United State* Office of Prevention, Pesticides H% 738-P/-93-011
Environmental Protection and Toxic Substances September 1993
Aoency IH-7S08WI
739R93011
&EPA Reregistration
Eligibility
Decision Document
DAMINOZIDE
Printed oh Recycled Paper
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION. PESTICIDES AND
TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide active ingredient daminozide. The
enclosed Reregistration Eligibility Decision (RED) document contains the Agency's evaluation of
the data base of this chemical, its conclusions of the potential human health and environmental risks
of the current product uses, and its decisions and conditions under which these uses and products
will be eligible for reregistration. The RED includes the data and labeling requirements for
products for reregistration.
To assist you with a proper response, read the enclosed document entitled "Pesticide
Reregistration Handbook". This handbook also refers to other enclosed documents which include
further instructions. You must follow all instructions and submit complete and timely responses.
The first set of required responses are due 90 days from the date of this letter. The second
set of required responses are due 8 months from the date of this letter. Complete and timely
responses will avoid the Agency taking the enforcement action of suspension against your products.
If you have questions on the product specific data requirements or wish to meet with the
Agency, please contact the Special Review and Reregistration Division representative Franklin Gee
at (703) 308-8008. Address any questions on required generic data to the Special Review and
Reregistration Division representative Andrew Ertman at (703) 308-8063.
Sincerely yours,
Daniel M. Barolo, Di
Special Review and
Reregistration Division
Enclosures
Recycled/Recyclable
Printed with Soy/Canola Ink on piper 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-93-007
September 1993
R.E.D. FACTS
Daminozide
Pesticide
Reregistration
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered years ago be reregistered to ensure
that they meet today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks. EPA then reregisters pesticides that can be used without
posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this
and explains why in a Reregistration Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
daminozide, or butanedioic acid mono (2,2-diemthylhydrazide), also known
by the trade name Alar.
Use Profile Daminozide is a systemic growth regulator registered for use on
ornamentals, including potted chrysanthemums and poinsettias, and bedding
plants in enclosed structures such as greenhouses, shadehouses and
interiorscapes. It is formulated as a soluble concentrate and applied as a
pre-plant dip and/or foliar spray.
Regulatory Daminozide was initially registered as a pesticide in the United States
History m 1963 for use on potted chrysanthemums. The first food use, apples,
was registered in 1968. EPA issued a Registration Standard for
daminozide in June 1984 (NTIS PB87-104782), requiring additional
product and residue chemistry, toxicology, worker exposure, ecological
effects and environmental fate data.
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In July 1984, EPA initiated a Special Review of pesticide products
containing daminozide based on findings that daminozide and its degradate
and metabolite, unsymmetrical dimethylhydrazine (UDMH), were
oncogenic (cajused the growth of tumors) at multiple organ sites, in
- multiple species and strains of test animals. The Agency issued a Data
Call-In in 1986 requiring additional toxicology and worker exposure data.
As a result" of the Special Review, the registrant, Uniroyal Chemical
Company, voluntarily cancelled all food use registrations of daminozide on
November 14, 1989. EPA revoked the tolerances (maximum residue
limits) for these food uses in March 1990.
EPA continued to evaluate the risks to workers (mixers, loaders and
applicators) posed by the remaining non-food uses of daminozide, and
: found that those uses did not pose an unreasonable risk. The Agency
allowed the non-food uses to continue in completing the Special Review of
daminozide in October 1992.
Currently, four products (two end-use, one technical and one
formulation intermediate) containing daminozide are registered in the U.S.
Human Health Toxicity
Assessment Daminozide is of very low acute and subacute toxicity. It is placed
in Tbxicity Category IV, indicating the lowest level of acute toxicity, for
oral and inhalation effects, and is placed in Ibxicity Category ffl,
indicating a slightly greater degree of acute toxicity, for dermal effects. A
subchronic feeding study using rats did not produce any discernable toxic
effects.
In carcinogenicity studies using mice, daminozide caused some
increase in the incidence of malignant and benign tumors. UDMH caused
a slight increase in liver tumors in rats, and produced liver vascular tumors
and lung tumors in mice. EPA has classified UDMH as a Group B2,
"probable human carcinogen." Since UDMH is dependent on the presence
of the parent chemical, daminozide also has been classified as a Group B2
carcinogen.
Daminozide produced some maternal toxicity but no developmental
toxicity in rats and rabbits. In a reproduction study using rats, daminozide
caused systemic toxicity at the highest dose levels, but did not cause
reproductive toxicity. Neither daminozide nor UDMH have been shown to
cause mutagenic effects. In metabolism studies, daminozide was rapidly
excreted by minipigs.
"• >C
Dietary Exposure
There are no longer any registered food or feed uses of daminozide,
and all tolerances have been revoked. Dietary exposure therefore is not
anticipated.
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Occupational and Residential Exposure
EPA performed a detailed analysis of the cancer risk to workers
(mixers, loaders and applicators) from exposure to daminozide and
UDMH. The total risk is a sum of the risk from direct exposure to
daminozide (which is converted to UDMH when it is absorbed through the
skin or lungs), plus the risk from exposure to the UDMH contaminant in
commercial products (which increases in the mixing tank, prior to
application).
EPA estimated risks from dermal and inhalation exposure to
daminozide and UDMH for large greenhouse and small greenhouse uses,
assuming application of fine spray (which would result in the greatest
exposure). The estimated combined cancer risks range from 1.4 in 1
million (for workers in large greenhouses) to 5.8 in 10 million (for
workers in small greenhouses). EPA considers these estimated risks to be
reasonable.
In view of the known lexicological properties of daminozide and
UDMH, however, as well as the likelihood of foliar residues, EPA is
strengthening the current 24 hour Reentry Interval, which allows workers
to reenter treated areas during the 24 hours after application if they wear
protective clothing. The Agency instead is requiring a 24-hour Restricted
Entry Interval, which prohibits reentry to perform hand labor for 24 hours
following treatment except under very narrow circumstances, described in
the Worker Protection Standard (WPS) for Agricultural Pesticides.
EPA also is requiring personal protective equipment (PPE) for early
entry workers, consistent with that required for pesticides classified as
Tbxicity Category n for acute dermal toxicity. Post-application exposure
to daminozide is mostly on the hands from handling treated plants.
Therefore, for early entry as allowed by the WPS, level H PPE including
chemical-resistant gloves must be used.
Human Risk Assessment
Daminozide does not pose human dietary risks since food-related uses
are no longer registered and dietary exposure is not anticipated.
Greenhouse workers may be exposed to daminozide dermally or by
inhalation, during or after application of the pesticide to plants. Risks
from this exposure should be mitigated by observing the more stringent 24-
hour Restricted Entry Interval and, in cases where reentry is necessary, by
using the required personal protective equipment including chemical-
resistant gloves. Daminozide is not expected to cause an unreasonable
cancer risk to workers when used in accordance with these requirements,
which will be reflected in product labeling as a result of this RED.
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Environmental
Assessment
Environmental Fate
Daminozide is stable to hydrolysis (it does not decompose readily by
reaction with water); hydrolysis does not contribute significantly to the
dissipation of daminozide in the environment. However, daminozide
degrades rapidly in soil, leaving only volatile compounds and bound
residues, including low levels of the degradate formaldehyde. Thus, its
mobility probably is not a concern. Since registered products are labeled
only for use in confined greenhouse areas, daminozide is not expected to
occur in agricultural runoff or ground water.
Ecological Effects
Since daminozide may be applied only inside greenhouses, eco-
toxicity data were used only to evaluate the hazard to non-target organisms
that could result from misuse or spillage during transport, and to determine
appropriate environmental hazard label statements. Daminozide is
practically non-toxic to mammals, birds and freshwater fish, on an acute
basis. It is slightly toxic to aquatic invertebrates.
Ecological Effects Risk Assessment
Environmental exposure is expected to be minimal when daminozide
is used according to product label directions. Therefore, the ecological
risk from use of daminozide also is expected to be very low.
Additional Data The generic data base for daminozide is substantially complete.
Required However, EPA is requiring additional information on a previously
submitted aerobic soil metabolism study as confirmatory data. EPA also is
requiring product-specific data, including product chemistry and acute
toxicity studies, as well as revised Confidential Statements of Formula and
revised labeling for reregistration of pesticide products containing
daminozide.
Product Labeling All end-use daminozide products must comply with EPA's pesticide
Changes Required product labeling requirements. In addition:
° Compliance with Worker Protection Standard (WPS) - Any
product whose labeling permits use in the production of an
agricultural plant on any agricultural establishment (farm, forest,
nursery or greenhouse) must comply with the labeling requirements
of: ' • • • '••-* -••-• ;- •
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• PR Notice 93-7, "Labeling Revisions Required by the
Worker Protection Standard (WPS)," and
•• PR Notice 93-11, "Supplemental Guidance for PR Notice
93-7."
Unless specifically directed in the RED, all statements required by
these two PR Notices must appear on product labeling exactly as
instructed in the Notices. Labels must be revised by April 21, 1994,
for products distributed or sold by the primary registrant or
supplementally registered distributors, and by October 23, 1995, for
products distributed or sold by anyone.
0 Exclusionary Statement - All end-use product labels must carry
the following statement on the front panel near the product name or
Directions for Use:
"For use only in commercial or research greenhouses or shade
houses."
0 Personal Protective Equipment (PPE) Requirements - All end-
use product labeling must carry the following PPE requirements:
"Applicators and other handlers must wear:
—Coveralls over short-sleeved shirt and short pants
-Chemical-resistant or waterproof gloves (*)
—Chemical-resistant footwear plus socks
—Chemical-resistant headgear for overhead exposure
-Chemical-resistant apron when cleaning equipment, mixing,
or loading" (**)
* See Supplement Three of PR Notice 93-7.
** "Mixing" or "loading" may be removed if the product is
formulated as "ready-to-use."
o Entry Restrictions - A 24-hour Restricted Entry Interval (REI) is
required for all uses, for all end-use products. The Personal
Protective Equipment (PPE) for early entry should be that which is
required for applicators of daminozide, except no apron or respirator
is required. These REI and PPE instructions should be inserted into
the standardized statements required by PR Notice 93-7.
• Single active ingredient products - Adopt these entry
restrictions and remove any conflicting ones from labeling.
• Multiple active ingredient products - Compare these entry
restrictions with those on current labeling and retain the more
protective restrictions.
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Regulatory
Conclusion
g
The use of currently registered pesticide products containin
daminozide in accordance with labeling consistent with the RED and
approved by the Agency will not pose unreasonable risks or adverse efiects
to humans or the environment. Therefore, all uses of these products are
eligible for leregistration.
These daminozide products will be reregistered once the product-
specific data, revised Confidential Statements of Formula and revised
labeling are received and accepted by EPA.
For More
Information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for daminozide during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register.
Tb obtain a copy of the RED document or to submit written comments,
please contact the Pesticide Docket, Public Response and Program
Resources Branch, Field Operations Division (H-7506C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Following the comment period, the daminozide RED document will
be available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
For more information about EPA's pesticide reregistration program,
the daminozide RED, or reregistration of individual products containing
daminozide, please contact the Special Review and Reregistration Division
(H-7508W), OPP, US EPA, Washington, DC 20460, telephone 703-
308-8000.
For information about the health effects of pesticides, or for
assistance in recognizing and managing pesticide poisoning symptoms,
please contact the National Pesticides Telecommunications Network
(NPTN). Call toll-free 1-800-858-7378, between 8:00 am and 6:00 pm
Central Time, Monday through Friday.
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DAMINOZIDE REREGISTRAITON ELIGIBILITY TEAM
r. re •
Office of Pesticide Programs:
Biological-and-Economic- Analysis-Division
Margaret Cogdell
Kitty Keough
Dhol Herzi
Environmental-Fate-and-Effects-Division
Stephanie Syslo
Harry A. Winnik
Jean Holmes
Health-Effects-Division
Shanaz Bacchus
Henry Spencer
Kathleen A. Martin
Flora Chow
Registration-Division
Dolphine Wilson
Sami Malak
Van M. Seabaugh
Special • Review • and • Reregistration • Divi sion
Andrew W. Ertman
Carol Stangel
Jean Frane
Biological-Analysis-Branch
Biological-Analysis-Branch
Economic-Analysis-Branch
Environmental-Fate-and-Groundwater-Branch
Ecological-Effects-Branch
Science-Analysis-and-Coordination-Staff
Occupational-and-Residential-Exposure-Branch
Toxicology-Branch-I
Chemical-Coordination-Branch
Chemical- Coordination-Branch
Fungicide-Herbicide-Branch
Registration-Support-Branch
Registration-Support-Branch
Reregistration-Branch
PolicyPlanning-and-Operations-Branch
Policyand-Special-Projects-Staff
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GLOSSARY OF TERMS AND ABBREVIATIONS
a.i. Active Ingredient
CAS Chemical Abstracts Service
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
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
HOT Highest Dose Tested
LC50 Median Lethal Concentration. A statistically derived concentration of a substance
that can be expected to cause death in 50% of test animals. It is usually
expressed as the weight of substance per weight or volume of water or feed, e.g.,
mg/1 or ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to
cause death in 50% of the test animals when administered by the route indicated
(oral, dermal). It is expressed as a weight of substance per unit weight of animal,
e.g., mg/kg.
LD,0 Lethal Dose-low. Lowest Dose at which lethality occurs
LEL Lowest Effect Level
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking
studies submitted.
N/A Not Applicable
LD
'50
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GLOSSARY OF TERMS AND ABBREVIATIONS (cont.)
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
PPE Personal Protective Equipment
ppm Parts Per Million
REI Restricted Entry Interval
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.
TEP Typical End-Use Product
TGAI Technical Grade of the Active Ingredient
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TABLE OF CONTENTS
DAMINOZIDE REREGISTRATION ELIGIBILITY TEAM i
GLOSSARY OF TERMS AND ABBREVIATIONS u
EXECUTIVE SUMMARY vi
I. INTRODUCTION . -„ i
n. CASE OVERVIEW 2
A. CHEMICAL OVERVIEW 2
B. USE PROFILE 2
C. ESTIMATED USAGE OF PESTICIDE 3
D. DATA REQUIREMENTS 3
E. REGULATORY HISTORY 4
III. SCIENCE ASSESSMENT 4
A. Physical Chemistry Assessment 4
B. Human Health Assessment ,. 5
1. Toxicology Assessment 5
a. Acute Toxicity 6
b. Subchronic Toxicity 6
c. Chronic Toxicity 6
d. Carcinogenicity 7
e. Developmental Toxicity 8
f. Reproductive Toxicity 8
g. Mutagenicity 8
h. Metabolism 9
i. Carcinogenicity Classification 10
j. Reference Dose 10
2. Exposure Assessment 10
a. Dietary Exposure 10
b. Occupational and Residential 11
3. Human Health Risk Assessment 13
a. Dietary 13
b. Occupational and Residential 14
C. Environmental Assessment 18
1. Environmental Fate 18
a. Environmental Chemistry, Fate and Transport 18
b. Environmental Fate Risk Assessment 18
2. Ecological Effects 19
a. Terrestrial Data 19
b. Aquatic Data 19
c. Ecological Effects Risk Assessment 19
3. Data Requirements 19
IV
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IV. RISK MANAGEMENT AND REREGISTRATION DECISION 20
A. Determination of Eligibility ] ' 20
1. Eligibility Decision '.'.'.'.".'.'.'. 20
2. Eligible and Ineligible Uses - 21
B. Regulatory Position 21
1. -Tolerance Reassessment 21
* 2. Labeling Rationale ." . 21
V. ACTIONS REQUIRED BY REGISTRANTS .22
A. Manufacturing-Use Products 22
1. Additional Generic Data Requirements 22
2. Labeling Requirements for Manufacturing-Use Products 22
B. End-Use Products 23
1. Additional Product-Specific Data Requirements 23
2. Labeling Requirements for End-Use Products 24
C. Existing Stocks 25
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 Daminozide
Appendix D - List of Available Related Documents
Appendix E - Pesticide Reregistration Handbook
Appendix F - Generic Data Call-In
Appendix G - Product Specific Data Call-In
Attachment A - Chemical Status Sheet
Attachment B - Product Specific DCI Response Forms (Form A) plus
Instructions
Attachment C - Requirements Status and Registrants' Response Forms
(Form B) plus Instructions
Attachment D - EPA's Grouping of End Use Products for meeting Acute
Toxicology Data Requirements.
Attachment E - EPA's Acceptance Criteria
Attachment F - List of all Registrant(s) sent this DCI
Attachment G - Cost Share/Data Compensation Forms
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EXECUTIVE SUMMARY
This Reregistration Eligibility Decision document (RED) will address the eligibility for
reregistration of products containing daminozide.
Daminozide is the common name for butanedioic acid mono (2,2-dimethylhydrazide).
The sole registrant, Uniroyal Chemical Company (Uniroyal), produces four products, B-Nine,
B-Nine SP, Alar-85, and Alar Technical, which contain daminozide as the active ingredient.
There is one Special Local Need currently registered. Daminozide is a systemic growth
regulator registered for use on ornamental and bedding plants in enclosed commercial structures
such as greenhouses, shadehouses, and interiorscapes.
Daminozide is formulated as a soluble concentrate. The registered products are applied
by either foliar spray, pre-plant dip, or a combination thereof.
Daminozide was initially registered in 1963 by the Uniroyal Chemical Company, Inc.,
for use on potted chrysanthemums. The first food use of daminozide (apples) was registered in
1968. A Registration Standard was issued in June, 1984 (NTIS PB87-104782). This
Registration Standard summarized the available data supporting the reregistration of products
containing daminozide. The Registration Standard also required additional product chemistry,
residue chemistry, toxicology, worker exposure, ecological effects, and environmental fate data.
On July 18, 1984, the Agency issued a Notice of Initiation of a Special Review of
pesticide products containing daminozide (49 FR 29186). This action was based on the Agency
finding that pesticide products containing daminozide met the risk criterion relating to
oncogenicity formerly at 40 CFR 162.11(a)(3)(ii)(A) and now found at 40 CFR 154.7(a)(2)(i).
Specifically, available data indicated that administration of daminozide and its degradate and
metabolite, unsymmetrical dimethylhydrazine (UDMH), to laboratory animals resulted in
statistically and biologically significant oncogenic responses at multiple organ sites in multiple
species and strains of animals. The Agency has classified both daminozide and UDMH as B2
probable human carcinogens. On November 14, 1989, during the Special Review process,
Uniroyal Chemical Company voluntarily canceled all the food use registrations of daminozide
(54 FR 47492). Following an evaluation of the risk to workers (mixer/loaders and/or
applicators) exposed to daminozide, the Agency concluded that the non-food uses of daminozide
did not pose an unreasonable risk to workers. The Special Review of daminozide was concluded
October 8, 1992 (54 FR 46436).
The Agency has determined that the uses of daminozide as currently registered will not
cause unreasonable risk to humans or the environment and these uses are eligible for
reregistration.
Before reregistering the products containing daminozide, the Agency is requiring that
product specific data, revised Confidential Statements of Formula (CSF) and revised labeling be
submitted within eight months of the issuance of this document. These data include product
chemistry for each registration and acute toxicity testing. After reviewing these data and any
revised labels and finding them acceptable, the Agency will reregister a product if it meets the
VI
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requirements in Section 3(c)(5) of FIFRA. Those products which contain other active
ingredients will be eligible for reregistration only when the other active ingredients are
determined to be eligible for reregistration.
Vll
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984. The amended Act provides a schedule for the reregistration process to be completed
in nine years. There are five phases to the reregistration process. The first four phases of the
process focus on identification *of data requirements to support the reregistration of an active
ingredient and the generation and submission of data to fulfill the requirements. The fifth phase
is a review by the U.S. Environmental Protection Agency (referred to as "the Agency") of all
data submitted to support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for registration" 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 section 3(c)(5).
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of daminozide. The document consists of six sections. Section I is the
introduction. Section II describes daminozide, its uses, data requirements and regulatory history.
Section in discusses the human health and environmental assessment based on the data available
to the Agency. Section IV presents the reregistration decision for daminozide. Section V
discusses the reregistration requirements for daminozide. Finally, Section VI is the Appendices
which support this Reregistration Eligibility Decision. Additional details concerning the Agency's
review of applicable data are available on request.1
1 EPA's reviews of data on the set of registered uses considered for EPA's analysis may be
obtained from the OPP Public Docket, Field Operations Division (H7506C), Office of Pesticide
Programs, EPA, Washington, DC 20460.
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H. CASE OVERVIEW
A. CHEMICAL OVERVIEW
The following active ingredient is covered by this Reregistration Eligibility
Decision:
• Common Name: Daminozide
• Chemical Name: Butanedioic acid mono (2,2-dimethylhydrazide)
• CAS Registry Number: 1596-84-5
• OPP Chemical Code: 035101
• OPP Case Number: 0032
• Empirical Formula: CeH^N^
• Trade and Other Names: Alar 85, B-Nine, B-Nine SP, Alar Technical
• Basic Manufacturer: Uniroyal Chemical Company, Inc.
B. USE PROFILE
The following is information on the current registered uses of daminozide with
an overview of use sites and application methods. A detailed table of these uses can be
found in Appendix A.
Type of Pesticide:
Plant growth regulator
Use Sites:
Greenhouse Non-Food (enclosed commercial structures; greenhouses,
shadehouses, interiorscapes); ornamental woody shrubs and vines;
ornamental herbaceous flowering/foliage plants.
Target Pests:
Not Applicable
•. • • - t . > ....
