further regulatory action under FIFRA,
including cancellation of the product's registration, is
warranted.
2. EPA will be responsible for the sampling and efficacy testing
of all general purpose chemical germicides that are intended
for use on devices other than critical and semicritical
devices, and for instituting appropriate enforcement and/or
regulatory action against any such chemical germicide that
does not comply with FIFRA. EPA will refer labels and other
evidence concerning inefficacious liquid chemical germicides
intended for use on medical devices other than critical or
semicritical to FDA for complementary action under the FD&C
Act.
3. Each agency will provide assistance upon request to support
compliance activities and litigation by the other Agency in
cases involving liquid chemical germicides that are intended
for use on devices. Assistance will be requested in accordance
with applicable procedures, statutory and regulatory
requirements including compliance with regulations of 21 CFR
Part 20, through the liaison officers listed below. Assistance
may include provision of sampling, inspection and audit data,
expert witnesses, certified statements, and affidavits.
Each Agency may consult with the other at any time to
determine if the initiation of regulatory and/or enforcement
action against a liquid chemical germicide in lieu of or
concurrently with the other agency's action is appropriate.
This Memorandum of Understanding has no effect on any pending
investigations or enforcement or regulatory actions undertaken
by EPA pursuant to FIFRA or by FDA pursuant to the FD&C Act.
C. Coordination of Activities
To ensure the continued coordinated regulatory, compliance, and
enforcement activities for liquid chemical germicides intended for
use on devices, an EPA/FDA interagency committee is established.
The Directors of the EPA's Registration Division and the Compliance
Division, Office of Prevention, Pesticides, and Toxic Substances,
and of FDA's Center for Devices and Radiological Health, Office of
Compliance and Surveillance, will serve as joint chairpersons who
will designate their respective agency members of the committee.
The committee will meet at a minimum of twice each fiscal year.
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V. FUTURE RULEMAKINGS TO ELIMINATE DUPLICATIVE AGENCY REVIEW
EPA will initiate a rulemaking proceeding under section 25(b) of
FIFRA to exempt liquid chemical sterilant products from regulation
under FIFRA. EPA believes that the efficacy data requirements and
product performance standards for liquid chemical sterilants are
fulfilled by FDA's section 510(k) requirements or premarket
approval requirements. When such exemption becomes effective, FDA
and EPA will cease to follow procedures described in Paragraph IV,
A.3. and these products will be subject solely to the regulatory
and enforcement requirements and procedures of FDA, and EPA will no
longer register such products. To the extent EPA receives
information regarding such products, it will share such information
with FDA.
FDA will initiate a rulemaking proceeding to classify liquid
chemical germicides used on devices under section 513 of the FD&C
Act. FDA believes that EPA's requirements under FIFRA for liquid
chemical germicides that are intended for use on medical devices
that are not critical or semicritical devices parallel the FD&C
Act's requirements under section 510(k) of the Act. Accordingly,
FDA will recommend to its classification advisory panel that liquid
chemical germicides intended for use on devices that are not
critical or semicritical devices be exempted from premarket
notification requirements under section 510(k) of the FD&C Act.
When any such exemption becomes effective, FDA and EPA will cease
to follow the procedures in paragraph IV. A. 4. To the extent FDA
obtains any information regarding such products, it will share the
information with EPA.
VI. NAME AND ADDRESS OF PARTICIPATING PARTIES
A. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
B. Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 20460
VII. LIAISON OFFICERS
A. For the Food and Drug Administration
Sterilization and Toxicology Project Officer
(currently: Dr. Virginia Chamberlain)
Office of Compliance and Surveillance
Center for Devices and Radiological Health
1390 Piccard Drive
Rockville, MD 20850
Telephone: (301) 427-1131
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For the Environmental Protection Agency:
Antimicrobial Program piranch Chief
(currently: Juanita Wills)
Registration Division
Antimicrobial Program Branch (H7505C)
401 M Street, S.W.
Washington, DC 20460
Telephone: (703) 305-6661
VIII. PERIOD OF AGREEMENT
This agreement becomes effective upon acceptance by both parties.
It may be modified by mutual written consent or terminated by
either party upon a thirty (30) day advance written notice to the
other party. The parties agree to evaluate the agreement every
three (3) years, at which time either party would have the option
of renewing, modifying, or canceling the agreement.
APPROVED AtfO ACCEPTED FOR TK£
ENVIRONMENTAL PROTECTION
APPROVED AND ACCEPTED FOR THE
FOOD AND D3UG ADMINISTRATION
•
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APPENDIX F
Generic Data Call-In
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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(s) identified in Attachment A of this Notice, the Data Call-In Chemical Status Sheet.
to submit certain data as noted herein to the U.S. Environmental Protection Agency (EPA, the
Agency). These data are necessary to maintain the continued registration of your product(s)
containing this active ingredient(s). Within 90 days after you receive this Notice you must
respond as set forth in Section IH below. Your response must state:
1. how you will comply with the requirements set forth in this Notice and its Attachments
A through D; or,
2. why you believe you are exempt from the requirements listed in this Notice and in
Attachment C, Requirements Status and Registrant's Response Form, (see section ffl-B);
or,
3. why you believe EPA should not require your submission of data in the manner specified
by this Notice (see section IH-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list of
all of your products subject to this Notice in Attachment B, Data Call-In Response Form, as well
as a list of all registrants who were sent this Notice (Attachment D).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-0107
(expiration date 12-31-92).
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This Notice is divided into six sections ;and five 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 K - Data Required By This Notice
Section ffl - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse
Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
Attachment A -
Attachment B -
Attachment C -
Attachment D -
Data Call-in Chemical Status Sheet
Data Call-In Response Form
Requirements Status And Registrant's Response Form
List Of All Registrants Sent This Data Call-In Notice
SECTION I. WHY YOU ARE RECEIVING TUTS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the
data needed to support continued registration of the subject active ingredient(s). This
revaluation identified additional data necessary to assess the health and safety of the continued
use of products containing this active ingredient(s). You have been sent this Notice because you
have product(s) containing the subject active ingredient(s).
SECTION H. DATA REQUIRED BY THIS NOTICE
A. DATA REQUIRED
The data required by this Notice are specified in Attachment C, Requirements
Status and Registrant's Response Form. Depending on the results of the studies required
in this Notice, additional testing may be required.
B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements
specified in Attachment C, Requirements Status and Registrant's Response Form, within
the time frames provided.
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c.
TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test
standards outlined in the Pesticide Assessment Guidelines for those studies for which
guidelines have been established.
These EPA Guidelines are available from the National Technical Information
Service (NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel:
703-487-4650).
Protocols approved by the Organization for Economic Cooperation 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.
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)j.
D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c](2)CS) NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede
or change the requirements of any previous Data Call-Infs). or any other agreements
entered into with the Agency pertaining to such prior Notice. Registrants must comply
with the requirements of all Notices to avoid issuance of a Notice of Intent to Suspend
their affected products.
SECTION
A.
COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice 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.
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B. OPTIONS FOR RESPONDING TO THE A(
The options for responding to this Notice are: 1) voluntary cancellation, 2) delete
use(s), (3) claim generic data exemption, (4) agree to satisfy the data requirements
imposed by this Notice or (5) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option,
the Delete Use(s) option or the Generic Data Exemption option is presented below. A
discussion of the various options available for satisfying the data requirements of this
Notice is contained in Section DI-C. A discussion of options relating to requests for data
waivers is contained in Section m-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 (Attachment B) and the Requirements Status and
Registrant's Response Form (Attachment C). The Data Call-In Response Form must be
submitted as part of every response to this Notice. Please note that the company's
authorized representative is required to sign the first page of the Data Call-in Response
Form and Requirements Status and Registrant's Response Form (if this form is required)
and initial any subsequent pages. The forms contain separate detailed instructions on the
response options. Do not alter the printed material. If you have questions or need
assistance in preparing your response, call or write the contact person identified in
Attachment A.
1. Voluntary Cancellation - You may avoid the requirements of this Notice
by requesting voluntary cancellation of your product(s) containing the active
ingredient(s) that is the subject of this Notice. If you wish to voluntarily cancel
your product, you must submit a completed Data Call-in Response Form.
indicating your election of this option. Voluntary cancellation is item number 5
on the Data Call-In Response Form. If you choose this option, this is the only
form that you are required to complete.
If you choose to voluntarily cancel your product, further sale and
distribution of your product after the effective date of cancellation must be in
accordance with the Existing Stocks provisions of this Notice which are contained
in Section IV-C.
