United States Prevention, Pesticides EPA 738-R-99-005
Environmental Protection And Toxic Substances November 1999
Agency (7508C)
&EPA Reregistration
Eligibility Decision (RED)
Pebulate
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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 chemical case Pebulate which
includes the active ingredients Pebulate. The enclosed Reregistration Eligibility Decision (RED),
which was approved on September 30, 1999, contains the Agency's evaluation of the data base of
these chemicals, its conclusions of the potential human health and environmental risks of the
current product uses, and its decisions and conditions under which these uses and products will be
eligible for reregistration. The RED includes the data and labeling requirements for products for
reregistration. It may also include requirements for additional data (generic) on the active
ingredients to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED." This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the receipt of this
letter. The second set of required responses is due 8 months from the date of this letter.
Complete and timely responses will avoid the Agency taking the enforcement action of suspension
against your products.
Please note that the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safely standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA implementation,
EPA recognizes that it will be necessary to make decisions relating to FQPA before the
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implementation process is complete. In making these early case-by-case decisions, EPA does not
intend to set broad precedents for the application of FQPA. Rather, these early determinations
will be made on a case-by-case basis and will not bind EPA as it proceeds with further policy
development and any rulemaking that may be required.
If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
RED.
If you have questions on the product specific data requirements or wish to meet with the
Agency, please contact the Special Review and Reregi strati on Division representative Venus
Eagle at (703) 308-8045. Address any questions on required generic data to the Special Review
and Reregi strati on Division representative Patricia Moe (703) 308-8011.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregi strati on Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1 DATA CALL-IN (PCI) OR "90-DAY RESPONSE"-If generic data are required for
reregi strati on, a DCI letter will be enclosed describing such data. If product specific data are
required, a DCI letter will be enclosed listing such requirements. If both generic and product
specific data are required, a combined Generic and Product Specific DCI letter will be enclosed
describing such data. However, if you are an end-use product registrant only and have been
granted a generic data exemption (GDE) by EPA, you are being sent only the product specific
response forms (2 forms) with the RED. Registrants responsible for generic data are being sent
response forms for both generic and product specific data requirements (4 forms). You must
submit the appropriate response forms (following the instructions provided) within 90 days
of the receipt of this RED/DCI letter; otherwise, your product may be suspended.
2 TIME EXTENSIONS AND DATA WAIVER REOUESTS-No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA in order to go into effect.
3 APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original application
form. Mark it "Application for Reregistration." Send your Application for Reregistration (along
with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregi strati on) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregi strati on. For further labeling
guidance, refer to the labeling section of the EPA publication "General Information on Applying
for Registration in the U.S., Second Edition, August 1992" (available from the National Technical
Information Service, publication #PB92-221811; telephone number 703-605-6000).
c. Generic or Product Specific Data Submit all data in a format which complies with
PR Notice 86-5, and/or submit citations of data already submitted and give the EPA identifier
(MRID) numbers. Before citing these studies, you must make sure that they meet the
Agency's acceptance criteria (attached to the DCI).
d Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
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comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal concentration.
You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
§158.175) or (2) provide certified limits that are supported by the analysis of five batches. If you
choose the second option, you must submit or cite the data for the five batches along with a
certification statement as described in 40 CFR §158.175(e). A copy of the CSF is enclosed;
follow the instructions on its back.
e Certification With Respect to Citation of Data Complete and sign EPA form 8570-
34 and 8570-35 for each product.
4 COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5 WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
By U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data waiver
and time extension requests within 60 days. EPA will also try to respond to all 8-month
submissions with a final reregi strati on determination within 14 months after the RED has been
issued.
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REREGISTRATION ELIGIBILITY DECISION
Pebulate
LISTB
CASE 2500
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TABLE OF CONTENTS
PEBULATE REREGISTRATION ELIGIBILITY DECISION TEAM i
EXECUTIVE SUMMARY v
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 2
C. Estimated Usage of Pesticide 4
D. Data Requirements 4
E. Regulatory History 5
III. SCIENCE ASSESSMENT 5
A. Physical/Chemical Properties Characterization 5
B. Human Health Assessment 6
1. Hazard Profile 6
2. Food Quality Protection Act Considerations 15
3. Dose Response Assessment 16
4. Risk Assessment 16
5. Aggregate Risk Assessments and Risk Characterization 28
6. Endocrine Disrupter Effects 29
7. Cumulative Effects 29
C. Environmental Assessment 31
1. Environmental Fate Assessment 31
2. Water Resources Assessment 32
3. Hazard Profile 32
4. Risk Assessment 37
5. Risk Characterization 41
6. Data Requirements 42
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 42
A. Determination of Eligibility 42
B. Determination of Eligibility Decision 43
C. Regulatory Position 43
D. Food Quality Protection Act Findings 44
1. Determination of Safety for U.S. Population 44
2. Determination of Safety for Infants and Children 45
3. Endocrine Disrupter Effects 46
E. Tolerance Reassessment 46
1. Codex Harmonization 47
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F. Human Health Risk Mitigation 47
G. Ecological Risk Mitigation 50
H. Occupational (WPS) Labeling Rationale 51
I. Other Labeling Requirements 52
1. Endangered Species Statement 52
2. Spray Drift Management 53
V. ACTIONS REQUIRED OF REGISTRANTS 53
A. Manufacturing-Use Products 53
1. Additional Generic Data Requirements 53
2. Labeling Requirements for Manufacturing-Use Products 54
B. End-Use Products 54
1. Additional Product-Specific Data Requirements 54
2. Labeling Requirements for End-Use Products 54
3. Required Labeling Changes Summary Table 54
C. Existing Stocks 59
VI. APPENDICES 61
A. Table of Use Patterns Subject to Reregistration 63
B. Table of the Generic Data Requirements and Studies Used to Make the
Reregistration Decision 66
C. Citations Considered to be Part of the Data Base Supporting the
Reregistration Decision 72
D. Generic Data Call-In 79
1. Generic Data Call-In Chemical Status Sheet 98
2. Generic DCI Response Forms Inserts (Insert A) plus Instructions . 99
3. Requirements Status and Registrants' Response Forms (Insert B) plus
Instructions 104
E. Product Specific Data Call-In 113
1. Product Specific Chemical Status Sheets 127
2. Data Call-in Response Form for the Product Specific Data(Form A
inserts) Plus Instructions 128
3. Product Specific Requirement Status and Registrant's Response
Forms (Form B inserts) and Instructions 130
4. EPA Batching of End-Use Products for Meeting Data Requirements
for Reregistration 137
5. List of All Registrants Sent This Data Call-In (insert) Notice 138
F. List of Available Related Documents and Electronically Available Forms. 139
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PEBULATE REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis
Margaret Cogdell
Virginia Dietrich
Timothy Kiely
Science Information and Analysis Branch
Herbicide and Insecticide Branch
Economic Analysis Branch
Environmental Fate and Effects Assessment
Brian Montague
Richard Mahler
Environmental Risk Branch I
Environmental Risk Branch I
Health Effects Risk Assessment
Yung Yang
William Hazel
Susan Hanley
Registration Support
Juanita Gilchrist
Risk Management
Patricia Moe
Toxicology Branch I
Reregi strati on Branch I
Reregi strati on Branch I
Herbicide Branch
Reregistration Branch III
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GLOSSARY OF TERMS AND ABBREVIATIONS
a.i. Active Ingredient
aPAD Acute Population Adjusted Dose
BUN Blood Urea Nitrogen
cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formula
DCI Data Call In
DEEM™ Dietary Exposure Evaluation Model
DWLOC Drinking Water Level of Concern
EC Emulsifiable Concentrate
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an
environment, such as a terrestrial ecosystem.
EPA U.S. Environmental Protection Agency
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
HOT Highest Dose Tested
HIARC Hazard Identification Assessment Review Committee
Koc Organic Partitioning Coefficient
Kow Octanol/Water Partition Coefficient
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in
50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LOG Level of Concern
LOD Limit of Detection
LOAEL Lowest Observed Adverse Effect Level
LOAEC Lowest Observed Adverse Effect Concentration
ug/g Micrograms Per Gram
/-ig/L Micrograms Per Liter
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MRID Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
N/A Not Applicable
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP Office of Pesticide Programs
PAD Population Adjusted Dose
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
ill
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RfD Reference Dose
RQ Risk Quotient
TGAI Technical Grade Active Ingredient
UF Uncertainty Factor
USDA United States Department of Agriculture
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
The Environmental Protection Agency (EPA) has completed its reregistration eligibility
decision (RED) for the pesticide pebulate (S-propyl butyl(ethyl)thiocarbamate) and determined that
all uses, when labeled and used as specified in this document, are eligible for reregistration. This
decision includes a comprehensive reassessment of the database of studies required to support the use
of currently registered products. The Agency made the decisions presented in this RED by
considering the requirements of the "Food Quality Protection Act of 1996" (FQPA), which amended
the Federal Food Drug and Cosmetic Act (FFDCA) and the Federal Insecticide Fungicide and
Rodenticide Act (FIFRA), the two Federal statutes that provide the framework for pesticide
regulation in the United States.
In establishing or reassessing tolerances, FFDCA, as amended, requires the Agency to
consider aggregate exposures to pesticide residues, including all anticipated dietary exposures and
other exposures for which there is reliable information. In addition, the potential for cumulative
effects from a pesticide and other compounds with a common mechanism of toxicity must be
considered. The Act further directs EPA to consider the potential for increased susceptibility of
infants and children to the toxic effects of pesticide residues and to develop a screening program to
determine whether pesticides produce endocrine disrupting effects.
Pebulate is a thiocarbamate herbicide used for preemergence control of germinating seeds of
broadleaf and grassy weeds in sugar beets, tobacco, and tomatoes. There are no registered uses of
pebulate in residential settings. There are currently two active registrations: one for the technical
grade product and one for an end-use product. Pebulate is typically applied preplant once per season
using ground or irrigation equipment and is soil-incorporated immediately after application to prevent
loss via volatilization.
Pebulate is a reversible cholinesterase inhibitor, although such effects are seen only at high
doses. Neurotoxicity is the major toxic effect of pebulate. Pebulate has low acute oral, dermal, and
inhalation toxicity. It is a slight to mild irritant to the eye or skin and is not a skin sensitizer. Based
on pebulate use patterns, no long-term inhalation exposure is expected to occur.
In addition to the conventional safety factors (lOx for interspecies extrapolation and lOx for
intraspecies variability), the FQPA safely factor of 1 Ox was applied for pebulate dietary and aggregate
risk assessments. The reason for the additional factor was due to (1) the severe neuropathology
exhibited in studies with adult animals, (2) the structural similarities to other thiocarbamates for which
increased susceptibility of developing fetuses has been demonstrated, and (3) the outstanding
requirement for a developmental neurotoxicity study. The lOx FQPA safety factor is not applied to
the general population when it is appropriate only to apply the factor to portions of the population.
In the case of pebulate, it is appropriate to apply the factor to infants, children, and woman of
reproductive age (13-50 years) only.
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Dietary risk assessments reflected highly refined exposure assessments; anticipated residues
and percent-crop-treated figures were incorporated. A probabilistic/Monte Carlo acute dietary
assessment was conducted using an acute population adjusted dose (aPAD) of 0.5 mg/kg/day for
adults andO.05 mg/kg/day for infants, children, and females (13-50 yr). Chronic risks were calculated
using a chronic PAD (cPAD) of 0.007 mg/kg/day for adults and 0.0007 mg/kg/day for infants,
children, and females (13-50 yr). Acute and chronic dietary risks to all population subgroups were
<1% of the aPAD and cPAD, respectively.
Pebulate was rarely detected in either surface or ground water in available water monitoring
studies, and when detected, was present at low concentrations. With the exception of the most
conservative estimate of chronic environmental concentrations, calculated by assuming that there
would be no binding of the chemical to soil whatsoever, estimated water concentrations of pebulate
do not exceed any Drinking Water Levels of Comparison (DWLOCs). The available monitoring data,
although not targeted to pebulate, support this assumption.
At this time, the Agency does not believe it has sufficient reliable information concerning
common mechanism issues to determine whether pebulate, a thiocarbamate, shares a common
mechanism of toxicity with other cholinesterase-inhibiting chemicals. Therefore, for the purposes of
this tolerance reassessment, the Agency has assumed that pebulate does not share a common
mechanism of toxicity with cholinesterase-inhibiting chemicals. Tolerances are currently 0.1 ppm for
pebulate in tomatoes and sugar beet roots and tops (40 CFR 180.238). The Agency recommends
reassessment of all tolerances to the limit of quantitation of the analytical method, 0.05 ppm, because
all residues were consistently less than the limit of quantitation.
For occupational handler dermal exposures, risks were below the Agency's level of concern,
which is a margin of exposure (MOE) greater than 100, for most scenarios involving pebulate mixers
and loaders with the use of personal protective equipment (PPE). In addition to the PPE that is
currently on the label (long-sleeved shirts, long pants, shoes, socks, protective eyewear, and chemical-
resistant gloves), organic vapor respirators are required when preparing solutions for application at
the highest use rates in the western states (defined as California, Arizona, and Nevada) and for
chemigation. For commercial operators, closed systems are required for mixing and loading of
pebulate for dry bulk fertilizer and in combination with fluid fertilizer. The MOEs for the pebulate
applicator exposures are acceptable with the use of the PPE specified on the current label, with only
one exception. Applying dry bulk fertilizer to tobacco in the western states requires that the
applicator use an organic vapor respirator or a truck with an enclosed cab and an organic vapor air
filtration system. In the absence of dermal exposure data, the Agency is also requiring that chemical-
resistant gloves be worn during transplanting of crop seedlings and is requiring additional data on this
practice.
For acute exposure, pebulate is practically nontoxic to birds and is slightly toxic to mammals.
The Agency is not overly concerned about chronic exposures to birds and mammals because of the
way pebulate is used, i.e., immediate soil incorporation. Pebulate runoff and drift to adjacent habitats
vi
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may prove hazardous to certain families of non-target terrestrial and semi-aquatic plants (mainly grass
related species). Risk to aquatic plants is not predicted based on estimated aquatic residue levels.
Although the pebulate database is sufficient to render a reregi strati on eligibility decision, a
deficiency exists for developmental neurotoxicity. Other requirements include labeling changes to
(1) increase the preharvest interval for tomatoes from 8 days to 30 days and (2) establish a 4-month
plantback interval (FBI) for all rotational crops. If a shorter FBI is desired, additional data must be
submitted to upgrade rotational crop studies or limited field rotational crop studies (which include
seeking metabolites of potential toxicological concern as well as the parent compound) can be
conducted. In addition, ecological effects and environmental fate studies are needed to fully assess
the impact of pebulate and its primary degradate, pebulate sulfoxide, on the environment.
Before reregistering any products containing pebulate, the Agency is requiring that product
specific data, revised Confidential Statements of Formula (CSF) and revised labeling be submitted
within eight months of the issuance of this document. These data include product chemistry for each
registration and acute toxicity testing. After reviewing these data and any revised labels and finding
them acceptable in accordance with Section 3(c)(5) of FIFRA, the Agency will reregister a product.
Those products that contain other active ingredients will be eligible for reregistration only when the
other active ingredients are determined to be eligible for reregistration.
vn
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) was amended to
accelerate the reregi strati on of products with active ingredients registered prior to November 1,
1984. The amended Act provides a schedule for the reregi strati on process to be completed in
nine years. There are five phases to the reregi strati on process. The first four phases of the
process focus on identification of data requirements to support the reregi strati on of an active
ingredient and the generation and the submission of data to fulfill the requirements. The fifth
phase is a review by the U.S. Environmental Protection Agency (EPA) of all data submitted to
support reregi strati on.
FIFRA Section 4(g)(2)(A) states that in Phase 5, "the Administrator shall determine
whether pesticides containing such active ingredients are eligible for reregi strati on" 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 underlying a
pesticide registration. The purpose of the Agency's review is (1) to reassess the potential hazards
arising from the currently registered uses of the pesticide; (2) to determine the need for additional
data on health and environmental effects; and (3) to determine whether the pesticide meets the
"no unreasonable adverse effects" criterion of FIFRA.
On August 3, 1996, the FQPA (Public Law 104-170) was signed into law. The FQPA
amends both the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 301 et seq., and the
FIFRA, 7 U.S.C. 136 et seq. The FQPA amendments went into effect immediately and EPA
initiated an intensive process, including consultation with registrants, States, and other interested
stakeholders, to make decisions on the new policies and procedures that will be appropriate as a
result of enactment of FQPA. This process will include a more in-depth analysis of the new safety
standard and how it should be applied to both food and nonfood use pesticides. The FQPA does
not, however, amend any of the existing reregistration deadlines set forth in Section 4 of FIFRA.
In addition, because statutory deadlines are unaffected with respect to reregistration, the Agency
will continue its ongoing reregistration program while it continues to determine how best to
implement FQPA.
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of pebulate including the risk to infants and children for any potential dietary,
drinking water, dermal or oral exposures, and cumulative effects as stipulated under the FQPA.
The document, which is in a revised format, consists of six sections. In an effort to simplify and
shorten the RED, the information presented herein is at a higher level than that presented in
previous documents; more detailed information can be found in the technical support documents.
Section I is the introduction, and Section II describes pebulate, its uses, data requirements, and
regulatory history. Section III discusses the human health and environmental assessment based on
the data available to the Agency. Section IV presents the reregistration decision for pebulate, and
Section V discusses the reregistration requirements for pebulate. Finally, Section VI contains the
1
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Appendices that support this Reregi strati on Eligibility Decision (RED). The supporting technical
documentation for this RED is listed in the Reference section at the back of this document. These
references are cited in this RED parenthetically and in italics. Additional details concerning the
Agency's review of applicable data are available on request.
II. CASE OVERVIEW
A. Chemical Overview
The following active ingredient is covered by this Reregi strati on Eligibility Decision:
! Common Name: Pebulate
! Chemical Name:
! Chemical Family:
! CAS Registry Number:
! OPP Chemical Code:
! Empirical Formula:
! Trade Name:
! Basic Manufacturer:
B. Use Profile
s-Propyl butyl ethylthiocarbamate
Thiocarbamate
1114-71-2
041403
C10H21NOS
Tillam 6-E
Zeneca Ag Products
The following summarizes the currently registered uses with an overview of use sites and
application methods. A detailed table of the uses of pebulate is contained in Appendix A.
Type of Pesticide:
Use Sites:
Herbicide
Soil incorporated application to tomatoes,
tobacco, and sugar beets
Target Pests: Grassy and broadleaf weeds
Formulation Types Registered: Emulsifiable concentrate (EC)
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Rates of Application:
• Sugar beets: 4-6 Ib of active ingredient (ai)/acre
• Tobacco: 4 Ib ai/acre
• Tomatoes: 3-6 Ib ai/acre may be applied; western region only, a maximum of 10 Ib ai/acre
rate may be applied
• Dry Bulk Fertilizer: Tobacco only, 4 Ib ai/acre
• Fluid Fertilizer: Tobacco and tomato crops only; the label gives application instructions
based on a field rate of 1 Ib ai/acre, but states that the amount of pebulate active ingredient
per acre may be increased to correspond to intended field rate.
Methods of Application
Pebulate is incorporated into the soil during or immediately after application. It can be
applied below the surface of the soil, by ground sprayer equipment (including chemigation),
subsurface sweeper application (tobacco only), or by soil injection. When pebulate is applied via
solid set sprinklers, 1A to l/2 inch of water must be applied to ensure 2- to 4-inch soil penetration of
the chemical. Pebulate is mixed with fluid fertilizer (tomato and tobacco use) and immediately
soil incorporated. For impregnation on dry bulk fertilizer (tobacco only), there are two scenarios:
commercial and on-board application. Commercial processing occurs with a closed rotary-drum
mixer or a similar type of closed blender equipped with suitable spray equipment. For on-board
applications, pebulate is metered onto dry bulk fertilizer as it is applied to the field, similar to a
groundboom application. This method also requires immediate soil incorporation.
Summary of Major Uses
Methods: Soil incorporated or soil injected
Equipment: Boom-type sprayers which precede the cultivation wheels;
Subsurface injection equipment
Timing: Typically applied once per season, preplant. Pebulate can have a second,
postemergence layby application, which occurs in conjunction with
mechanical weeding
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Use Limitations:
The product is to be applied prior to mechanical transplanting of tomatoes and
tobacco. Hand transplanting is not permitted.
C. Estimated Usage of Pesticide
The Agency estimates that, on average, approximately 536,000 pounds of pebulate are
applied to sugar beets, tomatoes, and tobacco per year. More than 90% of pebulate usage is on
tomatoes and tobacco. Application of pebulate to tomatoes constitutes the major use
(approximately 55% of the total pounds of pebulate applied), followed by tobacco (35%), and
sugar beets (about 10%). Total acreage treated annually with pebulate for the crops ranges from
an estimated maximum of 65,000 acres for tomatoes to 8,000 acres for sugar beets, with an
estimated 127,000 acres treated per year nationally (reference 7). More than 80% of the pebulate
usage on tomatoes and sugar beets is concentrated in California. Use of pebulate on tobacco is
primarily concentrated in southeastern states (NC, KY, SC, GA, and TN) and Indiana (reference
2).
Table 1 summarizes the best available estimates for the uses of pebulate. 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.
Table 1. Maximum Permitted Label Use Rate Table - Pebulate Crop Scenarios
Crop
Tomato
Tomato
Sugar beets
Tobacco
Rate Ib ai/A
10.0
10.0*
6.0
4.0
Method
Preplan! soil incorporated
Postplant irrigation spray equipment
usually followed by incorporation
Preplant soil incorporated
Preplant soil incorporated or injected
Major Area of Use
CA
CA (Western region only)
CA
NC, KY, SC, GA, IN, TN
* The only permitted multiple application is for tomatoes in western regions. With a second layby application,
which occurs in conjunction with mechanical weeding, the 10 Ib ai/A seasonal limit must still be observed.
D. Data Requirements
The Agency required the registrant to submit studies, as specified in 40 CFR Section 158.
Data from these studies are sufficient to characterize the risks associated with the uses described
in this document. Appendix B includes all data requirements identified by the Agency for
currently registered uses needed to support reregi strati on.
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E. Regulatory History
Pebulate was first registered as a pesticide in the United States in 1961. At that time three
products were registered that contained the active ingredient pebulate: Tillam Technical, Tillam
6E, and Tillam 10G. In 1987, these products were transferred from Stauffer Basic Chemical
Holdings, Inc., to ICI Americas, Inc., which later became Zeneca Ag Products.
In 1996, Tillam 10G was canceled at the request of the registrant following an Agency
request for residue data for the 10G formulation. The registrant determined that the product was
not marketed in quantities sufficient to justify generating the data. As of 1999, the registrant is
supporting continued registration of the technical grade product, EPA Reg. No. 10182-213, and
one end-use product, the 6 Ib. active ingredient per gallon emulsifiable concentrate (EC), EPA
Reg. No. 10182-158.
III. SCIENCE ASSESSMENT
A. Physical/Chemical Properties Characterization
Pebulate [S-propyl butylethylthiocarbamate] is a preplant selective herbicide used for
control of grassy and broadleaf weeds in sugar beets, tobacco, and tomatoes.
O
3 ^'^ S N —/ CH3
CH3
Empirical Formula: C10H21NOS
Molecular Weight: 203.36
Pebulate technical is an amber liquid with a boiling point of 142°C at 21 mm Hg, a density
of 0.9552 g/mL at 20°C, an octanol/water partition coefficient (Kow) of 9.6 x 103 at 25°C, and a
vapor pressure of 8.9 x 10"3 mm Hg at 25°C. Pebulate is slightly soluble in water (60 ppm at
20 °C), and is miscible with acetone, benzene, isopropanol, methanol, and xylene. No impurities
of toxicological concern have been identified. Because pebulate is volatile, exposure by the
inhalation route is expected.
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B. Human Health Assessment
1. Hazard Profile
Pebulate is in the class of thiocarbamates, which includes molinate, EPIC, butylate,
vernolate, and cycloate, and is a reversible cholinesterase inhibitor (that is, pebulate quickly binds
to the cholinesterase active site, but is easily replaced by acetylcholine). In contrast, the
carbamates, such as formetanate HCL, oxamyl, and aldicarb, are effective cholinesterase inhibitors
(although not as effective as the organophosphates). For the carbamates, however, cholinesterase
inhibition is rapidly reversible and therefore the anticholinesterase activity must be measured at the
optimal time. Consequently, for this class of chemicals, acetylcholine inhibition is the principal
toxicological effect of concern and is often the endpoint used for risk assessments.
The thiocarbamates, such as pebulate, are not particularly effective cholinesterase
inhibitors; rather, they appear to be direct acting neurotoxic agents. Because the principal toxic
effects observed by exposure to thiocarbamates are neurotoxicity (clinical signs, behavioral
effects, and/or changes in motor activity) and neuropathology, these neurotoxic effects are often
used for endpoint selection in risk assessments rather than cholinesterase inhibition. For this class
of compounds, acetyl cholinesterase inhibition is not the primary toxicity concern. Other toxic
effects, which are described below, were also observed in laboratory animal toxicology studies.
No significant differences were observed in the toxicology studies with regard to gender.
The acute toxicity data showed that pebulate had low acute oral, dermal, and inhalation
toxicity. It was a slight to mild irritant to the eye or skin and was not a skin sensitizer. Toxicity
categories, which are classified as 1 (most toxic) through 4 (least toxic), were either 3 or 4 for
pebulate. There was no evidence of increased tumor incidence in the carcinogen!city studies in
rats and mice, and the mutagenic test battery also indicated that pebulate was not mutagenic.
Therefore, pebulate was classified as "not likely" to be a human carcinogen.
In the rat, pebulate was readily absorbed, distributed, metabolized and eliminated,
primarily in urine, feces, and CO2. Less than 3% was detected in total tissues. Major metabolites
were identified in the urine as pebulate mercapturate, hydroxylated pebulate, butylamine and
ethylbutylamine, hydroxyethylbutylamine, and hydroxylated pebulate mercapturate.
Although pebulate sulfoxide and pebulate sulfone are not found as significant metabolites
in plants and livestock, they are major soil/water degradates. There is concern that these pebulate
degradates may be taken up by rotated crops. These degradates are assumed to be of equal
toxicity to parent pebulate in the absence of data showing otherwise. This assumption is
consistent with metabolite studies conducted with other thiocarbamates.
The studies the Agency used in making decisions related to pebulate toxicity are shown in
Table 2. The dose and endpoints selected for various exposure scenarios are shown in Table 3.
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These studies, which the Agency used in quantifying risk (reference 3), are summarized after the
table, as well as a discussion of the FQPA safety factors.