Formulation Types Registered:
Soluble concentrate/solid; 85%
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Method and Rates of Application:
Soluble Concentrate/Solid
, Apply as cutting, foliar, post-plant, or potted spray with standard spray
equipment at 0.01 to 0.0625 Ib Al/gal of spray;
Apply as a pre-plant dip at 0.0085 Ib Al/gal of solution.
Use Practices Limitations: ' .
Do not apply this product through any type of irrigation system;
Do not contaminate water, food, or feed;
Do not reenter treated areas until 24 hours after application, unless
wearing protective clothing;
Do not handle treated plants until sprays have dried;
For use only in enclosed commercial structures such as greenhouses,
shadehouses, and interiorscapes;
Stock solutions should not be held for more than 24 hours;
Do not syringe treated plant for 18-24 hours after spraying.
C. ESTIMATED USAGE OF PESTICIDE
This section summarizes the best estimates available for the pesticide uses of
daminozide. These estimates are derived from a variety of published and proprietary
sources available to the Agency. The data, reported on an aggregate and site (crop)
basis, reflect annual fluctuations in use patterns as well as the variability in using data
from various information sources.
The table below summarizes the pesticides use by site.
Domestic Usage of Daminozide
Site
Potted Mums
Poinsettias
Bedding Plants
Total Area x 1,000
(square feet)
23,753.0
73,500.0
261,063.0
Total Area Treated
x 1,000 (square feet)
21,377.7
18,375 - 36750
104,425.2 -
130,531.5
% Treated
90%
25% - 50%
40% - 50%
D. DATA REQUIREMENTS
Data requested in the 1984 Registration Standard for daminozide included studies
on product chemistry, residue chemistry, toxicology, ecological effects, environmental
fate, and worker exposure. These data were required to support the uses listed in the
Registration Standard. A Data Call-in issued in 1986 required that additional toxicology
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and worker exposure data be submitted. Appendix B includes all data requirements
identified by the Agency for currently registered uses needed to support reregistration.
E. REGULATORY HISTORY
Daminozide was first registered in the United States in 1963 for use on potted
chrysanthemums. The first food use of daminozide (apples) was registered in 1968. A
Registration Standard for daminozide.was issued in June, 1984 (NTIS #PB87-112025)
which evaluated the studies submitted to that date. A subsequent Data Call-In issued in
1986 called in additional toxicology and worker exposure data. This Reregistration
Eligibility Decision reflects a reassessment of all data which were submitted in response
to the Registration Standard and Data Call-In.
On July 18, 1984, the Agency issued a Notice of Initiation of a Special Review
of pesticide products containing daminozide (49 FR 29186). This action was based on
the Agency finding that pesticide products containing daminozide met the risk criterion
relating to oncogenicity formerly at 40 CFR 162.11(a)(3)(ii)(A) and now found at 40
CFR 154. On November 14, 1989, during the Special Review process, Uniroyal
Chemical Company voluntarily canceled all the food use registrations of daminozide (54
FR 47492). Following m_evaluation of the risk to workers (mixer/loaders and/or
applicators) exposed to daminozide, the Agency concluded that the non-food uses of
daminozide did not pose an unreasonable risk to workers. The Special Review of
daminozide was concluded October 8, 1992 (54 FR 46436).
There are currently two end-use products containing daminozide registered in the
United States. There is one registered technical product and one registered formulation
intermediate. Daminozide is currently registered for use on non-food crops in enclosed
commercial structures (greenhouses, shadehouses, and interiorscapes).
HI. SCIENCE ASSESSMENT
The Agency has conducted a thorough review of the scientific data base for
daminozide for the purposes of determining the reregistration eligibility of this pesticide.
A. Physical Chemistry Assessment
The physical and chemical properties of daminozide are as follows:
• TGAI
Color White
Physical State Solid
Odor Slight to no odor
Melting Point 154 to 156°C
Density 1.34 grams/cm3
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Solubility Soluble in water; 14.7 g/100 ml of solvent at 25° C
Soluble in methyl alcohol up to 5 grams
Soluble in acetone up to 2.2 grams
Soluble in acetonitrile at 0.2 grams
Insoluble in xylene
Insoluble in aliphatic hydrocarbons
Practically insoluble in hexane; 86 ppb
Vapor Pressure 1.7 x 10"4 torr at 23 ± 2°C
Dissociation Constant pl^ = 4.19 (amine)
pK2 = 5.59 (carboxylic acid group)
Octanol/Water Will partition almost completely into aqueous
Partition Coefficient solution
pH 3.8
Stability Stable after one year at room temperature (25°C)
Stable after 5 months at 50°C
• Analytical Method for Daminozide
The basis of the analysis of daminozide is the titration of N-
dimethylaminosuccinamic acid with sodium hydroxide, using Cresol Red as the indicator.
A second procedure consists of reacting daminozide in a closed flask with an excess of
bromate/bromide in acid for 30 minutes. After addition of potassium iodide the liberated
iodine is titrated with standard thiosulfate solution to determine the concentration of
daminozide by back titration.
• Conclusions
There is adequate physical chemistry information on the technical grade of the
active ingredient (TGAI) of daminozide to support its reregistration.
B. Human Health Assessment
1. Toxicology Assessment
Daminozide metabolizes or degrades to unsymmetrical dimethylhydrazine
(UDMH). The Agency, therefore, has investigated the hazards of both UDMH
and daminozide.
The lexicological data base for daminozide/UDMH is adequate to support
its reregistration.
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a. Acute Toxicity
TABLE T; Acute Toxicity Data for Daminozide (TGAI)
- TEST
Oral LD5ff rat (MRID 00009712)
Inhalation LC50 rat (MRID 00009712)
Dermal LD50 rabbits (MRID 00009737)
RESULT
>5.0g/kg
>20.0 mg/L/hour
> 16 g/kg
CATEGORY
rv
IV
m
-b. Subchronic Toxicity
Subchronic feeding of daminozide to rats for 13 weeks did not
produce any discernable toxic signs or effects at the highest dose of
greater than 2,160 mg/kg/day (MRID 00009727).
c. Chronic Toxicity
Daminozide has been tested in several chronic feeding studies using
rats, mice, and dogs. One rat study (MRID 00009413) fed daminozide up
to levels of 3,000 ppm (~ 150 mg/kg/day) in the diet with no effects
reported in the test animals. A second rat study (NCI Carcinogenesis
Technical Report Series No. 83, 1978) using dose levels as high as 10,000
ppm (-500 mg/kg/day) in the diet also reported a lack of toxicity in the
two-year study. A third rat study (MRID 40813101) also tested
daminozide in the diet at 10,000 ppm (-500 mg/kg/day) for two years
and found no toxicity in the test animals.
Beagle dogs were fed diets containing up to 7,500 ppm (-187
mg/kg/day) of daminozide for one year and showed no toxic effects
(MRID 40928101). Further testing with canines was not required. A
two-year feeding study with up to 10,000 ppm (~ 1,430 mg/kg/day) of
daminozide in the diet was performed with mice (MRID 40813102,
40093501) and though some incomplete reporting was noted, data
indicated that the red blood cell counts, hemoglobin levels, and
hematocrits were reduced in males at the highest dose. A NOEL for these
effects was 6,000 ppm (-860 mg/kg/day) in the interim report. The
effects on the hematological parameters were not reported in the two-year
sacrifice. An earlier study (NCI Carcinogenesis Technical Report Series
No. 83, 1978) in mice with up to 10,000 ppm (-1430 mg/kg/day) of
daminozide in the diet demonstrated decreased body weights and lowered
survival in females. The NOEL for those effects was 5,000 ppm (-720
mg/kg/day).
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d. Carcinogenicity
Daminozide Carcinogenicity. Daminozide has been tested in rats
at doses as high as 3,000 ppm (~ 150 mg/kg/day) in the diet with no
"tumorigenic response .noted (MRID 00009413). A second study of two
years' duration at doses of 5,000 (-250 mg/kg/day) or 10,000 ppm
(-500 mg/kg/day) of daminozide in the diet showed an increase of
adenocarcinomas of the endometrium and leiomyosarcomas of the uterus
of "female rats at the 5,000 ppm (-250 mg/kg/day) dose level (NCI
Carcinogenesis Technical Report Series No. 83, 1978). These two tumor
responses were not thought to be chemically related as the effects were not
statistically significant. A third feeding study tested Fischer 344 rats at
doses up to 10,000 ppm (-500 mg/kg/day) of daminozide in the diet with
only sporadically observed tumors which were not considered to be
chemically-related effects (MRID 40813101). Mice have been tested in
several two-year feeding studies. One study indicated hepatocellular
carcinomas in B6C3F1 male mice at the highest dose level of 10,000 ppm
(-1,430 mg/kg/day)-hut not at 5,000 ppm (NCI Carcinogenesis Technical
Report Series No. 83, 1978). A second study also tested CD-I mice at
up to 10,000 ppm (-1,430 mg/kg/day) levels in the diet with a
statistically significant dose-related increased trend in liver
hemangiosarcomas and combined hemangiosarcomas/hemangiomas but
without pair-wise comparisons being statistically significant. The
incidence of combined carcinomas and adenomas was significantly
increased in the 6,000 ppm (-857 mg/kg/day) dose group compared to
the controls (MRID 40813102).
UDMH Carcinogenicity. UDMH was given to Fischer 344 rats
in buffered drinking water at 1, 50, or 100 ppm (-0.06, 6.3, or 9.3
mg/kg/day for males) dose levels for two years (MRID 41253303). Only
a slight weight reduction was seen at the 100 ppm (-9.3-11.8 mg/kg/day)
dose in both sexes. Male test animals showed no clinical signs but did
have focal inflammation of the liver at doses of 50 and 100 ppm (6.3 and
9.3 mg/kg/day) when examined histologically. A slight increase in liver
tumors was noted. A maximally tolerated dose (MTD) was not reached
in the study.
Mice were tested in two different studies (in the same laboratory)
for a period of two years. The starting times of the two studies were
similar enough to allow the data to be evaluated together as a single study.
The first study tested dose levels of 0, 1, 5, or 10 ppm (-0, 0.18, 0.97,
or 1.9 mg/kg/day) of UDMH (low dose study) in the males with the
female mice receiving 0, 1, 5, or 20 ppm (-0, 0.27, 1.4, or 2.7
mg/kg/day) of UDMH in the drinking water (MRID 41253302). The
second study provided dose levels of .0, 40, or 80 ppm (-7.3 or
13mg/kg/day) in males and -11.6 and 21.7 mg/kg/day in females
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through their drinking water (high dose study) (MRID 41378001).
In the second year of the low dose study;-lung tumors were
statistically increased as well as a slight but non-statistically significant
increase in liver vascular tumors in female mice at 20 ppm (2.7
mg/kg/day). The MTD was not exceeded for the study.
Both sexes at both dose levels of the high dose study showed
increased vascular tumors of the liver and also lung tumors. However,
though the dose levels were high and caused some significant liver toxicity
to some of the test animals, tumors were early appearing and were not
thought to have been influenced by any excessive dosing over the MTD.
e. Developmental Toxicity
Daminozide has been tested in both rats and rabbits for its potential
to produce developmental toxicity. Rats (MRID 00053764) were
administered the test material by gavage at doses of 85, 390, or 1,800
mg/kg/day during the period of organogenesis with the result that maternal
toxicity (lowest effect level or LEL) was only seen at 1,800 mg/kg/day
with a NOEL of 390 mg/kg/day and developmental toxicity was not
produced at the highest dose tested (1,800 mg/kg/day) indicating a NOEL
of 1,800 mg/kg/day for the study. Rabbits (MRID 00150511) were dosed
with daminozide by gavage at levels of 50, 150, or 300 mg/kg/day and
produced some maternal toxicity expressed as slight reductions in weight
gains and changes in consistency of feces. Developmental toxicity was
not demonstrated. The NOEL was 150 mg/kg/day for the maternal
toxicity while the NOEL for developmental toxicity was 300 mg/kg/day.
f. Reproductive Toxicity
Rats were tested in a two-generation reproduction study with
dietary levels of 100, 1,000, or 10,000 ppm (-5, 50, or 500 mg/kg/day)
of daminozide (MRID 40233901). The NOEL was determined to be
1,000 ppm (~50 mg/kg/day) based on reduced body weights (which is
systemic toxicity) in Fl females at 10,000 ppm (-500 mg/kg/day).
There was otherwise no reproductive toxicity in the study and the NOEL
for reproductive toxicity was 10,000 ppm (-500 mg/kg/day).
g. Mutagenicity
Daminozide Mutagenicity. Mice have been dosed with up to
25,000 ppm (—3,570 mg/kg/day) of daminozide for 5 days and produced
only diarrhea at the highest dose tested. The NOEL for toxicity to the
animals was 10,000 ppm (1,430 mg/kg/day). A mutagenic effect was not
demonstrated at either dose level in this dominant lethal study (MRID
8
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00009683)3ie a
Daminozide technical was tested for its ability to cause DNA
damage and repair stimulation in E. coli strains WP-2, WP-67, and CM-
871 both with and without S-9 activation. No significant alterations in
DNA repair processes were found at up to 10,000 jig/mL of daminozide
(MRID 00143054).
A second study using Saccharomyces cerevisiae D-6 strain with
and without S-9 activation did not indicate positive mutagenicity from
daminozide exposure (MRID 00143055). Technical daminozide in
dimethyl sulfoxide (DMSO) did not cause a mutagenic response in
Salmonella and Saccharomyces at up to 500 jig/plate (MRID 00009681).
The mouse lymphoma test using L5178Y cells when exposed to up
to 3,000 jtg/mL to the thymidine kinase gene locus with and without
activation did not show a significant mutagenic effect (MRID 00143053).
UDMH Mutagenicity. UDMH, the metabolite of daminozide, has
been tested for its mutagenic activity in the Ames Salmonella organism
test (MRID 40319901) both with and without S-9 activation at doses from
25 to 5,000 jtg/plate with negative results. Chinese hamster ovary cells
(CHO) (MRID 40319901) were treated with and without activation by rat
liver microsomes and produced equivocal results with respect to the
hypoxanthine guanine phosphoribosyltransferase (HGPRT) gene locus.
The study was repeated; subsequent results were negative.
Chromosomal aberrations (MRID 40319901) were not produced
from CHO cells being treated with up to 500 ng/mL of UDMH.
DNA repair (MRID 40319901) tests were negative at up to 250
ng/mL with cytotoxicity appearing at that dose level. Additional testing
with the metabolite chemical, UDMH, is not warranted because the
chemical is already a proven carcinogen in live animal studies.
h. Metabolism
Daminozide has been studied in minipigs chosen because of the
similar stomach conditions to the human. They were given oral doses of
radio-labelled test material at 5 mg/kg body weight. It was found to be
rapidly excreted with approximately 60 percent excreted by 48 hours.
The metabolite (UDMH) was found in urine at up to 2.8 ppm; lesser
amounts were found in the feces. Radio-labelled 1,1-dimethylnitrosamine
at levels of 0.69 ppm levels were also found in the urine of the test
animals (MRID 40282901).
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A second study was performed with a dermal application of radio-
labelled daminozide covering dermal surfaces with concentrations of 0.5,
0.05, or 0.005 mg/cm2 for periods up to 24 hours. As much as 1.8
percent of the dose was absorbed and excreted by the test animals in 24
hours (MRID 40214501).
i. Carcinogenicity Classification
Daminozide Carcinogenicity. The Office's Cancer Peer Review
Committee has classified daminozide as a Group 63 probable human
carcinogen. The data from the mouse study were used to derive a Q,* for
the quantification of human risk. The data show that in the male mice,
there was a significant linear trend for combined lung carcinomas and
adenomas, and that the incidence of combined carcinomas and adenomas
was significantly increased in the 6,000 ppm (~857 mg/kg/day) dose
group compared to the controls (MRID 40813102). Based on this data
set, a Q,* of 0.0087 (mg/kg/day)-1 was calculated using the linearized
multistage model.
UDMH Carcinogenicity. Upon review of the chronic
feeding/carcinogenicity, metabolism, and mutagenicity studies, the
Office's Cancer Peer Review Committee classified UDMH as a Group Bj
probable human carcinogen. The Committee determined that because the
contaminant, metabolic, and/or break-down product, UDMH, was
dependent upon the presence of the parent chemical (i.e., daminozide),
then the parent chemical should also be classified as a 63 carcinogen. A
Qi* was determined for UDMH as 0.46 (mg/kg/day)-1 based on the
incidence of hemangiosarcomas in the male mice.
j. Reference Dose
A reference dose (RfD) for systemic toxicity was determined for
daminozide as 2.0 mg/kg/day based upon a NOEL of 187.5 mg/kg/day
from a long term feeding toxicity study in dogs (MRID 40928101). An
uncertainty factor of 100 was used to account for the interspecies
extrapolation and intraspecies variability.
2. Exposure Assessment
Greenhouse workers are exposed to both daminozide and its metabolite
UDMH. The exposure data base for daminozide/UDMH will support
reregistration eligibility.
i • ki i ' • /
a. Dietary Exposure
There are no registered food uses for daminozide.
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b. Occupational and Residential
Mixers/Loaders/Applicators: Exposure to Daminozide and UDMH
Exposure to daminozide/UDMH comes from two pathways: (1)
The direct .exposure to daminozide and the conversion of daminozide to
UDMH when it is ingested or absorbed through the skin or lungs (i.e., in
vivQ-eonversion); and (2) The presence of UDMH as a contaminant in the
commercial product and conversion of daminozide to UDMH when it is
left standing in the mixing tank. The total cancer risk from UDMH is
estimated by adding the individual risks from each pathway of exposure
to UDMH.
Direct Exposure to Daminozide. The worker exposure estimates
are derived from the study "B-Nine SP on Ornamentals - Greenhouse
Mixer/Loader/Applicator Exposure Study," which was submitted by
Uniroyal (MRID 41876001, 41876002). Also used in the exposure
estimates were typical use pattern data available to the Agency.
Typical use patterns were based on information from a survey of
greenhouse managers. The survey indicated that, on average, a worker
uses approximately 24 pounds of daminozide yearly in a large greenhouse
and about 10 pounds yearly in a small greenhouse. The amount of
daminozide used per application depends on solution concentrations, which
range from 0.0375 percent to 0.5 percent.
The Uniroyal study provided data correlating a worker's exposure
to the amount of daminozide used. The study was designed to measure
potential exposure to workers from the preparation and application of a
0.5 percent solution of daminozide to chrysanthemums in a greenhouse.
Because workers may function in the capacity of mixer/loader/applicator
(M/L/A), the sum of the mixer/loader and applicator exposures would
represent the maximum potential exposure for an individual worker.
Workers were exposed to coarse and fine sprays of 0.5 percent
solutions of daminozide during greenhouse operations. Exposure was
considered to be highest for the workers using fine sprays. Field trial and
field spiked samples were analyzed by the method of Conditt et.al.
(Conditt, M. K.; Baumgardner, J. R.; Hellman, L. M. (1988)). Workers
wore respirators, one-piece union suits (whole body dosimeter) over cotton
briefs and under long-sleeved shirts and long pants, socks, rubber or
leather boots, and rubber gloves. The average exposures (without
adjusting for typical use patterns) as a function of the amount of
daminozide are provided in Table 2. The units "mg/kg used" mean
milligrams of test material per kilogram of material handled:
11
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TABLE 2: Average Worker Exposure to Daminozide
Application Method Dermal Exposure Inhalation Exposure
(mg/kgused) (mg/kg used)
Coarse Spray 0.92 0.40
Fine Spray 1.14 0.75
Integrating the analysis of the Uniroyal data and the typical "use
patterns, the Agency estimates the following Atypical worker exposures
(Table 3). The units of "mg/kg/yr" mean milligrams of test material per
kilogram of body weight per year. The estimates are for the average
dermal and inhalation yearly exposures.
TABLE 3: Average Yearly Worker (M/L/A) Exposure to Daminozide
Application Method Dermal Exposure Inhalation Exposure
(mg/kg/yr) (mg/kg/yr)
Large Greenhouse
Coarse Spray 0.14 0.06
Fine Spray 0.18 0.12
Small Greenhouse
Coarse Spray 0.060 0.025
Fine Spray 0.075 0.049
Exposure to UDMH from Contamination and Hydrolysis of
Daminozide. UDMH is found as a 0.005 percent contaminant in
commercial daminozide products. Exposures to the contaminant are
estimated from the average yearly exposures that are provided in Table
3 (i.e., 0.005 percent multiplied by the average exposures). These
estimates are provided in Table 4; the units of "mg/kg/yr" mean
milligrams of test material per kilogram of body weight per year.
TABLE 4: Average Yearly Worker (M/L/A) Exposure to the UDMH
Contaminant
Application Method Dermal Exposure Inhalation Exposure
(mg/kg/yr) (mg/kg/yr)
Large Greenhouse
Coarse Spray 7.0E-06 3.0E-06
Fine Spray 9.0E-06 6.0E-06
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TABLE 4: (cont'd)
Small Greenhouse
Coarse Spray 3.0E-06 L3E-06
Fine Spray 3.8E-06 2.5E-06
The exposure assessment, additionally, examines the hydrolytic
degradation of daminozide and its contribution to worker exposure.
Because the current product label permits storage of a stock solution "of
daminozide for up to 24 hours after mixing, there exists a potential for
exposure to the degradation product UDMH. Using a degradation rate of
0.012 percent per day and the average exposures provided in Table 3, the
following amounts (i.e., Table 5) of daminozide would be degraded in 24
hours. The units of "mg/kg/yr" mean milligrams of test material per
kilogram of body weight per year.