2. Use Deletion - You may avoid the requirements of this Notice by
eliminating the uses of your product to which the requirements apply. If you
wish to amend your registration to delete uses, you must submit the Requirements
Status and Registrant's Response Form, a completed application for amendment,
a copy of your proposed amended labeling, and all other information required for
processing the application. Use deletion is option number 7 on the Requirements
Status and Registrant's Response Form. You must also complete a Data Call-In
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Response Form by signing the certification, item number 8. Application forms for
amending registrations niay^e^tam^d,from the Registration Support and
Emergency Response Branch, Registration Division, (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to
specific data requirements, further sale, distribution, or use of your product after
one year from the due date of your 90 day response, must bear an amended label.
3. Generic Data Exemption - Under section 3(c)(2)(D) of FIFRA, an
applicant for registration of a product is exempt from the requirement to submit
or cite generic data concerning an active ingredient(s) if the active ingredient(s)
in the product is derived exclusively from purchased, registered pesticide products
containing the active ingredient(s). EPA has concluded, as an exercise of its
discretion, that it normally will not suspend the registration of a product which
would qualify and continue to qualify for the generic data exemption in section
3(c)(2)(D) of FIFRA. To qualify, all of the following requirements must be met:
a. The active ingredient(s) in your registered product must be present
solely because of incorporation of another registered product which
contains the subject active ingredient(s) and is purchased from a source
not connected with you; and,
b. every registrant who is the ultimate source of the active
ingredient(s) in your product subject to this DCI must be in compliance
with the requirements of this Notice and must remain in compliance; and
c. you must have provided to EPA an accurate and current
"Confidential Statement of Formula" for each of your products to which
this Notice applies.
To apply for the Generic Data Exemption you must submit a completed
Data Call-in Response Form. Attachment B and all supporting documentation.
The Generic Data Exemption is item number 6a on the Data Call-in Response
Form. If you claim a generic data exemption you are not required to complete
the Requirements Status and Registrant's Response Form. Generic Data
Exemption cannot be selected as an option for product specific data.
If you are granted a Generic Data Exemption, you rely on the efforts of
other persons to provide the Agency with the required data. If the registrant(s)
who have committed to generate and submit the required data fail to take
appropriate steps to meet the requirements or are no longer hi compliance with
this Data Call-in Notice, the Agency will consider that both they and you are not
in compliance and will normally initiate proceedings to suspend the registrations
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c.
of both your and their product(s), unless you commit to submit and do submit the
required data within the specified time. In such cases the Agency generally will
not grant a tune extension for submitting the data.
4. Satisfying the Data Requirements of this Notice - There are various
options available to satisfy the data requirements of this Notice. These options
are discussed in Section ffl-C of this Notice and comprise options 1 through 6 on
the Requirements Status and Registrant's Response Form and option 6b and 7 on
the Data CaU-In Response Form. If you choose option 6b or 7, you must submit
both forms as well as any other information/data pertaining to the option chosen
to address the data requirement.
5. Request for Data Waivers. Data waivers are discussed in Section m-D
of this Notice and are covered by options 8 and 9 on the Requirements Status and
Registrant's Response Form. If you choose one of these options, you must
submit both forms as well as any other information/data pertaining to the option
chosen to address the data requirement.
SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-in Response Form that you agree to satisfy
the data requkements (i.e. you select option 6b and/or 7), then you must select one of
the six options on the Requirements Status and Registrant's Response Form related to
data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production
are the first six options discussed under item 9 in the instructions for completing the
Requirements Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide registrants to additional
instructions provided in this Section. The options are:
1. I will generate and submit data within the specified time frame
(Developing Data),
2. I have entered into an agreement with one or more registrants to develop
data jointly (Cost Sharing),
3. I have made offers to cost-share (Offers to Cost Share),
4. I am submitting an existing study that has not been submitted previously
to the Agency by anyone (Submitting an Existing Study),
5. I am submitting or citing data to upgrade a study classified by EPA as
partially acceptable and upgradeable (Upgrading a Study),
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6. I am citing an existing study that EPA has classified as acceptable or an
existing study that has-biSen 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 hi 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 CFRPart 160), be conducted according to the
Pesticide Assessment Guidelines (PAG), and be in conformance with the
requirements of PR Notice 86-5. In addition, certain studies require Agency
approval of test protocols in advance of study initiation. Those studies for which
a protocol must be submitted have been identified in the Requirements Status and
Registrant's Response Form and/or footnotes to the form. If you wish to use a
protocol which differs from the options discussed in Section n-C of this Notice,
you must submit a detailed description of the proposed protocol and your reason
for wishing to use it. The Agency may choose to reject a protocol not specified
in Section n-C. If the Agency rejects your protocol you will be notified in
writing, however, you should be aware that rejection of a proposed protocol will
not be a basis for extending the deadline for submission of data.
A progress report must be submitted for each study within 90 days from
the date you are required to commit to generate or undertake some other means
to address that study requirement, such as making an offer to cost-share or
agreeing to share in the cost of developing that study. A 90-day progress report
must be submitted for all studies. This 90-day progress report must include the
date the study was or will be initiated and, for studies to be started within 12
months of commitment, the name and address of the laboratories) or individuals
who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than
1 year, interim reports must be submitted at 12 month intervals from the date you
are required to commit to generate or otherwise address the requirement for the
study. In addition to the other information specified in the preceding paragraph,
at a minimum, a brief description of current activity on and the status of the study
must be included as well as a full description of any problems encountered since
the last progress report.
The time frames in the Requirements Status and Registrant's Response
Form are the time frames that the Agency is allowing for the submission of
completed study reports or protocols. The noted deadlines run from the date of
the receipt of this Notice by the registrant. If the data are not submitted by the
deadline, each registrant is subject to receipt of a Notice of Intent to Suspend the
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affected registration^). : . , .,.. ,
If you cannot submit the data/reports to the Agency in the time required
by this Notice and intend to seek additional time to meet the requirement(s), you
must submit a request to the Agency which includes: (1) a detailed description
of the expected difficulty and (2) a proposed schedule including alternative dates
for meeting such requirements on a step-by-step basis. You must explain any
technical or laboratory difficulties and provide documentation from the laboratory
performing the testing. While EPA is considering your request, the original
deadline remains. The Agency will respond to your request in writing. If EPA
does not grant your request, the original deadline remains. Normally, extensions
can be requested only hi cases of extraordinary testing problems beyond the
expectation or control of the registrant. Extensions will not be given in
submitting the 90-day responses, Extensions will not be considered if the request
for extension is not made in a timely fashion; in no event shall an extension
request be considered if it is submitted at or after the lapse of the subject
deadline.
Option 2. Agreement to Share in Cost to Develop Data —
If you choose to enter into an agreement to share hi the cost of producing
the required data but will not be submitting the data yourself, you must provide
the name of the registrant who will be submitting the data. You must also
provide EPA with documentary evidence that an agreement has been formed.
Such evidence may be your letter offering to join in an agreement and the other
registrant's acceptance of your offer, or a written statement by the parties that an
agreement exists. The agreement to produce the data need not specify all of the
terms of the final arrangement between the parties or the mechanism to resolve
the terms. Section 3(c)(2)(B) provides that if the parties cannot resolve the terms
of the agreement they may resolve their differences through binding arbitration.
Option 3, Offer to Share in the Cost of Data Development —
If you have made an offer to pay in an attempt to enter into an agreement
or amend an existing agreement to meet the requirements of this Notice and have
been unsuccessful, you may request EPA (by selecting this option) to exercise its
discretion not to suspend your registration(s), although you do not comply with
the data submission requirements of this Notice. EPA has determined that as a
general policy, absent other relevant considerations, it will not suspend the
registration of a product of a registrant who has in good faith sought and
continues to seek to enter into a joint data development/cost sharing program, but
the other registrant(s) developing the data has refused to accept your offer. To
qualify for this option, you must submit documentation to the Agency proving
that you have made an offer to another registrant (who has an obligation to submit
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data) to share in the burden of developing that data. You must also submit to the
Agency a Completed EPA F6rm^5^0-32v Certification of Offer to Cost Share in
the Development of Data, Attachment E. In addition, you must demonstrate that
the other registrant to whom the offer was made has not accepted your offer to
enter into a cost sharing agreement by including a copy of your offer and proof
of the other registrant's receipt of that offer (such as a certified mail receipt).