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Table 2. Toxicity Studies for Pebulate Technical
Guideline
MRID#
Type of Study
Results
Core
Grade
Acute Toxicity
§81-1
870.1100
§81-2
870.1200
§81-3
870.1300
§81-4
870.2400
§81-5
870.2500
§81-6
870.2600
41591701
41591701
41677301
00143575
41591703
41591702
41614808
Acute Oral-Rat
Acute Dermal-Rabbit
Acute Dermal- Rat
Acute Inhalation-Rat
Eye Irritation-Rabbit
Skin Irritation-Rabbit
Dermal Sensitization-
Guinea pig
LD50= 1750(o")/1550(?)mg/kg
Toxicity category 3
LD50 >2000 mg/kg (Rabbit or Rat)
Toxicity category 3
LC50=3.7(o")/3.5(?)mg/L
Toxicity category 4
Mild eye irritant
Toxicity category 3
Slight dermal irritant
Toxicity category 4
Not a skin sensitizer
Acceptable
Acceptable
Acceptable
Acceptable
Acceptable
Acceptable
Subchronic Toxicity
§82-l(a)
870.3100
§82-l(a)
870.3100
§82-l(b)
870.3150
§82-2
870.3200
§82-3
870.3465
N/A
N/A
N/A
41920701
00143576
90-day feeding-Rat
90-day feeding-Mouse
90-day feeding-Dog
28-day dermal-Rat
90-day Subchronic Inhalation-
Rat
N/A
N/A
N/A
NOAEL = 100 mg/kg/day (highest dose
tested)
NOAEL = 0.0034 mg/L
LOAEL = 0.016 mg/L
Waived*
Waived*
Waived*
Acceptable
Acceptable
Chronic Toxicity
§83-l(b)
870.4100
§83-2(b)
870.4200
40969701
41920705
1-year Chronic oral-Dog
Carcinogenicity-Mouse
(18 months)
NOAEL = <5(o")/5(? )mg/kg/day
LOAEL = 5(o")/25(?)mg/kg/day
NOAEL = 34(o")/47(? ) mg/kg/day
LOAEL = 116(o")/161(?) mg/kg/day
No evidence of Carcinogenicity
Acceptable
Acceptable
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Guideline
§83-5
870.4300
MRID#
41213001
Type of Study
Combined
Chronic/Oncogenicity
-Rat (2 years)
Results
NOAEL = 0.74(o")/0. 85(? ) mg/kg/day
LOAEL = 7. 12(o")/9.40(?) mg/kg/day
No evidence of Carcinogenicity
Core
Grade
Acceptable
Developmental / Reproductive Toxicity
§83-3(a)
870.3700
§83-3(b)
870.3700
§83-4
870.3800
40033301
40033201
40970001
Developmental-Rat
Developmental-Rabbit
Two-generation Reproduction-
Rat
Maternal
NOAEL= 30 mg/kg/day
LOAEL= 200 mg/kg/day
Developmental
NOAEL= 30 mg/kg/day
LOAEL= 200 mg/kg/day
Maternal
NOAEL= 30 mg/kg/day
LOAEL= 150 mg/kg/day
Developmental
NOAEL= 150 mg/kg/day (HOT)
Parental
NOAEL= 0.8 mg/kg/day
LOAEL= 6 mg/kg/day
Offspring
NOAEL= 6 mg/kg/day
LOAEL= 50 mg/kg/day
Reproductive
NOAEL= 50 mg/kg/day (HOT)
Acceptable
Acceptable
Unacceptable**
Neurotoxicity
§81-7
870.6100
§81-8ss
870.6200
§82-7
870.6200
00067869
92138016
43217401
43231001
Acute delayed Neurotox- Hen
Acute neurotoxicity-Rat
Subchronic neurotoxicity- Rat
Negative
NOAEL= 50 mg/kg
LOAEL= 150 mg/kg
Neurotoxicity
NOAEL= 3. 9(o")/4.5(?) mg/kg/day
LOAEL= 19.4(o")/21.5(?)mg/kg/day
Cholinesterase inhibition: Brain, plasma,
RBC
NOAEL= 3. 9(o")/4.5(?) mg/kg/day
LOAEL= 19.4(o")/21.5(?)mg/kg/day
Acceptable
Acceptable
Acceptable
Mutagenicity
§84-2
870.5100
41556803
Ames Assay fS. typhimurium)
Not mutagenic
Acceptable
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Guideline
§84-2
870.5375
§84-2
870.5550
MRID#
41556802
41614809
Type of Study
In vitro mammalian
cytogenetics
-human lymphocytes
Unscheduled DNA synthesis in
rat hepatocyte treated in vivo
Results
No induction of chromosomal
aberrations
No conclusion can be reached
Core
Grade
Acceptable
Unacceptable
Metabolism
§85-1
870.7485
42215201
42482501
42482502
42482503
Metabolism
Pebulate was readily absorbed,
distributed, metabolized and excreted,
primarily in urine (59-76%), feces and
CO2 (4-14% and 13-16%, respectively.)
Very little (0.4-1.0%) was detected in
tissues. Major metabolites were
identified in the urine as pebulate
mercapturate, hydroxylated pebulate,
butylamine and ethylbutylamine,
hydroxyethylbutylamine, hydroxylated
pebulate mercapturate. The data
suggested that metabolism of pebulate
does not appear to be sex- or dose-
related and does not bioaccumulate.
Acceptable
NOAEL, No observed adverse effect level; LOAEL, lowest observed adverse effect level; HDT, highest dose tested;
*Subchronic oral toxicity studies were required in the original data call in (DCI) but were never submitted; however, the
Agency waived these requirements because information from chronic toxicity studies in rats and dogs can be used in lieu of
these data.
"Although this study was unacceptable (reference 3), the Agency has determined that little additional information would be
obtained about the reproductive and developmental effects of pebulate by repeating this study.
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Table 3. Doses and lexicological Endpoints Selected for Various Exposure Scenarios*
Exposure
Scenario
Acute Dietary
Chronic Dietary
Carcinogenicity
(Dietary)
Short-Term
(Dermal)
Intermediate-Term
(Dermal)
Long-Term
(Dermal)
Short-term
(Inhalation)
Intermediate-term
(Inhalation)
Long-term
(Inhalation)
Dose
(mg/kg/day)
NOAEL = 50
(UF = 100)
[FQPA SF=10]
NOAEL = 0.74
(UF = 100)
[FQPA SF = 10]
Not Applicable
NOAEL=100
(MOE of concern - 100)
Not Applicable
NOAEL = 0.003 mg/L
(0.89 mg/kg/day)**
(MOE of concern - 100)
Not Applicable
Endpoint
Decreased motor activity at 1 50 mg/kg/day
Acute RfD = 0.5 mg/kg/day
(1) aPAD for infants, children, and females
(13-50 yr) = 0.05 mg/kg/day
(2) aPAD for adults other than females (13-50
yr) =0.5 mg/kg/day
Decreased body weights and increased
incidence of cataracts in both sexes at a dose
of 7.12 mg/kg/day
Chronic RfD = 0.007 mg/kg/day
(1) cPAD for infants, children, and females
(13-50 yr) = 0.0007 mg/kg/day
(2) cPAD for adults other than females (13-50
yr) = 0.007 mg/kg/day
Pebulate is not mutagenic and does not result
in increased tumor incidence in rats or mice.
pebulate is classified as not likely to be a
human carcinogen.
The highest dose tested (100 mg/kg/day )-No
effects observed
Based on the use pattern, no long-term dermal
exposure is expected to occur. Risk
assessment is not required.
Prolonged coagulation time, degenerative
effects in kidneys of both sexes at dose of
0.016 mg/L.
Based on the use pattern, no long-term
inhalation exposure is expected to occur. Risk
assessment is not required.
Study
Acute Neurotoxicity-
Rat
Chronic Toxicity -
Rat (2 year)
Not Applicable
28-Day Dermal
Toxicity- Rats
Not Applicable
Subchronic
Inhalation- (90 days)
Rats
Not Applicable
NOAEL, No observable adverse effects level; UF, uncertainty factor; RfD, reference dose; FQPA SF, Food Quality Protection Act Safety Factor;
MOE, margin of exposure.
Table is from references 1 and 4, as modified by the 5/26/99 HIARC decision regarding the NOAEL for dermal scenarios (report in preparation).
"Inhalation dose calculation is detailed in reference 5; the equation included the Sprague-Dawley rat mean respiratory volume of 10.26 L/hr (at rest)
and mean body weight of 0.236 kg.
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Acute Dietary
In an acute neurotoxicity study in rats (MRID 43217401), pebulate (purity: 96.1%) was
administered in a single gavage dose to groups of 10 male and 10 female Wistar derived rats
(Alpk:APfSD strain) at dose levels of 0, 50, 150 or 500 mg of pebulate (in corn oil) per kilogram
of body weight.
The following treatment-related findings were observed in the 500 mg/kg male and/or
female groups: (1) clinical findings (decreased activity, hunched posture, splayed gait, decreased
visual placement response, piloerection, irregular breathing, ptosis, chromodacryorrhea, rigidity
during handling, signs of salivation, and urinary incontinence); (2) decreases in group mean body
weight and food consumption during the first week after dosing; (3) increases in the landing foot
splay and time to tail flick; (4) decreases in the hindlimb grip strength (males) and motor activity;
and (5) increased incidence of neuronal cell necrosis in the pyriform and dentate gyrus cortices.
Clinical signs were observed at 5-6 hours after dosing and disappeared within 1-2 days.
Treatment-related effects, observed in the 150 mg/kg group, were (1) decreased activity,
increased breathing rate, and decreased motor activity in females; and (2) increased incidence of
neuronal cell necrosis in the brain of males and females.
Treatment-related findings were not observed in the 50 mg/kg group. Pebulate had no
effect on cholinesterase (brain, plasma and erythrocyte) and neurotoxicesterase activities, brain
measurements (weight, length and width), and macroscopic pathology.
The lowest observed adverse effect level (LOAEL) for neurotoxicity is 150 mg/kg based
on decreased motor activity and the no observed adverse effect level (NOAEL) is 50 mg/kg. This
study is classified acceptable and satisfies the guideline (§81-8; OPPTS 870.6200) requirement for
an acute neurotoxicity study in rats.
Chronic Dietary
In a two-year chronic toxicity/carcinogenicity study in rats (MRID 41213001), pebulate
technical (97.3% a.i.) was administered in the diet to Charles River rats (60 or 70/sex/group) at
dose levels of 0, 15, 150, or 1500 ppm (equivalent to 0, 0.74, 7.12, or 75.6 mg/kg/day for males
and 0, 0.85, 9.4, or 99.44 mg/kg/day for females, respectively) for two years.
Increased mortality was observed in the high-dose males only during the first 7 months of
the study. Clinical signs (pale eyes and extremities, red oral and nasal discharges, and general
poor condition) were observed in the high-dose males which died or were sacrificed moribund
during the first year of the study. Ophthalmological findings (zonal disjunction, retinal
degeneration, and cataracts) were observed mostly in the high-dose males and females, and less
frequently in the mid-dose males and females. Complete cataract was observed in 10.7% males
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and 14.7% females of high-dose group compared to that in 3.3% males and 0% females of the
control group.
Decreased body weights in the high-dose males (17-21.4%) and females (16.4-39.9%),
were observed throughout the study (weeks 2-105), and in the mid-dose males (13.4-8.2%)
during weeks 3-69 and the mid-dose females (14.2-16.6%) during weeks 3-97. Significant body
weight gain deficits were observed in the high-dose group (139% in males and 156.2% in
females) when compared to the control. Increased food consumption was observed in the high-
dose males and females; and occasionally for the mid-dose males and females.
Hematology parameters showed increased thromboplastin times in the high-dose males
and females and increased Factor VII values in the high-dose males at the 12 and 24 months
sampling intervals. Clinical chemistry showed increased blood cholesterol and blood urea
nitrogen (BUN) levels and decreased triglyceride and glucose values in the high-dose males and
females at most sampling times. Necropsy did not reveal treatment-related abnormalities when
compared with controls. No significant difference in organ weights was observed in the low- and
mid-dose males and females compared to the controls. In the high-dose group, most organ
weights and organ/body weight ratios were statistically different from those of the control group.
However, because these differences from control were secondary to the observed decreases in
body weight gain, they were not indicative of primary organ toxicity. There was an increased
incidence and severity of necrotic lesions in the livers of the high-dose male rats dying
prematurely. Other microscopic findings in the high-dose male rats dying prematurely included
hemorrhages in the epididymides, liver, testes, thoracic spinal cord and thymus; inflammation of
epididymides and skin; islet hyperplasia (pancreas) and extramedullary hematopoiesis (liver).
Although pebulate causes Wallerian-type degeneration in brain, spinal cord, and peripheral nerves
in dogs, this was not observed in this study.
There was no evidence of carcinogenic potential for pebulate in this study. The doses
were considered adequate for testing the carcinogenic potential for pebulate in both sexes. The
NOAEL for systemic toxicity was 15 ppm (equivalent to 0.74 mg/kg/day for males and 0.85
mg/kg/day for females) and the LOAEL was 150 ppm (equivalent 7.12 mg/kg/day for males and
9.4 mg/kg/day for females) based on decreased body weights of both sexes and increased
incidence of cataracts in both sexes. This study is classified acceptable and satisfies the guideline
(§83-5; OPPTS 870.4300) requirement for a combined chronic toxicity/carcinogenicity study in
rats.
Short and Intermediate Term (Dermal)
In a 28-day dermal toxicity study in rats (MRID 41920701), SPF Wistar-derived albino
rats (5/sex/group) received a 6-hour dermal application of pebulate (97.1%) at dose levels of 1,
10, or 100 mg/kg/day for 21 days (5 applications per week) over a period of 30 days. No
treatment related mortality was observed. Treatment-related clinical observations included the
13
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following: (1) Slight or moderate erythema and edema in the mid- and high-dose males and
females; (2) desquamation, skin sensitive to touch and thickening of the skin in the high-dose
males and females; and (3) upward curvature of the spine mostly in the high-dose females.
Significant body weight gain deficits (128.7%) and reduction of food utilization (129%) were
observed in the high-dose females only. Hematology showed a 48% reduction in neutrophils
count in the high-dose females compared to the control. There were dose-related increases in
absolute and relative adrenal weights of males and females, but statistical significance was reached
only in the high-dose females. For dermal irritation, the NOAEL was established at 1 mg/kg/day
(both sexes) and the LOAEL was 10 mg/kg/day based on erythema and edema. For systemic
toxicity, the NOAEL was established at 100 mg/kg/day (the highest dose tested) for both sexes,
and the LOAEL was not established. This study is selected because its duration and route of
exposure are appropriate for short and intermediate term dermal exposure. Slight to moderate
dermal irritations were observed at mid- and high-dose groups. Systemic effects were similar to
those observed in other studies. Although there were some body weight gain decrements and
decreased food utilization in females at 100 mg/kg/day, they were judged to be confounding
because of the following data: (1) there were no difference in absolute body weight; (2) the
decreased body weight gain was equivocal at all doses in the females; (3) the decreases were
significant only on sporadic days and did not exhibit any consistency over time; and (4) decreased
body weight gain can be attributed to the dermal irritation, which was severe in the high dose
groups. Based on these factors, the Hazard Identification Assessment Review Committee
concluded that the 100 mg/kg/day dose is the NOAEL (not the LOAEL), and this value should be
used for the risk assessment.
Inhalation
In a subchronic inhalation study in rats (MRTD 00143576), Sprague-Dawley rats
(24/sex/group) were exposed (whole body exposure) to pebulate technical (97.7%) aerosol at an
analytical concentration of 0, 0.0034, 0.016, or 0.079 mg/L (MMAD 3-7.7 //m) for 6 hours per
day, 5 days per week for 14 weeks. No treatment-related mortality was observed. An earlier
onset and an increased incidence of salivation were observed in a dose-related fashion. Body
weight gain was depressed (112% and 19% in males and females, respectively) at 0.079 mg/L at
the end of the study whereas food consumption remained unaffected by treatment. No treatment-
related changes were noted in hematology and clinical chemistry at 3, 9, or 14 weeks. Brain,
plasma, and red blood cell cholinesterase activities were measured at weeks 3, 9, and 14 of the
study. Significant inhibitions of red blood cell cholinesterase (142% in males and 139% in
females) and brain cholinesterase (126% in males only) were observed at the highest dose tested
in week 14 of the study.
Blood coagulation time (test for clotting factors) was prolonged in males and females at
0.016 and 0.079 mg/L; bleeding times (test for platelet function) were not significantly increased
by treatments. Relative liver weights in both sexes, relative adrenal weights in females, and
relative testes weight in males were significantly increased at the highest dose tested. However,
14
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none of these changes were correlated with histopathologic lesions in these organs. In contrast,
the relative kidney weights, which were significantly increased in both sexes of the high-dose at 14
weeks, are associated with histopathological changes in the kidney. In males, regenerative tubular
hyperplasia was observed to increase with doses at incidences of 4/12, 6/12, 8/11, and 9/11 in
control, 0.0034, 0.016, and 0.079 mg/L, respectively. Degeneration and vacuole formation in
kidney epithelium of female rats increased from 0/12 in control to 4/12 and 6/12 at the two
highest dose levels.
Furthermore, an increase in the incidence of mucigenic epithelial hyperplasia of the nasal
turbinate was observed in both sexes (becoming dose-related in females), suggesting possible
irritative effects of pebulate to the nasal passage at all doses over the 14-week course of exposure.
Under conditions of this study, the NOAEL was 0.0034 mg/L and the LOAEL was 0.016 mg/L
based on prolonged coagulation time, degenerative effects in kidney and increased incidences of
mucigenic epithelial hyperplasia of the nasal turbinate. This study is classified acceptable and
satisfies the guideline (§82-3; OPPTS 870.3465) requirement for a subchronic inhalation study.
2. Food Quality Protection Act Considerations
The Agency is retaining the Food Quality Protection Act (FQPA) safety factor of lOx for
protection of infants and children (references 6 and 7). The rationale for retention of the FQPA
safety factor is as follows:
• Severe neuropathology is exhibited in studies with adult animals (subchronic neurotoxicity
study in rats and one-year dog study indicate exposure to pebulate produced
neuropathologic changes);
• There is a structural similarity between pebulate and molinate (a thiocarbamate), which is
known to produce neurotoxicity/neuropathology;
• Molinate, a chemical analog of pebulate, is a reproductive toxicant in mice, rats, and dogs;
and
• There is uncertainty regarding the effect of pebulate on developmental neurotoxicity, as
there are no data. A developmental neurotoxicity study will provide additional
information about functional parameter development, potential increased susceptibility,
and the effects of pebulate on the development of the fetal nervous system.
In the current analysis, the lOx FQPA safety factor is applied to various subpopulations
including infants and children as well as females of childbearing age (13-50 years of age). The
Agency is concerned about potential developmental (in utero exposure) effects of pebulate. The
lOx FQPA safety factor is not applied to the general population when it is appropriate only to
15
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apply the factor to portions of the population. In the case of pebulate, it is not appropriate to
apply the factor to males or to the general population due to the in utero nature of the effect.
3. Dose Response Assessment
All the currently required guideline studies on pebulate were available and provided
reasonable confidence when the toxicity endpoints and doses for risk assessment were selected.
However, the Agency will require a developmental neurotoxicity study to determine whether or
not pebulate has neurologic effects in developing animals.
All of the toxicity endpoints and doses for risk assessment were selected based on the
most sensitive toxic effect and were derived from studies that used similar routes of exposure as
those expected in possible human exposure scenarios. The doses and toxicological endpoints
used in this study are summarized in Table 3.
The Agency calculated the occupational risks associated with dermal and inhalation
exposure separately rather than combined. The rationale for separating these exposures is as
follows: (1) toxicity studies are available that used administration via the dermal and inhalation
routes; and (2) different toxic effects resulted from dermal and inhalation exposure.
4. Risk Assessment
a. Dietary Exposure and Risk
Potential exposure to pebulate residues in the diet occurs through food and water.
Residues are possible in treated tomato and sugar beet crops. Data supporting food exposure are
adequate for this assessment (reference 2). Exposure to pebulate residues in ground and surface
water was estimated using conservative modeling techniques; available monitoring data were
assessed but were not considered adequate for quantitative risk assessment purposes (reference
8).
b. Food Exposure and Risk
Pebulate has an early season soil-incorporated application with extensive soil degradation,
soil dissipation, and plant metabolism. No parent compound is identified in plant metabolism
studies. Major metabolites found in plants are a series of three different butylamine compounds
resulting from hydrolysis of the thiocarbamate moiety; these metabolites are not of toxicological
concern at the concentrations expected from registered uses of pebulate (9). Pebulate residues
were below the limit of quantitation in all field trials and processing studies.
Pebulate was identified at low levels in milk and fat in livestock metabolism studies using
greatly exaggerated doses (up to 223x). However, livestock dietary exposure is expected to be
negligible even when using conservative assumptions for livestock diets.
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Tobacco was not included in the dietary risk assessment because it is not ingested. It is
the Agency's position that any exposure to pesticide residues through the use of tobacco products
is negligible when compared to other, well documented, human health risks associated with
tobacco use. Therefore, any risk from pebulate through the use of tobacco and tobacco products
is not addressed in this RED.
The Agency's dietary risk assessments use the Dietary Exposure Evaluation Model
(DEEM™), which incorporates consumption data generated in the U.S. Department of
Agriculture (USDA) Continuing Surveys of Food Intakes by Individuals (CSFII), 1989-1992.
For acute dietary risk assessments, the entire distribution of single day food consumption events is
combined with either a single residue level (deterministic analysis) or a distribution of residues
(probabilistic analysis, referred to as "Monte Carlo") to obtain a distribution of exposure in
milligrams per kilogram of bodyweight per day. For chronic dietary risk assessments, the three-
day average of consumption for each subpopulation is combined with residues in commodities to
determine average exposure in milligrams per kilogram of body weight per day. For deterministic
(Tier 1) analyses, the Agency regulates at the 95th percentile of exposure; for probabilistic
analyses, the Agency regulates at the 99.9th percentile of exposure.
The NOAEL and uncertainty factors (UF) are used to establish the "allowable" exposures
to a pesticide, which is referred to as the reference dose (RfD). When the FQPA safety factor is
also applied, the RfD is divided by the FQPA safety factor, which results in a potentially different
figure, the Population Adjusted Dose (PAD). This dose is intended to protect the most sensitive
population, and it is for this subpopulation that the Agency considers when making regulatory
decisions. Therefore, when the FQPA safety factor is retained, as in the case of pebulate, the
PAD is the value used for regulatory decisions rather than the RfD. The dose and endpoints
selected for various exposure scenarios are shown in Table 2. The Agency is not concerned when
a risk estimate is less than 100% of the acute Population Adjusted Dose (aPAD, which is the dose
that an individual could be exposed to on any given day and no adverse health effects would be
expected (RfD) divided by the FQPA safety factor).
Chronic dietary risk is calculated by using the average consumption values for food and
average residue values for those foods. A risk estimate that is less than 100% of the chronic PAD
(cPAD, which is the dose an individual could be exposed to over a lifetime and not expect an
adverse health effect, divided by the FQPA safety factor) does not exceed the Agency's risk
concern.
Acute and chronic dietary exposure to pebulate result in risk estimates that are
significantly below the Agency's level of concern (the aPAD and cPAD, respectively) at all tiers
of analysis (i.e., using existing tolerances, reassessed tolerances, and incorporating residue
refinements). Residue refinements included anticipated residues from field trials, adjustments for
percent crop treated, and a probabilistic/Monte Carlo acute analysis. No monitoring data have
been generated for pebulate by the USDA Pesticide Data Program or the U.S. Food and Drug
17
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Administration (FDA). Even though dietary risk was below the Agency's level of concern based
on existing tolerances, the maximum level of refinement was used in the event that a cumulative
risk assessment is required for pebulate and other chemicals having a common mechanism of
toxicity. Applying all of these refinements, acute and chronic dietary risk estimates are calculated
as <1% of the acute and chronic population adjusted doses (aPAD and cPAD, respectively) for
adults, infants, and children (Table 4) (10).
Table 4. Acute and Chronic Dietary Exposure and Risk Estimates for Pebulate.
Population Subgroup
General US
Population
Females 13-50
All Infants
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based on modeling predictions and, qualitatively, on available water monitoring data. Uncertainty
in modeling predictions of ground and surface water residues is due primarily to a lack of
environmental fate data for the degradate and the inability to accurately estimate the influence of
volatilization of the parent on dissipation. Because conservative input parameters for pebulate
sulfoxide were used, modeling of ground and surface water residues is considered to be
conservative. For a full discussion of the uncertainties associated with the environmental fate
modeling used for this assessment, refer to reference 8.
The modeling procedures were conducted for the tobacco use pattern because this use is
expected to contribute most to pebulate loading into surface waters due to the large geographical
area in which tobacco is grown. Ground water is not of concern for this use pattern, because
pebulate is not expected to leach to ground water based on its chemical properties.
Surface Water
Tier IIPRZM-EXAMS modeling provides upper-bound predictions of pebulate
concentrations in surface water. The assessment assumes 4 Ib ai/A of pebulate and 0.732 Ib ai/A
of pebulate sulfoxide are applied to a sandy loam soil in North Carolina, a major tobacco-growing
state. Concentrations of pebulate and pebulate sulfoxide in surface water are not likely to exceed
40 ppb pebulate equivalents for peak (acute) exposure and 2.6 ppb pebulate equivalents for mean
(chronic) exposure.
Ground Water
As previously state, pebulate is not expected to leach to ground water based on its
chemical properties. However, because of the lack of fate data associated with pebulate
sulfoxide, the SCI-GROW model was used to estimate ground water concentrations using the
same application rate input data as was used for PRZM/EXAMS. Concentrations of pebulate and
pebulate sulfoxide vary considerably with the assumptions made regarding the mobility of
pebulate sulfoxide. If the mobility is assumed to be equivalent to that of molinate sulfoxide, then
ground water modeling predicts peak and annual concentrations of 1.8 ppb. Although it is not
certain as to whether pebulate sulfoxide would behave like molinate sulfoxide in the environment,
the low soil:water partitioning for molinate sulfoxide used in the modeling is expected to yield
conservative water concentrations. Given the uncertainty associated with using surrogate data,
the Agency also considered a "worst case scenario," i.e., if pebulate sulfoxide is assumed to have
negligible binding affinity for soil (Koc = 0). In this case, the model predicts peak and annual
concentrations of 44 ppb, which would exceed the Agency's level of concern. The Agency is
requiring environmental fate data to permit refinement of the ground water exposure estimates.
19
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Drinking Water Levels of Comparison
Drinking water exposure to pesticides can occur through groundwater and surface water
contamination. The Agency considers both acute (one day) and chronic (lifetime) drinking water
risks and uses either modeling or actual monitoring data, if available, to estimate those risks. To
determine the maximum allowable contribution of water allowed in the diet, the Agency first
looks at how much of the overall allowable risk is contributed by food and then determines a
drinking water level of comparison (DWLOC) to ascertain whether modeled values exceed this
level. The Agency compared the DWLOCs and the estimated concentrations of pebulate and
pebulate sulfoxide in surface water and ground water generated by modeling with
PRZM/EXAMS and SCI-GROW, respectively (Tables 5 and 6).
Table 5. Summary of Acute DWLOC Calculations
Population
Subgroup
U.S. Population
Females 13-50 yr
All infants
Children 1-6 yr
Children 7-1 2 yr
aPAD
(mg/kg/day)
0.5
0.05
0.05
0.05
0.05
Food
Exposure
(mg/kg/day)
0.000134
0.000099
0.000126
0.000197
0.000200
Available
Water Exposure
(mg/kg/day)
0.5
0.05
0.05
0.05
0.05
Ground Water
(SCI-GROW
44/1.8
44/1.8
44/1.8
44/1.8
44/1.8
Surface
Water
(PRZM/
EXAMS)
(ppb)
40
40
40
40
40
Acute
DWLOC
17500
1,500
500
500
500
*The figure 44 //g/L was calculated with Koc = 0; the 1.8 //g/L was calculated with Koc = molinate sulfoxide (i.e., assumes that the mobilities of
pebulate sulfoxide and molinate sulfoxide are the same).
Table 6. Summary of Chronic DWLOC Calculations
Population
Subgroup
U.S. Population
Females 13-50 yr
All infants
Children 1-6 yr
Children 7-1 2 yr
cPAD
(mg/kg/day)
0.007
0.0007
0.0007
0.0007
0.0007
Food Exposure
(mg/kg/day)
0.000003
0.000002
0.000001
0.000005
0.000004
Available
Water
Exposure
(mg/kg/day)
0.007
0.0007
0.0007
0.0007
0.0007
Ground Water
(SCI-GROW
(Mg/L)*
44/1.8
44/1.8
44/1.8
44/1.8
44/1.8
Surface
Water
(PRZM/
EXAMS)
(ppb)
2.6
2.6
2.6
2.6
2.6
Chronic
DWLOC
(Mg/L)
245
21
7
7
7
*The figure 44 //g/L was calculated with Koc = 0; the 1.8 Aig/L was calculated with Koc = molinate sulfoxide (i.e., assumes that
the mobilities of pebulate sulfoxide and molinate sulfoxide are the same).