TABLE 5: Average Yearly M/L/A Exposure to UDMH from 24
Hours of Daminozide Degradation
Application Method Dermal Exposure Inhalation Exposure
(mg/kg/yr) (mg/kg/yr)
Large Greenhouse
Coarse Spray 1.7E-05 7.2E-06
Fine Spray 2.2E-05 1.4E-05
Small Greenhouse
Coarse Spray 7.2E-06 3.0E-06
Fine Spray 9.0E-06 5.9E-06
Reentry Workers: Foliar Dislodgeable Residue Study
The Agency finds the foliar dislodgeable residue (FDR) study
submitted by Uniroyal (MRID 40037001) to be supplemental. The study
did provide some data that were used to help establish a restricted entry
interval (REI) for post-application workers. In addition to the rough
estimates based on the FDR study, the Agency relied on the use pattern
as well as the risk reduction provisions of the Worker Protection Standard
in setting the REI.
3. Human Health Risk Assessment
a. Dietary
There are no registered food uses for daminozide.
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b. Occupational and Residential
RISK CHARACTERIZATION
As stated previously, the total risk to workers from exposure to
daminozide and UDMH. is a sum of the risk due to exposure to
daminozide (see Table 3) plus the risk due to the exposure from the
UDMH contaminant and hydrolysis of daminozide to UDMH (see Tables
4 and 5).
Assumptions Used to Estimate Cancer Risk from the in vivo
Conversion of Daminozide
The risk to workers from exposure to daminozide/UDMH may be
considered as a function of daminozide exposure (Approach I) or as a
function of UDMH exposure (Approach II), and characterized
accordingly. Each approach to risk characterization has different sets of
assumptions, and because of these assumptions, each approach introduces
some uncertainties. The preferred approach would be to base the risk on
exposure to UDMH, the primary chemical identified by the Agency in the
Special Review to address the carcinogenicity endpoint.
Approach I. For a risk characterized as a function of UDMH. the Agency
makes the following assumptions:
(1) Daminozide may be absorbed into the body at a rate of one percent
by the dermal route based on the data from a dermal absorption
study in rats (MRID 40214501). It is estimated to be 100 percent
absorbed by the inhalation route, as the worst-case scenario,
because inhalation absorption data are unavailable.
(2) Daminozide is converted to UDMH upon entering the human
body. The conversion is estimated to be one percent; this level of
conversion is considered as a maximum because the more neutral
pH of the blood is expected to cause less breakdown of daminozide
than the lower pH of the stomach.
(3) The molecular weight of UDMH is approximately 40 percent of
the molecular weight of daminozide.
(4) The extra cancer risk from exposure is based on a Q,* of 0.46
(mg/kg/dayy1, derived from the UDMH study in mice.
Because of limited information on the metabolic conversion of
daminozide to UDMH from dermal or inhalation exposure, the Agency is
also characterizing the risk as a function of daminozide so as to arrive at
14
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a reasonable assessment. The risk estimates obtained from these two
separate approaches may serve to define a potential range of risk for risk
assessment purposes.
Approach II. For a risk characterized as a function of daminozide, the
Agency makes the following assumptions:
(1) Daminozide may be absorbed into the body at a rate of one percent
by the dermal route based on data from a dermal absorption study
in rats (MRID 40214501). It is estimated to be 100 percent
absorbed by the inhalation route, as the worst-case scenario,
because inhalation absorption data are unavailable.
(2) The extra cancer risk from exposure is based on a Q/ of 0.0087
(mg/kg/day)"1, derived from the daminozide study in mice.
Assumptions Used to Estimate Cancer Risk from Contamination and
Hydrolysis
To the risk that is derived by either of the above two approaches
will be added two additional risk components: (1) the contribution from
the UDMH contaminant in the commercial product; and (2) the UDMH
formed from hydrolysis of daminozide during 24-hour storage of the stock
solution. To estimate the contribution of UDMH as a contaminant and
hydrolysis product, the following assumptions are used:
(1) The commercial product is contaminated with 0.005 percent
UDMH.
(2) Daminozide is degraded to succinic acid and UDMH upon storage
as a solution in water; at 24 hours, 0.012 percent of the
daminozide will have hydrolyzed.
(3) The human dermal absorption rate for UDMH is based on the rat
dermal absorption rate that most closely approximates the worker
use pattern. Because exposure depends on varying greenhouse
practices and information on bioaccumulation is unavailable, a
dermal absorption rate of 20 percent will be used as reasonable
worst-case scenario for risk assessment purposes.
(4) The inhalation absorption rate is assumed to be 100 percent, the
worst-case scenario, because inhalation absorption data are
unavailable.
(5) The extra cancer risk from exposure to UDMH is based on a Q,*
of 0,46 (mg/kg/day)-1.
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Estimation of Cancer Risk from Daminozide and UDMH
Contamination/Hydrolysis
The extra cancer risk may be estimated using the following equations:
Extra cancer risk = Q,* x lifetime average daily dose (LADDV
(Eq. 1)
where:
LADD = dose (mg/kg/day^ x 25 (Eq. 2)
365 days/yr 70
dermal doseApptwh, =
dermal doseApproachn
dermal absorption X in vivo
conversion rate x molecular weight
x dermal exposure (from Table 3)
dermal absorption x
exposure (from Table 4)
dermal
NOTE: The inhalation doses are calculated similarly, using relevant
parameters.
The dermal and inhalation cancer risk estimates are provided in
Table 6. Only the risk estimates for the fine spray application are
provided because exposure from this application method was higher than
from the coarse spray and thus represents a worst-case scenario.
TABLE 6: Summary of Cancer Risk Estimates for Greenhouse
Workers
LARGE
GREENHOUSE
SMALL
GREENHOUSE
RISK DUE TO DERMAL
EXPOSURE TO
DAMINOZIDE
RISK DUE TO
INHALATION
EXPOSURE TO
DAMINOZIDE
As a function
of UDMH
As a function
of daminozide
As a function
of UDMH
As a function
of daminozide
7.0E-09
2.4E-08
3.0E-07
1.4E-06
2.9E-09
9.7E-09
1.2E-07
5.8E-07
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Combining the dermal and inhalation cancer risks, the following
ranges for fine spray are observed:
3.0E-07 to 1.4E-06 for large greenhouse workers; and
1.2E-07 to 5.8E-07 for small greenhouse workers.
The cancer risk ranges for greenhouse workers represent a
reasonable characterization of risk. Risk to workers who use a coarse
spray is about half these estimates (inhalation exposure, which provides
the greater risk component, is approximately halved when a coarse spray
application is used).
Restricted Entry Interval (REI)
The Agency is requiring a 24-hour restricted-entry interval (REI).
The existing label prohibits workers from entering treated areas for 24
hours after application unless protective clothing is worn. In addition, the
existing label states that treated plants should not be handled until sprays
have dried and that treated plants should not be syringed for 18-24 hours
after application to allow the chemical to enter the plant. These use-
directions indicate that a 24-hour REI will not substantially interfere with
the cultural practices already in place when this chemical is applied.
Therefore, the Agency does not anticipate an economic hardship in
converting from a 24-hour reentry interval (where reentry with protective
clothing is allowed) to a 24-hour restricted-entry interval (where entry to
perform hand labor during the restricted period is prohibited except under
very narrow circumstances).
Furthermore, given the known lexicological concerns for
daminozide/UDMH and based on the risk to early entry workers found in
the foliar dislodgeable residue study (MRID 40037001), the Agency
considers the additional protections offered by the requirements in 40 CFR
Parts 156 and 170 ~ the Worker Protection Standard (WPS) for
Agricultural Pesticides - essential to its decision that a 24-hour restricted
entry interval for this chemical will offer sufficient risk mitigation to
workers. Therefore, during the REI the Agency will allow workers to
enter areas treated with daminozide before the expiration of the REI in
only the few narrow exceptions allowed in the WPS.
The Agency has determined that there are no currently registered
uses of daminozide outside the scope of the Worker Protection Standard
for Agricultural Chemicals. The registrant is adding an "exclusionary"
statement to clarify the use-sites.
Although daminozide has been classified as a Toxicity Category HI
chemical (MRID 00009737) for acute dermal toxicity, the Agency, for the
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reasons stated in the above paragraphs, is requiring personal protective
equipment (PPE) for early entry workers consistent with the PPE level (as
established in the WPS) required for pesticides classified as Toxicity
Category II for acute dermal toxicity. The Agency has determined that
post-application exposure to daminozide is mostly on the hands from
handling treated plants. Therefore, for early entry allowed by the WPS,
dermal exposure of workers should be mitigated if level n PPE, including
chemical-resistant gloves, is used. A glove permeability study (MRID
400326002) indicates that many types of gloves can be used to reduce
exposure to daminozide, including disposable, lightweight polyethylene
and polyvinyl chloride (PVC) gloves, natural latex and butyl rubber
gloves, and lightweight barrier laminate gloves.
C. Environmental Assessment
1. Environmental Fate
a. Environmental Chemistry, Fate and Transport
The environmental fate data submitted on daminozide indicate that
this chemical is stable to hydrolysis at 200 ppm in aqueous buffered
solutions at pHs 5, 7, and 9, and degrades slowly (observed half-life >
30 days) in a pH 1 solution during 30 days of incubation. The degradate
1,1-dimethylhydrazine was 33.5 ppm in the pH 1 solution at the day 30
sampling interval, and at relatively low concentrations in the other pH
solutions (MRID 00147749, 00154942). The data also indicate that
daminozide rapidly mineralizes to CO2 in aerobic soil (62% of the applied
radioactivity is degraded to CO2 after 72 hours, half-life of 9.5 hours).
The only identified degradate in the aerobic soil was formaldehyde
(present at very low levels); bound residues comprised less than 15% of
the applied radioactivity (MRID 42687201).
b. Environmental Fate Risk Assessment
Hydrolysis does not contribute significantly to the dissipation of
this chemical in the environment. However, supplemental aerobic soil
metabolism data suggest that daminozide is metabolized rapidly to CO2 in
aerobic sandy loam soil (half-life of 9.5 hours), with the only degradate
identified in the soil extracts being formaldehyde at low concentrations;
bound residues comprised »15% of the applied radioactivity (MRID
42687201). Because daminozide degrades so rapidly in aerobic soil to
volatile compounds and bound residues, the mobility of daminozide could
not be determined, but probably is not a concern. In addition, products
containing daminozide are labeled for use only in confined greenhouse
situations, therefore, the chemical is not expected to occur in ground
water or agricultural runoff.
18
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2. Ecological Effects
The Agency has sufficient data to support the non-food, enclosed
commercial structure (greenhouses, shadehouses, interiorscapes) uses of
daminozide. Due to daminozide's use pattern, the required studies are
used only to evaluate the hazard to nontarget organisms that could result
from misuse or spillage during transport and for determining the
environmental hazard statements on the label.
a. Terrestrial Data
*
Available mammalian data indicate that daminozide is practically
non-toxic to mammals on an acute basis (acute oral LD50 8.4 gm/kg for
rats). The results of avian toxicity studies indicate that the technical grade
(TGAI) of daminozide is practically non-toxic to birds on an acute oral
basis (LD50 on mallard duck (waterfowl) is >2250 mg/kg; MRID
42429001), and on a dietary basis (LC50 on mallard duck (waterfowl) and
bobwhite quail (upland game bird) was determined to be greater than
10,000 ppm; MRID 00009705, 00009575).
b. Aquatic Data
Data were submitted to characterize the toxicity of daminozide to
non-target aquatic organisms. The results of these studies indicate that
daminozide is practically non-toxic to freshwater fish (LC 50 values of 448
ppm and > 100 ppm were reported for bluegill (warm water fish) and
rainbow trout (cold water fish) respectively; MRID 00009704, 00009706).
The results of a study using Daphnia magna as the test species suggest that
daminozide is slightly toxic to aquatic invertebrates (the 96-hour EC50 was
71 mg/L; MRID 42429002).
c. Ecological Effects Risk Assessment
Environmental exposure is expected to be minimal when
daminozide is used according to the directions on the label; therefore, the
ecological risk is expected to be low.
3. Data Requirements
The Agency received an Aerobic Soil Metabolism study (162-1;
MRID 42687201) that needs additional data to be upgraded and fulfill this
guideline data requirement. However, this required additional information
is not expected to change the overall qualitative assessment for daminozide
or affect its reregistration eligibility. Additional data are needed on a
confirmatory basis to fully characterize the radioactive contents of the
ethylene glycol trap from this study. These data are expected to provide
19
-------
s , information on the nature and relative quantities of the volatiles present in
-: the vapor phase. Based on the results of the original submission (MRID
42687201), it appears highly unlikely that volatile degradates (other than
COj) exceeding 10% of the applied radioactivity would be produced.
- Therefore, data on the photodegradation in air (161-4), laboratory
volatility (163-2), and field volatility (163-3) of daminozide are not
necessary to characterize the risks associated with the use of daminozide
and are no longer required.
IV. RISK MANAGEMENT AND REREGISTRAT1ON DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission
of relevant data concerning an active ingredient, whether products containing the active
ingredients are eligible for reregistration. The Agency has previously identified and
required the submission of the generic (i.e. active ingredient specific) data required to
support reregistration of products containing daminozide as the active ingredient. The
Agency has completed its review of these generic data, and has determined that the data
are sufficient to support reregistration of all products containing daminozide. Appendix
B identifies the generic data requirements that the Agency reviewed as part of its
determination of reregistration eligibility of daminozide, and lists the submitted studies
that the Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess
the registered uses of daminozide and to determine that daminozide can be used without
resulting in unreasonable adverse effects to man and the environment. The Agency
therefore finds that all products containing daminozide as the active ingredient are
eligible for reregistration. The reregistration of particular products is addressed in
Section V of this document.
The Agency made its reregistration eligibility determination based upon the target
data base required for reregistration, the current guidelines for conducting acceptable
studies to generate such data and the data identified in Appendix B. Although the
Agency has found that all uses of daminozide 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
daminozide, if new information comes to the Agency's attention or if the data
requirements for reregistration (or the guidelines for generating such data) change.
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient
daminozide, the Agency has sufficient information on the health effects of
daminozide and on its potential for causing adverse effects in fish and wildlife and
the environment. The Agency concludes that products containing daminozide for
20
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use in enclosed commercial structures such as greenhouses, shadehouses and
interiorscapes are eligible for reregistration.
. The Agency has determined that daminozide products, labeled and used
as specified in this Reregistration Eligibility Decision, will not pose unreasonable
risks or adverse effects to humans or the environment.
2. Eligible and Ineligible Uses
The Agency has determined that the uses of daminozide in enclosed
commercial structures such as greenhouses, shadehouses and interiorscapes are
eligible for reregistration. These are the only registered uses of daminozide.
B. Regulatory Position
The following is a summary of the regulatory positions and rationales for
daminozide. Where labeling revisions are imposed, specific language is set forth in
Section V of this document.
1. Tolerance Reassessment
t
All food uses for daminozide were voluntarily cancelled on November 14,
1989. There are no longer any registered uses for daminozide in or on food or
feed. All tolerances have been revoked.
2. Labeling Rationale
All daminozide end-use products within the scope of the Worker
Protection Standard for Agricultural Pesticides (see PR Notice 93-7) - must,
within the timeframes listed in PR Notice 93-7 and 93-11, revise their labeling
to be consistent with the WPS, as directed in those notices. The personal
protective equipment and restricted-entry interval for daminozide end-use products
are listed below.
Although daminozide has been classified as a Toxicity Category m
chemical (MRID 00009737) for acute dermal toxicity, the Agency is requiring
personal protective equipment (PPE) for all pesticide handlers as well as early
entry workers consistent with the PPE level (as established in the WPS) required
for pesticides classified as Toxicity Category II for acute dermal toxicity. As
noted previously in this document, this is due to the known lexicological concerns
for daminozide/UDMH and the residue dissipation study indicating risks to early
entry workers from foliar residues (MRID 40037001).
The Agency is requiring a 24-hour restricted-entry interval (REI) for all
uses for all daminozide end-use products. All currently registered uses are within
21
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the scope of the WPS (see PR Notice 93-7). The registrant must add an
"exclusionary" statement to clarify the use-sites.
To remain in compliance with FIFRA, it is the Agency's position that the
"Environmental Hazards" section should include the following for all
manufacturing use products:
"Do not discharge effluent containing this product into lakes, streams,
ponds, estuaries, oceans or other waters unless in accordance with the
requirements of a National Pollutant Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product into
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance contact your State Water Board or Regional
Office of the the Agency."
To remain in compliance with FIFRA, it is the Agency's position that
under the heading "Directions for Use," all manufacturing use products (MP)
must be labeled in accordance with PR Notice 91-8. This notice requires, among
other things, that all MP labels specify which uses can be contained on end use
products formulated from each manufacturing use product. The specific label
language for MPs containing daminozide is found in Part V.
V. ACTIONS REQUIRED BY REGISTRANTS
This section specifies the data requirements and responses necessary for the reregistration
of both manufacturing-use (MP) and end-use products (EUP). In addition to the data listed
below, the Agency is requiring that revised Confidential Statements of Formula (CSFs) and
revised labeling be submitted within 8 months from receipt of this document.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
There are no new generic data being called-in for daminozide. The generic
data base supporting the reregistration of daminozide for the above eligible uses
has been reviewed and determined to be substantially complete. However,
additional confirmatory information is needed to fulfill the aerobic soil
metabolism data requirement.
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, it is the Agency's position that the
"Environmental Hazards" section, to be consistent with PR Notice 93-10, must
include the following:
22 ^
-------
"Do not discharge effluent containing this product into lakes, streams,
ponds, estuaries, oceans or other waters unless in accordance with the
requirements of a National Pollutant Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product into
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance contact your State Water Board or Regional
Office of the the Agency."
To remain in compliance with FIFRA, and be consistent with PR Notice
91-8, it is the Agency's position that under the heading "Directions for Use" the
following labeling statement is required:
"Only for formulation into products for (1) The following uses (list those
uses that are being supported by each MP registrant) (2) Uses for
which USEPA has accepted the required data and/or citations of data that
the formulator has submitted in support of reregistration; and (3) Uses for
experimental purposes that are in compliance with USEPA requirements."
Also, as noted in PR Notice 91-8, the Agency recognizes that some
manufacturing products (MP) manufacturers may have concerns over liability
which may result from a use or uses that they have not supported with scientific
data. Therefore, the Agency will permit MP registrants/applicants to amend or
include on their labels an additional liability disclaimer for the unsupported
(unlisted) uses that disclaims liability for crop damage or failed efficacy resulting
from the use of a formulated product containing an MP registrants's product.
Any such disclaimer must otherwise be consistent with 40 CFR 156.10(a)(5).
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed
product-specific data regarding the pesticide after a determination of eligibility
has been made. The product specific data requirements are listed in Appendix
G, the Product Specific Data Call-In Notice.
Registrants must review previous data submissions to ensure that they meet
current Agency acceptance criteria (Appendix G; Attachment E) and if not,
commit to conduct new studies. If a registrant believes that previously submitted
data meet current testing standards, then study MRID numbers should be cited
according to the instructions in the Requirement Status and Registrants Response
Form provided for each product.
23
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2. Labeling Requirements for End-Use Products
Any product whose labeling reasonably permits use in the production of
an agricultural plant on any agricultural establishment (farm, forest, nursery, or
greenhouse) must comply with the labeling requirements of PR Notice 93-7,
"Labeling Revisions Required by the Worker Protection Standard (WPS), and PR
Notice 93-11, "Supplemental Guidance for PR Notice 93-7," which reflect the
requirements of EPA's labeling regulations for worker protection statements (40
CFR part 156, subpart K). These labeling revisions are necessary to implement
the Worker Protection Standard for Agricultural Pesticides (40 CFR Part 170) and
must be completed in accordance with, and within the deadlines specified in, PR
Notices 93-7 and 93-11. Unless otherwise specifically directed in this RED, all
statements required by PR Notices 93-7 and 93-11 are to be on the product
labeling exactly as instructed in those notices.
After April 21, 1994, except as otherwise provided in PR Notices
93-7 and 93-11, all products within the scope of those notices must bear
WPS PR-Notice-complying labeling when they are distributed or sold by
the primary registrant or any supplementally registered distributor.
After October 23, 1995, except as otherwise provided in PR
Notices 93-7 and 93-11, all products within the scope of those notices
must bear WPS PR-Notice-complying labeling when they are distributed
or sold by any person.
Exclusionary Statement: All end-products must carry the following statement
located (1) on the front panel of the label in association with the product name or
(2) near the beginning of the Directions For Use section:
"For use only in commercial or research greenhouses or shade
houses."
Personal Protective Equipment Requirements
AH End-Use Products: The personal protective equipment (PPE) requirement
for pesticide handlers on all end-use products is:
"Applicators and other handlers must wear:
Coveralls over short-sleeved shirt and short pants
Chemical-resistant or waterproof gloves (see instructions * below)
Chemical-resistant footwear plus socks
Chemical-resistant headgear for overhead exposure
Chemical-resistant apron when cleaning equipment, mixing, or
loading" (see instructions ** below)
24
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* The glove statement for daminozide is the statement established
through the instructions in Supplement Three of PR Notice 93-7.
** . - The words "mixing, or loading" may be removed if the product is
formulated as "ready-to-use."
"End-use products that contain daminozide must compare the personal
protective equipment requirements set forth in this section to the personal
protective equipment requirements, if any, on their current labeling and retain the
more protective. For guidance in choosing which requirement is more protective,
see Supplement Three of PR Notice 93-7. If the existing labeling requires a
"protective mask for mixers and loaders," use the guidance in Supplement Three
of PR Notice 93-7 to determine the appropriate respirator statement.
