REREGISTRATION ELIGIBILITY DECISION
FRONAMIDE
IISTA
CASE 0082
ENV1KONMENTALPROTECTION AGENCY
OITICE Of PESTICIDE PROGRAMS
SPECIAL REVIEW AND KEKEGISTRATION DIVISION
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
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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 proiiamide
which includes the active ingredient Rfl:dtl.«lJMmethylpropynyl)-3 t5-dichlorobeiizaimde1 or
3^-dichIoro-N (l.l-dimethvl-2-propynyl) benzamide. The enclosed Reregistration
Eligibility Decision (RED) contains the Agency's evaluation of the data base of this
chemicalfs], its conclusions of the potential human health and environmental risks of the
current product uses, and its decisions and conditions under which these uses and products
will be eligible for reregistration. The RED includes the data and labeling requirements for
products for reregistration. It may also include requirements for additional data (generic) on
the active ingredient to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED". This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses are due 90 days from
the date of this letter. The second set of required responses are due 8 months from the
date of this letter. Complete and timely responses will avoid the Agency taking the
enforcement action of suspension against your products.
If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Special Review and Reregistration Division representative
Franklin Gee at (703) 308-8008. Address any questions on required generic data to the
Special Review and Reregistration Division representative Karen Jones at (703) 308-8047,
Sincerely yours,
Daniel M. Barolo, Director
Special Review and
Reregistration Division
Enclosures
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STJMMARY QF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRAHQN ELIGIBILrrY DECISION (RED)
1. DATA CALL-IN (PCD OR "90-DAY RESPOMSEll-If generic data are required for
reregistration, a DCI letter will be enclosed describing such data. If product specific data
are required, another DCI letter will be enclosed listing such requirements. Complete the
two response forms provided with each DCI letter by following the instructions contained in
each DCI, You must submit the response forms for each product and for each DCI
within 90 days of the date you receive the RED; otherwise, your product may be
suspended.
2. TIME EXTENSIONS AND DATA WAIVER REQTJESTS-No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only
with respect to actual data submissions. Requests for data waivers must be submitted as part
of the 90-day response. Requests for time extensions should be submitted in the 90-day
response, but certainly no later than the 8-month response date. All data waiver and time
extension requests must be accompanied by a full justification. All waivers and time
extensions must be granted by EPA in order to go into effect.
3. APPLICATION FOR REREGISTRAHON OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the RED issuance
date (tbe cover letter date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original
application form. Mark it "Application for Reregistration." Send your Application for
Reregistration (along with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current
regulations and requirements. Only make labeling changes which are required by the RED
and current regulations (40 CFR 156.10) and policies. Submit any other amendments (such
as formulation changes, or labeling changes not related to reregistration) separately. You
may delete uses which the RED says are ineligible for reregistration. For further labeling
guidance, refer 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; 703-487-4650).
c. Generic or Product Specific Data. Submit all data in a format which complies
with PR Notice 86-5, and/or submit citations of data already submitted and give the EPA
identifier (MRID) numbers. Before citing these studies, you must make sure that they meet
the Agency's acceptance criteria (attached to the DCI),
d. Two copies of the Confidential Statement of Formula (CSD for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P,R, Notice 91-2 by declaring the active Ingredient as the nominal
concentration. You have two options for submitting a CSF: (1) accept the standard
certified limits (see 40 CFR §158.175) or (2) provide certified limits that are supported by
the analysis of five batches. If you choose the second option, you must submit or cite the
data for the five batches along with a certification statement as described in 40 CFR
§158.175(e). A copy of the CSF is enclosed; follow the instructions on its back.
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e. Certification With Respect to Citation of Data. Complete and sign this form
(EPA form 8570-29) for each product. Cite-all is not a valid option for reregistration,
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 ALL PCI RESPONSES f90*PAY) AND APPLICATIONS FOR
REREGISTRATION rS-MONTH RESPONSES)
Bv ILS. Mail:
Document Processing Desk (RED-SRRD-PRB-0082)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By
Document Processing Desk (RED-SRRD-FRB-0082)
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 ^registration determination within 14 months after the RED
has been issued.
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TABLE OF CONTENTS
PRONAMIDE REREGISTRATJON ELIGIBILITY DECISION TEAM ......... i
GLOSSARY OF TERMS AND ABBREVIATIONS ii
EXECUTIVE SUMMARY iv
I. INTRODUCTION 1
IL CASE OVERVIEW 2
A. Chemical Overview . 2
B. Use Profile . . 2
C. Estimated Usage of Pesticide 4
D. Data Requirements 5
E. Regulatory History 6
HI. SCIENCE ASSESSMENT . ' 7
A. Physical Chemistry Assessment 7
1. Identification of the Active Ingredient 7
2. Other Product Chemistry Issues 7
B. Human Health Assessment , 8
1. Toxicology Assessment 8
a. Acute Toxkfty 8
b. Subchronic Toxkity 9
c. Chronic toxicity , 10
d, Carcinogenicity 10
e. Developmental Toxicity 14
f. Reproductive Toxicity 15
g. Mutagenicity 15
h. Metabolism . , 16
!. Dermal Absorption 17
j. Other Toxicity Considerations 18
k. Reference Dose 18
2. Exposure Assessment 19
a. Dietary Exposure 19
b, Occupational and Residential , 21
3. Risk Assessment 25
a. Dietary 25
b. Occupational and Residential 28
C. Environmental Assessment 29
1, Environmental Fate 29
a. Environmental Chemistry, Fate and Transport ...... 29
b. Environmental Fate Assessment 33
2. Ecological Effects 34
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a. Ecological Hazard , 34
(1) Effects to Non-Target Birds 34
(2) Effects to Other Non-Target Terrestrial
Organisms 35
(3) Effects to Non-Target Rsh 35
(4) Effects to Non-Target Aquatic Invertebrates .... 35
(5) Effects to Non-Target Estuarine and Marine
Organisms 36
(6) Effects to Non-Target Insects (Beneficial
Insects) 36
(7) Effects to Non-Target Plants 37
b. Ecological Effects Risk Assessment 38
(1) Non-Endangered Species 38
(2) Endangered Species 39
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 40
A. Determination of Eligibility 40
I. Eligibility Decision 41
2. Eligible and Ineligible Uses 41
B. Regulatory Position 41
1. Tolerance Reassessment 41
2. Restricted Use Classification 45
3. Endangered/Threatened Species Statement . 46
4. Labeling Rationale 46
a. Postapplication/Reentry Requirements 46
b. Personal Protective Equipment (PFE) Requirements ... 47
V. ACTIONS REQUIRED BY REGISTRANTS 47
A. Manufacturing-Use Products 47
1. Additional Generic Data Requirements 47
2. Labeling Requirements for Manufacturing-Use Products 48
B. End-Use Products , 48
1. Additional Product-Specific Data Requirements 48
2. Labeling Requirements for End-Use Products 49
a. Compliance with the Worker Protection Standard .... 49
b. Entry Restrictions; Labeling . 49
c. Personal Protective Equipment Requirements;
Fueling 50
d. Other labeling Requirements 51
C. Existing Stocks 52
VL APPENDICES . 53
APPENDIX A, Table of Use Patterns Subject to Reregistratioo 55
APPENDIX B. Table of the Generic Data Requirements and Studies Used
to Make the Registration Decision 75
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APPENDIX C. Citations Considered to be Fart of the Data Base
Supporting the Reregistration of Pronamide 91
APPENDIX D. IM of Available Related Documents 107
APPENDIX £. Combined Generic and Product Specific Data Call-In ..... 115
Attachment 1. Chemical Status Sheets . 137
Attachment 2. Generic and Product Specific Data Call-in Response
Forms (Form A inserts) and Instructions 143
Attachment 3. Generic and Product Specific Requirement Status
and Registrant's Response Forms (Form B inserts) and
Instructions , 151
Attachment 4, EPA Grouping of End-Use Products for Meeting
Data Requirements for Reregistration 177
Attachment 5. EPA Acceptance Criteria , . 181
Attachment 6. List of All Registrants Sent This Data Call-In (insert)
Notice .195
Attachment 7. Cost Share and Data Compensation Forms and
Confidential Statement of Formula Form with Instructions . . . 197
APPENDIX F. FACT SHEET 207
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PRQNAMIDE MEREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Division
Sieve Jarboe Biological Analysis Branch
James Saulmon Biological Analysis Branch
Eric Maurer Economic Analysis Branch
Environmental Fate and Effects Division
Mike Davy Ecological Effects Branch
Larry Liu Environmental Fate and Groundwater Branch
Kathy Monk Science Analysis and Coordination Staff
Health Effects Division
Laura Moms Occupational and Residential Exposure Branch
Leung Cheng Reregistration Support Chemistry Branch
Nguyen Thoa Toxicology Branch I and Chemical Coordination Branch
John Bariun Science Analysis Branch
Registration Division
Wesley Allen Fungicide-Herbicide Branch
Joanne Hayes Registration Support Branch
Special Review and Reregistration Division
Karen Jones Reregistration Branch
Carol Stangel Policy, Planning and Operations Branch
Policy and Special JSrojects Section
Jean Frane Special Review and Reregistration Section
Office of General Counsel
Philip Ross
Office of Compliance Monitoring
Beverly Updike Pesticides Enforcement Policy Branch
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GLOSSARY OF TERMS AND ABBREVIATIONS
a.i. Active Ingredient
CAS Chemical Abstracts Service
CSF Confidential Statement of Formula
EEC Estimated Environmental Concentration. The estimated pesticide concentration
in an environment, such as a terrestrial ecosystem,
EP End-Use Product
EPA U.S. Environmental Protection Agency
FDA Food and Drag Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
GRAS Generally Recognized As Safe as designated by FDA
HDT Highest Dose Tested
LCj0 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 ppin.
Median Lethal Dose, A statistically derived single dose that can be expected
to cause death in 50% of the test animals when administered by the route
indicated (oral, dermal, inhalation). It is expressed as a weight of substance
per unit weight of animal, e.g., mg/kg.
Lethal Dose-low, Lowest Dose at which lethality occurs
LEL Lowest Effect Level
LOEL Lowest Observed Effect Level
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
LD
'50
LD,
la
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GLOSSARY OF TERMS AND ABBREVIATIONS
MOB Margin Of Exposure (PAD)
MRID Master Record Identification (number). EPA's system of recording and
tracking studies submitted.
N/A Not Applicable
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
ppm Parts Per Million
Q"i The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer
Kisk Model
RED Reregistration Eligibility Decision
RfD Reference Dose
RS Registration Standard
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TC Toxic Concentration. The dose at which a substance produces a toxic effect.
TGAI Technical Grade Active Ingredient.
TMRC Theoretical Maximum Residue Contribution.
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EXECUTIVE SUMMARY
Reregistration Decision
The Agency has determined that all of the uses of pronamide, as currently registered,
with the exception of the late season use (1-day PHI) on amchokes and residential lawn and
turf uses, will not cause unreasonable risk to humans. However, pronamide may pose
adverse effects to terrestrial plants and aquatic plants may also be at risk. All of the uses of
pronamide, except for the broadcast application on residential lawns and turf and the late
season use on artichokes, are eigible for reregistration. Due to a lack of exposure
information, a reregistration eligibility decision on the granular and wettable powder
formulations applied by broadcast application for use on residential lawn and turf cannot be
made at this time. Postapplication/reentry data on foliar dislodgeable dissipation and dermal
passive dosiinetry studies are required before a regulatory decision can be made on the
residential lawn and turf uses. Similarly, due to a lack of residue data, a regulatory decision
cannot be made at this time on the late season use on artichokes. The amendment of
product labels deleting the late season use on artichokes or submission of replacement
cropfield trial data is required.
Background
Pronamide is a selective, preemergence and/or postemergence herbicide registered for
the control of grassy and broadleaf weeds on terrestrial food crops [artichoke, blackberry,
blueberry, boysenberry, cherry, endive (escarole), lettuce, nectarine, peach, pear, plum,
prune, raspberry (black,red), rhubarb]; terrestrial food and feed crops (agricultural
fallow/idleland, apple, grapes, peas, sugar beet); terrestrial feed crops (alfalfa, clover,
sainfoin, trefoil, vetch); terrestrial non-food crop (christmas tree plantations, golf course turf,
ornamental herbaceous plants, recreation area lawns, pyrethrum) and terrestrial non-food
crop and outdoor residential (ornamental and/or shade trees, ornamental woody shrubs and
vines). The registered formulations of pronamide include a wettable powder (50% a.i.) and
a granular (0.57-1% a.i.). There is a registered formulation intermediate (50% a.i,) product
and technical grade (92% a.i.) product. Maximum application rates range from 0.25 to 4 Ib
a.i./A. Pronamide may be applied using conventional ground spray equipment, soil
incorporation, or aircraft.
Pronamide was initially registered as a pesticide in 1972. In 1977 the Agency
initiated a Special Review of pronamide based on a Medical College of Virginia (MCV) 18-
month mouse careinogenicity study which indicated that mice given diets containing 0, 1000,
or 2000 ppm pronamide showed a treatment-related increase in hepatocelMar carcinomas.
The incidence of tumors was observed at 18 months in male mice only. At that time, this
study provided the only evidence that pronamide might possess human carcinogenic potential.
The Special Review was completed in 1979, and the final decision included the following; 1)
restricted use classification for 50% wettable powder end-use products; 2) use of protective
clothing during mixing and application of wettable powder formulations; 3) implementation
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of water-soluble packaging for wettable powder formulations; and 4) tolerance on lettuce
lowered from 2 ppm to 1 ppm to reduce dietary exposure. In April 1986, a Registration
Standard was issued for pronamide (NTIS #PB87-103735), The Registration Standard
summarized available data supporting the reregistration of products containing pronamide
used for control of grassy and broadleaf weeds on lettuce, endive, alfalfa, rhubarb, pome and
stone fruits, artichokes, berries, legumes, lawns and turf (commercial and residential), fallow
land, woody ornamentals, nursery stock, and Christmas tree plantations. The Registration
Standard also required additional product chemistry, toxicology, environmental fate, and
residue chemistry data. The Agency has now completed its review of the pronamide target
data base including data submitted in response to the 1986 Registration Standard.
SupportirigJRationales for Reregistration Decision
Pronamide is in Category in for acute dermal toxicity. The Agency has classified
Pronamide as a Group B2 (Probable Human) Carcinogen based on uncommon benign
testicular interstitial cell and thyroid tumors in rats and liver carcinomas in mice. The
Agency has also determined that dietary exposure to pronamide may be associated with an
excess carcinogenic risk of 5 x 10~7 to the general population.
Based on the known toxicological concerns for pronamide, including its Group B2
classification, the Agency is requiring Personal Protective Equipment (PPE) for applicators
and other handlers, as well as early entry workers, in accordance with the PPE level required
in the Worker Protection Standard (WPS). The Agency is also requiring a Restricted Entry
Interval (RET) of 24 hours for all WPS sites as a conservative measure to mitigate risk to
workers entering treated areas after application.
The Reference Dose (RfD) is 0.08 mg/kg/day based on the chronic/carcinogenicity
feeding study in rat, with respective male and female NOELs of 8.46 and 10.69 mg/kg/day
and an uncertainty factor of 100. The percent of RfD utilized is 0.039%. A reassessment
of tolerances is also included in this document.
There is a potential for postapplication dermal exposure to foliar dislodgeable residues
and soil residues from use of both granular and wettable powder formulations. The Agency
has determined that a reregistration decision on the broadcast use of pronamide on residential
lawns cannot be made at this time. It was not feasible for the Agency to estimate the risk to
homeowners and children from the broadcast treatment of pronamide granular and wettable
powder formulations on residential lawns because of the numerous uncertainties in potential
exposure levels. Regulatory decisions relating to postapplication reentry will be developed
after the foliar dislodgeable dissipation and dermal passive dosimetry studies required to
support the residential lawn uses of pronamide are submitted and reviewed. However, the
broadcast treatment of pronamide for commercial turf is eligible for reregistration. Foliar
dislodgeable dissipation and dermal passive dosimetry studies are required to confirm the
postapplication reentry assessment for commercial turf uses. The Agency has imposed a
restricted entry interval for commercial turf. The foliar dislodgeable dissipation and dermal
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passive dosimetry studies will confirm this interval. Similarly, postapplication reentry data
are required for pronamide use on lettuce because there is the potential for significant hand
contact following the treatment of lettuce. These data are considered confirmatory for the
lettuce use.
Because there is also a potential for mixer/loader/applicator (handlers) exposure to
pronamide sprays and dusts through dermal and inhalation routes, following ground boom,
aerial, and hand-spray applications for the wettable powder formulation and no adequate
mixer/loader/applicator exposure data for the granular formulation of pronamide are
currently available. Potential exposure from granular formulation is expected to be less than
that from wettable powder formulations according to the exposure assessment in the 1986
Pronamide Registration Standard, The Agency is requiring confirmatory
mixer/loader/applicator data for the granular formulation of pronamide. Data relating to
estimation of dermal and inhalation exposure at outdoor sites are required to confirm the
mixer/loader/applieator exposure for the granular formulation use on commercial and
residential turf.
Pronamide is practically non-toxic to birds and mammals. It is moderately toxic to
freshwater invertebrates and slightly toxic to freshwater fish. Currently, there are no data
available for estuarine organisms. Based on the low toxicity of pronamide to freshwater fish
and moderate toxicity to freshwater invertebrates, the Agency anticipates that additional data
will confirm that pronamide does not represent a major problem to aquatic organisms.
Estuarine data are required to confirm this assessment. The Agency beEeves that given the
persistence of pronamide in water, a potential chronic exposure to aquatic invertebrates is
possible. Therefore, the Agency is requiring the aquatic invertebrate life cycle study to
assess this potential risk. Potential risks to endangered terrestrial plants will be addressed
through the evaluation of additional data. When the Agency completes its Endangered
Species program, additional precautionary labeling may be required to mitigate the risk to
terrestrial plants. Also, aquatic plants may be at risk, but there are insufficient phytotoxicity
data to ascertain the risk. Based on the data for algae, the risks to aquatic plants are not
likely to be unreasonable; however, these risks will be further assessed when additional
phytotoxicity data (which are not part of the target database for this reregistration review) on
aquatic plants are submitted and evaluated.
Pronamide is stable to hydrolysis, to photolysis in water and on soil, and to
aerobic/anaerobic microbial degradation in soil. This chemical has a relatively low vapor
pressure and it is relatively mobile in soil. Therefore, pronamide is expected to be relatively
persistent and mobile in the field and leaching appears to be the major route of dissipation,
Although results from an unacceptable field dissipation study indicate that pronamide is
neither persistent or mobile under field conditions, the Agency cannot rely on this data since
it was generated by Craven Laboratories. The Agency is requiring a new field dissipation
study to confirm the findings from this study. The new study will provide useful information
for a better understanding of pronamide dissipation through the combined fate processes (i.e.,
degradation, metabolism, adsorption, leaching, volatilization, runoff) in the field. The
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Agency is also requiring field rotational crop and spray drift studies which will provide
additional information for the understanding of the fete of pronamide in the environment.
A Confidential Statement of Formula for the 92% technical pronamide is required for
product identity. Similarly, a confirmatory independent lab validation for the residue
analytical method (plant/animal) study is required. For FDA enforcement monitoring
purposes, the Agency is requiring that representative plant and animal tissue samples bearing
metabolites of pronamide be subjected to analysis by FDA multi-residue protocols C, D, and
E from PAM Vol. I,
In addition, some of the existing residue data were generated by Craven Laboratories.
The Agency does not consider Craven-generated data to be reliable or adequate to support
continued registration or tolerance levels for the pesticide uses founded upon these data.
Therefore, the Agency has determined that some of these data must be replaced. Storage
stability data on alfalfa, apples, and lettuce were generated by Craven Laboratories and no
other storage stability data for other crops are available. The Agency will extrapolate and
apply storage stability data on poultry Ever to ruminants and plants; based on the storage
stability data on poultry, residues of pronamide and its metabolites are assumed to be stable
in plant and animal commodities for up to 34 months. Storage stability data on milk, lettuce,
apples, plums, grapes, and alfalfa, and the processed commodities of apples, grapes, and
plums are required to confirm this assessment.
Furthermore, based on the available data, the Agency concluded that residues of
pronamide are not likely to concentrate significantly in processed commodities of these crops,
and no food or feed additive tolerances are currently required. The Agency is requiring data
on the processed commodities of apples, grapes, plums to confirm this assessment.
Because the late season use of pronamide on artichokes is based on data generated by
Craven Laboratories, a reregistration eligibility decision for this use cannot be made at this
time. Registrants are required to amend their labels by deleting the late season use on
artichofces or submit the required replacement cropfield trial data. Residue data on alfalfa
seed were generated by Craven Laboratories; therefore, confirmatory residue data are
required. However, tolerances which exist on alfalfa forage will support the alfalfa seed use
until these data are generated. Likewise, the tolerance for dried winter peas was established
using data generated by Craven Laboratories and confirmatory residue data are required.
Alternate data from Europe are available to support the tolerance on dried winter peas until
the required data are generated.
In summary, the Agency is requiring that additional confirmatory data be submitted.
These data include the following:
Product Identity - Confidential Statement of Formula for 92% Technical
Aquatic Invertebrate Life Cycle - required for use on turf, hay, clover, alfalfa,
and pasture use sites
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Estuarine and Marine Organisms (Mollusc and Shrimp) - required for use on turf,
hay, clover, alfalfa, and pasture use sites
Terrestrial Field Dissipation - required for all use sites
Field Rotational Crop - required for lettuce and fallowland use sites
Droplet Size Spectrum and Drift Field Evaluation - required because of aerial
application to lettuce, artichoke, endive, Xmas tree plantations and fallowland
Foliar Dislodgeable Dissipation - required for commercial turf and lettuce
Dermal Passive Dosimetry - required for commercial turf and lettuce
Estimation of Dermal/Inhalation Exposure at Outdoor Sites - required for granular
formulation use on commercial and residential turf
Residue Analytical Method - plant/animal (Independent Lab Validation)
Storage Stability - required for milk, lettuce, apples, plums, grapes, and alfialfa and
the processed commodities of apples, grapes, and plums
Magnitude of Residue - Plants (Alfalfa Seed and Dried Winter Peas)
Processed Food - required for apples, grapes, plums
Certain data, which are not part of the target database for pronamide, are required.
These data include:
Seed Germination/Seedling Emergence
Aquatic Plant Growth
Accordingly, the Agency has determined that only the products containing pronamide
as the sole active ingredient for the uses declared eligible for reregistration will be
reregistered when acceptable labeling and product specific data are submitted and/or cited.
Before reregistering each product, the Agency is requiring that product specific data be
submitted by the registrants within eight months of the issuance of this document.
Additionally, in order to remain in compliance with FIFRA, it is the Agency's position that
revised labeling be submitted by the registrants within that same time period. After
reviewing these data and revised labels, the Agency will determine whether the conditions
and requirements of FIFRA 3(c)(5) have been met for the reregistration of these products.
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L INTRODUCTION
fa 1988, the Federal Insecticide, Fungicide, and Rodentieide Act (FIFRA) was
amended to accelerate the reregisiration of products with active ingredients registered prior to
November 1, 1984. The amended Act provides a schedule for the reregistration process to be
completed in nine years. There are five phases to the reregistration process. The first four
phases of the process focus on identification of data requirements to support the reregistration
of an active ingredient and the generation and submission of data to fulfill the requirements.
The fifth phase is a review by the U.S. Environmental Protection Agency (referred to as "the
Agency") of all data submitted to support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for reregistration" before
calling in data on products and either reregistering products or taking "other appropriate
regulatory action." Thus, reregistration involves a thorough review of the scientific data base
underlying a pesticide's registration. The purpose of the Agency's review is to reassess the
potential hazards arising from the currently registered uses of the pesticide; to determine the
need for additional data on health and environmental effects; and to determine whether the
pesticide meets the "no unreasonable adverse effects" criterion of FIFRA.
This document presents the Agency's decision regarding the reregistration eligibility
of the registered uses of pronamide as of (insert date). The document consists of six
sections. Section I is the introduction. Section n describes pronamide, its uses, data
requirements and regulatory history. Section in discusses the human health and
environmental assessment based on the data available to the Agency. Section IV presents the
reregistration decision for pronamide . Section V discusses the reregistration requirements for
pronamide. Finally, Section VI is the Appendices which support this Reregistration Eligibility
Decision document. Additional details concerning the Agency's review of applicable data are
available on request.1
'EPA's reviews of data on the gel of registered uses considered for EPA's analysis may be obtained from
the OPP PuWic Docket, Field Operations Division (H7S06Q, Office of Pesticide Programs, EPA, Washington,
DC 20460.
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H. CASE OVERVIEW
A, Chemical Overview
The following active ingredient is covered by this Meregistration Eligibility
Decision document:
» Common Name: Pronamide
• Chemical Name: [N-(l ,l-Dimethylpropynyl)-3,5-
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Terrestrial Food 4-_ JPeed Crop: agricultural fallow/idleland,
apple, grapes, peas.
Terrestrial Feed Crop: alfalfa, clover, sainfoin, trefoil, vetch.
Terrestrial Non-Food Crop: Christmas tree plantations, golf
course turf, ornamental herbaceous plants, recreation area
lawns, pyrethrum, sugar beet grown for seed.
Terrestrial Non-Food Crop ± Outdoor Residential: ornamental
and/or shade trees, ornamental woody shrubs and vines.
Target Pests: (grasses: barley, foxtail barley, barnyardgrass*, marsh
bentgrass, annual bluegrass, Kentucky bluegrass,
[perennial bluegrass], downy brome, eheatgrass,
canarygrass, large crabgrass, oat, wild oat, foxtail,
yellow foxtail, goosegrass, lovegrass, orchardgrass, fall
panicum, quackgrass, rye, Italian ryegrass, perennial
ryegrass, wheat,
Broadleaf weeds: carpetweed*, common chickweed,
mouseear chickweed, nettleaf goosefoot, henbit,
knotweed, common lambsquarters, cypressvine
morningglory, tall morningglory, wild mustard*, nettle,
burning nettle, stinging nettle, nightshade, black
nightshade, hairy nightshade*, redroot pigweed*,
common purslane, London rocket*, shepherdspurse*,
smartweed, pale smartweed, red sorrel, tomato.
[* pest claimed to be suppressed on at least one of the
labels for pronamide]
Formulation Types Registered:
Granular - 0.57 to 1.0 %
Wettable powder - 50.0 %
Formulation Intermediate - 50.0%
Technical grade - 92.0%
Method and Rates of Application:
Granular - Rates for golf course turf include 1.5 Ib AI/A applied (equipment
not on label) in the fall or late winter. Use sites include: commercial areas
(such as golf courses and athletic fields) and residential lawns.
-------
Wettable Powder: Wettable powder formulation is registered for all
pronamide use sites.
—One of three rates for lettuce is 6 Ib AI/A allowed by SLNs (MI880004 and
OH88001); remaining rates for lettuce are 1.5 Ib AI/A and 2 Ib AI/A.
—Rates for apples are from 2 to 4 Ib AI/A applied by band at nonbearing or at
postharvest via low pressure ground equipment; or by directed spray at
nonbearing or postharvest via low pressure ground equipment.
—Rate for blackberries is 3 Ib AI/A applied by band in the fall or winter via
low pressure ground equipment; or appBed as a low volume (concentrate) in
the fall or winter via low pressure ground equipment.
—Rate for agricultural fallow/idleland is 0.5 Ib AI/A applied as a broadcast in
September via aircraft, ground, or low pressure ground equipment; or in
December via aircraft, ground, or low pressure ground equipment.
Current Limitations on Use Practices:
For all formulations: Do not apply through any type of irrigation system.
Moisture is required after application.
C. Estimated Usage of Pesticide
This section summarizes the best estimates available for the pesticide uses of
pronamide. These estimates are derived from a variety of published and proprietary
sources available to the Agency. The data, reported on an aggregate and site (crop)
basis, reflect annual fluctuations in use patterns as well as the variability in using data
from various information sources.
The table below summarizes the pesticide's use by site.
Percent of Various U.S. Crops Treated with Pronamide, 1989 - 1991
Apple
480.2
<1
<1
<1
Alfalfa
63,254.0
15-28
<1
10-20
Artichoke
Blackberry
11.8
6.7
1-2
<1 -1
8-17
2-
-------
:^?Mf?^Si|i^Sp!iKSf
•;^y^f"\i::i$m?^KK
<1
<1
<1
3- <5
<1 - 1
<1 - 1
75 - 180
-------
E. Regulator} History
Pronamide was registered in the United States in 1972 for use as a herbicide to
control grassy and broadleaf weeds on field and vegetable, and orchard crops, forage and
fodder, fallow land, woody ornamentals, nursery stock, and Christmas tree plantations.
In 1977, a RPAR (Rebuttable Presumption Against Reregistration or Special Review) of
pronamide was initiated on the basis of a Medical College of Virginia (MCV) 18-month
mouse carcinogenicity study which indicated that mice given diets containing 0, 1000,
or 2000 ppm pronamide showed a treatment-related increase in hepatocellular
carcinomas. The incidence of tumors was observed at 18 months in male mice only.
At that time, this study provided the only evidence that pronamide might possess human
carcinogenic potential. After reviewing all the available information, the Agency
determined that the cancer risk presumption had not been rebutted, and that the uses of
pronamide posed unacceptable riski of cancer to certain exposed groups. The Agency
also reviewed information relating to benefits of these uses, and after considering risks
in relation to benefits, determined that these risks could be reduced by modifying the
terms and conditions of registration for some uses. The RPAR review was completed
in 1979, and the final decision included the following;
1) Restricted use classification for 50% wettable powder end-use
products.
2) Use of protective clothing during mixing and application of
wettable powder formulations.
3) Implementation of water-soluble packaging for wettable powder
formulations.
4) Tolerance on lettuce lowered from 2 ppm to 1 ppm to reduce
dietary exposure.