20
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Acute DWLOCs
Acute DWLOCs greatly exceed even the most conservative estimated environmental
concentrations in both surface water and ground water (Table 5). This result indicates that there
is no acute dietary concern for pebulate residues in drinking water.
Chronic DWLOCs
Comparing the chronic DWLOCs with the environmental concentrations of pebulate and
pebulate sulfoxide (which were estimated using conservative modeling), surface water
concentrations are less than the DWLOCs (Table 6). If mobility is assumed to be equivalent to
molinate sulfoxide, ground water concentrations are also estimated to be less than the chronic
DWLOCs. However, if the mobility is assumed to be much greater [a soil binding affinity of
zero (Koc = 0)], then the estimated concentration of pebulate and pebulate sulfoxide in ground
water exceeds the chronic DWLOC for infants, children, and females (13-50 years). Thus, there
appears to be the slight potential for pebulate residues in ground water to occur at levels of
concern, i.e., >DWLOC of 7 or 21 ppb (Table 6). Although the affinity of pebulate sulfoxide to
soil could be less than that of molinate sulfoxide, it is unlikely that it will not bind to soil
whatsoever. Because of the uncertainties about the environmental fate properties of pebulate
sulfoxide (such as Koc), the Agency is requiring data that will permit refinement of these
modeling estimates.
d. Other Dietary Concerns
The current pebulate label requires an 8-day preharvest interval (PHI) for tomatoes. This
interval is inconsistent with the typical agronomic practices associated with the use of this
chemical (i.e., pebulate is primarily a preplant, preemergent pesticide) and the available residue
data. Therefore, the Agency is requiring a PHI of 30 days. If the registrant wishes to retain the
8-day PHI, supporting residue data must be submitted.
In addition, based on confined crop rotational studies, residues of likely toxicological
concern remain in raw agricultural commodities (RACs) planted up to 4 months after soil
treatment and the actual rate of pebulate decline in the environment is unknown. Although
residues of the parent compound are not found in significant amounts in plants, there is expected
to be much greater exposure to the sulfoxide metabolite than to the parent in rotational crops.
The reason is the degradates are expected to be more persistent than the parent compound due
to their more polar nature and lower volatility. The degradates are therefore more likely to be
the major soil, water, and plant residues (references 9 and 10). Therefore, the pebulate label
must be amended to require that all crops, including sugar beets and tomatoes, not be rotated
earlier than 4 months after treatment with pebulate. Alternatively, a shorter plantback interval
may be supported by (1) providing additional data to upgrade existing confined rotational crop
21
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studies or (2) performing limited field crop rotational studies wherein metabolites of potential
toxicological concern are sought.
e. Occupational/Residential Risk
The Agency believes that people involved in the application of pebulate can be exposed
while working with the pesticide. These people are referred to as handlers and represent those
who plant the crop and those who prepare solutions and fertilizer mixtures for use (referred to as
mixer/loaders) and those who make the applications by driving the groundboom tractor or other
application equipment (referred to as applicators). According to the label, workers can re-enter
a pebulate-treated field 12 hours after application. Any worker entering the field before that time
must wear personal protective equipment if coming in contact with treated soil (i.e., hoeing
tomatoes).
Due to the rapid volatilization of pebulate, there is concern over the use of pebulate in an
enclosed area. There are currently no known uses of pebulate in greenhouses, but the label does
not prohibit such a use. The pebulate label should be amended to prohibit greenhouse use.
There are no residential uses of pebulate or products available for sale to homeowners.
Applications are made using ground-based agricultural equipment, and aerial application is not
allowed. If pebulate is applied using common groundboom equipment, it must be incorporated
into the soil during or immediately after application to prevent volatilization. It can be also be
applied below the surface of the soil to prevent volatility using subsurface sweeper application
(tobacco only) or using soil-injection methods. Applications of pebulate in irrigation water,
referred to as chemigation, are also allowable. If pebulate is applied during irrigation, it must be
watered in with approximately /^ inch of water (as specified on the label) to ensure that it
penetrates the surface of the soil to depths between 2 to 4 inches. Pebulate can also be mixed
and applied along with fluid fertilizer to tomatoes and tobacco or it can be impregnated on dry
bulk fertilizer for application to tobacco. Soil incorporation is also required after the application
of pebulate in either liquid or dry fertilizers. There are two methods for the addition of pebulate
to dry bulk fertilizer: on-board and in-plant impregnation. With the on-board application (which
is not widely used), pebulate is metered onto the dry fertilizer as it is being applied to the field;
the equipment used is similar to a groundboom. The in-plant impregnation method is a
commercial operation conducted by a dealer or distributor. The pebulate is mechanically mixed
with the dry bulk fertilizer using a closed system.
A summary of the use patterns for the occupational exposure and risk assessments is
shown in Table 7. All assessments used a single registered end-use product, the 6 Ib ai/ gal
emulsifiable concentrate (EC). Additional considerations are as follows: (1) as a preemergent
herbicide, it must be soil-incorporated for efficacy; and (2) as a postemergent or after transplant
application (allowed on tomatoes only), applications must be covered.
22
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Table 7. Summary of Use Patterns
Equipment used for
mixing/loading and
application
Chemigation equipment
Groundboom sprayer
Drop-type tractor- drawn
spreader, specialized truck,
soil injection equipment
Use Site
Tomatoes
Tomatoes
Tobacco
Sugar Beets
Tobacco
Application rate range
4 - 6 Ib ai/A
3 - 10 Ib ai/A
(10 Ib ai/A is tomato only)
4 Ib ai/A
(dry bulk fertilizer application)
Frequency of
application
1 x / season
1-2 x/ season
1 x / season
The results of the risk assessment (reference 5) indicate that risks to mixers and loaders
can be mitigated with the use of personal protective equipment (PPE), i.e, long sleeved shirt,
long pants, coveralls, and chemical-resistant gloves. In addition, unless a closed system is being
used, an organic vapor respirator (Table 8) is required for mixer/loaders. The risk assessments
are identical for short-term (one week or less) and intermediate-term (one week to several
months) exposure durations.
23
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Table 8. Summary of Short-Term and Intermediate-Term Risks: MOEs for Dermal and Inhalation Scenarios
No.
1
2
3
4
Exposure Scenario
Crop Type/Use
Acres Treated
or Amount
Handled per
Day
Application Rate
Baseline PPE*
MOE
Dermal
Inhalation
Additional PPE*
MOE
Dermal
Inhalation
Engineering Controls*
MOE
Dermal
Inhalation
Mixer Loader Exposures
Mixing/Loading Emulsifiable
Concentrate for Chemigation
Mixing/Loading Emulsifiable
Concentrate for Soil Injection
and Groundboom Application
In-Plant Mixing/Loading
Emulsifiable Concentrate for
Impregnation on Dry Bulk
Fertilizer (Closed System)
Mixing/Loading Fluid
Formulation for Combination
with Liquid Fertilizer*
Tomatoes
Tomatoes
(Western
Region)
Sugar Beets,
Tomatoes,
Tobacco
Tobacco
Tobacco
(assuming
40 ten ton trucks
loaded per day)
Tomatoes
350 acres
80 acres
3,200 Ib ai/day
1,600 Ib ai/day
No Data
No Data
No Data
6 Ib ai/A
4 Ib ai/A
10 Ib ai/A
6 Ib ai/A
4 Ib ai/A
3 Ib ai/A
4 Ib ai/A
4 Ib ai/A
10 Ib
ai/A
10 Ib
ai/A
10 Ib
ai/A
1,000 Ib
fertilizer/A
2,000 Ib
fertilizer/A
10 gallons
fertilizer/A
20 gallons
fertilizer/A
40 gallons
fertilizer/A
1
2
3
5
8
10
NA
NA
No Data
No Data
No Data
25
37
65
110
160
220
NA
NA
No Data
No Data
No Data
200
290
510
860
1300
1700
NA
NA
No Data
No Data
No Data
250
370
640
NA
NA
NA
NA
NA
No Data
No Data
No Data
NA
NA
NA
NA
NA
NA
250
510
No Data
No Data
No Data
NA
NA
NA
NA
NA
NA
230
470
No Data
No Data
No Data
24
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No.
5
6
7
8
9
Exposure Scenario
Crop Type/Use
Acres Treated
or Amount
Handled per
Day
Application Rate
Baseline PPE*
MOE
Dermal
Inhalation
Additional PPE*
MOE
Dermal
Inhalation
Engineering Controls*
MOE
Dermal
Inhalation
Applicator Exposures
Applying with a Groundboom
Sprayer
Applying Dry Bulk Fertilizer
with a Drop- Type, Tractor-
Drawn Spreader
Applying Dry Bulk Fertilizer
with a Specialized Truck
Applying Fluid Fertilizer**
Soil Injection**
Tomatoes
(Western
Region)
Sugar Beets,
Tomatoes
Sugar Beets,
Tomatoes,
Tobacco
Tobacco
Tobacco
Tobacco
Tomatoes
Tobacco
80 acres
80 acres
500 acres/day
No Data
No Data
10 Ib ai/A
6 Ib ai/A
4 Ib ai/A
3 Ib ai/A
4 Ib ai/A
4 Ib ai/A
10 Ib ai/A
No Data
630
1000
1600
2100
2200
350
No Data
No Data
110
180
260
350
160
26
No Data
No Data
NA
NA
NA
NA
NA
NA
No Data
No Data
NA
NA
NA
NA
NA
260
No Data
No Data
NA
NA
NA
NA
NA
NA
No Data
No Data
NA
NA
NA
NA
NA
NA
No Data
No Data
For occupational risk, margins of exposure (MOEs) greater than 100 are considered above the Agency's level of concern. Baseline PPE is defined by PHED as long-sleeved shirts, long pants, shoes, and
socks. Additional PPE includes coveralls and chemical-resistant gloves (for dermal) and an organic vapor respirator (inhalation). Engineering Controls are closed systems.
* No data exists in PHED for mixer/loader combining pebulate with a liquid fertilizer. Therefore, no MOEs could be calculated. However, based on information provided by the registrant, the Agency
made assumptions and evaluated the risks associated with these scenarios (discussed in the text, above).
** No data exists in PHED for applicators using specialized equipment for the application of a combination of pebulate and fluid fertilizer and for application by soil injection. Therefore, no MOEs could be
calculated. However, based on information provided by the registrant, the Agency made assumptions and evaluated the risks associated with these scenarios (discussed in the text, above).
25
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Risk to applicators only exceed the Agency's level of concern for the dry bulk fertilizer to
tobacco scenario (No. 7, Table 8). This is due to the large area treated (500 acres/day), which is
accomplished using a specialized truck. The risk assessment indicates that there is an inhalation
risk which will require the applicator to use an organic vapor respirator. However, this
inhalation risk can also be mitigated with the use of engineering controls, i.e., an enclosed cab
with an air filtration system equal to that of an organic vapor respirator.
One mixer/loader scenario (No. 4, Table 8) and two applicator scenarios (No. 8 and No.
9, Table 8) are not represented by corresponding surrogate exposure unit values in the Agency's
library of actual exposure monitoring data known as Pesticide Handlers Exposure Database
(PHED) or any pebulate-specific study data. However, based on information supplied by the
registrant characterizing these scenarios (MRTD 44875900), the Agency has made the following
determinations as to the associated risks.
As described by the registrant, the risk assessment for mixing/loading and applying
pebulate with fluid fertilizer (Nos. 4 and 8, respectively, Table 8) would be equal to the scenarios
for groundboom (Nos. 2 and 5, respectively, Table 8). Therefore, the same mitigation measures
would apply.
For the soil injection applicator (No. 9, Table 8), the risk would be less than for that of
the groundboom scenario (No. 2, Table 8). With soil injection, the chemical is sprayed directly
into the soil at a depth from 4-6 inches below the soil surface, which would result in even less
exposure than for that of a groundboom applicator. Therefore, the mitigation measures would
be the same for soil injection and groundboom applicators.
In addition, the registrant identified a noncommercial method for impregnation of drybulk
fertilizer, referred to as on-board impregnation. Only the commercial, or in-plant scenario, is
shown in Table 8 (No. 3). The Agency concurs that the mixing/loader exposure scenario for on-
board impregnation procedure would result in risks similar to that of the groundboom
mixer/loader (No. 2, Table 8) and is therefore requiring the same risk mitigation measures. The
applicator for this scenario would be equal to that of applying with a groundboom sprayer (No.
5, Table 8); therefore, and the same mitigation measures are required.
Occupational Handler Characterization
Information used in this risk assessment was obtained from the pebulate product label,
PHED, and other Agency offices. Maximum application rates stated on the label were used
along with more typical use rates to help characterize the range of worker exposures. The
PHED values are characterized as central tendency, and do not represent the worst or best case
of worker exposure. Further, the PHED unit exposure values for many of the scenarios were AB
grade, i.e., the unit exposure values were generated using high quality analytical techniques.
Most of the scenarios used from PHED also had many replicates, which increases the confidence
26
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in the data and better represents the worker exposure. Although one mixer/loader and two
applicator scenarios did not have corresponding exposure unit values in PHED or any study data,
the Agency was able to characterize these scenarios based on additional information provided by
the registrant.
Post-Application Risk
The Agency generally completes risk assessments for those individuals who can be
exposed from entering previously treated areas to work (i.e., referred to as postapplication
exposures). The most common examples of these kinds of exposures are farmworker activities
such as picking grapes or citrus. When these kinds of assessments are completed by the Agency,
the cultural practices associated with raising the crop and the reason for using the chemical are
considered. Pebulate is primarily a preplant or pre-emergent herbicide that is applied only to
sugar beets, tobacco, and tomatoes. The Agency does not believe that there are any
postapplication exposure concerns associated with the use of pebulate on sugar beet because
there are no activities that would involve exposure (such as hand transplanting). Likewise, the
Agency did not complete a risk assessment on tomatoes and tobacco because there are no major
activities that contribute to postapplication exposure. According to the label, workers can re-
enter a pebulate treated field 12 hours after application. Any worker entering the field before
that time must wear personal protective equipment if coming in contact with treated soil (i.e.,
hoeing tomatoes or plug planting into treated soil).
In addition, the current pebulate label addresses a potential risk to personnel who
transplant seedlings of tomatoes and tobacco with the following language:
"... mechanical transplanting only. DO NOT apply Tillam 6-E prior to hand
transplanting."
However, current practices may not adequately reduce exposure to such personnel. As
described by the registrant (MRTD 448759), mechanical transplanting via totally automated
systems would only occur in some very large operations. The usual practice is what has been
referred to as "mechanically assisted" hand transplanting. For this method, an individual places a
starter plant on a wheel that rotates downward, releasing the plant into a mechanically cut
furrow. The furrow is then mechanically closed. This semi-mechanized scenario may involve
human contact with treated soil. The Agency is therefore requiring that chemical-resistant gloves
be worn by the handlers, which would include the transplanters, and is requiring additional
confirmatory data to assess the actual exposure and risks involved with this method.
The Agency is aware of a growing interest in the use of pebulate as a partial alternative to
methyl bromide, an ozone-depleting pesticide that is being phased out of production. The
registrant, as well as USDA researchers, believe that the use of methyl bromide on tomatoes
could be replaced by a pebulate and Telone combination. To use a combination that includes a
27
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fumigant such as Telone, however, requires tomato growers to use plastic mulch. Such a
cultural practice would in turn necessitate the use of hand transplanting, which is currently
prohibited on the pebulate label. If the registrant agrees to conduct the post-application dermal
exposure study mentioned above, the Agency would consider whether to lift or relax the current
hand transplanting prohibition.
f. Residential Exposure
There are no products containing pebulate that may be used in a residential setting.
Therefore, no exposure and risk assessment is necessary for residential scenarios. The Agency
recognizes there are many issues related to the use of agricultural chemicals and exposures in the
general population. For example, the issues of spray drift and exposures to farmworker children
are often raised. However, application methods for pebulate do not include aerial or airblast; as
a result, drift is expected to be minimal. The Agency is in the process of developing guidance
and procedures for characterizing these kinds of exposures. They are not specifically assessed in
this document. This guidance will be included in the revised Standard Operating Procedures for
Residential Exposure Assessment, scheduled for publication in 1999.
5. Aggregate Risk Assessments and Risk Characterization
Aggregate risk combines exposure through food, drinking water, and residential uses of a
pesticide. Generally, the combined risks from those exposures must be less than 100% of the
aPAD and cPAD.
a. Acute Aggregate Risk
Acute aggregate risk estimates do not exceed the Agency's level of concern (0.05
mg/kg/day). This is based on an assessment of the most sensitive subpopulation (children 1-6
years of age). The aggregate acute dietary risk estimates include exposure to pebulate residues
in food and water. The Agency used anticipated residues derived from field trial data, percent-
crop-treated data, and a probabilistic assessment to refine acute dietary risk (food only). Acute
dietary food risk to all population subgroups is <1% of the aPAD. Although the most
conservative assumptions (tolerance level residues and 100% crop treated) resulted in risk due to
food alone that was below the Agency's level of concern, refinements were made to permit a
more realistic calculation of DWLOCs and in anticipation of a cumulative risk assessment.
Estimated peak concentrations of pebulate residues in both surface water and ground water were
well below the calculated DWLOCs for all population subgroups. Thus, pebulate is not expected
to pose an acute risk of concern to any population.
28
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b. Chronic (Noncancer) Aggregate Risk
The Agency has determined that there is not a chronic aggregate risk of concern for
pebulate when considering the cPAD (0.0007 mg/kg/day) for the most sensitive subpopulation,
children (1-6 years of age). While aspects of the Agency's chronic aggregate risk assessment
show a potential concern, the Agency finds that there is insufficient information at this time to
conclude that such a risk is valid. The exposure contribution by the consumption of residues in
food is small (i.e., <1% of the cPAD for all population subgroups using anticipated residue and
percent-crop-treated data) and there is no residential exposure component. However, the
modeled drinking water component of the aggregate risk calculation is equivocal.
The Agency finds a potential concern from drinking water only when considering certain
extreme assumptions about the properties of pebulate degradates. When using less extreme
assumptions on the environmental fate of pebulate degradates, the Agency finds that modeled
water concentration levels do not result in drinking water concerns, and thus, do not result in an
aggregate risk of concern. Although sufficiently representative monitoring data are not available
to permit quantitative inclusion of drinking water residues in the aggregate risk, the available
monitoring data also do not support the modeled estimates.
Even though the Agency believes these modeled estimates may overestimate the
aggregate risk, the Agency is requiring additional confirmatory environmental fate data on the
degradate, pebulate sulfoxide. These data will allow for the refinement of these assessments and
serve to confirm the position that aggregate risk is not a concern.
6. Endocrine Disrupter Effects
EPA is developing a screening program to determine whether certain substances
(including all pesticides and inerts) "may have an effect in humans and wildlife that is similar to
an effect produced by a naturally occurring estrogen, or such other endocrine effect...." The
Agency is currently working with interested stakeholders, including other government agencies,
public interest groups, industry and research scientists in developing a screening and testing
program and a priority setting scheme to implement this program. When this program is
implemented, the Agency may require further testing of pebulate for endocrine effects. At this
time, there is no evidence of endocrine disruption caused by pebulate.
7. Cumulative Effects
Section 408(b)(2)(D)(v) of the Food Quality Protection Act requires that, when
considering whether to establish, modify, or revoke a tolerance, the Agency consider "available
information" concerning the cumulative effects of a particular pesticide's residues and "other
substances that have a common mechanism of toxicity." The Agency believes that "available
information" in this context might include not only toxicity, chemistry, and exposure data, but
29
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also scientific policies and methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although the Agency has some
information that may be used for determining whether a pesticide shares a common mechanism
of toxicity with any other substances, EPA does not at this time have the methodologies to
resolve the complex scientific issues concerning common mechanism of toxicity in a meaningful
way. EPA has begun a pilot process to study this issue further through the examination of
particular classes of pesticides. The Agency hopes that the results of this pilot process will
increase the Agency's scientific understanding of this question such that EPA will be able to
develop and apply scientific principles for better determining which chemicals have a common
mechanism of toxicity and evaluating the cumulative effects of such chemicals. The Agency
anticipates, however, that even as its understanding of the science of common mechanisms
increases, decisions on specific classes of chemicals will be heavily dependent on chemical
specific data, much of which may not be available at present.
The Agency is examining whether and to what extent some or all organophosphorous and
carbamate (including, but not limited to, methyl carbamate, N-methyl carbamate, thiocarbamate,
and dithiocarbamate) pesticides may share acetylcholinesterase inhibition as a common
mechanism of toxicity. In contrast to the methyl and N-methyl carbamates, the Agency has a less
fully developed understanding of whether the thiocarbamates share acetylcholinesterase inhibition
as a common mechanism of toxicity with other cholinesterase-inhibiting chemicals. While
current data are limited, the thiocarbamates appear to be comparatively weak cholinesterase
inhibitors and are generally regulated based on other toxic endpoints. As a result, the Agency
has not determined if it would be appropriate to include them in a cumulative risk assessment
with other such chemicals (e.g., the organophosphorous and carbamate pesticides) [see the
August 31, 1999, EPA Memorandum entitled September 1999 Meeting of the FIFRA Science
Advisory Panel: Working Documents for the Session: "Proposed Guidance for Conducing
Cumulative Hazard Assessments for Pesticides that Have a Common Mechanism of Toxicity"
and "The Carbamate Pesticides and the Grouping of Carbamate with the Organophosphorous
Pesticides'"}. Also see 40 CFR section 180.3(e)(5), which presents the Agency's initial grouping
of chemicals that would be considered together for the purpose of tolerance reassessment. This
grouping includes some carbamate pesticides but not thiocarbamate pesticides as members of the
class of acetylcholinesterase-inhibiting compounds.
In September 1999, the Agency presented a paper (cited above) on the common
mechanism of toxicity of the carbamate pesticides to the SAP. In that presentation, the Agency
noted that although various classes of compounds may inhibit acetylcholinesterase, the potency,
reversibility, and related factors may influence whether or not related pesticides should be
included in a cumulative risk assessment. The Agency is currently awaiting a report from the
SAP.
At this time, the Agency does not believe it has sufficient reliable information concerning
common mechanism issues to determine whether pebulate, a thiocarbamate, shares a common
30
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mechanism of toxicity with other cholinesterase-inhibiting chemicals. Therefore, for the
purposes of this tolerance reassessment, the Agency has assumed that pebulate does not share a
common mechanism of toxicity with cholinesterase-inhibiting chemicals.
C. Environmental Assessment
In this section, the fate of pebulate in the environment and the ecological effects are
described. An assessment was performed to determine the ecological risks associated with the
use of pebulate. These data are reviewed by the Agency for making the decisions regarding the
reregi strati on of pebulate.
1. Environmental Fate Assessment
Volatilization appears to be an important route of pebulate dissipation in the
environment. Laboratory data show that pebulate volatilizes rapidly (40% of the total amount of
pebulate that was applied volatilized from soil in 25 hours). However, pebulate and its
degradates did not degrade readily in the other laboratory studies. It did not hydrolyze
significantly (>90% of the parent remained after 30 days), and it photodegraded very slowly
(half-lives were observed of >30 days) in water and on soil. In aerobic sandy loam soil, pebulate
degraded with a half-life of 36 to 60 days; in anaerobic soil, the half-life was >60 days. In an
anaerobic aquatic metabolism study, no significant degradation occurred (although volatilization
was observed). Pebulate has high to medium mobility in soil (Freundlich Kds 1.24, 3.25, 4.46,
and 7.44 mL/g and with corresponding Kocs = 422, 291, 446, and 576 mL/g) and can run off to
surface water. Other data suggest that pebulate is not persistent under field conditions (with
half-lives of 4 to 20 days). Significant volatilization of pebulate may occur under field
conditions, even with soil incorporation.
A major uncertainty in the environmental fate of pebulate is associated with pebulate
sulfoxide, a significant degradation product. A half-life of 103 days for pebulate sulfoxide was
calculated from the residue data in the aerobic soil metabolism study submitted for pebulate
parent. The organic partitioning coefficient (Koc) for pebulate sulfoxide was estimated as 93
mL/g. This value was calculated using batch equilibrium data on molinate sulfoxide, a chemical
analog of pebulate sulfoxide. As with molinate sulfoxide, pebulate sulfoxide is considered very
mobile in soil and has the potential to leach in the soil profile and to move with water in surface
runoff. Environmental fate data are needed for pebulate sulfoxide to clarify the fate of pebulate
residues in the environment.
The moderate value of the calculated Henry's Constant (2.41 x 10"5 atm-m3/mol) for
pebulate, combined with the compound's volatility, suggest that if pebulate reaches the
atmosphere, it could be transported in fog, mist, rainwater, and on air currents.
31
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2. Water Resources Assessment
Pebulate is not included among regulated or unregulated chemicals required as analytes in
testing of public drinking water supplies. Therefore, drinking water monitoring results are not
readily available. Simulation modeling of pebulate along with monitoring data (reference 8)
indicates the following:
(1) The maximum total pebulate residues (pebulate and pebulate sulfoxide)
concentrations in surface water are 40 //g/L for acute exposure and 2.6 //g/L for chronic
exposure. These values are based on the PRZM-EXAMS models.
(2) U.S. Geological Survey (USGS) monitoring data report a maximum pebulate
concentration of 0.8 //g/L in surface water. However, these data were not targeted to a pebulate
use event (that is, water monitoring did not occur in conjunction with a pebulate application in a
particular area). This is significantly less than model predicted residues, although it is possible
that targeted monitoring for pebulate could result in higher residues.
(3) SCI-GROW modeling indicates that total pebulate residue concentrations in ground
water are not likely to exceed 1.8 //g/L for both peak (acute) and annual average (chronic)
concentration. The most conservative modeling scenario [where the pebulate sulfoxide organic
partitioning coefficient is equal to zero (Koc = 0)] predicts total residues of 44 //g of pebulate
equivalents per liter.
(4) Nontargeted USGS groundwater monitoring data report maximum pebulate
concentrations of 0.005 //g/L, although it is possible that targeted monitoring could show higher
residues.
3. Hazard Profile
Birds: Acute and Subacute Dietary Toxicity
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) was
required to establish the toxicity of pebulate to birds. The preferred test species is either mallard
duck (a waterfowl) or bobwhite quail (an upland gamebird). Two subacute dietary studies are
required to establish the toxicity of a pesticide to birds; the preferred test species are mallard
duck and bobwhite quail. For acute oral and subacute dietary toxicity, pebulate is classified as
practically nontoxic to avian species (Table 9).
32
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Table 9. Avian Acute Oral and Subacute Dietary Toxicity
Acute Oral Toxicity (Guideline 71-1)
Species
Mallard duck
%ai
96%
LD50
(mg/kg)
>2000
mg/kg
NOAEL
N.R.
Toxicity
Category
Practically
nontoxic
MRID
41920702
Guideline Status
Fulfilled
Subacute Dietary Toxicity (Guideline 71-2)
Species
Bobwhite
quail
Mallard duck
%ai
95%
96%
LC50
>5200 ppm
>5606 ppm
NOAEL
N.R.
650 ppm
Toxicity
Category
Practically
nontoxic
Practically
nontoxic
MRID
41614803
42294201
41614804
42294201
Guideline Status
Fulfilled
Fulfilled
N. R, Not reported
Birds: Chronic Effects
Avian reproduction studies are usually required for pesticides when the following
conditions are met: (1) birds may be subject to repeated or continuous exposure to the pesticide,
especially preceding or during the breeding season, and (2) information derived from mammalian
reproduction studies indicates reproduction in terrestrial vertebrates may be adversely affected by
the anticipated use of the product. Due to the use pattern associated with pebulate (a single
application with immediate soil incorporation), repeated exposure to residues is not expected and
chronic toxicity data for avian species is waived.