Entry Restrictions
All End-Use Products: A 24-hour restricted entry interval (REI) is required for
all uses for all end-use products. All uses are within the scope of the WPS (see
PR Notice 93-7). This REI should be inserted into the standardized REI
statement required by PR Notice 93-7. The personal protective equipment (PPE)
for early entry should be the PPE required for applicators of daminozide (except
no apron or respirator is required). This PPE should be inserted into the
standardized early entry PPE statement required by PR Notice 93-7.
Sole-active-ingredient end-use products that contain daminozide must be
revised to adopt the entry restrictions set forth in this section. Any conflicting
entry restrictions on their current labeling must be removed.
Multiple-active-ingredient end-use products that contain daminozide must
compare the entry restrictions set forth in this section to the entry restrictions on
their current labeling and retain the more protective. A specific time-period in
hours or days is considered more protective than "sprays have dried" or "dusts
have settled."
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling
for 26 months from the date of issuance 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"; Federal Register.
Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell daminozide
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.
25
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APPENDIX A
Table of Use Patterns
Subject to Reregistration
26
-------
The following table shows the eligible uses of Daminozide. It does not show any changes resulting from the RED review itself. Changes that result from the RED review; e.g. PHI. application rates etc are
specified in section IV.
APPENDIX A - Case 0032, [Daminozide) Chemical 035101
Application Application Application
Typ« Timing Equipment
Form
Maximum
Application
Rata
Max. *
Apps.
Max. *
App«. 9
Max. Rata
Min. Interval
Batwean Apps.
@ Max. Rata
(Day*)
Rastrictad
Entry
Interval
(Daysl
Geographic
Limitations
Allowed
Disallowed
Use Pattern Limitations
USES ELIGIBLE FOR R E R E G 1 S T R A Tl O N
NON-FOOD/NON-FEED USES
Site: Ornamental Herbaceous Plants Use Group: Greenhouse Non-Food Crop
Dip, Cutting, Dip Tank
Dip, Foliar, Dip Tank
Spray, Foliar, Sprayer
Spray, Foliar, Sprayer
sc/s
sc/s
sc/s
sc/s
1V% tsp
per gal
1% tsp
per gal
8 tsp per
gal
8 tsp per
gal
NS
NS
NS
NS
NS
NS
NS
NS
NS
7
7
NS
1
1
1
1
NS
AZ
AZ
NS
NS
NS
NS
NS
NPOES licansa restriction; Do not apply in
marina and/or astuarina environments, oil
fields, or discharge affluent into lakes,
streams, pond* or public water (NPOES
licansa restriction)
NPDES licansa restriction; Do not apply in
marina and/or astuarina environments, oil
fields, or discharge affluent into lakes,
streams, ponds or public water (NPOES
license restriction)
NPDES license restriction; Do not apply in
marine and/or estuarina environments, oil
fields, or discharge effluent into lakes,
streams, ponds or public water (NPDES
license restriction)
NPDES license restriction; Do not apply in
marine and/or astuarine environments, oil
fields, or discharge effluent into lakes,
streams, ponds or public water (NPDES
license restriction)
Site: Herbaceous Plants Use Group: Indoor Non-Food
Spray, Foliar, Sprayer
sc/s
8 tsp per
gal
NS
NS
NS
1
NS
NS
NPDES license restriction; Do not apply in
marina and/or astuarina environments, oil
fields, or discharge effluent into lakes,
stream*, ponds or public water (NPDES
Site: Ornamental Woody Shrubs and Vines Use Group: Greenhouse Non-Food Crop
Spray, Foliar, Sprayer
Spray, Foliar, Sprayer
sc/s
sc/s
12 tsp
per gal
12 tsp
per gal
NS
NS
NS
NS
NS
7
1
1
NS
AZ
NS
NS
NPDES license restriction; Do not apply in
marine and/or aetuarin* environments, oil
fields, or discharge effluent into lake*.
streams, ponds or public water (NPDES
license restriction)
NPDES license restriction; Do not apply in
marine* and/or aatuarine environments, oil
fields, or discharge effluent into lakes,
stream*, pond* or public water (NPDES
license restriction)
27
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APPENDIX A- Case 0032. [Daminozide] Chemical 035101
Application Application Application
Typa Timing Equipment
Form
Maximum
Application
Rata
Max. *
App».
Max. *
Appt. @
Max. Rata
Min. Interval
Batwaan App*.
9 Max. Rata
IDayt)
USES ELIGIBLE FOR R E R E G 1 S T R A T 1 O N
Restricted
Entn/
Interval
(Days)
Geographic
Limit ationt
Allowed
' j
Disallowed
Usa Pattarn Limitationa
«, r; •.:••!.,,,,.
Site: Ornamental Woody Shrubs and Vines Use Group: Indoor Non-Food
Spray, Foliar, Sprayer
SC/S
1 2 tsp
per gal
NS
NS
NS
1
NS
NS
NPDES license restriction; Do not apply in
marina and/or aatuatina environments, oil
fields, or discharge effluent into lakes,
streams, ponds or public water (MPDES
license restriction)
Abbreviations used
Header:
Formulation:
In general:
Geographic
Codes:
Max. t Apps. •= maximum number of applications
Max. * Apps. @ Max. Rate «• maximum number of applications at maximum rate " ' ' • > -
Min. Interval Between Apps. @ Max. Rata (Days) «* minimum interval between applications at maximum rate (in days)
SC/S • Soluble Concentrate/Solid
NA • not applicable; NS « not specified
AZ - Arizona
28
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APPENDIX B
Table of the Generic Data Requirements
and Studies Used to Make the
Reregistration Decision
29
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for the
pesticide daminozide covered by this Reregistration Eligibility Decision. It contains generic data
requirements that apply to daminozide 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 MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
30
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
REQUIREMENT USE PATTERN CITATION
PRODUCT CHEMISTRY
61-1
61-2
61-3
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-7
63-8
63-9
Chemical Identity
Starting Materials &
Manufacturing Process
Formation of Impurities
Preliminary Analysis
Certification of Limits
Analytical Method
Color
Physical State
Odor
Melting Point
Density
Solubility
Vapor Pressure
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
00009540
GS032003, 00009511, 00009514
I
GS032003, GS032040, 42025201
GS032040
GS032040
»
00022043, 00009423, 00009540, 00009511
00009540
00009540
00009540
00009540
00154941
00009540, 41603401
41603402
31
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozitte
REQUIREMENT USE PATTERN CITATION
63-10
63-11
63-12
63-13
Dissociation Constant
Octanol/Water Partition
pH
Stability
ALL
ALL
ALL
ALL
00009540
00009540
00009540
32
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
REQUIREMENT USE PATTERN CITATION
ECOLOGICAL EFFECTS
* Additional Ecological Effects data were levied in the June, 1984 Daminozide Registration Standard;
However, these requirements have since been waived due to the change in use pattern. The
guidelines cited below are those necessary to support the greenhouse/non-food use pattern.
71-la
71-2a
71-2b
72-la
72-lc
72-2a
Acute Avian Oral-Quail/Duck
Avian Dietary (LC^ - Quail
Avian Dietary (LCg,) - Duck
Fish Acute (LC^ - Bluegill
Fish Acute (LD^ - Trout
Aquatic Invertebrate (ECSO)
I
I
I
I
I
I
42429001
00009705
00009575
00009704
00009706
424290022
2 Although no core aquatic invertebrate acute toxicity study was submitted, because the use of daminozide is restricted to greenhouses,
there are sufficient data to provide labeling statements.
33
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
REQUIREMENT USE PATTERN CITATION
TOXICOLOGY
81-1
81-2
81-3
82-la
83-la
83-lb
83-2a
83-2a
83-2b
83-2b
83-3a
83-3b
83-4
84-2a
84-2a
Acute Oral Toxicity - Rat
Acute Dermal Toxicity
Acute Inhalation - Rat
90-Day Feeding - Rodent
Chronic Toxicity - Rodent
Chronic Toxicity - Non-rodent
Oncogenicity - Rat (Daminozide)
Oncogenicity - Rat (UDMH)
Oncogenicity - Mouse
(Daminozide)
Oncogenicity - Mouse (UDMH)
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
2-Generation Reproduction - Rat
Gene Mutation (Daminozide)
Gene Mutation (UDMH)
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
00009712
00009737
00009712
00009727
00009413, 40813101
40928101
00009413, 40813101
41253303
40093501, 40813102
41253302, 41378001
00053764
00150511
40233901
00143054,00009681
40319901, 40319901
34
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
D
REQUIREMENT
USE PATTERN CITATION
84-2b
84-2b
84-4
84-4
85-1
Structural Chromosomal
Aberration (Daminozide)
Structural Chromosomal
Aberration (UDMH)
Other Genotoxic Effects
(Daminozide)
Other Genotoxic Effects (UDMH)
General Metabolism
00009683
i
40319901
00143055
40319901
40282901, 40214501
35
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
REQUIREMENT
USE PATTERN CITATION
ENVIRONMENTAL FATE
* Additional Environmental Fate data were levied in the Daminozide Registration Standard of June,
1984; However, these data have since been waived due to the change in use pattern. The guidelines
stated below are those necessary to support the greenhouse/non-food use pattern.
161-1
161-4
162-1
163-1
163-2
163-3
Hydrolysis
Photodegradation - Air
Aerobic Soil Metabolism
Leaching/Adsorption/Desorption
Laboratory Volatility
Field Volatility
00147749,00154942
WAIVED1
•
42687201 DATA GAP*
426872013
WAIVED1
WAIVED1
1 Based on the results of the supplemental Aerobic Soil Metabolism study (MRID 42687201), it appears highly unlikely that volatile
degradates (other than C02) exceeding 10% of the applied would be produced. Therefore, data on the photodegradation in air (1.61-4),
laboratory volatility (163-2), and field volatility (163-3) of daminozide are no longer required. '
2 One study (Yu and Kobryn, 42687201) was reviewed and provides supplemental information that daminozide degrades with a half-life
of 9.5 hours when incubated aerobically in a sandy loam soil. The major degradate was C02, with formaldehyde detected in the soil
in small quantities during the study. Additional information regarding the characterization of radioactivity present in the ethylene glycol
volatiles trap is required.
3 Because daminozide degrades so rapidly in aerobic soil (half-life of 9.5 hours), and the only degradation products are volatile
compounds and bound residues (Yu and Kobryn, 42687201), the Agency considers the data requirement fulfilled.
36
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
REQUIREMENT USE PATTERN CITATION
RESIDUE CHEMISTRY
* Residue chemistry data were levied in the June, 1984 Daminozide Registration Standard. These
requirements were waived when the food uses of daminozide were voluntarily cancelled on November
14, 1989.
37
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Daminozide
REQUIREMENT
USE PATTERN CITATION
EXPOSURE
133-1-A Foliar Residue Dissipation
133-3A-S Glove Permeability
133-3-SS Exposure to Greenhouse Workers
40037001'
40032602
41876001, 41876002
1 This study was found to be supplemental but provided data that were used to help establish a 24 hour restricted entry interval (RED
for post-application workers.
38
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APPENDIX C
BIBLIOGRAPHY
Citations Considered to be Part of the Data Base
Supporting Reregistration
39
-------
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by the Agency 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 the Agency and its predecessor
agencies in support of past regulatory decisions. Selections from other sources including
published literature, in those instances where they have been considered, are included."
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the case
of published materials, this corresponds closely to an article. In the case of unpublished
materials submitted to EPA, the Agency has sought to identify documents at a level parallel
to the published article from within the typically larger volumes in which they were
submitted. The resulting "studies" generally have a distinct title (or at least a single subject),
can stand alone for purposes of review and can be described with a conventional
bibliographic citation. The Agency has also attempted to unite basic documents and
commentaries upon them, treating them as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically
by Master Record Identifier, or "MRID Number". This number is unique to the citation,
and should be used whenever a specific reference is required. It is not related to the six-
digit "Accession Number" which has been used to identify volumes of submitted studies (see
paragraph 4(d)(4) below for further explanation). In a few cases, entries added to the
bibliography late in the review may be preceded by a nine character temporary identifying
number which is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material submitted
to the Agency, 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
a 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.
40
-------
c. Title. In some cases, it has been necessary for the Agency's bibliographers to create or
enhance a document title. Any .such editorial insertions are contained between square
brackets.
-d._ Trailing Parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following elements
describing the earliest known submission:
(1) Submission Date. The date of the earliest known submission appears immediately
following the word "received".
(2) Administrative Number. The next element immediately following the word
"under" is the registration number, experimental use permit number, petition
number, or other administrative number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter. When authorship is de-faulted to
the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers'). The final element in the trailing
parentheses identifies the Agency 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.
41
-------
GS032003
GS032040
00009413
00009575
00009681
00009683
00009704
BIBLIOGRAPHY
Conditt, M. K.; Baumgardner, J. R.; Hellman, L. M. (1988). JAOAC., 71
735-739. . .
NCI Carcinogenesis Technical Report Series No. 83, 1978. Bioassay of
Daminozide for possible carcinogenicity.
Von Schmelling, B. (1981) Letter sent to J. Schwemley dated March 23, 1981.
[Concerns Uniroyal Chemical's evaluation of the 1980 study by Newsome (MRID
05021600)]
Von Schmelling, B. (1983) Uniroyal submission of May 27, 1983. (Accession
Number 250943, MRID 00130644)
Oser, B.L. (1966) Report: Chronic (2-Year) Feeding Studies with B995 in Rats
and Dogs. (Unpublished study including letters dated Nov 1, 1966 from S.S.
Steinberg to Bernard L. Oser and from M.N. Daniels to Bernard L. Oser,
received Dec 15, 1966 under 7F0552; prepared by Food and Drug Research
Laboratories, Inc., submitted by United States Rubber Co., Naugatuck, Conn.-
CDL:090684-E)
Fink, R. (1974) Final Report: Eight-Day Dietary LC5o~Mallard Ducks: Project
No. 117-104. (Unpublished study received Oct 13, 1976 under 6F1752; prepared
by Truslow Farms, Inc., submitted by Uniroyal Chemical, Bethany, Conn.;
CDL:095567-A)
Brusick, D.J.; Weir, RJ. (1977) Mutagenicity Evaluation of B995: Final Report:
LB1 Project No. 2683. (Unpublished study received Mar 10, 1978 under
400-117; prepared by Litton Bionetics, Inc., submitted by Uniroyal Chemical,
Bethany, Conn.; CDL:233200-D)
Palmer, A.K.; Lovell, M.R. (1973) Dominant Lethal Assay of Alar in the Male
Mouse. (Unpublished study received Mar 10, 1978 under 400-117; prepared by
Huntingdon Research Centre, submitted by Uniroyal Chemical, Bethany, Conn.;
CDL:233200-F)
Sleight, B.H., IH.(1972) Bioassay Report Submitted to Uniroyal Chemical,
Naugatuck, Connecticut: Acute Toxicity of Alar» to Bluegill (Lepomis
macrochirus\. (Unpublished study received Aug 25,1977 under 400-79; prepared
by Bionomics, Inc., submitted by Uniroyal Chemical, Bethany, Conn.;
CDL:096322-B)
42
-------
00009705 Beavers, J.B. (1977) Final Report: Eight-Day Dietary LC50~Bobwhite Quail:
Project No. 117-126. (Unpublished study received Aug 25, 1977 under 400-79;
prepared by Wildlife International, Ltd., submitted by Uniroyal Chemical,
Bethany, Conn.; CDL:096322-C)
0000970(5 Kuc, W.J. (1977) Acute Toxicity of Alar Technical, Lot BL 8190 to the Rainbow
Trout, Salmo gairdneri. Richardson: UCES Project No. 11506-29-04.
(Unpublished study received Aug 25, 1977 under 400-79; prepared by Union
Carbide Corp.,' submitted by ^Uriiroyal Chemical, Bethany, Conn.;
CDL:096322-D)
00009712 " Shapiro, R. (1977) Report No. T-204. (Unpublished study received Mar 10,
1978 under 400-79; prepared by Nutrition International, Inc., submitted by
Uniroyal Chemical, Bethany, Conn.; CDL: 233201-B)
00009727 Carson, S. (1964) Report: Subacute (90-Day) Feeding Studies with B-995 in Rats.
(Unpublished study including supplement, received May 19,1966 under unknown
admin, no.; prepared by Food and Drug Research Laboratories, Inc. for United
States Rubber Co., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:
104894-B)
00053764 Knickerbocker, M.; Re, T.A. (1979) Report: Teratologic Evaluation of Alar
Technical in Sprague-Dawley Rats: Laboratory No. 5992. (Unpublished study
received Mar 20, 1979 under 400-17; prepared by Food and Drug Research
Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.;
CDL:237850-A)
00143053 Bootman, J.; Rees, R.; Anderson, C. (1982) P7642 : Investigation of Mutagenic
Activity in the Tkt/Mouse Lymphoma Cell Mutation Assay: Final Report:
82/UR0004/389. Unpublished study prepared by Life Science Research. 27 p.
00143054 Bootman, J.; Lodge, D.; May, K. (1982) P7642 : Assessment of Its Ability to
Induce Primary DNA Damage in Strains of Escherichia coli: 82/UR0005/308.
Unpublished study prepared by Life Science Research. 17 p.
00143055 Bootman, J.; Lodge, D. (1983) P7642 : Assessment of Its Ability to Induce
Genetic Damage in Saccharomyces cerevisiae: Amended Final Report:
82/UR0006/407. Unpublished study prepared by Life Science Research. 20 p.
00147749 Lengen, M. (1985) Addendum to: Hydrolysis of Daminozide... and Daminozide
Photolysis in Water and on Soil-Interim Report: Project No. 84244/84246.
Unpublished study prepared by Uniroyal Chemical. 59 p.
43
-------
00150511 Arnold, K. (1985) Teratology Study in Rabbits: Alar: 399-057. Unpublished
study prepared by International Research and Development Corporation. 79 p.
00154942 Lengen, M.; Abdel-Kader, H.; Peterson, G. (1984) Hydrolysis of Daminozide:
Project No. 84244.. Unpublished study prepared by Uniroyal Chemical. 21 p.
- u. _"'•'• "
40032602 Anderson, R. (1986) Daminozide/UDMH Glove Permeability. Unpublished
, compilation prepared by Radian Corp. 74 p.
; ' ' • -.' C'l ". ' ': - _i " H
40037001 Ames, R.; Ball, J. (1986) Dislodgeable Residue Study of Daminozide on Apples
and Chrysanthemums: Laboratory Project ID: UR203. Unpublished study
"^prepared byiJm'royal Chemical Co., Inc. 139 p.
, f -..--. • :
40093501 Jefferson, N.; Johnson, D. (1986) Two Year Dietary Oncogenicity Study in
Mice—12 Month Interim Report: Alar Technical: Laboratory Project ID
#399-054. Unpublished study prepared by International Research & Development
Corp. 27 p.
40214501 ~ Chadwick, M. (1987) Dermal Absorption of Alar in Rats-Final Report: ADL
_Ref: C-56508: Uniroyal Project No. .8643. Unpublished study prepared by
^Arthur D, Little, Inc. 40 p.
40233901 Mackenzie, K. (1987) Two-generation Reproduction Study with Alar in Rats (One
Litter per Generation): Final Report: HLA Study No. 6111-102. Unpublished
study prepared by Hazleton Laboratories America, Inc. 837 p.
40282901 Harned, W.; Tortora, N.; Billings, T. (1987) Metabolism of Daminozide in
Miniature Swine: Uniroyal Project No. 8637: Southwest Bio-Labs, Inc. Project
No. 863IS. Unpublished study prepared by Uniroyal Chemical Co., Inc. in
cooperation with Southwest BioLabs, Inc. 146 p.
40319901 Hastings, C. (1987) Uniroyal Response to EPA Comments of June 1, 1987 on
Four Mutagenicity Studies Performed Using UDMH. Unpublished study
prepared by Uniroyal Chemical Co., Inc. 7 p.
40813101 Johnson, D. (1988) Alar Technical (Daminozide): Two Year Dietary Toxicity and
Oncogenicity Study in Rats: Report No. 399-055. Unpublished study prepared by
International Research and Development Corp. 1875 p.
40813102 Johnson, D. (1988) Alar Technical (Daminozide): Two Year Oncogenicity Study
in Rats: Report No. 399-054. Unpublished study prepared by International
Research and Development Corp. 1563 p.
.1-.fr --:
44
•4 -: *
-------
40928101
41253302
41253303
41378001
41876001
41876002
42429001
42687201
Johnson, D. (1988) One Year Dietary Toxicity Study in Dogs: Alar Technical:
Laboratory Product ID: 399-066. Unpublished study prepared by International
Research and Development Corp. 320 p.
Goldenthal, E. (1989) Two Year Oncogenicity Study in Mice: UDMH: Report
No. 399-063. Unpublished study prepared by International Research and
Development Corp. 2082 p.
Goldenthal, E. (1989) Two Year Oncogenicity Study in Rats: UDMH: Report
No. 399-062. Unpublished study prepared by International Research and
Development Corp. 1757 p.
Goldenthal, E. (1990) Two Year Oncogenicity Study in Mice: UDMH: Lab
Project Number: IRDC/399/065. Unpublished study prepared by International
Research and Development Corp. 1734 p.
Rotondaro, A. (1991) B-Nine SP on Ornamentals Greenhouse Mixer/
Loader/Applicator Exposure Study: Lab Project Number: PAL-EF-89RP-89053:
89-6532-16. Unpublished study prepared by Hill Top Biolabs, Inc., in coop, with
Pan-Agricultural Labs, Inc. 308 p.