A Registration Standard for pronamide was issued in April 1986 in which the
Agency required data to be submitted to support the existing uses of the pesticide and
determined whether existing data were acceptable and sufficient to satisfy the
requirements. Under the 1986 Registration Standard, registrants were required to
generate data, supply missing data and to replace unacceptable data. A Data Call-In was
issued in 1990 for pronamide requiring additional product chemistry, residue chemistry,
plant protection, and environmental fate data. This Reregistration Eligibility Decision
document reflects a reassessment of all data which were submitted in response to the
Registration Standard and the Data Call-in.
-------
SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
1« Identification of the Active Ingredient
Pronamide [N-(l»l-dimethylpropynyl)-3,5-dichlorobenzamide], a
restricted use pesticide (1979 Special Review), is a systemic herbicide which is
registered for use on a variety of food and feed crops as well as for certain non-
food/non-feed sites. The structural formula for pronamide is:
Empirical Formula:
Molecular Weight:
CAS Registry No.:
Shaughnessy No.:
256,13
23950-58-5
101701
Technical pronamide is a white crystalline solid with a melting point of 155-
156° C and a specific gravity of 0.48 g/cc. The solubility of pronamide in water
at 25° C is 15 ppm. Pronamide is soluble in dimethyl sulfoxide and dimethyl
formamide at 33 ppm; in mesityl oxide, isophorone, methyl ethyl ketone, and
cyclohexanone at 20 ppm; in methanol, isopropanol, and chlorobenzene at 12-15
ppm; in batyl cellosolve, xylene, acetonitrile, and kerosene at 10 ppm; and in
nitrobenzene and ethylene dichloride at 5 ppm.
2. Other Product Chemistry Issues
Products registered for use include a 92% a.i. technical grade manufacturing
product (TGAI; 92%T), a 50% a.i. formulation intermediate (FI), thirteen 50% a.L
wettable powder end-use products, and three granular end-use products (< 1 % a.i.).
The wettable powder end-use products are registered for terrestrial food/feed use and
non-food/non-feed outdoor residential use. The granular end-use products are
registered only for terrestrial non-food residential uses (e.g., ornamental lawns/turf
and recreation area lawns).
-------
The following required product chemistry data, GLf 61-1 Product Identity
(Confidential Statement of Formula (CSF, EPA Form 8570-4)) for the 92%T and
GL# 61-2 Beginning Materials and Manufacturing Processes for the FI must be
submitted.
B. Human Health Assessment
1. Toxicology Assessment
The lexicological data base is adequate and will support reregistratkm,
a. Acute Toxiclty
The acute toxicity data on pronamide technical (92% a.L) are
summarized below:
Acute Toxicity
Oral LD« in rats
> 5000 mg/kg (I)
IV
Dermal LDm in rabbits
> 3160 mg/kg (D*
HI
Inhalation LCa, in rats
>3.2mg/l©
* Unacceptable (test material was administered as a powder cm unmoistened skin) for 92% technical,
however the study performed with the Kerb-50W is acceptable.
(1) Refer to M1ID# 00085505.
(2) Refer to MR1D# 00083663. The inhalation/rat study performed with Kerb-50W is acceptable and
satisfies the tnhalnrinn rat requirement for the pronamide technical.
Acute toxicity studies with pronamide technical oral/rat
(GL# 81-1), dermal/rabbit (GU81-2), inhalation/rat (GL# 81-3), are
considered adequate for regulatory purposes upon consideration of the acute
toxicity studies performed with the Ketb-5QW (MSJD 00083663). The
results of the dermal LD50 in rabbits for the Kert>-50W is a LDSO value
greater than 10 g/kg. Also, the results of the inhalation LC50 in rats for the
Kerb-50W is a LCso value greater than 3.2 mg/L The combined results
observed with pronamide technical and Kerb-50W will satisfy the acute
toxicity data requirement for pronamide technical. An acute dekyed
neurotoxicity study in the hen (GL# 81-7) is not required because
pronamide is not an organophosphate. An acute neurotoxicity screening
battery (GL# 81-8) is not required at this time because there was no
evidence of neurotoxicity in any of the existing studies with pronamide.
-------
b. Subchronic Toxicity
In a 90-day feeding study in rodents, pronamide was administered in
the diet to Sprague Dawley CD rats (10/sex/group) for 13 consecutive
weeks, at concentrations of 0, 50, 150, 450, 1350, or 4050 ppm (0, 2.5,
7.5, 22.5, 67.5, or 202.5 rag/kg/day). A systemic NOEL was established
at 50 ppm (2.5 mg/kg/day), A systemic LOEL was established at 150 ppm
(7.5 mg/kg/day), based on increases in liver weight (absolute and relative)
in both sexes. The high dose (4050 ppm; 202.5 mg/kg/day) caused
decreases in body weight and increases in liver weight in both sexes and
increases in testes weight in males. This study was classified "core
supplementary" because there were no individual data on many parameters
(body weight, feed consumption, hematology, urinalysis, and organ weight),
no clinical observations, and no analysis for test material concentration and
stability. This study did not fully satisfy the lexicological data requirement
for a subchronic feeding study (GL# 82-1) in rodents. (MRID 00085506).
In another 90-day feeding study in rodents, pronamide was
administered in the diet to Crl:CD«lBR rats (10/sex/group) for 13
consecutive weeks, at concentrations of 0, 40, 200, 1000, or 4000 ppm (0,
2.5, 12.3, 60.0, or 254.0 mg/kg in males; 0, 3.1, 15.0, 74.6, or 289.2
mg/kg in females). A systemic NOEL was established at 200 ppm (12.3
mg/kg/day/male; 15.0 mg/kg/day/female). A systemic LOEL was
established at 1000 ppm (60.0 mg/kg/day/male; 74.6 rng/kg/day/female),
based on increased Hver relative weight and incidence of liver
histopathology (centrilobular hypertrophy) in both sexes, decreased body
weight/weight gain and feed consumption in females, and increased blood
cholesterol level in males. At the high dose (4000 ppm; 254.0
mg/kg/day/male; 289.0 mg/kg/day/female) decreases in body weight/weight
gain and feed consumption (without any alteration in feed efficiency) in
both sexes, and increases in liver-related effects [increases in cholesterol
(both sexes), transaminase and alkaline phosphatase (males), triglycerides
(females), liver absolute/relative weights (both sexes), incidence/severity of
liver centrilobular hypertrophy (both sexes)] and in histopathology of the
thyroid (thyroid folJicular hypertrophy in both sexes) and anterior pituitary
(cellular hypertrophy in males) were observed. Based on the results, the
liver, thyroid, and pituitary appear to be the target organs in subchronic
oral intoxication of rats with pronamide. This study has satisfied the
toxicological data requirement for a subchronic feeding study (GL # 82-1)
in rodents (MlID 42669403).
In a 90-day feeding study in non-rodents, beagle dogs (I/sex/group)
were fed diets containing 0, 450, 1350, or 4050 ppm pronamide (0, 11.25,
33.75, or 101.25 mg/kg/day) for 3 months (MRID 00085507), The results
-------
indicated the liver as a possible target organ; serum alkaline phosphatase
and liver (absolute and relative) weight were higher in the single male and
female dogs treated with the high dose than in the respective control dogs.
This study was classified "core supplementary" because the number of
animals used was inadequate. The requirement for a subchronie study in
non-rodent (GL# 82-1) is, however, satisfied by a chronic 1-year feeding
study in dogs (MRIDs 41807601 and 41807602).
c. Chronic toxicity
The required chronic toxicity study in rodents (GL# 83-1) is satisfied
by a chronic/carcinogenicity feeding study in rats (See section ffl.B.d.
Carcinogenicity for details on the results of this study), (MRIDs 41714001
and 41714002)
In a chronic toxicity feeding study in non-rodents, beagle dogs
(6/sex/group) were fed diets containing 0, 300, 875, or 1750 ppm
pronamide (0, 11.9, 33.1, or 67.7 mg/kg/day in males; 0, 11.9, 36.1, or
69.0 mg/kg/day in females) for 52 consecutive weeks. A NOEL was
established at 300 ppm (11.9 mg/kg/day). A LOEL was established at 875
ppm [33.1 mg/kg/day (M); 36.1 mg/kg/day (F)], based on increases in
serum alkaline phosphatase in males and thyroid weight in females, and in
liver pathology in both sexes (increases in liver absolute and relative weight
and in incidence of hepitocyte hypertrophy, granular brown pigmentation,
mononuclear infiltration, and granular brown pigmentation in Kupffer
cells). The high dose additionally caused decreases in body weight/feed
consumption without any alteration in feed efficiency and increases in serum
alkaline phosphatase and gamma glutamyl transferase in both sexes,
increases in serum alanine aminotransferase in females, and increases in
testes relative weight in males. Based on the results, the liver appears to be
a target organ in chronic oral intoxication of dogs with pronamide. This
study has satisfied the lexicological data requirement for a chronic feeding
study (GL f 83-1) in non-rodent (MRIDs 41807601 and 41807602).
d. Carcinogenicity
In a carcinogoiicity feeding study k mice, B6C3F1 mice
(100/sex/group) were fed diets containkg 0, 1000, or 2000 ppm pronamide
(approximately 0, 150, or 300 mg/kg/day) for 18 months. Additional
groups of 25 mice/sex/group were assigned to the 6-month interim
sacrifice. Survival rates (> 90%) were comparable between groups with
no gender differences. A dose-related increase in incidence of
hepatocellular carcinomas (respective rates at 0, 1000, and 2000 ppm were
7/100, 18/100, and 24/99) was observed in male mice sacrificed at 18
10
-------
months. The increases in tumor rates observed at 1000 and 2000 ppm were
both statistically significant by pair-wise comparison with the controls,
Pronamide did not induce hepatocellular carcinomas in female mice
(respective rates at 0, 1000, and 2000 ppm were 0/100, 1/100, and 2/100 at
18 month). The dosing was considered to be adequate based on body
weight gain depressions in high dose females and increases m relative (to
body) weight of the liver at 5:1000 ppm in both sexes. This study has
satisfied the data requirement for a carcinogenicity study (GLI 83-2) in
mice (MMD 00107968).
The results of the above study were confirmed by a special
caicmogenieity feeding study conducted in male mice. In this study male
B6C3F1 mice (63/group) were fed diets containing 0 (control 1), 0 (control
2), 20, 100, 500, or 2500 ppm pronamide (approximately 0, 0, 3, 15, 75,
or 375 mg/kg/day) for 24 months. Additional groups were assigned to
interim sacrifices at 6 months (42 at 0 ppm; 42 at 2500 ppm) and at 15 and
18 months (42/group including controls 1 and 2, and 20, 100, 500, and
2500 ppm groups). Survival rates were >93% for all groups. The results
confirmed that long term exposure (24 months) of male mice to pronamide
was associated with an increased incidence of hepatocellular carcinomas
(respective rates at 0, 0, 20, 100, 500, or 2500 ppm at the 24-month
sacrifice were 5/63, 5/63, 9/63, 12/63, 18/63, and 14/61; positive trend
observed with significant pair-wise comparison with controls at > 100
ppm). Additionally, hepatocellular adenomas were observed (respective
rates at 0, 0, 20, 100, 500, or 2500 ppm at the 24-month sacrifice were
4/63, 6763, 6/63, 7/63, 8/63, and 28/61; positive trend observed with
significant pair-wise comparison with controls at 2500 ppm). There was an
apparent progression from benign to malignant tumors. This special study
provided confirmatory information regarding the carcinogenic effect of
pronamide in mice (MMD No. 00114114).
In a chronic/carcinogenicity feeding study in rats, Crl:CD (SD)BR
rats (60/sex/group) were fed diets containing 0, 40, 200, or 1000 ppm
pronamide (0, 1.73, 8.46, or 42.59 mg/kg/day/male and 0, 2.13, 10.69. or
55.09 mg/kg/day/female) for 24 months. Ten extra animals/sex/dose group
were assigned to be sacrificed after 6 and 12 months of treatment. The
following neoplastic findings were observed; (1) rats treated with the high
dose for 24 months showed an increased incidence of thyroid follicular cell
adenomas (respective rates at 0, 40, 200, and 1000 ppm were 4/68, 2/70,
6/69, and 14/67 for males and 1/59, 2/58, 1/58, and 6/59 for females) and
benign testicular interstitial cell tumors (respective rates at 0, 40, 200, and
1000 ppm were 5/58, 5/60, 3/59, and 15/56 for males), (2) thyroid tumors
were not observed until week 53 for males and week 82 for females and
testicular tumors were not observed until week 67, (3) both increases in
11
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thyroid tumor rate (statistically significant by pair-wise comparison with
controls in males; positive trend for both sexes) and testicular tumor rate
(statistically significant by pair-wise comparison with controls; positive
trend) exceeded historical control ranges, and (4) there was no progression
to carcinomas. The following non-neoplastic findings were observed; (1)
liver pathology in both sexes (centrilobular hypertrophy and eosinqphilic
cell alteration; dose-related; significant pair-wise comparison with controls
at the high dose; observed during both the 1st and second year), (2) thyroid
follicular cell hypertrophy (positive trend in both sexes; significant pair-
wise comparison with controls at the high dose in females; observed during
the first year), and (3) ovarian iertoliform tubular hyperplasia in females
(positive trend with significant pair-wise comparison with controls at the
high dose; observed during the 2nd year). The dosing was considered to be
adequate based on body weight gain depression. Survival rates were
comparable between groups with no gender differences. This study has
satisfied the data requirement for a chronic feeding/carcinogenicity study
(GUs 83-1 and 83-2) in rats (MlIDs 41714001 and 41714002).
Two special studies were conducted to evaluate pronamide's effect on
hormonal balance in support of a threshold mechanism for the induction of
thyroid and testicular neoplasms.
In the first study, a special thyroid function study, male CrUCD
(SD)BR rats were fed diets containing 0, 40, 1000, or 4000 ppm pronamide
(approximately 0, 3, 67, or 279 mg/kg/day) for 4 or 15 weeks.
Reversibility of the thyroid effects was studied by feeding a group of rats
with a diet containing 4000 ppm pronamide for 4 weeks followed by control
diet for 11 weeks. The following findings were observed:
1. Serum T4 was reduced in a dose-related manner both after 4 and
15 weeks, serum TSH was reduced after 4 weeks of treatment with
1000 ppm but not with 4000 ppm, and serum levels of T3 and rT3
were not affected.
2. Incidence of thyroid follicular cell hypertrophy/hyperplasia was
equally increased at 1000 and 4000 ppm (respective incidences at 0,
40, 1000, and 4000 ppm were 2/10, 4/10,10/10, and 10/10 after 4
weeks and 3/10, 5/10, 9/10, and 10/10 after 15 weeks.
3. Hepatic UDP-glucuronosyl transferase activity was increased at
4000 ppm, both after 4 or 15 weeks of treatment (the effect at 1000
ppm was not studied).
12
-------
4. Bile flow, biliary clearance of 12SI-T4 and 125I-T4-glucuronide, and
I2SI bile/plasma ratio were increased at 4000 ppm, both after 4 or 15
weeks of treatment (the effect at 1000 ppm was not studied).
5. The changes in T4, thyroid histology, hepatic UDP-glucuronosyl
transferase activity, and biliary parameters observed after 4 weeks of
treatment with 4000 ppm were either partially or totally reversed after
11 weeks of recovery. This study provided supplemental information
regarding a possible endocrine-related mechanism of action for the
observed thyroid carcinogenic effect of pronamide in rats (MRID
42093401).
In the second study, a special pilot testicular function study, male
Crl:CD (SD)BR rats were fed diets containing 0 or 4000 ppm pronamide
(approximately 0 or 273 mg/kg/day) for 13 weeks. Animals treated with
pronamide showed the following effects: (1) increase in the number of
testicular interstitial cells, (2) increases in serum LH and FSH
unaccompanied by a decrease in serum testosterone, (3) modest increases in
liver weight and liver microsomal protein content, and (4) increases in the
rate of oxidation of testosterone and in activity of the hepatic microsomal
enzymes cytochrome-P450, cytochrome-BS, and NADPH-cytochrome C
reductase (expressed as junol product/whole liver). This study provided
some supplemental information regarding a possible endocrine-related
mechanism of action for the observed testicular carcinogenic effect of
pronamide in rats (MRID 42139601). A 13-week testicular hormonal
study, voluntarily submitted by the registrant, was also reviewed by the
Agency. The information contained in the 13-week testicular hormonal
study did not alter the weight of evidence with respect to the cancer
classification or the use of a unit risk to estimate excess cancer risk to
humans. (MRID No. 42987501)
On September 30, 1992, the OPP Carcinogenicity Peer Review
Committee concluded that 1) the data on thyroid mechanism were
suggestive of a thyroid-pituitary hormonal control mechanism but were not
conclusive, based on the Agency's six criteria for a threshold model for
thyroid carcinogenicity (e.g., there were no dose-related and/or sustained
increases in TSH levels, no dose-related increases in incidence of thyroid
hypectrophy/hyperplasia, and no information on thyroid hormone synthesis
....) and 2) the Agency currently has no policy regarding a threshold model
for testicular neoplasm, but, even if a testes-pituitary hormonal control
mechanism exists for the testes, the evidence that pronamide-induced
testicular tumors in the rat may be related to a disruption in the testes-
pituitary balance is very limited (e.g., there was no clear increase in
interstitial cell hypertrophy/hyperplasia, no alteration in testosterone level,
13
-------
no information on testicular hormone synthesis and reversibility of testicular
lesions). Consequently, the Peer Review Committee ^classified pronamide
as a Group 62 carcinogen - a probable human carcinogen with inadequate
evidence in humans (a change from the previous classification as a Group C
carcinogen - possible human carcinogen, based on carcinogenic effect on
the liver of mice; 1986 Registration Standard). The classification was based
on the findings of two types of tumors in the rat (uncommon benign
testicular interstitial cell tumors and thyroid follicular cell adenomas) and
one type (liver carcinomas) in the mouse. Hie estimated Qi* is 1.54 x 10"2
(mg/kg/day)-1 based on the 18-month mouse carcinogenicity study [a
3.75% reduction from the previously estimated value of 1.63 x 10 2
(mg/kg/day)-1; 1986 Registration Standard].
e. Developmental Toxicity
In a developmental toxicity study in rabbits, artificially inseminated 6-
month old New Zealand white rabbits (18/group) were administered 0, 5,
20, or 80 mg/kg/day of pronamide by gavage, during gestation days 1
through 19. The liver appeared to be the target organ. Hie maternal
NOEL was established at 20 mg/kg/day, based upon the recommendations
of the OPP Rfl> Committee which met on January 21, 1993. The maternal
LOEL was established at 80 rng/lqg/day, based on one mortality, 5/16
abortions, body weight loss, and liver histopathology (punctate vacuolation
of hepatocytes, swollen hepatocytes, necrosis, pigmentation of Kupffer
cells, and eoiinophilic hepatocytes). The developmental NOEL was 20
mg/kg/day. The developmental LOEL was 80 mg/kg/day, based on late
resorption (two of the 5 high dose does which aborted each showed one
incidence of late resorption). This study has satisfied the data requirement
for a developmental toxicity study (GL# 83-3) in rabbits (MRID 00148064
and 00148065).
In a developmental toxicity study in rats, groups of 25 mated female
Crl;CD®(SD)BR rats were given pronamide at doses of 0, 5, 20, 80, or 160
mg/kg/day by oral gavage, on gestation days 6 through 15. The only
effects observed were minimal decreases in (1) group mean body weight
(4.6% below control) for the 160 mg/kg/day dose group at day 13 of
gestation and (2) body weight gains (<3% of the absolute body weight) for
the 80 mg/kg/day group (gestation days 6*8) and the 160 mg/kg/day group
(gestation days 6-8 and 8*10). Because of the absence of clinical signs of
toxicity, these minor changes in body weight/weight gain were not
considered adverse maternal effects. The study was classified core
supplementary, based on the absence of maternal toxicity or developmental
toxicity and no explanation for selection of the dose levels tested.
However, this study need not be repeated since the rabbit developmental
14
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toxicity study demonstrated a lower NOEL; the developmental study in rati
was considered adequate for risk assessment purposes (MRJD 41540301).
f. Reproductive Toxicity
In a two-generation reproduction study, Crl:CD*(SD)BR rats
(25/sex/group) were fed diets containing 0, 40, 200, or 1500 ppm
pronamide through two successive generations (approximately 0, 3.0, 15.4,
or 114.0 mg/kg/day/Pl males and 0, 3.2, 16.5, or 127.3 mg/kg/day/P2
males during pre-mating period; group time-weighted average
approximately 0, 4.1, 20.2, and 158.2 mg/kg/day/Pl females and 0, 4.0,
19.8, or 157.4 mg/kg/day/P2 females), with one mating per generation.
No treatment-related mortalities and/or clinical signs were observed in
either parental generations. A NOEL for parental systemic effects was
established at 200 ppm (15.4 mg/kg/day/Pl male; 16.2 mg/kg/day/P2 male;
20.2 mg/kg/day/Pl female; 19.8 mg/kg/day/P2 female). The LOEL was
1500 ppm (114.0 mg/kg/day/Pl male; 127.3 mg/kg/day/P2 male; 158.2
mg/kg/day/Pl female; 157.4 mg/kg/day/P2 female), based on decreased
body weight and food consumption and hi stbpathology of the liver
(centrilobular hypertrophy) arid adrenal (zona glomerulosa cellular
hypertrophy) in both sexes, the thyroid (follicular cell hypertrophy) in
females, and the anterior pituitary (cellular hypertrophy) in males. These
effects were observed in both PI and P2 generations. The reproductive
NOEL was 200 ppm. The reproductive LOEL was 1500 ppm, based on
decreased combined male/female pup weight per litter (Fl pups at birth and
through lactation period; F2 pups at lactation days 14 and 21); pups were
not weighed separately by sex. This study has satisfied the data
requirement for a 2-generafion reproduction toxicity study (GL# 83-4) in
rats (MRID 40334501).
g. Mutagenicity
Results of mutagenicity studies indicate that pronamide does not
appear to be mutagenic. The results of these studies are summarized in the
table below.
Mutagenicity Studies With Pronamide
Gene Mutation/Ames
Forward Gtne Mutation
(CH V79 cells)
::$y$:Sx::-?vi!:^;fe:^:^¥;W^
84-2
84-2
SJiJSss^SfeSliliJilS
.i1:^*;*^:'*-:^! :£;; :2?3^
Negative, with or without metabolic activation
(HDT = 5 mg/plate). (METO 40090602)
Negative, with or without metabolic activation
(HDT = 4Gug/nil). (MRID 40211106)
15
-------
;i:%;i3ill:iisii?s^
^:-'^"«s,*x'x~i: •: '• :*'";'• : '?'" :• :::': '"'•'^t^i^'^^i^:''' '• :«•' ?' •«•£:-: '•'-~^' ''. '''•:'• iv'":' ;":"-' -' :': ': :";' vv ? ! ':• w! sfftofc: *f •'• • '.'-•"- •"••-'"•
'^^m^^^i^^f^^M^^i^^^^^^^MM^s^S'^.
Negative, with or without metabolic in CHO cells
(HOT = 1.5 mg/nd), (MRID 4021110g)
Negative in mouse bone marrow cells
(HOT = 4.94 g/kg by oral gavage).
(MRID 40211105)
Negative in primary hepatocytes of rats
(HDT = 50mg/ml). {MRID 40211107)
h. Metabolism
Two complementary metabolism studies are available. In the first study
(MRID 41801801), single doses (2 or 100 mg/kg) of 14C-pronamide were
administered by oral gavage to male and female Crl:CD®BR rats to study
radioactivity distribution and excretion. The following results were observed:
1. Over a 7-day period, most of the radioactivity administered
(93-103% of dose) was recovered in the urine (40-61% of dose)
and feces (40-60% of dose).
2, Following a low dose (2 mg/kg), urinary and fecal radioactivity
excretion were comparable in males (47% of dose in urine; 46%
in feces). In females, urinary excretion (57% of dose) was higher
than fecal excretion (40% of dose). Absorption of pronamide (as
reflected by urinary excretion of radioactivity) appears to be
slightly higher in females than in males.
3. Following a high dose (100 mg/kg), urinary radioactivity
excretion 05-39% of dose) was lower than fecal excretion (57-
60% of dose) in both sexes, indicating that the absorption process
was likely saturated.
4. Peak plasma radioactivity occurred within 8 hours of dosing,
and the label was detected throughout the body with the highest
concentrations (in decreasing order) in fat, adrenal gland, bone
marrow, thyroid, liver, kidney, and plasma. No sex difference
was apparent in the rate of excretion of the test material. Plasma
half-life (tjo) of a low dose was biphasic [rapid (a) phase = 12.6
hrs (males) and 12.7 hrs (females); slow phase (ff) = 36.6 hrs
(males) and 45.3 hrs (females)], and that of the high dose rats was
monophasic [tw = 24.1 hrs (males) and 24.8 hrs (females)].
16
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5. Very little radioactivity was recovered in tissues (< 0.22% of
dose) and carcasses (< 2.44% of dose) 7 days after dosing.
In the second study (MRID 41922901), a partial characterization of 14C-
pronamide urinary metabolites was conducted, using the samples collected in
the first study. The results indicated that;
1. Very little unchanged pronamide (< 0,5% urine total
radioactivity) was recovered in urine.
2. Twenty metabolites were found but only thirteen (constituting
£ 51.6% of the total radioactivity in urine) were clearly
identified.
The previous two studies combined did not completely satisfy the data
requirement for a metabolism study in rats (GL# 85-1). Additional data
providing a complete characterization of fecal and urinary metabolites were
reviewed and found acceptable in a third study. In this study, (MRID
42858001) identification of the urinary and fecal metabolites of pronamide in
rats given single oral dose (2 or 100 mg/kg) or multiple low doses (20 ppm
a.i. in diet for 14 days) followed by as low dose (2 mg/kg) of 14C-pronamide
was made. The following results were observed:
1, No significant difference in urinary metabolite profile was observed
between sexes or dose. The major urinary metabolites were SS47-70
(3.0-5.9% of the dose) and metabolite 10 (12.7-18.9%). In the urine,
approximately 27 unidentified metabolites were found and none exceeded
3.3% of the dose.
2. Fecal excretion of parent ranged from 9.2-10.9% of the dose for the
low dose and low repeated dose groups and 37.4-40.9% for the high
dose group. In the feces, almost all of the unknowns are under 1 % of
the dose. The registrant postulated metaboEc pathways of the test
compound in rats.
The data from the previous studies (MRIDs 418018001 and 41929901)
when combined with the results from the present study (MEID 42858001),
satisfy the toxicologies! requirement for adequate metabolism studies in rats
(GU 85-1).
i. Dermal Absorption
A dermal absorption study is available (MRIDs 40256701C and
41117201). The following briefly describes the study and results;
17
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1. Rats were dermally exposed for six hours to SOW and 3.3F
formulations at nominal doses of 0,08 or 4,40 mg/cm2.
2. The dermal absorption rates per 6 hours were 19% and 17%
for SOW and 15.1% and 5.4% for 3.3F, respectively.
The study was considered unacceptable because 1) the actual doses
applied to the skin were not determined and 2) there were discrepancies in
recovery for the SOW doses (78% and 122% of nominal doses). However,
another study is not required because based on worst-case assumptions, the
risk appears acceptable.
j. Other Toxicity Considerations
Pronamide appears to be a liver toxicant. Adverse liver-related effects
(increases in liver weight and/or liver-related serum enzymes and/or
histopathology) were consistently observed in every animal species studied,
including the rat (subchronic, chronic, and 2-generation studies), mouse
(carcinogenicity study), rabbit (developmental study), and dog (subchronic and
chronic studies). Pronamide also appears to be a toxicant to several endocrine
organs including the thyroid (in rats; increase in weight and/or histopathology
observed in subchronic, special 13-week thyroid, chronic/carcinogenicity, and
2-generation reproduction studies), testes [in rats (histopathology in
chronic/carcinogenicity study) and dogs (increase in weight in chronic study)],
and pituitary (in rats; histopathology observed in subchronic and 2-generation
reproduction studies). Many chemicals belonging to the class of
organochlorine chemicals are known to produce disruption of the endocrine
system (Hilernan 1993). Pronamide is related to this class of chemicals.
k. Reference Dose
A RfD was established for pronamide at 0.08 mg/kg/day, based on the
chronic/carcinogenicity feeding study in rat, with respective male and female
NOELs of 8.46 and 10.69 mg/kg/day and an uncertainty factor of 100 to
account for inter species extrapolation and intraspecies variability. Critical
effects (observed at 42.59 mg/kg/day/male and 55.09 mg/kg/day/female) were
decreased body weight/body weight gain and increased liver weight, as well
as an increased incidence of hepatic cen.trilob.ular hypertrophy, eosinophilic cell
alterations, and thyroid follicular cell hypertrophy in both sexes. This RfD
was approved by the OPP RfD Committee on January 29, 1993, but has not
yet been verified by the Agency RfD Committee. A lexicological evaluation
has not been performed by the Joint FAO/WHO Meeting on Pesticide Residues
(JMPR) to establish an Acceptable Daily Intake (ADI). (MRIDs 41714001 and
41714002).
18
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2. Exposure Assessment
a. Dietary Exposure
PJanLMetebQlism
Studies with alfalfa and lettuce indicate that pronamide is readily
absorbed by plants through the root system, translocated upward, and
distributed into the entire plant. The degree of translocation from leaf
absorption is not appreciable. Metabolism primarily occurs by conjugation to
malonyl glucose. No evidence of fragmentation or loss of the chloro
substituent from the aromatic ring was observed. The terminal residues of
concern are pronamide and its metabolites containing the 3,5-dichlorobenzoyl
moiety. (MRIDs 00107957, 00107958, 40494802, and 40494803).