Mammals: Acute and Chronic Toxicity
The Agency requires wild mammal acute toxicity testing on a case-by-case basis,
depending on the results of lower tier laboratory mammalian studies, intended use pattern, and
pertinent environmental fate characteristics. For pebulate, as in most cases, rat or mouse acute
toxicity values (Table 2) are substituted for wild mammal testing. Based on laboratory rat acute
toxicity data, pebulate is slightly toxic to mammals (Table 10). Chronic exposure is not expected
to occur based on the use pattern and chemical characteristics of pebulate (reference 8).
33
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Table 10. Mammalian Acute Oral Toxicity
Species
Rat (male)
Rat (female)
LD50 mg/kg
1,750 mg/kg
1,550 mg/kg
NOAEL
N.R.
N.R.
Toxicity Category
3
3
N.R., Not reported
Terrestrial Insects
Honey bee acute contact and dietary exposure studies are not required because bee
exposure on blooming plants is unlikely because of the predominant use pattern for pebulate
(preplant application). A layby application, which is an application of pesticide concurrent with
mechanical weeding, occurs after planting. It is intended to be applied to clean, cultivated soils
and is also immediately soil-incorporated. A honey bee foliar residue contact toxicity study is
therefore waived because there is no significant potential for honey bee exposure to vegetative
surfaces after application.
Terrestrial Wildlife or Insect Incidents
Section 6(a)(2) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA)
requires pesticide product registrants to submit adverse effects information about their products
to the Agency. At the time of publication of this RED, the Agency has not received any reports
of adverse effects to nontarget terrestrial wildlife or insects from the use of pebulate.
Fish: Acute Toxicity
Two acute toxicity studies are required to establish the toxicity of a pesticide to
freshwater fish. The preferred test species are rainbow trout (a coldwater fish) and bluegill
sunfish (a warmwater fish). Acute toxicity testing with estuarine/marine fish species is desirable
when the end-use product active ingredient is expected to reach an estuarine environment.
Based on the data reviewed for pebulate, the pesticide is classified as slightly toxic to the
freshwater and marine/estuarine fish species tested species (Table 11). Use on tobacco crops is
expected to occur adjacent to estuarine areas, and therefore acute testing of an estuarine species
is needed to provide a complete risk assessment for this crop use. The studies reviewed to date
are not acceptable due to the use of shorter than the recommended exposure times (Table 12).
However, because no significant level of toxicity has been observed in other studies, at this time
the Agency is reserving the requirement for this test.
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Table 11. Freshwater Fish Acute Toxicity of Pebulate (Guideline 72-1)
Species Tested
Bluegill sunfish
Bluegill sunfish
Rainbow trout
Mosquitofish
%ai
95.9
77.3
95.9
77.5
LC50 and CLs*
(ppb)
6,300 (5,200 - 8,300)
7,900 (6,000 -10,400)
7,400 (6,000 - 9,300)
1 0.000 fN.R.1
MRID
41614805
4761615
41614806
00084743
Guideline
Status
Fulfilled
Fulfilled
Fulfilled
Fulfilled
*A11 studies were 96-hours of exposure; Cls, 95% confidence limits
Table 12. Marine/Estuarine Fish Acute Toxicity of Pebulate (Guideline 72-3)
Species Tested
Longnose killifish
Striped mullet
%ai
78
78
LCsn (CLs) in PPB
48 hr = 7,400 (N.R.)
48 hr = 6,300 (N.R.)
MRID
40228401
40228401
Guideline status
Not fulfilled
Not fulfilled
Fish: Chronic Toxicity
A freshwater fish early life-stage test, estuarine fish early life stage test or full life-cycle
test is required for pesticides when end-use products are expected to produce residues that may
be transported to water from the various intended use sites. Chronic testing guideline conditions
may be required if (1) the presence of the chemical in water is likely to be recurrent, (2) aquatic
acute median lethal dose is <1 mg/L, (3) the estimated environmental concentration (EEC) in
water is 1/100th of any acute median lethal dose, or (4) studies of other organisms indicate the
reproductive physiology offish may be affected. Because low acute toxicity is displayed in
freshwater fish exposed to pebulate, and the chronic toxicity values are not expected to be as low
as predicted EEC levels, the chronic testing guidelines for pebulate are waived.
Aquatic Invertebrates: Acute Toxicity
Pebulate is classified as only slightly to moderately toxic to freshwater aquatic
invertebrates on an acute basis (Table 13a). An acute toxicity test with estuarine/marine
molluscs is required because the end-use pebulate product is expected to reach this environment
due to its use on tobacco. The shrimp study reviewed to date was not conducted for 96 hours
and does not fulfill the guideline requirements (Table 13b). However, because no significant
level of toxicity has been observed in other studies, at this time the Agency is reserving the
requirement for this test in shrimp.
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Table 13a. Freshwater Invertebrate Acute Toxicity (Guideline 72-2)
Species Tested
Water flea, Daphnia magna
Scud, Gammarus fasciatus
%ai
96%
96%
48 hr EC50 or 96 hr LC50 (ppb)
48 hr = 6,630(5,400-8,600)
96 hr =10,000(7,000-13,400)
MRID
41614807
40098001
Guideline
Status
Fulfilled
Fulfilled
Table 13b. Marine/Estuarine Invertebrate Acute Toxicity of Pebulate (Guideline 72-3)
Species Tested
White shrimp, Penaeus
setiferous
%ai
68%
LC50 (CLs)
48 hr= 10,000 ppb (N.R.)
MRID
40228401
Guideline
Status
Supplemental
N.R., Not reported
Freshwater and Marine Invertebrates: Chronic Toxicity
Pebulate displays low acute toxicity to freshwater invertebrates. Predicted EEC levels
are at least 50 times below acute toxicity levels; therefore, the chronic testing guidelines for
pebulate are not required.
Freshwater, Estuarine and Marine Aquatic Incidents
Section 6(a)(2) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA)
requires pesticide product registrants to submit adverse effects information about their products
to the Agency. At the time of publication of this RED, no aquatic organism kills that directly
implicate pebulate usage have been submitted.
Toxicity to Plants
Terrestrial plant testing (seedling emergence and vegetative vigor) is required if an
herbicide meets the following criteria: (1) it has a terrestrial nonresidential outdoor use pattern
and may move off the application site through volatilization (vapor pressure is >1.0 x 10"5 mm
Hg at 25°C) or drift (aerial or irrigation); or (2) there may be endangered or threatened plant
species associated with the application site. Therefore, these tests were called in for pebulate.
For seedling emergence and vegetative vigor testing, the response of various plant
species relative to a control, are measured at various levels relative to the use rate of the
chemical. Some of these data are shown in Table 14; the entire list of species tested can be
found in reference 8. The results showed that pebulate runoff and drift to adjacent habitats may
prove hazardous to certain families of nontarget terrestrial and semiaquatic plants (mainly grass
related species). No risk to aquatic plants is predicted based on estimated aquatic residue levels
(Tables 15).
36
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Table 14. Terrestrial Plant Toxicity (Guideline 122-1: Fulfilled)*
Species Tested
Tomato
Cabbage
Onion
Soybean
Ryegrass
Purple nutsedge
Seed Emergence (MRID
42285301)
EC25
N/A
N/A
N/A
5.78 Ib ai/A
N/A
0.521bai/A
NOAEL
N/A
N/A
N/A
3.0 Ib ai/A
N/A
N/A
Vegetative Vigor (MRID
44735901)
EC25
>3.6 Ib ai/A
> 4.3 Ib ai/A
> 6.0 Ib ai/A
2. 4 Ib ai/A
0.65 Ib ai/A
N/A
NOAEL
1.51bai/A
1.51bai/A
6.0 Ib ai/A
1.51bai/A
0.38 Ib ai/A
N/A
Most sensitive affected parameter
Vegetative vigor; phytotoxicity
Vegetative vigor; phytotoxicity
Vegetative vigor; no affects
Vegetative vigor; phytotoxicity
Vegetative vigor; dryweight
Seed emergence; dryweight
*The entire list of species tested can be found in reference 8.
Table 15. Aquatic Plant Toxicity (Guideline 123-2: Fulfilled)
Species Tested
Anabaenaflos aquae
Skeletonema costatum
Navicula pelliculosa
Selenastrum capricornutum
Lemnagibba
%ai
95.5%
95.5%
95.5%
95.5%
95.5
EC50 (CLs)
8,200 ppb (7,200 - 9,300 ppb)
260 ppb (240 - 280 ppb)
2,850 ppb (2,100 - 4,000 ppb)
230 ppb (150 -350 ppb)
1,800 ppb (1,500 - 2,200 ppb)
MRID
42265105
42265102
42265101
42265103
42265102
Guideline Status
Fulfilled
Fulfilled
Fulfilled
Fulfilled
Fulfilled
CL= 95% Confidence limits
4.
Risk Assessment
Risk assessment integrates the results of the exposure and ecotoxicity data to evaluate the
likelihood of adverse ecological effects. The means of this integration is called the risk quotient
(RQ) method. Risk quotients are calculated by dividing exposure estimates by acute and chronic
ecotoxicity values.
Risk quotients are then compared to the Agency's levels of concern (LOCs). These
LOCs are used to analyze potential risk to nontarget organisms and the need to consider
regulatory action. The criteria are used to indicate when a pesticide used as directed has the
potential to cause adverse effects on nontarget organisms. LOCs currently address the following
risk presumption categories: (1) acute high - potential for acute risk is high and regulatory action
may be warranted in addition to restricted use classification; (2) acute restricted use - the
potential for acute risk is high, but may be mitigated through restricted use classification; (3)
acute endangered species - endangered species may be adversely affected; and (4) chronic risk -
the potential for chronic risk is high regulatory action may be warranted. Currently, the Agency
does not perform assessments for chronic risk to plants, acute or chronic risks to nontarget
insects, or chronic risk from granular/bait formulations to birds or mammals.
37
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Exposure and Risk to Nontarget Terrestrial Wildlife
The acute risk quotients (RQs) for broadcast applications of nongranular products are
tabulated below. They are based on estimated environmental residue levels calculated in the
terrestrial exposure portion of this document divided by the median lethal concentration or
chronic no observable adverse effects concentration (NOAEC) of the most sensitive species
tested. The exposure estimates used for the terrestrial risk assessment are based on Hoerger and
Kenega (1972) as modified by Fletcher et al. (1972) (reference 8}.
Birds
Pebulate is not expected to exceed half of the median lethal concentration for bobwhite
quail or mallard duck at the maximum permitted application rate of 10 Ibs ai/acre, and therefore
hazard from a single application of pebulate is unlikely (Table 16). Due to the use practice of
immediate soil incorporation of pebulate, there is no continuous exposure to birds; therefore
there is no expected chronic risk to birds. The study results show that the residues of pebulate on
the bare ground and in incorporated soil residues are much below the dietary levels of concern
(RQ <0.1). The RQs for insects and seeds would apply to liquid applications before
incorporation only and therefore exposure is briefer unlikely.
Table 16. Avian Acute Dietary Maximum Risk Quotient Ranges on Day of Application
Crop
Tomato
Tomato
Sugar
beets
Tobacco
Maximum
Application
Rate of Pebulate
10 Ib ai/A
6.0 Ib ai/A
6.0 Ib ai/A
4.0 Ib ai/A
EEC of
Pebulate in
Soil* (ppm)
220-3.6
132-2.2
132-2.2
88-1.4
Maximum EEC
Range of
Pebulate on
Insects (ppm)
1,350
810
810
540
Maximum EEC
Range of
Pebulate on
Seeds (ppm)
70
42
42
28
Soil
RQ
<0.08
<0.05
<0.05
<0.03
Insects
RQ
O.5
0.3
0.3
0.2
Seeds
RQ
O.012
0.007
0.007
0.004
LC50 of > 5,200 ppm for bobwhite quail used in calculation of risk quotient
*Soil Surfaces = 22 ppm for each 1.0 pound of active ingredient applied; 6" incorporation = 0.36 ppm every pound of active ingredient applied
(reference 8).
Mammals
Risk quotients are usually calculated for three separate weight classes of mammals (15,
35, and 1000 g), each presumed to consume four different kinds of food (grass, forage, insects,
and seeds). Because pebulate is soil incorporated, exposure to residues are expected only from
insects and seeds (Tables 17a and 17b); foliar residues are not expected. Large mammals (1000
g) are less likely to feed on insects, seeds, or soil invertebrates; therefore they were not included
in this analysis.
38
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Table 17a. Risk Quotients for Dietary Consumption of Insects by Small Mammals
Crop
Tomato
Sugar Beet
Tobacco
Rate
(Ibs ai/A)
10
6.0
4.0
Single Application
EEC for Insects
(ppm)
1,350
810
540
Acute RQ for a 15g
Mammal
0.8
0.5
0.3
Acute RQ for a
35 g Mammal
0.5
0.3
0.2
Table 17b. Risk Quotients for Dietary Consumption of Seeds by Small Mammals
Crop
Tomato
Sugar Beet
Tobacco
Rate
(Ibs ai/A)
10
6.0
4.0
Single Application EEC
for Seeds (ppm)
70
42
24
Acute RQ for a 15 g
Mammal
0.02
0.03
0.014
Acute RQ for a
35 g Mammal
0.014
0.018
0.01
Risk quotients were calculated using the following parameters: LD50 = 1,550 mg/kg for female rat; 15 g mammal consumes 95% of food matter as
small insects or fruit per day; 35 g mammal consumes 66% of food matter as small insects or fruit per day; all applications were EC formulations
applied by ground equipment.
Exposure and Risk To Aquatic Organisms
Pebulate estimated concentrations in surface water do not exceed concern levels for acute
effects to fish or invertebrates (reference 8). No conclusions regarding potential chronic risk are
possible due to lack of chronic data. Modeling indicates that pebulate will not degrade rapidly in
aquatic habitats and prolonged exposure is possible. The Agency is requiring estuarine
invertebrate testing for molluscs, because the use of pebulate on tobacco could result in estuarine
exposure. The studies for fish and shrimp or mysid are reserved at this time.
Exposure and Risk to Nontarget Plants
Calculated runoff and drift from a 10 Ib ai/A application to tomatoes suggest that levels
of concern for growth and toxicity are exceeded for nontarget terrestrial and semiaquatic plants
from runoff (Tables 18a and 18b). Risk to aquatic plants (nonendangered and endangered) is
possible for runoff and/or drift at maximum application rates (Table 19).
39
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Table 18a. Terrestrial Plant Risk Quotient Table (Seed Emergence)
Most
Sensitive
Species
Purple
nutsedge
Velvet
leaf
EC25
0.52 Ib
ai/A
3.05 Ib
ai/A
Amount
of
Pebulate
lOlbs
ai/A
lOlbs
ai/A
EEC with 2"
soil
incorporation
0.04 Ib ai/A
0.04 Ib ai/A
EEC for a
Semiaquatic
10 Acre
Watershed to
1 Acre
Shoreline
0.4 Ib ai/A
0.4 Ib ai/A
Terrestrial
Plant RQ
0.08
0.01
Semi-
Aquatic
Plant RQ
0.8
0.13
Endangered
plants
0.11
N/A
Table 18b. Terrestrial Plant Risk Quotient Table (Vegetative Vigor)
Most
Sensitive
Species
Ryegrass
EC25
0.65 Ib
ai/A
Amount
of
Pebulate
10 Ib
ai/A
EEC with
5% drift
EEC
0.5 Ib ai/A
EEC for a
Semiaquatic
10 Acre
Watershed
to 1 Acre
Shoreline
N/A
Terrestrial
Plant RQ
0.76
Semi-
Aquatic
Plant
RQ
N/A
Endangered
plants
1.3
Seed Emergence EC25, ground incorporated uses; Vegetative Vigor EC25, solid set sprinkler system with 5% drift.
Table 19. Aquatic Plant Risk Quotient*
Species
Selenastrum
capricornutum
EC50
260 ppb
Rate
10 Ib
ai/A
6.0 Ib
ai/A
4.0
EEC
141 ppb
(GENEEC)
85 ppb
(GENEEC)
35 ppb
(PRZM/EXAMS)
RQ Pond
0.54
0.33
0.13
RQ Drift 5%
to Surface
1.41
0.84
0.56
Endangered
Species RQ
1.85
1.12
0.46
* Based on NOAEC for Lemna gibba of 76 ppb. There are no endangered algal plants, only macrophytes.
40
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Endangered Species
Endangered species LOCs are exceeded for pebulate for acute hazard to endangered
plants (grasses and sedges) for several uses. Use on tomatoes, sugar beets and tobacco are
expected to be located in counties where endangered plants are known to exist. Nearly 100
endangered or threatened species are in counties with tomato crops, 35 listed species are in
counties with tobacco production, and 55 species are in counties with sugar beet production.
Sensitivity of these species may be variable, as was observed in terrestrial plant test results.
Locations of listed habitats for these species may also be localized within individual counties.
The Endangered Species Protection Program is expected to become final in the future.
Limitations in the use of pebulate may be required to protect endangered and threatened plant
species, but these limitations have not yet been defined. The Agency anticipates that a
consultation with the U.S. Fish and Wildlife Service may be conducted in accordance with the
species-based priority approach described in the Program. After completion of consultation,
registrants will be informed if any required label modifications are necessary. Such modifications
would most likely consist of the generic label statement referring pesticide users to use
limitations contained in county bulletins.
5. Risk Characterization
Based on low acute toxicity to birds and mammals, probable low exposure potential due
to soil incorporation, and high volatility, pebulate is not likely to pose an acute risk to birds or
most mammals. Some acute and chronic risk to strictly insectivorous mammals may exist before
incorporation, although exposure may be mitigated by volatility and incorporation of pebulate
into soils. No chronic data are available to characterize long-term effects to birds from pebulate.
Pebulate does not appear to pose a significant risk to aquatic organisms. Risk quotients
for freshwater fish, invertebrates, and aquatic plants were below the Agency's levels of concern
for acute effects. Chronic toxicity endpoints are not expected to be substantially lower than
predicted EEC levels, although no direct conclusions are possible due to the lack of actual
chronic toxicity data. Chronic aquatic data may be requested if pebulate uses are increased.
Although pebulate use on tobacco could result in estuarine exposure, the potential risk to
estuarine species is difficult to predict because there are no acceptable estuarine toxicity data.
Little hazard to nontarget terrestrial plants is expected from incorporated applications of
pebulate. However, risk quotients based on default spray drift assumptions from irrigation
systems and possible runoff exposure suggest potential adverse effects on growth in nontarget
terrestrial plants exposed to pebulate. There is uncertainty for this conclusion because (1) there
are no data from which to directly estimate drift exposure and (2) pebulate is volatile, which is
likely to reduce exposure. There is also some uncertainty associated with the potential for
exposure from volatilized residues depositing on nontarget plants.
41
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The risk to honeybees or other nontarget beneficial insects from direct pebulate contact
or contact with foliar pebulate residues cannot be assessed due to lack of insect toxicity data.
However, risk to honeybees or other beneficial insects is expected to be minimal because
pebulate is soil-incorporated.
6. Data Requirements
Environmental Fate
Because of the lack of key data, a complete quantitative environmental fate assessment
cannot be completed at this time. However, volatilization may be the principal route of
dissipation in the environment. Field data measuring volatility is required to substantiate this
qualitative assessment and to quantify the extent to which volatilization occurs under actual use
conditions. The Agency is requiring two new field dissipation studies be conducted in tobacco
(Southeast) and tomato (California) crops to account for agricultural and geographical
variability.
Although pebulate volatilizes substantially, the absorption spectrum of pebulate and lack
of photodegradation on soil and in water indicate that pebulate probably will not undergo
degradation in air. Furthermore, because there is insufficient guidance available for the data
requirement and the study is difficult to carry out, a photodegradation in air study is not required
at the present time. However, once the methodologies for photodegradation of pesticides in air
are resolved, the need for such a study will be reassessed.
At this time, the only environmental fate parameter for pebulate sulfoxide is an aerobic
soil metabolism half-life (t1/2= 103 days, estimated from the degradate's decline in the aerobic soil
metabolism study). Environmental fate data are needed for pebulate sulfoxide to perform a
quantitative assessment of the environmental fate of pebulate residues.
Ecological Effect Data Requirements
The Agency is requiring a study for acute toxicity of pebulate to estuarine molluscs. It is
reserving the studies on estuarine fish and shrimp at this time.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active ingredient
are eligible for reregistration. The Agency has previously identified and required the submission
42
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of the generic (i.e., active ingredient-specific) data required to support reregi strati on of products
containing pebulate as an active ingredient. The Agency has completed its review of these
generic data, and has determined that the data are sufficient to support reregi strati on of all
products containing pebulate. Appendix B identifies the generic data requirements that the
Agency reviewed as part of its determination of reregi strati on eligibility of pebulate.
These data were sufficient to allow the Agency to determine that pebulate can be used
without resulting in unreasonable adverse effects to humans and the environment. The Agency
therefore finds that all products containing pebulate as the active ingredient are eligible for
reregi strati on. Actions needed to reregister particular products are addressed in Section V of
this document.
The Agency made its reregi strati on eligibility determination based on the data required
for reregistration, the current guidelines for conducting acceptable studies to generate such data,
and published scientific literature. The Agency has found that all uses of pebulate are eligible for
reregistration; however, the Agency may take appropriate regulatory action if new information
comes to the Agency's attention regarding the reregistration of pebulate. The Agency may also
require the submission of additional data (1) to support the registration of products containing
pebulate, (2) if the data requirements for registration change, or (3) the guidelines for generating
such data change.
B. Determination of Eligibility Decision
Based on the reviews of the generic data for the active ingredient pebulate, the Agency
has sufficient information on the human health effects of pebulate and on its potential for causing
adverse effects in fish and wildlife and the environment. The Agency has determined that
pebulate products, labeled and used as specified in this RED, will not pose unreasonable risks of
adverse effects to humans or the environment. Therefore, the Agency concludes that products
containing pebulate for all uses are eligible for reregistration when labeled and used as specified
in this document.
C. Regulatory Position
To lessen the risks posed by pebulate, the Agency is requiring the following mitigation
measures for products containing pebulate. The specific language for the label is specified in
Section V.
To reduce the amount of residue in food crops.
- Require a PHI of 30 days for tomatoes
- Establish a 4 month plantback interval (FBI) for all food crops
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To protect workers
- Require the use of PPE (including coveralls, chemical-resistant gloves, and organic
vapor respirators) for all chemigation mixers/loaders
- Require the use of PPE (including coveralls, chemical-resistant gloves, and organic
vapor respirators) for all mixer/loaders when preparing solutions for an application in the
western states at the highest use rate (>6 Ib ai/Acre)
- Require the use of PPE (including chemical-resistant gloves and coveralls) for all
mixer/loaders when preparing solutions for an application in all states other than the
western states (i.e., at rates of <6 Ib ai/Acre)
- Require closed mixing/loading systems for commercial operations that impregnate dry
bulk fertilizer with pebulate
- Require closed mixing/loading systems for commercial operations that combine
pebulate (fluid formulation) with liquid fertilizer.
- Require the use of organic vapor respirators or an enclosed cab with a filtration system
equal to that of an organic vapor respirator for commercial applicators when applying dry
bulk fertilizer impregnated with pebulate to tobacco
- Prohibit greenhouse uses
- Require the use of chemical-resistant gloves for workers involved with mechanical
transplanting or mechanically assisted transplanting of tomatoes and tobacco and require
the submission of data on these exposure scenarios. As specified on the current label,
hand transplanting is not permitted.
To protect nontarget plant species
- Require labeling to implement best management practices to protect nontarget
terrestrial and semiaquatic plants (mainly grass related species) from runoff and drift.
D. Food Quality Protection Act Findings
1. Determination of Safety for U.S. Population
EPA has determined that the established tolerances for pebulate, with the amendments
and changes specified in this document, meet the safety standards under the FQPA amendments
to section 408(b)(2)(D) of the FFDCA, that there is a reasonable certainty of no harm for the
general population. In reaching this determination, EPA has considered all available information
on the toxicity, use practices and scenarios, and the environmental behavior of pebulate.
There are no pebulate products registered for home use; therefore there is no residential
exposure factored into the aggregate risk assessment. The Agency has concluded that for the
acute and chronic dietary risk assessments, risks to all population subgroups were <1% of the
aPAD and cPAD, respectively, and therefore are not at levels of concern to the Agency.
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For the water assessment, using surrogate data, the acute and chronic drinking water
levels of concern are not exceeded. However, taking another approach and using a worst case
assumption (where the binding affinity to soil is assumed to be 0), the Agency finds a concern for
chronic dietary exposure to residue-containing groundwater. However, residues at the modeled
level are not supported by available monitoring data (NAWQA database: 4 detections in 3023
samples; STORET database: 0 detections in 3197 samples). Although these monitoring data are
not ideal for assessing pebulate (i.e., they were not targeted for pebulate), they do provide some
real world data on the amount of pebulate in the environment. For these reasons, the worst case
data are considered too conservative and probably not realistic. The Agency is therefore not
taking action to restrict pebulate at this time but is requiring environmental fate data to verify
these conclusions. Using the surrogate data for the water assessment, the Agency has no
concern for aggregate acute or chronic dietary risks.
The Agency is concerned with not only the effects of the parent compound, but also the
chemical degradates (such as pebulate sulfoxide). There are currently no environmental fate data
available for pebulate sulfoxide, so surrogate data on molinate sulfoxide was used. Molinate
sulfoxide is a degradate of molinate, which is also a thiocarbamate and a chemical analog of
pebulate. Pebulate degradates are assumed to have the same toxicity as the parent and are
expected to be more persistent than the parent compound in the environment due to their more
polar nature and lower volatility. They are therefore more likely to be the major soil, water, and
plant residues. The Agency has concerns regarding the environmental fate of these compounds
and their impact on rotational crops and therefore is requiring a 4-month plantback interval for
all food crops, including tomatoes or sugar beets. A shorter rotational interval can be established
if data are submitted that demonstrate a shorter plantback interval is sufficient.
Pebulate is a thiocarbamate, which is a class of chemicals known to have neurotoxic
effects. Pebulate has been shown to cause brain weight decrements in a subchronic neurotoxicity
study in rats. Neurohistopathologic findings (such as degeneration in the sciatic nerve fibers)
have also been observed in rat and dog studies. The Agency is requiring a developmental
neurotoxicity study as a condition of reregi strati on.
2. Determination of Safety for Infants and Children
The Agency has determined that the established tolerances for pebulate, with
amendments and changes as specified in this document, meet the safety standards under the
FQPA amendments to section 408(b)(2)(C) of the FFDCA, and that there is a reasonable
certainty of no harm for infants and children. The safety determination for infants and children
considers the factors noted above for the general population, but also takes into account the
possibility of increased dietary exposure due to the specific consumption patterns of infants and
children, as well as the possibility of increased susceptibility to the toxic effects of pebulate
residues in this population subgroup.
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All doses for risk assessment purposes were assessed using the conventional safety
factors of lOx for interspecies extrapolation and lOx for intraspecies variability. In addition, the
FQPA safety factor of lOx was retained for pebulate because of (1) the severe neuropathology
exhibited in studies with adult animals, (2) the structural similarities to other thiocarbamates for
which increased susceptibility of developing fetuses has been demonstrated, and (3) the
outstanding requirement for a developmental neurotoxicity study. In the current analysis, the
lOx FQPA safety factor was applied to the various populations of infants and children as well as
to females (13-50 years, i.e., females of childbearing age), because the Agency is concerned
about potential developmental (in utero exposure) effects of pebulate. The lOx FQPA safety
factor is not applied to males or to the general population. As discussed above, acute and
chronic dietary risk estimates for pebulate were calculated to be <1% of the acute and chronic
population adjusted doses (aPAD and cPAD, respectively) for adults, infants, and children
(reference 6).