Your offer must, in addition to anything else, offer to share in the burden of
producing the data upon terms to be agreed or failing agreement to be bound by
binding arbitration as provided by FIFRA section 3(c)(2)(B)(iii) and must not
qualify this offer. The other registrant must also inform EPA of its election of
an option to develop and submit the data required by this Notice by submitting
a Data Call-in Response Form and a Requirements Status and Registrant's
Response Form committing to develop and submit the data required by this
Notice.
In order for you to avoid suspension under this option, you may not
withdraw your offer to share in the burdens of developing the data. In addition,
the other registrant must fulfill its commitment to develop and submit the data as
required by this Notice. If the other registrant fails to develop the data or for
some other reason is subject to suspension, your registration as well as that of the
other registrant will normally be subject to initiation of suspension proceedings,
unless you commit to submit, and do submit the required data in the specified
time frame. In such cases, the Agency generally will not grant a time extension
for submitting the data.
Option 4. Submitting an Existing Study ~
If you choose to submit an existing study in response to this Notice, you
must determine that the study satisfies the requirements imposed by this Notice.
You may only submit a study that has not been previously submitted to the
Agency or previously cited, by anyone. Existing studies are studies which predate
issuance of this Notice. Do not use this option if you are submitting data to
upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not
acceptable, the Agency will require you to comply with this Notice, normally
without an extension of the required date of submission. The Agency may
determine at any time that a study is not valid and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing
study, all of the following three criteria must be clearly met:
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a. You must certify at the time that the existing study is submitted
that the raw data and specimens from the study are available for audit and
review and you must identify where they are available. This must be
done in accordance with the requirements of the Good Laboratory Practice
(GLP) regulation, 40 CFR Part 160. As stated in 40 CFR 160.3(7) " raw
data means any laboratory worksheets, records, memoranda, notes, or
exact copies thereof, that are the result of original observations and
activities of a study and are necessary for the reconstruction and
evaluation of the report of that study. In the event that exact transcripts
of raw data have been prepared (e.g., tapes which have been transcribed
verbatim, dated, and verified accurate by signature), the exact copy or
exact transcript may be substituted for the original source as raw data.
Raw data may include photographs, microfilm or microfiche copies,
computer printouts, magnetic media, including dictated observations, and
recorded data from automated instruments." The term "specimens",
according to 40 CFR 160.3(7), 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 FEFRA 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.
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>•>* *
If you submit an existing study, you must certify that the study
meets all requirements^ of :tti^ criteria outlined above.
If EPA has previously reviewed a protocol for a study you are
submitting, you must identify any action taken by the Agency on the
protocol and must indicate, as part of your certification, the manner in
which all Agency comments, concerns, or issues were addressed in the
final protocol and study.
If you know of a study pertaining to any requirement in this Notice
which does not meet the criteria outlined above but does contain factual
information regarding unreasonable adverse effects, you must notify the
Agency of such a study. If such a study is in the Agency's files, you
need only cite it along with the notification. If not in the Agency's files,
you must submit a summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study —
If a study has been classified as partially acceptable and upgradeable, you
may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the
requirement is not satisfied, you may still be required to submit new data
normally without any time extension. Deficient, but upgradeable studies will
normally be classified as supplemental. However, it is important to note that not
all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call
or write the contact person listed in Attachment A. If you submit data to upgrade
an existing study you must satisfy or supply information to correct all deficiencies
in the study identified by EPA. You must provide a clearly articulated rationale
of how the deficiencies have been remedied or corrected and why the study
should be rated as acceptable to EPA. Your submission must also specify the
MRID number(s) of the study which you are attempting to upgrade and must be
in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study
classified as unacceptable and determined by the Agency as not capable of being
upgraded.
This option 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.
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The criteria for submitting; an existing study, as specified in Option 4
above, apply to all data submissions intended to upgrade studies. Additionally
your submission of data intended to upgrade studies must be accompanied by a
certification that you comply with each of those criteria as well as a certification
regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies —
If you choose to cite a study that has been previously submitted to EPA,
that study must have been previously classified by EPA as acceptable or it must
be a study which has not yet been reviewed by the Agency. Acceptable
toxicology studies generally will have been classified as "core-guideline" or "core
minimum." For ecological effects studies, the classification generally would be
a rating of "core." For all other disciplines the classification would be
"acceptable." With respect to any studies for which you wish to select this option
you must provide the MRID number of the study you are citing and, if the study
has been reviewed by the Agency, you must provide the Agency's classification
of the study.
If you are citing a study of which you are not the original data submitter,
you must submit a completed copy of EPA Form 8570-31, Certification with
Respect to Data Compensation Requirements.
D. REQUESTS FOR DATA WAIVERS
There are two types of data waiver responses to this Notice. The first is a request
for a low volume/minor use waiver and the second is a waiver request based on your
belief that the data requirement(s) are inapplicable and do not apply to your product.
1. Low Volume/Minor Use Waiver ~ Option 8 on the Requirements Status
and Registrant's Response Form. Section 3(c)(2)(A) of FIFRA requires EPA to
consider the appropriateness of requiring data for low volume, minor use
pesticides. In implementing this provision EPA considers as low volume
pesticides only those active ingredient(s) whose total production volume for all
pesticide registrants is small. In determining whether to grant a low volume,
minor use waiver the Agency will consider the extent, pattern and volume of use,
the economic incentive to conduct the testing, the importance of the pesticide, and
the exposure and risk from use of the pesticide. If an active ingredient(s) is used
for both high volume and low volume uses, a low volume exemption will not be
approved. If all uses of an active ingredient(s) are low volume and the combined
volumes for all uses are also low, then an exemption may be granted, depending
on review of other information outlined below. An exemption will not be granted
if any registrant of the active ingredient(s) elects to conduct the testing. Any
registrant receiving a low volume minor use waiver must remain within the sales
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figures in their forecast supporting the waiver request in order to remain qualified
for such waiver. If granted a waiver;; a registrant will be required, as a condition
of the waiver, to submit annual sales reports. The Agency will respond to
requests for waivers in writing,
To apply for a low volume, minor use waiver, you must submit the
following information, as applicable to your product(s), as part of your 90-day
response to this Notice:
a. Total company sales (pounds and dollars) of all registered
product(s) containing the active ingredient(s). If applicable to the active
ingredient(s), include foreign sales for those products that are not
registered in this country but are applied to sugar (cane or beet), coffee,
bananas, cocoa, and other such crops. Present the above information by
year for each of the past five years.
b. Provide an estimate of the sales (pounds and dollars) of the active
ingredient(s) for each major use site. Present the above information by
year for each of the past five years.
c. Total direct production cost of product(s) containing the active
ingredient(s) by year for the past five years. Include information on raw
material cost, direct labor cost, advertising, sales and marketing, and any
other significant costs listed separately.
d. Total indirect production cost (e.g. plant overhead, amortized plant
and equipment) charged to product(s) containing the active ingredient(s)
by year for the past five years. Exclude all non-recurring costs that were
directly related to the active ingredient(s), such as costs of initial
registration and any data development.
e. A list of each data requirement for which you seek a waiver.
Indicate the type of waiver sought and the estimated cost to you (listed
separately for each data requirement and associated test) of conducting
the testing needed to fulfill each of these data requirements.
f. A list of each data requirement for which you are not seeking any
waiver and the estimated cost to you (listed separately for each data
requirement and associated test) of conducting the testing needed to fulfill
each of these data requirements.
g. For each of the next ten years, a year-by-year forecast of company
sales (pounds and dollars) of the active ingredient(s), direct production
costs of product(s) containing the active ingredient(s) (following the
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parameters in item c above), indirect production costs of product(s)
containing the active ingredient(s) (following the parameters in item d
above), and costs of data development pertaining to the active
ingredient(s).
h. A description of the importance and unique benefits of the active
ingredient(s) to users. Discuss the use patterns and the effectiveness of
the active ingredient(s) relative to registered alternative chemicals and
non-chemical control strategies. Focus on benefits unique to the active
ingredient(s), providing information that is as quantitative as possible. If
you do not have quantitative data upon which to base your estimates, then
present the reasoning used to derive your estimates. To assist the Agency
in detenriining the degree of importance of the active ingredient(s) in
terms of its benefits, you should provide information on any of the
following factors, as applicable to your product(s):
(1) documentation of the usefulness of the active ingredient(s)
in Integrated Pest Management, (b) description of the beneficial impacts
on the environment of use of the active ingredient(s), as opposed to its
registered alternatives, (c) information on the breakdown of the active
ingredient(s) after use and on its persistence in the environment, and (d)
description of its usefulness against a pest(s) of public health significance.