Animal Metabolism
Studies with lactating goats and laying hens indicate that the primary
route of elimination is by excretion (urine arid feces). Minimal residues were
distributed to goat and poultry muscle. The metabolic pathway involves
modification of the aliphatic portion of pronamide. The terminal residues of
concern are pronamide and its rnetaboEtes containing the 3,5-dichlorobenzoyl
moiety. (MRIDs 00107954, 00107958, 42043401, and 42614201).
Residue Analytical Method
A Gas Liquid Chromatography (GLC) method with electron capture
detection (designated as Method I, PAM Vol. U) converts residues of
pronamide and its metabolites to methyl 3,5-dichlorobenzoate. The listed
detection limits are 0.2 ppm in/on plant commodities and 0.01 ppm in animal
commodities. A revised version of the PAM n method, which includes an
alkaline hydrolysis to release bound residues, resulted in increased method
efficiency and has been submitted for the enforcement of tolerances in animal
commodities. The revised method remains to be validated by an independent
laboratory.
The FDA Pestrak database (PAM Vol. I, Appendix n) contains data
concerning the applicabilty of all FDA multi-residue methods (except Protocol
E for fatty food) to pronamide per se. No data are available concerning the
applicability of multi-residue methods to pronamide metabolites containing the
3,5-dichlorobenzoyl moiety. For FDA enforcement monitoring purposes, the
Agency currently requires that representative plant and animal tissue samples
bearing metabolites of pronamide be subjected to analysis by FDA multi-
residue protocols C, D, and E from PAM Vol. I. In addition, the Agency
19
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requires that representative samples containing residues of pronamide per se
be analyzed according to protocol E for fatty foods. (MRIDs 00035563,
00035565, 00035566, 00070933,00070934, 00074523, 00077215, 00107957,
00107958, 00107959,00107960,00107961, 00107965, 00107967,00125382,
42043401, 42614201).
Storage Stability
In plant commodities, storage stability data [GU 171-4(e)] have been
submitted for alfalfa, apples, and lettuce; however, these data were generated
by Craven Laboratories and no storage stability data for other crops are
available. In animal commodities, pronamide is stable in poultry eggs and
tissues under frozen conditions for up to 34 months. For the purposes of
reregistration, the Agency will extrapolate and apply storage stability data on
poultry liver to ruminants and plants; based on the storage stability data on
poultry, residues of pronamide and its metabolites are assumed to be stable in
plant and animal commodities for up to 34 months. Confirmatory storage
stability data on milk, lettuce, apples, plums, grapes, and alfalfa, and the
processed commodities of apples, grapes, and plums are required. (MRIDs
41570101 and 42614201).
Magnitude of Residue in Meat. Milk, Poultry and Eggs
Studies in which cattle and poultry were fed pronamide at several dose
levels are available. Based on animal diets of alfalfa hay in cattle and alfalfa
meal in poultry, the current tolerances are adequate to cover the secondary
residues of pronamide that may transfer to meat, milk, poultry, and eggs. All
data requirements for magnitude of the residue in animals have been fulfilled,
(MRIDs 00107958, 00107959, 00107967, 40494801, 40782201,, 42043401,
and 42614201).
Magnitude of the Residue in Plant!
Residue data are available reflecting the use pattern as prescribed on the
current labels for the various crops. All data for the magnitude of the residue
in plants have been evaluated and deemed acceptable except for alfalfa seed,
artichoke, and dried winter peas. Data are still required as follows:
Alfalfa seed: Confirmatory residue data are required since all
available seed residue data were generated by Craven Laboratories.
Tolerances which currently exist on alfalfa forage will support this
use until these data are generated. (MRIDs 00033380, 00107958,
00107965, 00107967, and 00157804).
20
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Artichoke: Data reflecting early season use are acceptable. Data
reflecting the established 1-day PHI were generated by Craven
Laboratories; therefore, label revision deleting the 1-day PHI or
replacement of artichoke field trial data is required. (MRIDs
00077215 and 00125382).
Dried winter peas: Confirmatory residue data are required since
the tolerance was established using data generated by Craven
Laboratories (alternate data from Europe are available to support
the established tolerance in the interim, until the required data are
submitted and reviewed).
Processed Food/Feed
The only available data for the processed commodities of alfalfa, apples,
grapes, and plums were generated by Craven Laboratories. However, field
residue data resulting from up to 2x label rates show non-detectable residues
of pronamide and its metabolites in apples, grapes and plums. Based on the
available data, the Agency concluded that residues of pronamide are not likely
to concentrate significantly in processed commodities of these crops, and no
food or feed additive tolerances are currently required. However, the Agency
is requiring data on the following processed commodities of the following
RACs to confirm this assessment: apples, grapes, and plums.
b. Occupational and Residential
Pronamide is a selective systemic pre- and postemergent herbicide used
to control grasses and broadleaf weeds in lettuce, endive, alfalfa, rhubarb,
pome and stone fruits, artichokes, berries, grapes, legumes, woody
ornamentals, Christmas trees, nursery stock, lawns, turf, and fallow land.
Pronamide end-use products (Kerb*) are formulated as granulars
(0.125% - 1.0% a.L) and wettable powders (50% a.L; in water-soluble
pouches). The wettable powder formulations are used for all crop spray uses
and commercial and residential lawns and turf; the granular products are
applied to both commercial and residential areas (i.e., ornamental and
Bermuda grass turf (such as golf courses), lawns, and athletic fields).
Application methods include ground boora, aerial, and hand-spray
applications (the latter method is used only for ornamentals and nursery stock).
Depending on the site and weed problem, the application rates range from 0.5
to 4.0 Ibs. of product per acre, (0.125 - 2.0 Ibs a.i.).
21
-------
Based on Iti carcinogenic potential, the following restrictions were
imposed in the 19S6 Pronamide Registration Standard and are assumed for this
exposure assessment. These restrictions currently exist on pronamide product
registration labels:
o All 50% wettable powder end-use products are classified as
restricted use and must be packaged in water-soluble
pouches.
o All end-use products with outdoor agricultural uses which
are applied to crops involving hand labor are required to
bear precautionary label language regarding farmworker
safety.
o Protective clothing [Midforearm waterproof gloves, long-
sleeved shirts and long pants, preferably one piece
(coveralls)] are required during the mixing and application
of wettable powder formulations with die following
exceptions:
- When using water soluble packaging, mixers/loaders are
exempt from protective clothing requirements and,
- Applicators in enclosed tractor cabs with filtered air
supply or in enclosed cockpits are exempt from protective
clothing requirements.
- Waterproof boots or shoe coverings are additionally required for
workers using hand-sprayers or hand-spreaders.
o Hand-spray applications are limited to ornamentals and
nursery stock.
o Sites treated with granular formulations must be thoroughly
watered after application.
Mixer/Loader/Applicator Exposure
There is a potential for mixer/loader/applicator exposure to pronamide
sprays and dusts via the dermal and inhalation routes during the ground boom,
aerial, and hand-spray applications. The major route of exposure is via the
dermal route. Inhalation exposure appears to be very low via either ground
boom or hand-spray method of application, according to the data available in
Pesticide Handlers Exposure Database (PHED),
22
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Mixer/loader/applieator dermal exposure data were submitted by the
registrant for the end-use product Kerb* SOW herbicide packed in water-
soluble packages arid applied by pound boom (MRID 41117202). The results,
based on a worker weighing 70 kg, wearing currently required protective
clothing, and treating 50 acres/day at the rate of 2.0 Ibs a.L/aere, indicate the
following:
A mixer/loader is exposed to 0,025 mg/lb active
ingredient. Without protective clothing (which provides
approximately 80% protection), the exposure would be 0.10
mg/lb active ingredient.
- An applicator is exposed to 1.2 mg a.i./hr. Assuming that
6 hours are needed 60 treat 50 acres, the applicator is
exposed daily to 0.10 mg a.i./kg/day,
There are no chemical-specific data on dermal exposure of the applicator
using a low pressure hand sprayer. Based on the data available in the
Pesticide Handlers Exposure Database (PHED), such an applicator, treating 2
acres/day, at a rate of 2.0 Ib a.i./acre, is exposed to 2.84 mg/lb a.i.
Estimated daily exposure (EDE), average daily exposure (ADE) and
lifetime average daily exposure (LADE), in mg/kg/day, may be estimated
using the above exposure values (actual/PHED) and the following equations
and assumptions:
EDE (mixer/loader or applicator using hand-spray) =
mg/lb a.i. x If acres/day x application rate
kg b.w.
EDE (applicator using ground boom) =
mg/lb a.i./hr x 6-hr day x # acres/6 hrs x application rate
kg b.w.
ADE = EDE x # application/yr x 1 day/365 days
LADE = ADE x 35 yrs/70 yrs
Assumptions:
a mixer/loader/applicator weighs 70 kgs,
23
-------
the individual wears PPE as currently required in 1986 Registration
Standard,
water soluble packaging or protective clothing (as described in
Registration Standard) provides 80% protection,
# applications/yr = 10,
f acres treated/day = 50/ground boom and 2/hand-spray,
application rate — 2 Ibs a.i./acre, and
100% dermal absorption.
EDE, ADE, and LADE for handlers of wettable powder formulations in water-
soluble pouches are shown in the following table;
Dermal Exposure tor Handlers of Wettable Powder Formulations
;'^:;:;"'v:: •-'•—' ;':"-"-*"":!"~;'::"- '; f- w^xi-O: ;C:: '•-!-:-;':';-• ---•-'- •:'£-; '£'!'! ':•''!; r';|s:-:j;
;•,•:':' ;:;|:;;-,;;>;;;,::x !:;:•>•.' >>:' ^:'';^ j::;f j:!'i-::!v;';^i^^:y;|;?:j:-:|:::^:Jx|:y-V
';';-•' :::':'::L::tfL::':':*::::'"'::;y::*:::v;:-:^
Mixer/loader
withPPB
without PP1
Applicator with PPE
Ground boom
Hand-sprayer
Combined
Mixer/loader/applicator
Mixer/loader with PPE
Mixer/loader no PPE
?«ISilw;?S'||:||^:S::;;|;:i;|;:;Si:;:B:fi
::S:::ffiS:':ffi:'::s:::SS»Mi'iSx?J;3::.f:S>:JS.:S:«
lliliipi^lllllll
•^^^^Lfi^^^^mxfx^
;;j>*3:v°—: :—!- i':v;:;*"^^
!S:-^SSiS':H8K%::^ y-;.vsi:vs!"i'3&'.-yli£tsx':&&e;&:i$&: >«;¥
i«m»¥*gr^
0.04
0.18
1.10 x 10-3
4.93 x ID'3
5.47 x ID-4
2.47 x 10-3
0.10
0.40
2.74 x IO-3
1.12 x Iff*
1.37 x ID"3
5.60 xlO-3
0.14
0.28
3.84 x 10-3
7.67 x 10-'
1.92 x Iff3
3.84 x 10-'
All values are rounded to the nearest two decimals.
Adequate mixer/loader/applicator exposure data for the granular formulations
are not currently available. Potential exposure to the granular formulation is
expected to be less than exposure to the wettable powder formulation according to
the exposure assessment provided in the 1986 Pronamide Registration Standard.
Therefore, the Agency is requiring confirmatory mker/loader/applicator exposure
data for granular formulations of pronamide because there is a potential for
mixer/loader/applicator exposure to pronamide through the dermal and inhalation
routes following ground boom, aerial and handspray applications of the wettable
powder formulation.
24
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Post-application/Reentry Exposure (Worker and Residential)
There is a potential for post-application dermal exposure to foliar disLodgeable
residues and soil residues resulting from the use of both granular and wettable
powder formulations. There may be less dermal exposure on agricultural sites, if
pronamide is applied as a pre-emergence herbicide when the protected crop is still
dormant. Despite several factors which aid in the reduction of available foliar
dislodgeable residues and soil residues (i.e., watering in the granular formulation for
the turf use), the potential for post-application dermal exposure exists and may be
significant.
Currently, the Agency does not have the data to make a reregistratlon decision
on pronamide for use on residential lawns. An estimate of risk is not feasible
because of numerous uncertainties in potential exposure levels, especially for
children. Regulatory decisions relating to postappKcation reentry will be developed
after the foliar dislodgeable dissipation [GL# 132-l(a)] and dermal passive dosimetry
(G1J 133-3) studies required to support the residential lawn use are submitted and
reviewed. However, pronamide is acceptable for commercial turf, because the
restricted entry interval imposed by the Agency is expected to provide an adequate
margin of exposure for commercial turf uses. Regulatory decisions data relating to
postapplication reentry to commercial turf will also be determined after the foliar
dislodgeable dissipation and dermal passive dosimetry studies required to support
commercial turf uses are submitted and reviewed. Also, because of the potential for
significant hand contact associated with the use of pronamide on lettuce, the Agency
is requiring the same post-application reentry data for use on lettuce. These data
will be considered confirmatory. Post-application inhalation exposure is expected
to be minimal.
3. Risk Assessment
a. Dietary
The following were used to assess pronamide's dietary risk:
ToxicologicaLEndpoints
- A RfD of 0.08 mg/kg bodyweifht per day (See B.l.k, above for
details), and
- An upper bound (95%) of the estimated unit risk (Qi*) which is 1.54
x lO"2 (mg/kg/day)4 (See B.l.d. above for details).
25
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Tolerance. Anticipated Residue, and Percent Crop Treated
Dietary risk analysis was done using 1) percent crop treated data
(for several commodities) and anticipated residue data, and 2) all
reassessed tolerances values from the Tolerance Reassessment Summary
table (See Section IV.B.L).
Results
In January 1994, anticipated residue assessment resulted in an
estimated excess carcinogenicity risk of 1.52 x 10"6. However,
additional anticipated residue information, as well as percent crop treated
data (alfalfa) allowed the refinement of the data supporting the
pronamide dietary exposure estimates and provided a more accurate (and
lower) estimate of the dietary exposure and concomitant risk.
The following table represents the revised anticipated residues and
risk assessment for red meat and milk (commodities that contributed the
most to the anticipated residue contribution exposure assessments). In
the previous assessment, alfalfa hay was assumed to be only major feed
item for both beef and dairy cattle with pronamide tolerances. The
previous assessment utilized the average pronamide residues in animal
tissues and milk resulting from the highest dosing levels, and used a
linear extrapolation to the dietary burdens of beef and dairy cattle of
1,35 ppm and 4.27 ppm, respectively. The assessment assumed 100%
crop treated. This revised assessment assumes that in any given region,
10 % of alfalfa crop consumed by dairy cattle was treated with pronamide
since the percent crop treated for alfalfa is < 1 %, Since the assessment
included only alfalfa in estimating the dietary burden, and used linear
extrapolation to estimate anticipated residues and risks for red meat and
milk, the previous values are divided by 10 (100% CT /10% CT = 10).
Revised Anticipated Residues and Risk Estimates for Pronamide Residues in
Red Meat and Milk
.^::^:::1:^^
^:V;;!^•:-!':^'i::>-:';y:i:•^.'•-^,';:^::,^"^'.::^;^^^o•?:.:;^•:.::!::: '-•&•:'• .'•!•*: '<[-!•?:•:-:-?:-:<-•:;
•mrnfmmmmm
-------
The new dietary exposure of the U.S. Population as a whole to
pronamide based on Anticipated Residue Contribution (ARC) and
reassessed tolerances- is estimated at 3,2 B"5 mg/kg/day or 0,040% of
the Reference Dose (RfD). Based on the incorporation of the anticipated
residues and percent of crop treated in the risk analysis, the upper bound
estimated excess carcinogenic risk for the dietary exposure for the
general population to pronamide is approximately 5 x 10"7.
Conclusions
Dietary exposure to pronamide is associated with an estimated
upper bound excess carcinogenic risk of 5 x 10"7.
Pronamide's dietary exposure/risk that have been calculated by
DRES in the analysis discussed above are likely to be overestimates for
the following reasons:
1. For the commodity milk, the percent crop treated is < 1%,
actually ca. 0.05 % for alfalfa (the major animal feed item to
which pronamide may be applied). Our calculations
assumed that no more than 10% of the alfalfa crop consumed
by dairy cattle was treated with pronamide.
2. Where a range of percent crop treated data is presented for
a commodity, the highest value in the range was used in the
DRES analysis. Twelve crops are affected: artichokes,
blackberries, blueberries, boysenberries, cherries, endive,
grapes, lettuce, nectarines, peaches, pears, and raspberries.
3. Where no percent crop treated data ire available for a
commodity, the level is assumed to be 100%.
Incorporation of reassessed tolerance levels instead of just
anticipated residue data in the pronamide DRES data increased the
exposure/caxcinogenicity risk estimate but only by a small amount. This
incremental exposure does not significantly change the general level of
the carcinogenicity exposure/risk estimate.
Chronic exposure to pronamide in the diet is only a very small
fraction of the RfD and does not appear to be a cause for concern at this
time.
27
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b. Occupational and Residential
There is a concern for carcinogenicity associated with lifetime exposure
of mixer/loader/applicators and homeowoners to pronamide.
Estimates of Occupational Carcinogenic Risk
Mixers/loaders/applicators may be at risk for carcinogenic effects. For
workers handling the wettable powder formulations and applying the pesticide
by either ground boom equipment or low pressure hand-sprayers, excess
carcinogenic risks may be estimated using the equation;
Excess carcinogenic risk = Q!* x LADD
Lifetime average daily dose (LADD) is identical to the lifetime average
daily exposure (LADE) because 100% dermal absorption is assumed, LADE
estimates may be found under B.2.b,
Mixer/loader/applicator excess upper bound carcinogenic risks are shown
in the following table:
•:-•':•: ^:Vx';::'X;xVy'v:***:yfe*W^.::::'^^\*^^
::;^;;:i':Ox;::':K::-x::-:^:^
r::;::':t:'^.-:::::^:S^:-i^
Mixer/loader
with PPH+
without PPE
Applicator with PEE
Ground boom
Hand-sprayer
Combined
Mixer/loader/applicator
Mixer/loader with PPi
Mixer/loader no PPE
5.47 x ICT*
2.47 x Ifr3
8x10*
4x 10-J
1.37 x 10*
5.60 x l
-------
The pronamide occupational exposure/risks that have been estimated are
conservative for the following reasons:
1. Dermal absorption was assumed to be 100%. Although the dermal
absorption study was judged supplementary, the results, nevertheless,
were suggestive of a dermal absorption rate well below 100% (MRIDs
40256701C and 41117201). Based on information from these studies,
use of 10% as a dermal absorption factor would lead to estimates of
carcinogenic risk one order of magnitude lower for workers.
2. Worst-case scenarios of exposure were used for the applicator, based
on maximum rates of application (2 Ibs. a.i./acre), number of
applications per year (# = 10), and number of acres treated per day (50
acres/ground boom; 2 acres/hand-spray).
Carcinogenic risk for the worker applying granular formulations will be
estimated when the required dermal/inhalation exposure data at outdoor sites are
submitted and evaluated. Based on information available for the 1986 Pronamide
Registration Standard, potential risk is expected to be less for this use than the
wettable powder formulation.
C. Environmental Assessment
1. Environmental Fate
a. Environmental Chemistry, Fate and Transport
Detailed information regarding the fate of pronamide in the environment
is presented below:
Degradation
Carbonyl-labeled [14C]pronamide» at 1.5 ppm, was stable in sterile
buffered solutions (pH 4.7, 7.4, and 8.8) during 28 days of incubation at 20°C
followed by 14 days at 40°C. Less than 4% of the extractable residues were
identified as RH24644, SH2458Q, and RH25891 at each of the 7 sampling
periods (MSID 00107980).
Phenyl-labeled [MC]pronamide degraded with a half-life of 41 days in a
sterile, nonsensitized aqueous pH 7 buffer solution that was irradiated with
artificial light (xenon arc lamp) continuously for 30 days. The half-life would
be equivalent to 82 days on the basis of 12 hour light/12 hour dark cycle.
Seven degradation products (1H24644, RH24580, 1H26702, RH25891,
RH25059, S^-dichlorobemamide, and 3,5-dichlorobenzoic acid) were
identified in the irradiated solutions during the study. In the dark control for
29
-------
nonsensitized pronamide buffered solution, pronamide remained relatively
stable during the testing period of 30 days (MRIDs 40320601 and 40420301).
Phenyl-labeled [MC]pronamide photodegraded with a half-life of 57 days
on sandy loam soil that was continuously irradiated with an artificial light
source (xenon lamp) at 19-25°C for up to 28 days. Two degradates (RH2458Q
and RH24644) were identified; a compound "similar to RH267Q2" was also
detected. The half-life of pronamide in the dark control samples was 110 days
(MKID 41913504).
Metabolism
Phenyl-labeled [14C]pronamide degraded with a half-life of 392 days
when applied to sandy loam soil incubated under aerobic conditions in the dark
at 25°C for 12 months. Three major degradation products (RH24644,
RH24580, and RH26521) were identified at maximum concentrations of 27%,
14%, and 4% of the applied material (MKID 41568901 and 41913502).
Phenyl-labeled [MC]pronamide degraded slowly in sandy loam soil
incubated anaerobically for 60 days following a 31-day aerobic incubation in
the dark at 21-29°C. The registrant did not estimate, based on the available
data, the half-life of pronamide in this soil under anaerobic conditions.
Instead, the registrant reported that the half-life of pronamide under aerobic
and/or anaerobic conditions is greater than 90 days. Although there were
limited data available for the estimation of the half-life in the anaerobic soil
metabolism study, it appears that the anaerobic soil half-life for pronamide
could be greater than 392 days. Only one degradation product (RH24644) was
identified in the soil. At 90 days posttreatment (or 60 days of anaerobic
incubation), RH24644 comprised 6-13% of the recovered radioactivity (MRID
41913505).
Mobility
Pronamide was shown to be relatively mobile in soils [adsorption
coefficient (K^=3.2-10.1; or soil organic carbon adsorption coefficient (K^
=548-1,340). One of the two major degradation products (RH24644) has a
medium mobility (1^=2.3-9.9; or Kw=993-3»910). However, the other
major degradation product (RH24580) is very mobile and its K,^ ranges from
L3-2.4 (or K«=96-210) (MRIDs 40211103, 40211104, and 41913501).
Dissipation
Based on supplemental data from an unacceptable field dissipation study,
pronamide dissipated with half-lives of 36 and 16 days in the upper 12 inches
of bare ground plots containing loam and loamy sand soils, respectively, that
30
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were located in Central California. During the course of the study, pronamide
was not detected below 6 inches in the loam soil or 12 inches in the loamy
sand soil. The registrant characterized the degradation products as total
residues by converting the degradates and the parent to a common moiety.
The total residues, however, remained unidentified. The unidentified residues
were detected in the soil as early as 7 days after application and the percentage
of the total residues unidentified increased with time. Two months after
treatment approximately half of the total residues in the 0-3 inch soil were the
unidentified degradation products. This study has a number of deficiencies.
In addition r soil residue data for this study were generated by Craven
Laboratories. The Agency has determined that these data must be replaced.
The deficiencies for this study include;
1) The study sites are not representative of the areas where the
pesticide is expected to be used because they are located in two
counties (approximately 100 miles apart) in central California.
2) Pronamide was apparently not applied at the maximum rate at
the Madera site in CA. The total residues recovered from the 0-3
inch soil depth on Day 0 were a maximum of 1.7 ppm, equivalent
to an approximate rate of 1,5-2 Ibs a.i. per acre.
3) The registrant did not analyze for degradation products; rather,
soil samples were analyzed for parent compound and for total
pronamide residues only, using two different analytical methods.
The analytical method for the total pronamide residues would
determine parent compound, and its degradation products which
could be converted to methyl 3,5-dichlorobenzoate (the final
analyte for GC analysis). These degradation products include two
commonly-detected degradates (RH24644 and BH24580), and
others (i.e., EH26521, RH25891, RH25059, RH26702).
Based on the laboratory data, pronamide is very stable in water,
photolytically persistent in water and on soil. It is very persistent in soil under
aerobic conditions and even more persistent under anaerobic conditions. A
chemical with these properties is expected to be relatively persistent and
mobile in the field. Supplemental data from an unacceptable field dissipation
study suggested that pronamide is neither persistent nor mobile under field
conditions. However, this data is not reliable since it was generated by
Craven Laboratories. A new field dissipation study is required.
Accumulation
In a confined rotational crop study, pronamide residues accumulated in
lettuce, carrots, and wheat planted 30 days, 6 months, and 1 year after phenyl-
31
-------
labeled [14C]pronamide was applied at 4 Ibs a.i, per acre to sandy loam soil.
In mature lettuce, total residues were 0.737 ppm in plants from the 30-day
rotation interval, 0.055 ppm in plants from the 6-month rotation, and 0,021
ppm in plants from the 1-year rotation. In mature carrot greens from the 6-
month rotation, pronamide was 0.020 ppm. In the mature wheat straw from
the 1-year rotation, pronamide was not detected. In the 0-3 inch soil layer,
pronamide residues were 1.96 ppm immediately posttreatment, 1.39 ppm at the
30-day planting, 0,318 ppm at the 182-day planting, and 0.432 ppm at the
365-day planting. This study has a number of deficiencies;
(1) The revised application rate (62%) was significantly lower than the
theoretical value.
(2) The effects of the low application rate on the failure to identify the
low residue levels in carrots from the 6-month and 1 year rotation
interval, and in wheat grains from the 1-year interval are unknown. The
registrant did not address the concerns raised by the Agency on the
identification of two unknown degradation products at levels of 0.069-
0.216 ppm. Furthermore, only 44% of the residues recovered in the
mature lettuce from the 6-month rotation were characterized.
(3) The fate of pronamide under frozen conditions is unknown, because
the Agency does not have available storage stability data on pronamide
in soil samples.
(4) The effects of long-term storage on the residue levels in plant
samples remain unknown, since the submitted storage stability data were
generated by Craven Laboratories.
Although, there are a number of deficiencies in the confined rotational crops
study, a new confined rotational crop study is not required because sufficient
data are available for risk assessment purposes. However, the field rotational
crop study is now required in order to determine proper plantback intervals
and whether crop rotational tolerances are needed. The registrant will be
required to revise their current rotational crop restrictions for pronamide. The
plantback intervals for leafy vegetables and carrots should be expanded. Field
rotational crop studies are to be conducted on lettuce and carrots in order to
determine the plantback intervals. Also, in order to determine the plantback
interval or whether tolerances are needed for rotational grain crops, field
rotational crop studies are to be conducted on wheat.
Because the octanol water partition coefficient (K^) is greater than 1,000
and the aqueous photolysis half-life is 82 days, once pronamide reaches a
water body, it has the potential to bioaccumulale in fish. However, because
the required bioaccumulation in fish study has not been submitted, the uptake
32
-------
and accumulation of pronamide in fish is uncertain. A fish bioaccumulation
study is currently being reviewed by the Agency.
gpiay Drift
Data are needed to support the spray drift data requirements (201-1
Droplet Size Spectrum and 202-1 Drift Field Evaluation) because: (1)
pronamide can be applied by aerial equipment to lettuce, artichoke, endive,
Christmas tree plantations, and fallow lands; and (2) the Agency is concerned
about the off-target damage by drift of a toxic substance. The registrant is not
currently a member of the Spray Drift Task Force; therefore, data are needed
to support the spray drift data requirements. If the registrant commits to join
the Spray Drift Task Force, the Agency will hold these two data requirements
in reserve pending submission of the final task force report. If the findings of
the task force are inconclusive, then new studies may be required.
b. Environmental Fate Assessment
Based on laboratory data, pronamide is very stable in water, and
photolytically persistent in water and on soil. It is very persistent in soil under
aerobic conditions, with an estimated half-life of 13 months, and even more
persistent under anaerobic conditions, with an estimated half-life greater than
13 months. Two major degradation products (RH24644 and RH2458G) were
detected in soil under aerobic conditions. Only RH24644 was found in the
anaerobic soil metabolism study. Pronamide has a relatively low vapor
pressure (8.5xlO"s mmHg at 25°C), It is relatively mobile in soil [adsorption
coefficient (Kd)=3.2-10.1; Koc=548-l,340). KH24644 has a medium
mobility (Kd=2.3-9.9; or Koc=993-3,910). RH24580 is very mobile and its
Kd ranges from 1.3-2.4 (or Koc =96-210). A chemical with the above
properties is expected to be relatively persistent and mobile in the field.
Supplemental data from an unacceptable field dissipation study suggested that
pronamide is neither persistent nor mobile under field conditions. However,
the Agency cannot rely on this date because the soil data was generated by
Craven Laboratories. A new field dissipation study is required.
The field dissipation study is expected to provide useful information to
demonstrate the rates of pronamide dissipation through the combined-fate
processes (i.e., degradation, metabolism, adsorption, leaching, volatilization,
runoff) in the field.
The following data are required to confirm the environmental fate
assessment for pronamide:
(1) A field dissipation study must be conducted in at least two locations
at representative use areas (such as one site in California for the use on
33
-------
lettuce; another site in Wisconsin for the use in forage). The maximum
application rate must be used.
(2) A field rotational crop is required in order to determine plantback
intervals and whether tolerances are needed,
(3) Spray drift studies are required but may be fulfilled through the
Spray Drift Task Force if the registrant joins the Spray Drift Task Force
and the Task Force studies are timely and adequate.
2. Ecological Effects
a. Ecological Hazard
(1) Effects to Non-Target Birds
Jap. Quail
75
8770
Practically uontoxic
Mallard
75
20,000
There is sufficient information from the study cited above to characterize
technical grade pronamide as practically nontoxic to birds when exposed orally
to a single dose. (MWD 00107997)
Bobwhite1
94,5
>4000
Practically nontoiic
Mallard2
94,9
> 10,000
Bobwhite?
94.9
> 10,000
Bobwhite4
94.5
>30*
*4-week dietary study, 30 ppra was highest level tested.
1-4 refer to MWDs 00107993, 00108002, 00108003, and 00107994.
The studies listed above are sufficient to characterize technical pronamide
as practically nontoxic when exposure is through the diet to upland game birds
(bobwhite quail) and waterfowl (mallard duck).