Ball, J. (1991) UDMH Greenhouse Worker Exposure Assessment. Unpublished
study prepared by Uniroyal Chemical Co. 9 p.
Campbell, S.; Lynn, S. (1992) Alar Technical: An Acute Oral Toxicity Study
with the Mallard: Lab Project Number: 117-165. Unpublished study prepared by
Wildlife International, Ltd. 18 p.
Yu, W.; Kobryn, K. (1993) Daminozide Aerobic Soil Metabolism: Lab Project
Number: 92123. Unpublished study prepared by Uniroyal. 53 p.
45
-------
APPENDIX D
List of Available Related Documents
46
-------
APPENDIX D
The following is a list of available documents related to daminozide. Its purpose is to provide
a pathlo more detailed information if it is required. These accompanying documents are part
of the Administrative Record for Daminozide and are included in the the Agency's Office of
Pesticide Programs Public Docket.
1. Health and Environmental Effects Science Chapters
2. Detailed Label Usage Information System (LUIS) Report
3. Daminozide RED Fact Sheet (included in this RED)
4. PR Notice 91-2 (Included in this RED) Pertains to the Label Ingredient Statement
Federal publications on daminozide are available and may be purchased from the National
Technical Information Service (NTIS), 5285 Port Royal Road, Springfield, VA 22161.
1. Guidance for the Reregistration of Pesticide Products Containing Daminozide as the
Active Ingredient (The 1984 Registration Standard): NTIS Stock No. PB87-104782
2. Pesticide Fact Sheet (No. 26) for daminozide: NTIS Stock No. PB87-112025
47
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. r.j,vv APPENDIX £ , .
Pesticide Reregjstration Handbook
48
-1-' k- iiiiiUCi,. .Lilt. tl.1 .>.•"„.*> I J i -.". •'., ..-_-•.
-------
United States Office of Prevention, Pesticides October 1991
Environmental Protection and Toxic Substances
Agency (H-7508W)
&EPA Pesticide
Reregistration
Handbook
How to Respond to
the Reregistration
Eligibility Decision
Document
-------
PRODUCT RZRZGX8TRATZON HANDBOOK
.'•_.V TABLE OF CONTENTS
I. Introduction
A. Purpose arid content
• •" - •.
B. R«r«gistration Eligibility Document
C. Reregistration Process
XI. Instructions for Responding
A. How and When to Respond
B. When No Response Is Needed
B. Where to Respond
"III. ' Submission of Data and'Labels/Labeling
A. Generic Data
B. Product Specific Data
1. Product Chemistry
2. Acute Toxicity
3. Product Performance
C. Labels/Labeling
Appendix
A. Confidential Statement of Formula and Instructions
B. Label Contents
•
C. Sssple Label Formats—General Use £ Restricted Use
D. Label Regulations (40 CFR 156.10)
-------
PESTICIDE REREGISTRATION HANDBOOK
I. INTRODUCTION
A. Purpose and Content of this Handbook
This Handbook provides instructions to registrants on how to
respond to the Reregistration Eligibility Document (hereafter
referred to as the "RED") and how to reregister products.
Seu^fon I is this introduction.
Section II contains step-by-step instructions which must be
followed by registrants responding to the RED.
section III provides additional instructions on the format,
content ^nd other aspects of generic data, product specific data
and labels/labeling which may be required to be submitted.
Detailed instructions are in the Appendix.
B. The RereeriBtration Eligibility Poeunenl: fami
M ??d?5 SfC?i?n 4 Of thc Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA), as amended in 1988, EPA is required to
reregister pesticides that were first registered before November 1,
1984. The RED describes in detail the subject chemical, its uses
*??
-------
,, ,If *h« RED declares that some or all uses of the chemical are
eligible for reregistration, affected registrants must first
respond within 90 days of receipt to the data call-in portion of
the RED. Within 8 months of receiving the RED, registrants must
submit or cite any data and labels/labeling required for each
product. EPA has until 14 months after the RED is issued (i.e..
6 months after the -registrants1 -8 month deadline) to review the
submission for each product and decide whether to reregister it
based on the 'following criteria:
— whether all of the product specific data and labels/labeling
are acceptable,
—whether all of the uses on the label/labeling are eligible,
--whether all of the active ingredients in the product are
eligible, and
—if no List 1 toxic inert ingredient -is contained in the
product (a List 1 inert is permitted only if all data
for it have been submitted and EPA determines
that the inert does not pose any unreasonable adverse
effects in that product) .
Products which meet all of these criteria will be
reregistered. Products which do not meet all of these criteria
but which have acceptable product specific data and labeling, will
be processed as amendments in order to implement label changes
required by the RED.. *
II- INSTRUCTIONS TOR REfiPQKPTNQ
A. Hov and When to Respond
This section provides directions for submitting timely and
adequate responses necessary to reregister products containing the
active ingredient covered by the RED. Registrants must follow
these steps exactly to avoid suspension of their products. All
products containing tbe active ingredient in the RED [i.e.,
manufacturing use products, end use products and special local need
{«™ *; Seetiea 24c) registrations] are subject to the requirements
of the RED. Figure 1 summarizes how and when to respond to the
RED. A step-by-step explanation follows.
fijfclp__l. Are Expedited Uibel Chanaas Reeniirad? m SOme
instances, EPA may conclude that certain changes to product
labels/labeling must be implemented rapidly. If the RED requires
expedited label/labeling changes, registrants must submit the items
below by the deadline specified in the RED. if expedited label
changes are not required, go to Step- 2 y— -; — _,.,.. ...... ...
- a. 'Application for Registration (EPA Form 8570-1) . Complete
-------
and sign the form. In Section II, insert the phrase "Expedited
.Amendment in Response to the Reregistration Eligibility Document
for (insert ease name for chemical)." Applications for expedited
label changes will be processed as applications for amended
registration. Use only an original application form with a red
identifier number in the upper right-hand corner.
b. Five (5) copies of revised draft label and labeling.
Refer to the RED for label/labeling changes, and follow the
instructions in Section XII. C. and the Appendix of this Handbook
for revising the label and labeling for each product.
_ Are cia-ba required? If the RED requires generic or
product specific data, you must follow the directions in the data
call-in notice in the RED. All registrants must respond for all
products within 90 dava of receipt; products for which an adequate
response is not received on time will be subject to suspension. No
be oiven for responding yjthiB «o
_.. Are Uges Of a Pesticide Eligible for
If any uses of the active ingredient's) covered by the RED are
eligible for reregistration, follow these instructions. If no uses
are eligible, no. further response may be needed (see page 5).
EPA's decision on the eligibility of each of the uses of the
active ingredient (s) is presented in the RED. Xf anv uses of a
chemical are eligible for reregistration, registrants for
manufacturing-use products (KPs), end-use products (EPs) and
special local needs registrations (SLNs), must submit the items
*flow for each areduyt within B montha of the date of issuance of
the RED:
a. Application for. Reregistration (use EPA Form 8570-1).
SS^iSJ? *? *& ^2. S1™' In Section JI °* that form, check the
box "Other" and insert the phrase "Application for Reregistration."
Ose only an original application form with a red identifier number
.in the upper right-hand corner.
b. Five (5) copies of revised draft label and labeling
Refer to the RED for labeling changes specific to the active
ingredient, follow the instructions in Section XXI.c. of this
Handbook and refer to the Appendix of this Handbook for guidance on
current requirements for labels and labeling. If there are
ineligible uses on the label or labeling, you may delete such uses
and avoid all requirements and consequences which may be associated
with ineligible uses (e.g, generic data requirements, cancellation
suspension, etc.). If you delete certain uses now and those use4
become eligible for reregistration later, you must submit an
amendment application to add those uses back to the label.
-------
.1.
TO
(RED)
"REGISTRATION
USE
(EP')
STEP Is
Are expedited label revisions required?
i No
Submit application
and labels on
expedited schedule
specified in RED.
BTEP 2s Are data required?
STEP 3s
No
Submit forms within
»0 days for generic
and product specific
data.
->^.
Are any of the uses on the label
eligible for reregistration?
Yes
Are any uses on the label
ineligible for reregistration?
Yes
Do you wish to
_ ineligible
from label?
For eacb XV «
« SIN (24e) submit
application within
• months, if
the submission
is acceptable,
the label will be
stamped accepted
as aa amendment.
£2 reregistretioa
will be issued.
No
.Yes
For each KP i EP
t BLN (24e) submit
application within
• months, if
the submission
is acceptable,
the label will be
stamped accepted
and a. notice of .
reregistration
will be issued.
i
No further response
necessary. Await
the outcome of
EPA's review.
-------
. »• Product Specific Data. You Bust follow the instructions
in the Data-call-in notice;in the RED and in Section III of this
Handbook.. Responses to the data call in are due within »o d«v« Of
receipt of the RED and submission or citation of data is due within
8 nofltha of the issuance of the RED.
d. Two (2) copies of the current Confidential Statement of
Formula UFA.Form 8570-4, revised February 85). Two completed and
signed CSF forms must be submitted for the basic formulation and
for each alternate formulation. If CSFs are not provided for the
alternate formulas, they will not be reregistered and will no
J£n?er £? acceptable. The Appendix of this Handbook has specific
instructions for completing the CSF form.
•
C*J^fH*tioB w!th*"P«et to Citation of Data (EPA Form
This form must be completed, signed and submitted for
*..*0 assure to»t the data compensation provisions" of
are met.
B. WhenNo Resoonee is Wm*A»
of a Pcsticia« are eligible for reregistration, it
t y°U TVi11 bc "Wiir«I to submit product splcif ic
?a!?<£?Hi Jling* ,Uscs ?f an active ingredient may be declared
ineligible for reregistration for two possible reasons:
an in";£«aila5le
-------
C. Where to
^•
U.S. Mail: :
v - s
Document Processing Desk (insert distribution code)
Office ;of -Pesticide Programs (H7504C) =
Environmental Protection Agency
401 M street, s.W. :
Washington, D.C. 20460-0001
express aail or by hand delivery: -,.,.. ,
Document Processing Desk (insert distribution eode)
Office of Pesticide Programs (H7504C)
Room 266A, Crystal Mall 2
= 1921 Jefferson Davis Highway
Arlington, VA 22202.
These mailing addresses and the following distribution codes
must bemused to assure the timely receipt and processing of you?
o? o"1:Smi.s'iong "" "Y •***«•»«* "1 th.'handliSJ
.. « . -** (*fc«re xxx is the ease eode given on the front of
the RED)--use this distribution code for all responses pertaining
to or containing generic «3flU. Such responses include thTto-dal
response forms for generic data or hard copies of generic data?
RED-RD-PMxx (where xx is the Product Manager team number)~
use this distribution code for all responses pertaining to or
containing product specific data er labeling, such responses would
include expedited labeling amendments, 90-day responses to product
specific data requirements, hard copies of product specific data
and applications for ^registration. p«c«ic aata
III. SUBMISSION OF DATA AKH
This section provides additional instructions concerning
responses required for generic data, product specific data and
A. Generic Data
During EPA's evaluation of an active ingredient for
reregistration, Additional generic data requirements may be
identified that registrants must fulfill, in some instances these
£at.a requirements would have t*
-------
Any new data requirements and how they affect reregistration
eligibility of a chemical are discussed in the RED. If new generic
data requirements are imposed in a Data Dall-ln Notice in the RED,
registrants must respond ms described in that Notice. The RED also
contains instructions for completing these forms, a citation of
EPA«s legal authority for requiring the new data, a listing of
options available to registrants for satisfying the data
requirements and the neae of the contact person for.- inquiries.
B. Product Specific Data
Product specific data may be required for the rereglrtration
of each pesticide product in tlwse areas—product chemistry, acute
toxicity and efficacy. •
1. Product Chemistry
Following are instructions for submitting product-specific
data and a discussion of EPA's policy on inert ingredients.
a. Data '
All data requirements for HPs, EPs and SLNs (24c*s) are
specified in the Data Call-in Notice in the RED. In addition:
--If you cite data from another identical, registered
product, you must identify the EPA registration number of that
product.
--If the product-specific data submitted or cited do not
pertain to an identical formulation to the product submitted for
reregistration, then new product-specific data are required to be
submitted by the deadline specified in the Data Call-in Notice.
The only exception is for products which EPA "groups" together a
being similar enough to depend on the same data. Such groupings
are discussed in the appendix to the RED (for acute toxicity
purposes, for example), if it was feasible to do so.
b. Inert Ingredients
< ??* *hal, j*Pj««nt«» « strategy for regulating inert
ingredients which affects the reregistration of pesticide products
This strategy, issued on April 22, 1987 (52 FR 13305-13309) and
updated on November 22, 1989 (54 FR 48314-48316), adopted certain
policies designed to reduce the potential for adverse effects from
pesticide products containing intentionally added inert
ingredients. EPA divided the known inert ingredients into four
categories:
—Inerts of toxicological concern (List 1) for which available
data demonstrate toxic effects of concern (includes about 50
chemicals).
-------
~ Potentially :toxic inert* (List 2) for which only limited
data are available, :but such data or the chemical structure suggest
the potential for toxicity (includes about 60 chemicals) .
--Inerts of unknown toxicity (List 3) for which no data or
?*JJJ for •"•footing toxic effects-are available (includes up to
2,000 chemicals). '
--Inerts of minimal concern (List 4) which are generally
regarded as innocuous (includes about 290 chemicals).
.4* *?* *** «»•« of «n active ingredient are
?„! ^i*1! f?r ,rer«9*«tration, all products containing that
•,?redl*nt, 1?H.J* «ubject to reregistration. EPA will, as
J? the reregistration review, examine the inert ingredienti of
P^ UCt Prl°3 , to f«f«9i*tration to ensure that they do not
5 J '•n«T!nr?ff»on!51* Tisk8-, In ^viewing the product chemistry
data, EPA will identify List 1 inerts. EPA will continue to
encourage registrants to eliminate any List 1 inerts present
*?? ?giStrati°.n °f V*0**** -containing only List 2, 3 or 4 iSJrti
will be unaffected by the inerts strategy. ««ra
. »4 Consistent with the strategy on inerts, a product containing
a List 1 inert ingredient will n^ be reregistered until a full
risk assessment of the product has been conducted, based on the
data called in for that inert ingredient. However, the existing
vXiS^S °f If*0*™? "?tainin' • "* 1 inert win rSaSn
valid as long as «ie product bears the required label warning and
is in compliance with any outstanding DM, or other activity under
tne inerts strategy.
Any product containing a List 2, 3 or 4 inert mav be
Kr?S f**!! 4f*itf**tsim1} °th*r r«**"»«ats for reregistration.
As the inerts strategy is implemented and data for the List 2 and
3 inerts are reviewed, EPA may move these inerts to the other
*«!£?• J 1^ JCrt Wer! "TrtJ^ List lf Products containing that
inert would become ineligible for reregistration. Inert
ingredients must also meet normal registration and tolerance
requirements, as applicable.
Acute Toxieitv
«. * 15* fa-.ta cal}'ln notice in the RED specifies the acute
toxicity data required for reregistration of each UP or EP. It
indicates whether any of the standard tests have been waived and,
'if 'SO, ' '• • •
If feasible, EPA will "batch" products that are similar with
respect to their- acute *oxieity so that one set of tests can
support reregistration of each baatch of products. This approach
will impose the least amount of testing necessary to adequately
support the -registration and labeling-for pesticide products. The
-------
aain benefits of this approach are to minimize the need for animal
testing, reduce the expense to registrants to generate the tests
and decrease the resources EPA must spend on reviewing data.
Registrants may contact other registrants with products in the same
"batch" to decide whether to provide or depend on one set of data;
alternatively, registrants may choose to conduct their own studies.
3. Product Performance :
Consult the Data Call-In section of the RED to determine
whether Product Performance data are required for your product.
Product performance (efficacy) data are generated in studies
designed to document how candidate pesticide formulations perform
as pest control agents. These data include tests run to determine
whether a formulation is lethal to certain pest species, to
document the effectiveness of the formulation in controlling pest
species in actual use situations, and to determine whether certain
claims beyond mere control of a pest (e.g., "six-month residual
effect," "kills Warfarin resistant house mice," etc.) are
justified. ° '*"''.'_
EPA has standard protocols for certain efficacy tests. In
general, standard methods have been developed for tests needed to
substantiate claims that have been made frequently for pesticide
products. As the scope of potential pesticidal claims is extremely
broad, the Agency does not have standard methods for tests needed
to substantiate many pesticide claims, especially those that are
uncommon. The Product Performance Guidelines, Subdivision 6, offer
general guidance for developing protocols for efficacy testing.
Proposed protocols should be submitted to EPA for review before
tests are initiated.
a. Efficacy Data Submission Waiver Poliev
FIFRA gives the Administrator of EPA authority "to waive data
requirements pertaining to efficacy" but does not require that
efficacy data requirements be waived for any class of pesticide
product registered under Section 3 of the Act. As a matter of
policy, EPA does not require submission of efficacy data to support
wany tyr*.* of pesticidal claims but does require submission of such
data for certain types of claims. As noted in 40 CFR 158.640. this
waiver applies to the submission of efficacy data rather than to
the generation of efficacy data. EPA expects each registrant to
"ensure through testing that his products are efficacious when used
in accordance with commonly accepted pest control practices."
This general policy notwithstanding, EPA may, at any time,
require a registrant to submit efficacy data to support any claim
made for a product. EPA also aay require that certain claims of
effectiveness be established before a Section 3 registration is
granted. . •
-------
Confidential Business Information: Does Not Contain National Securit
&EPA
United SIMM Environmental Protection Agency
Office of Pesticide Programs (TS-7671
Washington. DC 20460
Confidential Statement of Formula
Information (f.O. 12065)
LJ Basic Formulation ..
I—I Alternate Formulation
Form Approved. OMB No. 2070-0060. Approval expires 11 -3f>93
Page
See metruetions on Back
2. Nam* and Address of Producer (Include ZIP Code)
4. Registration No /File Symbol
7. Pounds/Gal or Bulk Density
6. EPA Product Mgr/Team No.
6 pH
6. Country Where Formulated
9. Flash Point/Flame Extension
EPA USE ONLY
10. Component* in Formulation (Lift M ecfue/ry imroducKt
into tht nxmulMwn. Gnv commanry accepted cnenwca/
neme. ir»0» name, end CAS number.)
11. Supplier Name ft. Address
12. EPA Reg. No.
13. Each Component
In Formulation
8. Amount
14 Cictilwd Limilt
% by «V«iaht
•>1
-------
b. Claims and Products tor Which Efficacy Data Generally
Are Required
Submission of efficacy data at reregistration typically is
required for the following ty?
-------
APPEHDXX
.-. . ...-.-. - . , A -
A. - Confidential Statement of Poraula and Instructions
B. Instructions for Label contents
C. Sample Label Ponnats—General Use £ Restricted Use
D. Label Regulations (40 CFR 156.10)
-------
Instructions far Completing the Confidential Statement a?
Formula
The. Confidential Statement of Formula (CSF) Form 8570-4 must
be used. Two legible,, signed copies of the form are required.
Following are basic instructions:
a. All the .Blocks on the form must be filled in and answered
completely.
b. If any block is not applicable, nark it N/A.
c. The CSF must be signed, dated and the telephone number of
the responsible party ~'
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B. -INSTRUCTIONS FOR IABEL
4° CF* 15V" *nd Pestieide Regulatory (P.R.) Notices require
Iabel}n9 •tatements appear at certain location^ on
in ndij£ c
J1' *I?°DUCIvNAI? " The nan*' brand or trademark is required to
fJ^S? °n ^ fr£nt Panel» Preferably centered in the upper
part of the panel. The name of a product will not be accepted if
it is false or misleading. [40 CFR 156. 10 (b)]
Item 2. COMPANY NAM* AND ADDRESS - The name and address of the
producer, registrant or person for whom the product is produced are
required on the label and should be located at the bottom of the
front panel or at the end of the label text. [40 CTR 156.lO(c)]
* P* TON*EKTS ' *net contents statement is required on all
labels or on the container of the pesticide. The preferred
location is the bottom of the front panel immediately Ibove S2
company name and address, or at the end of the label text. The net
contents must be expressed in the largest suitable unit/ e.a ?!
pound 10 ounces" rather than "26 ouncis." in addition to English
f content« »ay »>• expressed in metric units. fJocFR
J *
h^ REGISTRATION NUMBER - The registration number assigned
S?J? S™1?1*? Product Bust °PPear on the label, preceded by the
phrase "EPA Registration No.," or "EPA Reg. No." The registration
number must be set in type of a size and style similar to "the?
Saralle? ^ ff* °^^ ^l « «W«* it appears an5 mus? ™
?J I7*1! to w11' The registration number and the required
identifying phrase must not appear in such a manner as to suggest
by"the
Item 5. EPA ESTABLISHMENT NUMBER - The EPA establishment number
PET°!!d!!i by ^C Phra*e "EPA Est'" ls the final «stablishmeUt at
which the product was produced, and may appear in any suitable
location on the label or immediate container. It must also appear
on the wrapper or outside container of the package if the EPA
establishment number on the immediate container cannot be clearlv
read through such wrapper or container. [40 CFR 156. 10 (f)]
Item 6A. INGREDIENTS STATEMENT - An ingredients statement is
normally required on the front panel. The ingredients statement
must contain the name and percentage by weight of each active
ingredient and the total percentage by weight of all inert
ingredients. The preferred location is immediately below the
product name. The ingredients statement must run parallel with
and be clearly r distinguished from, other text on "the panel, it
must not be placed in the body of other text. [40 CFR 156.10(0)1
' ~*' " ----- " *'*' •"** •"-*a'J - *• — ' «-T»J«a«*i . , ',- . ! , *
Item 6B. "POUNDS 'TOR GALLON STATEMENT - For liquid agricultural
-------
formulations, the pounds per gallon of active ingredient must be
indicated on the label. [40 CFR 156.10(h)(iv)]
Item 6C. NAMES TO BE USED IN INGREDIENT STATEMENT - The acceptable
common name, if there is one, shall be used, followed by the
chemical name. If no common name has been established, the
chemical name alone shall be used. Chemicals related to the -Active
ingredient are allowed to be listed enlv if efficacy data
supporting such claims are submitted or referenced. If su;h data
are provided, the related chemicals must be lifted separately and
not as a portion of the active ingredient.