Failure to submit sufficient information for the Agency to make a determination
regarding a request for a low volume minor use waiver will result in denial of the request
for a waiver.
2. Request for Waiver of Data —Option 9 on the Requirements Status and
Registrant's Response Form. This option may be used if you believe that a
particular data requirement should not apply because the corresponding use is no
longer registered or the requirement is inappropriate. You must submit a
rationale explaining why you believe the data requirements should not apply.
You must also submit the current label(s) of your product(s) and, if a current
copy of your Confidential Statement of Formula is not already on file you must
submit a current copy.
You will be informed of the Agency's decision in writing. If the Agency
determines that the data requirements of this Notice do not apply to your
product(s), you will not be required to supply the data pursuant to section
3(c)(2)(B). If EPA determines that the data are required for your productfs). you
must choose a method of meeting the requirements of this Notice within the time
frame provided by this Notice. Within 30 days of your receipt of the Agency's
written decision, you must submit a revised Requirements Status and Registrant's
Response Form indicating the option chosen.
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IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
A. NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this
Notice due to failure by a registrant to comply with the requirements of this Data Call-In
Notice, pursuant to FIFRA section 3(c)(2)(B). Events which may be the basis for
issuance of a Notice of Intent to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your
receipt of this Notice.
2. Failure to submit on the required schedule an acceptable proposed or final
protocol when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on
a study as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by
this Notice.
5. Failure to take a required action or submit adequate information pertaining
to any option chosen to address the data requirements (e.g., any required
action or information pertaining to submission or citation of existing
studies or offers, arrangements, or arbitration on the sharing of costs or
the formation of Task Forces, failure to comply with the terms of an
agreement or arbitration concerning joint data development or failure to
comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of
submitted studies, as required by Section EI-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in
the cost of developing data and provided proof of the registrant's receipt
of such offer, or failure of a registrant on whom you rely for a generic
data exemption either to:
a. inform EPA of intent to develop and submit the data required by
this Notice on a Data Call-in Response Form and a Requirements Status
and Registrant's Response Form: or,
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b. fulfill the commitment to develop and submit the data as required
by this Notice; or,
c. otherwise take appropriate steps to meet the requirements stated in
this Notice, unless you commit to submit and do submit the required data
in the specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at
any time following the issuance of this Notice.
B. BASIS FOR DETERMINATION THAT SUBMITTED
UNACCEPTABLE
STUDY IS
The Agency may determine that a study (even if submitted within the required
time) is unacceptable and constitutes a basis for issuance of a Notice of Intent to
Suspend. The grounds for suspension include, but are not limited to, failure to meet any
of the following:
1. EPA requirements specified in the Data Call-in Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment
Guidelines, Data Reporting Guidelines, and GeneTox Health Effects Test
Guidelines) regarding the design, conduct, and reporting of required studies.;
Such requirements include, but are not limited to, those relating to test material,
test procedures, selection of species, number of animals, sex and distribution of
animals, dose and effect levels to be tested or attained, duration of test, and, as
applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner
of reporting, the completeness of results, and the adequacy of any required
supporting (or raw) data, including, but not limited to, requirements referenced
or included in this Notice or contained in PR 86-5. All studies must be submitted
in the form of a final report; a preliminary report will not be considered to fulfill
the submission requirement.
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 Federal Insecticide, Fungicide, and
Rodenticide Act.
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The Agency has determined that such disposition by registrants of existing stocks
for a suspended registration When a/section 3(c)(2)(B) data request is outstanding would
generally not be consistent with the Act's purposes. Accordingly, the Agency anticipates
granting registrants permission to sell, distribute, or use existing stocks of suspended
product(s) only in exceptional circumstances. If you believe such disposition of existing
stocks of your product(s) which may be suspended for failure to comply with this Notice
should be permitted, you have the burden of clearly demonstrating to EPA that granting
such permission would be consistent with the Act. You must also explain why an
"existing stocks" provision is necessary, including a statement of the quantity of existing
stocks and your estimate of the time required for their sale, distribution, and use. Unless
you meet this burden the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this
Notice and your product is in full compliance with all Agency requirements, you will
have, under most circumstances, one year from the date your 90 day response to this
Notice is due, to sell, distribute, or use existing stocks. Normally, the Agency will allow
persons other than the registrant such as independent distributors, retailers and end users
to sell, distribute or use such existing stocks until the stocks are exhausted. Any sale,
distribution or use of stocks of voluntarily cancelled products containing an active
ingredient(s) for which the Agency has particular risk concerns will be determined on
case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period
required by this Notice will not result in the Agency granting any additional time to sell,
distribute, or use existing stocks beyond a year from the date the 90 day response was
due unless you demonstrate to the Agency that you are in full compliance with all
Agency requirements, including the requirements of this Notice. For example, if you
decide to voluntarily cancel your registration six months before a 3 year study is
scheduled to be submitted, all progress reports and other information necessary to
establish that you have been conducting the study in an acceptable and good faith manner
must have been submitted to the Agency, before EPA will consider granting an existing
stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE UNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FDFRA 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.
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SECTION VI.
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person listed in Attachment A, 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 (Attachment B) and
a completed Requirements Status and Registrant's Response Form (Attachment C) and any other
documents required by this Notice, and should be submitted to the contact person identified in
Attachment A. If the voluntary cancellation or generic data exemption option is chosen, only the
Data CaU-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,
Dan Barolo, Direc/o?
Special Review
and Reregistration Division
96
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Attachment A
Chemical Status Sheet
101
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THYMOL: DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have produces)
containing thymol.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required
by this notice, and point of contact for inquiries pertaining to the reregistration of thymol. This
attachment is to be used in conjunction with (1) the Generic Data Call-Li Notice, (2) the Generic
Data Call-In Response Form (Attachment B), (3) the Requirements Status and Registrant's Form
(Attachment C), (4) EPA's Grouping of End-Use Products for Meeting Acute Toxicology Data
Requirement (Attachment D).
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for thymol are
contained in the Requirements Status and Registrant's Response. Attachment C. The Agency
has concluded that additional data on thymol are needed for technical grade of the active
ingredient. 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 thymol products.
INQUIRIES. AND RESPONSES TO THIS NOTICE
If you have any questions regarding the product specific database of thymol, please
contact Frank Rubis at (703) 308-8184.
If you have any questions regarding the product generic data requirements and procedures
established by this Notice, please contact Kathleen Depukat at (703) 308-8587.
All responses to this Notice for the Generic data requirements should be submitted to:
Kathleen Depukat
Accelerated Reregistration Branch (H7508W)
Special Review and Reregistration Division
Office of Pesticide Programs
401 M Street, S.W.
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: THYMOL
103
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Attachment B
Generic DCI Response Forms (Form A) plus Instructions
105
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SPECIFIC INSTRUCTIONS FOR THE GENERIC DATA CALL-IN RESPONSE FORM
This Form is designed to be used to respond to call-ins for generic and product specific data for
the purpose of reregistering pesticides under the Federal Insecticide Fungicide and Rodenticide
Act. Fill out this form each time you are responding to a data call-in for which EPA has sent
you the form entitled "Requirements Status and Registrant's Response."
Items 1-4 will have been preprinted on the form Items 5 through 7 must be completed by the
registrant as appropriate Items 8 through 11 must be completed by the registrant before
submitting a response to the Agency.
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 suggesting for reducing this burden, to Chief, Information Policy Branch,
PM-223, U S Environmental Protection Agency, 401M St., S.W., Washington, DC 20460; and
to the Office of Management and Budget, Paperwork Reduction Project 2070-0107, Washington,
DC 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number and address.
Item 2. This item identifies the ease number, ease name, EPA chemical number and
chemical name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the EPA product registrations relevant to the data call-in.
Please note that you are also responsible for informing the Agency of your
response regarding any product that you believe may be covered by this data
call-in but that is not listed by the Agency in Item 4. You must bring any such
apparent omission to the Agency's attention within the period required for
submission of this response form.
Item 5. Cheek this item for each product registration you wish to cancel voluntarily. If
a registration number is listed for a product for which you previously requested
voluntary cancellation, indicate in Item 5 the date of that request. You do not
need to complete any item on the Requirements Status and Registrant's Response
Form for any product that is voluntarily cancelled.