34
-------
Because of the persistence of pronamide demonstrated in laboratory
studies, the Agency considered requesting two avian reproduction studies (GL#
71-4) on mallard duck and bobwhite quail. These studies are not being
required in spite of the persistence because pronamide is typically applied only
once a year, either in faE, winter or spring; is soluble in water and would
wash off avian food items; and has low toxicity to birds.
(2) Effects to Other Non-Target Terrestrial Organisms
Pronamide is practically non-toxic to mammals. The reproduction two-
generation test on rats concluded with a decrease in body weight and feed
consumption with a NOEL=200 ppm. Carcinogenicity studies in rats and
mice indicated that pronamide was carcinogenic at or above 1000 ppm (rats)
and 100 ppm (mice).
(3) Effects to Non-Target Fish
Bluegfll1
Trout2
Catfish.2
Goldfish2
Guppy2
50
>100
Slightly toxic
75
72
75
>200<500
75
350
75
150
-2 refer to MRIDs 00107196 and 001079%, respectively.
The studies listed above are sufficient to characterize pronamide as
slightly toxic to coldwater and warmwater fish. Because of the persistence of
pronamide demonstrated in laboratory studies, the Agency considered
requesting (GL# 72-4) Early life Stage of Fish. This study is not being
nequired because of low acute toxicity to fish.
(4) Effects to Non-Target Aquatic Invertebrates
Conclusions
Daphnia magna
93.8
>5.6*
Moderately toxic
Several solvents were use
but 5.6 ppm was the highest solution that could be tested.
35
-------
There is sufficient information to characterize technical pronamide as
moderately toxic to freshwater invertebrates. The Aquatic Invertebrate Life
Cycle study (GLJ 72-4B) is inquired due to the possible persistence of
pronamide in the aquatic environment; acute toxicity for Daphnids; and the
solubility of pronamide which indicates that it may be transported to aquatic
habitat. Based on existing data, the Agency anticipates that these new data
would confirm that pronamide does not represent a major problem for aquatic
organisms, however, this study is required to confirm this assessment for
pronamide because a potential chronic risk to aquatic invertebrates is possible.
(M1ID 00098313),
(5) Effects to Non-target Estuarine and Marine
Organisms
No data on estuarine studies were required in the 1986 Registration
Standard for pronamide. The Agency is now requiring estuarine studies
because the use on turf, hay, clover, alfalfa and pasture may expose estuarine
species to pronamide. Historically, the Agency has found that at least one of
the estuarine species will usually exhibit greater sensitivity to a pesticide than
any freshwater species. Therefore, the Agency is now requiring estuarine
studies for a pesticide used on sites adjacent to estuaries, including turf, hay,
clover, alfalfa and pasture land.
In order to establish the toxicity to estuarine and marine organisms, the
foEowing tests are typically required using the technical grade material: either
a Mollusc 48-hour embryo larvae study using Pacific oyster. Eastern oyster,
mussel (preferably Mytilw edulis) or Quahog (Mercewria) or a Mollusc 96-
hour How-Through Shell Deposition study using Pacific oyster or Eastern
oyster; and a Shrimp 96-hour acute toxicity test using white, pink, brown,
grass or mysid shrimp species; and a 96-hour toxicity testing using estuarine
fish (preferably silverside or sheepshead minnow). However, because of the
low toxicity pronamide demonstrates for freshwater fish, only the 72-3(b)
mollusc and 72-3(c) shrimp study are required. The 72-3(a) estuarine fish
study is not required. Based on the low toxicity of pronamide to freshwater
fish and moderate toxicity to freshwater invertebrates, the Agency anticipates
that these new data will confirm that pronamide does not represent a major
problem to aquatic organisms. To confirm this assessment, the Agency is
requiring the testing of other estuarine species.
(6) Effects to Non-Target Insects (Beneficial Insects)
No studies were evaluated under this topic. Application of pronamide
is made in the fall or early winter when bees are not generally expected to be
exposed to pronamide.
36
-------
(7) Effects to Non-Target Plants
Terrestrial
!!!•
;:;v'x:iv;v::;-i:jji™:!-x^
:$f:||j^^
Oat
Tomato
•^'^•^•^•''B^'x^:^:''^^-^:':^-''^-^^:^:;;;
96.8
96.8
Illllll^
.*>:*:•:•:•:' :::: ::x •: ::-:; ::: ::-: ; :: 'sffijSrfK : •;•: ':'• :•;•. " :•;"-•, :;:"-v :':*•":' x':-:' :';' ;•• '
mmmm^i^mammm
:;:;;;:::;;::;: ;.;!;:•: ^:::;:;:;:::*r^:^!^r:,^*/.:::;v:::::::;:::;:::::;;>:>;:;;;Y
0.0067
0.0720
^iSilSvliiillllilSSS
The study is classified as
supplemental because an N DEC
was not determined. For
terrestrial plants, die grasses
seem to be the most susceptible.
•$i&¥&®W&&^Z&:g&&ffzm&?g.
Ryegrass
96.8
^KvE&.tfx^
0.006?
-'•'v!v!:;:;v;-;-!' -.•:'!•: •I'!v!:S::i.'!v ''!•!<-"•''*''• >':* ';!'>!v>^ •>:•"•:•;•":•:•: ::•:•.-:•:•:•>:;:•:•:;:;'•:-:-:;•:-:•••
;',: !•;• :-;•;•:•:-•;••-:>;'••:•>•: :•:• >: "•: -:fjj. •-->' '•.-:• '"-: jjt::-: : '"-', '• i':;: :-: :::":;. >>:•.' :'v : ::: ' '--'• ''•', '•'-'< ••', •"•;•;•; :';;>;: >:';••
^lllPiP»icWaMiB|^ippii
This study was classified as
supplemental. The results were
valid for monocot species;
however, the results were
considered invalid for ths dicot
species. Additional data are
needed to determine, die most
sensitive dicot species.
Oat
96.S
0.0088
Tomato
96.8
0.0104
The study is classified as
supplemental because an NOEC
was not determined.
There are supplemental data available for the seed germination and
vegetative vigor studies. These studies are classified as supplemental because
a NOEC was not determined; however, they are acceptable for risk
asssessment purposes (MSTDs 42176801 and 42176802). For the seedling
emergence study, the data are classified as supplemental due to invalid
cucumber results. The tomato and cucumber were found to be the most
sensitive dicot species. Since a large number of endangered plant species may
be affected, the results of the dicots would determine the certainty of risk to
endangered plant species as well as other non-target terrestrial plants, A new
37
-------
cucumber test is required. The tomato test must be repeated along with the
cucumber test for comparative analysis.
Aquatic
Selenasmtm
capricornutum
96,8
0,76
Pronamide is toxic to green
algae.
There are supplemental data to characterize pronamide as toxic to green
algae. The only species tested is Selenastnm capncornutum (MRID
42176802). However, additional testing is required on the other four species
of aquatic plants: Lemna gibba, Skeletonema costatum, Anabaenaflos-aquae,
and freshwater diatom. These data are needed for assessing the effects to
endangered aquatic plant species and aquatic habitat in general.
b. Ecological Effects Risk Assessment
(1) Non-Endangered Species
Terrestrial Organisms
The maximum expected residues immediately after application do not
exceed the avian acute LCW or the mammalian acute LC}0. Application of
pronamide is made in the fall or early winter when bees are not generally
expected to be exposed to pronamide. Therefore, it appears that the use of
pronamide at the labeled rate will have minimal adverse acute effects on
insects, birds and mammals. Calculated residues immediately after application
exceed the mammalian NOEL as determined in a reproduction two-generation
study. In addition, immediate residues on short grasses in lettuce fields in
Michigan exceed the mammalian carcinogenic NOEL. However, pronamide
is applied only once per season and due to the solubility of the chemical, it
would likely wash off much of the treated mammal and bind food items before
chronic exposure at maximum exposure levels could occur. Chronic data are
not available on birds but chronic exposure is expected to be limited for both
birds and mammals.
Aquatic Organisms
The aquatic invertebrate life cycle is considered very important in
conducting a risk assessment for pronamide. The Daphnids are possibly the
most sensitive of the aquatic organisms (LC^, > 5.6 ppm). Historical data have
38
-------
shown that it is not uncommon for some pesticides to have chronic effects at
levels as low as 0.01 of the LC*, (5.6/100= 0.056 ppm). The aquatic EEC
does not exceed the LCK for fish or the LC^ for aquatic invertebrates. In this
case, with expected aquatic exposures of 0.024 to 0.073 ppm in deep water (6
feet) and 0.25 to 0.881 ppm in shallow water (6 inches), and given the
possible persistence of pronamide in water, chronic exposure potentially
suggests that chronic risk to aquatic invertebrates is likely. Chronic concern
for fish is minimal because of the high LCW values. Based on existing data,
the Agency anticipates that additional data would confirm that pronamide does
not represent a major problem for aquatic organisms. However, a chronic
aquatic invertebrate study is required to confirm this assessment because a
potential chronic risk to aquatic invertebrates is possible.
Aquatic JPIants
Although it appears that there may be minimal adverse effects for algae,
the aquatic plant data are insufficient to accurately assess hazards to aquatic
plants in general. Testing on the additional four species of aquatic plants is
required.
Terrestrial Plants
Non-target terrestrial plants may be adversely affected from runoff
and/or drift from the application of pronamide at the labeled rates on all of the
use sites except hay and grass forage. For hay and grass forage sites, drift
from aerial application may adversely affect non-target plants. Data on dicots
are insufficient to accurately assess hazard. Additional testing with tomato and
cucumber for the seedling emergence study is required to determine the most
sensitive dicot species.
(2) Endangered Species
Calculated residues on terrestrial food items exceed l/10tii the avian
LCjo's on lettuce sites in Michigan. However, endangered birds in Michigan
are either predatory or insect eaters. These birds will not eat short grasses
located near lettuce fields. Therefore, it appears that pronamide may not
adversely affect endangered birds.
In six inches of water, the aquatic EEC exceeds l/20th the IXVs for
endangered aquatic invertebrates. However, habitats for endangered species
of aquatic invertebrates comprising six inches of lentic water could not be
found near sites on which pronamide may be used. Therefore, it appears that
pronamide may not adversely affect endangered aquatic invertebrates.
39
-------
Data are incomplete for assessing aquatic and terrestrial plant hazard.
With no data, on Lemna gibba, it has not been determined if there are adverse
effects to aquatic microphytes. Therefore, risk to aquatic plants is uncertain
at this time.
For terrestrial plants, the estimated ground application EEC exceeds the
seedling emergence EC^ for all sites except hay and grass forage. The
estimated aerial application EEC exceeds the seedling emergence EC^ for all
sites when application is at the maximum labeled rate. Therefore, endangered
terrestrial plants may be adversely affected by pronamide applied at maximum
labeled rates.
IV. RISK MANAGEMENT AND REREGISTRATICW DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active
ingredients are eligible for reregistration. The Agency has previously identified and
required the submission of the generic (i.e. active ingredient specific) data required to
support reregistration of products containing pronamide active ingredients. The Agency
has completed its review of these generic data, and has determined that the data are
sufficient to support reregistration of all products containing pronamide as the sole active
ingredient. Appendix B identifies the generic data requirements that the Agency reviewed
as part of its determination of reregistration eligibility of pronamide, and lists the
submitted studies that the Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess the
registered uses of pronamide and to determine that pronamide can be used without
resulting in unreasonable adverse effects to humans; however, pronamide exceeded
endangered species triggers for terrestrial plants and there may also be a risk to aquatic
plants. The Agency, therefore, finds that all products containing pronamide as the sole
active ingredient, except for those products registered for use on residential lawns and late
season use (1-day PHI) on artichokes, are eligible for reregistration. The reregistration
of particular products is addressed in Section V of this document.
The Agency made its reregistration eligibility determination based upon the target
data base required for reregistration, the current guidelines for conducting acceptable
studies to generate such data and the data identified in Appendix B, Although the Agency
has found that all, but two uses of pronamide are eligible for reregistration, it should be
understood that the Agency may take appropriate regulatory action, and/or require the
submission of additional data to support the registration of products containing pronamide,
if new information comes to the Agency's attention or if the data requirements for
reregistration (or the guidelines for generating such data) change.
40
-------
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredients pronamide,
the Agency has sufficient information on the human health effects of pronamide and
on its potential for causing adverse effects in fish and wildlife and the environment.
Therefore, the Agency concludes that products containing pronamide as the sole
active ingredient for all uses, except for the broadcast application on residential
lawns and turf and the late season use on artichokes, are eligible for reregistration.
The Agency has determined that pronamide products, labeled and used as
specified in this Reregistration Eligibility Decision document, will not pose
unreasonable risks or adverse effects to humans; however, they may pose adverse
effects to terrestrial plants and there may be a risk to aquatic plants as weE.
2. Eligible and Ineligible Uses
The Agency has determined that pronarnide wettable powder and granular
products registered for use on the food crops listed in the Tolerance Reassessment
Summary Table (See Section IV.B.1.)> as well as, woody ornamentals, Christmas
trees, nurserystock, commercial turf, and fallow land uses are eligible for
reregistration.
There are insufficient exposure data for use of pronamide by broadcast
application on residential lawns and turf and a reregistration eligibility decision for
this use cannot be made until appropriate postapplication/reentry exposure data on
foliar dislodgeable dissipation and dermal passive dosirnetry studies are submitted
and evaluated.
En addition, residue data on late season use on artichokes were generated by
Craven Laboratories, The Agency has determined that these data must be replaced.
A reregistration eligibility decision for this use cannot be made until these residue
data are submitted and evaluated.
B. Regulatory Position
The following is a summary of the regulatory positions and rationales for pronamide.
Where labeling revisions are needed, specific language is set forth in Section V of this
document.
1. Tolerance Reassessment
The Agency will propose modifying the 40 CFR tolerance expression under
§180.317(a) and (b) to state: "... are established for the combined residues of the
herbicide 3,5nlicMoro-N-(l,lHaimemyl-2-propynyl)benzamide and its metabolites
(containing the 3,5-dichlorobenzoyl moiety and calculated as 3,5-dichloro-N-(l,l-
41
-------
dimethyl-2-propynyl)benzamide),.." to clarify which metabolites of pronamide are
determined by the enforcement methods and are included in the tolerance expression.
Tolerances Listed Under 40 CFR SlgQ.317ral:
The tolerances listed in 40 CFR §180.317(a) are for the combined residues of
3,5-dichloro-N-(l»l-dimethyl-2-propynyl)benzamide and its metabolites calculated
as 3,5-dichloro-N-(l» l-dimethyl-2-propynyl)ben2amide. Sufficient data are available
to ascertain the adequacy of the established tolerances listed in 40 CFR §180.317(a)
for: alfalfa, fresh; alfalfa, forage; alfalfa, hay; apples; artichokes; blackberries;
blueberries; boysenberries; cattle, fat; cattle, kidney; cattle, liver; cattle, meat
byproducts (except kidney, liver); cattle, meal; cherries; clover; crown vetch; eggs;
endive; goats, fat; goats, kidney; goats, liver; goats, meat byproducts (expect
Mdney, liver); goats, meat; grapes; hogs, fat; hogs, Mdney; hogs, liver; hogs, meat
byproducts (except kidney, liver); hogs, meat; horses, fat; horses, Mdney; horses,
liver; horses, meat byproducts (except kidney, Ever); horses, meat; lettuce; milk;
nectarines; peaches; pears; plums; poultry, fat; poultry, kidney; poultry, liver;
poultry, meat byproducts (except kidney, liver); poultry, meat; raspberries; sainfoin;
sheep, fat; sheep, Mdney; sheep, liver; sheep, meat byproducts (except Mdney,
liver); sheep, meat; and trefoil, (See Tolerance Reassessment Summary Table for
modifications in commodity definitions).
A crop group tolerance of 10 ppm must be proposed for residues of pronamide
in/on the forage and hay of the non-grass animal feeds group. The available data
satisfy the requirements for crop group tolerance establishment. Tolerances for
alfalfa (fresh, forage, and hay at 10 ppm) and clover (5 ppm) do not vary by more
than a factor of 5 from the tolerances for any other crop in the group. Concomitant
with this tolerance proposal, the established tolerances for "alfalfa, fresh", "alfalfa,
forage", "alfalfa, hay", "clover", "crown vetch", "sainfoin", and "trefoil" should be
deleted.
A crop group tolerance of 0.1 ppm must be proposed for residues of
pronamide in/on the stone fhiits group. Adequate data are available to support the
established tolerances for the representative commodities, cherries, peaches, and
plums/fresh prunes, all at 0.1 ppm. The registered uses on these crops are also
identical. Concomitant with this tolerance proposal, the established tolerances for
"chemes", "nectarines", "peaches", and "plums" must be deleted.
The available residue data support a reduction in the tolerance for residues
in/on endive from 2,0 ppm to 1.0 ppm.
The available residue data support a tolerance of 1.0 ppm for head lettuce only
but not leaf lettuce; the correct commodity definition in this case must be "lettuce,
head." Alternatively, the label must incorporate a PHI of 35 days for leaf lettuce
(direct seeded or transplanted).
42
-------
As a result of the improvement in the enforcement method for animal
commodities, the Agency will propose to amend the tolerances for the kidney and
liver of cattle, goats, hogs, horses, and sheep from 0.2 ppm to 0.4 ppm. In
addition, the tolerance for sheep meat was incorrectly listed in 40 CFR §18Q.317(a)
as 0.2 ppm and must be changed to the correct tolerance of 0.02 ppm.
Tolerances listed Under 40 CFR gl80.317fb):
The tolerances listed in 40 CFR §180.317(b) have regional registration and are
for thecombined residues of 3,5-dichloro-N-(l, l-dimethyl-2-propynyl)benzamideand
its metabolites calculated as 3,5^cMoro-N-(l,l-dimethyl-2-propynyl)benzamide.
Sufficient data are available to ascertain the adequacy of the established tolerance
listed in 40 CFR § 180.317(b) for rhubarb.
The tolerance for dried winter peas was established using data generated by
Craven Laboratories; alternate data from Europe were submitted and will be used
to support the established tolerance until acceptable confirmatory data from studies
conducted in the U.S. have been submitted.
Tolerance Reassessment Summary
!li|illi|liillilil;iiilll
Alfalfa, fresh
Alfalfa, forage
Alfalfa, hay
Clover
Crown vetch
Sainfoin
Trefoil
Apples
Artichokes
Blackberries
Blueberries
Boysenbenies
Cattle, fat
Cattle, kidney
Cattle, liver
:::Kft:s4«:S«!M:*;s;*l?-KSsS«B5S«;;w;*:i*-SK¥S
!x!:j:£;*:;.!:!:;.V^
>•;-:':^y:•;'!i:-A''!:--:;:^:t^i;::^y:":'::^•:irI::^:::^:^:i:;^s::":^';>::^:::^:.:^^,;::
•:-:-;-:• i-M-i-.-M-:-.-:-:-:-:^^:-:-;^- :-;•;-:-;-;-;-;•;•>;-:•:•;-:-:•:•;•-;•;•••: •;•; ••;•;!" ;>!>;•
lliil|M|Cili;il;lli:;
::¥::^:'->£-:-;^-;^-;:^
Reassessrnejit {ppm)::
Tolerances listed under 180.317(a):
10.0
10.0
10.0
5.0
5.0
5.0
5.0
0.1
0.1
0.05
0.05
0.05
0.02
0.2
0.2
Include all in a group
and establish at 10
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
0.4
0.4
mfmKxmmmmtmwmm&t
Non-grass animal
feeds group
Change due to
improved efficiency
in the enforcement
procedure for animal
commodities.
43
-------
J:i§si?l>SS«;'«;¥;S:fS::S;p!i:|;iliii:l:;:gl:
'-;Vi^«XSWSfim^SmMVW$:!m
:;::'!::'XSf"!:S*^^^j*^*i&:S::F¥S:K5«i
?;XXXv&:yH£Wt**UMJUUilfaf!t-Xitti*:y:
•X.Xf^.-.£&.Z&ffJtt-ZttxX.yy:.K*&.&»F('.-&!!'.
Cattle, mbyp (except
kidney, Ever)
Cattle, meat
Cherries
Nectarines
Peaches
Plum
Eggs
Endive (escarole)
Goats, fat
Goats, kidney
Goats, liver
Goats, mbyp (except
kidney. Ever)
Goats, meat
Grapes
Hogs, fat
Hogs, kidney
Hogs, liver
Hogs, mbyp (except
kidney, liver)
Hogs, meat
Horses, fat
Horses, Mdney
Horses, liver
Horses, mbyp
(except Mdney, Ever)
::' :'>::'::ii!i-': ' :"— ; P:I "v !'>->'.' ivX' i£|i" ''•li'f; £!•!•! '•f'-l- &'•'•'"'• •,'',•"•'••>-•"•'•
j:^:"-;*::?::::-:::^
0,02
0.02
0.1
0.1
0.1
0.1
0.02
2.0
0.02
0.2
0.2
0.02
0.02
0.1
0.02
0.2
0.2
0.02
0.02
0.02
0.2
0.2
0.02
Unchanged
Unchanged
Include all in a group
and establish at 0.1
Unchanged
1.0
Unchanged
0,4
0.4
Unchanged
Unchanged
Unchanged
Unchanged
0.4
0.4
Unchanged
Unchanged
Unchanged
0.4
0.4
Unchanged
.;•:••-•!':•. •:.;.>!.:•)-.;•„•• :-;-:-:•:•:•:-:-:•:':-: .•:-;•: :-:-:• :->:-; -:•:•:-:-:•:•"•: .-•••'. -.-.*.;•:
Stone fruits group
Residue data support
a tolerance
reduction.
Change due to
improved efficiency
in the enforcement
procedure for animal
commodities.
Change due to
improved efficiency
in the enforcement
procedure for animal
commodities.
Change due to
improved efficiency
in the enforcement
procedure for animal
commodities.
44
-------
Horses, meat
Lettuce
Milk
Pears
Poultry, fat
Poultry, kidney
Poultry, liver
Poultry, mbyp
(except Mdney, liver)
Poultry, meat
Raspberries
Sheep, fat
Sheep, kidney
Sheep, liver
Sheep, mbyp (except
kidney, liver)
Sheep, meat
0.02
1.0
0.02
0.1
0.02
0.2
0.2
0.02
0.02
0.05
0,02
0.2
0.2
0.02
0.2
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
Unchanged
0.4
0.4
Unchanged
0.02
l!iiiiilii§illliifiiiii:ii
::::;0:;::-:!:i-j' K'S^
•-^x";'^;":v,W;^v:::^^:;':-;^'^>::^^v:i:"J';^^v;;^>;^;^::^;;;i:^•;^:^;:=
Lettuce (head); only
head lettuce is
supported by
acceptable data;
otherwise, label
must add PHI for
leaf lettuce.
Change due to
improved efficiency
in the enforcement
procedure for animal
commodities.
Tolerance was
incorrectly listed in
the 40 CFR.
Tolerances listed under 180.317(5):
Peas, dried (winter)
Rhubarb
0.05
0.1
Unchanged
Unchanged
2. Restricted Use Classification
The wettable powder formulations of pronamide as currently registered will
maintain the restricted use classification imposed in the 1979 Special Review for
pronamide.
45
-------
3. Endangered/Threatened Species Statement
The Agency does have concerns about the exposure of endangered terrestrial
plant species to pronamide as discussed above in the science assessment chapter.
Currently, the Agency is developing a program ("The Endangered Species
Protection Program") to identify all pesticides whose use may cause adverse impacts
on endangered and threatened species and to implement mitigation measures that will
eliminate the adverse impacts. The program would require use modifications or a
generic product label statement, requiring users to consult county-specific bulletins.
These bulletins would provide information about specific use restrictions to protect
endangered and threatened species in the county. Consultations with the Fish and
Wildlife Service will be necessary to assess risks to newly listed species or from
proposed new uses. The Agency plans to publish in the Federal Register in 1994
a description of the program and by 1995 have available enforceable county-specific
bulletins. 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. Rather, any requirements for product use modifications will occur in the
future under The Endangered Species Protection Program.
4. Labeling Rationale
In order to remain in compliance with FIFRA, it is the Agency's position that
the labeling of all registered pesticide products containing pronamide must comply
with the Agency's current pesticide labeling requirements. The Agency has
determined that the current manufacturing and end-use label precautions are still
appropriate and required for product reregistration. In addition, it is the Agency's
position that the label statements/precautions listed in Section V of this RED must
be included on all affected products in order to remain in compliance with FIFRA.
a. Postapplication/Reentry Requirements
The Worker Protection Standard (WPS) for Agricultural Pesticides - 40
CFR Parts 156 and 170 — established an interim restricted-entry interval of 12
hours for pronamide, because the acute toxicity category of pronamide for
acute dermal toxicity is Toxicity Category IH. However, since pronamide is
classified as a Group B2 carcinogen, the Agency requires a REI of 24 hours
for all WPS sites as a more conservative measure to mitigate risk to workers
entering treated areas after application. Furthermore, given the known
toxicological concerns for pronamide, the Agency considers the additional
protections offered by the requirements in the WPS essential to its decision
that a 24-hour restricted entry interval for this chemical will offer sufficient
risk mitigation to workers. Therefore, during the REI the Agency will allow
workers to enter areas treated with pronamide during the REI only for the few
narrow exceptions allowed in the WPS.
46
-------
The Agency has determined that the entry restrictions discussed in this
section for uses within the scope of the WPS do NOT apply to uses of
pronamide not within the scope of the Worker Protection Standard for
Agricultural Chemicals (e.g., residential lawns). The predicted frequency,
duration, and degree of exposure due to such uses should not warrant the risk
mitigation measures being required for persons engaged in the production of
agricultural plants for commercial or research purposes.
All pronamide end-use products within the scope of the Worker
Protection Standard for Agricultural Pesticides (see PR Notice 93-7) — must,
within the timeframes listed in PR Notice 93-7 and 93-11, revise their labeling
to be consistent with the WPS, as directed in those notices and the
requirements of this RED.
b. Personal Protective Equipment (PPE) Requirements
Although pronamide has been classified as a Toxicity Category in
chemical for acute dermal toxicity, the Agency is requiring PPE for applicators
and other handlers as well as early entry workers consistent with the PPE level
(as established by 40 CFR Part 156, the Worker Protection Standard) required
for pesticides classified as Toxicity Category n for acute dermal toxicity. This
is due to the known toxicological concerns for pronamide, including its
classification as a Group B2 carcinogen.
V. ACTIONS REQUIRED BY REGISTRANTS
This section specifies the data requirements and responses necessary for the reregistration
of both manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of pronamide for the above
eligible uses has been reviewed and determined to be substantially complete for all
uses except residential kwns and turf and the late season use on artichokes.
However, additional confirmatory data are needed to fulfill requirements for the
studies listed below:
Product Identity - Confidential Statement of Formula for 92% Technical
Aquatic Invertebrate life Cycle - required for use on turf, hay, clover, alfalfa, and
pasture use sites
Estuarme and Marine Organisms (Mollusc and Shrimp) - required for use on turf,
hay, clover, alfalfa, and pasture use sites
Terrestrial Field Dissipation - required for all use sites
47
-------
Field Rotational Crop - required for lettuce and fallowland use sites
Droplet Size Spectrum and Drift Field Evaluation - requited because of aerial
application to lettuce, artichoke, endive, Xmas tree plantations and fallowland
Foliar Dislodgeable Dissipation - required for commercial turf and lettuce
Dermal Passive Dosimetry - required for commercial turf and lettuce
Estimation of Dermal/Inhalation Exposure at Outdoor Sites - required for granular
formulation use on commercial and residential turf
Residue Analytical Method - plant/animal (Independent Lab Validation)
Storage Stability - required for milk, lettuce, apples, plums, grapes, and alfalfa and
the processed commodities of apples, grapes, and plums
Magnitude of Residue - Plants (Alfalfa Seed and Dried Winter Peas)
Processed Food - required for apples, grapes, plums
Certain data, which are not part of the target database for pronamide, are required
to support the continued registration of pronamide. These data include:
Seed Germination/Seedling Emergence
Aquatic Plant Growth
The following data are required to support the use of granular and wettable powder
formulations by broadcast application on residential lawn and turf:
Foliar dislodgeable dissipation
Dermal passive dosimetry
In order to support the late season use of pronamide on artichokes, registrants are
required to amend their labels by deleting the late season use on artichokes or submit the
required magnitude of residue data,
2. Labeling Requirements for Manufacturing-Use Products
The Agency has determined that the current label precautions are still
applicable and are required for product reregistration if the product is to remain in
compliance with FIFRA (see 1986 Pronamide Registration Standard).
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, including product chemistry and acute dermal toxicity data for all end-use
products. The product specific data requirements are listed in Appendix E, the
Product Specific Data Call-in Notice.
48
-------
Registrants must review previous data submissions to ensure that they meet
current EPA acceptance criteria (Appendix E; Attachment 5) and if not, commit to
conduct new studies. If a registrant believes that previously submitted data meet
current testing standards, then study MEOD 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
a. Compliance with the Worker Protection Standard
In order to remain in compliance with FIFRA, it is the Agency's position
that any product whose labeling reasonably permits use in the production of
an agricultural plant on any agricultural establishment (farm, forest, nursery,
or greenhouse) must comply with the labeling requirements of EPA's labeling
regulations for worker protection statements (40 CFR part 156, subpart K).
These labeling revisions are necessary to implement the Worker Protection
Standard for Agricultural Pesticides (40 CFR Part 170) and must be completed
in accordance with the deadlines specified in the WPS, unless official EPA
guidance specifies otherwise. EPA has issued PR Notice 93-7, "Labeling
Revisions Required by the Worker Protection Standard (WPS), and PR Notice
93-11, "Supplemental Guidance for PR Notice 93-7," which contain specific
instructions to registrants about how to complete the required WPS labeling
changes and offer guidance and deadline-options for making those changes.