Item 6D. INERT INGREDIENTS DECLASSIFIED AS ACTIVE INGREDIENTS - If
EPA has reclassified chemicals from inert ingredient status to
active ingredient status, registrants of affected products muse.
change the ingredient statement accordingly (See 52 FR 13307-8,
April 22, 1987). If such pesticides have food uses, tolerances
must either be established for such uses, or an exemption from the
requirement for tolerances must be obtained.
Item 6E. NOMINAL CONCENTRATION - The amount of active ingredient
declared in the ingredient statement must be the nominal
concentration of the product as defined in 40 CFR 158.153(i) and
described in P.R. Notice 91-2.
Item 7. WARNINGS AND PRECAUTIONARY STATEMENTS - Front panel
precautionary statements must be grouped together, preferably
within a block outline. The table below shows the minimum type
size requirements for various size labels.
Size of Label on Signal Word "Keep Out of Reach
Front Panel Minimum Type Size of Children*!
in Sou a re Inches All Capitals Minimum Type Size
5 and under 6 point 6 point
above 5 to 10 10 point 6 point
•above 10 to 15 12 point 8 point
above 15 to 30 14 point 10 point
over 30 * 18 point , 12 point
Item 7A. CHILD HAZARD WARNING STATEMENT - The statement "Keep Out
of Reach of Children" must be located on the front panel above the
signal word except where contact with children during distribution
or use is unlikely. [40 CFR 156.10(h)(i)(ii)]
Item 7B. SIGNAL WORD - The signal word (DANGER, WARNING, or
CAUTION) is required on the front panel immediately below the child
hazard warning statement. [40 CFR 156.10(h)(1)(i)].
-------
Item 7C. SKULL t CROSSBONES AND WORD "POISON" - On products
assigned a toxicity Category I on the basis of oral, dermal, or
inhalation toxicity, the word "Poison" shall appear on the label in
red on a background of distinctly contrasting color and the skull
and crossbones shall appear in immediate proximity to the word
POISON. [40 CFR 156.10(h)(l)(i)].
L ' STATEMENT OF PRACTICAL TREATMENT,.- A Statement of
practical ^ treatment (first aid or other) shall appear on the label
- • . -'--I . .
I tear 7E. REFERRAL STATEMENT - The statement "see Side (or Back)
Panel for Additional Precautionary Statements" is required on the
ti^nt panel for
-------
1. All uses restricted. The following statements Bust be placed
in a black box at the top of the front panel of the label and
labeling: •
a. The statement "Restricted Use Pesticide" must appear at
the top of the front panel of the label. The statement
must be set in type of the same minimum size as required
for human hazard signal word [see , table in 40 CFR
156 . 10 (h) ( 1 ) ( iv) ] . NO statements of any Xind nay appear
above this RUP statement.
b. The reason .for the the restricted use classification must
appear below the RDP statement. The RED will prescribe
"•his statement.
c. A summary statement of the terms of restriction must
appear directly below this reason statement on the front
£vnel\, If, use is restricted to certified applicators,
the following statement is required: "For retail sale to
J? < US-4 °nl/ by Ce^if ied Applicators or persons under
their direct supervision and only for those uses covered
by the Certified Applicator's Certification." The RED
will specify what statement must be used.
2. some but not all uses restricted, if the RED states that some
USCf *f!, classified for restricted use, and some m
unclassified, several courses of action are available:
a. You may label the product for Restricted use. If you do
so, you may include on the label uses that are
unrestricted, but you may not distinguish them on the
label as being unrestricted.
b' SSL??*.!*"*?1? .f1^ reswtrie*ed «*« from your label and
submit draft labeling bearing only unrestricted uses.
c. You may "split" your registration, i.e., register two
separate products with identical formulations, one
bearing only unrestricted uses, and the other biaring
restricted uses. To do so, submit two applications fo?
reregistration, each containing all form? and necessary
labels. Both applications should be submitted
simultaneously. Note that the products will be assigned
separate registration numbers. ««i9n«a
Item 9B. MISUSE STATEMENT - All products aust bear the misuse
statement, "It is a violation of Federal law to use Sis product "
incoiJ8i*tent with its labeling." This statement
Item IDA. REENTRY STATEMENT - If a restricted entry interval (RED
?fS ^n^tablishedt by, the Agency,, it must , be Included on thi
label. Additional worker protection statements may be xequired in
-------
accordance with PR Notice 83-2, March 29, 1983.
Item 1 OB. STORAGE AND DISPOSAL BLOCK - All labels are required to
bear storage and disposal statements. These statements are
developed for specific containers, sizes, and chemical content.
These-instructions must be .grouped and appear under the heading
^Storage and Disposal" in the directions for use. This heading
must be set in the same type sizes as required for the child hazard
warning. Refer to P.R. Notices 83-3 and 84-1 to determine the
storage and disposal instructions appropriate for your products.
Item IOC. DIRECTIONS FOR USE - Directions for use must be stated
in terms which can be easily read and understood by the average
person likely to use or to supervise the use of the pesticide.
When followed, directions must be adequate to protect the public
from fraud and from personal injury and to prevent unreasonable
adverse effects on the environment. [40 CFR 156.10(i)(2)]
COLLATERAL LABELING .
Bulletins, leaflets, circulars, brochures, data sheets, flyers, or
other written or graphic printed matter which is referred to on the
label or which,^s .to accompany .the product .are, termed collateral
labeling. Such labeling may not bear claims or representations
that differ in substance from those accepted in connection with
registration of the product. Collateral labeling must be made part
of the response to the RED and submitted for review.
-------
LABEL FORMAT FOR UNCLASSIFIED PRODUCTS
-------
LABEL FORMAT FOR PRODUCTS CLASSIFIED FOR RESTRICTED USE
-------
Protection Agency
•ubmltter has asserted a confidential
business information claim concerning
the material).
(5) A copy of each document, propos-
al or other item of written material
concerning the Registration Standard
provided by the Agency to any person
or party outside of government
(within 15 working days ' Jter the item
is made available to si ch person or
party).
(6) A copy of the Registration Stand-
ard:
(7) With respect to a Registration
Standard for which the Agency has
determined that a substantial i» 'Com-
plete chronic health and teratology
data base exists, a copy of the FEDERAL
REGISTER notice concerning availabil-
ity of a proposed Registration Stand-
ard, and a copy of each comment re-
ceived in response to that notice
(within 10 working days after receipt
by the Agency, or 15 working days If
the submitter has asserted a confiden-
tial business information claim con-
cerning the material). ,
(8) A copy of the FEDERAL REGISTER
notice announcing the issuance of the
Registration Standard (within 10
working days after the publication of
the notice).
(c) Index of the docket The Agency
wfll establish and keep current an
index to the docket for each Registra-
tion Standard. The index will include.
but is not limited to:
(1) A list of each meeting between
the Agency and any person or party
outside of government, containing the
date and subject of the meeting, the
names of participants and the name of
the person requesting the meeting.
(2) A list, of each document in the
docket by title, source or redpientCs).
szi£ the d£tc the document was re-
ceived or provided by the Agency.
(d) Availability of docket and indi-
ces. (1) The Agency will make avail-
able to the public for inspection and
copying the docket and index for any
Registration Standard.
(2) The Agency wfll establish and
maintain a mailing list of persons who
have specifically requested that they
receive indices for Registration Stand-
ard dockets. On a quarterly basis. SPA
will distribute the indices of new mate-
rials placed in the public docket to
§156.10
these persons. Annually. EPA1 wfll re-
quire that persons on the list renew
their requests for inclusion on the list.
(8) The Agency will issue «"*MaMy in
the FEDERAL REGISTER (in conjunction
with the annual schedule notice speci-
fied in 1155.25) a notice announcing
the availability of docket indices.
(4) Each FEDERAL REGISTER notice of
availability of a Registration Standard
wfll announce the availability of the
docket index for that Standard. -
116644 Notice of •TallabUitr.
(a) The Agency wfll issue in the FED-,
XRAL REGISTER a notice announcing the'
issuance and availability of Registra-
tion Standard which:
(1) Concerns a previously unregis-
tered active ingredient: or
(2) Concerns a previously registered
active ingredient, and the Registration-
Standard states that registrants wfll
be required (under FZFRA section
8(cX2KB)) to submit chronic health
(including, but not limited to. chronic
feeding, oncogenidty and reproduc-
tion) or teratology studies.
(b) Interested persons may submit
comments concerning any Registra-
tion Standard described by paragraph
(a) of this section at any time.
(c) The Agency wfll issue in the FED-
ERAL REGISTER a notice announcing the
availability of. and providing opportu-
nity for comment on, each proposed
Registration Standard which concerns
a previously registered active ingredi-
ent for which the Agency has deter-
mined that a substantially complete
chronic health and teratology data
base exists. Following the comment
period and issuance of the Registra-
tion Standard, the Agency wfll issue in
the FEDERAL REGISTER a notice of avail-
ability of the Registration Standard.
PART 156—LABELING REQUIRE-
MENTS POR PESTICIDES AND DE-
VICES
AcTMOEirr 7 U.B.C. U6-l»6y.
• 166.10 LabeliBtnaniraBentL
(a) GeneraX-Cl) Contents of the
label Every pesticide products shall
bear a label containing the informa-
tion specified by the Act and the regu-
-------
*mi°
40 CR Ch. I (7-I.W
paragraph
producer, registrant. or penon lor
of this sec- er of the pesttcidelSSdSS
s
tttr) The product mntm wrapper or eutaide
br.swcrib«ltoi«rmf»ph which the
(rt) An tojredlent itotement u pre-
to pmgnph Se
plied equally to both the English and product; w»posiuon ox me
-------
Protection Agon*?
§ 1S6 10
^^^^£*?% •s~*
2S2?68 Other thiB ** * PfcrtteWa or (2) No name, brand, or trademark
^rAf^ormWe^dlngoomp^ra "a^'SSJ S^SS
with other pesticide, or devices:
JJ? ^ i!?*6*?1! directly or toil-
rectly Implying that the pesticide or
device is recommended or endorsed by
any agency of the Federal Govern.
-w -
(vl) The name of a pesticide which
contains two at -more principal active
togre^ents If the name suggests one
2tiSOIS> J5Sun? *" «*<* Principal
active Ingredients even though the
2*?^ ff Sf* °P*T to'^dients are
"*!£!? ??*htTt to ^ >»beling;
(vii) A true statement used in such a
way as to give a false or misleading im-
pression to the purchaser. ^^
(viii) Label disclaimers which negate
or detoact from labeling statements re-
quired under the Act and these regula-
_ ,
palms as to the safety of the
pesticide or its ingredients, Including
statements such as "safe." "nonpoison-
ous," "noninjurious/' "harmless" or
•nontoxic to humans and pets" with
or without such a qualifying phrase as
"when used as directed"; and
(x) Non-numerical and/or compara-
tive statements on the safety of the
product, including but not limited to-
(A) "Contains all natural tarredi.
ents"; *" n*lurM mgredl-
(B) "Among the least toxic chcml-
eals known-
"Pollution approved
(II) Has not beenroroved by the
Administrator through JegisteaSono*
ropplemental registraUM as in addK
tional name pursuant to 1 152.132 -
<« Name and address of producer
registrant, or person lor whom pit*
duced. An unqualified name and acT
*«« liven on the label shall be con-
«Wered as the name and addresi Tof %
Producer. If the registranrsiume a^
Pe*rs on the label and the iWtetrantte
not the producer, or 3 the £Sei5rthe
Person for whom the pestSde WM
produced appears on the label. It must.
** Qualified by appropriate
»uch as "Packed f or • • V
•?**!• *•" w "Sold by • •
"»* the name Is not that of the
ducer-
, »« "*9ht or measure o/ eon-
*?*• cl) *** n«t weight or measure
of «>atent «hall be exclusive of wrap-
E61* or other materials and shall be
H*e, *vera»« content unless explicitly
gt*ted ** a m«««*nnm quantity
(2) u thc Pesticide is a liquid, the
net content statement shall be to
ISPfL0?,1!?111* measure at 68' P (20*C)
V"1 S1*11 ^ expressed to conventional
American units of fluid ounces Dint*
'"Srts. »»<» Wllons. P *
<3) If the pesticide Is solid or semi.
!SrilJ|?acSuf1 °' Pressurized, or is a
mixture of liquid and solid, the net
statement shall be to terms of
PI
m
-------
§156,10 40 C« Ch. I (7-M9 Idttlen)
tent of toe packages In a shipment fall toe label. If there to an outside con-
below the stated average content. tainer or wrapper through which the
(e) Product registration number, ingredient statement cannot be clearly
The registration number assigned to read, toe ingredient statement must
toe iSScide product at toe time of also appear on such outside container
rert tnUon shall appear on the label, or wrapper. If toe size or form of toe
JJSeded by the phrase "EPA Regis- package makes it Impracticable to
tration No..- or the phrase "EPA Reg. place toe ingredient statement on the
No." The registration number shall be front panel of toe label, permission
rti£«S^W3ir'£S S^KSSASSJ?"*5
:aW«rsa±S!SB; ^^^SJ^S1^
and toe required Identifying phrase Sxton^na^S?Siiih^5t?«Other
g^e^por»^^mSss:ss awSj^^ssssK
£en£»ement of toe .-oduct by toe bo^ oFoto^text?* * PUOCd * "*
(f) Producing establishments reyii- .£* Nam^J° ** **** in ingredient
tration number. The producing estab- Illxi*1 Mane used for each in-
lishment registration number preced- fredlent •hall be toe accepted
ed by toe phrase "EPA Est". of toe f0™011 name, if there to one. fol-
final establishment at 7hlch toe prod- lowed °y the chemical name. The
uct was produced may aypear in any f???1011 aame m** oe used alone only
suitable location on toe label or imm£ if ttte»ell known. If no common name
diate container. It must appear on toe *** been established, toe chemical
wrapper or outside container of toe 55™* al°DC Ih*u °e used. In no case
package if toe EPA establishment reg- fSL*** use of a trademark or proprie-
istration number on toe immediate Ury nftme ^ Permitted unless such
SSSSfL ?nnot ** ***** wad 5SJ! S"*J**? •"•i*^ « » common
through such wrapper or container. ?*m« *? the Administrator under toe
(gKIngredient *tatement-tl) Oener- *uthority of section 25(cX6).
ol The label of each pesticide product <*> Statements '
must bear a statement which contains
.. — — —— •—••••• •»•••*** " — "-Binn •-—- •••.^oH w« "*B"Tvivnuf Mnan n*
toe name and percentage by weight of *tated in terms of weight-to-weiffhZ
each active ingredient, toe total per- The sum of pm^tSfS^uSS^
2?^e S9^^ ct •H mert tog»di- *** the inert ingredients shall belOO
S& t? .1? Ve ****** contains ar- Percentages shall not be expressedI by
!^J°?n7_fJ)!m- » «tatement of toe fJ«we of values such as «-- ^ ~ Dy
and water-soluble the uses of toe pesticide
as elemental ar- expressed as weight of at
ingredients must be ent per unit area, a statement of
, . by toe wlume of toe pesticide formulation
^^«J.to«»dients.''or toe singu- *bHl also appear in toe
lar forms of these terms when appro- statement.
-------
|j,ylr«nintntal Protection Agency
jo eases where it is determined
ft pesticide formulation changes
ical composition significantly,
product must bear the following
Statement in a prominent position on
- the label: "Not for sale or use after
- -[date]." '
(ii) The product must meet all label
claims up to the expiration time indi-
cted on the label. . *
(7) Inert ingredients. The Adminis-
trator may require the name of any
inert ingredlentCs) to be listed in the
Ingredient statement if he determines
that such ingredientts) may pose a
hazard to man or the environment.
(b) Warning* end precautionary
statement*. Required warnings and
precautionary statements concerning
§1S«.JIO
the general areas of toxicologies!
hazard including hazard to children,
environmental hazard, and physical or
chemical hazard fall into two groups;
those required on- the front panel of
the labeling and those which may
appear elsewhere. Specific require-
ments concerning content, placement.
type auv;, and prominence are given"
below. r
(1) A* wired front panel statement!.
With die exception of the child
hazard warning statement, the text re-
quired on the front panel of the label
is determined by the Toxicity Catego-
ry of the pesticide. The category is as-
signed on th«, huis of the highest
hazard shown by any of the indicators
in the table below:
IV
UptovrtMuOngSO
ing/kg.
Up to and Mudta .2
mg/Mw.
UptoandtnducCnoZOO
torn M ttm MO ing/kg..
fnn 200 MM 2000.
horn 100 tvulOOORV/
Fmm 2. ton SO mo/Mir..
horn 2,000 tou 20,000—
••n SO fng/Mw.
OOVTDWIrVw
tor T d*yt.
S*ww» Mutton st 72
tan.
No eomMl epwKy:
WWion iwvUbto
•BWn 7 dfeyt.
ModvMi Mttttofilt 72
tan.
QrMlwMntOMO.
NoMMton.
MW or tfght MMion «
72 tan.
(i) Human Aaeard signal word—(A)
Toxicity Category I. All pesticide prod-
ucts meeting the criteria of Toxicity
Category I shall bear on the front
panel the signal word "Danger." In ad-
dition if the product was assigned to
Toxicity Category I on the basis of its
oral, inhalation or dermal toxidty (as
distinct from skin and eye local ef-
fects) the word "Poison" shall appear
in red on a background of distinctly
contrasting color and the skull and
crossbones shall appear in immediate
proximity to the word "poison."
(B) Toxicity Category II. All pesti-
cide products meeting the criteria of
Toxicity Category U shall bear on the
front panel the signal word "Warn-
ing."
(C) Toxicity Category III. All pesti-
cide products meeting the criteria of
Toxicity Category m shall bear on
the front panel the signal word "Cau-
tion."
(D) Toxicity Category TV. All pesti-
cide products meeting the criteria of
Toxicity Category IV shall bear on the
front panel the signal word "Caution."
(E) U»e of tignal words. Use of any
signal word(s) associated with a higher
Toxicity Category is not permitted
except when the Agency determines
that such labeling is necessary to pre-
vent unreasonable adverse effects on
man or the environment. In no case
shall more than one human hazard
signal word appear on the front panel
of a label
(ii) Child haeard warning. Every pes-
ticide product laoel shall bear on the
front panel the statement "keep out of
reach of children." Only in cases
where the likelihood of contact with
children during distribution, market-
ing, storage or use is demonstrated by
the applicant to be extremely remote,
or if the nature of the pesticide is such
-------
1156.10
that It is approved for use on infants
or small children, may the Administra-
tor waive this requirement.
(Ill) Statement of practical treat'
ment-(A) Toxicity Category /• A
statement of practical treatment (first
aid or other) shall appear on the front
Panel of the label of all pesticides fall-
ing into Toxicity Category I on the
basis of oral, inhalation or dermal tox-
idty. The Agency may. however.
permit reasonable variatiorj m the
placement of the statement of practi-
cal treatment is some reference such
as "See statement of practical treat-
ment on back panel" appears on the
front panel near the word "Poison"
o^Lfial U^C •tlCtt^U s^2o\ifl CPOottiOODififta
(B) Other toxicity categories. The
statement of practical treatment is not
required on the front panel except as
described in paragraph (hXIXillXA) of
this section. The applicant may. how-
ever, include such a front panel state-
ment at his option. Statements of
practical treatment are. however, re-
quired elsewhere on the label in
accord with paragraph (hX2) of this
section if they do not appear on the
front panel. -w— •*«
(iv) Placement and prominence. All
the require front panel warning state-
ments shall be grouped together on
the label, and shall appear with suffi-
cient prominence relative to other
front panel text and graphic material
to make them unlikely to be over-
looked under customary conditions of
purchase and use. The following table
ahows the minimum type size require-
40 C« Ch. I (7.109 idlti*,)
ments for the front panel wanun*
statements on various sizes of labels'^
) of Mool from oonol In
• ond
Abo* • to 10-
Abo* 10 to 18.
AbovolttoSO.
to
IS
14
It
I
10
12
mother required warning* and pre-
cautionary statements. The warning
and precautionary statements asre!
S?^d^?low *hmu •W"* together on
the label under the general heading
"Precautionary Statements" and
under appropriate subheadings of
"Hazard to Humans and Domestic Art-
mals." "Environmental Hazard" and
"Physical or Chemical Hazard."
animalt. (A) Where a hazard exists to
humans or domestic animals, precau-
tionary statements are required indi-
cating the particular hazard, the
route
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Protection Agency
Environmental hazard*. Where a
exists to non target organisms
humans -and domestic anl-
** U. precautionary statements are re-
•" stating the nature of the
and the appropriate precau-
to avoid potential accident.
or damage. Examples of the
statements and the drcum-
jjjnces under which they are required
*° if * PwttcW* intended for out-
use contains an active ingredient
acute oral LD* of
too or less, the statement "This Pesti-
dde is Toxic to Wildlife" is required.