Item 6a. Check this item if this data call-in is for generic data as indicated in Item 3 and
if you are eligible for a Generic Data Exemption for the chemical listed in Item
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2 and used in the subject product. By electing this exemption, you agree to the
terms and conditions of a Generic Data Exemption as explained in the Data
Call-in Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA
registration Number of each registered source of that active ingredient that
you use in your product.
Typically, if you purchase an EPA-registered product from one or more
other producers (who, with respect to the incorporated product, are in
compliance with this and-any other outstanding Data Call-in Notice), and
incorporate that product into all your products, you may complete this
item for all products listed on this form If, however, you produce the
active ingredient yourself, or use any unregistered product (regardless of
the fact that some of your sources are registered), you may not claim a
Generic Data Exemption and you may not select this item.
Item 6b. Check this Item if the data call-in is a generic data call-in as indicated in Item 3
and if you are agreeing to satisfy the generic data requirements of this data
call-in. Attach the Requirements Status and Registrant's Response Form that
indicates how you will satisfy those requirements.
Item 7a. Check this item if this call-in if a data call-in as indicated in Item 3 for a
manufacturing use product (MUP), and if your product is a manufacturing use
product for which you agree to supply product-specific data. Attach the
Requirements Status and Registrants' Response Form that indicates how you will
satisfy those requirements.
Item 7b. Check this item if this call-in is a data call-in for an end use product (EUP) as
indicated in Item 3 and if your product is an end use product for which you agree
to supply product-specific data. Attach the Requirements Status and Registrant's
Response Form that indicates how you will satisfy those requirements.
Item 8. This certification statement must be signed by an authorized representative of
your company and the person signing must include his/her title. Additional pages
used in your response must be initialled and dated in the space provided for the
certification.
Item 9. Enter the date of signature.
Item 10. Enter the name of the person EPA should contact with questions regarding your
response.
Item 11. Enter the phone number of your company contact.
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Attachment C
Requirements Status and Registrants' Response Forms
(Form B) plus Instructions
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SPECIFIC INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANTS RESPONSE FORM
Generic Data
This form is designed to be used for registrants to respond to call-in- for generic and
product-specific data as part of EPA's reregistration program under the Federal Insecticide
Fungicide and Rodenticide Act. Although the form is the same for both product specific and
generic data, instructions for completing the forms differ slightly. Specifically, options for
satisfying product specific data requirements do not include (1) deletion of uses or (2) request
for a low volume/minor use waiver. These instructions are for completion of generic data
requirements.
EPA has developed this form individually for each data call-in addressed to each registrant, and
has preprinted this form with a number of items. DO NOT use this form for any other active
ingredient.
Items 1 through 8 (inclusive) will have been preprinted on the form. You must complete all
other items on this form by typing or printing legibly.
Public reporting burden for this collection of information is estimated to average 30 minutes per
response, including time for reviewing instructions, searching existing data sources, gathering
and mamtaining 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 suggesting for reducing this burden, to Chief, Information Policy Branch,
PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, D.C. 20460;
and to the Office of Management and Budget, Paperwork Reduction Project 2070-0107,
Washington, D.C. 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number, and address.
Item 2. This item identifies the case number, case name, EPA chemical number and
chemical name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the guideline reference numbers of studies required to support
the product(s) being reregistered. These guidelines, in addition to requirements
specified in the Data Call-In Notice, govern the conduct of the required studies.
Item 5. This item identifies the study title associated with the guideline reference number
and whether protocols and I, 2, or 3-year progress reports are required to be
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Item 6.
submitted in connection with the study. As noted in Section m of the Data
Call-in Notice, 90-day progress reports are required for all studies.
If an asterisk appears in Item 5, EPA has attached information relevant to
this guideline reference number to the Requirements Status and
Registrant's Response Form.
This item identifies the code associated with the use pattern of the pesticide. A
brief description of each code follows:
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
K.
L.
M.
N.
O.
Terrestrial food
Terrestrial feed
Terrestrial non-food
Aquatic food
Aquatic non-food outdoor
Aquatic non-food industrial
Aquatic non-food residential
Greenhouse food
Greenhouse non-food crop
Forestry
Residential
Indoor food
Indoor non-food
Indoor medical
Indoor residential
Item 7.
This item identifies the code assigned to the substance that must be used for
testing. A brief description of each code follows.
EP
MP
MP/TGAI
PAI
PAI/M
PAI/PAIRA
PAIRA
PAIRA/M
PAIRA/PM
TEP
TEP *
End-Use Product
Manufacturing-Use Product
Manufacturing-Use Product and Technical
Grade Active Ingredient
Pure Active Ingredient
Pure Active Ingredient and Metabolites
Pure Active Ingredient or Pure Active
Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled and
Metabolites
Pure Active Ingredient Radiolabelled and
Plant Metabolites
Typical End-Use Product
Typical End-Use Product, Percent Active
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TEP/MET
TEP/PAI/M
TGAI/PAIRA
TGAI
TGAI/TEP
TGAI/PAI
MET
IMP
DEGR
*See: guideline comment
Ingredient Specified
Typical End-Use Product and Metabolites
Typical End-Use Product or Pure Active
Ingredient and Metabolites
Technical Grade Active Ingredient or Pure
Active Ingredient Radiolabelled
Technical Grade Active Ingredient
Technical Grade Active Ingredient of
Typical End-Use Product
Technical Grade Active Ingredient or Pure
Active Ingredient
Metabolites
Impurities
Degradates
Item 8. This item identifies the time frame allowed for submission of the study or
protocol identified in item 2. The time frame runs from the date of your receipt
of the Data Call-In Notice.
Item 9. Enter the appropriate Response Code or Codes to show how you intend to comply
with each data requirement. Brief descriptions of each code follow. The Data
Call-In Notice contains a fuller description of each of these options.
1. (Developing Data) I will conduct a new study and submit it within the
time frames specified in item 8 above. By indicating that I have chosen
this option, I certify that I will comply with all the requirements
pertaining to the conditions for submittal of this study as outlined in the
Data Call-in Notice and that I will provide the protocol and progress
reports required in item 5 above.
2. (Agreement to Cost Share) I have entered into an agreement with one or
more registrants to develop data jointly. By indicating that I have chosen
this option, I certify that I will comply with all the requirements
pertaining to sharing in the cost of developing data as outlined in the Data
Call-in Notice.
3. (Offer to Cost Share) I have made an offer to enter into an agreement with
one or more registrants to develop data jointly. I am submitting a copy of
the form "Certification of Offer to Cost Share in the Development of
Data" that describes this offer/agreement. By indicating that I have
chosen this option, I certify that I will comply with all the requirements
pertaining to making an offer to share in the cost of developing data as
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outlined in the Data Call-In Notice.
4. (Submitting Existing Data) I am submitting an existing study that has
never before been submitted to EPA. By indicating that I have chosen this
option, I certify that this study meets all the requirements pertaining to the
conditions for submittal of existing data outlined in the Data Call-in
Notice and I have attached the needed supporting information along with
this response.
5. (Upgrading a Study) I am submitting or citing data to upgrade a study that
EPA has classified as partially acceptable and potentially upgradeable. By
indicating that I have chosen this option, I certify that I have met all the
requirements pertaining to the conditions for submitting or citing existing
data to upgrade a study described in the Data Call-in Notice. I am
indicating on attached correspondence the Master Record Identification
Number (MRID) that EPA has assigned to the data that I am citing as well
as the MRID of the study I am attempting to upgrade.
6. (Citing a Study) I am citing an existing study that has been previously
classified by EPA as acceptable, core, core minimum, or a study that has
not yet been reviewed by the Agency. I am providing the Agency's
classification of the study.
7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-in Notice
and I request a low-volume minor use waiver of the data requirement. I
am attaching a detailed justification to support this waiver request
including, among other things, all information required to support the
request. I understand that, unless modified by the Agency in writing, the
data requirement as stated in the Notice governs.
9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than low volume minor-use data waivers in the Data Call-in
Notice and I request a waiver of the data requirement. I am attaching an
identification of the basis for this waiver and a detailed justification to
support this waiver request. The justification includes, among other
things, all information required to support the request. I understand that,
unless modified by the Agency in writing, the data requirement as stated
in the Notice governs.
Item 10. This item must be signed by an authorized representative of your company. The
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person signing must include his/her title, and must initial and date all other pages
of this form. ••-'•- •"•. >.r;;^^S: ••-'; '••-'-••' ,-•'.•-.:•
Item 11. Enter the date of signature.
Item 12. Enter the name of the person EPA should contact with questions regarding your
response.
Item 13. Enter the phone number of your company contact.