Unless otherwise specifically directed in this RED, all statements required by
the WPS (and reflected in PR Notices 93-7 and 93-11) are to be on the product
labeling,
—In order to remain in compliance with FIFRA, after April 21, 1994, except
as otherwise provided in PR Notices 93-7 and 93-11, or other EPA guidance,
all products within the scope of those notices must bear WPS PR-Notice-
eomplying labeling when they are distributed or sold by the registrant or any
supplementally registered distributor, or any repackager under the Agency's
Bulk Repackaging Policy.
—In order to remain in compliance with FIFRA, after October 23, 1995,
except as otherwise provided in PR Notices 93-7 and 93-11 or other EPA
guidance, all products within the scope of those notices must bear WPS PR-
Notice-complying labeling when they are distributed or sold by any person.
b. Entry Restrictions; Labeling
—Uses Within the Scope of the WPS: In order to be in compliance with
FIFRA, a 24-hour restricted entry interval (RFJ) is required for all uses within
the scope of the WPS (see PR Notice 93-7) on all end-use products, except
49
-------
those intended primarily for home use (see scope criteria in PR Notice 93-7
and 93-11). TMs REI must be inserted into the standardized REI statement
specified the WPS as explained in teh EPA guidance in PR Notice 93-7. The
personal protective equipment for early entry must be the PPE required for
applicators of pronamide (except no apron or respirator (if any) is required).
This PPE must be inserted into the standardized REI statement specified by the
WPS as explained in the EPA guidance in PR Notice 93-7.
In order to be in compliance with FIFRA, labels of sole-
active-ingredient end-use products that contain pronamide must be
revised to adopt the entry restrictions set forth in this section. Any
conflicting entry restrictions on their current labeling must be
removed.
In order to be in compliance with FIFRA, labels of multiple-
active-ingredient end-use products that contain pronamide must bear the
more protective of either the entry restrictions set forth in this section or
the entry restrictions on the current labeling. For purposes of
implementation, a specific time-period in hours or days is considered
more protective than "sprays have dried" or "dusts have settled" and a
longer REI is more protective than a shorter one.
—Uses Not Within the Scope of the WPS; Do not add any additional
entry restrictions for uses not within the scope of the WPS; however, any
entry restrictions on the current product labeling for those uses must be
retained.
c. Personal Protective Equipment Requirements; Labeling
-Uses On Products NOT Primarily Intended for Home Use: The
personal protective equipment (PPE) requirement for "pesticide handlers on all
end-use products is:
"Applicators and other handlers must wear:
—Coveralls over short-sleeved shirt and short pants
—Chemical-resistant or waterproof gloves (see
instructions * below)
-Chemical-resistant footwear plus socks
-Chemical-resistant headgear for overhead exposure
—Chemical-resistant apron when cleaning equipment,
mixing, or loading"
* The glove statement for pronamide end-use products should be the
statement established through the instructions in PR Notice 93-7.
50
-------
In order to remain in compliance with FDFRA, labels of end-use products
that contain pronamide must bear the more protective of either the personal
protective equipment requirements set forth in this section or the personal
protective equipment requirements, if any, on their current labeling. For
guidance in choosing which requirement is more protective, see Supplement
Three of PR Notice 93-7.
d. Other labeling Requirements
(1) Labeling for Lawn and Turf Uses.
If a registrant chooses to support lawn and turf uses, he must submit the
data required in this Reregistration Eligibility Decision document associated
with the lawn and turf uses of pronamide. If a registrant chooses to support
the residential lawn uses only, he must add the following exclusionary
statement to his labels in order to remove the turf use site from the scope of
the WPS in accordance with PR Notice 93-11.
Exclusionary Statement: All granular and wettable powder end-use products
that contain pronamide must carry the following statement located (1) on the
front panel of the label in association with the product name or (2) near the
beginning of the Directions For Use section:
"Not for use on turf being grown for sale or other
commercial use as sod, or for commercial seed
production, or for research purposes."
If registrant does not support the residential lawn uses, the registrant
must amend his product label by deleting the residential lawn and turf uses in
accordance with the procedures in PR Notice 91-1.
The labels and labeling of all products must comply with EPA's current
regulations and requirements as specified in 40 CFR §156,10.
(2) Labeling for fish and Wildlife Hazard
In order to remain in compliance with FIFRA, labels must bear the
following in the Precautionary Statements section under the subheading
Environmental Hazards:
51
-------
End Use - Wettable Powder and Granular Formulations
"Do not apply directly to water, or to areas where
surface water is present or to intertidal areas below the
mean high water mark. Do not contaminate water
when disposing of equipment wash waters."
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for
26 months from the date of the issuance of this Reregistration Eligibility Decision
Document (RED). Persons other than the registrant may generally distribute or sell such
products for 50 months from the date of the issuance of this RED. However, existing
stocks time frames will be established case-by-case, depending on the number of products
involved, the number of label changes, and other factors. Refer to "Existing Stocks of
Pesticide Products; State of Policy"; Federal Register. Volume 56, No. 123, June 26,
1991.
The Agency has determined that registrants may distribute and sell pronamide
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.
52
-------
VI. APPENDICES
53
-------
-------
APPENDIX A. Table of Use Patterns Subject to
Reregistration
55
-------
-------
APPENDIX A - CASE 0082, IPronamidel Chemical 101701 [Propyzamidej
SITE Application Type, Application Form Minimum
Timing, Application Equipment - Application
Surface Type 1 Efficacy Influen- Rate
cing Factor (Antimicrobial only)
FOOD/FEED USES
Broadcast., December., Aircraft. UP MA
Broadcast., December., Ground. UP MA
Broadcast., September., Aircraft. UP NA
Broadcast., September., Ground. UP MA
Broadcast., Post emergence.. Ground. UP NA
Broadcast., Preemergervce., Ground. UP MA
Soil incorporated treatment., Preemergence. , UP MA
Irrigation.
Band treatment., Nonbearing., Lou pressure UP MA
ground.
Band treatment., Postharvest., Lou pressure UP MA
ground.
Directed spray., Nonbearing., Low pressure UP NA
ground.
Directed spray., Postharvest., Lou pressure UP NA
ground.
Maximum
Application
Rates
.5
.§
.5
.5
2
2
2
^iiitlii
2
3
4
2
3
4
2
3
4
Z
3
4
SJ^TsSssSfi
Ib A
Ib A
Ib A
Ib A
Ib A
Ib A
Ib A
ffiiSii
Ib
Ib
Ib
Ib
Ib
Ib
Ib
Ib
Ib
Ib
Ib
tb
Soil
Text
(M&x
Dse)
.
*
*
*
•
•
*
C
H
F
C
H
F
C
H
F
C
H
F
Msx. Hax i mum Dose Nfn.
Apps /crop cycle, Interv
a MBX or /year (days)
Rate
1/C NS NS
1/C NS NS
1/C NS NS
1/C NS NS
NS NS NS
NS NS NS
NS NS NS
NS
1/C 4 Ib AI/C
NS
1/C 4 Ib AI/C
NS
1/C 4 Ib AI/C
NS
1/C 4 Ib AI/C
Restr. Geographic
Entry Allowed
Interv
(days)
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
Geographic Use
Disallowed Limitations
Codes
C46
C46
C46
C46
C46
C4e
C46
C46,
C46,
C46,
C4fi,
G99
G99
G99
G99
57
-------
APPENDIX A - CASE 0032, [Pronamide] Chemical 101701 [Propyzanidel
SITE Application Type, Application
Timing! Application Equipment -
Surface Type & Efficacy Influen-
cing Factor (Antimicrobial only)
FOOD/FEED USES (can't)
Fora Mini mum Max 1 nun Soil Max. Maximum Dose
Application Application Text Apps /crop cycle,
Rate Rates (Hex a Max or /year
Dae) Rate
Band treatment., Ratoon., Low pressure UP
ground.
Band treatment., Transplant., Low pressure
ground.
Broadcast., Postplant., Aircraft.
Broadcast., Postplant., Ground.
Broadcast., Preemergence., Aircraft.
Broadcast., Preemergence,, Ground,
Broadcast., Ratoon., Aircraft.
Broadcast., Batoon., Ground.
Broadcast,, Transplant., Aircraft.
Broadcast., Transplant., Ground.
Band treatment., fall.. Low pressure ground.
Bend treatment., Winter., Low pressure
ground.
Low volume spray (concentrate).. Fall., Low
pressure ground.
Low volume spray (concentrate).. Winter.,
Low pressure ground.
UP
HP
yp
HP
UP
UP
UP
UP
yp
Saw**
UP
UP
UP
MP
m
HA
HA
HA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
4
2
2
2
2
2
4
4
2
2
3
3
3
3
Nin. ftestr. Geographic Geographic Use
Inter*/ Entry Allowed Disallowed Limitations
(days) interv Codes
(days)
Ib A *
Ib A *
Ib A *
Ib A *
Ib A «
Ib A *
Ib A *
ib A *
Ib A *
Ib A *
Ib A *
Ib A *
Ib A *
Ib A *
Z/C
2/C
1/C
Vc
1/C
Vc
2/C
z/c
2/C
Z/C
1/t
1/r
1/Y
1/Y
8ra|J!ii|pJS^tpipllj
NS
NS
NS
MS
NS
NS
NS
NS
NS
NS
MS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
MS
NS
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
OR, WA
OR, VA
OR, UA
OR, WA
C46,
C46,
C46,
C46,
C46,
C46,
C44,
C46t
M6,
C46,
C4&
C46
C46
C46
H01(60)
HDK6D)
H01(60)
HOI (60)
H01C60)
HOK603
HOK60)
HOI (60)
H01C60)
HOK60}
land treatment., Fall., Low pressure ground. UP
NA
2 Ib A
1/T
MS NS
MS
C4&
58
-------
APPENDIX A - CASE 0082, [Pronamide] Chemical 101701 [PrepyzamideJ
SITE Application Type, Application
Timing, Application Equipment -
Surface Type & Efficacy Influen-
cing factor {Antimicrobial only)
Form Minimum
Maximum Soil Hex. Maximum Dose Min. ft«str. Geographic
Application Application Text Apps /crop cycle, Interv Entry Allowed
Rate Rates (Max i Max or /year (days) Interv
Dsc) Rate (days)
Geographic
Disallowed
Use
Limitations
Codea
FOOD/FEED USES (con'tj
land treatment., Winter., Low pressure
ground.
WP NA
2 lb A *
Low volume spray {concentrate)., Fall., Low UP NA
pressure ground.
Low volume spray (concentrate)., Winter., UP MA
Lou pressure ground.
1/r
2 lb A * 1/Y
2 Ib A * 1/Y
us MS us
m NS HS
us NS us
C46
C4e
Band treatment., Fall., Lou pressure ground. WP NA
Bond treatment., I/inter,, lorn pressure UP NA
ground.
Low volume spray (concentrate).. Fall,, Lou UP NA
pressure ground.
Low volume spray (concentrate)., winter., UP NA
Low pressure ground.
3 lb A * 1/Y
3 Ib A * 1/Y
3 lb A « 1/Y
3 lb A *
1/Y
NS NS NS OR, UA
NS NS NS OR, WA
NS NS NS OR, WA
NS NS NS OR, WA
C46
C46
Band treatment., Nonbearing., Low pressure UP MA
ground.
Band treatment., Postharvest.. Low pressure UP NA
ground.
Directed spray.,, NonbeaHng., Low pressure UP NA
ground.
Directed spray., Postharvest.r Low pressure UP NA
ground.
2 lb A C
3 lb A H
4 lb A F 1/C
2 lb A C
3 lb A M
4 lb A F
2 lb
3 lb
4 lb
2 lb
3 lb
4 Ib
1/C
C
H
F 1/C
C
H
F 1/C
NS NS
4 lb Al/C
NS NS
4 lb AI/C
NS NS
4 lb Al/C
NS NS
4 lb AI/C
NS
NS
NS
NS
C46, G99
C46, 099
C46, 1199
C46, S99
59
-------
APPENDIX A - CASE 0082, tPronamfde) Chemical 101701 IPropyzemide)
SITE Application Type, Application
Timing, Application iojufpment -
Surface Type & Efficacy Influen-
cing Factor (Antimicrobial only)
FOOD/ FEED USES (con't>
Broadcast., pestemergence.. Ground.
Broadcast., Preetnergence. , Ground.
Band treatment., Poetemergence., Low
pressure ground.
Band treatment., Postplent., Low pressure
ground.
Band treatment., Preplant., Lou pressure
ground.
Band treatment.. Transplant., Low pressure
ground.
Broadcast., Postenergence. , Ground.
Broadcast., Postplant., Aircraft.
Broadcast., Postplant., around.
Broadcast., Preplant., Aircraft.
Broadcast., Preplant., Ground.
Form Minimum
Application
Rate
yp NA
WP NA
WP NA
UP NA
yp NA
yp NA
yp NA
yp NA
yp NA
WP NA
WP NA
Maxinun
Application
Rates
2 Ib A
2 IbA
1.5 IbA
1.5 Ib A
2 IbA
1.5 IbA
1.5 IbA
Z IbA
1.5 Ib A
1.5 IbA
2 IbA
1.9 IbA
1.5 Ib
2 Ib
1.5 Ib
1.5 Ib
2 Ib
2 IbA
1.5 IbA
1.5 Ib A
2 Ib A
2 IbA
1.S IbA
1.5 IbA
2 Ib A
Soil
Text
(Max
Use)
'•OUR'
*
*
Hit
c
n
f
c
M
f
C
M
F
C
M
F
C
N
F
*
C
M
f
*
C
M
f
Max. Maximum Dose Nin. Rcstr. Geographic
Apps /crop cycle, Inter v Entry Aliened
3 Hex or /year (days) tnterv
Rate (days)
HS NS NS NS
NS NS HS HS
tIS NS NS HS
NS NS NS NS
HS NS NS NS
MS KS NS NS
NS MS MS NS
1/C NS NS NS AZ
NS NS NS NS
1/C NS NS NS AZ
MS NS MS NS
Geograph i c Use
Disallowed Limitations
Codes
C46
«&
C46
C46
C46
C46
C46
C46
C46
60
-------
APPEND IK A - CASE 0082, [PronaimcJe] Chemical 101701 [Propyzamide]
SITE Application Type, Application Form Mini nun
Timing, Application Equipment - Application
Surface Type & Efficacy Influen- Rate
clng Factor (Antimicrobial only)
FOOD/FEED USES (con't)
Broadcast., Transplant., Ground, UP NA
Soil incorporated treatment., UP HA
Postemergence. , Ground.
Soil Incorporated treatment., Postptant., UP NA
Ground.
Soli Incorporated treatment.. Preplan!., UP NA
Ground.
Soil incorporated treatment.. Transplant., UP NA
Ground.
Band treatment., Nonbearing., log pressure UP NA
ground.
Band treatment., Postharvest., Lou pressure UP NA
grdund.
Directed spray., Nonbearing., Low pressure UP NA
ground.
Directed spray., Postharvest., Lou pressure UP KA
ground.
H»x I nun
Application
Ratea
1.5 Ib A
1.5 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
3 Ib A
4 Ib A
* 2 Ib A
3 Ib A
4 Ib A
2 Ib A
3 Ib A
4 Ib A
2 Ib A
3 Ib A
ft Ib A
Soi t Max.
Text Apps
(Mm 9 Max
Dee) Rate
c m
K
F
C NS
H
F
C NS
N
F
C NS
H
F
C NS
H
F
C
M
F 1/C
C
H
f 1/C
C
M
F 1/C
C
N
F 1/C
Maximum Doie Min. Restr. Geographic
/crop cycle, Interv Entry Allowed
or /year (days) Interv
(days)
MS MS NS
NS NS NS
US NS MS
NS NS NS
US MS NS
jpfpij^nil^ipjl^^
NS NS
4 tb AI/C
NS NS
4 Ib AI/C
NS NS
4 Ib AI/C
NS NS
4 Ib AI/C
Geographic Use
Disallowed Limitations
Codes
C46
C46
C46
C46
C4&
C46, Q99
C4A, G99
C46, fi99
C46, G99
61
-------
APPENDIX A - CASE DD82, IPronwnlde] Chemical 101701 [Propyzamide]
SITE Application Type, Application
Timing, Application Equipment -
Surface Type & Efficicy Inf luen-
cing Factor (Antimicrobial only)
FOOD/ FEED USES (con't)
Band treatment., Post emergence., Low
pressure ground.
Band treatment., Post pi ant., Ground.
Band treatment,, Postplant,, Low pressure
ground.
Band treatment., Preemergence., Ground.
Band treatment., Preplant., Lou pressure
ground.
Form Hiniimm Maximum
Application Application
Rate Rates
UP NA 1.5 lb A
1.5 IbA
2 lb A
UP NA 1.5 IbA
1.5 lb*
1.5 IbA
UP NA 6 lb A
UP NA 6 lb A
UP NA 1.5 lb A
1.5 IbA
2 lb A
UP NA 1.5 lb A
1.5 lb A
1.5 lb A
UP NA 6 Ib A
UP NA 6 lb A
UP NA 1.5 lb A
1.5 Ib A
2 IbA
yp m 1.5 lb A
1.5 IbA
1.5 IbA
Soil
Text
CA6, MOU55)
H01<35)
HOU55)
H01(55)
C46, HO 1(55)
H01<35>
62
-------
APPENDIX A - CASE 0082, [PronBinide] Chemical 101701 [Propyzamidt]
SITE Application Type, Application
Timing, Application Equipment -
Surface Type & Efficacy Influen-
cing factor (Antimicrobial only)
FOOO/FE6B
USES Ceon't)
Band treatment.. Transplant., Lou pressure
ground.
Broadcast., Not on label., Aircraft.
Broadcast., Post emergence,. Aircraft.
Broadcast.
Broadcast.
ground.
Broadcast .
Broadcast .
Broadcast.
Broadcast.
Broadcast .
, Post emergence., Ground.
, Paatemergence. , LCH pressure
, Post plant.. Aircraft.
, Postplent., Ground.
, Postplant., Lou pressure ground.
, Preemergence.., Ground.
, Preplant,, Aircraft.
Form Minimum
Application
Rate
UP NA
UP HA
WP NA
UP MA
UP MA
UP NA
UP NA
UP NA
UP NA
UP HA
UP HA
UP NA
UP MA
UP NA
Maxima
Application
Rates
1.5 Ib A
1.5 Ib A
2 Ib A
1.5 Ib A
1.5 Ib A
1.5 Ib A
2 Ib A
2 Ib A
1.S Ib A
1.5 Ib A
2 tb A
1.5 Ib A
1.5 Ib A
1.5 Ib A
2 Ib A
1.5 Ib A
1.5 Ib A
2 Ib A
6 Ib A
6 Ib A
1.5 Ib A
13 tb A
1.S Ib A
6 Ib A
6 Ib A
2 Ib A
Soil
Text
Cflax
Dse)
C
H
F
C
M
f
•
*
C
N
F
C
M
f
»
C
H
r
*
»
c
N
F
*
*
*
Max.
Apps
a Max
Rate
1/C
1/C
NS
1/C
1/C
1/C
1/C
1/C
1/C
1/c
1/C
1/C
1/C
1/C
Max f nun Dose
/crop cycle,
or /year
US
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
HS
NS
Hin.
tnterv
(days)
NS
NS
HS
MS
HS
NS
NS
NS
NS
NS
NS
HS
NS
HS
Restr.
Entry
Interv
(days}
NS
NS
NS
NS
NS
HS
KS
NS
NS
NS
NS
NS
HS
NS
Geographic
Allowed
Geographic Use
Disallowed Limitations
Codes
CW, HOH55}
CA
CA
AZ
CA
AZ
H01O5)
C46, H01
HOI (35)
C555
C46, H0 1(55}
MI
OH
CA
HI
OH
AZ
HOK55)
H01<55>
HOI (35)
H01(55)
H01(55)
63
-------
APPENDIX A - CASE 0082, [Pronamide] Chemical 101701 [Propyiamfde]
SITE Application Type, Application Form Ninitnun
Timing, Application Equipment - Application
Surface Type I Efficacy Influen- Rate
cirtg Factor (Antimicrobial only)
FOOD/ FEED USfS (con't)
Broadcast., Preplan t., Ground. WP HA
Broadcast., Preplant., Lou pressure ground. WP NA
Broadcast., Transplant., Ground. WP NA
Broadcast., Transplant., Lou pressure WP NA
ground.
Sod Incorporated treatment., WP NA
Post emergence., GroLnd.
S«il incorporated treatment., PostpUnt., WP M
Ground.
Soil Incorporated treatment., Preplant., WP NA
Ground.
Soil incorporated treatment., Transplant., UP NA
Ground.
Band treatment., Nonbenrlng., Low pressure UP MA
ground.
Maxinun
Application
Rates
1.5 Ib A
1.5 Ib A
2 Ib A
1.5 Ib A
1.5 Ib A
1.5 Ib A
1.5 Ib A
1.5 Ib A
2 tb A
1.5 Ib A
1.5 Ib A
1.$ Ib A
2 (b A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
2 Ib A
3 Ib A
4 tb A
Soil Max. Maxirntm Dose Min. Restr. Geographic
Text Apps /crop cycle, tnterv Entry Allowed
(Max B Max or /year (days) Interv
Dse) Rate (days)
C 1/C NS MS NS
H
f
C 1/C NS US NS CA
M
f
C 1/C NS NS NS
M
f
C 1/C NS MS NS CA
H
F
C 1/C NS NS NS
N
F
C 1/C NS MS NS
N
F
C 1/C NS NS NS
N
F
C 1/C NS NS NS
H
F
C N5 NS NS
H
f 1/C 4 Ib Al/C
Geographic Use
Disallowed Limitations
Codes
C4&, H01C553
HOI (35)
C46, HOK55)
HOK35)
C46, HOI CSS)
C46, H01C55)
C46, HOI (55)
C46, H01(55)
C4&, C99
64
-------
APPENDIX A - CASE 0082, EPronamidel Chemical 101701 [Propyzamfdel
SITE Application Type, Application
Timing, Application Equipment -
Surface Type I Efficacy Influen-
cing Factor
-------
ft - CASE 0082, [PronamideJ Chemical 101701 IPropyzamitfe]
SITE Application Type, Application Form Minimum
Timing, Application Equipment - Application
Surface Type & Efficacy Inf luen- Rate
eing Factor (Antimicrobial ontyj
FOOD/FEED USES (can't)
Band treatment., Post harvest., Lou pressure UP MA
ground.
Directed spray., Nonbearing., Low pressure UP HA
ground.
Directed spray., Post harvest., Low pressure UP HA
ground.
Broadcast., Early winter., Ground. UP MA
Broadcast., Fall., Ground. UP NA
Band treatment,, Nonbearing., Low pressure UP MA
ground.
Band treatment., Postharvest., Lou pressure UP HA
ground.
Directed spray., Nonbearing., Lou pressure UP MA
ground.
Directed spray.. Post harvest., Lou pressure UP MA
ground.
Maximum
Application
Rates
2 IbA
3 Ib A
4 tb A
2 Ib A
3 IbA
4 Lb A
2 IbA
3 IbA
4 Lb A
1.5 Ib A
1.5 Ib A
2 IbA
3 Ib A
4 Ib A
2 Ib A
3 IbA
4 Ib A
2 IbA
3 IbA
4 Ib A
2 Ib A
3 Ib A
4 tb A
Soil
Text
(Max
Dse)
sBfiMs
C
N
F
C
M
F
C
M
f
*
*
Max.
Apps
8 Max
Rate
mm
1/C
1/C
t/c
1/C
Hi
1/C
1/C
C
M
F
C
N
f
C
M
F
C
N
F
1/C
1/C
1/C
1/C
Maximum Dose Nin. Restr. Geographic
/crop cycle, Interv Entry Allowed
or /year (days) Interv
{days)
S^K^wW^^^W^^
NS NS NS
4 Ib AI/C
NS NS NS
4 Ib AI/C
NS NS NS
4 Ib AI/C
MS NS NS ID, OR, UA
NS NS NS 10, OR, UA
NS NS NS
4 Ib AI/C
NS NS NS
4 Ib AI/C
NS HS NS
4 tb AI/C
NS NS NS
4 Ib AI/C
Geographic Use
Disallowed Limitations
Codes
C46, C99
C46, G99
•"" C46, G99
C46, CB7,
C46, GB7,
C46, G99
C46, G99
C46, Q99
C46, 699
G03
603
66
-------
APPENDIX A - CASE 0082, IPronamideJ Chemical 101701 [PropyzamfdeJ
SITE Application Type, Application Form Mini nun
Timing, Application Equipment - Application
Surface Type t Efficacy Inf luen- Rate
cing Factor (Antimicrobial only)
FOOD/ FEED (con't)
Band treatment., Nonbearfng., LOM pressure UP NA
ground.
Band treatment., Postharvest., LOM pressure up NA
ground.
Directed spray., Nonbearing,, LOM pressure UP NA
ground.
Directed spray., Posthervest., LOM pressure up NA
ground.
Band treatment., Fall., LOM pressure ground. UP NA
Band treatment,, Winter., LOM pressure UP NA
ground.
Low votune spray (concentrate)., Fall., Low UP NA
pressure grouid.
LOM volune spray (concentrate)., Winter., UP NA
Low pressure ground.
Band treatment., Dormant., Lou pressure UP NA
ground.
BnrvH treAtment. . Fall _ Inu nrettRure around. UP HA
Naxfnun Soil H»x.
Application Text Apps
dates (Max • Max
Due) Rate
2 lb
3 lb
4 lb
2 lb
3 lb
4 lb
2 lb
3 lb
4 lb
2 lb
3 lb
4 lb
C
M
F 1/C
C
M
F 1/C
C
M
F 1/C
C
N
F 1/C
3 lb A • 1/T
3 Ib A * 1/T
3 lb A * 1/T
3 Ib A * 1/T
2 Ib A * 1/T
? Ih A * 1/T
Max 1 nun Dose Min. Restr. Geographic Geographic Use
/crop cycle, Interv Entry Allowed Disallowed Limitations
or /year (days) Interv Codes
(days)
HS NS NS
4 lb Al/C
HS NS NS
4 lb Al/C
HS HS NS
4 lb AI/C
HS HS NS
4 lb AI/C
HS NS NS OR, UA
HS NS NS OR, UA
HS HS NS OR, UA
HS NS NS OR, UA
siiBppittiiiB
HS NS NS OR, UA
US NS NS OR. UA
C46, 699
C46, 699
C46, 699
C46, 699
C46
C46
C46
C46
C46, HOH38)
ruf, nnif^
Bond treatment., Winter., Low pressure
ground.
WP NA
2 lb A " 1/Y
NS NS NS OR, UA
C46, HO1(38)
67
-------
APPENDIX A - CASE OOB2, [Pronamide] Chemical 101701 [Prcpyiemi del
SITE Application Type, Application
Timing, Application Equipment -
Surface Type & Efficacy Influen-
cing Factor (Antimicrobial only)
Form Mfnimun
Application
Rate
Naxinun Soft Ha*. Maximum Dose Mfn. Restr. Geographic Geographic Use
Application Text Apps /crop cycle, Irterv Entry Allowed Oisal lowed limitations
Rates (Max i Hax or /year (days) Interv Codes
Dse) Rate (days)
FOOD/FEED (eon'tj
Broadcast., Dormant., Low pressure ground. WP MA
Broadcast,, Fall., Lou pressure ground. UP NA
Broadcast., Winter., Lou pressure ground. WP NA
2 Ib A *
2 Ib A *
2 Ib A *
1/T
1/r
Broadcast., Post (mergence., Ground.
Broadcast., Preeraergence., Ground.
M
NA
Broadcast., Early winter., Sprayer.
Broadcast., Fall., Sprayer.
Broadcast., Postetnergence., Sprayer.
UP
MA
UP NA
UP NA
Broadcast,, Coatemergence., Ground
Broadcast., Preewergence., Ground.
UP MA
yp HA
1 Ib A *
1 Ib A *
MS
NS
MS
2 Ib A *
2 Ib A *
NS
MS
NS NS
NS NS
NS NS
MS NS
NS MS
NS NS
NS OR, UA
NS OR, UA
NS OR, WA
NS
MS
NS NS
NS
NS
NS
HS
NS
OR
OR
OR
C46, H01<3B)
C46, HOI (33)
C46, H01(38>
C46
C44
C46, C14
C46, C14
C46, C14
C46
Broadcast., Posteirwrgence., Ground.
Broadcast., Preemergence., Ground.
NOM-FOQO/NON-FEED
UP
NA
MA
2 Ib A *
2 Ib A *
NS
NS
NS NS
NS NS
NS
NS
C46
«6
Band treatment.. Fall., Lou pressure ground. UP NA
2 Ib A * NS
NS NS NS
C46
68
-------
APPENDIX A - CASE 0082, JPronanitdeJ Chemical 101701 [Propyiamide]
SITE Application Type, Application
Timing, Application Equipment -
Surface Type I Efficacy Influen-
cing Factor CAntimicrobial only)
Form Mini mm
Appl1 cat I on
Rate
Maximum Soi I Max. Maximum Dose Hln. Restr. Geographic Geographic Use
Application Text Apps /crop cycle, Interv Entry Allowed Disallowed Limitations
Rates (Max a Max or /year (days) Interv Codes
Dae) Rate (days)
NON-FOOD/BON-FEED tcon't)
Broadcast., Fall., Low pressure ground. UP NA
Broadcast., When needed.. Aircraft. yp NA
UP NA
Broadcast., Fall., Not on label. G NA
Broadcast., Fall., Sprayer. yp NA
Broadcast., Late winter.. Not on label. G UA
Broadcast., Late winter., Sprayer. yp NA
Broadcast., Not on label.. Not on label. G NA
Broadcast., Hot on label., Sprayer. WP NA
Band treatment., Fall., Low pressure ground. UP NA
Band treatment., Nuraerystock., Low pressure UP NA
ground.
Broadcast., Fall., low pressure ground. UP NA
Broadcast., Nurserystock., Low pressure UP NA
ground..