3. Endocrine Disrupter Effects
The FQPA requires the Agency to develop a screening program to determine whether
certain substances (including all pesticides and inerts) "may have an effect in humans that is
similar to an effect produced by a naturally occurring estrogen, or such other endocrine effect...."
EPA has been working with interested stakeholders, including other government agencies, public
interest groups, industry and research scientists to develop a screening and testing program as
well as a priority setting scheme to implement this program. The Agency's proposed Endocrine
Disrupter Screening Program was published in the Federal Register of December 28, 1998 (63
RE 71541). The Program uses a tiered approach and anticipates issuing a Priority List of
chemicals and mixtures for Tier 1 screening in the year 2000. As the Agency proceeds with
implementation of this program, further testing of pebulate and end-use products for endocrine
effects may be required.
E. Tolerance Reassessment
Section 408(b)(2)(D)(v) of the Food Quality Protection Act requires that, when
considering whether to establish, modify, or revoke a tolerance, the Agency consider "available
information" concerning the cumulative effects of a particular pesticide's residues and "other
substances that have a common mechanism of toxicity." The Agency is examining whether and
to what extent some or all organophosphorous and carbamate (including, but not limited to,
methyl carbamate, N-methyl carbamate, thiocarbamate, and dithiocarbamate) pesticides may
share acetylcholinesterase inhibition as a common mechanism of toxicity. Although current data
are limited, the thiocarbamates appear to be comparatively weak cholinesterase inhibitors and are
generally regulated based on other toxic endpoints. As a result, the Agency has not determined if
it would be appropriate to include them in a cumulative risk assessment with other such
chemicals (e.g., the organophosphorous and carbamate pesticides). This issue is currently under
review by the SAP, as discussed previously (Chapter III, Cumulative Effects).
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At this time, the Agency does not believe it has sufficient reliable information concerning
common mechanism issues to determine whether pebulate, a thiocarbamate, shares a common
mechanism of toxicity with other cholinesterase-inhibiting chemicals. Therefore, for the
purposes of this tolerance reassessment, the Agency has assumed that pebulate does not share a
common mechanism of toxicity with cholinesterase-inhibiting chemicals.
Tolerances are established for residues of pebulate in tomatoes and sugar beet roots and
tops at 0.1 ppm (40 CFR 180.238). Based on field trial data, the Agency recommends
reassessment of all tolerances to the limit of quantitation of the analytical method, 0.05 ppm,
because all residues were consistently less than the limit of quantitation (Table 20).
Table 20. Tolerance Reassessment Summary for Pebulate.
Commodity
Sugar beets
(roots and
tops)
Tomatoes
Current
Toleranc
e (ppm)
0.1
0.1
Tolerance
Reassessment
(ppm)
0.05
0.05
Reason
Reduce tolerance to the
limit of quantitation
(LOQ), because detected
residues were consistently
less than the LOQ
Reduce tolerance to the
LOQ, because detected
residues were consistently
less than the LOQ
Comment
Separate tolerance
should be listed as
follows:
Beet, sugar, root
Beet, sugar, tops
(leaves)
Tomato
1.
Codex Harmonization
No maximum residue limits for pebulate have been established by CODEX for any
agricultural commodities. Therefore there are no issues regarding compatibility with respect to
U.S. tolerances.
F. Human Health Risk Mitigation
Dietary
The current pebulate label requires an 8-day preharvest interval (PHI) for tomatoes. This
interval is inconsistent with typical agronomic practice (i.e., pebulate is a preemergent pesticide)
and the available residue data. Therefore, the Agency is requiring a PHI of 30 days. If the
registrant wishes to retain the 8-day PHI, supporting residue data must be submitted.
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The Agency is also requiring a 4 month plantback (crop rotation) interval for all crops,
including sugar beets and tomatoes. The reason is that based on confined crop rotational studies,
residues of likely toxicological concern (such as pebulate sulfoxide) are likely to be found in raw
agricultural commodities (RACs) planted up to 4 months after soil treatment for the primary
crop. The actual rate of pebulate decline and that of its degradates in the environment is
unknown. However, there is expected to be much greater exposure to the degradates in
rotational crops because the degradates are more persistent than the parent compound due to
their more polar nature and lower volatility. To support a FBI shorter than 4 months, the
existing confined crop studies must be upgraded or limited field rotational crop studies (to
include seeking metabolites of potential toxicological concern as well as the parent compound)
must be conducted.
Occupational
The Agency believes there is risk to workers from exposure to pebulate. To ensure
worker safety, the Agency is requiring mitigation measures in the form of PPE and engineering
controls. The Agency is also requiring confirmatory data in some instances; these data will be
used to reevaluate the risks, which could result in revision of the mitigation measures. For most
applicators and handlers, the PPE that is specified on the current label (long sleeve shirt, long
pants, closed shoes, protective eyewear, and chemical resistant gloves) is unchanged. Most
mixers/loaders are also required to use a double layer of clothes (coveralls); organic vapor
respirators are additionally required for people who prepare emulsifiable concentrate solutions
for chemigation. The PPE on the current label and organic vapor respirators are also required
for mixers and loaders who are preparing solutions for soil injection and groundboom
applications at the concentrations in the western states, because of the amount of exposure at the
highest use rate (>6 Ibs ai/acre). The use of respirators in these instances result in acceptable
MOEs for these handlers. Commercial applicators who prepare large quantities of dry bulk
fertilizer impregnated with pebulate must use a closed mixing and loading system. In addition,
applying dry bulk fertilizer requires the use of an enclosed cab truck with a air filtration system
equal to that of an organic vapor respirator. With the use of engineering controls, PPE can be
reduced [according to the Worker Protection Standard (WPS)].
On October 18, 1995, a data call-in (DCI) notice was issued under section 3(c)(2)(B) of
FIFRA, 7 U.S.C. Section 136a (c)(2)(B). This Notice required submission of data necessary to
evaluate exposure to persons entering fields and/or areas treated with pesticides.
The DCI required the following three studies: (1) Guideline 132-l(a), Foliar Residue
Dissipation; (2) Guideline 133-3, Dermal Exposure Upon Reentry; and (3) Guideline 133-4,
Inhalation Exposure Upon Reentry. Guideline 132-l(a) requires data to estimate postapplication
residue exposure resulting from a pesticide used at the use site. This information is compound
and product specific and the use of generic or surrogate data is not possible. Guidelines 133-3
and 133-4 will be used in estimating postapplication exposure. These data are used to develop
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transfer coefficients which relate the amount of pesticide residue available on the treated surface
area with how much pesticide residue is deposited onto or inhaled by an individual performing
activities in a treated area. These data will enable the Agency to determine appropriate reentry
intervals for re-entering fields after pesticide treatments. These data requirements may require
registrants to generate data, to supply missing data, and to replace unacceptable data to support
product registration and reregi strati on.
The registrant requested a data waiver based on the following reasons: (1) there are no
foliar uses registered, (2) layby applications are applied as a directed spray to the soil at the base
of the plant or banded and immediately soil incorporated, and (3) chemigation applications are
confined to preplant and preemergent crop situations only. The Agency agreed that exposure to
foliar residues should be minimal. However, the potential for worker dermal exposure exists
during transplanting activities (e.g., hand exposure). If the transplanting were done
mechanically, then exposure should be minimal and dermal exposure data would not be
necessary. The Agency agreed to waive the dermal study if there was no contact with the soil.
Consequently, the registrant added the following restriction to the label: "TILLAM 6-E may be
applied prior to mechanical transplanting only. DO NOT apply TILLAM 6-E prior to hand
transplanting." The rationale was that with this restriction in place, there would be no dermal
exposure, negating the need for the studies.
However, as explained by the registrant (MRTD 44875900), mechanical transplanting via
totally automated systems only occurs in some very large operations. The normal cultural
practice is for a person to place a plant into a wheel, root upward. The wheel rotates downward,
releasing the plant into a mechanically cut furrow. The furrow is then closed mechanically while
the wheel continues to move around for reloading. This scenario involves possible human
exposure, which was not the expectation when the Agency agreed to the mechanical transplant
restriction and waived the studies. In addition, a handler walks behind this machine to straighten
misaligned plants. The Agency is therefore requiring that chemical resistant gloves be worn by
all such handlers and is calling in the data for the dermal and inhalation studies (guidelines 133-3
and 133-4, respectively).
Zeneca, the registrant for pebulate, is part of an industry-wide Agricultural Reentry Task
Force, which was formed by several registrants to develop reentry exposure data required by the
October 18, 1995 DCI. This Task Force will genetically address the inhalation (133-4) guideline
requirement and will submit these data to the Agency by October 29, 2001. As stated
previously, the dermal study is chemical specific and must be conducted specifically for pebulate
and the degradants of concern, such as pebulate sulfoxide. The PPE required for all exposure
scenarios of pebulate are shown in Table 21.
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Table 21. Summary of Worker Personal Protective Equipment"
No.
1
2
3
4
5
6
7
8
9
10
11
Exposure Scenario
Mixing/Loading EC for Chemigation
Mixing/Loading EC for soil injection and ground boom
application in regions other than the western states
Mixing/Loading EC for soil injection and ground boom
application in the western states only**
Mixing/Loading EC for impregnation on dry bulk
fertilizer (In-Plant Commercial Operation)
Mixing/Loading EC for impregnation on dry bulk
fertilizer (On-board Operation)
Mixing/Loading Fluid Formulation for Combination
with Liquid Fertilizer (Commercial Operation)
Mixing/Loading Fluid Formulation for Combination
with Liquid Fertilizer (Noncommercial Operation)
Applying with a Groundboom Sprayer
Applying Dry Bulk Fertilizer with a Drop Type Tractor
Drawn Sprayer
Applying Dry Bulk Fertilizer with Specialized Truck
Equipment**
Soil Injection Application
Additional Required PPE
Organic vapor respirator;
Coveralls
Coveralls
Organic vapor respirator;
Coveralls
N/A
Organic vapor respirator;
Coveralls
N/A
Organic vapor respirator;
Coveralls
No
No
Organic vapor respirator
No
No
Engineering
Controls
None
None
None
Closed System
Required
None
Closed System
Required
None
None
None
None
Enclosed cab with
organic vapor
filtration system
No
*The PPE specified on the pebulate label at the time of publication of this RED is long sleeve shirt, long pants, closed shoes,
protective eyewear, and chemical resistant gloves.
"Either an organic vapor respirator or an enclosed cab may be used.
G. Ecological Risk Mitigation
The use of herbicides such as pebulate poses concern for nontarget plants in the vicinity
of the application sites. There is low potential for risk to aquatic plants from the use of pebulate
on estimated aquatic residue levels from runoff. Present labeling language does advise the user
that pebulate should not be applied directly to water, surface water, or intertidal areas. This
advisory language must continue to appear on all product labels.
Based on its use on tobacco, pebulate is expected to reach estuarine environments in the
Southeast. In addition, modeling indicates that pebulate will not degrade appreciably in aquatic
habitats and prolonged exposure is possible for aquatic organisms. At this time, information is
not available on the effects of pebulate in the estuarine environment, particularly on molluscs.
The Agency is therefore calling in data to determine the effects of pebulate on this environment.
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Pebulate does not exceed risk concerns for acute effects to birds or most mammals.
Estimated concentrations of pebulate do not exceed concern for acute effects to fish or
invertebrates. Chronic risks to these groups is not expected due to the soil incorporation of
pebulate and subsequent reduced exposure potential. Volatility may also reduce the likelihood of
continuous exposure. In addition, the Agency has not received any reports of adverse effects to
nontarget terrestrial wildlife, insects, or aquatic organisms from uses of pebulate.
H. Occupational (WPS) Labeling Rationale
During the reregistration process, EPA considers all relevant generic and product-specific
information to decide what protections and risk mitigation measures are needed for all products.
Products may have more than one occupational use; thus, these uses may or may not be covered
by the WPS.
The 1992 Worker Protection Standard for Agricultural Pesticides established certain
worker-protection requirements [such as PPE and restricted-entry intervals (REIs)] to be
specified on the label of all products that contain uses covered by the WPS. These requirements
are to be reviewed and revised, as appropriate, during reregistration and other Agency review
processes. Uses covered by the WPS include all commercial and research uses on farms, forests,
nurseries, and in greenhouses to produce agricultural plants (including food, feed and fiber
plants, trees, turf grass, flowers, shrubs, ornamentals, and seedlings). The WPS covers not only
uses on plants, but also uses on the soil or planting medium the plants are (or will be) grown in.
The WPS labeling requirements pertaining to PPE, REI, and notification are interim measures.
At this time, all products containing pebulate are intended solely for occupational use (i.e.
mixed, loaded, and applied by commercial applicators) and is not available to homeowners.
Therefore, all of these uses are covered by the WPS.
Personal Protective Equipment for Handlers (Mixers, Loaders, and Applicators)
For the end-use product, PPE requirements for pesticide handlers is long sleeve shirt,
long pants, closed shoes, protective eyewear, and chemical-resistant gloves. In addition, for
pebulate, the use of an organic-vapor respirators is required in some instances to mitigate the
risks of inhalation exposure (Table 21). For occupational-use products, PPE is established using
the process described in PR Notice 93-7 or more recent EPA guidelines.
Post Application Restrictions
Under the WPS, interim REIs for all uses covered by the WPS are based on the acute
toxicity of the active ingredient. The toxicity categories of the active ingredient for acute dermal
toxicity, eye irritation potential, and skin irritation potential are used to determine the interim
WPS REI. If one or more of the three acute toxicity effects are in toxicity category 1, the
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interim WPS REI is established at 48 hours. If none of the acute toxicity effects are in category
1, but one or more of the three is classified as category 2, the interim WPS REI is established at
24 hours. If none of the three acute toxicity effects are in category 1 or 2, the interim WPS REI
is established at 12 hours. A 48-hour REI is increased to 72 hours when an organophosphate
pesticide is applied outdoors in arid areas. In addition, the WPS specifically retains two types of
REI's established by the Agency prior to the promulgation of the WPS: (1) product-specific
REI's established on the basis of adequate data, and (2) interim REI's that are longer than those
that would be established under the WPS.
The WPS prohibits routine entry to perform hand labor tasks during the REI and requires
PPE to be worn for other early-entry tasks that require contact with treated surfaces. Under the
WPS, these personal protective equipment requirements for persons who must enter areas that
remain under a restricted-entry interval are based on the acute toxicity category of the active
ingredient.
For pebulate, EPA has determined that no additional regulatory action is needed on the
basis of acute or other adverse effects of the active ingredient; the REI of 12 hours is maintained.
During the reregi strati on process, the early-entry PPE requirements will be established on the
basis of the acute dermal toxicity category, skin irritation potential category, and eye irritation
potential category of the active ingredient. The acute toxicity endpoints used in this RED may
not meet current acceptability criteria. The acceptability status of these data may be reassessed
during product reregi strati on.
I. Other Labeling Requirements
1. Endangered Species Statement
Currently, the Agency is developing "The Endangered Species Protection Program" to
identify all pesticides that may cause adverse effects on endangered and threatened species. The
Program will also implement mitigation measures that will eliminate the adverse impacts. The
program would require use restrictions to protect endangered and threatened species at the
county level. Consultations with the Fish and Wildlife Service may be necessary to assess risks
to newly listed species or from proposed new uses. In the future, the Agency plans to publish a
description of the Endangered Species Program in the Federal Register and have available
voluntary county-specific bulletins. The Agency is in the process of developing county-specific
bulletins that specify measures to protect endangered and threatened species. Because the
Agency is taking this approach for protecting endangered and threatened species, it is not
imposing label modifications at this time through the RED.
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2. Spray Drift Management
The Agency has been working with the Spray Drift Task Force, EPA Regional Offices
and State Lead Agencies for pesticide regulation, and other parties to develop the best spray drift
management practices. The Agency is now requiring interim mitigation measures for aerial
applications that must be placed on product labels/labeling as specified in section V. The Agency
has completed its evaluation of the new data base submitted by the Spray Drift Task Force, a
membership of U.S. pesticide registrants, and is developing a policy on how to appropriately
apply the data and the AgDRTFT computer model to its risk assessments for pesticides applied
by air, orchard airblast and ground hydraulic methods. After the policy is in place, the Agency
may impose further refinements in spray drift management practices to reduce off-target drift and
risks associated with aerial as well as other application types where appropriate. In the interim,
the following spray drift related language is required on product labels that are applied outdoors
in liquid sprays (except mosquito adulticides), regardless of application method: "Do not allow
this product to drift."
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements, responses and labeling changes necessary for
the reregistration of both manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of pebulate for the eligible uses has
been reviewed and determined to be substantially complete. The following studies are required:
New Guideline Old Guideline No. Description
830.6313 63-13 Stability to Metals
850.1025 72-3 b Oyster Acute Toxicity (Shell Deposition)
850.1055 72-3 b Bivalve Acute Toxicity (Embryo Larvae)
870.6300 83-6 Developmental Neurotoxicity in Rats
875.2400 133-3 Dermal Exposure
875.2500 133-4 Inhalation Exposure*
835.1220 163-1 Leaching/Adsorption/Desorption
835.8100 163-3 Field Volatility from Soil**
835.6100 164-1 Terrestrial Field Dissipation***
860.1900 165-2 Field Accumulation in Rotational Crops|
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Note: To ensure that the studies will cover all of the areas of concern to the Agency, the
registrant should submit a protocol to the Agency for these studies prior to conducting the trials.
*This data requirement will be submitted by the Agricultural Reentry Task Force.
**The volatilization measurements required for this study can be conducted in conjunction with
the terrestrial field dissipation studies.
***The Agency is requiring two new field dissipation studies, which will account for cultural
practices and geographical variability: one for tobacco (Southeast region) and one for tomato
(California) crops. These data will enable confirmation of pebulate dissipation pathways.
|This data is required to support a preharvest interval of less than 30 days for tomatoes.
Additionally, if a plantback harvest interval of less than 4 months is desired, existing confined
crop rotational studies must be upgraded or limited field studies (to include seeking metabolites
of potential toxicological concern and the parent) must be submitted for all crops (including
tomatoes and sugar beets).
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing use product (MP) labeling must be
revised to comply with all current EPA regulations, PR Notices and applicable policies. The MP
labeling must contain the labeling language presented in Table 22.
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. Registrants must
review previous data submissions to ensure that they meet current EPA acceptance criteria and if
not, commit to conduct new studies. If a registrant believes that previously submitted data meet
current testing standards, then study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrants Response Form provided for each
product.
2. Labeling Requirements for End-Use Products
Label changes are necessary to implement mitigation measures outlined in Section IV
above. Specific language to implement these changes is specified in the following table.
3. Required Labeling Changes Summary Table
The changes to the pebulate label as a result of this RED are summarized in Table 22.
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Table 22: Summary of RED Labeling Requirements for Pebulate
Description
Required Labeling
Placement on Label
Manufacturing Use Products
Required on all MUPs
One of these statements may be added to a
label to allow reformulation of the product
for specific use or all additional uses
supported by a formulator or user group.
Environmental Hazards Statements
Required by the RED and Agency Label
Policies
General Application Restrictions for
products applied as liquid sprays
(regardless of type of application
equipment)
"Only for formulation into herbicide products for the following use(s): " \fill blank only with those uses that are being supported by MP
registrant}.
"This product may be used to formulate products for specific use(s) not listed on the MP label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the MP label if the formulator, user group, or
grower has complied with U.S. EPA submission requirements regarding support of such use(s)."
"Drift or runoff may adversely affect non-target plants. 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 EPA.
"Do not allow this product to drift"
Directions for Use
End Use Products Intended for Occupational Use (WPS)
PPE Requirements Established by the
RED Based on the Active Ingredient.
"Personal Protective Equipment (PPE)
Some materials that are chemical-resistant to this product are listed below. If you want more options, follow the instructions for category
[insert A,B,C,D,E,F,G,or H] on an EPA chemical-resistance category selection chart."
Commercial handlers engaged in impregnating this product onto dry bulk fertilizer or in mixing this product with liquid fertilizer must
wear (in addition to using the enclosed system described below):
— long-sleeved shirt & long pants,
— shoes plus socks, and
— chemical-resistant gloves, such as (registrant inserts correct glove types).
Precautionary Statements:
Hazards to Humans and
Domestic Animals
55
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Table 22: Summary of RED Labeling Requirements for Pebulate
Description
PPE Requirements Established by the
RED Based on the Active Ingredient.
User Safety Requirements
User Safety Requirements (Required on
Products Which Require Coveralls in the
PPE)
Required Labeling
[Personal Protective Equipment (PPE), continued]
Mixers and loaders must wear:
— long-sleeved shirt & long pants,
— shoes plus socks,
— chemical-resistant gloves, such as (registrant, insert correct glove types) and
— an organic-vapor removing cartridge with a prefilter approved for pesticides (MSHA/NIOSH approval number prefix TC-23C), or
— a canister approved for pesticides (MSHA/NIOSH approval prefix TC-14G), or
— an organic vapor (OV) cartridge or canister with any N*, R, P, or HE prefilter."
EXCEPTIONS: A RESPIRATOR IS NOT REQUIRED FOR MIXERS AND LOADERS SUPPORTING SOIL INJECTION AND
GROUNDBOOM AT RATES < 1 GALLON (4 QTS)
Applicators, persons assisting in mechanical transplanting after Tillam 6-E has been applied, and other handlers exposed to the dilute
product must wear:
— Long-sleeved shirt & long pants,
— Shoes plus socks,
— Chemical-resistant gloves, such as (registrant inserts correct glove types)
In addition, applicators applying dry-bulk fertilizers with specialized equipment designed to cover more than 80 acres per day must use
and enclosed cab with a filtration system equal to that of the respirator (described below) or wear a NIOSH-approved respirator with
— an organic-vapor removing cartridge with a prefilter approved for pesticides MSHA/NIOSH approval number prefix TC-23C), or
— a canister approved for pesticides (MSHA/NIOSH approval prefix TC-14G), or
— an organic vapor (OV) cartridge or canister with any N*, R, P, or HE prefilter
[* If Tillam 6-E contains oil or has instructions that would allow concurrent application with an oil-containing material, registrant must
remove the "N" in the respirator statement]
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for washable exist, use detergent and hot water.
Keep and wash PPE separately from other laundry."
In addition to the above statements
"Discard clothing or other absorbent materials that have been drenched or heavily contaminated with this product's concentrate. Do not
reuse them."
Placement on Label
Precautionary Statements:
Hazards to Humans and
Domestic Animals
Precautionary Statements:
Hazards to Humans and
Domestic Animals
(immediately following the
PPE requirements)
Precautionary Statements:
Hazards to Humans and
Domestic Animals
(immediately following the
PPE requirements)
56
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Table 22: Summary of RED Labeling Requirements for Pebulate
Description
Engineering Controls
User Safety Recommendations
Environmental Hazards
Restricted-Entry Interval
Early Entry Personal Protective
Equipment
Required Labeling
Engineering Controls
Commercial (for-hire) handlers engaged in impregnating this product onto dry bulk fertilizer or in mixing this product with liquid
fertilizer must:
— use a closed system that meets the requirements listed in the Worker Protection Standard (WPS) for agricultural pesticides (40 CFR
170.240(d)(4), and
— in addition to wearing the required PPE, have immediately available for use in case of an accident: chemical-resistant footwear, and a
NIOSH-approved respirator with (1) an organic- vapor removing cartridge with a prefilter approved for pesticides (MSHA/NIOSH
approval number prefix TC-23C), or (2) a canister approved for pesticides (MSHA/NIOSH approval prefix TC- 14G), or (3) an organic
vapor (OV) cartridge or canister with any N*, R, P, or HE prefilter."
"When other handlers use closed systems or enclosed cabs in a manner that meets the requirements listed in the Worker Protection
Standard (WPS) for agricultural pesticides (40 CFR 170.240(d)(4, 5), the handler PPE requirements may be reduced or modified as
specified in the WPS."
[* If Tillam 6-E contains oil or has instructions that would allow concurrent application with an oil-containing material, registrant must
remove the "N" in the respirator statement.]
User Safety Recommendations"
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet."
"Users should remove clothing/PPE immediately if pesticide saturates the clothing layers and reaches the skin. User should then wash
thoroughly and put on clean clothing."
"Users should remove PPE immediately after handling this product. Wash the outside of gloves before removing. As soon as possible,
wash thoroughly and change into clean clothing."
"Environmental Hazards"
"Drift or runoff may adversely affect nontarget plants. Do not apply directly to water, or to area where water is present or to intertidal
areas below the mean high water mark. Do not contaminate water when cleaning equipment or disposing of equipment washwaters
"Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of 12 hours. Note: persons assisting in
mechanical transplanting in fields after Tillam 6-E has been applied are classified as handlers and must wear the personal protective
equipment listed for handlers in the Precautionary Statements during and after expiration of the REI."
"PPE required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with
anything that has been treated, such as plants, soil, or water, is:
— coveralls,
— chemical-resistant gloves, and
— shoes plus socks"
Placement on Label
Precautionary Statements:
Hazards to Humans and
Domestic Animals
(immediately following PPE
and User Safety
Requirements.)
Precautionary Statements:
Hazards to Humans and
Domestic Animals
(immediately following PPE
and User Safety
Requirements.)
Precautionary Statements
under Environmental
Hazards
Directions for Use,
Agricultural Use
Requirements Box
57
-------
Table 22: Summary of RED Labeling Requirements for Pebulate
Description
General Application Restrictions
Site Specific Application Restrictions
Required Labeling
"Do not apply this product in a way that will contact workers or other persons, either directly or through drift. Only protected handlers
may be in the area during application."
"Mechanical transplanting only. Do not apply Tillam 6-E prior to hand transplanting."
"For use outdoors only. Do not use in a greenhouse."
The label must specify a preharvest interval (PHI) of 30 days.
The label must specify a 4-month plantback interval (FBI) for all crops.
The label must specify the following industry best management practices to protect nontarget terrestrial and semiaquatic plants.
Placement on Label
For WPS Products place in
the Directions for Use
directly above the
Agricultural Use Box. For
non-WPS Products, Place in
Directions for Use in General
Precautions and Restrictions
Directions for Use under
General Precautions and
Restrictions and or
Application Instructions
58
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C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this 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. For additional
information, refer to "Existing Stocks of Pesticide Products; Statement of Policy," Federal
Register, Volume 56, No. 123, June 26, 1991.
In accordance with the above policy, the Agency has determined that registrants may
distribute and sell pebulate products bearing old labels/labeling for 26 months from the date of
issuance of this RED. Persons other than the registrant may distribute or sell such products for
50 months from the date of the issuance of this RED. Registrants and persons other than
registrants remain obligated to meet pre-existing Agency imposed label changes and existing
stocks requirements applicable to products they sell or distribute.
59
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REFERENCES
1. Hazel, William J., Ph.D., Pebulate Human Health Risk Assessment. HED Chapter for the
Reregistration Eligibility Decision (RED) Document, EPA Memorandum, June 7, 1999.
2. Hazel, William J., Ph.D., Pebulate. Residue Chemistry and Product Chemistry Chapters of
the Reregistration Eligibility Decision Document, May 18, 1999.
3. Yang, Yung G., Ph.D., Pebulate-The Toxicology Chapter for the RED., EPA Memorandum,
March 30, 1999.
4. Yang, Yung, G., Ph.D., Pebulate-Report of the Hazard Identification Assessment Review
Committee., EPA Memorandum, December 7, 1998.
5. Hanley, Susan, Pebulate: Occupational and Residential Exposure Assessment and
Recommendations for the Reregistration Eligibility Decision, EPA Memorandum, June 2, 1999.
6. Swartz, Christina, Pebulate. List B Reregistration Case No. 2500/Chemical ID No. 041403.
Acute and Chronic Dietary Exposure Analyses for the HED Reregistration Eligibility Decision
Document (RED), EPA Memorandum, May 13, 1999.
7. Tarplee, Brenda, Pebulate-Report of the FQPA Safety Factor Committee, EPA
Memorandum, January 26, 1999.