(B) If * pesticide intended for out-
door use contains an active ingredient
with a fish acute LC« of 1 ppm or less,
the statement "This Pesticide is Toxic
to Fish" is required.
(C) If * pesticide intended for out-
door use contains an active ingredient
with an avian acute oral ID** of 100
me/kg or less, or a subacute dietary
§156.10
LCw of 500 ppm or less, the statement
"This Pesticide is Toxic to Wildlife" is
required. -
(D) If either accident history or field
studies demonstrate that use of the
pesticide may result in fatality to
birds, fish or mammils, the statement
"This pesticide Is extremely toxic to
wildlife (fish)" to required.
(E) For uses invrfring foliar applica-
tion to agricultur J crops, forests, or
•hade trees, or lor mosquito abate-
ment treatments, pesticides toxic to
pollinating insects must bear appropri-
ate label cautions.
(F) For all outdoor uses ,*her than
aquatic applications the label must
bear the caution "Keep out of lakes,
ponds or streams. Do not contaminate
water by cleaning of equipment oir dis-
posal of wastes."
(Hi) Physical or chemtert hazard*.
Warning statements on the flammabil-
ity or explosive characteristics of the
pesticide are required as follows:
FtMhpott
1
(A) AttMUftOIO COWTMNOtt
any veto opening.
tCT F; I tare to • fettMCk at
29* Fend net ever WFerRta
•tm« «t«n«ion to men* tan IS to tang at a
of e to torn ta tamo.
Do not punehra or
130* F
tarn*. Do not
and open tamo. Do net punctur* or
to temperatures aoovo 130* F may
Do not UM or
ISO* F may
bunrtng.
IB)
AtorMewSTF.
«T F and net
«T F
Mevt SO* F and not ever ISO* F.
Do not i
torn Ira.
end open
(!? Zirsstisxs for lbe-U> General
requirement*—
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ft 156.10
(B) The label bean a reference to
the direction! for v*f in accompanying
leaflet* or circulars, such at "See di-
rections in the enclosed circular:" and
(C) The Administrator determines
that it is not necessary for such direc-
tions to appear on the label,
(ill) Exception* to requirement for
'direction for «*«—^yMifartMr1ng process-
es;
(J) The product wfll not come into
the hands of the general public except
after incorporation into finished prod-
ucts: and
The Administrator determines
that such directions are not necessary
to prevent unreasonable adverse ef-
fects on man or the environment.
(2) Content* of Direction* tor Vte.
The £4rections for use «>**ii include
the following, under the headings "Di-
rections for Use":
(i) The statement of use rlsstlflrm
tion as prescribed in paragraph (j> of
this section immediately under the
heading "Directions for Use."
Cii) Immediately below the state-
ment of use classification, the state-
ment "It is a violation of Federal law
to use this product in a manner incon-
sistent with its labeling."
(Ill) The sited) of application, as for
example the crops, *«im«i« areas, or
objects to be treated.
(iv) The target pestcs) associated
with each site.
(v) The dosage rate associated with
each site and pest.
(vi) The method of application, in-
cluding instructions for dilution, if re-
quired. and typed) of application ap-
paratus or equipment required.
(vii) The frequency and timing of ap-
plications necessary to obtain effective
results without causing unreasonable
adverse effects on the environment.
(viii) Specific limitations on reentry
to areas where the pesticide has been
applied, meeting the requirements
concerning reentry provided by 40
CFR Part 170.
-------
Prof^tlon Agency
Any limitations or restrictions on
required to prevent unreasonable
verse effects, such as:
(A) ReQttfred intervals between ap-
olication and harvest of food or feed
oops. _ - _,
(B) Rotational crop restrictions.
Front panel statement ofrttMct-
•* «•* c*«« 40
, Feb. f.
Redes-
has both restricted use(s) and general
used), both of these uses may appear
on a product labeled for restricted use.
Such products shall be subject to the
provisions ox paragraph (JX2) of this
section.
(1) General Vie Clarification. Pesti-
cide products *>^rlng directions lor
use(s) classified general «**«ii be la-
beled with the exact words "General
Classification" Immediately below the
heading 'Directions for Use." And ref-
erence to the general rliurtlflrttlfm
that suggests or implies that the gen-
eral utility of the pesticide extends
beyond those purposes and uses con-
tained in the Directions lor Use wfll be
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APPENDIX F
Generic Data Call-In
49
-------
No generic data are being called in for daminozide
50
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APPENDIX G
Product Specific Data Call-In
51
-------
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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 product(s) containing this active ingredient. Within 90 days after you receive this Notice
you must respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its Attachments
A through G; or
2. Why you believe you are exempt from the requirements listed in this Notice and in
Attachment C, Requirements Status and Registrant's Response Form, (see section HI-B);
or
3. Why you believe EPA should not require your submission of product specific data in
the manner specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with
its requirements or should be exempt or excused from doing so, then the registration of your
product(s) subject 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 3-31-96).
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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 II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
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 Form
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the data
needed to support continued registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product specific data. No additional
generic data requirements are being imposed. You have been sent this Notice because you have
product(s) containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment C, Requirements
Status and Registrant's Response Form. Depending on the results of the studies required in this
Notice, additional testing may be required.
II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment C, Requirements Status and Registrant's Response Form, within the timeframes
provided.
53
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II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined.in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines are available from the National Technical Information Service (NTIS),
Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation 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)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(V\ NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change the
requirements of anv previous Data Call-Infsl. or any other agreements entered into with the Agency
pertaining to such prior Notice. Registrants must comply with the requirements of all Notices to
avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for product specific data must be
submitted to the Agency within 90 days after your receipt of this Notice. Failure to adequately
respond to this Notice within 90 days of your receipt will be a basis for issuing a Notice of Intent
to Suspend (NOIS) affecting your products. This and other bases for issuance of NOIS due to
failure to comply with this Notice are presented in Section IV-A and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this notice or
(c) request a data waiver(s).
54
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A discussion of how to respond if you chose the Voluntary Cancellation option is presented
below. A discussion of the various options available for satisfying the product specific data
requirements of this Notice is contained in Section III-C. A discussion- of options relating to
requests "for data waivers is contained in Section III-D.
There are two forms that accompany this Notice of which, depending upon your response, one
or both must be used in your response to the Agency. These forms are the Data-Call-in Response
Form, and the Requirements Status and Registrant's Response Form. Attachment 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 tne 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 III-C of this Notice and comprise options 1 through 6 on the Requirements
Status and Registrant's Response Form and item numbers 7a and 7b on the Data Call-In Response
Fprm. Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements.
3. Request for Product Specific Data Waivers. Waivers for product specific data are discussed
in Section III-D of this Notice and are covered by option 7 on the Requirements Status and
Registrant's Response Form. If you choose one of these options, you must submit both forms as
well as any other information/data pertaining to the option chosen to address the data requirement.
55
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III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge dh the Data Call-In Response Form that you agree to satisfy the product
specific data requirements (i.e. you select item number 7a or Tbj, 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 g'enerate and submit data within the specified timeframe (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1. Developing Data — If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced herein and
in the attachments. All data generated and submitted must comply with the Good Laboratory
Practice (GLP) rule (40 CFR Part 160), be conducted according to the Pesticide Assessment
Guidelines (PAG), and be in conformance with the requirements of PR Notice 86-5.
The time frames in the Requirements Status and Registrant's Response Form are the time
frames that the Agency is allowing for the submission of completed study reports. The noted
deadlines run from the date of the receipt of this Notice by the registrant. If the data are not
submitted by the deadline, each registrant is subject to receipt of a Notice of Intent to Suspend the
affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice and
intend to seek additional time to meet the requirements(s), you must submit a request to the Agency
which includes: (1) a detailed description of the expected difficulty and (2) a proposed schedule
including alternative dates for meeting such requirements on a step-by-step basis. You must 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
56
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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 texicity 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 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
57
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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 166;iiAs stated in 40 CFR 160.30) " 'Maw 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."
b. Health and safety studies completed after May 1984 must also contain all GLP-required
quality assurance and quality control information, pursuant to the requirements of 40 CFR Part
160. Registrants must also certify at the time of submitting the existing study that such GLP
information is available for post-May 1984 studies by including an appropriate statement on or
attached to the study signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline relevant to
the study provided in the FIFRA Accelerated Reregistration Phase 3 Technical Guidance and
that the study has been conducted according to the Pesticide Assessment Guidelines (PAG) or
meets the purpose of the PAG (both available from NTIS). A study not conducted according
to the PAG may be submitted to the Agency for consideration if the registrant believes that the
study clearly meets the purpose of the PAG. The registrant is referred to 40 CFR 158.70
which states the Agency's policy regarding acceptable protocols. If you wish to submit the
58
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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.
Potion 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 aU 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.
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
59
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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.
III-D REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because you believe it is inappropriate, you
must attach a complete justification for the request, including technical reasons, data and references
to relevant EPA regulations, guidelines or policies. (Note: any supplemental data must be
submitted in the format required by PR Notice 86-5). This will be the only opportunity to state the
reasons or provide information in support of your request. If the Agency approves your waiver
request, you will not be required to supply the data pursuant to section 3(c)(2)(B) of FIFRA. If
the Agency denies your waiver request, you must choose an option for meeting the data
requirements of this Notice within 30 days of the receipt of the Agency's decision. You must
indicate and submit the option chosen on the Requirements Status and Registrant's Response Form.
Product specific data requirements for product chemistry, acute toxicity and efficacy (where
appropriate) are required for all products and the Agency would grant a waiver only under
extraordinary circumstances. You should also be aware that submitting a waiver request will not
automatically extend the due date for the study in question. Waiver requests submitted without
adequate supporting rationale will be denied and the original due date will remain in force.
SECTION IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol when
such is required to be submitted to the Agency for review.
60
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3. Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any option
chosen to address the data requirements (e.g., any required action or information pertaining
to submission or citation of existing studies or offers, arrangements, or arbitration on the
sharing of costs or the formation of Task Forces, failure to comply with the terms of an
agreement or arbitration concerning joint data development or failure to comply with any
terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies, as
required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or failure of a
registrant on whom you rely for a generic data exemption either to:
a. inform EPA of intent to develop and submit the data required by this Notice on a Data Call-
in Response Form and a Requirements Status and Registrant's Response Form:
b. fulfill the commitment to develop and submit the data as required by this Notice; or
c. otherwise take appropriate steps to meet the requirements stated in this Notice, unless you
commit 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,
61
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Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols,, including the incorporation of any
changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of reporting, the
completeness of results, and the adequacy of any required supporting (or raw) data, including,
but not limited to, requirements referenced or included in this Notice or contained in PR 86-5.
All studies must be submitted in the form of a final report; a preliminary report will not be
considered to fulfill the submission requirement.
IV-C EXISTING StOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing stocks of
a pesticide product which has been suspended or cancelled if doing so would be consistent with the
purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally not be
consistent with the Act's purposes. Accordingly, the Agency anticipates granting registrants
permission to sell, distribute, or use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your produces) 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 afier 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
62
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to establish that you have been conducting the study in an acceptable and good faith manner must
have been submitted to the Agency, before EPA will consider granting an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a pesticide
is registered a registrant has additional factual information regarding unreasonable adverse effects
on the environment by the pesticide, the registrant shall submit the information to the Agency.
Registrants must notify the Agency of any factual information they have, from whatever so'urce,
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.
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,
y /
Daniel M. Barolo, Director
Special Review and ^
Reregistration Division
Attachments
A - Data Call-In Chemical Status Sheet
B - Product-Specific Data Call-In Response Form
C - Requirements Status and Registrant's Response Form
for the Product Specific Data Call-In
63
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D - EPA Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Registration
E - EPA Acceptance-Criteria
F - List of Registrants Receiving This Notice
G - Cost Share and Data Compensation Forms, and Product
Specific t)ata Report Form
64
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ATTACHMENT A
Product Specific DCI Chemical Status Sheet
65
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DAMINOZIDE: DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing daminozide.
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 daminozide.
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) the Agency'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 daminozide 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 daminozide are contained
in the Requirements Status and Registrant's Response, Attachment C. The Agency has concluded
that additional data on daminozide 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 daminozide products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic database of daminozide, please contact Mr.
Andrew Ertman at (703) 308-8063.
If you have any questions regarding the product specific data requirements and procedures
established by this Notice, please contact Franklin Gee at (703) 308-8008.
All responses to this Notice for the Product Specific data requirements should be submitted to:
Franklin Gee
Special Review and Reregistration Division (H7508W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: Daminozide
66
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ATTACHMENT B
Product Specific Data Call-in Response Forms (Form A)
plus Instructions
-------
INSTRUCTIONS FOR COMPLETING THE "DATA CALL-IN RESPONSE" FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already'completecLby the Agency.
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 8-11.Self-explanatory.
Note: You may provide additional information that does not fit on this form in a signed letter that
accompanies this form. For example, you may wish to report that your product has already
been transferred to another or that you have already voluntarily cancelled this product. For
these cases, please supply all relevant details so that the Agency can ensure that its records
are correct.
68
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DRAFT COPY
Page 1 of 1
United States Environmental Protection Agency Form Approved
Washington. D. C. 20460
* ' OMB No. 2070-0107
DATA CALL-IN RESPONSE 2070-0057
Approval Expires 03-31-96
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply the information requested on this form.
Use additional sheet(s) if necessary.
1. Company name and Address 2. Case # and Name 3. Date and Type of OCI
SAMPLE COMPANY 0032 Daminozide PRODUCT? SPECIFIC
NO STREET ADDRESS
NO CITY, XX 00000
t
4. EPA Product
Registration
NNNNNN-NNNNN
5. I wish to
cancel this
product regis-
tration volun-
tarily.
6. Generic Data
6a. 1 am claimimg a Generic
Data Exemption because I
obtain the active ingredient
from the source EPA regis-
tration number listed below.
N.A.
6b. 1 agree to satisfy Generic
Data requirements as indicated
on the attached form entitled
"Requirements Status and
Registrant's Response."
N.A.
7. Product Specific Data
7a. Hy product is a HUP and
I agree to satisfy the HUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
»
t
7b. My product is an EUP and
I agree to satisfy the EUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response.1* '
'
8. Certification 9. Date
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or. both under applicable law.
Signature and Title of Company's Authorized Representative ,
10. Name of Company Contact 11. Phone Number
-------
-------
ATTACHMFJ^TC
Product Specific Data Call-In Requirements Status and
Registrant's Response Forms (Form B) plus Instructions
69
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND REGISTRANT'S
RESPONSE" FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by the Agency. Note the unique identifier number assigned by the
Agency 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, Subpart c.
Item 5. The study title associated with the guideline reference number is identified.
Item 6. The use patters (s) of the pesticide associated with the product specific requirements
is (are) identified. For most product specific data requirements, all use patterns are
covered by the data requirements. In the case of efficacy data, the required studies
only pertain to products which have the use sites and/ or pests indicated.
Item 7. The substance to be tested is identified by the Agency. 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 Decisions unless the Agency
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 the Agency indicates in an attachment
to this notice that my product is similar. Enough to another product to qualify for this option
I certify that another party in the agreement is committing to submit or provide the required
data; if the required study is not submitted on time, my product my be subject to suspension.
3. I have made offers to share in the cost to develop data (Offers to Cost Share). I understand that
70
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this option is available only for acute toxicity or certain efficacy data and only if the Agency
indicates in an attachment to this Data Call-In Notice that my product is similar enough to
another product to qualify for this option. 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 otherterms under Option-3 in the Data Call-In Notice (Section IH-C.l.) apply
as well.
4. By the specified due date, I will submit an existing study that has not^een submitted previously
to the Agency by anyone (submitting an Existing Study). I certify that this study will meet all
the requirements for submittal of existing data outlined in option 4 in the Data Call-In Notice
(Section III-C. 1.) 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 HI-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 the Agency has "grouped"
with one or more other products for purposes of depending on the same data. I may also
choose this option if I am citing my own data. In either case, I will provide the MRID or
Accession number (s) number (s) for the cited data on a "Product Specific Data Report" form
or in a similar format. If I cite another registrant's data, I will submit a completed
"Certification With Respect To Data Compensation Requirements" form.
7. I request a waiver for this study because it is inappropriate for my product (Waiver Request).
I am attaching a complete justification for this request, including technical reasons, data and
references to relevant EPA regulations, guidelines or policies. [Note: any supplemental data
must be submitted in the format required by P.R. Notice 86-5], I understand that this is my
only opportunity to state the reasons or provide information in support of my request. If the
Agency approves my waiver request, I will not be require to supply the data pursuant to Section
3(c) (2) (B) of FIFRA. If the Agency denies my waiver request, I must choose a method of
71
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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 the Agency can ensure that its records are correct.
72
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DRAFT COPY
Page 1 of 2
United States Environmental Protection Agency Form Approved
Washington, D. C. 20460 OMB NO. 2070-0107
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE Approval^iJeToS-SI-W
INSTRUCTIONS: Please type or print in ink. Please read carefully
Use additional sheet(s) if necessary.
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requi rement
Number
61-1
61-2 (a)
61-2 (b)
62-1
62-2
62-3
63-2
63-3
63-4
63-7
63irl2
63-14
the attached instructions and supply the information requested on this form.
2. Case « and Name 3. Date and Type of DCI
0032 Daminozide PRODUCT SPECIFIC
MD# NNNNNN-RD-NNNN
EPA Reg. No. NNNNNN-NNNNN
5. Study Title
Prod Che* - Regular Chemical
Product identity ft compos ition(l)
bescrtp of starting materials, (1,2)
production ft formulation
proc
Discussion of formation of (1,3)
, impurities
Preliminary analysis (1,4)
Certification of limits (1,5)
Analytical method (1)
Color
Physical state
Odor
Density
pH (9)
Oxidizing or reducing action (10)
10. Certification
R
I
o
Progress
Reports
1
2
3
6. Use
Pattern
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
7. Test
Substance
MP/EP
MP/EP
MP/EP
(
MP/EP
MP/EP
MP/EP
MP
MP/EP
MP
MP/EP
MP/EP
MP/EP
8. Time
Frame
8 mos.
8 mos.
8 mos.
8 mos .
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
9. Registrant
Response
^
-
11. Date
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or1 both under applicable law.
Signature and Title of Company's Authorized Representative
12. Name of Company Contact
13. Phone Number
-------
u K t\ r i uufi
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print in ink. Please read carefully
Use additional sheet(s) if necessary.
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
63-15
63-16
63-17
63-18
63-19
63-20
63-21
81-1
81-2
81-3
81-4
81-5
81-6
the attached instructions and supply the information requested
2. Case # and Name
0032 Daminozide
EPA Reg. No. NNNNNN-NNNNN
5. Study Title
fUmebfttty (11)
Explodability (12)
Storage stability
Viscosity (13)
MtsclbiHty (14)
Corrosion characteristics
Dielectric breakdown voltage (15)
Acute toxic - Regular Chemical
Acut« oral toxtclty-rat (1,36,37)
Acute dermal (1,2,37)
toxtcity- rabbit/rat
Acute inhalation toxicity-rat (3)
Primary eye irritation-rabbit (2)
Primary dermal irritation (1,2)
Dermal sensitization (4)
initial to frdicate certification as to information on this page
(full text of certification is on page one).
f
Progress
Reports
1
2
3
6. Use
Pattern
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHtJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
7. Test
Substance
MP/EP
MP/EP
MP/EP
MP/EP
MP/EP
MP/EP
EP
MP/EP and
MP/EP and
MP/EP and
MP/EP
MP/EP
MP/EP
i
on this form.
3. Date and
Page 2 of 2
Form Approved
'OMB No. 2070-0107
2070-0057
Approval Expires 03-31-96
Tvoe of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
,
.
TGAI
TGAI
TGAI
8> Time
Frame
S
8
B
8
8
8
B
B
8
8
B
8
8
mos,,
mos.
mos*
mos.
mos.
mos.
mos.
mos.
mos.
mos.
mos.
mos.
mos.
9. Registrant
Response
'
•:
••<•
X
Date
-------
DRAFT COPY
Page 1 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
FOOTNOTES AND KEY DEFINATIONS FOR GUIDELINE REQUIREMENTS
Case f and Name: 0032 Daminozide
Key: HP = manufacturing-use product; EP » end-use product; provided formulators purchase their active ingredient(s) from a registered source, they need not submit or eft*
data pertaining to the purchased product.[NOTE: If a product is a 100 percent repackage of another registered product that is purchased, and any use for the product docs
not differ from those of the purchased and registered source, users are not subject to any data requirements identified in the tables.]; TEP « typical end-use product;
TGAI = technical grade of the active ingredient; PAI = "pure" active ingredient; PAIRA = "pure" active ingredient, radiolabeled. V
Use Categories Key:
C - Terrestrial nonfood crop
H - Greenhouse food crop
H - Indoor nonfood
A - Terrestrial food crop
F - Aquatic nonfood Industrial
K - Residential outdoor
B - Terrestrial food feed crop
G - Aquatic nonfood residential
L - Indoor food
D - Aquatic food crop
I - Greenhouse nonfood crop
N - Indoor Medical
E - Aquatic 'nonfood outdoor
J - Forestry i
0 - Indoor residential
Footnotes: [The following notes are referenced in column two (5. Study Title) of the REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE form.]