2 Ib A
3 Ib A
3 Ib A
1 Ib A
1 Ib A
1 Ib A
f IbA
1.5 Ib A
1.5 IbA
2 Ib A
2 Ib A
2 Ib A
2 Ib A
*
F
f
m
*
*
*
*
*
*
*
*
*
*
HS
NS
MS
NS
NS
NS
NS
NS
NS
NS
US
NS
NS
NS NS
NS NS
NS NS
iPHi
NS NS
NS NS
NS NS
IS NS
HS NS
HS NS
NS NS
NS NS
NS NS
NS NS
NS
NS OR
NS WA
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
C46
C46
C46
C46
C46
Broadcast., Postemergence., Low pressure
ground.
HA
2 Ib A
4/C
16 tb/f NS
NS
69
-------
APPENDIX A - CASE 0082, [Pronamfde] Chemical 101701 [Propyzamide]
SITE Application type, Application
Timing, Application Equipment -
Surface Type I Efficacy Influen-
cing Factor (Antimicrobial only)
Form Minfnun
Application
Rate
HaxIfflJn Soil Max. Hex {nun Dose Min. Hestr, Geographic Geographic Use
Application Text Apps /crop cycle, Interv Entry At Lowed Disallowed Limitations
Rates (Max a Max or /year (days) Interv Codes
Dse) Rate (days)
MOB-FOOO/HON-FEED (con't)
Broadcast,, Postplant., ton pressure ground. UP NA
Broadcast., Preemergence., Low pressure UP HA
ground.
Broadcast., Dormant., Not on label. G NA
Broadcast., Early winter., Lou pressure WP NA
ground.
Broadcast., Fall., Low pressure ground.
Broadcast., Fall., Hot on label.
Broadcast,, Fall., Sprayer.
Broadcast., Late winter., Not on label.
Broadcast., Late winter., Sprayer,
Broadcast., Not on label., Not on label.
Broadcast,, Hot on label.. Sprayer.
Broadcast., Postemergence., Not on label.
Broadcast., Winter,, Hot on label.
Band treatment.. Fall., Low pressure ground. UP
Bond treatment., Hurserystock., Low pressure UP
ground.
Z Ib A * 4/C
2 Ib A * 4/C
m
16 lb/¥ MS
16 Ib/Y NS
.0228 Ib 1K
1 .5 Ib A *
MS
HS
MS NS
NS
HS
NS NS NS
HS
FL
Fl
UP
c
G
UP
i
UP
G
UP
G
C
UP
UP
NA
NA
NA
NA
NA
NA
HA
NA
NA
NA
NA
HA
1.5 Ib A *
1 Ib A *
.0228 Ib IK sq.ft *
1 Ib A *
1 Ib A *
1 Ib A •
l.i IbA *
1.5 Ib A *
.0228 Ib IK aq.ft *
.Q22S Ib IK sq.ft *
2 Ib A *
2 Ib A »
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS NS
NS NS
NS NS
NS NS
NS NS
NS NS
NS NS
NS NS
NS NS
NS NS
pipmfi
NS NS
MS NS
NS
NS
NS
HS
NS
MS
NS
NS
NS
NS
PJp|SiHtil
MS
MS
CB9
C46, C14, GB9, GC1
MS, C14, GB9, fid
CB9
CB9
C99
C46
C46
70
-------
APPENDIX A - CASE 0082, (Pronamide) Chemical 101701 IPropyiamtde]
SITE Application Type, Application
Timing, Application Equipment -
Surface Type & Efficacy Influen-
cing Factor {Antimicrobial onlyj
Form Minimum Hex I mum
Application Application
Rate Rates
Soil Max.
Text Apps
(Max 8 Max
Ose) Rate
Maximum Dose Kin, Restr. Geographic Geographic Dae
/crop cycle, Interv Entry Allowed Disallowed Limitations
or /year (days) Interv Codes
-------
APPENDIX A - CASi OOS2, [PronamideJ Chemical 101701 [Propyiemide]
SITE Application Type, Application form Minimum Maximum Soil Max, Max inuti Dose Hln. Restr. Geographic Geographic Use
Tffliins, Application Equipment - Application Application Text Apps /crop cycle, Interv Entry Aliened Disallowed Limitations
Surface Type & Efficacy Influen- Kate Rates (Max 8 Max or /year (days) Interv Codes
cing Factor (Antimicrobial only) Ose) Rate (days)
FOOD/FEED USES
Band treatment., Ratoon.
ground.
, Low pressure UP
Band treatment., Transplant., Low pressure UP
ground.
Broadcast . ,
Broadcast.,
Broadcast.,
Broadcast.,
Broadcast . ,
Broadcast . ,
Broadcast,,
Broadcast . ,
PostpUnt.,
Postplant.,
Preemergence
Preemerseree
Aircraft. UP
Ground. up
., Aircraft. UP
., Ground. UP
Rotoon., Afrcreft. UP
Ratoon., Ground. UP
Transplant.,
Transplant,,
Aircraft. UP
Ground. UP
NA
NA
MA
MA
MA
NA
NA
MA
NA
NA
4
2
2
2
2
I
4
4
2
2
m
li^iSiliiiiMK
lb
lb
lb
lb
lb
lb
lb
lb
lb
lb
A *
A *
A »
A *
A *
A *
A *
A *
A *
A *
2/C NS NS NS CA
2/C NS NS NS CA
1/C HS NS NS CA
1/C NS NS NS CA
1/C HS NS NS CA
1/C NS NS NS CA
2/C NS NS NS CA
2/C NS NS NS CA
2/C NS NS NS CA
2/C NS NS NS CA
C46.
C46,
C46,
C46,
C46,
C46,
G46,
C46,
C46,
C46,
H01C60)
H0 1(60)
HOK60)
H01 (60)
HOH60)
H01(60)
H01C60)
HQU60)
H0 1(60}
HO 1(60)
NON-FOOO/HON-FEED
fe»ii*a&jti,Pi
lPliliPs»P
is^sSH^^^Is^KS^!?'
^^^8^i^liSK^^r^wiSi!Sis?^^w^^^^^^^
^
M^^^^^^fe^
S38ffi'M«W»2"«te
-------
APPENDIX A - CASE 0082, [Pronamfde] Chemical 101701 [Propyzamide]
SITE Application Type, Application
Timing, Application Equipment -
Surface Type & Efficacy Influen-
cing Factor (Antimicrobial only)
Foi
mi
NON-FOCD/NOH-FEIB
-------
APPENDIX A - CASE 0082, IPronamide] Chemical 101701 [Propyiamide]
LEGEND
HEADER ABBREVIATIONS
Max. Apps 3 Max Rat* : Haxlimtn number of Applications at Maxlnun Dosage Rate
Mfn. Interv (days) : Minium Interval between Applications (days)
Restr. Entry Inter* (days) : Restricted Entry Interval (days)
SOIL TEXTURE FOR HAX M»P. BATE
* Non-specffie
C Course
N Medium
f Fine
0 Others
FORMULA! OH
G
WP
AiBREVIA IONS
AN
HA
NS
UC
COOES
GRANULAR
WET TABLE POWER
As Needed
Not Applicable
Mot Specified (en label)
Unconverted due to lack of data (on label)
APPLECAT OH RATE
DCNC Dosage Can Not be Calculated
No Calc No Calculation cen be made
W PPH calculated by uetght
V PPM Calculated by volume
cut Hundred Weight
nnE-xx nn times (10 pouer -xx)j for instance,
USE LIMITATIONS CODES
"1,2341-04" Is equivalent to «.0001214"
C14
C46
G03
G99
SB?
GB9
GC1
H01
Grown for seed only.
Da not apply through eny type of Irrigation system.
Do not graze livestock in treated areas,
Do not feed or graze animals on treated areas.
Do not feed treated vines to livestock.
Do not feed clippings to livestock.
Do not graze treated areas.
day(s) preharvest Interval.
* NUMBER IH PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.} DESCRIBED IN THE LIMITATION.
GEOGRAPHIC CODES
AZ
CA
Fl
ID
MI
OH
OR
UA
Ari zona
California
Florida
Idaho
Michigan
Ohio
Oregon
Washington
74
-------
APPENDIX B. Table of the Generic Data Requirements
and Studies Used to Make the Reregistration Decision
75
-------
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active ingredients within the
ase pronamide covered by this Reregistration Eligibility Decision Document. It contains generic data
xyiirements that apply to pronamide in all products, including data requirements for which a "typical
emulation" 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
0 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
.oad, Springfield, VA 22161 (703) 487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data requirements apply.
he 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. BibMographic citation (Column 3). If the Agency has acceptable data in its files, this column lists the
lentifying number of each study. This normally is the Master Record Identification (MRID) number, but may be
"GS" number if no MRID number has been assigned. Refer to the Bibliography appendix for a complete
tation of the study.
77
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-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregi strut ion of Pro n amide
REQUIREMENT
USE
PATTERN
CITATION
PRODUCT CHEMISTRY
61-1
61-2
61-3
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of Limits
Analtyical Method
Color
Physical State
Odor
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Dissociation Constant
OctanoIAVater Partition
pH
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
ABK
40211 101 -DATA GAP
00165026, 42078501
40211101, 42078501
40211101
40211101
40211101
00061661, 00107962, 00107964
00061661, 00107962, 00107964
00165026
00061661, 00107962, 00107964
N/A - Not required.
00061661, 00107962, 00107964
00061661, 00107962, 00107964
00061661, 00107962, 00107964
00165026
00143745
00165026
79
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pronamide
REQUIREMENT
USE
PATTEPN
CITATION
PRODUCT CHEMISTRY
63-13 Stability
63-17 Storage Stability
64-1 Submittal of Samples
ECOLOGICAL EFFECTS
71-1A Acute Avian Oral - Quail/Duck
71-1B Acute Avian Oral - Quail/Duck
TEP
71-2A Avian Dietary (LCSO) - Quail
71-2B Avian Dietary (LCSB) - Duck
71-3 Wild Mammal Toxicity
71-4A Avian Reproduction - Quail
71-4B Avian Reproduction - Duck
7I-5A Simulated Field Study
71-5B Actual Meld Study
72-1A Fish Acute (LC^) - Bluegill
ABK 00165026,42078502
Not required.
Not required.
ABCK 00107997
ABCK 00107997
ABCK 00107993, 00107994, 00108003
ABCK 00108002
ABCK N/A - Not required.
ABCK WAIVED
ABCK WAIVED
ABCK N/A - Not required.
ABCK N/A - Not required.
ABCK 00107996
80
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pronam ide
REQUIREMENT
USE CITATION
PATTERN
ECOLOGICAL EFFECTS
72-IB fish Acute (LC^l - BluegUl
(TEP)
72-1C Fish Acute (LCW) - Rainbow
Trout
72-1D Fish Acute (LC^ - Rainbow
Trout (TEP)
72-2A Aquatic Invertebrate (EC«)
72-2B Aquatic Invertebrate (EC^
(TEP)
72-3A Estuariney Marine Toxicity - Fish
72-3B Estuarine/Marine Toxicity -
Mollusk
72-3C Estuarine/Marine Toxicity -
Shrimp
72-4A Early Life Stage Fish
72-4B Life Cycle Invertebrate
72-5 Life Cycle Fish
ABCK 00107196
ABCK 00107996
ABCK N/A - Not required.
ABCK 00098313
ABCK N/A - Not required.
BC N/A - Not required
BC DATA GAP
BC DATA GAP
ABCK N/A - Not required
ABCK DATA GAP
ABCK RESERVED - pending the results of 72-4 Fish Early Life Cycle or
Aquatic Invertebrate Life Cycle
81
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pronamide
REQUIREMENT USE CITATION
PATTERN
ECOLOGICAL EFFECTS
72-6 Aquatic Organism Accumulation
72-7A Simulated field - Aquatic
Organisms
72-7B Actual Field - Aquatic
Organisms
123-1A Seed Germination/Seedling
Emergence
123-1B Vegetative Vigor
123-2 Aquatic Plant Growth
124-1 Terrestrial Field Study
124-2 Aquatic Field Study
141-1 Honey Bee Acute Contact
Toxicity
141-2 Honey Be« Toxicity Of Residues
on Foliage
141-5 Field Testing for Pollinators
142-1 Acute Toxicity to Aquatic
Insects
142-2 Aquatic Insect Life Cycle Study
ABCK RESERVED - pending enviommental fate data on bioaccumulation.
ABCK N/A - Not required due to low toxicily and low expected ecological
effect.
ABCK N/A - Not required due to low toxicity and low expected ecological
effect,
ABCK 42176801 - DATA GAP
ABCK 42176801
ABCK 42176802 - DATA GAP
ABCK N/A - Not required.
ABCK RESERVED - pending results of Tier II tests,
ABCK 00028772
ABCK N/A - Not required.2
ABCK N/A - Not required.1
ABCK RESERVED
ABCK RESERVED
2 Application of pronamide is made in fall or early winter when bees are not expected to be exposed to this chemical.
82
-------
APPENDIX B
Data Supporting Guideline Requirements for the Registration of Pronamide
REQUIREMENT
1KB CITATION
PATTERN
ECOLOGICAL EFFECTS
142-3
143-1
thru
143-3
Simulated or Actual Held
Testing for Aquatic Insects
NonTarget Insect Testing -
Predators and Parasites
TOXICOLOGY
81-1 Acute Oral Toxicity - Rat
81-2 Acute Dermal Toxicity -
Rabbit/Rat
81-3 Acute Inhalation Toxicity - Rat
81-4 Eye Irritation
81-5 Dermal Irritation
81-6 Dermal Sensitization
81-7 Acute Delayed Neurotoxicity -
Hen
82-1A 90-Day Feeding - Rodent
82-1B 90-Day Feeding - Non-rodent
82-2 21-Day Dermal - Rabbit/Rat
82-3 90-Daj Dermal - Rodent
82-4 90-Day Inhalation - Rat
ABCK RESERVED
ABCK RESERVED
ABK
ABK
ABK
ABCK
ABK
ABK
00083663
00083663
00083663
00083663
00126574
00062605
N/A - Not required because pronamide is neither an
organophosphate, nor an analog of a neurotoxic compound,
N/A - Not required.
N/A
N/A
N/A
N/A
83
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pronamide
REQUIREMENT
USE
PATTERN
CITATION
TOXICOLOGY
82-5A 90-Day Neurotoxidly - Hen
82-5B 90-Day Neurotoxicity - Mammal
83-1A Chronic Feeding Toxicity -
Rodent
83-1B Chronic Feeding Toxicity - Non-
Rodent
83-2A Oncogenicity - Rat
83-2B Oncogenicity - Mouse
83-3 A Developmental Toxicity - Rat
83-3B Developmental Toxicity - Rabbit
83-4 2-Generation Reproduction -
Rat
84-2A Gene Mutation (Ames Test)
84-2B Structural Chromosomal
Aberration
84-4 Other Genotoxic Effects
85-1 General Metabolism
N/A - Not required because pronamide is neither an
organophosphate, nor an analog of a neurotoxic compound.
N/A - Not required because pronamide is neither an
organophosphate, nor an analog of a neurotoxic compound.
ABK 41714001
ABK 00107949
ABK 41714002
ABK 00107968
ABK 40334501
ABK 00148064, 00148065
ABK 41540301
ABK 40090602,40211108
ABK 40211106
ABK 40211105
ABK 41929901, 42858001
84
-------
APPENDIX B
Data Supporting Guideline Requirements for the Registration of Fronamide
REQUIREMENT USE CITATION
USE
PATTERN
TOXICOLOGY
85-2 Dermal Penetration
86-1 Domestic Animal Safety
POST-APPLICATION/REENTRY
EXPOSURE
132-1A
13MB
133-3
133-4
Foliar Residue Dissipation
Soil Residue Dissipation
Dermal Passive Dosimetry
Exposure
Inhalation Passive Dosimetry
Exposure
APPLICATION EXPOSURE
231
232
Estimation of Derail Exposure
at Outdoor Sites
Estimation of Inhalation
Exposure at Indoor Sites
ENVIRONMENTAL FATE
161-1 Hydrolysis
161-2 Photodegradation - Water
ABK Although submitted studies were unacceptable, a new study is not
required because based on worst-case assumptions, the risk appears
acceptable.
N/A - Not required.
ABCK DATA GAP
AC N/A - Not required.
ABCK DATA GAP
N/A - Not required.
ABCK
DATA GAP
ABCK DATA GAP
ABCK 00107980
ABC 40320601, 40420301
85
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Pronamide
REQUIREMENT USE CITATION
USE
PATTERN
FATE
161-3
161-4
162-1
162-2
162-3
162-4
163-1
163-2
163-3
164-1
164-2
164-3
164-4
164-5
165-1
165-2
165-3
Photodegradation - Soil
Photodegradation - Air
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Aerobic Aquatic Metabolism
Leaching/ Adsorption/Desorption
Volatility -Lab
Volatility - Field
Terrestrial Field Dissipation
Aquatic Field Dissipation
Forest Field Dissipation
Combination and Tank Mixes
Long-Term Soil Dissipation
Confined Rotational Crop
Meld Rotational Crop
Irrigated Crops
ABC
ABCK
ABC
ABCK
AB
AB
ABCK
ABCK
ABC
ABC
41913504
N/A - Not required because of relatively low vapor pressure.
41568901, 41913502
41913505
WAIVED
N/A - Not required.
40211104,40420103,41913501
WAIVED
N/A - Not required because 163-2 Volatility - Lab study was
waived.
40925401 - DATA GAP
N/A - Not required.
WAIVED
N/A - Not required because pronamide is not registered for
combination and tank mixes with other chemicals.
RESERVED - pending the results of field dissipation study.
N/A - Not required.
DATA GAP
N/A - Not required.
86
-------
APPENDIX B
Data Supporting Guideline Requirements for the Registration of Pronamide
REQUDUMENT
ENVIEONMENTAL FATE
165-4 Bioaccuimilatin in Fish
165-5 Bioaccumulation - Aquatic
Non-Target Organisms
201-1 Droplet Size Spectrum
202-1 Drift Field Evaluation
HESIDUE CHEMISTRY
171 -4 A Nature of Residues - Plants
17I-4B Nature of Residues - Livestock
171-4C Residue Analytical Method -
USE CITATION
PATTERN
ABC DATA GAP - study currently being reviewed by the Agency,
ABC N/A - Not required.
ABC DATA GAP
ABC DATA GAP
00107953, 00107957, 00107958, GS008201, 40494802, 40494803
00107954, 00107958, 42043401, 42614201
00035563, 00035565, 00107958, 00107959 - DATA GAP5
Plants
171-4D Residue Analytical Method -
Animal
171-4E Storage Stability
171-4F Magnitude of Residue - Potable
H20
171-4G Magnitude of Residue - Fish
00035566, 00070933, 00070934, 00074523, 00077215, 00107957,
00107960, 00107961, 00107965, 00107967, 00125382 -
DATA GAP2
41559101, 42614201 - DATA GAP
N/A
N/A
3 Validation of the revised residue analytical method for animal commodities is required. Representative plant and animal
tissue samples must be tested by MEM protocols C, D, and E.
87
-------
APPENDIX B
Data Supporting Guideline Requirements for the Registration of Pronamide
REQUIREMENT
USE CITATION
PATTERN
RESIDUE CHEMISTRY
171-411 Magnitude of Residue -
Irrigated Crop
171-41 Magnitude of Residue - Food
Handling Establishment
17 MJ Magnitude of Residues -
Meat/ Milk/Poultry
171-4K Cropfield Trials
Leafy Vegetables
Endive
Lettuce
Rhubarb (Pacific Northwest)
Legume Vegetables Group
Peas, dried (winter) [Pacific
Northwest]
Stone Fruits Group
Cherries
Nectarines
Peaches
Plums (fresh prunes)
ABC
N/A
N/A
00107958, 00107959, 00107967, 40494801, 40782201, 42043401,
42614201
00107957
00070933, 00107957, 00107958
N/A - Not required.
DATA GAP
00074523
00074523
00035565, 00074523
00074523
88
-------
APPENDIX B
Data Supporting Guideline Requirements for the Re registration of Pr on amide
REQUIREMENT
USE
PATTERN
CITATION
RESIDUE CHEMISTRY
171-4K Cropfield Trials - continued
Small Fruits and Berries Group
Blackberries
Blueberries
Boysenberries
Grapes
Raspberries
Non-Grass Animal Feeds
Alfalfa
Clover
Sainfoin
Trefoil
Vetch
Miscellaneous Commodities
Artichoke
171-4L Processed Food
Apples
Grapes
Plums
ABC
171-5
Reduction of Residues
00107960
00035566, 00153419
N/A
00074523
00107960
00033380, 00107958, 00107965,
00107967 - DATA GAP
00107958, 00107965
00107965
00107965
00107965
00077215, 00125382 - DATA GAP
DATA GAP
DATA GAP
DATA GAP
N/A
89
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-------
APPENDIX C. Citations Considered to be Part of the
Data Base Supporting the Reregistration of Pronamide
91
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-------
GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all
studies considered relevant by EPA in arriving at the positions and conclusions stated
elsewhere in the Reregistration Eligibility Document. Primary sources for studies in
this bibliography have been the body of data submitted to EPA and its predecessor
agencies in support of past regulatory decisions. Selections from other sources
including the published literature, in those instances where they have been considered,
are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In
the case of published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a
distinct title (or at least a single subject), can stand alone for purposes of review and
can be described with a conventional bibliographic citation. The Agency has also
attempted to unite basic documents and commentaries upon them, treating them as a
single study.
3. IDENTinCATION 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 Pvecord 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
93
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the date from the evidence contained in the document. When the date appears
as (19??)» the Agency was uoable to determine or estimate the date of the
document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained
between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the
trailing parentheses include (in addition to any self-explanatory text) the
following elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received,"
(2) Administrative number. The next element immediately following the
word "under" is the registration number, experimental use permit
number, petition number, or other administrative number associated
with the earliest known submission,
(3) Submitter. The third element is the submitter. When authorship is
defaulted to the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the
trailing parentheses identifies the EPA accession number of the volume
in which the original submission of the study appears. The six-digit
accession number follows the symbol "CDL," which stands for
"Company Data Library." This accession number is in turn followed
by an alphabetic suffix which shows the relative position of the study
within the volume.
94
-------
BIBLIOGRAPHY
MRID
CITATION
Hileman, B., April 19, 1993. Concerns Broaden over Chlorine and
Chlorinated Hydrocarbons- Calls for Gradual Phaseout of Classes of
Chlorinated Organics Are Being Made in Response to Evidence of Adverse
Health Effects on Humans and Wildlife. C & E News, Volume 71, No. 16,
pp. 11-20.
00002646 Agamalian, H. (1973) Report of Planned Work Accomplished: Selective
Herbicides in Vegetables (Tomatoes): Report No. 38169. (Unpublished study
received May 6, 1976 under 3125-277; prepared by Univ. of California,
Agricultural Extension Service, submitted by Mobay Chemical Corp,,
Agricultural Chemicals Div.3 Kansas City, Mo.; CDL:224187-Z)
00028772 Atkins, E.L.; Greywood, E.A.; Macdonald, R.L. (1973) Toxicity of Pesticides
and Other Agricultural Chemicals to Honey Bees: Laboratory Studies. Rev.
By Univ. of California—Riverside, Dept of Entomology. Riverside, Calif.:
UC, Agricultural Extension Service, (Also in unpublished submission received
Apr 2, 1980 under 464-556; submitted by Dow Chemical U.S.A.,
Midland, Mich.; CDL:242149-Z)
00033380 Lodge, M.D.; Santelmann, P.W.; Lawrence, S.C.; et al. (1972) Analytical
Results of Kerb Residue: R.A.R. No. 2-71-128. (Unpublished study including
R.A.R. nos. 2-70-71, 2-70-86, 2-70-78..., received Dec 20, 1972 under
3F1317; submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:092251-A)
00035563 Chollet, C.C.; Chennault, B.; Ryan, J.B.; et al. (1973) Analytical Results of
Kerb Residue: R.A.R. No. 2-69-160. (Unpublished study including R.A.R.
nos. 2-71-240, 2-71-241, 2-71-242..., received Aug 23, 1973 under 4G1426;
submitted by Rohm &. Haas Co., Philadelphia, Pa.; CDL:093801-D)
00035564 (Met, C.C.; Lawrence, S.C. (1972) Analytical Results of Kerb Residue:
R.A.R. No. 2-71-239. (Unpublished study including R.A.R, no. 2-72-333,
received Aug 23, 1973 under 4G1426; submitted by Rohm & Haas Co.,
Philadelphia, Pa.; CDL:093801-E)
00035565 Chollet, C.C.; Lawrence, S.C. (1972) Analytical Results of Kerb Residue:
R.A.R. No. 2-71-195. (Unpublished study including R.A.R. no. 2-72-110,
95
-------
BIBLIOGRAPHY
MMD
CITATION
received Aug 23, 1973 under 4G1426; submitted by Rohm & Haas Co.,
Philadelphia, Pa.; CDL:Q938Q1-F)
00035566 Lawrence, S.C.; Neidlinger, T.J.; Doughty, C.C.; et al. (1972) Analytical
Results of Kerb Residue: R.A.R. No, 2-69-66. (Unpublished study including
E.A.R. nos. 2-71-155, 2-71-268, 2-72005.,., received Aug 23, 1973 under
4G1426; submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:093801-G)
00062605 Sinkeldam, E.J. (1974) Sensitization Test with Kerb Technical in Guinea Pigs;
Report No. R 4448. (Unpublished study received Feb 25, 1977 under 707-98;
prepared by Central Instituut voor Voedingsonderzoek TNO, Netherlands,
submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:233726-C)
00070933 Rohm and Haas Company (1981) Kerb(R) 50-W Herbicide (707-98): Lettuce
Residue Studies. Interim rept. (Unpublished study received Mar 5, 1981
under 707-98; prepared in cooperation with Craven Laboratories, Inc.;
CDL;244519-A)
00070934 Adler, IX.; Gordon, C.F.; Haines, L.D.; et al. (1972) Determination of
residues from herbicide ~ N ~ -(1,1 -dimethylpropynyl)-3 ,5dichlorobenzamide
by electron capture gas-liquid chromatography. Journal of the Association of
Official Analytical Chemists 55(4): 802-805. (Also~In~unpubEshed
submission received Mar 5, 1981 under 707-98; submitted by Rohm & Haas
Co., Philadelphia, Pa.; CDL:244519-B)
00074523 Rohm & Haas Company (1979) Summary and Discussion: Kerb.
(Compilation; unpublished study received Jun 24, 1981 under 707-159;
CDL:070157-A)
00077215 Rohm & Haas Company (1980) Summary and Discussion: Kerb(R).
(Compilation; unpublished study received Jun 24, 1981 under 707-159;
CDL;Q70158-A)
00083663 Powers, M.B. (1970) Final Report: Acute Oral-Rats; Draize Eye-Rabbits;
Acute Dermal—Rabbits; Primary Skin—Rabbits; Acute Inhalation
Exposure-Rats: Project Nos. 417-337; 417-339; 417-341; 417-340; 417-338.
(Unpublished study received Mar 13, 1971 under IF 1139; prepared by TRW,
Inc., submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:09Q919~C)
96
-------
BIBLIOGRAPHY
MRID
CITATION
00085504 Larson, P.S.; Borzelleca, J.F. (1968) Acute Oral Toxicity of RH315, W.P. in
Albino Rats. (Unpublished study received Jun 15, 1969 under 9G0821;
prepared by Medical College of Virginia, Dept. of Pharmacology, submitted
by Rohm & Haas Co., Philadelphia, Pa.; CDL:091422-B)
00085511 Larson, P.S.; Borzelleca, J.F. (19??) Percutaneous Toxicity Study of RH-315
WP in Rabbits. (Unpublished study received Jun 15, 1969 under 9G0821;
prepared by Medical College of Virginia, Dept. of Pharmacology, submitted
by Rohm & Haas Co., Philadelphia, Pa.; CDL:091422-1)
00098313 Vilkas, A.G.; Browne, A.M. (1980) The Acute Toxicity of Kerb Technical
(No Clay) to the Water Flea-Daphnia magna- Straus; UCCES Project No.
11506-33^3. (Unpublished study received Apr 1, 1982 under 707-159;
prepared by Union Carbide Corp., submitted by Rohm & Haas Co.,
Philadelphia, Pa.; CDL:247155-A)
00107196 McCann, L (1971) Kerb 50-W: Bluegill; Test No. 325. (U.S. Agricultural
Research Service, Pesticides Regulation Div., Animal Biology Laboratory;
unpublished study; CDL:13Q346-A)
00107949 Larson, P.; Borzelleca, J. (1970) Toxicologic Study on the Effect of Adding
RH-315 to the Diet of Beagle Dogs for a Period of Two Years. (Unpublished
study received Mar 12, 1971 under 1F1139; prepared by Medical College of
Virginia, Dept. of Pharmacology, submitted by Rohm & Haas Co.,
Philadelphia, PA; CDL:Q9Q918-A)
00107953 Yih, R.; Swithenbank, C. (1970) Identification of Metabolites of
N^l^-diniethylpropynyy-a^-dichlorobenzamide in Soil and Alfalfa.