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Attachment D
List of Registrants) sent this DCI
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APPENDIX G
Product Specific Data Call-in
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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 A of this Notice, the Data Call-in Chemical Status Sheet, to
submit certain product specific data as noted herein to the U.S. Environmental Protection
Agency (EPA, the Agency). These data are necessary to maintain the continued registration of
your produces) containing this active ingredient. Within 90 days after you receive this Notice
you must respond as set forth in Section HI below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments A through G; or
2. Why you believe you are exempt from the requirements listed in this Notice and
in Attachment C, Requirements Status and Registrant's Response Form, (see
section ffl-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 ni-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list of
all of your products subject to this Notice in Attachment B, Data Call-in Response Form, as well
as a list of all registrants who were sent this Notice (Attachment F).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-0107
(expiration date 12-31-92).
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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 n - Data Required By This Notice
Section HI- Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse
Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
A- Data Call-In Chemical Status Sheet
B - Product-Specific Data Call-In Response Form
C - Requirements Status and Registrant's Response Form
D - EPA Grouping of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
E - EPA Acceptance Criteria
F - List of Registrants Receiving This Notice
G - Cost Share and Data Compensation Forms, and Product Specific Data Report
~3rm
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
DATA REQUIRED BY THIS NOTICE
n-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment C,
Requirements Status and Registrant's Response Form. Depending on the results of the studies
required in this Notice, additional testing may be required.
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n-B.
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment C, Requirements Status and Registrant's Response Form, within the time frames
provided.
n-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 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.
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)].
H-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c¥2)(K) 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 m. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
m-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
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failure to comply with this Notice are presented in Section IV-A and IV-B.
ffi-B. OPTIONS FOR RESPONDING TO TELE 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 ffl-C. A discussion of options relating to
requests for data waivers is contained in Section ffl-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 B and
Attachment C. 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 voluntary
cancellation option is selected or unless the product is identical to another (refer to the instructions
for completing the Data Call-In Response Form in Attachment B). Please note that the company's
authorized representative is required to sign the first page of the Data Call-In Response Form and
Requirements Status and Registrant's Response Form (if this form is required) and initial any
subsequent pages. The forms contain separate detailed instructions on the response options. Do not
alter the printed material. If you have questions or need assistance in preparing your response, call
or write the contact person(s) identified in Attachment A.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by requesting
voluntary cancellation of your product(s) containing the active ingredient that is the subject of this
Notice. If you wish to voluntarily cancel your product, you must submit a completed Data Call-in
Response Form, indicating your election of this option. Voluntary cancellation is item number 5
on the Data -Call-In Response Form. If you choose this option, this is the only form that you are
required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your product
after the effective date of cancellation must be in accordance with the Existing Stocks provisions
of this Notice which are contained in Section IV-C.
2. Satisfying the Product Specific Data Requirements of this Notice There are various
options available to satisfy the product specific data requirements of this Notice. These options are
discussed in Section m-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 of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements.
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3- Request for Product Specific Data Waivers. Waivers for product specific data are
discussed in Section ffl-D of this Notice and are covered by option 7 on the Requirements Status
and Registrant's Response Form. If you choose one of these options, you must submit both forms
as well as any other information/data pertaining to the option chosen to address the data
requirement.
m-C. SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-in Response Form that you agree to satisfy the product
specific data requirements (i.e. you select item number 7a or 7b), then you must select one of the
six options on the Requirements Status and Registrant's Response Form related to data production
for each data requirement. Your option selection should be entered under item number 9,
"Registrant Response." The six options related to data production are the first six options discussed
under item 9 in the instructions for completing the Requirements Status and Registrant's Response
Form. These six options are listed immediately below with information in parentheses to guide
registrants to additional instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified time frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1. Developing Data — If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced herein and
in the attachments. All data generated and submitted must comply with the Good Laboratory
Practice (GLP) rule (40 CFR Part 160), be conducted according to the Pesticide Assessment
Guidelines (PAG), and be in conformance with the requirements of PR Notice 86-5.
The time frames in the Requirements Status and Registrant's Response Form are the time
frames that the Agency is allowing for the submission of completed study reports. The noted
deadlines run from the date of the receipt of this Notice by the registrant. If the data are not
submitted by the deadline, each registrant is subject to receipt of a Notice of Intent to Suspend the
affected registration(s).
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If you cannot submit the data/reports to the Agency in the time required by this Notice and
intend to seek additional time to meet the requirements(s), you must submit a request to the Agency
which includes: (1) a detailed description of the expected difficulty and (2) a proposed schedule
including alternative dates for meeting such requirements on a step-by-step basis. You must explain
any technical or laboratory difficulties and provide documentation from the laboratory performing
the testing. While EPA is considering your request, the original deadline remains. The Agency
will respond to your request in writing. If EPA does not grant your request, the original deadline
remains. Normally, extensions can be requested only in cases of extraordinary testing problems
beyond the expectation or control of the registrant. Extensions will not be given in submitting the
90-day responses. Extensions will not be considered if the request for extension is not made in a
timely fashion; in no event shall an extension request be considered if it is submitted at or after the
lapse of the subject deadline.
Option 2, Agreement to Share in Cost to Develop Data — 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 formed. Such evidence
may be your letter offering to join in an agreement and the other registrant's acceptance of your
offer, or a written statement by the parties that an agreement exists. The agreement to produce the
data need not specify all of the terms of the final arrangement between the parties or the mechanism
to resolve the terms. Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the
agreement they may resolve their differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development — This option only applies to
acute toxicity and certain efficacy data as described in option 2 above. If you have made an offer
to pay in an attempt to enter into an agreement or amend an existing agreement to meet the
requirements of this Notice and have been unsuccessful, you may request EPA (by selecting this
option) to exercise its discretion not to suspend your registration(s), although you do not comply
with the data submission requirements of this Notice. EPA has determined that as a general policy,
absent other relevant considerations, it will not suspend the registration of a product of a registrant
who has in good faith sought and continues to seek to enter into a joint data development/cost
sharing program, but the other registrant(s) developing the data has refused to accept your offer.
To qualify for this option, you must submit documentation to the Agency proving that you have
made an offer to another registrant (who has an obligation to submit data) to share in the burden
of developing that data. You must also submit to the Agency a completed EPA Form 8570-32,
Certification of Offer to Cost Share in the Development of Data, Attachment G. In addition, you
must demonstrate that the other registrant to whom the offer was made has not accepted your offer
to enter into a cost sharing agreement by including a copy of your offer and proof of the other
registrant's receipt of that offer (such as a certified mail receipt). Your offer must, in addition to
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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 arbitration aspr%!ded by FEFRA section 3(c)(2)(B)(iii) and must
not qualify this offer. The other registrant must also inform EPA of its election of an option to
develop and submit the data required by tins 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 to initiation of suspension proceedings, unless
you commit to submit, and do submit the required data in the specified time frame. In such cases,
the Agency generally will not grant a time extension for submitting the data.
Option 4. Submitting an Existing Study — If you choose to submit an existing study in
response to this Notice, you must determine that the study satisfies the requirements imposed by
this Notice. You may only submit a study that has not been previously submitted to the Agency
or previously cited by anyone. Existing studies are studies which predate issuance of this Notice.
Do not use this option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the required
date of submission. The Agency may determine at any time that a study is not valid and needs to
be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly met:
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 160.3ft') " 'raw data' means any laboratory worksheets, records,
memoranda, notes, or exact copies thereof, that are the result of original
observations and activities of a study and are necessary for the reconstruction and
evaluation of the report of that study. In the event that exact transcripts of raw data
have been prepared (e.g., tapes which have been transcribed verbatim, dated, and
verified accurate by signature), the exact copy or exact transcript may be substituted
for the original source as raw data. 'Raw data' may include photographs, microfilm
or microfiche copies, computer printouts, magnetic media, including dictated
observations, and recorded data from automated instruments." The term
"specimens", according to 40 CFR 160.3(k), means "any material derived from a
test system for examination or analysis."
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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 CER Part 160. Registrants must also certify at the tune 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 EEFRA 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 you know of a study pertaining to any requirement in this Notice which does not meet
the criteria outlined above but does contain factual information regarding unreasonable adverse
effects, you must notify the Agency of such a study. If such study is in the Agency's files, you
need only cite it along with the notification. If not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study - If a study has been classified as partially acceptable and
upgradeable, you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the requirement is
not satisfied, you may still be required to submit new data normally without any time extension.