Prod Che« - Regular Chemical
1 Requirements pertaining to product identity, composition, analysis, and certification of ingredients are detailed further in the following sections: *158.155 for
product identity and composition (61-1); M58.160, 158.162, and 158.165 for description of starting materials and manufacturing process (61-2); *158.167 for
discussion of formation of impurities (61-3); *158.170 for preliminary analysis (62-1); *158.175 for certification of limits (62-2); and *158.180 for enforcement
analytical methods (62-3).
2 A schematic diagram and/or brief description of the production process will suffice if the pesticide is not already under full scale production and an experimental
use permit is being sought.
3 If the pesticide is not already under full scale production and an experimental use permit is sought, a discussion of unintentional ingredients shall be submitted to
the extent this information is available.
4 To support registration of an MP or EP, whether produced by an integrated system or not, the technical grade of Active Ingredient must be analyzed. If the technical
grade of Active Ingredient cannot be isolated, a statement of composition of the practical equivalent of the technical grade of Active Ingredient must be submitted.
Data on EPs or MPs will be required on a case-by-case basis.
5 Certified limits are not required for inert ingredients in products proposed for experimental use.
9 Required if test substances are dispersible with water.
10 Required if product contains an oxidizing or reducing agent.
11 Required if product contains combustible liquids.
12 Required if product is potentially explosive.
13 Required if product is a liquid.
U Required If product is an emulsiftable liquid and is to be diluted with petroleum solvents.
15 Required if end-use product is liquid and is to be used around electrical equipment.
Acute Toxic - Regular Chemical
1 Not required if test material is a gas or highly volatile.
2 Not required if test material is corrosive to skin or has pH less than 2 or greater than 11.5; such a product will be classified as Toxicity Category I on the basis
of potential eye and dermal irritation effects. '
I Required if the product consists of, or under conditions of use will result in, an inhalable material (e. g., gas, volatile substances, or aerosol/particulate).
A Required unless repeated dermal exposure does not occur under conditions of use.
36 Special testing (acute, subchronic, and/or chronic) is required for organophospates, and may be required for other cholinesterase inhibitors and other pesticides
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DRAFT COPY
Page 2 of 2
United States Environmental Protection Agency
Washington, D. C. ^20460
FOOTNOTES AND KEY DEFINATIONS FOR GUIDELINE REQUIREMENTS
Case | and Name: 0032 Daminozide
Footnotes (cont.):
which have demonstrated a potential to adversely affect the visual system. Registrants should consult with the agency for development of protocols and methodology
prior to initiation of studies.
37 Testing of the EP dilution is required if it can be reasonably anticipated that the results of such testing may meet the criteria for restriction to use by certified
applicators specified in 40 CFR 152.170(b) or the criteria for initiation of special revfew specified in 40 CFR 154.7 (1>. . ' certmea
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ATTACHMENT D
EPA's Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Reregistration
73
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ATTACHMENT D
EPA'S BATCHING OF DAMINOZIDE [BUTANEDIOIC ACID MONO (2,2-DIMETHYL
HYDRAZIDE)] END-USE PRODUCTS FOR MEETING ACUTE TOXICITY DATA
REQUIREMENTS FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of end-use products containing the active ingredient
Daminozide [butanedioic acid mono (2,2-dimethylhydrazide)], the Agency has batched products
which can be considered similar for purposes of acute toxicity. Factors considered in the sorting
process include each product's active and inert ingredients (identity, percent composition and
biological activity), type of formulation (e.g., emulsifiable concentrate, aerosol, wettable powder,
granular, etc.), and labeling (e.g., signal word, use classification, precautionary labeling, etc.).
Note that the Agency is not describing batched products as "substantially similar" since some
products within a batch may not be considered chemically similar or have identical use patterns.
Batching has been .accomplished using the readily available information described above.
Frequently acute toxicity data on individual end-use products has been found to be incomplete.
Notwithstanding the batching process, the Agency reserves the right to require, at any time, acute
toxicity data for an individual end-use product should the neeti arise.
The registrant of the end-use products within a batch may choose to generate, submit or cite
a single battery of six acute lexicological studies to represent all the products within that batch. If
a registrant chooses to generate the data for a batch, he/she must use one of the products within
the batch as the test material. If a registrant chooses to rely upon previously submitted acute
toxicity data, he/she may do so provided that the data base is complete and valid by today's
standards (see acceptance criteria attached), the formulation tested is considered by the Agency to
be similar for acute toxicity, and the formulation has not been significantly altered since submission
and acceptance of the acute toxicity data. Regardless of whether new data is generated or existing
data is cited, the registrant must clearly identify the material tested by its EPA registration number.
In deciding how to meet the product specific data requirements, the registrant must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED document. 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. If the registrant supplies the data to support a batch of products,
he/she must select one of the following options: Developing Data (Option 1), Submitting an
Existing Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study
(Option 6).
74
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The following table (Table I) lists 1 batch containing 2 products containing Daminozide.
Table I.
Batch
Number
1
EPA
Registration
Number
400-69
400-110
% Daminozide [butanedioic
acid mono
(2, 2-dimethylhydrazide) ]
85.0
: 85.0
Formulation Type
Soluble Concentrate
Soluble Concentrate
The following table (Table II) lists two products that were considered not to be similar for
purposes of acute toxicity, and were not placed in any batch. The registrant is responsible for
meeting the acute toxicity data requirements for each product.
Table II.
EPA Registration Number
400-79
400-117
% Daminozide [butanedioic
acid mono
(2, 2-dimethylhydrazide)]
85.0
99.0
Formulation Type
Formulation Intermediate
Technical
75
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ATTACHMENT E ,.
»A Acceptance Criteria
76
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SUBDIVISION D
Guideline Study Title
Series 61 Product Identity and Composition
Series 62 Analysis and Certification of Product Ingredients
Series 63 Physical and Chemical Characteristics
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• 61 Product Identity and Composition
ACCEPTANCE CRITERIA
Does your study -meet the following acceptance criteria?
*'— feS^W'gpS^)*^ (includc *roduc
2' n Concentration, and certified limits (upper and
««* intentionally!1*
. .
-. certain toxicologically significant impuriils (2g
dioxins,. nitrqsamines) present at
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8. (continued)
_ 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 toxicologically significant impurities
(see #3)
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61 Product Identity and Composition
GUIDANCE FOR SUMMARIZING STUDIES
«»-£ the Active
« n°St ^istered pS5u?ts ' by ' submi«lon o f* tSe
?;rifV*d sfateBent of Formula Ingredients P/ge (EPA Fora 8570-4)
Items 7 and 8 can be satisfied for most technical grade active
ingredients (TGAIs) by submission of a flow chart with cheSica?
° eaCh intcnded chemical reactioS The flow Sa?J
- — * -2
Mterial
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62 Analysis and Certification of Product Ingredients
ACCEPTANCE CRITERIA .
The following criteria apply to the technical grade of the active
ingredient being reregistered. Use a table to present the
information in items 6, 7, and 8.
Does your study meet the following acceptance criteria?
l. Five or more representative samples (batches in case of
batch process) analyzed for each active ingredient and all
impurities present at > 0.1%
2. Degree of accountability or closure > ca 98*
3- 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
5. Statement of precision and accuracy of analytical method
used to analyze above samples
6. Identities and quantities (including mean and standard
deviation) provided for each analyzed ingredient
7. Upper and lower certified limits proposed for each active
ingredient and intentionally added inert along with
explanation of how the limits were determined
8. Upper certified limit proposed for each impurity present at
> 0.1% and for certain toxicologically significant
impurities at <0.1% along with explanation of how limit
determined
9. Analytical methods to verify certified limits of each
active ingredient and impurities (latter not required if
exempt from requirement of tolerance or if generally
recognized as safe by FDA) are fully described
10. Analytical methods (as discussed in #9) to verify certified
limits validated as to their precision and accuracy
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62 Analysis and Certification of Product Ingredients
GUIDANCE FOR SUMMARIZING STUDIES •
technical 9r"u et
for a11 active
2. Degree of accountability or closure in analyses in item #1.
3 * levelsa
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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
SJunsell 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 fi£ the specific gravity of liquids reported with
reference to water at 20° C. [Note: Bulk density of
registered products may be reported in Ibs/ft or
Ibs/gallon.]
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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)
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
Experimentallydetermined 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
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63 Physical and Chemical Characteristics
GTJIDANCE FOR SUMMARIZING STUDIES :
The following criteria apply to rhe technical grade of the active
ingredient being reregistered.
1. Description of color.
2. Description of physical state.
3. Description of odor.
4. Indication of meltii.cr point (in C°).
5. Indication of boiling point (in C°).
6. Indication of density, bulk density, and specific gravity.
7. Indication of solubility.
8. Indication of vapor pressure.
9. Indication of dissociation constant.
10. Indication of octanol/vater partition coefficient.
11. Indication of PH.
12. Description of stability.
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SUBDIVISION F
study
Oral Toxicity in the Rat
fi 1 1 % j_ **•*•*» A **jf ^Lil ^vXl^S KcL^w • R2U^^3^^to ^3IT ^St^ i T%'A jfe
Ji'J -Jrlnary Eye Irritation in the Rabbit
81-5 ' Primary Dermal Irritation Study
Bi-6 Dermal Sensitization in the Guinea Pio
81-7 Acute Neurotoxicity in the Hen
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81-1 Acute Oral Toxicity in the Rat
ACCEPTANCE CR CTERIA ;
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, snd-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 a * are supplemental and may not be required
for every study.
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81-1 Acute Oral Toxicity in the Rat
GUIDANCE FOR SUMMARIZING STUDIES
teSted' e'g< 80lid' 1*W*A. Percent
., -/ end-use product, etc.
2. The number of aninals/dose/sex tested.
3. Dosing route and regimen.
4. Vehicle used
5. Doses tested and results
6* ?2di*id?ai observations on day of dosing and for at
•least j.4 days.
7. Summarization of body weights
8. Summarization of gross necropsy
9. Significance, of changes from the Acceptance Criteria
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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?
Identify material tested (technical, end-use product, etc)
At least 5 animals/sex/group
Rats 200-300 gin, rabbits 2.0-3.0 kg or guinea pigs 350-
450 gn.
Dosing, single dermal.
Dosing duration at least 24 hours.
Vehicle control, only if toxicity of vehicle is unknown.
Doses tested, sufficient to determine a toxicity category
or a limit dose (2000 mg/kg).
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 nonirritating cover
to retain test material and to prevent ingestion.
11 • Individual observations at least once a day.
12• Observation period to last at least 14 days.
13. Individual body weights.
Gross necropsy on all animals.
Criteria marked with a * are supplemental and may not be required
for every study.
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81-2 Acute Dermal Toxicity in the Rat, Rabbit or Guinea Pig
GUIDANCE FOR SUMMARIZING STUDIES
1
1. The form orpesticide tested, e.g., solid, liquid, percent AI
in technical, end-use product, etc.
2. The number of animals/sex/dose
3. Weight range of animals
4. Verification of single, dermal exposure
5. Duration of dermal exposure
6. Statement of vehicle control
7. Doses tested and results
8. Preparation of application site
s». Area of application site (percent body surface)
10. Occlusion of test material on application site
11. Individual observations on day of dosing and for at
least 14 days or until all animals appear normal - (whichever is
longer).
12. Summarization of body weights
13. Summarization of gross necropsy
14. Significance of changes from Acceptance Criteria
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81-3 Acute Inhalation Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
!• Identify material tested (technical, end-use product, etc)
2- Product is a gas, a solid which may produce a significant
vapor hazard based on toxicity and expected use or contains
particles of inhalable size for man (aerodynamic diameter
15 urn or less).
3- At least 5 young adult rats/sex/group
«• Dosing, at least 4 hours by inhalation.
5- Chamber air flow dynamic, at least 10 air changes/hour, at
least 19% oxygen content.
6-—— Chamber temperature, 22* C (±2), relative humidity 40-60%.
7. Monitor rate of air flow
8- Monitor actual concentrations of test material in breathing
zone.
9- Monitor aerodynamic particle size for aerosols.
10• Doses tested, sufficient to determine a toxicity category
or a limit dose (5 mg/L actual concentration of respirable
substance).
11- Individual observations at least once a day.
12. Observation period to last at least 14 days.
13. Individual body weights.
14. Gross necropsy on all animals.
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8~l-3 -Acute inhalation Toxicity in the Rat
GUIDANCE FOR SUMMARIZING STUDIES
~
~Si~iPeStCide teSS0d' e'g-' fiolid' li^uid' Percent AI
technical, end-use product, etc.
2. Statement of the inhalability of test substance
3. The number of animals/sex/dose
4. Duration of inhalation exposure
t. Kangu for chamber air t«np«ratur« and r«lativ. humidity
' • Air z low rate
Q' ^i^°«i concenjra^ions of test material in breathing zone
9. Results of aerosol particle-size determination
dK(°r 1i?it dose of 5Bg/L or h^hest attainable)
observations on day of dosing and for at least 14
12. Summarization of body weights
13. Summarization of gross necropsy
14. Significance of changes from Acceptance Criteria
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81-4 Primary Eye Irritation in the Rabbit
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
!• Identify material tested (technical, end-use product, etc)
2. Study not required if material is corrosive, causes severe
dermal irritation or has a pH of < 2 or > 11.5.
3. 6 adult rabbits "
4« Dosing, instillation into the conjunctival sac of one eye
per animal.
5. Dose, 0.1 ml if a liquid; 0.1 ml or not more than 100 mg if
a solid, paste or particulate substance.
»• — Solid or granular test material ground to a'fine dust.
7. Eyes not washed for at least 24 hours.
8- — Eyes examined and graded for irritation before dosing and
at 1, 24, 48 and 72 hr, then daily until eyes are normal or
21 days (whichever is shorter).
9-*, individual daily observations.
Criteria marked with a * are supplemental and may not be required
for every study.
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81-4 Primary Eye Irritation in the Rabbit
GUIDANCE FOR SUMMARIZING STUDIES
solid-
or
3. Number of adult rabbits tested
4" SSSnSSS °f dofin*' *•«•< instillation into the
con^unctival sac of one eye per animal
5. Dose administered
6* ° granular test ^terial has been ground to
?* ?«a^?,Yhf^her eyes were Wftshed and at what time post
instillation (not less than 24 hours) P
We cy?s were exanin«° and graded for irritation
d at what periods after dosino •L"r"at;Lon
°bservations afterwards/untiTeyes are normal
« dosin9 and at what periods after dosino
ofi d
10. Significance of changes from Acceptance Criteria
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81-5 Primary Dermal Irritation Study
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
!• Identify material tested (technical, end-use product, etc)
2- Study not required if material is corrosive or has a
pH of <2 or > 11.5.
3. 6 adult animals.
4. Dosing, single dermal.
5. Dosing duration 4 hours.
6- Application site shaved or clipped at least 24 hours prior
to dosing
7- Application site approximately 6 cm.
8' Application site covered with a gauze patch held in place
with nonirritating tape
9* Material removed, washed with water, without trauma to
application site
10 • Application site examined and graded for irritation at 1,
24, 48 and 72 hr, then daily until normal or 14 days
(whichever is shorter).
11-* Individual daily observations.
Criteria marked with a * are supplemental and may not be required
for every study.
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81-5 Primary Dermal Irritation study
GUIDANCE FOR SUMMARIZING STUDIES
solid' llquid- peroent M
' PH <2 or ""•'• or ha* a
3. Number of adult animals tested
4. Amount applied
5. Duration of dermal exposure
'• 52T2fiSi do.?^1)1""0" site (shiv*d or clipp«d at -p««i«i
7. Area of application site
8. Method for occlusion of application site
10* SU r??0val of 5est ^terial and if skin was washed with water
10. state times post application when site was graded for
irritation
11 " H-f^idKal obfervations for day of dosing and individual
daily observations thereafter
12. Significance of changes from Acceptance Criteria.
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81-6 Dermal Sensitization in the Guinea Pig
ACCEPTANCE CRITERIA
dose your study meet the following acceptance criteria?
!• Identify material tested (technical, end-use product, etc)
2- Study not required if material is corrosive or has a
pH of <2 or > 11.5.
3. 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
4. Complete description of test
5.*. Reference for test.
6' Test followed essentially as described in reference
document.
7-_ Positive control included (may provide historical data
conducted within the last 6 months)
Criteria marked with a * are supplemental and may not be required
for every study.
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81-6 Dermal Sensitization in the Guinea Pig
GUIDANCE FOR SUMMARIZING STUDIES
oi tes*ed' e-9" 8olid' "«»id. percent AI
in technical , end-use product, etc.
!5aJe if naSerial is corrosive or has pH <2 or >11.5.
State specific method utilized
Complete description of specific method
Reference for the specific method employed
7. State the positive control tested
8. Significance of changes from Acceptance Criteria
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.81-7 Acute Neurotoxicity in the Hen
ACCEPTANCE CRITERIA
Does your study meet -the following acceptance criteria?
i- Study performed on an organophosphate cholinesterase
inhibiting compound.
2- Technical form of the active ingredient tested.
3.J* Positive control utilized.
4- Species utilized, domestic laying hen 8-14 months of age.
5-—— Dosing oral by gavage or capsule (dermal or inhalation
may be used).
6. An acute oral LD is determined.
7* Dose tested equal to an acute oral LD or a limit test of
5000 mg/kg.
8-i, Dosed animals may be protected with atropine and/or 2-
PAH.
Sufficient test animals so that at least 6 survive.
Negative (vehicle) control group of at least 6 hens
Positive control of at least 4 hens, (if used)
Test dose repeated if no signs of delayed neurotoxicity
observed by 21 days after dosing.
Observation period 21 days after each dose.
Individual daily observations.
Individual body weights.
Individual necropsy not required.
Histopathology performed on all animals. Tissue to be
fixed in sin preferably using whole animal perfusion
techniques. At least three sections of each of the
following tissues:
_brain, including medulla oblongata
_spinal cord; upper cervical, mid-thoracic and
lumbro-sacral regions
_tibial nerve; proximal regions and branches
sciatic nerve
Criteria marked with a * are supplemental and may not be required
for every study.
'*"*f- •^"•' ItltS —if
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ATTACHMENT F . .,
List of Registrants sent this DCI
77
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Page 1 of 1
United States Environmental Protection Agency
Washington, D. C. 20460
LIST OF ALL REGISTRANTS SENT THIS DATA CALL-IN NOTICE
Case # and Name: 0032 Daminozide
Co. Nr. Company Name Additional Name Address City & State Zip
000400 UNIROYAL CHEMICAL CO INC 74 AMITY RD BETHANY CT 06524
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ATTACHMENT G
Product Specific Data Call-in Cost Share and
Data Compensation Forms
78
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&EPA
United Statea Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
,
the collection of Wonn«ttoru Send comments
, -, . Environmental Protection Ap^ncy, 401 M SU S.W
of Management and Budget, Paperwork Reduction Project (MTCWloej
fin m blanks below.
PA Bteg. Me.
I Certify that:
My company is willing to develp and submit the data
airthortty of the Federal
^'^^^^^M^^}'Kn90' Ho^.r.mymweto
enter into an agreement with one or more registrants to develop Jointly or share In the ooct of developing
My firm has offered in writing to anter Into such an agreement That offer was Irrevocable and Inducted an
ISS^S^SXL* ^H^^!?3^^ 8ectton a««MWW o» PIPRA K final agreement on all
tenns could not be reached otherwise. This offer was made to the following firm(s) on thVfollowing
nrm(»)
Date «f Offer
CgrtMleation;
this form and all attachments therein are true, accurate, and complete. 1 acknowledge that ai
nusieaoinoataterMrBinaybepuiilshebtehyflnanrlnip^
SletMtur* «f Company** AMherix^ ItoptMMiUtfw
•teiM and TMto (PIMM Type «r Pitaq
•nvuwi nawmBoeon
V knowingly false or
Oat*
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SEPA
United Statea Environmental Protection Agency
Waahlngton, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
S^XS^^
' " lorct$' ***** «^n«
OKI M*. 1070-0107
3070-0017
AMWtf EnlfM 3-31-M
'
8i"d «""«• "Bwtflnfl «* burden estimate or any other
. nitlont IncWin8 awstions for reducing this burden, to Chief. Information Policy
' i?n!£!!D7lertal Pmtt?Uc)n *e§ncy. 401 M SU S.W.. Washington. DC 20460: and to the Office
and Budget, Paperwork Reduction Project (20704106). Washington. DC 20503.
Pleaae fill In blanks below.
I Certify that
Company Number
FA Stog. Me.
1. For each study dted in support of registration or ^registration under the Federal Insecticide Fungicide and
Rodenticide Act (FlFRA) that is an exclusive use study. I am the original data submlBer. or I have obtained the
wrttenpermi»toncrftr»orioirialo^ ««im«,..QrIn.veoKaineoine
2. That for each study dted in support of registration or reregistrationiindernFrV that is NOT an exclusive use
S^f ' I!!!!!!^!!!^^?1 •"''^
have notified in writing the company(ies) that submitted data I have dted and have offeredio: (a) Pay
S!!!?^"?'.1^^1^"1*"6* "*" itcfon* •WnXD) «nd 3(0(2)(D) of FlFRA: and (b) Commence
negotiation to determine which data are subject to the compewation requirement of FlFRA and the amount of
compensation due. I any. The companies I have notified are: (check one)
U The companies who have submitted the studies feted on the back of this form or attached
aheets. or indicated on the attached -Requirements Status and Registrants' Response Form.'
3. Tta! I have previousr/conplirtwim section 3^^
registration or reregfctratioo under FlFRA. ^^
OUflMtur*
NMM «* lltto (PIMM TyM «r MHO.
Oat*
EM farm Mm.** ««.•*%
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I ''
V
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