(Unpublished study received Mar 12, 1971 under 1F1139; submitted by Rohm
& Haas Co., Philadelphia, PA; CDL:090918-G)
00107954 Yih, R.; Swithenbank, C. (1970) Identification of Metabolites of
N-(l}l-dimethylpropynyl)-355-dichloroben2amide in Rat and Cow Urine and
Rat Feces. (Unpublished study received Mar 12, 1971 under 1F1139;
submitted by Rohm & Haas Co., Philadelphia, PA; CDL:09Q918-H)
00107957 Rohm & Haas Co. (1971) Results of Tests on the Amount of Residue
Remaining in or on Lettuce and Related Crops and Soil Including a
97
-------
BIBLIOGRAPHY
MMD
CITATION
Description of the Analytical Method: Kerb. (Compilation; unpublished study
received Mar 11, 1971 under 1F1139; CDL: 090917-A; 090916)
00107958 Rohm & Haas Co. (1969) Results of Tests on the Amount of Residues
Remaining on or in Crops, Animal Tissues, Milk, and Soil Investigated and
the Analytical Methods Used: RH-315, (Compilation; unpublished study
received Jun 16, 1969 under 900821; CDL: 091423-A)
00107959 Rohm & Haas Co. (1970) Kerb: 3,5-Dichloro-N-(l»l-dimethyl-2-propvnyl)
Benzamide: Report on a Study To Determine Residue Levels in Eggs and
Tissues from Poultry Feed Kerb. (Compilation; unpublished study received on
unknown date under 9G0821; CDL: 091424-A)
00107960 Rohm & Haas Co. (1972) Results of Tests on the Amount of Residues
Remaining in the Treated Canefruit Crops; A Description of the Analytical
Method: Kerb 75-W. (Compilation; unpublished study received May 15, 1973
under 3F1317; CDL:092128-A)
00107961 Rohm & Haas Co. (1969) Residues of RH-315 in Lettuce, Alfalfa and Milk.
(Compilation; unpublished study received Feb 17, 1971 under 1F1139;
CDL:093447-A)
00107962 Rohm & Haas Co, (1969) The Name, Chemical Identity and Composition of
the Pesticide Chemical: Kerb, (Compilation; unpublished study received Feb
17, 1971 under 1F1139; CDL:093447-B)
00107963 Rohm and Haas Co. (19??) Kerb ... Report on a Study to Determine Residue
Levels in Eggs and Tissues From Poultry Feed Kerb. (Unpublished study
received Apr 2, 1969 under 9G0821; CDL:093523-A)
00107964 Rohm & Haas Co. (1969) The Name, Chemical Identity and Composition of
the Pesticide Chemical; RH-315. (Compilation; unpublished study received
Apr 2, 1969 under 900821; CDL:093523-B)
00107965 Rohm & Haas Co, (1972) Results of Tests on the Amount of Residue
Remaining in or on Alfalfa, Clover, Crown Vetch, Sainfoin and Trefoil
(Birdsfoot), Including a Description of the Analytical Method: Kerb.
(Compilation; unpublished study received Dec 20, 1972 under 3F1317;
CDL:092250-A; 092252)
98
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BIBLIOGRAPHY
MRTO
CITATION
00107967 Rohm & Haas Co. (1974) Analytical Methods and Residues: Kerb.
(Compilation; unpublished study received Sep 9, 1974 under 5F1552;
CDL:094214-A)
00107968 Smith, J. (1974) Eighteen Month Study on the Carcinogenic Potential of Kerb
(RH-315; Pronamide) in Mice. (Unpublished study received Sep 16, 1974
under 3F1317; prepared in cooperation with Medical College of Virginia,
submitted by Rohm & Haas Co., Philadelphia, PA; CDL:094304-A)
00107980 Rohm and Haas Co. (1973) A Study of the Hydrolysis of the Heibicide Kerb
in Water: Laboratory 23 Technical Report No. 23-73-8. (Unpublished study
received Apr 27, 1973 under 707-113; CDL: 120314-A)
00107993 Shellenberger, T. (1971) Subacute Toxicity Evaluation of Kerb
3,5dichloro-N-(l,l-dimethyl-2-propynyl)-benzamide with Young Adult
Bobwhite Quail (A Seven Day Range Finding Study): GSRI Project No,
NC-501. (Unpublished study received May 16, 1972 under 70798; prepared
by Gulf South Research Institute, submitted by Rohm & Haas Co.,
Philadelphia, PA; CDL:12Q402-N)
00107994 Shellenberger, T. (1971) A Subacute Toxicity and Tissue Residue Study of
Kerb 3,5-dicnloro-N-(l,l-dimethyl-2-propynyl)-benzamide Herbicide in Young
Adult Bobwhite Quail: GSM Project No. NC-501. Final rept. (Unpublished
study received May 16, 1972 under 707-98; prepared by Gulf South Research
Institute, submitted by Rohm & Haas Co., Philadelphia, PA; CDL:120402-O)
00107996 Binns, R.; Clark, G. (1969) The Acute Toxicity to Fish of An Experimental
Herbicide RH-315-75WP: 2932/69/358. (Unpublished study received Jun 22,
1970 under 707-EX-63; prepared by Huntingdon Research Centre, Eng,,
submitted by Rohm & Haai Co., Philadelphia, PA; CDL:123888-A)
00107997 Robinson, D.; Shillam, K. (1969) Toxicity of RH-315 to the Japanese Quail
and the Mallard Duck: 2839/69/265. (UnpubEshed study received Jun 22,
1970 under 707-EX-63; prepared by Huntingdon Research Centre, Eng.,
submitted by Rohm & Haas Co., Philadelphia, PA; CDL:123888-B)
00108002 Fink, R, (1975) Eight-day Dietary LC50--Malkrd Duck; Technical Kerb:
Project No. 129-107. Final rept. (Unpublished study received Feb 25, 1977
99
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BIBLIOGRAPHY
MRID
CITATION
under 707-98; prepared by Truslow Farms Inc., submitted by Rohm & Haas
Co., Philadelphia, PA; CDL: 233723-A)
00108003 Fink, R, (1975) Eight-day Dietary LC50~Bobwhite Quail: Technical Kerb;
Project No. 129-106. Final rept. (Unpublished study received Feb 25, 1977
under 707-98; prepared by Truslow Farms Inc., submitted by Rohm & Haas
Co., Philadelphia, PA; CDL: 233723-B)
00114114 Newberne, P.; McConnel, R.; Essigmann, E.; et al. (1982) Kerb: Chronic
Toxicity Study in the Mouse: Project No. 77-1. (Unpublished study received
Aug 31, 1982 under 707-98; prepared by Massachusetts Institute of
Technology, Dept. of Nutrition and Food Science, Animal Pathology
Laboratory, submitted by Rohm and Haas Co., Philadelphia, PA;
CDL:248233-A)
00125382 Rohm & Haas Co. (1982) Kerb 50-W Herbicide Use on Artichokes.
(Compilation; unpublished study received Feb 4, 1983 under 707-159;
CDU249475-A)
00126574 WARF Institute, Inc. (1972) Report: WARF No. 2060619. (Unpublished
study received Apr 23, 1974 under 538-115; submitted by O.M. Scott & Sons
Co., Marysville, OH; CDL:028337-B)
00133112 Powers, M. (1970) Acute Oral-Rats/Draize Eye-Rabbits/Acute
Dermal-Rabbits/Primary SMn--Rabbits/Aeute Inhalation Exposure-Rats: Kerb
50-W, Final rept. (Unpublished study received Feb 25, 1971 under 707-98;
prepared by Hazleton Laboratories, Inc., submitted by Rohm & Haas Co.,
Philadelphia, PA; CDL:004358-A)
00143745 Martinson, J. (1985) Qctanol/Water Partition Coefficient of Pronamide:
Project No. 84-E-216POW: Second Revised Final Report. Unpublished study
prepared by Biospherics Incorporated, 37 p,
00148064 Costlow, R.; Kane, W. (1985) Range-finding Teratology Study with Kerb in
Rabbits: Report No. 83R-025. Unpublished study prepared by Rohm and
Haas Co. 145 p.
100
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BIBLIOGRAPHY
MMD
CITATION
00148065
00153419
00165026
40090602
40211101
40211104
40211105
40211106
40211108
Costlow, R.; Kane, W. (1985) Teratology Study with Kerb Technical (No
inert ingredient) in Rabbits: Report No. 83R-026. Unpublished study prepared
by Rohm and Haas Co. 151 p.
Rohm and Haas Co. (1985?) Residue Chemistry; Kerb 50-W Herbicide in
Water Soluble Pouches: Use on Blueberries: Includes Analytical Methods
1809-1 and JAOAC-55-72, and Residue Data. Unpublished compilation. 91
P-
Rohm and Haas Co. (1986) KERB Product Chemistry. Unpublished
compilation. 104 p,
Shirasu, Y.; Moriya, M,; KoyashiM} R. (1978) Mutagenieity of Kerb
(Propyzamide) in Bacteria: Report No. 78RC-1018. Unpublished study
prepared by Institute of Environmental Toxicology. 9 p.
Nichols, R. (1987) Kerb Product Chemistry: Laboratory Project ID:
RWN-87-051. Unpublished compilation prepared by Rohm and Haas Co.
P-
74
Nelson, S. (1987) Adsorption/Desorption of Carbon 14 RH-24,580 and Carbon
14 RH-24,644: Rohm and Haas Technical Report No. 31C-87-15.
Unpublished study prepared by Rohm and Haas Co, 350 p.
Sames, J.; Mcleod, P.; McCarthy, K. (1984) Kerb in vivo Cytogenic Study in
Mice: Final Report: Report No. 84R-112. Unpublished study prepared by
Rohm and Haas Co. 47 p.
Tippins, R.; McSheehy, T.; Forster, R.; et al. (1984) Gene Mutation in
Chinese Hamster V79 Cells: Kerb Technical: Final Report: Report No.
84RC-038. Unpublished study prepared by Life Science Research, Roma
Toxicology Center. 51 p.
Kumaroo, P, (1987) Kerb Technical Herbicide; Test for Chemical Induction of
Chromosome Aberration Using Monolayer Cultures of Chinese Hamster Ovary
(CHO) Cells with and without Metabolic Activation: SITEK Study No.
0046-3100. Unpublished study prepared by Sitek Research Laboratories. 107
P-
101
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BIBLIOGRAPHY
MMD
CITATION
40256701 DiDonato, L.; Hazelton, G. (1987) Kerb Herbicide: Dermal Absorption Study
in Male Rats: Protocol No. 86P-467: Report No. 86R-225. Unpublished study
prepared by Rohm and Haas Co. 136 p.
40320601 Nelson, S. (1987) Characterization of Degradates from the Photolysis of
Pronarnide: Rept. No. 31C-87-27. Unpublished supplemental report prepared
by Rohm and Haas Co. 58 p.
40334501 Solomon, H.; Holz, J. (1987) Kerb Herbicide: Oral (Gavage) Developmental
Toxicity Study in Rats: Protocol No. 86P-354B: Rept. No. 87R-003.
Unpublished study prepared by Rohm and Haas Co. 265 p.
40420301 Carpenter, M.; Fennessey, M. (1987) Determination of the Photolysis Rate of
Carbon 14-phenyl Pronamide in pH-7 Aqueous Solution: ABC Final Report
No. 35172. Unpublished study prepared by Rohm and Haas Co. in
cooperation with Analytical Bio-Chernistry Laboratories, Inc. 1028 p.
40494801 Jameson, C.; Tillman, A. (1987) Metabolism of Carbon 14-Pronamide in
Lactating Goats: ABC Final Report No. 35133; Technical Report No.
31C-88-G1. Unpublished compilation prepared by Analytical Bio-chemistry
Laboratories, Inc., and Rohm and Haas Research Laboratories. 1343 p.
40494802 Nelson, S. (1987) Metabolism of Carbon 14-Pronamide in Lettuce: Technical
Report No. 31C-88-02. Unpublished study prepared by Rohm and Haas Co.,
in cooperation wuth Pan-Agricultural Labs, Inc., and Others. 357 p,
40494803 Reibach, P. (1988) Metabolism of Pronamide by Alfalfa Under Field
Conditions: Technical Report No. 31C-88-03. Unpublished study prepared by
Rohm and Haas Research Laboratories in cooperation with Pan Agricultural
Labs., and Others. 323 p.
40782201 Jameson, C.; Korsch, B.; Smith, S. (1988) Metabolism of carbon 14
Pronamide in Laying Hens: Technical Report No. 34C-88-44; Final Report
No. 35133. Unpublished study prepared by Rohm and Haas Co., in
cooperation with Analytical Bio-chemistry Labs, Inc., and Others. 816 p.
40925401 Nelson, S.; Zogorski, W. (1988) Kerb Herbicide Terrestrial Field Dissipation:
Two Sites: Project ID. 34C-88-54. Unpublished study prepared by Rohm and
102
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BIBLIOGRAPHY
MRID
CITATION
Haas Co. in cooperation wtih Craven Laboratories and Pan-Agricultural
Associates. 1609 p.
41117201 DiDonato, L.; Hazelton, G. (1989) Report Amendment 1 to Kerb Herbicide:
Dermal Absorption Study in Male Rats: Protocol No. 86P467. Unpublished
study prepared by Rohm and Haas Co. 35 p.
41540301 Solomon, H.; Brown, W, (1990) Pronamide: Two-generation Reproduction
Study in Rats: Protocol No. 88P-309: Report No. 88R-257. Unpublished study
prepared by Rohm and Haas Co., Toxicology Dept. 582 p.
41568901 Olson, G., Lawrence, L. (1990) Aerobic Metabolism of Carbon 14 Pronamide
in Sandy Loam Soil: Lab Project Number: 1250: 309. Unpublished study
prepared by Pharmacology and Toxicology Research Laboratory. 67 p.
41714002 Bailey, D. (1990) Kerb Herbicide (Technical, No Clay): 24-Month Dietary
Chronic Toxicity/Oncogenicity Study in Rats: 24-Month Oncogenicity Study in
Rats: Lab Project Number: HLA 417-426M: 87RC-62. Unpublished study
prepared by Hazleton Laboratories America, Inc. 2218 p.
41913501 Ndson, S. (1987) Mobility Studies Related to Pronamide: Response to EPA
review (Shaughnessy No. 101701): Lab Project Number: 3491-40.
Unpublished study prepared by Rohm amd Haas Company. 8 p.
41913502 Nelson, S. (1991) Aerobic Soil Metabolism of 14C-Profiamide in Sandy Loam
Soil: Response to EPA Review (Shaughnessy No. 101701): Lab Project
Number: 34-91-39. Unpublished study prepared by Rohm and Haas
Company, 7 p.
41913504 Carpenter, M. (1987) Soil Photolysis of 14-C-Phenyl Pronamide: Lab Project
Number; 35238. Unpublished study prepared by Rohm and Haas Company.
683 p.
41913505 Olson, G.; Lawrence, L. (1989) Anaerobic Metabolism of Carbon 14
Propamide in Sandy Loam Soil: Lab Project Number: 1175: 271. Unpublished
study prepared by Pharmacology and Toxicology Research Laboratory. 54 p.
103
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BIBLIOGRAPHY
MRID
CITATION
41929901 Smith, S. (1991) Rat Metabolism of carbon 14 Pionamide: Lab Project
Number: R&H 34-91-43, Unpublished study prepared by Rohm & Haas Co.
248 p.
42043401 Hofmann, C.; Nelson, S. (1991) Pronamide Metabolism in Goats: Residue
Analysis of Goat Liver: Supplement to: Lab Project Number: 34-91-63.
Unpublished study prepared by Rohm and Haas Co. 53 p.
42078501 Graves, D. (1991) Kerb Technical Product Chemistry: Additional Data : Lab
Project Number: APR/SH-91-246. Unpublished study prepared by Rohm and
Haas Co. 27 p.
42078502 Graves, D. (1991) Product Chemistry Series: Physical and Chemical
Characterization Studies of Kerb Technical 63-13 Sensitivity to light: Lab
Project Number: APR/SH/91/247. Unpublished study prepared by Rohm and
Haas Co. 23 p.
42176801 Hoberg, J. (1992) Kerb Techiucal-Determinalion of Effects on Seed
Germination, Seedling Emergence and Vegetative Vigor of Ten Plant Species:
Final Report: Lab Project Number: 91-10-3974: 86.0591.6138.610: RH
91RC-0069. Unpublished study prepared by Springbom Labs, Inc. 218 p.
42176802 Hoberg, J. (1991) Kerb Technical-Toxicity to the Freshwater Green Alga,
Selenastroni capricornutum: Lab Project Number: 91-11-4005: 91RC-0070:
86. 0591. 6137. 430. Unpublished study prepared by Springbom Labs, Inc.
65 p.
42614201 Smith, S. (1992) Metabolism of (carbon 14)-Pronamide in Laying Hens: An
Addendum: Lab Project Number: 34-92-94, Unpublished study prepared by
Rohm and Haas Co. 279 p.
42858001 Smith, S, (1993) Metabolism of (carbon 14) Pronamide in Rats: Supplement A
to: (carbon 14)-pronamide (Kerb Herbicide): Pharmacokinetic Study in Rats:
Lab Project Number: 34-93-57: 89R-163A. Unpublished study prepared by
Rohm and Haas Company, Toxicology Department. 314 p.
42987501 Hazelton, G.; DiDonato, L.; KaminsM, E.; et al.. (1993) pronamide (Kerb
Herbicide): Effect of Endocrine Regulation on Rat Testes: Finalized Report:
104
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BIBLIOGRAPHY
MRID CITATION
Lab Project Number; 92P-053: 92R-053. Unpublished study prepared by
Rohm and Haas Co. 29i p,
GS0082001 Yih, R.; Swithenbank, C.; McRae, D. (1970) Transformation of Heibicide N-
(l.l-dimethylpropynyO-SjS-dichlorobenzainideinSoil. Weed Sci. 18:604-607,
105
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APPENDIX D. List of Available Related Documents
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The following is a list of available documents related to pronamide. It's purpose is to
provide a path to more detailed information if it is needed. These accompanying documents
are part of the Administrative Record for pronamide and are included in the EPA's Office of
Pesticide Programs Public Docket.
1. Health and Environmental Effects Science Chapters
2, Detailed Label Usage Information System (LUIS) Report
3. Pronamide RED Fact Sheet (Appendix F)
4, PR Notice 91-2 (included in this appendix) pertains to the Label Ingredient
Statement
Federal publications on pronamide are available and may be purchased from the National
Technical Information Service (NTIS), 5825 Port Royal Road, Springfield, VA 22161.
1. Guidance for the Reregistration of Pesticide Products Containing Pronamide as
the Active Ingredient (The 1987 Registration Standard): NTIS Stock No.
PB87-103735
2. Pesticide Fact Sheet (No. 70) for Pronamide: NTIS Stock No. PB87-124723
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
PR NOTICE 91-2
NOTICE TO MANUFACTURERS, PRODUCERS, FQRMULATORS,
AND REGISTRANTS OF PESTICIDES
ATTENTION: Persons Responsible for Federal Registration of
Pesticide Products.
SUBJECT: Accuracy of Stated Percentages for Ingredients
Statement
I. PURPOSE:
The purpose of this notice is to clarify the Office of
Pesticide Program's policy with respect to the statement of
percentages in a pesticide's label's ingredient statement.
Specifically, the amount (percent by weight} of ingredient(s)
specified in the ingredient statement on the label must be stated
as the nominal concentration of such ingredient(s), as that term
is defined in 40 CFR 158.153(i). Accordingly, the Agency has
established the nominal concentration as the only acceptable
label claim for the amount of active ingredient in the product.
II. BACKGROUND
For some time the Agency has accepted two different methods
of identifying on the label what percentage is claimed for the
ingredient(s) contained in a pesticide. Some applicants claimed a
percentage which represented a level between the upper and the
lower certified limits. This was referred to as the nominal
concentration. Other applicants claimed the lower limit as the
percentage of the ingredient(s) that would be expected to be
present in their product at the end of the product's shelf-life.
Unfortunately, this led to a great deal of confusion among the
regulated industry, the regulators, and the consumers as to
exactly how much of a given ingredient was in a given product.
The Agency has established the nominal concentration as the only
acceptable label claim for the amount of active ingredient in the
product.
Current regulations require that the percentage listed in
the active ingredient statement be as precise as possible
reflecting good manufacturing practices 40 CFR 156.10(g)(5). The
certified limits required for each active ingredient are intended
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to encompass any such "good manufacturing practice" variations 40
CFR 158.175(C) (3) .
The upper and lower certified limits, which must be proposed
in connection with a product's registration, represent the
amounts of an ingredient that may legally be present 40 CFR
158.175. The lower certified limit is used as the enforceable
lower limit for the product composition according to FIFRA
section i2(a){i}(C), while the nominal concentration appearing on
the label would be the routinely achieved concentration used for
calculation of dosages and dilutions.
The nominal concentration would in fact state the greatest
degree of accuracy that is warranted with respect to actual
product composition because the nominal concentration would be
the amount of active ingredient typically found in the product.
It is important for registrants to note that certified
limits for active ingredients are not considered to be trade
secret information under FIFRA section 10(b). In this respect the
certified limits will be routinely provided by EPA to States for
enforcement purposes, since the nominal concentration appearing
on the label may not represent the enforceable composition for
purposes of section 12(a)(1)(C).
III. REQUIREMENTS
As described below under Unit V. " COMPLIMICE SCHEDULE,11 all
currently registered products as well as all applications for new
registration must comply with this Notice by specifying the
nominal concentration expressed as a percentage by weight as the
label claim in the ingredient(s) statement and equivalence
statements if applicable (e.g., elemental arsenic, metallic zinc,
salt of an acid). In addition, the requirement for performing
sample analyses of five or more representative samples must be
fulfilled. Copies of the raw analytical data must be submitted
with the nominal ingredient label claim. Further information
about the analysis requirement may be found in the 40 CFR
158,170. All products are required to provide certified limits
for each active, inert ingredient, impurities of toxicological
significance(i.e., upper limit(s) only) and on a case by case
basis as specified by EPA.. These limits are to be set based on
representative sampling and chemical analysis(i.e., quality
control) of the product.
The format of the ingredient statement must conform to 40
CFR 156-Labeling Requirements For Pesticides and Devices.
After July l, 1997, all pesticide ingredient Statements must
be changed to nominal concentration.
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IV. PRODUCTS THAT REQUIRE EFFICACY DATA
All pesticides are required to be efficacious. Therefore,
the certified lower limits may not be lower then the minimum
level to achieve efficacy. This is extremely important for
products which are intended .to control pests which threaten the
public health, e.g., certain antimicrobial and rodenticide
products. Refer to 40 CFR 153.640.
In those cases where efficacy limits have been established,
the Agency will not accept certified lower limits which are below
that level for the shelf life of the product.
V. COMPLIANCE SCHEDULE
As described earlier, the purpose of this Notice is to make
the registration process more uniform and more manageable for
both the agency and the regulated community. It is the Agency's
intention to implement the requirements of this notice as
smoothly as possible so as not to disrupt or delay the Agency's
high priority programs, i.e., reregistration, new chemical, or
fast track (FIFRA section 3(c)(3)(B). Therefore,
applicants/registrants are expected to comply with the
requirements of this Notice as follows:
(l) Beginning July i, 1991, all new product registrations
submitted to the Agency are to comply with the
requirements of this Notice.
(2) Registrants having products subject to reregistration
under FIFRA section 4(a) are to comply with the
requirements of this Notice when specific products are
called in by the Agency under Phase V of the
Reregistration Program.
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(3) All other products /applications that are not subject to
(1) and (2) above will have until July i, 1997, to
comply with this Notice. Such applications should, note
"Conversion to Nominal Concentrations on the
application form. These types Or amendments will not be
handled as "Fast Track" applications but will be
handled as routine requests.
VI. FOR FURTHER INFORMATION
Contact Tyrone Aiken for information or questions concerning
this notice on (703) 308-7031.
fi. tindaay, Director
~wg iatnefmr Dtvlftton "in -raws
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APPENDIX E. Combined Generic and Product Specific
Data Call-in
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
GENERIC AND PRODUCT SPECIFIC
DATA CALL-IN NOTICE
OFPICE OF
CERTIFIED MAIL PREVENTION. PESTICIDES
ftND TOXIC SUBSTANCES
JUN 13 1994
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the
active ingredient identified in Attachment A of this Notice, the Data^all-In Chemical Status
Sheet, to submit certain data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your
product(s) containing this active ingredient. Within 90 days after you receive this Notice you
must respond as set forth in Section ffl below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 7; or
2. Why you believe you are exempt from the requirements listed in this Notice
and in Attachment 3 (for both generic and product specific data), the
Requirements Status and Registrant's Response Form, (see section ffl-B); or
3. Why you believe EPA should not require your submission of data in the
manner specified by this Notice (see section ffi-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 produces) subject to this Notice will be subject to suspension. We have
provided a list of all of your products subject to this Notice in Attachment 2. All products
are listed on both the generic and product specific Data Call-in Response Fonms^ Also
included is a list of all registrants who were sent this Notice (Attachment 6),
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 3-31-96).
BeeydedJHecyellB*
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This Notice is divided into six sections and seven Attachments. The Notice itself
contains information and instructions applicable to all Data Call-In Notices. The Attachments
contain specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You are Receiving this Notice
Section n - Data Required by this Notice
Section in - Compliance with Requirements of this Notice
Section IV - Consequences of Failure to Comply with this Notice
Section V - Registrants' Obligation to Report Possible Unreasonable Adverse
Effects
Section VI - Inquiries and Responses to this Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-in and Product Specific Data Call-In Response Forms with
Instructions
3 - Generic Data Call-In and Product Specific Data Call-In Requirements Status
and Registrant's Response Forms with Instructions
4 - EPA Grouping of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - EPA Acceptance Criteria
6- List of Registrants Receiving This Notice
7 - Cost Share and Data Compensation Form$and Confidential Statement of
Formula Form with Instructions
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
revaluation identified additional data necessary to assess the health and safety of the
continued use of products containing this active ingredient(s). You have been sent this Notice
because you have product(s) containing the subject active ingredients.
SECTION H. DATA REOTTTRTTB BY THIS NOTICE
n-A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and
Registrant's Response Forms: Attachment 3 (for both generic and product specific data
requirements). Depending on the results of the studies required in this Notice, additional
studies/testing may be required.
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H-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements
specified in the Requirements Status and Registrant's Response Forms (Attachment 3) within
the timeframes provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test
standards outlined in the Pesticide Assessment Guidelines for those studies for which
guidelines have been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (Telephone
number: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the
study will satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend
deadlines for complying with data requirements when the studies were not conducted in
accordance with acceptable standards. The OECD protocols are available from OECD, 2001
L Street, N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone
number 202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160].
H-D. REGISTRANTS RECETONG 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
changejthe requirements of any previous Data Call-In(s>. or any other agreements entered
into with the Agency pertaining to such prior Notice. Registrants must comply with the
requirements of all Notices to avoid issuance of a Notice of Intent to Suspend their affected
products.
SECTION m. COMPLIANCE WITH REQUIREMENTSOF/THIS NOTICE
You must use the correct forms and instructions when completing your response to
this Notice. The type of Data Call-In you must comply with (Generic or Product Specific) is
specified in item number 3 on the four Data Call-in forms (Attachments 2 and 3).
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m-A. SCHEDULE FOR RESPONDING TO THE AGEMCY
The appropriate responses initially required by this Notice for generic and product
specific data must be submitted to the Agency within 90 days after your receipt of this
Notice. Failure to adequately respond to this Notice within 90 days of your receipt will be a
basts 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.
m-B. OPTIONS FOR RESPONDING TO THE AGENCY
1. Generic Data Requirements
The options for responding to this Notice for generic data requirements are: (a)
voluntary cancellation, (b) delete use(s), (c) claim generic data exemption, (d) agree to
satisfy the generic data requirements imposed by this Notice or (e) request a data waiver(s),
A discussion of how to respond if you choose the Voluntary Cancellation option, the
Delete Use(s) option or the Generic Data Exemption option is presented below. A discussion
of the various options available for satisfying the generic data requirements of this Notice is
contained in Section ffl-C, A discussion of options relating to requests for data waivers is
contained in Section ffl-D.
Two forms apply to generic data requirements, one or both of which must be used in
responding to the Agency, depending upon your response. These two forms are the
Data-Call-in Response Form, and the Requirements Status sfld Registrant's Response Form.
(contained in Attachments 2 and 3, respectively).
The Data Call-in Response Forms must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Forms also must be submitted if
you do not qualify for a Generic Data Exemption or are not requesting voluntary cancellation
of your registration(s). Please note that the company's authorized representative is required
to sign the first page of both Data Call-In Response Forms and the Requirements Status and
Registrant's Response Forms (if this form is required) and initial any subsequent pages. The
forms contain separate detailed instructions on the response options. Do not alter the printed
material. If you have questions or need assistance in preparing your response, call or write
the contact person(s) identified in Attachment 1.
a. Voluntary Cancellation -
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your product(s) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit completed Generic and Product Specific
Data Call-In Response Forms (Attachment 2), indicating your election of this option.
Voluntary cancellation is item number 5 on both Data Call-In Response FoTm|g). If you
choose this option, these are the only forms that you are required to complete.
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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.
b. Use Deletion -
You may avoid the requirements of this Notice by eliminating the uses of your
product to which the requirements apply. If you wish to amend your registration to delete
uses, you must submit the Requirements Status and Registrant's Response Form (Attachment
3), a completed application for amendment, a copy of your proposed amended labeling, and
all other information required for processing the application. Use deletion is option number
7 under item 9 in the instmclions for the Requirements Status and Registrant's Response
Forms. You must also complete a Data Call-In Response Form by signing the certification,
item number 8. Application forms for amending registrations may be obtained from the
Registration Support Branch, Registration Division, Office of Pesticide Programs, EPA, by
calling (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to specific data
requirements, further sale, distribution, or use of your product after one year from the due
date of your 90 day response, is allowed only if the product bears an amended label,
c. Generic Data Exemption -
Under section 3(c)(2)(D) of FIFRA, an applicant for registration of a product is
exempt from the requirement to submit or cite generic data concerning an active ingredient if
the active ingredient in the product is derived exclusively from purchased, registered
pesticide products containing the active ingredient. EPA has concluded, as an exercise of its
discretion, that it normally will not suspend the registration of a product which would qualify
and continue to qualify for the generic data exemption in section 3(c)(2)(D) of FIFRA. To
qualify, aU of the following requirements must be met:
(i). The active ingredient in your registered product must be present solely because
of incorporation of another registered product which contains the subject active
ingredient and is purchased from a source not connected with you;
(ii). Every registrant who is the ultimate source of the active ingredient in your
product subject to this DCI must be in compliance with the requirements of this
Notice and must remain in compliance; and
(iii). You must have provided to EPA an accurate and current "Confidential
Statement of Formula" for each of your products to which this Notice applies.