Deficient, but upgradeable studies will normally be classified as supplemental. However, it is
important to note that not all studies classified as supplemental are upgradeable. If you have
questions regarding the classification of a study or whether a study may be upgraded, call or write
the contact person listed in Attachment A. 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
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and why the study should be rated as acceptable to EPA. Your submission must also specify the
MRID number(s) of the study which you are attempting to upgrade and must be in conformance
with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as unacceptable
and determined by the Agency as not capable of being upgraded.
This option 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 Option 4 above, apply to all
data submissions intended to upgrade studies. Additionally your submission of data intended to
upgrade studies must be accompanied by a certification that you comply with each of those criteria
as well as a certification regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies - - If you choose to cite a study that has been previously
submitted to EPA, that study must have been previously classified by EPA as acceptable or it must
be a study which has not yet been reviewed by the Agency. Acceptable toxicology studies
generally will have been classified as "core-guideline" or "core minimum," For all other
disciplines the classification would be "acceptable." With respect to any studies for which you wish
to select this option you must provide the MRID number of the study you are citing and, if the
study has been reviewed by the Agency, you must provide the Agency's classification of the study.
If you are citing a study of which you are not the original data submitter, you must submit
a completed copy of EPA Form 8570-31, Certification with Respect to Data Compensation
Requirements.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Form and the Requirements
Status and Registrant's Response Form, as appropriate.
m-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 FEFRA. If the Agency denies your waiver request, you must choose an option for
meeting the data requirements of this Notice within 30 days of the receipt of the Agency's decision.
You must indicate and submit the option chosen on the Requirements Status and Registrant's
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Response Form. Product specific data requirements for product chemistry, acute toxicity and
efficacy (where appropriate) are required for all products and the Agency would grant a waiver only
under extraordinary circumstances. You should also be aware that submitting a waiver request will
not automatically extend the due date for the study in question. Waiver requests submitted
without adequate supporting rationale will be denied and the original due date will remain in force.
IV-A.
OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-in Notice, pursuant to
FEFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study
as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task Forces,
failure to comply with the terms of an agreement or arbitration concerning joint data
development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies,
as required by Section ni-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or failure
of a registrant on whom you rely for a generic data exemption either to:
a. inform EPA of intent to develop and submit the data required by this Notice
on a Data CaU-In Response Form and a Requirements Status and Registrant's
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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 to submit and do submit the required data in the
specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds for
suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-In Notice or other documents incorporated
by reference (including, as applicable, EPA Pesticide Assessment Guidelines, Data
Reporting Guidelines, and GeneTox Health Effects Test Guidelines) regarding the design,
conduct, and reporting of required studies. Such requirements include, but are not limited
to, those relating to test material, test procedures, selection of species, number of animals,
sex and distribution of animals, dose and effect levels to be tested or attained, duration of
test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation of
any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of reporting,
the completeness of results, and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or included in this Notice or contained
in PR 86-5. All studies must be submitted in the form of a final report; a preliminary
report will not be considered to fulfill the submission requirement.
IV-C. EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing stocks
of a pesticide product which has been suspended or cancelled if doing so would be consistent with
the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally not be
consistent with the Act's purposes. Accordingly, the Agency anticipates granting registrants
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permission to sell, distribute, or use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your product(s) which may be
suspended for failure to comply with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be consistent with the Act. You
must also explain why an "existing stocks" provision is necessary, including a statement of the
quantity of existing stocks and your estimate of the time required for their sale, distribution, and
use. Unless you meet this burden the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice and
your product is in full compliance with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this Notice is due, to sell, distribute,
or use existing stocks. Normally, the Agency will allow persons other than the registrant such as
independent distributors, retailers and end users to sell, distribute or use such existing stocks until
the stocks are exhausted. Any sale, distribution or use of stocks of voluntarily cancelled products
containing an active ingredient for which the Agency has particular risk concerns will be
determined on case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required by
this Notice will not result in the Agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was due unless you demonstrate
to the Agency that you are in full compliance with all Agency requirements, including the
requirements of this Notice. For example, if you decide to voluntarily cancel your registration six
months before a 3 year study is scheduled to be submitted, all progress reports and other
information necessary to establish that you have been conducting the study in an acceptable and
good faith manner must have been submitted to the Agency, before EPA will consider granting an
existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT
SONABLE
ADVERSE
SCTS
Registrants are reminded that EEFRA 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 A, the Data Call-in Chemical Status Sheet.
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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 B for generic data and
Attachment C for product specific data) and any other documents required by this Notice, and
should be submitted to the contact person(s) identified in Attachment A. If the voluntary
cancellation or generic data exemption option 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,
Daniel M. Barolo, Direoror
Special Review and
Reregistration Division
Attachments
A-
B-
C-
D-
E-
F-
G-
Data Call-in Chemical Status Sheet
Product-Specific Data Call-in Response Form
Requirements Status and Registrant's Response Form for the Product Specific Data
Call-in
EPA Grouping
of End-Use Products for Meeting
Toxicology Data
Requirements for Reregistration
EPA Acceptance Criteria
List of Registrants Receiving This Notice
Cost Share and Data Compensation Forms, and Product Specific Data Report Form
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ATTACHMENT A
CHEMICAL STATUS SHEET
141
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THYMOL: DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing thymol.
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 thymol.
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 B), (3) the Requirements Status and
Registrant's Form (Attachment C), (4) EPA's Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirement (Attachment D), (5) the EPA Acceptance Criteria (Attachment E),
(6) a list of registrants receiving this DCI (Attachment F) and (7) the Cost Share and Data
Compensation Forms in replying to this thymol Product Specific Data Call-in (Attachment G).
Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for thymol are contained
in the Requirements Status and Registrant's Response. Attachment C. The Agency has concluded
that additional data on thymol are needed for specific products. These data are required to be
submitted to the Agency within the time frame listed. These data are needed to fully complete the
reregistration of all eligible thymol products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic database of thymol, please contact Kathleen
Depukat at (703) 308-8587.
If you have any questions regarding the product specific data requirements and procedures
established by this Notice, please contact Frank Rubis at (703) 308-8184.
to:
All responses to this Notice for the Product Specific data requirement should be submitted
Frank Rubis
Planning and Reregistration Branch (H7508W)
Special Review and Reregistration Division
Office of Pesticide Programs
401 M Street, S.W.
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: THYMOL
143
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ATTACHMENT B
PRODUCT SPECIFIC DATA CALL-IN RESPONSE FORMS (Form A)
PLUS INSTRUCTIONS
145
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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 reregistration 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 Srll. 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 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.
147
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ATTACHMENT C
PRODUCT SPECIFIC REQUIREMENT STATUS AND
REGISTRANT'S RESPONSE
FORMS (Form B) PLUS INSTRUCTIONS
149
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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 of the required studies.
Note that series 61 and 62 in product chemistry are now listed under 40 CFR
158.155 through 158.180, Subpartc.
Item 5. 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 on 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 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 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).
151
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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
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 m-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 ffl-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 m-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 format. If I cite another 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
152
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request, I will not be require to supply the data pursuant to Section 3(c) (2) (B) of
FEFRA. If the Agency denies my waiver request, I must choose a method of
meeting the data requirements of this Notice by the due date stated by this Notice.
In this case, I must, within 30 days of my receipt of the Agency's written decision,
submit a revised "Requirements Status 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 FJ»A can ensure that its records
are correct.
153
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ATTACHMENT D
, GROUPING OF END-USE PRODUCTS FOR MEETING
DATA REQUIREMENTS FOR REREGISTRAHON
155
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EPA'S DECISION NOT TO BATCH END-USE PRODUCTS CONTAINING THYMOL
FOR PURPOSES OF MEETING ACUTE TOXICITY DATA REQUIREMENTS FOR
REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the
acute toxicity data requirements for reregistration of products containing the active ingredient
thymol, the Agency considered batching products. This process involves grouping similar
products for purposes of acute toxicity. Factors considered in the sorting process include each
product's active and inert ingredients (identity, percent composition and biological activity), type
of formulation (e.g., emulsifiable concentrate, aerosol, wettable powder, granular, etc.), and
labeling (e.g., signal word, use classification, precautionary labeling, etc.).
However, batching of products containing thymol was not possible after considering the
available information described above. Table I lists all the end-use products containing thymol.
These products were either considered not to be similar for purposes of acute toxicity or the
Agency lacked sufficient information for decision making purposes. Registrants of these
products are responsible for meeting the acute toxicity data requirements for each product.