8. Montague, Brian, et al., EFED RED chapter for Pebulate, EPA Memorandum, June 9, 1999.
9. Olinger, Christine L., Molinate, Pebulate, and Cycloate Plant Metabolism; Issues to be
Presented to the Metabolism Committee on May 18, 1992, EPA Memorandum, May 14, 1999.
10. Hazel, William, J., PhD, Pebulate. Reassessment of Confined Crop Rotational Studies,
EPA Memorandum, May 12, 1999.
60
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VI. APPENDICES
61
-------
62
-------
Appendix A: PEBULATE (CASE 2500): USE PATTERNS ELIGIBLE FOR REREGISTRATION
Application Type
Timing
Equipment
Formulation
[EPA Reg.
No.]
Max.
Single
App.
Rate
(Ib ai/A)
Max.
No. of
Apps.
Min.
Re treatment
Interval
Restrictions/Comments
Tomatoes
Preplant, at-plant,
post-plant soil
incorporated
Broadcast or banded*
Groundboom
Soil injection
Chemigation
Preplant, at-plant,
post-plant soil
incorporated
Broadcast or banded*
Groundboom
Soil injection
Chemigation***
Postemergence soil
incorporated
Broadcast or banded*
Ground equipment
6 Ib/gal EC
[10182-158]
6 Ib/gal EC
[10182-158]
6 Ib/gal EC
[10182-158]
6
10
3
]_ •*• *
]_ •*• *
1**
N/A
N/A
N/A
Use on direct seeded or transplanted
(mechanical only) tomatoes; do not use
prior to hand transplanting
Direct seeded, western region (defined as
California, Arizona, and Nevada) use
maximum rate on heavy textured soils, 4 Ib
ai/A on light textured soils (<10% organic
matter)
Use on plug-planted tomatoes, western
region (defined as California, Arizona, and
Nevada) only
Do not use prior to hand transplanting
Use in SC only
63
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Application Type
Timing
Equipment
Pre- or post-plant
Broadcast
Sprinkler
Formulation
[EPA Reg.
No.]
6 Ib/gal EC
[10182-158]
Max.
Single
App.
Rate
(Ib ai/A)
6
Max.
No. of
Apps.
]_ •*• *
Min.
Re treatment
Interval
N/A
Restrictions/Comments
Western region (defined as California,
Arizona, and Nevada) , use maximum rate on
heavy textured soils, 4 Ib ai/A on light
textured soils (<10% organic matter)
64
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Application Type
Timing
Equipment
Tomatoes (continued)
Layby (directed) ,
soil incorporated
Banded
Ground equipment
Formulation
[EPA Reg.
No.]
6 Ib/gal EC
[10182-158]
Max.
Single
App.
Rate
(Ib ai/A)
6
Max.
No. of
Apps.
]_ •*• *
Min.
Re treatment
Interval
N/A
Restrictions/Comments
Use maximum rate on heavy textured soils, 4
Ib ai/A on light textured soils (<10%
organic matter)
Sugar beets
Preplant soil
incorporated
Broadcast or
banded
Ground equipment
6 Ib/gal EC
[10182-158]
6
1
N/A
Use maximum rate on heavy textured soils, 4
Ib ai/A on light texture soils (<10%
organic matter)
Tobacco
Preplant soil
incorporated
Broadcast or
banded**
Ground equipment
Impregnation on dry
bulk
fertilizer
6 Ib/gal EC
[10182-158]
4
1
N/A
Do not use prior to hand transplanting
EC, emulsifiable concentrate
* For banded application, reduce the amount per acre proportionately, depending on band width, and row spacing.
**Split applications are permitted as long as the seasonal total does not exceed the single maximum use rate.
***Solid set sprinkler type
65
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregi strati on for active
ingredients within the case Pebulate covered by this Reregi strati on Eligibility Decision Document.
It contains generic data requirements that apply to Pebulate 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) 605-6000.
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.
66
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pebulate
REQUIREMENT
USE
PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-11
63-12
63-13
63-14
Chemical Identity
Start. Mat. & Mfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Octanol/Water Partition
PH
Stability
Oxidizing/Reducing Action
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
41556805
41614802
41614802
41614801
41614801
41614801
41556805
41556805
41556805
41556805
41556805
41556805
41556805
41556805
41556805
41556805
Required
41556805
67
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pebulate
REQUIREMENT
USE
PATTERN
CITATION(S)
63-15
63-16
63-17
63-18
63-19
63-20
Flammability
Explodability
Storage stability
Viscosity
Miscibility
Corrosion characteristics
All
All
All
All
All
All
41556805
41556805
41556805
41556805
41556805
41556805
ECOLOGICAL EFFECTS
71-1A
71-2A
71-2B
72-1A
72-1C
72-2A
72-3B
123-1A
123-1B
123-2
Acute Avian Oral - Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Fish Toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
Estuarine/Marine Toxicity - Mollusk
Seed Germination/Seedling
Emergence
Vegetative Vigor
Aquatic Plant Growth
41920702
41614804, 42294201
41614803, 42294201
41614805,41614806
41614806
41614807
Required
42285301
44735901
42265101, 42265102, 42265103, 42265104, 42265105
TOXICOLOGY
68
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pebulate
REQUIREMENT
USE
PATTERN
CITATION(S)
81-1
81-2
81-3
81-4
81-5
81-6
81-7
82-1A
82-1B
82-2
82-4
82-5B
83-1A
83-1B
83-2A
83-2B
83-3A
83-3B
Acute Oral Toxicity - Rat
Acute Dermal Toxicity - Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization - Guinea Pig
Acute Delayed Neurotoxicity - Hen
90-Day Feeding - Rodent
90-Day Feeding - Non-rodent
21-Day Dermal - Rabbit/Rat
90-Day Inhalation - Rat
90-Day Neurotoxicity - Mammal
Chronic Feeding Toxicity - Rodent
Chronic Feeding Toxicity - Non-
Rodent
Oncogenicity - Rat
Oncogenicity - Mouse
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
415191701
41591701,41677301
00143575
41591703
41591702
41614808
00067869, 92138016
Waived
Waived
41920701 (28-day study)
00143576
Waived
41213001
40969701
41213001
41920705
40033301
40033201
69
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pebulate
REQUIREMENT
USE
PATTERN
CITATION(S)
83-4
83-6
84-2A
84-2B
84-4
85-1
2-Generation Reproduction - Rat
Developmental Neurotoxicity
Gene Mutation (Ames Test)
Structural Chromosomal Aberration
Other Genotoxic Effects
General Metabolism
40970001
Required
41556803
41556802
4164809
42215201, 42482501, 42482502, 42482503
OCCUPATIONAL/RESIDENTIAL EXPOSURE
132-1A
132-1B
133-3
133-4
Foliar Residue Dissipation
Soil Residue Dissipation
Dermal Passive Dosimetry Exposure
Inhalation Passive Dosimetry
Exposure
Waived
Waived
Required
Required
ENVIRONMENTAL FATE
160-5
161-1
161-2
161-3
162-1
162-2
Chemical Identity
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
41556805
151943
41920703
D 154348, Dl 54351, review dated 6/28/93
42810901, 44875900, 4063710102
42791001
70
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pebulate
REQUIREMENT
USE
PATTERN
CITATION(S)
162-3
163-1
163-2
163-3
164-1
165-2
165-3
165-4
Anaerobic Aquatic Metabolism
Leaching/Adsorption/Desorption
Volatility - Lab
Volatility - Field
Terrestrial Field Dissipation
Field Rotational Crop
Accumulation - Irrigated Crop
Bioaccumulation in Fish
42791001
41556801, 43040901, Required
41920704
Required
Required
Required*
43040901, 43042201
41614810, 43042201
RESIDUE CHEMISTRY
171-4A
171-4B
171-4C
171-4E
171-4K
Nature of Residue - Plants
Nature of Residue - Livestock
Residue Analytical Method - Plants
Storage Stability
Crop Field Trials
42519901,42519902
43327802, 43327801
43030701, 43016303, 43016304, letter dated 29 April from B.
Hazel
44080801, 44080802
43503801
*These data are required to support a preharvest interval of less than 30 days for tomatoes. To support a plantback harvest interval of less
than 4 months, upgraded confined rotational studies or limited field studies (to include seeking metabolites of potential toxicological concern
and the parent) must be submitted for all crops, including tomatoes and sugar beets.
71
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GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies considered
relevant by EPA in arriving at the positions and conclusions stated elsewhere in the Reregi strati on
Eligibility Document. Primary sources for studies in this bibliography have been the body of data
submitted to EPA and its predecessor agencies in support of past regulatory decisions. Selections from
other sources including the published literature, in those instances where they have been considered,
are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the case of published
materials, this corresponds closely to an article. In the case of unpublished materials submitted to the
Agency, the Agency has sought to identify documents at a level parallel to the published article from
within the typically larger volumes in which they were submitted. The resulting" studies" generally have
a distinct title (or at least a single subject), can stand alone for purposes of review and can be described
with a conventional bibliographic citation. The Agency has also attempted to unite basic documents
and commentaries upon them, treating them as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by Master
Record Identifier, or "MRID number". This number is unique to the citation, and should be used
whenever a specific reference is required. It is not related to the six-digit "Accession Number" which
has been used to identify volumes of submitted studies (see paragraph 4(d)(4) below for further
explanation). In a few cases, entries added to the bibliography late in the review may be preceded by
a nine character temporary identifier. These entries are listed after all MRID entries. This temporary
identifying number is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists of a
citation containing standard elements followed, in the case of material submitted to EPA, by a
description of the earliest known submission. Bibliographic conventions used reflect the standard of
the American National Standards Institute (ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to show
a personal author. When no individual was identified, the Agency has shown an identifiable
laboratory or testing facility as the author. When no author or laboratory could be identified,
the Agency has shown the first submitter as the author.
b. Document date. The date of the study is taken directly from the document. When the date is
followed by a question mark, the bibliographer has deduced the date from the evidence
contained in the document. When the date appears as (19??), the Agency was unable to
determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or enhance
a document title. Any such editorial insertions are contained between square brackets.
72
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d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing parentheses
include (in addition to any self-explanatory text) the following elements describing the earliest
known submission:
(1) Submission date. The date of the earliest known submission appears immediately
following the word "received."
(2) Administrative number. The next element immediately following the word "under" is
the registration number, experimental use permit number, petition number, or other
administrative number associated with the earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to the
submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing
parentheses identifies the EPA accession number of the volume in which the original
submission of the study appears. The six-digit accession number follows the symbol
"CDL," which stands for "Company Data Library." This accession number is in turn
followed by an alphabetic suffix which shows the relative position of the study within
the volume.
73
-------
BIBLIOGRAPHY
00067869 Sprague, G.L. (1980) Acute Delayed Neurotoxicity Study with Technical Tillam in
Adult Hens: T-6456. (Unpublished study received Jan 26, 1981 under 476-1615;
submitted by Stauffer Chemical Co., Richmond, Calif.; CDL:244253-A)
00084743 Bullock, C. (1968) Thiocarbamate Herbicides-Mosquito Fish Bio-assay:
Toxicological Summary T-1272. (Unpublished study received Oct 8, 1981 under
476-2107; submitted by Stauffer Chemical Co., Richmond, Calif; CDL:246020-G)
00143575 Miller, J. (1978) Acute Inhalation Toxicity of Tillam Technical in Albino Rats:
T-6456. Unpublished study prepared by Stauffer Chemical Co. 49 p.
00143576 Knapp, H.; Frank, D. (1982) Subchronic Inhalation Study with Tillam Technical in
Rats: T-10480. Unpublished study prepared by Stauffer Chemical Co. 284 p.
40033201 Sauerhoff, M. (1986) A Teratology Study in Rabbits with Tillam Technical:
Laboratory Project No. WIL-27036. Unpublished study prepared by WIL Research
Laboratories, Inc. 223 p.
40033301 Sauerhoff, M. (1986) A Teratology Study in Rats with Tillam Technical: Laboratory
Project ID: WTL-27034. Unpublished study prepared by WIL Research Laboratories,
Inc. 242 p.
40969701 Pettersen, J.; Taylor, D. (1988) One-Year Toxicity Study with Tillam in Beagle Dogs
T-13000: Final Report. Unpublished study prepared by ICI Americas Inc.,
Environmental Health Center.
40970001 Keller, K. (1988) Two Generation Reproduction/Fertility study in Rats: T-12922:
Final Report: Project ID: 153-196. Unpublished study prepared by International
Research and Development Corp. 558 p.
41213001 Daly, I. (1989) A Two Year Chronic Toxicity/Oncogenicity of Tillam Technical in
Rats: Bio/dynamics, Inc. Project No. 86-3036. Unpublished study prepared by ICI
Americas, Inc. 3037 p.
41556802 Randall, V.; Mackay, J. (1990) Pebulate: An Evaluation in the in vitro Cytogenic
Assay in Human Lymphocytes: Lab Project Number: TL/P2826: SV0347.
Unpublished study prepared by ICI Central Toxicology Lab. 34 p.
41556803 Majeska, J. (1987) Mutagenicity Evaluation in Salmonella typhimurium Tillam: Final
Report. Unpublished study prepared by Stauffer Chemical Co. 23 p.
41556805 Eya, B. (1990) Pebulate-Physical and Chemical Properties: Lab Project Number:
ENV-025: RR 90-102B. Unpublished study prepared by ICI Americas Inc. 46 p.
74
-------
BIBLIOGRAPHY
41591701 Billow, T. (1990) Pebulate ("Tillam" Technical): Acute Oral Toxicity to the Rat: Lab
Project Number: T-6548. Unpublished study prepared by Stauffer Chemical Co. 47
P-
41591702 Billow, T. (1981) Pebulate ("Tillam" Technical): Skin Irritation to the Rabbit: Lab
Project Number: T-6548. Unpublished study prepared by Stauffer Chemical Co. 47
P-
41591703 Billow, T. (1990) Pebulate ("Tillam" Technical): Primary Eye Irritation-Rabbit: Lab
Project Number: T-6548. Unpublished study prepared by Stauffer Chemical Co. 47
P-
41614801 Swanson, M. (1990) Analysis and Certification of Product Ingredients in Tillam
Selective Herbicide: Lab Project Number: APP-009: RPT. NO. RR 90-405B.
Unpublished study prepared by ICI Americas Inc., Western Research Ctr. 130 p.
41614803 Hakin, B.; Anderson, A. (1990) Pebulate: Dietary Toxicity (LC 50) to the Mallard
Duck: Lab Project Number: ISN 225/90737. Unpublished study prepared by
Huntingdon Research Ctr. Ltd. 29 p.
41614804 Hakin, B.; Anderson, A. (1990) Pebulate: Dietary Toxicity (LC 50) to the Bobwhite
Quail: Lab Project Number: ISN 226/90669. Unpublished study prepared by
Huntingdon Research Ctr. 29 p.
41614805 Sankey, S.; Tapp, J.; Caunter, J. et al. (1990) Pebulate: Determination of Acute
Toxicity to Bluegill Sunfish (Lepomis macrochirus): Lab Project Number: S1059/B
(FT 14/90): BL3803/B. Unpublished study prepared by ICI, PLC. 20 p.
41614807 Stewart, K.; Tapp, J.; Sankey, S., et al. (1990) Pebulate: Determination of Acute
Toxicity to Daphnia magna: Lab Project Number: S 1059/D (FT49/90): BL3846/B.
Unpublished study prepared by ICI Agrochemicals, Haslemere. 18 p.
41614809 Kennelly, J. (1990) Pebulate: Assessment for the Induction of Unscheduled DNA
Synthesis in Rat Hepatocytes In Vivo: Lab Project Number: RPT. NO. CTL/P/3032:
SRO416. Unpublished study prepared by ICI/CTL, Macclesfield. 44 p.
41677301 McCall, J. (1990) Pebulate: Acute Dermal Toxicity to the Rat: Lab Project Number:
CTL P 3098: CR2779. Unpublished study prepared by ICI Americas, Adderly Park,
UK. 26 p.
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BIBLIOGRAPHY
41920701 Kinsey, D.; Leach, A. (1990) Pebulate: 21-Day Dermal Toxicity to the Rat: Lab
Project Number: CTL/P/3096: LRO549. Unpublished study prepared by ICI, Aderley
Park.. 286 p.
41920702 Hakin, B.; Johnson, A.; Anderson, A. (1991) Pebulate: Acute Oral Toxicity (LD50)
to Mallard Duck: Lab Project Number: ISN 243/91290. Unpublished study prepared
by Huntingdon Research Centre Ltd. 30 p.
41920705 Tinston, D. (1991) Pebulate: 18-Month Carcinogenity Study in Mice: Lab Project
Number: CTL/P/3119: PMO729. Unpublished study prepared by ICI, Alderley Park.
1995 p.
42215201 Williams, S.; Cameron, B.; McGuire, G. (1991) The Identification of the Major
Radioactive Components in Urine and Faeces from Rats Following Oral
Administration of [carbon 14]-Pebulate. Unpublished study prepared by Inveresk
Research International. 90 p.
42265101 Smyth, D.; Sankey, S.; Stanley, R. (1992) Pebulate: Toxicity to the Freshwater
Diatom Navicula pelliculosa: Lab Proj ect Number: BL4403/B: V743/E (FT76/91).
Unpublished study prepared by Imperial Chemical Industries PLC. 23 p.
42265102 Smyth, D.; Sankey, S.; Stanley, R. (1992) Pebulate: Toxicity to the Marine Alga
Skeletonema costatum: Lab Project Number: BL4413/B: V743/C (FT74/91).
Unpublished study prepared by Imperial Chemical Industries PLC. 23 p.
42265103 Smyth, D.; Sankey, S.; Stanley, R. (1992) Pebulate: Toxicity to the Green Alga
Selenastrum capricornutum: Lab Project Number: BL4347/B: V743/B (FT73/91).
Unpublished study prepared by Imperial Chemical Industries PLC. 23 p.
42265105 Smyth, D.; Sankey, S.; Stanley, S. (1992) Pebulate: Toxicity to the Blue-Green Alga
Anabaena flos-aquae: Lab Project Number: BL4411/B: V743/A (FT72/91).
Unpublished study prepared by Imperial Chemical Industries PLC. 23 p.
42285301 Canning, L.; Farmer, D. (1992) Pebulate: A Glasshouse Study of Pre-emergence
Effects of a 718 g ai litre (61b ai US gal) Emulsifiable Concentrate Formulation on
Terrestrial Non-target PI ants: Lab Proj ect Number: 91JH277;RJ1125B. Unpublished
study prepared by ICI Agrochemicals, Jealotts Hill, UK. 46 p.
42482501 Johnston, A.; Mutch, P.; Scott, G. (1990) The Elimination of [Carbon 14]-Pebulate
in the Rat Following Single Oral Administration (Low Dose Level): Lab Project
Number: 7451:150032. Unpublished study prepared by Inveresk Research Int'l. 48
P-
76
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BIBLIOGRAPHY
42482502 Johnston, A.; Mutch, P.; Scott, G. (1990) The Elimination of [Carbon 14]-Pebulate
in the Rat Following Single Oral Administration (High Dose Level): Lab Project
Number: 7427:150027. Unpublished study prepared by Inveresk Research Int'l. 48
P-
42482503 Johnston, A.; Mutch, P.; Scott, G. (1990) The Elimination of [Carbon 14]-Pebulate
in the Rat Following Multiple Oral Administration (Low Dose Levels): Lab Project
Number: 7501:150011. Unpublished study prepared by Inveresk Research Int'l. 50
P-
42791001 Spurgeon, C. (1993) Pebulate: Anaerobic Aquatic Soil Metabolism: Lab Project
Number: PMS-377: RR 93-048B. Unpublished study prepared by Zeneca Inc. 75 p.
43217401 Horner, S. (1994) Pebulate: Acute Neurotoxi city Study in Rats: Lab Project Number:
CTL/P/4181: AR5628. Unpublished study prepared by Zeneca Central Toxicology
Lab. 321 p.
43231001 Brammer, A. (1994) Pebulate: Subchronic Neurotoxi city Study in Rats: Lab Proj ect
Number: CTL/P/4246: PR0953. Unpublished study prepared by Zeneca Central
Toxicology Lab. 315 p.
44735901 Chetram, R. (1998) Tier 2 Vegetative Vigor Nontarget Phytotoxicity Study Using
Tillam 6E: Lab Proj ect Number: 41137:98738. Unpublished study prepared by ABC
Laboratories, Inc. 198 p.
44875900 Hillebrecht, W.R. (1999) Pebulate Chemical # 041403, Case #2500 submission of
comments on the Draft RED Chapters. Correspondence from Zeneca Ag Products
to EPA 3 p.
44875901 Diaz, D. G. (1999) Zeneca AG Products Response to EPA Review comments on the
Pebulate Confined rotational Crop Study (MRID 42593801). Unpublished study
prepared by Zeneca AG Products Western Research Center. 7 p.
44875902 Diaz, D.W, and Yeh, S. (1999) Zeneca Ag Products Response to Pebulate EFED
Science Chapers Chemical 041403, Case #2500. Unpublished study prepared by
Zeneca AG Products Western Research Center. 5 p.
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BIBLIOGRAPHY
Citations Not Identified By A MRID Number
Fletcher, J.S., Nellessen, I.E., and Pfleegger, T. 1994, Evaluation of the EPA food-chain (Kenaga)
nomogram, and instrument for estimating pesticide residues on plants, environmental Toxicology and
Chemistry, vol.13, no. 9, pg. 1383-1391.
Hoerga, F.D., and Kenaga, E.E., 1972. Pesticide residues on plants and correlation of representative
data as a basis for estimation of their magnitude in the environment. Environmental Quality.
Academic Press, New York. 1:9-28.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active ingredient(s)
identified in Attachment 1 of this Notice, the Data Call-In Chemical Status Sheet, to submit certain
data as noted herein to the U. S. Environmental Protection Agency (EPA, the Agency). These data are
necessary to maintain the continued registration of your product(s) containing this active ingredient(s).
Within 90 days after you receive this Notice you must respond as set forth in Section III below. Your
response must state the following:
1. How you will comply with the requirements set forth in this Notice and its Attachments 1
through 4; or,
2. Why you believe you are exempt from the requirements listed in this Notice and in Attachment
3, Requirements Status and Registrant's Response Form, (see section III-B); or,
3. Why you believe EPA should not require your submission of data in the manner specified by
this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with
its requirements or should be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will be subject to suspension. We have provided a list of all of your
products subject to this Notice in Attachment 2, Data Call-In Response Form, as well as a list of all
registrants who were sent this Notice (Attachment 4).
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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 and 2070-0057
(expiration date 3-31-99).
This Notice is divided into six sections and five Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain specific
chemical information and instructions. The six sections of the Notice are as follows:
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 as follows:
Attachment 1 - Data Call-In Chemical Status Sheet
Attachment 2 - Data Call-In Response Form (Insert A)
Attachment 3 - Requirements Status And Registrant's Response Form (Insert B)
Attachment 4 - List Of All Registrants Sent This Data Call-In Notice
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the data
needed to support continued registration of the subject active ingredient(s). This reevaluation
identified additional data necessary to assess the health and safety of the continued use of products
containing this active ingredient(s). You have been sent this Notice because you have product(s)
containing the subject active ingredient(s).
SECTION II. DATA REQUIRED BY THIS NOTICE
A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and
Registrant's Response Form (Insert B). Depending on the results of the studies required in this
Notice, additional testing may be required.
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B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified
in Attachment 3, Requirements Status and Registrant's Response Form (Insert B), within the
time frames provided.
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 PortRoyal Road, Springfield, Va 22161 (tel: 703-605-6000).
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 2001 L Street,
N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone number
202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
D. REGISTRANTS RECEIVING PREVIOUS SECTION 3 (cĄ2ĄB) NOTICES ISSUED
BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or
change the requirements of any previous Data Call-In(sX 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.
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SECTION HI. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice must be submitted to the
Agency within 90 days after your receipt of this Notice. Failure to adequately respond to this
Notice within 90 days of your receipt will be a basis for issuing a Notice of Intent to Suspend
(NOIS) affecting your products. This and other bases for issuance of NOIS due to failure to
comply with this Notice are presented in Section IV-A and IV-B.
B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice are: 1) voluntary cancellation, 2) delete
use(s), (3) claim generic data exemption, (4) agree to satisfy the data requirements imposed
by this Notice or (5) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option, the
Delete Use(s) option or the Generic Data Exemption option is presented below. A discussion
of the various options available for satisfying the data requirements of this Notice is contained
in Section 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 (Insert A) and the Requirements Status and Registrant's Response
Form (InsertB). The Data Call-In Response Form (Insert A) must be submitted as part of every
response to this Notice. Please note that the company's authorized representative is required
to sign the first page of the Data Call-In Response Form (Insert A) and Requirements Status
and Registrant's Response Form (InsertB) and initial any subsequent pages. The forms contain
separate detailed instructions on the response options. Do not alter the printed material. If
you have questions or need assistance in preparing your response, call or write the contact
person identified in
Attachment 1.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by
requesting voluntary cancellation of your product(s) containing the active ingredient(s)
that is the subject of this Notice. If you wish to voluntarily cancel your product, you
must submit a completed Data Call-In Response Form (Insert A), indicating your
election of this option. Voluntary cancellation is item number 5 on the Data Call-In
Response Form (Insert A). If you choose this option, this is the only form that you are
required to complete.
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If you choose to voluntarily cancel your product, further sale and distribution
of your product after the effective date of cancellation must be in accordance with the
Existing Stocks provisions of this Notice which are contained in Section IV-C.
2. Use Deletion - You may avoid the requirements of this Notice by eliminating
the uses of your product to which the requirements apply. If you wish to amend your
registration to delete uses, you must submit the Requirements Status and Registrant's
Response Form (Insert B), a completed application for amendment, a copy of your
proposed amended labeling, and all other information required for processing the
application. Use deletion is option number 7 on the Requirements Status and
Registrant's Response Form (Insert B). You must also complete a Data Call-In
Response Form (Insert A) by signing the certification, item number 8. Application
forms for amending registrations may be obtained from the Registration Support and
Emergency Response Branch, Registration Division, (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to
specific data requirements, further sale, distribution, or use of your product after one
year from the due date of your 90 day response, must bear an amended label.
3. Generic Data Exemption - Under section 3 (c)(2)(D) of FIFRA, an applicant for
registration of a product is exempt from the requirement to submit or cite generic data
concerning an active ingredient(s) if the active ingredient(s) in the product is derived
exclusively from purchased, registered pesticide products containing the active
ingredient(s). EPA has concluded, as an exercise of its discretion, that it normally will
not suspend the registration of a product which would qualify and continue to qualify
for the generic data exemption in section 3(c)(2)(D) of FIFRA. To qualify, all of the
following requirements must be met:
a. The active ingredient(s) in your registered product must be present
solely because of incorporation of another registered product which contains
the subject active ingredient(s) and is purchased from a source not connected
with you; and,
b. every registrant who is the ultimate source of the active ingredient(s)
in your product subject to this DCI must be in compliance with the
requirements of this Notice and must remain in compliance; and
c. you must have provided to EPA an accurate and current" Confidential
Statement of Formula" for each of your products to which this Notice applies.
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To apply for the Generic Data Exemption you must submit a completed Data
Call-In Response Form (Insert A), and all supporting documentation. The Generic
Data Exemption is item number 6a on the Data Call-In Response Form (Insert A). If
you claim a generic data exemption you are not required to complete the Requirements
Status and Registrant's Response Form (Insert B). Generic Data Exemption cannot be
selected as an option for product specific data.
If you are granted a Generic Data Exemption, you rely on the efforts of other
persons to provide the Agency with the required data. If the registrant(s) who have
committed to generate and submit the required data fail to take appropriate steps to
meet the requirements or are no longer in compliance with this Data Call-In Notice,
the Agency will consider that both they and you are not in compliance and will
normally initiate proceedings to suspend the registrations of both your and their
product(s), unless you commit to submit and do submit the required data within the
specified time. In such cases the Agency generally will not grant a time extension for
submitting the data.