Registrants must generate all the required acute lexicological studies for each of their
products. If a registrant chooses to rely upon previously submitted acute toxicity data, he/she
may do so provided that the data base is complete and valid by today's standards (see acceptance
criteria attached), the formulation tested is considered by EPA to be similar for acute toxicity,
and the formulation has not been signfficanfly altered since submission and acceptance of the
acute toxicity data. Regardless of whether new data is generated or existing data is cited, the
registrant must clearly identify the material tested by its EPA registration number.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-in Notice and its attachments appended to the RED. The DCI
Notice contains two response forms which are to be completed and submitted to the Agency
within 90 days of receipt. The first form, "Data Call-In Response," asks whether the registrant
will meet the data requirements for each product. The second form, "Requirements Status and
Registrant's Response," lists the product specific data required for each product, including the
standard six acute toxicity tests. A registrant must select one of the following options:
Developing Data (Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing
Study (Option 5) or Citing an Existing Study (Option 6). Since the end-use products containing
thymol could not be batched, registrants cannot choose from the remaining options: Cost
sharing (Option 2) or Offers to Cost Share (Option 3).
Table I. End-Use Products Containing Thymol
EPA KEG. NO.
11715-211
34810-18
34810-19
34810-22
45735-2
% of Thymol &
Other Active Ingredients
1.300
0.065 Bitrex
13.00
7.00
7.00 Orthp-phenyl phenol
.0.027
0.027 Orthb-phenyl phenol
o;o35
0.065 Benzyldiethyl [(2,6-Xylycarbomyl)methyl]
ammonium saccharide
Formulation Type
aerosol
liquid
liquid
liquid
liquid
157
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ATTACHMENT E
EPA ACCEPTANCE CRITERIA
159
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SUBDIVISION D
Guideline
Series 61
Series 62
Series 63
Study Title
Product Identity and Composition
Analysis and Certification of Product Ingredients
Physical and Chemical Characteristics
161
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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 at < 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.
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.
7.
163
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_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.
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).
164
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62 Analysis and Certification of Product Ingredients
2.
3.
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, 7, and 8.
Does your study meet the following acceptance criteria?
*• Five or more representative samples (batches in case of batch
process) analyzed for each active ingredient and all impurities
present at >_ 0.1%.
_ Degree of accountability or closure _>. ca 98 %.
_ Analyses conducted for certain trace toxic impurities 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.].
Complete and detailed description of each step in analytical method
used to analyze above samples.
Statement of precision and accuracy of analytical method used to
analyze above samples.
Identities and quantities (including mean and standard deviation)
provided for each analyzed ingredient.
Upper and lower certified limits proposed for each active
ingredient and intentionally added inert along with explanation of
how the limits were determined.
Upper certified limit proposed for each impurity present at _>.
0.1% and for certain toxicologically significant impurities at
<0.1 % along with explanation of how limit determined.
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.
Analytical methods (as discussed in #9) to verify certified limits
validated as to their precision and accuracy.
4.
5-.
6.
7.
10.
165
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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 20-25° 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 °C
Any observed decomposition reported
63-6 Boiling Point
Reported in °C
Pressure under which B.P. measured reported
Any observed decomposition reported
63-7 Density, Bulk Density, Specific Gravity
Measured at about 20-25° C
Density of technical grade active ingredient reported in g/ml or the specific gravity of
liquids reported with reference to water at 20° C. [Note: Bulk density of registered
products may be reported in Ibs/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 20-25° C
Reported in g/100 ml (other units like ppm acceptable if sparingly soluble)
167
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63-9 Vapor Pressure
Measured at 25° C (or calculated by extrapolation from measurements made at higher
temperature if pressure too low to measure at 25° 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
20-25 °C)
63-11 Octanol/water Partition Coefficient
Measured at about 20-25° 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 20-25° 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
168
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SUBDIVISION F
Guideline Study Title
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
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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. 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.
171
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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 before dosing.
9. Application site at least 10% of body surface area.
10. Application site covered with a porous nomrritating 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.
172
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81-3 Acute Inhalation Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the foEowing acceptance criteria?
1.
2."
3.
4."
6.
7.
8."
9.
10."
11.
12."
13."
14.
Identify material tested (technical, end-use product, etc).
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 /tm or less).
At least 5 young adult rats/sex/group.
Dosing, at least 4 hours by inhalation.
Chamber air flow dynamic, at least 10 air changes/hour, at least 19 % oxygen
content.
Chamber temperature, 22° C (±2°), relative humidity 40-60%.
Monitor rate of air flow.
Monitor actual concentrations of test material in breathing zone.
Monitor aerodynamic particle size for aerosols.
Doses tested, sufficient to determine a toxicity category or a limit dose (5 mg/L
actual concentration of respirable substance).
Individual observations at least once a day.
Observation period to last at least 14 days.
Individual body weights.
Gross necropsy on all animals.
173
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81-4 Primary Eye Irritation in the Rabbit
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1.
3.
4."
5-.
6.
7.
8.
Identify material tested (technical, end-use product, etc).
Study not required if material is corrosive, causes severe dermal irritation or has
a pH of <2 or _>_11.5.
6 adult rabbits.
Dosing, instillation into the conjunctiva! sac of one eye per animal.
Dose, 0.1 ml if a liquid; 0.1 ml or not more than 100 mg if a solid, paste or
particulate substance.
Solid or granular test material ground to a fine dust.
Eyes not washed for at least 24 hours.
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).
Individual daily observations.
Criteria marked with an * are supplemental and may not be required for every study.
174
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81-5 Primary Dermal Irritation Study
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1.
2."
3."
4."
5.
6."
7.
8."
9."
10."
11.*
Identify material tested (technical, end-use product, etc).
Study not required if material is corrosive or has a pH of <2 or J>.11.5.
6 adult animals.
Dosing, single dermal.
Dosing duration 4 hours.
Application site shaved or clipped at least 24 hours prior to dosing.
Application site approximately 6 cm2.
Application site covered with a gauze patch held in place with nonirritating tape.
Material removed, washed with water, without trauma to application site.
Application site examined and graded for irritation at 1, 24, 48 and 72 hr, then
daily until normal or 14 days (whichever is shorter).
Individual daily observations.
Criteria marked with an * are supplemental and may not be required for every study
175
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81-6 Dermal Sensitization in the Guinea Pig
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1.
2.
3."
7.
Identify material tested (technical, end-use product, etc).
Study not required if material is corrosive or has a pH of <2 or _>_11.5.
One of the 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.
Complete description of test.
Reference for test.
Test followed essentially as described in reference document.
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.
176
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ATTACHMENT F
LIST OF ALL REGISTRANTS SENT THIS DATA CALL-IN
NOTICE
177
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ATTACHMENT G
COST SHARE AND DATA COMPENSATION FORMS
179
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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
Approval Expires 12-31-92
Public reporting burden forthis 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 ^formation, 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 Nam*
Chemical Nam*
Company Number
EPA Chemical Number
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
ofi'er to be bound by arbitration decision under section 3(c)(2)(B)(Hi) 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)
L
Oat* 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'* Authorized Representative
Date
Nam* and Title (Pleas* Typ* or Print)
EPA Form 8570-32
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EPA
Protection Agency
20460
United States Environmental
Washington, DC
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Farm Approval
OUB No. 20704108
Approval Expire* 12<31«92
Public reporting burden for this collection off 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 ClWJnfenn^ Potty
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 Nam*
Chamlcal Nam*
Company Numbar
I Certify that:
1 For ^ch study cited in support of reregfetratten under the Federal Insecticide, Fungicide and Rodentidde Afit
(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 reregistratfon under FIFRA that is NOT an exdusivejUse 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 section 3(c)(D(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, H any. The
companies I have notified are: (check one)
[ 1 An companies on the data submitters' Kst for he active ingredient listed on this form (Cite-All
Method or Cite-All option under the Selective Method). (Also sign the General Offer to Pay
below.)
[ 1 The companies who have submitted the studies listed on the back of this form or attached
sheets, or indicated on the attached •Requirements Status and Registrants' Response Form,"
3. That I have previously complied with section 3(C)(1)(D) of RFRA for the studies I have cfted In support of
ceregistratton under FIFRA.
Slgnstura
Nama and Tltla (Piaaaa Typ* or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regart to the
leregistratfen of my products, to th extent required by FIFRA section 3(c)(1)(D) and 3(c)(2)(D).
Signature
Nama and Till* (Pteaaa Typa or Print)
EPA Form §570-31 (4-90)
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