4. Satisfying the Data Requirements of this Notice - There are various options
available to satisfy the data requirements of this Notice. These options are discussed
in Section III-C of this Notice and comprise options 1 through 6 on the Requirements
Status and Registrant's Response Form (Insert B) and option 6b and 7 on the Data
Call-In Response Formdnsert A). If you choose option 6b or 7, you must submit both
forms as well as any other information/data pertaining to the option chosen to address
the data requirement.
5. Request for Data Waivers. Data waivers are discussed in Section III-D of this
Notice and are covered by options 8 and 9 on the Requirements Status and Registrant's
Response Form (Insert B). 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.
C. SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form (Insert A) that you agree to
satisfy the data requirements (i.e. you select option 6b and/or 7), then you must select one of
the six options on the Requirements Status and Registrant's Response Form (Insert A) 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 (Insert B). These six options are listed immediately below
with information in parentheses to guide registrants to additional instructions provided in this
Section. The options are:
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1. I will generate and submit data within the specified time frame (Developing
Data),
2. I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing),
3. I have made offers to cost-share (Offers to Cost Share),
4. I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study),
5. I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study),
6. I am citing an existing study that EPA has classified as acceptable or an
existing study that has been submitted but not reviewed by the Agency (Citing
an Existing Study).
Option 1. Developing Data
If you choose to develop the required data it must be in conformance with
Agency deadlines and with other Agency requirements as referenced herein and in the
attachments. All data generated and submitted must comply with the Good Laboratory
Practice (GLP) rule (40 CFR Part 160), be conducted according to the Pesticide
Assessment Guidelines (PAG), and be in conformance with the requirements of PR
Notice 86-5. In addition, certain studies require Agency approval of test protocols in
advance of study initiation. Those studies for which a protocol must be submitted
have been identified in the Requirements Status and Registrant's Response Form
(Insert B) and/or footnotes to the form. If you wish to use a protocol which differs
from the options discussed in Section II-C of this Notice, you must submit a detailed
description of the proposed protocol and your reason for wishing to use it. The
Agency may choose to reject a protocol not specified in Section II-C. If the Agency
rejects your protocol you will be notified in writing, however, you should be aware
that rejection of a proposed protocol will not be a basis for extending the deadline for
submission of data.
A progress report must be submitted for each study within 90 days from the
date you are required to commit to generate or undertake some other means to address
that study requirement, such as making an offer to cost-share or agreeing to share in
the cost of developing that study. A 90-day progress report must be submitted for all
studies. This 90-day progress report must include the date the study was or will be
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initiated and, for studies to be started within 12 months of commitment, the name and
address of the laboratory(ies) or individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than 1
year, interim reports must be submitted at 12 month intervals from the date you are
required to commit to generate or otherwise address the requirement for the study. In
addition to the other information specified in the preceding paragraph, at a minimum,
a brief description of current activity on and the status of the study must be included
as well as a full description of any problems encountered since the last progress report.
The time frames in the Requirements Status and Registrant's Response Form
(Insert B) are the time frames that the Agency is allowing for the submission of
completed study reports or protocols. The noted deadlines run from the date of the
receipt of this Notice by the registrant. If the data are not submitted by the deadline,
each registrant is subject to receipt of a Notice of Intent to Suspend the affected
registration(s).
If you cannot submit the data/reports to the Agency in the time required by this
Notice and intend to seek additional time to meet the requirement(s), you must submit
a request to the Agency which includes: (1) a detailed description of the expected
difficulty and (2) a proposed schedule including alternative dates for meeting such
requirements on a step-by-step basis. You must explain any technical or laboratory
difficulties and provide documentation from the laboratory performing the testing.
While EPA is considering your request, the original deadline remains. The Agency
will respond to your request in writing. If EPA does not grant your request, the
original deadline remains. Normally, extensions can be requested only in cases of
extraordinary testing problems beyond the expectation or control of the registrant.
Extensions will not be given in submitting the 90-day responses. Extensions will not
be considered if the request for extension is not made in a timely fashion; in no event
shall an extension request be considered if it is submitted at or after the lapse of the
subject deadline.
Option 2, Agreement to Share in Cost to Develop Data ~
If you choose to enter into an agreement to share in the cost of producing the
required data but will not be submitting the data yourself, you must provide the name
of the registrant who will be submitting the data. You must also provide EPA with
documentary evidence that an agreement has been formed. Such evidence may be
your letter offering to j oin 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
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parties cannot resolve the terms of the agreement they may resolve their differences
through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development —
If you have made an offer to pay in an attempt to enter into an agreement or
amend an existing agreement to meet the requirements of this Notice and have been
unsuccessful, you may request EPA (by selecting this option) to exercise its discretion
not to suspend your registration(s), although you do not comply with the data
submission requirements of this Notice. EPA has determined that as a general policy,
absent other relevant considerations, it will not suspend the registration of a product
of a registrant who has in good faith sought and continues to seek to enter into a joint
data development/cost sharing program, but the other registrant(s) developing the data
has refused to accept your offer. To qualify for this option, you must submit
documentation to the Agency proving that you have made an offer to another registrant
(who has an obligation to submit 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. 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 (Insert A)
and a Requirements Status and Registrant's Response Form (Insert B) committing to
develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw
your offer to share in the burdens of developing the data. In addition, the other
registrant must fulfill its commitment to develop and submit the data as required by
this Notice. If the other registrant fails to develop the data or for some other reason is
subject to suspension, your registration as well as that of the other registrant will
normally be subject to initiation of suspension proceedings, unless you commit to
submit, and do submit the required data in the specified time frame. In such cases, the
Agency generally will not grant a time extension for submitting the data.
Option 4. Submitting an Existing Study —
If you choose to submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this Notice. You may
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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
CFRPart 160. As stated in 40 CFR 160.3(7)" raw data means any laboratory
worksheets, records, memoranda, notes, or exact copies thereof, that are the
result of original observations and activities of a study and are necessary for
the reconstruction and evaluation of the report of that study. In the event that
exact transcripts of raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature), the exact copy
or exact transcript may be substituted for the original source as raw data. Raw
data may include photographs, microfilm or microfiche copies, computer
printouts, magnetic media, including dictated observations, and recorded data
from automated instruments." The term "specimens", according to 40 CFR
160.3(7), means "any material derived from a test system for examination or
analysis."
b. Health and safety studies completed after May 1984 must also contain
all GLP-required quality assurance and quality control information, pursuant
to the requirements of 40 CFR Part 160. Registrants must also certify at the
time of submitting the existing study that such GLP information is available
for post-May 1984 studies by including an appropriate statement on or
attached to the study signed by an authorized official or representative of the
registrant.
c. You must certify that each study fulfills the acceptance criteria for the
Guideline relevant to the study provided in the FIFRA Accelerated
Reregistration Phase 3 Technical Guidance and that the study has been
conducted according to the Pesticide Assessment Guidelines (PAG) or meets
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the purpose of the PAG (both available from NTIS). A study not conducted
according to the PAG may be submitted to the Agency for consideration if the
registrant believes that the study clearly meets the purpose of the PAG. The
registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in
addition to certifying that the purposes of the PAG are met by the study,
clearly articulate the rationale why you believe the study meets the purpose of
the PAG, including copies of any supporting information or data. It has been
the Agency's experience that studies completed prior to January 1970 rarely
satisfied the purpose of the PAG and that necessary raw data are usually not
available for such studies.
If you submit an existing study, you must certify that the study meets
all requirements of the criteria outlined above.
If EPA has previously reviewed a protocol for a study you are
submitting, you must identify any action taken by the Agency on the protocol
and must indicate, as part of your certification, the manner in which all Agency
comments, concerns, or issues were addressed in the final protocol and study.
If you know of a study pertaining to any requirement in this Notice
which does not meet the criteria outlined above but does contain factual
information regarding unreasonable adverse effects, you must notify the
Agency of such a study. If such a study is in the Agency's files, you need only
cite it along with the notification. If not in the Agency's files, you must submit
a summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study —
If a study has been classified as partially acceptable and upgradeable, you may
submit data to upgrade that study. The Agency will review the data submitted and
determine if the requirement is satisfied. If the Agency decides the requirement is not
satisfied, you may still be required to submit new data normally without any time
extension. Deficient, but upgradeable studies will normally be classified as
supplemental. However, it is important to note that not all studies classified as
supplemental are upgradeable. If you have questions regarding the classification of a
study or whether a study may be upgraded, call or write the contact person listed in
Attachment 1. If you submit data to upgrade an existing study you must satisfy or
supply information to correct all deficiencies in the study identified by EPA. You
must provide a clearly articulated rationale of how the deficiencies have been
remedied or corrected and why the study should be rated as acceptable to EPA. Your
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submission must also specify the MRID number(s) of the study which you are
attempting to upgrade and must be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified
as unacceptable and determined by the Agency as not capable of being upgraded.
This option should also be used to cite data that has been previously submitted
to upgrade a study, but has not yet been reviewed by the Agency. You must provide
the MRID number of the data submission as well as the MRID number of the study
being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above,
apply to all data submissions intended to upgrade studies. Additionally your
submission of data intended to upgrade studies must be accompanied by a certification
that you comply with each of those criteria as well as a certification regarding protocol
compliance with Agency requirements.
Option 6. Citing Existing Studies —
If you choose to cite a study that has been previously submitted to EPA, that
study must have been previously classified by EPA as acceptable or it must be a study
which has not yet been reviewed by the Agency. Acceptable toxicology studies
generally will have been classified as "core-guideline" or "core minimum." For
ecological effects studies, the classification generally would be a rating of "core." For
all other disciplines the classification would be "acceptable." With respect to any
studies for which you wish to select this option you must provide the MRID number
of the study you are citing and, if the study has been reviewed by the Agency, you must
provide the Agency's classification of the study.
If you are citing a study of which you are not the original data submitter, you
must submit a completed copy of Certification with Respect to Citations of Data (in
PR Notice 98-5) EPA Form 8570-34 .
D. REQUESTS FOR DATA WAIVERS
There are two types of data waiver responses to this Notice. The first is a request for
a low volume/minor use waiver and the second is a waiver request based on your belief that
the data requirement(s) are inapplicable and do not apply to your product.
1. Low Volume/Minor Use Waiver — Option 8 on the Requirements Status and
Registrant's Response Form (Insert B). Section 3(c)(2)(A) of FIFRA requires EPA to
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consider the appropriateness of requiring data for low volume, minor use pesticides.
In implementing this provision EPA considers as low volume pesticides only those
active ingredient(s) whose total production volume for all pesticide registrants is
small. In determining whether to grant a low volume, minor use waiver the Agency
will consider the extent, pattern and volume of use, the economic incentive to conduct
the testing, the importance of the pesticide, and the exposure and risk from use of the
pesticide. If an active ingredient(s) is used for both high volume and low volume uses,
a low volume exemption will not be approved. If all uses of an active ingredient(s) are
low volume and the combined volumes for all uses are also low, then an exemption
may be granted, depending on review of other information outlined below. An
exemption will not be granted if any registrant of the active ingredient(s) elects to
conduct the testing. Any registrant receiving a low volume minor use waiver must
remain within the sales figures in their forecast supporting the waiver request in order
to remain qualified for such waiver. If granted a waiver, a registrant will be required,
as a condition of the waiver, to submit annual sales reports. The Agency will respond
to requests for waivers in writing.
To apply for a low volume, minor use waiver, you must submit the following
information, as applicable to your product(s), as part of your 90-day response to this
Notice:
a. Total company sales (pounds and dollars) of all registered product(s)
containing the active ingredient(s). If applicable to the active ingredient(s),
include foreign sales for those products that are not registered in this country
but are applied to sugar (cane or beet), coffee, bananas, cocoa, and other such
crops. Present the above information by year for each of the past five years.
b. Provide an estimate of the sales (pounds and dollars) of the active
ingredient(s) for each major use site. Present the above information by year for
each of the past five years.
c. Total direct production cost of product(s) containing the active
ingredient(s) by year for the past five years. Include information on raw
material cost, direct labor cost, advertising, sales and marketing, and any other
significant costs listed separately.
d. Total indirect production cost (e.g. plant overhead, amortized plant
and equipment) charged to product(s) containing the active ingredient(s) by
year for the past five years. Exclude all non-recurring costs that were directly
related to the active ingredient(s), such as costs of initial registration and any
data development.
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e. A list of each data requirement for which you seek a waiver. Indicate
the type of waiver sought and the estimated cost to you (listed separately for
each data requirement and associated test) of conducting the testing needed
to fulfill each of these data requirements.
f A list of each data requirement for which you are not seeking any
waiver and the estimated cost to you (listed separately for each data
requirement and associated test) of conducting the testing needed to fulfill
each of these data requirements.
g. For each of the next ten years, a year-by-year forecast of company sales
(pounds and dollars) of the active ingredient(s), direct production costs of
product(s) containing the active ingredient(s) (following the parameters in
item c above), indirect production costs of product(s) containing the active
ingredient(s) (following the parameters in item d above), and costs of data
development pertaining to the active ingredient(s).
h. A description of the importance and unique benefits of the active
ingredient(s) to users. Discuss the use patterns and the effectiveness of the
active ingredient(s) relative to registered alternative chemicals and
non-chemical control strategies. Focus on benefits unique to the active
ingredient(s), providing information that is as quantitative as possible. If you
do not have quantitative data upon which to base your estimates, then present
the reasoning used to derive your estimates. To assist the Agency in
determining the degree of importance of the active ingredient(s) in terms of its
benefits, you should provide information on any of the following factors, as
applicable to your product(s):
(1) documentation of the usefulness of the active ingredient(s) in
Integrated Pest Management, (b) description of the beneficial impacts on the
environment of use of the active ingredient(s), as opposed to its registered
alternatives, (c) information on the breakdown of the active ingredient(s) after
use and on its persistence in the environment, and (d) description of its
usefulness against a pest(s) of public health significance.
Failure to submit sufficient information for the Agency to make a determination
regarding a request for a low volume minor use waiver will result in denial of the request for
a waiver.
2. Request for Waiver of Data —Option 9 on the Requirements Status and
Registrant's Response Form (Insert B). This option may be used if you believe that a
particular data requirement should not apply because the corresponding use is no
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longer registered or the requirement is inappropriate. You must submit a rationale
explaining why you believe the data requirements should not apply. You must also
submit the current label(s) of your product(s) and, if a current copy of your
Confidential Statement of Formula is not already on file you must submit a current
copy.
You will be informed of the Agency's decision in writing. If the Agency
determines that the data requirements of this Notice do not apply to your product(s),
you will not be required to supply the data pursuant to section 3(c)(2)(B). If EPA
determines that the data are required for your productlsX you must choose a method
of meeting the requirements of this Notice within the time frame provided by this
Notice. Within 30 days of your receipt of the Agency's written decision, you must
submit a revised Requirements Status and Registrant's Response Form (Insert B)
indicating the option chosen.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
A. NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice
due to failure by a registrant to comply with the requirements of this Data Call-In Notice,
pursuant to FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice
of Intent to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of
this Notice.
2. Failure to submit on the required schedule an acceptable proposed or final
protocol when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a
study as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this
Notice.
5. Failure to take a required action or submit adequate information pertaining to
any option chosen to address the data requirements (e.g., any required action
or information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration
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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 (Insert A) and a Requirements Status
and Registrant's Response Form (Insert B); or,
b. fulfill the commitment to develop and submit the data as required by
this Notice; or,
c. otherwise take appropriate steps to meet the requirements stated in this
Notice, unless you commit to submit and do submit the required data in the
specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any
time following the issuance of this Notice.
B. BASIS FOR DETERMINATION THAT SUBMITTED 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
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of species, number of animals, sex and distribution of animals, dose and effect levels
to be tested or attained, duration of test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of
reporting, the completeness of results, and the adequacy of any required supporting (or
raw) data, including, but not limited to, requirements referenced or included in this
Notice or contained in PR 86-5. All studies must be submitted in the form of a final
report; a preliminary report will not be considered to fulfill the submission
requirement.
C. EXISTING STOCKS OF SUSPENDED OR CANCELED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or canceled if doing so would be
consistent with the purposes of the Federal Insecticide, Fungicide, and Rodenticide Act.
The Agency has determined that such disposition by registrants of existing stocks for
a suspended registration when a section 3(c)(2)(B) data request is outstanding would generally
not be consistent with the Act's purposes. Accordingly, the Agency anticipates granting
registrants permission to sell, distribute, or use existing stocks of suspended product(s) only
in exceptional circumstances. If you believe such disposition of existing stocks of your
product(s) which may be suspended for failure to comply with this Notice should be
permitted, you have the burden of clearly demonstrating to EPA that granting such permission
would be consistent with the Act. You must also explain why an "existing stocks" provision
is necessary, including a statement of the quantity of existing stocks and your estimate of the
time required for their sale, distribution, and use. Unless you meet this burden the Agency
will not consider any request pertaining to the continued sale, distribution, or use of your
existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice
and your product is in full compliance with all Agency requirements, you will have, under
most circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use
such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily canceled products containing an active ingredient(s) for which the Agency has
particular risk concerns will be determined on case-by-case basis.
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Requests for voluntary cancellation received after the 90 day response period required
by this Notice will not result in the Agency granting any additional time to sell, distribute, or
use existing stocks beyond a year from the date the 90 day response was due unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3 year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study
in an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE UNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a pesticide
is registered a registrant has additional factual information regarding unreasonable adverse effects on
the environment by the pesticide, the registrant shall submit the information to the Agency.
Registrants must notify the Agency of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of studies, regarding unreasonable adverse
effects on man or the environment. This requirement continues as long as the products are registered
by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary cancellation requests and generic data
exemption claims) must include a completed Data Call-In Response Form (Insert A) and a completed
Requirements Status and Registrant's Response Form (Insert B) and any other documents required by
this Notice, and should be submitted to the contact person identified in Attachment 1. If the voluntary
cancellation or generic data exemption option is chosen, only the Data Call-In Response Form (Insert
A) need be submitted.
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The Office of Compliance (OC) of the Office of Enforcement and Compliance Assurance
(OECA), EPA, will be monitoring the data being generated in response to this Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
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PEBULATE DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s) containing
Pebulate.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required by
this notice, and point of contact for inquiries pertaining to the reregi strati on of Pebulate. This
attachment is to be used in conjunction with (1) the Generic Data Call-In Notice, (2) the Generic Data
Call-In Response Form (Attachment 2), (3) the Requirements Status and Registrant's Form
(Attachment 2), (4) a list of registrants receiving this DCI (Attachment 4), (5) the EPA Acceptance
Criteria (Attachment 5), and (6) the Cost Share and Data Compensation Forms in replying to this
Pebulate Generic Data Call In (Attachment F). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for Pebulate are
contained in the Requirements Status and Registrant's Response. Attachment C. The Agency has
concluded that additional product chemistry data on Pebulate are needed. These data are needed to
fully complete the reregi strati on of all eligible Pebulate products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures established
by this Notice, please contact Patricia Moe at (703) 308-8011.
All responses to this Notice for the generic data requirements should be submitted to:
Patricia Moe, Chemical Review Manager
Special Review and Registration Division (7508C)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: Pebulate
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SPECIFIC INSTRUCTIONS FOR THE GENERIC DATA CALL-IN RESPONSE FORM
(INSERT A)
This Form is designed to be used to respond to call-ins for generic and product specific data
for the purpose of reregistering pesticides under the Federal Insecticide Fungicide and Rodenticide
Act. Fill out this form each time you are responding to a data call-in for which EPA has sent you the
form entitled "Requirements Status and Registrant's Response."
Items 1-4 will have been preprinted on the form Items 5 through 7 must be completed by the
registrant as appropriate Items 8 through 11 must be completed by the registrant before
submitting a response to the Agency.
Public reporting burden for this collection of information is estimated to average 15 minutes
per response, including time for reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the collection of information. Send
comments regarding the burden estimate or any other aspect of this collection of information,
including suggesting for reducing this burden, to Chief, Information Policy Branch, PM-223, U S
Environmental Protection Agency, 401 M St, S W , Washington, D C 20460; and to the Office of
Management and Budget, Paperwork Reduction Project 2070-0107, Washington, D C 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number and address.
Item 2. This item identifies the ease number, ease name, EPA chemical number and
chemical name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the EPA product registrations relevant to the data call-in.
Please note that you are also responsible for informing the Agency of your
response regarding any product that you believe may be covered by this data
call-in but that is not listed by the Agency in Item 4. You must bring any such
apparent omission to the Agency's attention within the period required for
submission of this response form.
Item 5. Cheek this item for each product registration you wish to cancel voluntarily.
If a registration number is listed for a product for which you previously
requested voluntary cancellation, indicate in Item 5 the date of that request.
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You do not need to complete any item on the Requirements Status and
Registrant's Response Form for any product that is voluntarily canceled.
Item 6a. Check this item if this data call-in is for generic data as indicated in Item 3 and
if you are eligible for a Generic Data Exemption for the chemical listed in Item
2 and used in the subject product. By electing this exemption, you agree to
the terms and conditions of a Generic Data Exemption as explained in the
Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA
registration Number of each registered source of that active ingredient that
you use in your product.
Typically, if you purchase an EPA-registered product from one or more other
producers (who, with respect to the incorporated product, are in compliance
with this and-any other outstanding Data Call-In Notice), and incorporate that
product into all your products, you may complete this item for all products
listed on this form If, however, you produce the active ingredient yourself, or
use any unregistered product (regardless of the fact that some of your sources
are registered), you may not claim a Generic Data Exemption and you may
not select this item.
Item 6b. Check this Item if the data call-in is a generic data call-in as indicated in Item
3 and if you are agreeing to satisfy the generic data requirements of this data
call-in. Attach the Requirements Status and Registrant's Response Form
(Insert A) that indicates how you will satisfy those requirements.
Item 7a. Check this item if this call-in if a data call-in as indicated in Item 3 for a
manufacturing use product (MUP), and if your product is a manufacturing use
product for which you agree to supply product-specific data. Attach the
Requirements Status and Registrants' Response Form (Insert A) that indicates
how you will satisfy those requirements.
Item 7b. Check this item if this call-in is a data call-in for an end use product (EUP) as
indicated in Item 3 and if your product is an end use product for which you
agree to supply product-specific data. Attach the Requirements Status and
Registrant's Response Form (Insert A) that indicates how you will satisfy
those requirements.
Item 8. This certification statement must be signed by an authorized representative of
your company and the person signing must include his/her title. Additional
pages used in your response must be initialed and dated in the space provided
for the certification.
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Item 9. Enter the date of signature.
Item 10. Enter the name of the person EPA should contact with questions regarding
your response.
Item 11. Enter the phone number of your company contact.
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SPECIFIC INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANTS RESPONSE FORM (INSERTS)
Generic Data
This form is designed to be used for registrants to respond to call-in- for generic and product-specific
data as part of EPA's reregi strati on program under the Federal Insecticide Fungicide and Rodenticide
Act. Although the form is the same for both product specific and generic data, instructions for
completing the forms differ slightly. Specifically, options for satisfying product specific data
requirements do not include (1) deletion of uses or (2) request for a low volume/minor use waiver.
These instructions are for completion of generic data requirements.
EPA has developed this form individually for each data call-in addressed to each registrant, and has
preprinted this form with a number of items. DO NOT use this form for any other active ingredient.
Items 1 through 8 (inclusive) will have been preprinted on the form. You must complete all other
items on this form by typing or printing legibly.
Public reporting burden for this collection of information is estimated to average 30 minutes per
response, including time for reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the collection of information. Send
comments regarding the burden estimate or any other aspect of this collection of information,
including suggesting for reducing this burden, to Chief, Information Policy Branch, PM-223, U.S.
Environmental Protection Agency, 401 M St., SW., Washington, D.C. 20460; and to the Office of
Management and Budget, Paperwork Reduction Project 2070-0107, Washington, D.C. 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number, and address.
Item 2. This item identifies the case number, case name, EPA chemical number and chemical
name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the guideline reference numbers of studies required to support the
product(s) being reregistered. These guidelines, in addition to requirements specified
in the Data Call-In Notice, govern the conduct of the required studies.
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Item 5. This item identifies the study title associated with the guideline reference number and
whether protocols and 1, 2, or 3-year progress reports are required to be
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submitted in connection with the study. As noted in Section III of the Data Call-In
Notice, 90-day progress reports are required for all studies.
If an asterisk appears in Item 5, EPA has attached information relevant to this
guideline reference number to the Requirements Status and Registrant's
Response Form (Insert B).
Item 6. This item identifies the code associated with the use pattern of the pesticide. A brief
description of each code follows:
A. Terrestrial food
B. Terrestrial feed
C. Terrestrial non-food
D. Aquatic food
E. Aquatic non-food outdoor
F. Aquatic non-food industrial
G. Aquatic non-food residential
H. Greenhouse food
I. Greenhouse non-food crop
J. Forestry
K. Residential
L. Indoor food
M. Indoor non-food
N. Indoor medical
O. Indoor residential
Item 7. This item identifies the code assigned to the substance that must be used for testing.
A brief description of each code follows.
EP End-Use Product
MP Manufacturing-Use Product
MP/TGAI Manufacturing-Use Product and Technical Grade
Active Ingredient
PAI Pure Active Ingredient
PAI/M Pure Active Ingredient and Metabolites
PAI/PAIRA Pure Active Ingredient or Pure Active Ingredient
Radiolabelled
PAIRA Pure Active Ingredient Radiolabelled
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PAIRA/M Pure Active Ingredient Radiolabelled and Metabolites
PAIRA/PM Pure Active Ingredient Radiolabelled and Plant
Metabolites
TEP Typical End-Use Product
TEP _ * Typical End-Use Product, Percent Active Ingredient
Specified
TEP/MET Typical End-Use Product and Metabolites
TEP/PAI/M Typical End-Use Product or Pure Active Ingredient
and Metabolites
TGAI/PAIRA Technical Grade Active Ingredient or Pure Active
Ingredient Radiolabelled
TGAI Technical Grade Active Ingredient
TGAI/TEP Technical Grade Active Ingredient or Typical End-Use
Product
TGAI/PAI Technical Grade Active Ingredient or Pure Active
Ingredient
MET Metabolites
IMP Impurities
DEGR Degradates
*See: guideline comment
Item 8. This item identifies the time frame allowed for submission of the study or protocol
identified in item 2. The time frame runs from the date of your receipt of the Data
Call-In Notice.
Item 9. Enter the appropriate Response Code or Codes to show how you intend to comply
with each data requirement. Brief descriptions of each code follow. The Data Call-In
Notice contains a fuller description of each of these options.
1. (Developing Data) I will conduct a new study and submit it within the time
frames specified in item 8 above. By indicating that I have chosen this option,
I certify that I will comply with all the requirements pertaining to the
conditions for submittal of this study as outlined in the Data Call-In Notice
and that I will provide the protocol and progress reports required in item 5
above.
2. (Agreement to Cost Share) I have entered into an agreement with one or more
registrants to develop data jointly. By indicating that I have chosen this
option, I certify that I will comply with all the requirements pertaining to
sharing in the cost of developing data as outlined in the Data Call-In Notice.
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3. (Offer to Cost Share) I have made an offer to enter into an agreement with
one or more registrants to develop data jointly. I am submitting a copy of the
form "Certification of Offer to Cost Share in the Development of Data" that
describes this offer/agreement. By indicating that I have chosen this option,
I certify that I will comply with all the requirements pertaining to making an
offer to share in the cost of developing data as outlined in the Data Call-In
Notice.
4. (Submitting Existing Data) I am submitting an existing study that has never
before been submitted to EPA. By indicating that I have chosen this option,
I certify that this study meets all the requirements pertaining to the conditions
for submittal of existing data outlined in the Data Call-In Notice and I have
attached the needed supporting information along with this response.
5. (Upgrading a Study) I am submitting or citing data to upgrade a study that
EPA has classified as partially acceptable and potentially upgradeable. By
indicating that I have chosen this option, I certify that I have met all the
requirements pertaining to the conditions for submitting or citing existing data
to upgrade a study described in the Data Call-In Notice. I am indicating on
attached correspondence the Master Record Identification Number (MRID)
that EPA has assigned to the data that I am citing as well as the MRID of the
study I am attempting to upgrade.
6. (Citing a Study) I am citing an existing study that has been previously
classified by EPA as acceptable, core, core minimum, or a study that has not
yet been reviewed by the Agency. I am providing the Agency's classification
of the study.
7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-In Notice and
I request a low-volume minor use waiver of the data requirement. I am
attaching a detailed justification to support this waiver request including,
among other things, all information required to support the request. I
understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than low volume minor-use data waivers in the Data Call-In
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Notice and I request a waiver of the data requirement. I am attaching an
identification of the basis for this waiver and a detailed justification to support
this waiver request. The justification includes, among other things, all
information required to support the request. I understand that, unless modified
by the Agency in writing, the data requirement as stated in the Notice
governs.
Item 10. This item must be signed by an authorized representative of your company. The
person signing must include his/her title, and must initial and date all other pages of
this form.
Item 11. Enter the date of signature.
Item 12. Enter the name of the person EPA should contact with questions regarding your
response.
Item 13. Enter the phone number of your company contact.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 1 of this Notice, the Data Call-In Chemical Status Sheet, to
submit certain product specific data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your
product(s) containing this active ingredient. Within 90 days after you receive this Notice you must
respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 5; or
2. Why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3, Requirements Status and Registrant's Response Form, (see section
III-B); or
3. Why you believe EPA should not require your submission of product specific data
in the manner specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with
its requirements or should be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will be subject to suspension. We have provided a list of all of
your products subject to this Notice in Attachment 2, Data Call-In Response Form, as well as a list
of all registrants who were sent this Notice (Attachment 5).
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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
and 2070-0057 (expiration date 03-31-99).
This Notice is divided into six sections and six Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse
Effects
Section VT - Inquiries And Responses To This Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form (Insert A)
3 - Requirements Status and Registrant's Response Form (Insert B)
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
SECTIONI. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the data
needed to support continued registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product specific data. No additional generic
data requirements are being imposed. You have been sent this Notice because you have product(s)
containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment 3, Requirements
Status and Registrant's Response Form (Insert B). Depending on the results of the studies required in
this Notice, additional testing may be required.
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II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in Insert B,
Requirements Status and Registrant's Response Form (Insert B), within the time frames provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have
been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-605-6000).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD-recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the
study will satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend
deadlines for complying with data requirements when the studies were not conducted in
accordance with acceptable standards. The OECD protocols are available from OECD, 2001
L Street, N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone
number 202-785-03 50).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B) NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change
the requirements of any previous Data Call-In(sX 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
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Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for issuance
of NOIS due to failure to comply with this Notice are presented in Section IV-A and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this notice
or (c) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product
specific data requirements of this Notice is contained in Section III-C. A discussion of
options relating to requests for data waivers is contained in Section III-D.
There are two forms that accompany this Notice of which, depending upon your
response, one or both must be used in your response to the Agency. These forms are the Data-
Call-in Response Form (Insert A), and the Requirements Status and Registrant's Response
Form (Insert B). 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 (Insert B) must be submitted for each product listed on the Data Call-In Response Form
(Insert A) 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(Insert A). Please note that the company's authorized representative is required to sign
the first page of the Data Call-In Response Form (Insert A) and Requirements Status and
Registrant's Response Form (Insert B), initial any subsequent pages. The forms contain
separate detailed instructions on the response options. Do not alter the printed material. If
you have questions or need assistance in preparing your response, call or write the contact
person(s) identified in Attachment 1.
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 (Insert AX indicating your election of this option.
Voluntary cancellation is item number 5 on the Data Call-In Response Form (Insert B). 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 5 on the
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Requirements Status and Registrant's Response Formdnsert A) and item numbers 7a and 7b
on the Data Call-In Response Formdnsert B). 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 (Insert B). If you choose one of these options, you
must submit both forms as well as any other information/data pertaining to the option chosen
to address the data requirement.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form (Insert A) that you agree to
satisfy the product specific data requirements (i.e. you select item number 7a or 7b), then you
must select one of the six options on the Requirements Status and Registrant's Response Form
(Insert A) 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 Formdnsert A). These six options are
listed immediately below with information in parentheses to guide registrants to additional
instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified time frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing study
that has been submitted but not reviewed by the Agency (Citing an Existing Study)
Option 1, Developing Data ~ If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced here
in and in the attachments. All data generated and submitted must comply with the Good
Laboratory Practice (GLP) rule (40 CFRPart 160), be conducted according to the Pesticide
Assessment Guidelines(PAG), and be in conformance with the requirements of PR Notice 86-
5.
The time frames in the Requirements Status and Registrant's Response Form (Insert A)
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
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data are not submitted by the deadline, each registrant is subject to receipt of a Notice of
Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to
the Agency which includes: (1) a detailed description of the expected difficulty and (2) a
proposed schedule including alternative dates for meeting such requirements on a step-by-step
basis. You must explain any technical or laboratory difficulties and provide documentation
from the laboratory performing the testing. While EPA is considering your request, the
original deadline remains. The Agency will respond to your request in writing. If EPA does
not grant your request, the original deadline remains. Normally, extensions can be requested
only in cases of extraordinary testing problems beyond the expectation or control of the
registrant. Extensions will not be given in submitting the 90-day responses. Extensions will
not be considered if the request for extension is not made in a timely fashion; in no event shall
an extension request be considered if it is submitted at or after the lapse of the subject
deadline.
Option 2, Agreement to Share in Cost to Develop Data ~ Registrants may only choose this
option for acute toxicity data and certain efficacy data and only if EPA has indicated in the
attached data tables that your product and at least one other product are similar for purposes of
depending on the same data. If this is the case, data may be generated for just one of the
products in the group. The registration number of the product for which data will be
submitted must be noted in the agreement to cost share by the registrant selecting this option.
If you choose to enter into an agreement to share in the cost of producing the required data but
will not be submitting the data yourself, you must provide the name of the registrant who will
be submitting the data. You must also provide EPA with documentary evidence that an
agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of the
terms of the final arrangement between the parties or the mechanism to resolve the terms.
Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
Option 3, Offer to Share in the Cost of Data Development — This option only applies to
acute toxicity and certain efficacy data as described in option 2 above. If you have made an
offer to pay in an attempt to enter into an agreement or amend an existing agreement to meet
the requirements of this Notice and have been unsuccessful, you may request EPA (by
selecting this option) to exercise its discretion not to suspend your registration(s), although
you do not comply with the data submission requirements of this Notice. EPA has determined
that as a general policy, absent other relevant considerations, it will not suspend the
registration of a product of a registrant who has in good faith sought and continues to seek to
enter into a joint data development/cost sharing program, but the other registrant(s)
developing the data has refused to accept your offer. To qualify for this option, you must
submit documentation to the Agency proving that you have made an offer to another registrant
(who has an obligation to submit data) to share in the burden of developing that data. You
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must also submit to the Agency a completed EPA Form 8570-32, Certification of Offer to
Cost Share in the Development of Data, Attachment 7. In addition, you must demonstrate that
the other registrant to whom the offer was made has not accepted your offer to enter into a
cost sharing agreement by including a copy of your offer and proof of the other registrant's
receipt of that offer (such as a certified mail receipt). Your offer must, in addition to anything
else, offer to share in the burden of producing the data upon terms to be agreed 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 (Insert A) and a Requirements Status and Registrant's Response Form (Insert
B) committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your
offer to share in the burdens of developing the data. In addition, the other registrant must
fulfill its commitment to develop and submit the data as required by this Notice. If the other
registrant fails to develop the data or for some other reason is subject to suspension, your
registration as well as that of the other registrant will normally be subject to initiation of
suspension proceedings, unless you commit to submit, and do submit the required data in the
specified time frame. In such cases, the Agency generally will not grant a time extension for
submitting the data.
Option 4, Submitting an Existing Study ~ If you choose to submit an existing study in
response to this Notice, you must determine that the study satisfies the requirements imposed
by this Notice. You may only submit a study that has not been previously submitted to the
Agency or previously cited by anyone. Existing studies are studies which predate issuance of
this Notice. Do not use this option if you are submitting data to upgrade a study. (See Option
5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of
the following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted that the raw data and
specimens from the study are available for audit and review and you must identify
where they are available. This must be done in accordance with the requirements of
the Good Laboratory Practice (GLP) regulation, 40 CFR Part 160. As stated in 40 CFR
160.3(j)" 'raw data' means any laboratory worksheets, records, memoranda, notes, or
exact copies thereof, that are the result of original observations and activities of a
study and are necessary for the reconstruction and evaluation of the report of that
study. In the event that exact transcripts of raw data have been prepared (e.g., tapes
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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 study, you must, in addition
to certifying that the purposes of the PAG are met by the study, clearly articulate the
rationale why you believe the study meets the purpose of the PAG, including copies of
any supporting information or data. It has been the Agency's experience that studies
completed prior to January 1970 rarely satisfied the purpose of the PAG and that
necessary raw data are usually not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements
of the criteria outlined above.
If you know of a study pertaining to any requirement in this Notice which does not
meet the criteria outlined above but does contain factual information regarding unreasonable
adverse effects, you must notify the Agency of such a study. If such study is in the Agency's
files, you need only cite it along with the notification. If not in the Agency's files, you must
submit a summary and copies as required by PR Notice 86-5.
Option 5, Upgrading a Study ~ If a study has been classified as partially acceptable and
upgradeable, you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the requirement
is not satisfied, you may still be required to submit new data normally without any time
extension. Deficient, but upgradeable studies will normally be classified as supplemental.
However, it is important to note that not all studies classified as supplemental are
upgradeable. If you have questions regarding the classification of a study or whether a study
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may be upgraded, call or write the contact person listed in Attachment 1. If you submit data to
upgrade an existing study you must satisfy or supply information to correct all deficiencies in
the study identified by EPA. You must provide a clearly articulated rationale of how the
deficiencies have been remedied or corrected and why the study should be rated as acceptable
to EPA. Your submission must also specify the MRID number(s) of the study which you are
attempting to upgrade and must be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option should also be used to cite data that has been previously submitted to
upgrade a study, but has not yet been reviewed by the Agency. You must provide the MRID
number of the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to
all data submissions intended to upgrade studies. Additionally your submission of data
intended to upgrade studies must be accompanied by a certification that you comply with each
of those criteria as well as a certification regarding protocol compliance with Agency
requirements.
Option 6, Citing Existing Studies ~ If you choose to cite a study that has been previously
submitted to EPA, that study must have been previously classified by EPA as acceptable or it
must be a study which has not yet been reviewed by the Agency. Acceptable toxicology
studies generally will have been classified as "core-guideline" or "core minimum." For all
other disciplines the classification would be "acceptable." With respect to any studies for
which you wish to select this option you must provide the MRID number of the study you are
citing and, if the study has been reviewed by the Agency, you must provide the Agency's
classification of the study.
If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of EPA Form 8570-34, Certification with Respect to Citations of
Data (in PR Notice 98-51.
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 (Insert A) and
the Requirements Status and Registrant's Response Form (Insert B), 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
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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.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice
due to failure by a registrant to comply with the requirements of this Data Call-In Notice,
pursuant to FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice
of Intent to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task Forces,
failure to comply with the terms of an agreement or arbitration concerning joint data
development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies,
as required by Section III-C of this Notice.
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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 Formdnsert A) and a Requirements Status and
Registrant's Response Formdnsert B):
b. fulfill the commitment to develop and submit the data as required by this
Notice; or
c. otherwise take appropriate steps to meet the requirements stated in this Notice,
unless you commit to submit and do submit the required data in the specified
time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The
grounds for suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-In Notice or other documents incorporated by
reference (including, as applicable, EPA Pesticide Assessment Guidelines, Data Reporting
Guidelines, and GeneTox Health Effects Test Guidelines) regarding the design, conduct, and
reporting of required studies. Such requirements include, but are not limited to, those relating
to test material, test procedures, selection of species, number of animals, sex and distribution
of animals, dose and effect levels to be tested or attained, duration of test, and, as applicable,
Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation of
any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of reporting, the
completeness of results, and the adequacy of any required supporting (or raw) data, including,
but not limited to, requirements referenced or included in this Notice or contained in PR 86-5.
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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 CANCELED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or canceled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally
not be consistent with the Act's purposes. Accordingly, the Agency anticipates granting
registrants permission to sell, distribute, or use existing stocks of suspended product(s) only in
exceptional circumstances. If you believe such disposition of existing stocks of your
product(s) which may be suspended for failure to comply with this Notice should be
permitted, you have the burden of clearly demonstrating to EPA that granting such permission
would be consistent with the Act. You must also explain why an "existing stocks" provision is
necessary, including a statement of the quantity of existing stocks and your estimate of the
time required for their sale, distribution, and use. Unless you meet this burden the Agency
will not consider any request pertaining to the continued sale, distribution, or use of your
existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice
and your product is in full compliance with all Agency requirements, you will have, under
most circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use
such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily canceled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required
by this Notice will not result in the Agency granting any additional time to sell, distribute, or
use existing stocks beyond a year from the date the 90 day response was due unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3 year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study
in an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
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SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLEUNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a pesticide
is registered a registrant has additional factual information regarding unreasonable adverse effects on
the environment by the pesticide, the registrant shall submit the information to the Agency.
Registrants must notify the Agency of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of studies, regarding unreasonable adverse
effects on man or the environment. This requirement continues as long as the products are registered
by the Agency.
SECTION VI.INOUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by
this Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status
Sheet.
All responses to this Notice (other than voluntary cancellation requests and generic
data exemption claims) must include a completed Data Call-In Response Form (Insert A) and
a completed Requirements Status and Registrant's Response Form (Insert B) for product
specific data) and any other documents required by this Notice, and should be submitted to
the contact person(s) identified in Attachment 1. If the voluntary cancellation or generic data
exemption option is chosen, only the Data Call-In Response Form (Insert A) 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,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Attachments
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1 - Data Call-in Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form (Insert A)
3 - Requirements Status and Registrant's Response Form (Insert B)
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data Requirements
for Reregistration
5 - List of Registrants Receiving This Notice
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PEBULATE DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s) containing
Pebulate.
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 reregi strati on of Pebulate. This attachment is
to be used in conjunction with (1) the Product Specific Data Call-In Notice, (2) the Product Specific Data Call-
in Response Form (Attachment 2), (3) the Requirements Status and Registrant's Form (Attachment 3), (4)
EPA's Grouping of End-Use Products for Meeting Acute Toxicology Data Requirement (Attachment 4), (5)
the EPA Acceptance Criteria (Attachment 5), (6) a list of registrants receiving this DCI (Attachment 6) and
(7) the Cost Share and Data Compensation Forms in replying to this Pebulate Product Specific Data Call-In
(Attachment 7). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for Pebulate are contained in the
Requirements Status and Registrant's Response. Attachment 3. The Agency has concluded that additional data
on Pebulate 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 reregi strati on of all eligible Pebulate products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures established
by this Notice, please contact Venus Eagle at (703) 308-8045.
All responses to this Notice for the Product Specific data requirements should be submitted to:
Chemical Review Manager Team 81
Product Reregi strati on Branch
Special Review and Reregi strati on Branch 7508C
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: Pebulate
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer "yes." If you choose this option, you
will not have to provide the data required by the Data Call-In Notice and you will not have to
complete any other forms. Further sale and distribution of your product after the effective date
of cancellation must be in accordance with the Existing Stocks provision of the Data Call-In
Notice (Section IV-C).
Item 6.
Item 7a.
Item 7b.
Not applicable since this form calls in product specific data only. However, if your product is
identical to another product and you qualify for a data exemption, you must respond with
"yes" to Item 7a (MUP) or 7B (EUP) on this form, provide the EPA registration numbers
of your source(s); you would not complete the "Requirements Status and Registrant's
Response" form. Examples of such products include repackaged products and Special Local
Needs (Section 24c) products which are identical to federally registered products.
For each manufacturing use product (MUP) for which you wish to maintain registration, you
must agree to satisfy the data requirements by responding "yes."
For each end use product (EUP) for which you wish to maintain registration, you must agree
to satisfy the data requirements by responding "yes." If you are requesting a data waiver,
answer "yes" here; in addition, on the "Requirements Status and Registrant's Response" form
under Item 9, you must respond with Option 7 (Waiver Request) for each study for which you
are requesting a waiver. See Item 6 with regard to identical products and data exemptions.
Items 8-11. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed letter that
accompanies this form. For example, you may wish to report that your product has already
been transferred to another company or that you have already voluntarily canceled this product.
For these cases, please supply all relevant details so that EPA can ensure that its records are
correct.
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INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number assigned by EPA in Item 3. This
number must be used in the transmittal document for any data submissions in response
to this Data Call-In Notice.
Item 4. The guideline reference numbers of studies required to support the product's continued
registration are identified. These guidelines, in addition to the requirements specified in the
Notice, govern the conduct 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 pattern(s) of the pesticide associated with the product specific requirements is (are)
identified. For most product specific data requirements, all use patterns are covered by the data
requirements. In the case of efficacy data, the required studies only pertain to products which
have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For product specific data, the product as
formulated for sale and distribution is the test substance, except in rare cases.
Item 8. The due date for submission of each study is identified. It is normally based on 8 months after
issuance of the Reregistration Eligibility Document unless EPA determines that a longer
time period is necessary.
Item 9. Enter only one of the following response codes for each data requirement to show how
you intend to comply with the data requirements listed in this table. Fuller descriptions
of each option are contained in the Data Call-In Notice.
1. I will generate and submit data by the specified due date (Developing Data). By indicating that
I have chosen this option, I certify that I will comply with all the requirements pertaining to the
conditions for submittal of this study as outlined in the Data Call-In Notice. By the specified
due date, I will also submit: (1) a completed "Certification with Respect to Citations of Data
(in PR Notice 98-5)" form (EPA Form 8570-34) and (2) two completed and signed copies
of the Confidential Statement of Formula (EPA Form 8570-4)
2. I have entered into an agreement with one or more registrants to develop data jointly (Cost
Sharing). I am submitting a copy of this agreement. I understand that this option is available
only for acute toxicity or certain efficacy data and only if EPA indicates in an attachment to this
Notice that my product is similar enough to another product to qualify for this option. I certify
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that another party in the agreement is committing to submit or provide the required data; if the
required study is not submitted on time, my product may be subject to suspension. By the
specified due date, I will also submit: (1) a completed "Certification with Respect to
Citations of Data (in PR Notice 98-5)" form (EPA Form 8570-34) and (2) two completed
and signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
3. I have made offers to share in the cost to develop data (Offers to Cost Share). I understand
that this option is available only for acute toxicity or certain efficacy data and only if EPA
indicates in an attachment to this Data Call-In Notice that my product is similar enough to
another product to qualify for this option. I am submitting evidence that I have made an
offer to another registrant (who has an obligation to submit data) to share in the cost of that
data. I am also submitting a completed "Certification of Attempt to Enter into an
Agreement with other Restraints for Development of Data " (EPA Form 8570-32). I am
including a copy of my offer and proof of the other registrant's receipt of that offer. I am
identifying the party which is committing to submit or provide the required data; if the required
study is not submitted on time, my product may be subject to suspension. I understand that
other terms under Option 3 in the Data Call-In Notice (Section III-C. 1.) apply as well. By the
specified due date, I will also submit: (1) a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-34) and (2) two completed and signed
copies of the Confidential Statement of Formula (EPA Form 8570-4)
4. By the specified due date, I will submit an existing study that has not been submitted previously
to the Agency by anyone (Submitting an Existing Study). I certify that this study will meet
all the requirements for submittal of existing data outlined in Option 4 in the Data Call-In
Notice (Section III-C. 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. By the specified due date, I will also submit a completed
"Certification With Respect To Data Compensation Requirements" form (EPA Form
8570-34) to show what data compensation option I have chosen. By the specified due date,
I will also submit: (1) a completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-34) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4)
5. By the specified due date, I will submit or cite data to upgrade a study classified by the Agency
as partially acceptable and upgradable (Upgrading a Study). I will submit evidence of the
Agency's review indicating that the study may be upgraded and what information is required
to do so. I will provide the MRID or Accession number of the study at the due date. I
understand that the conditions for this option outlined Option 5 in the Data Call-In Notice
(Section III-C. 1.) apply. By the specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation Requirements" form (EPA Form
8570-34) and (2) two completed and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4)
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6. By the specified due date, I will cite an existing study that the Agency has classified as
acceptable or an existing study that has been submitted but not reviewed by the Agency (Citing
an Existing Study). If I am citing another registrant's study, I understand that this option is
available only for acute toxicity or certain efficacy data and only if the cited study was
conducted on my product, an identical product or a product which EPA has "grouped" with one
or more other products for purposes of depending on the same data. I may also choose this
option if I am citing my own data. In either case, I will provide the MRID or Accession
number(s) for the cited data on a "Product Specific Data Report" form or in a similar format.
By the specified due date, I will also submit: (1) a completed "Certification With Respect To
Data Compensation Requirements" form (EPA Form 8570-34) and (2) two completed and
signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
7. I request a waiver for this study because it is inappropriate for my product (Waiver Request).
I am attaching a complete justification for this request, including technical reasons, data and
references to relevant EPA regulations, guidelines or policies. [Note: any supplemental data
must be submitted in the format required by P.R. Notice 86-5]. I understand that this is my
only opportunity to state the reasons or provide information in support of my request. If the
Agency approves my waiver request, I will not be required to supply the data pursuant to
Section 3(c)(2)(B) of FIFRA. If the Agency denies my waiver request, I must choose a
method of meeting the data requirements of this Notice by the due date stated by this Notice.
In this case, I must, within 30 days of my receipt of the Agency's written decision, submit a
revised "Requirements Status and Registrant's Response" Form indicating the option chosen.
I also understand that the deadline for submission of data as specified by the original data call-in
notice will not change. By the specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation Requirements" form (EPA Form
8570-34) and (2) two completed and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4)
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed letter that
accompanies this form. For example, you may wish to report that your product has already
been transferred to another company or that you have already voluntarily canceled this product.
For these cases, please supply all relevant details so that EPA can ensure that its records are
correct.
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Part B form page number 3 in the actual Printed version of the Red document
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Part B form page number 4 in the actual Printed version of the Red document
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EPA'S BATCHING OF PEBULATE PRODUCTS FOR MEETING ACUTE TOXICITY DATA
REQUIREMENTS FOR REREGISTRATION
There is no batching for pebulate, as there are is only one end-use product.
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Registrants page number 1 in the actual Printed version of the Red document
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Pesticide Registration Forms are available at the following EPA internet site:
http ://www. epa. gov/opprdOO I/forms/.
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader)
Instructions
1. Print out and complete the forms. (Note: Form numbers that are bolded can be filled out on
your computer then printed.)
2. The completed form(s) should be submitted in hardcopy in accord with the existing policy.
3. Mail the forms, along with any additional documents necessary to comply with EPA
regulations covering your request, to the address below for the Document Processing Desk.
DO NOT fax or e-mail any form containing 'Confidential Business Information' or 'Sensitive
Information.'
If you have any problems accessing these forms, please contact Nicole Williams at (703) 308-5551
or by e-mail atwilliams.nicole@epamail.epa.gov.
The following Agency Pesticide Registration Forms are currently available via the internet at the
following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
8570-30
8570-32
Application for Pesticide
Registration/Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of
Distribution of a Registered Pesticide
Product
Application for an Experimental Use
Permit
Application for/Notification of State
Registration of a Pesticide To Meet a
Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data
Gap Procedures
Pesticide Registration Maintenance Fee
Filing
Certification of Attempt to Enter into an
Agreement with other Registrants for
Development of Data
http://www.epa.gov/opprd001/forms/8570-l.pdf.
http://www.epa.gov/opprd001/forms/8570-4.pdf.
http://www.epa.gov/opprd001/forms/8570-5.pdf.
http://www.epa. gov/opprdOO l/forms/8570- 1 7.pdf.
http://www.epa.gov/opprd001/forms/8570-25.pdf.
http://www.epa.gov/opprd001/forms/8570-27.pdf.
http://www.epa.gov/opprd001/forms/8570-28.pdf.
http://www.epa.gov/opprd001/forms/8570-30.pdf.
http://www.epa.gov/opprd001/forms/8570-32.pdf.
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8570-34
8570-35
8570-36
8570-37
Certification with Respect to Citations
of Data (in PR Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical
Properties (in PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (in PR
Notice 98-1)
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-l .pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-l .pdf.
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Pesticide Registration Kit www.epa.gov/pesticides/registrationkit/.
Dear Registrant:
For your convenience, we have assembled an online registration kit which contains the following
pertinent forms and information needed to register a pesticide product with the U.S. Environmental
Protection Agency's Office of Pesticide Programs (OPP):
1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug
and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act (FQPA) of 1996.
2. Pesticide Registration (PR) Notices
a 83-3 Label Improvement Program—Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation Systems
(Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This document is
in PDF format and requires the Acrobat reader.)
Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR_Notices.
3. Pesticide Product Registration Application Forms (These forms are in PDF format and will
require the Acrobat reader.)
a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
4. General Pesticide Information (Some of these forms are in PDF format and will require the
Acrobat reader.)
a. Registration Division Personnel Contact List
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Biopesticides and Pollution Prevention Division (BPPD) Contacts
Antimicrobials Division Organizational Structure/Contact List
c. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF
format)
d. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF format)
e. 40 CFR Part 158, Data Requirements for Registration (PDF format)
f 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985)
Before submitting your application for registration, you may wish to consult some additional sources
of information..
These include
1. The Office of Pesticide Programs' Web Site
2. The booklet "General Information on Applying for Registration of Pesticides in the United
States", PB92-221811, available through the National Technical Information Service (NTIS)the
following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000. Please note that EPA is currently in the
process of updating this booklet to reflect the changes in the registration program resulting from the
passage of the FQPA and the reorganization of the Office of Pesticide Programs. We anticipate that
this publication will become available during the Fall of 1998.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue University's Center for
Environmental and Regulatory Information Systems. This service does charge a fee for
subscriptions and custom searches. You can contact NPIRS by telephone at (765) 494-6614
or through their Web site.
4. The National Pesticide Telecommunications Network (NPTN) can provide information on active
ingredients, uses, toxicology, and chemistry of pesticides. You can contact NPTN by telephone
at 1-800-858-7378 or through their Web site: ace.orst.edu/info/nptn.
The Agency will return a notice of receipt of an application for registration or amended registration,
experimental use permit, or amendment to a petition if the applicant or petitioner encloses with the
submission a stamped, self-addressed postcard. The postcard must contain the following entries to be
completed by OPP:
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Date of receipt
EPA identifying number
Product Manager assignment
Other identifying information may be included by the applicant to link the acknowledgment of receipt
to the specific application submitted. EPA will stamp the date of receipt and provide the EPA
identifying File Symbol or petition number for the new submission. The identifying number should be
used whenever you contact the Agency concerning an application for registration, experimental use
permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded and
assigned to your company, please include a list of all synonyms, common and trade names, company
experimental codes, and other names which identify the chemical (including "blind" codes used when
a sample was submitted for testing by commercial or academic facilities). Please provide a CAS number
if one has been assigned.
Documents Associated with this RED
The following documents are part of the Administrative Record for this RED document and may
included in the EPA's Office of Pesticide Programs Public Docket. Copies of these documents are not
available electronically, but may be obtained by contacting the person listed on the respective Chemical
Status Sheet.
1. Detailed Label Usage Information System (LUIS) Report.
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