To apply for the Generic Data Exemption you must submit a completed Data Call-in
Response Form. Attachment 2 and all supporting documentation. The Generic Data
Exemption is item number 6a on the Data Call-in Response Form. If you claim a generic
data exemption you are not required to complete the Requirements Status and Registrant's
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Response Form. Generic Data Exemption cannot be selected as an option for responding to
product specific data requirements.
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 requirements or
are no longer in compliance with this Data Call-in Notice, the Agency will consider that both
they and you are not compliance and will normally initiate proceedings to suspend the
registrations of both your and their product(s), unless you commit to submit and do submit
the required data within the specified time. In such cases the Agency generally will not grant
a time extension for submitting the data.
d. Satisfying the Generic Data Requirements of this Notice
There are various options available to satisfy the generic data requirements of this
Notice. These options are discussed in Section ffl-C.l, of this Notice and comprise options 1
through 6 of item 9 in the instructions for the Requirements Status and Registrant's Response
Farm and item 6b on the Data Call-In Response Eonm. If you choose item 6b (agree to
satisfy the generic data requirements), you must submit the Data Call-In Response Form and
the Requirements Status and Registrant's Response Form as well as any other
information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "GENERIC" in item number 3.
e. Request for Generic Data Waivers.
Waivers for generic data are discussed in Section ffl-D.1. of this Notice and are
covered by options 8 and 9 of item 9 in the instructions for the Requirements Status and
Registrant's Response Form. If you choose one of these options, you must submit both forms
as well as any other information/data pertaining to the option chosen to address the data
requirement.
2. Product Specific Data Requirements
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this
Notice or (c) request a data waiver(s).
A discussion of how to respond if you choose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product
specific data requirements of this Notice is contained in Section ffl-C.2. A discussion of
options relating to requests for data waivers is contained in Section M-D.2.
Two forms apply to the product specific data requirements one or both of which must
be used in responding to the Agency, depending upon your response. These forms are the
Data-Call-in Response FormT and the Requirements Status and Registrant's Response Form.
for product specific data (contained in Attachments 2 and 3, respectively). The Data Call-In
Response Form must be submitted as part of every response to this Notice. In addition, one
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copy of the Requirements Status and Registrant's Response, Form also must be submitted for
each product listed on the Data Call-In Response Form unless the voluntary cancellation
option is selected. Please note that the company's authorized representative is required to
sign the first page of the Daja J^ajl-Jn Response Form and Requirements Status and
Registrant's Response Form (if this form is required) and initial any subsequent pages. The
forms contain separate detailed instructions on the response options. Do not alter the printed
material. If you have questions or need assistance in preparing your response, call or write
the contact person(s) identified in Attachment i.
a. Voluntary Cancellation
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your produces) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit a completed Data Call-In Response
Form, indicating your election of this option. Voluntary cancellation is item number 5 on
both the Generic and Product Specific Data Call-in Response Forms. If you choose this
option, you must complete both Data Call-In response forms. These are the only forms that
you are required to complete.
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
b. Satisfyingjhe_ Product Specific Data Requirements of this Notice.
There arc various options available to satisfy the product specific data requirements of
this Notice. These options are discussed in Section ffl-C.2. of this Notice and comprise
options 1 through 6 of item 9 in the instructions for the product specific Requirements Status
and Registrant's Response Form and item numbers 7a and 7b (agree to satisfy the product
specific data requirements for an MOT or EOT as applicable) on the product specific Data
Call-in Response Form. Note that the options available for addressing product specific data
requirements differ slightly from those options for fulfilling generic data requirements.
Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements. It is important to ensure that you are using the correct
forms and instructions when completing your response to the Reregistration Eligibility
Decision document.
c. Request for Product Specific Data Waivers.
Waivers for product specific data are discussed in Section HI-D.2. of this Notice and
are covered by option 7 of item 9 in the instructions for the Requirements Status and
Registtmlis Response Form. If you choose this option, you must submit the Data Call-In
Response Form and the Requirements Status and Registrant's Response Fjorrn as well as any
other information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "PRODUCT SPECIFIC" in item number 3.
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ni-C SATISFYING THE DATA REOTJTRy.MF.lSTra OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-In Response Form that you agree to
satisfy the generic data requirements (i.e. you select item number 6b), then you must select
one of the six options on the Generic Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production are
the first six options discussed under item 9 in the instructions for completing the
Requirements Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide you to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified timeframe (Developing
Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an
existing study that has been submitted but not reviewed by the Agency (Citing
an Existing Study)
Option1. Developing Data
If you choose to develop the required data it must be in conformance with Agency
deadlines and with other Agency requirements as referenced herein and in the attachments.
All data generated and submitted must comply with the Good Laboratory Practice (GLP) rule
(40 CFR Part 160), be conducted according to the Pesticide Assessment Guidelines (PAG)
and be in conformance with the requirements of PR Notice 86-5. In addition, certain studies
require Agency approval of test protocols in advance of study initiation. Those studies for
which a protocol must be submitted have been identified in the Requirements Status and
Registrant's Response Form and/or footnotes to the form. If you wish to use a protocol
which differs from the options discussed in Section n-C of this Notice, you must submit a
detailed description of the proposed protocol and your reason for wishing to use it The
Agency may choose to reject a protocol not specified in Section n-C. If the Agency rejects
your protocol you will be notified in writing, however, you should be aware that rejection of
a proposed protocol will not be a basis for extending the deadline for submission of data.
A progress report must be submitted for each study within 90 days from the date you
are required to commit to generate or undertake some other means to address that study
requirement, such as making an offer to cost share or agreeing to share in the cost of
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developing that study. This 90-day progress report must include the date the study was or
will be initiated and, for studies to be started within 12 months of commitment, the name and
address of the 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 weU as a full
description of any problems encountered since the last progress report.
The time frames in the Reguirements Status and Registrant's Response Form are the
time frames that the Agency is allowing for the submission of completed study reports or
protocols. The noted deadlines run from the date of the receipt of this Notice by the
registrant. If the data are not submitted by the deadline, each registrant is subject to receipt
of a Notice of Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this
Notice and intend to seek additional time to meet the requirements(s), you must submit a
request to the Agency which includes; (1) a detailed description of the expected difficulty and
(2) a proposed schedule including alternative dates for meeting such requirements on a
step-by-step basis. You must explain any technical or laboratory difficulties and provide
documentation from the laboratory performing the testing. While EPA is considering your
request, the original deadline remains. The Agency will respond to your request in writing.
If EPA does not grant your request, the original deadline remains. Normally, extensions can
be requested only in cases of extraordinary testing problems beyond the expectation or
control of the registrant. Extensions will not be given in submitting the 90-day responses.
Extensions will not be considered if the request for extension is not made in a timely fashion;
in no event shall an extension request be considered if it is submitted at or after the lapse of
the subject deadline.
Option 2. Agreement to Share in Cost to Develop Data
If you choose to enter into an agreement to share in the cost of producing the required
data but will not be submitting the data yourself, you must provide the name of the registrant
who will be submitting the data. You must also provide EPA with documentary evidence that
an agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of
the terms of the final arrangement between the parties or the mechanism to resolve the terms.
Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development
If you have made an offer to pay in an attempt to enter into an agreement or amend
an existing agreement to meet the requirements of this Notice and have been unsuccessful,
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you may request EPA (by selecting this option) to exercise its discretion not to suspend your
registration^), 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 the offer. To qualify for this option, you must submit documentation to the Agency
proving that you have made an offer to another registrant (who has an obligation to submit
data) to share in the burden of developing that data. You must also submit to the Agency a
completed EPA Form 8570-32, Certification of Offer to Cost Share in the Development of
Data, Attachment 7, In addition, you must demonstrate that the other registrant to whom the
offer was made has not accepted your offer to enter into a cost-sharing agreement by
including a copy of your offer and proof of the other registrant's receipt of that offer (such
as a certified mail receipt). Your offer must, in addition to anything else, offer to share in
the burden of producing the data upon terms to be agreed to or, failing agreement, to be
bound by binding arbitration as provided by HFRA section 3(c)(2)(B)(iii) and must not
qualify this offer. The other registrant must also inform EPA of its election of an option to
develop and submit the data required by this Notice by submitting a Data Call-in Response
Form and a Requirements Status and Registrant's Response Form committing to develop and
submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your
offer to share in the burden of developing the data. In addition, the other registrant must
fulfill its commitment to develop and submit the data as required by this Notice. If the other
registrant fails to develop the data or for some other reason is subject to suspension, your
registration as well as that of the other registrant normally will be subject to initiation of
suspension proceedings, unless you commit to submit, and do submit, the required data in
the specified time frame. In such cases, the Agency generally will not grant a time extension
for submitting the data.
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this Notice. You may only
submit a study that has not been previously submitted to the Agency or previously cited by
anyone. Existing studies are studies which predate issuance of this Notice. Do not use this
option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable,
the Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of
the following three criteria must be clearly Met:
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a. You must certify at the time that the existing study is submitted that the raw
data and specimens from the study are available for audit and review and you
must identify where they arc 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 "'[r]aw data' means any laboratory
worksheets, records, memoranda, notes, or exact copies thereof, that are the
result of original observations and activitiei of a study and are necessary for
the reconstruction and evaluation of the report of that study. In the event that
exact transcripts of raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature), the exact copy
or exact transcript may be substituted for the original source as raw data. 'Raw
data' may include photographs, microfilm or microfiche copies, computer
printouts, magnetic media, including dictated observations, and recorded data
from automated instruments." The term "specimens", according to 40 CFR
160.3, means "any material derived from a test system for examination or
analysis,"
b. Health and safety studies completed after May 1984 also must also contain all
GLP-required quality assurance and quality control information, pursuant to
the requirements of 40 CFR Part 160. Registrants also must certify at the time
of submitting the existing study that such GLP information is available for post
May 1984 studies by including an appropriate statement on or attached to the
study signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfils the acceptance criteria for the
Guideline relevant to the study provided in the FIFKA Accelerated
Reregistration Phase 3 Technical Guidance and that the study has been
conducted according to the Pesticide Assessment Guidelines (PAG) or meets
the purpose of the PAG (both available from NTIS). A study not conducted
according to the PAG may be submitted to the Agency for consideration if the
registrant believes that the study clearly meets the purpose of the PAG. The
registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in
addition to certifying that the purposes of the PAG are met by the study,
clearly articulate the rationale why you believe the study meets the purpose of
the PAG, including copies of any supporting information or data. It has been
the Agency's experience that studies completed prior to January 1970 rarely
satisfied the purpose of the PAG and that necessary raw data usually are not
available for such studies.
If you submit an existing study, you must certify that the study meets all requirements
of the criteria outlined above.
If EPA has previously reviewed a protocol for a study you are submitting, you must
identify any action taloen by the Agency on the protocol and must indicate, as part of your
certification, the manner in which all Agency comments, concerns, or issues were addressed
in the final protocol and study.
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If you know of a study pertaining to any requirement in this Notice which does not
meet the criteria outlined above but does contain factual information regarding unreasonable
adverse effects, you must notify the Agency of such a study. If such study is in the Agency's
files, you need only cite it along with the notification. If not in the Agency's files, you must
submit a summary and copies as required by PR Notice 86-5,
Option 5. Upgrading a Study
If a study has been classified as partially acceptable and upgradeable, you may submit
data to upgrade that study. The Agency will review the data submitted and determine if the
requirement is satisfied. If the Agency decides the requirement is not satisfied, you may still
be required to submit new data normally without any time extension. Deficient, but
upgradeable studies will normally be classified as supplemental. However, it is important to
note that not all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call or write the
contact person listed in Attachment 1. If you submit data to upgrade an existing study you
must satisfy or supply information to correct all deficiencies in the study identified by EPA,
You must provide a clearly articulated rationale of how the deficiencies have been remedied
or corrected and why the study should be rated as acceptable to EPA. Your submission must
also specify the MUD number(s) of the study which you are attempting to upgrade and must
be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option also should be used to cite data that has been previously submitted to
upgrade a study, but has not yet been reviewed by the Agency. You must provide the MRID
number of the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to
all data submissions intended to upgrade studies. Additionally, your submission of data
intended to upgrade studies must be accompanied by a certification that you comply with
each of those criteria, as well as a certification regarding protocol compliance with Agency
requirements.
Option 6. Citing Existing Studies
If you choose to cite a study that has been previously submitted to EPA, that study
must have been previously classified by EPA as acceptable, or it must be a study which has
not yet been reviewed by the Agency. Acceptable toxicology studies generally will have been
classified as "core-guideline" or "core-minimum," For ecological effects studies, the
classification generally would be a rating of "core." For all other disciplines the classification
would be "acceptable." With respect to any studies for which you wish to select this option,
you must provide the MRID number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's classification of the study.
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If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of EPA Form 8570-31, Certification with Respect to Data
Compensation Requirements.
2, Product Specific Data
If you acknowledge on the product specific fiata Call-in Response Form that you
agree to satisfy the product specific data requirements (i.e. you select option 7a or 7b), then
you must select one of the six options on the Requirements Status and Registrant's Response
Form related to data production for each data requirement. Your option selection should be
entered under item number 9, "Registrant Response." The six options related to data
production are the first six options discussed under item 9 in the instructions for completing
the Requirements Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide registrants to additional
instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified time-frame (Developing
Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an
existing study that has been
submitted but not reviewed by the Agency (Citing an Existing Study)
Option 1. Developing Data -- The requirements for developing product specific data are the
same as those described for generic data (see Section in.C.l, Option 1) except that normally
no protocols or progress reports are required.
Option 2. Agree to Share in Cost to Develop Data — If you enter into an agreement to cost
share, the same requirements apply to product specific data as to generic data (see Section
HI,C.I, Option 2). However, registrants may only choose this option for acute toxitity data
and certain efficacy data and only if EPA has indicated in the attached data tables that your
product and at least one other product are similar for purposes of depending on
the same data. If this is the case, data may be generated for just one of the products in the
group. The registration number of the product for which data will be submitted must be
noted in the agreement to cost share by the registrant selecting this option.
Option 3. Offer to Share in the Cost of Data Development -The same requirements for
generic data (Section nLC.I.» Option 3) apply to this option. This option only applies to
acute toxicity and certain efficacy data as described in option 2 above
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Option 4. Submitting an Existing Study — The same requirements described for generic data
(see Section in.C,l,, Option 4) apply to this option for product specific data,
Option 5^ Upgrading a Study — The same requirements described for generic data (see
Section M.C.L, Option 5) apply to this option for product specific data.
Option 6. Citing Existing Studies — The same requirements described for generic data (see
Section m.C.i., Option 6) apply to this option for product specific data.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Form and the
Requirements Status and Registrant's Response Form, and in the generic data requirements
section (LH.C.1,), as appropriate.
m-D REQUESTS FOR DATA WAIVERS
1. Generic Data
There are two types of data waiver responses to this Notice. The first is a request for
a low volume/minor use waiver and the second is a waiver request based on your belief that
the data requirement(s) are not appropriate for your product.
a. Low Volume/Minor TJae Waivec
Option 8 under item 9 on the Requirements Status and Registrant's Response
Form. Section 3(c)(2)(A) of FIFRA requires EPA to consider the appropriateness of
requiring data for low volume, minor use pesticides. In implementing this provision,
EPA considers low volume pesticides to be only those active ingredients whose total
production volume for all pesticide registrants is small. In determining whether to
grant a low volume, minor use waiver, the Agency will consider the extent, pattern
and volume of use, the economic incentive to conduct the testing, the importance of
the pesticide, and the exposure and risk from use of the pesticide. If an active
ingredient is used for both high volume and low volume uses, a low volume
exemption will not be approved. If all uses of an active ingredient are low volume
and the combined volumes for all uses are also low, then an exemption may be
granted, depending on review of other information outlined below. An exemption will
aot be granted if any registrant of the active ingredient elects to conduct the testing.
Any registrant receiving a low volume minor use waiver must remain within the sales
figures in their forecast supporting the waiver request in order to remain qualified for
such waiver. If granted a waiver, a registrant will be required, as a condition of the
waiver, to submit annual sales reports. The Agency will respond to requests for
waivers in writing.
To apply for a low volume, minor use waiver, you must submit the following
information, as applicable to your product(s), as part of your 90-day response to this
Notice:
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(i). Total company sales (pounds and dollars) of all registered product(s)
containing the active ingredient. If applicable to the active ingredient, include foreign
sales for those products that are not registered in this country but are applied to sugar
(cane or beet), coffee, bananas, cocoa, and other such crops. Present the above
information by year for each of the past five years.
(ii) Provide an estimate of the safes (pounds and dollars) of the active
ingredient for each major use site. Present the above information by year for each of
the past five years.
(iii) Total direct production cost of product(s) containing the active ingredient
by year for the past five years. Include information on raw material cost, direct labor
cost, advertising, sales and marketing, and any other significant costs listed
separately.
(iv) Total indirect production cost (e.g. plant overhead, amortized plant and
equipment) charged to product(s) containing the active ingredient by year for the past
five years. Exclude all non-recurring costs that were directly related to the active
ingredient, such as costs of initial registration and any data development.
(v) A 1st of each data requirement for which you seek a waiver. Indicate the
type of waiver sought and the estimated cost to you (listed separately for each data
requirement and associated test) of conducting the testing needed to fulfill each of
these data requirements.
(vi) A list of each data requirement for which you are not seeking any waiver
and the estimated cost to you (listed separately for each data requirement and
associated test) of conducting the testing needed to fulfill each of these data
requirements.
(vii) For each of the next ten years, a year-by-year forecast of company sales
(pounds and dollars) of the active ingredient, direct production costs of product(s)
containing the active ingredient (following the parameters in item 2 above), indirect
production costs of produces) containing the active ingredient (following the
parameters in item 3 above), and costs of data development pertaining to the active
ingredient.
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(viM) A description of the importance and unique benefits of the active
ingredient to users. Discuss the use pattens and the effectiveness of the active
ingredient relative to registered alternative chemicals and non-chemical control
strategies. Focus on benefits unique to the active ingredient, providing information
that is as quantitative as possible. If you do not have quantitative data upon which to
base your estimates, then present the reasoning used to derive your estimates. To
assist the Agency in determining the degree of importance of the active ingredient in
terms of its benefits, you should provide information on any of the following factors,
as applicable to your product(s): (a) documentation of the usefulness of the active
ingredient in Integrated Pest Management, (b) description of the beneficial impacts on
the environment of use of the active ingredient, as opposed to its registered
alternatives, (c) information on the breakdown of the active ingredient after use and
on its persistence in the environment, and (d) description of its usefulness against a
pest(s) of public health significance,
Failure to submit sufficient information for the Agency to make a
determination regarding a request for a low volume/minor use waiver will result in
denial of the request for a waiver.
b. Request for Waiver of Data
Option 9, under Item 9, on the Requirements Status and Registrant's Response
Form. This option may be used if you believe that a particular data requirement
should not apply because the requirement is inappropriate. You must submit a
rationale explaining why you believe the data requirements should not apply. You also
must submit the current label(s) of your product(s) and, if a current copy of your
Confidential Statement of Formula is not already on file you must submit a current
copy.
You will be informed of the Agency's decision in writing. If the Agency
determines that the data requirements of this Notice are not appropriate to your
product(s), you will not be required to supply the data pursuant to section 3(c)(2)(B).
If EPA determines that the data arc required for your product(¥)t you mast choose a
method of meeting the requirements of this Notice within the time frame provided by
this Notice. Within 30 days of your receipt of the Agency's written decision, you
must submit a revised Requirements Status and Registrant's Response Form indicating
the option chosen.
2. Product Specific Data
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request including
technical reasons, data and references to relevant EPA regulations, guidelines or
policies. (Note: any supplemental data must be submitted in the format required by
PR Notice 86-5). This will be the onjy 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
132
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the Agency denies your waiver request, you must choose an option for meeting the
data requirements of this Notice within 30 days of the receipt of the Agency's
decision. You must indicate and submit the option chosen on the product specific
Requirements Statiis and Rggistemt'j! Response Form. Product specific data
requirements for product chemistry, acute toxicity and efficacy (where appropriate)
are required for all products and the Agency would grant a waiver only under
extraordinary circumstances. You should also be aware that submitting a waiver
request will not automatically extend the due date for the study in question. Waiver
requests submitted without adequate supporting rationale will be denied and the
original due date will remain in force.
SECTION IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS
NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice
due to failure by a registrant to comply with the requirements of this Data Call-in Notice,
pursuant to
FDFRA 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 ffl-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
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S. 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 iely for a generic data exemption
either to:
i. Inform EPA of intent to develop and submit the data required by this
Notice on a Data Call-in Response Form and a Requirements Status and
Registrant's Response Form.
ii. Fulfill the commitment to develop and submit the data as required by this
Notice; or
iii. Otherwise take appropriate steps to meet the requirements stated in this
Notice,
unless you commit to submit and do submit the required data in the specified
time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any
time following the issuance of this Notice.
IV-B. BASIS FOR DF^ERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time)
is unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The
grounds for suspension include, but are not limited to, failure to meet any of the following:
1) EPA requirements specified in the Data Call-in Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment
Guidelines, Data Reporting Guidelines, and GeneTox Health Effects Test Guidelines)
regarding the design, conduct, and reporting of required studies. Such requirements
include, but are not limited to, those relating to test material, test procedures,
selection of species, number of animals, sex and distribution of animals, dose and
effect levels to be tested or attained, duration of test, and, as applicable, Good
Laboratory Practices.
2) EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3) EPA requirements regarding the reporting of data, including the manner of
reporting, the completeness of results, and the adequacy of any required supporting
(or raw) data, including, but not limited to, requirements referenced or included in
this Notice or contained in PR 86-5. All studies must be submitted in the form of a
final report; a preliminary report will not be considered to fulfill the submission
requirement.
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IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for
a suspended registration when a section-3(c)(2)(B) data request is outstanding generally
would not be consistent with the Act's purposes. Accordingly, the Agency anticipates
granting registrants permission to sell, distribute, or use existing stocks of suspended
product(s) only in exceptional circumstances. If you believe such disposition of existing
stocks of your product(s) which may be suspended for failure to comply with this Notice
should be permitted, you have the burden of clearly demonstrating to EPA that granting such
permission would be consistent with the Act. You also must explain why an "existing stocks"
provision is necessary, including a statement of the quantity of existing stocks and your
estimate of the time required for their sale, distribution, and use. Unless you meet this
burden, the Agency will not consider any request pertaining to the continued sale,
distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice
and your product is in full compliance with all Agency requirements, you will have, under
most circumstances, one year from the date your 90 day response to this Notice is due, to
sell, distribute, or use existing stocks. Normally, the Agency will allow persons other than
the registrant such as independent distributors, retailers and end users to sell, distribute or
use such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks
of voluntarily cancelled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on a case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required
by this Notice will not result in the agency granting any additional time to sell, distribute, or
use existing stocks beyond a year from the date the 90 day response was due, unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3-year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study
in an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
SECTION V. REGISTRANTS* OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional tactual 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
135
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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 VL PjOUIRIES ANDRESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by
this Notice, call the contact person(s) Isted in Attachment 1, the Data Call-In Chemical
Status Sheet.
All responses to this Notice must include completed Data _Call-In Response Forms
(Attachment 2)and completed Requirements Status and Registrant's Respgnse Forms
(Attachment 3), for both (generic and product specific data) and any other documents
required by this Notice, and should be submitted to the contact person(s) identified in
Attachment 1. If the voluntary cancellation or generic data exemption option is chosen, only
the Generic and Product Specific Data Call-in Response Forms need be submitted.
The Office of Compliance Monitoring (OCM) of the Office of Prevention, Pesticides
and Toxic Substances (OPPTS), EPA, will be monitoring the data being generated in
response to this Notice.
Sincerely yours,
Daniel M. Barolo, Director
Special Review and
Reregistration Division
Attachments
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-in and Product Specific Data Call-in Response Forms with
Instructions
3 - Generic Data Call-In and Product Specific Data Call-in Requirements Status
and Registrant's Response Forms with Instructions
4 - EPA Grouping of End_-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - EPA Acceptance Criteria
6- List olRegistrants Receiving This Notice
7 - Cost Share and Data Compensation Forms and Confidential Statement of
Formula Form with Instructions
136
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Attachment 1. Chemical Status Sheets
137
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Generic and Product Specific Data Call-In
Chemical Status Sheet
for
Pronamide
INTRODUCTION
You have been sent this combined Generic and Product Specific Data Call-In
Notice because you have registered pesticide product(s) containing pronamide and these
products have uses and/or tolerances which were supported with data generated by Craven
Laboratories which the Agency has determined must be replaced.
This combined Generic and Product Specific Data Call-in Chemical Status Sheet
contains the rationale behind the Agency's requirement for replacement of Craven-generated
data, an overview of data required by this combined notice, and points of contact for
inquiries pertaining to the reregistration of pronamide. This attachment is to be used in
conjunction with:
• The Combined Generic and Product Specific Data Call-In Notice (Appendix
E),
" The Generic Data Call-in and Product Specific Data Call-In Response Forms
with Instructions (Attachment 2)
• The Generic Data Call-In and Product Specific Data Call-In Requirements
Status and Registrant's Response Forms with Instructions (Attachment 3),
" EPA's Grouping of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration (Attachment 4),
• The EPA Acceptance Criteria (Attachment 5),
• list of registrants receiving this combined DCI (Attachment 6), and
« The Cost Share, Data Compensation,, and Confidential Statement of Formula
Forms (Attachment 7)
Instructions and guidance accompany each form.
WHY THE REPLACMENT OF CRAVEN-GENERATED DATA IS REQUIRED
This Data Call-In Notice also requires the submission of new, replacement studies in
cases where existing data were generated by Craven Laboratories and where the Agency
found that such Craven-generated data were the basis for the registration of uses or the
setting of associated tolerances. The circumstances necessitating this requirement are
discussed further below.
139
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In the latter part of 1990, the Agency received allegations of wrongdoing concerning
Craven Laboratories* conduct of studies which may have been submitted to support pesticide
registrations and tolerance actions. The Agency immediately initiated its own inquiry into
the status of registration and tolerance actions which may be affected by the alleged
wrongdoing. Additionally, a criminal investigation commenced relating to the allegations.
Based on these allegations and the admissions of wrongdoing by Craven employees, the
Agency no longer considers Craven data reliable.
As part of its effort to determine if any studies were in need of replacement, in 1991,
the Agency formally asked you and other affected registrants to respond to two voluntary
requests. These requests sought information pertaining to Craven-generated data and
requested submission of existing alternate data which might be used in place of Craven-
generated data. As a result of its comprehensive inquiry and the information obtained from
affected registrants, the Agency was able to better define the scope of the Craven situation
and the extent of its concerns over the lack of reliability of Craven-generated data. First, the
Agency determined that some of the Craven data was not essential to support previous
regulatory decisions. Second, the Agency concluded that certain data gaps do exist in areas
where Craven data were used to support regulatory decisions (and for which existing
alternate data was either not available or inadequate). For this latter group, the Agency has
concluded that the Craven-generated data must be replaced in order to provide adequate and
reliable data upon which to base decisions on affected pesticide registrations and tolerances in
the face of existing concerns. Accordingly, the Agency is requiring through this Data Call-
in Notice that these replacement studies be generated and submitted.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the data base for pronamide are
contained in the Requirements Status and Registrant's Response Forms. (Attachment 3).
The Agency has concluded that additional data on pronamide 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 fuEy complete the reregistration of all eligible pronamide
products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic database of pronamide, please
contact Ms. Karen Jones at (703) 308-8047.
140
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All responses to this Notice for the generic data requirements should be submitted
to:
Ms. Karen Jones, Chemical Review Manager
Reregistration Branch
Special Review and Reregistration Division (7508W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, DC 20460
RE; Pronamide
If you have any questions regarding the product specific data requirements and
procedures established by this Notice, please contact Mr. Franklin Gee at (703) 308-8008.
All responses to this Notice for the product specific data requirements should be
submitted to:
Ms. Sue S. Rathman
Special Review and Reregisteation Division (7508W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D,C, 20460
RE: Pronamide
141
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Attachment 2. Generic and Product Specific Data Call-in
Response Forms (Form A inserts) and Instructions
143
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Instructions For Completing
The
"Data Call-In Response Forms"
For The Generic And Product Specific Data Call-In
INTRODUCTION
These instructions apply to the Generic and Product Specific "Data Call-in Response
Forms" and are to be used by registrants to respond to generic and product specific Data
Call-ins as part of EPA's Reregistration Program under the Federal Insecticide, Fungicide,
and Rodenticide Act The type of data call-in (generic or product specific) is indicated in
item number 3 ("Bate and Type of DCI") on each form. BOTH "Data Call-In Response"
forms must be completed.
Although the form is the same for both generic and product specific data, instructions
for completing these forms are different. Please read these instructions carefully before
filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted
these forms with a number of items. DO NOT use these forms for any other active
ingredient.
Items 1 through 4 have been preprinted on the form. Items 5 through 7 must be
completed by the registrant as appropriate. Items 8 through 11 must be completed by the
registrant before submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average
15 minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggestions for reducing tMs burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget,
Paperwork Reduction Project 2070-0107, Washington, D.C. 20503.
145
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON BOTH FORMS; This item identifies the case number, case name, EPA
chemical number and chemical name.
Item 3. ON BOTH FORMS: This item identifies the type of Data Call-in. The date
of issuance is date stamped.
Item 4. ON BOTH FORMS? This item identifies the EPA product registrations
relevant to the data call-in. Please note that you are also responsible for
informing the Agency of your response regarding any product that you believe
may be covered by this Data Call-In but that is not listed by the Agency in
Item 4. You must bring any such apparent omission to the Agency's attention
within the period required for submission of this response form.
Item 5. ON BOTH FORMS: Check this item for each product registration you wish
to cancel voluntarily. If a registration number is listed for a product for which
you previously requested voluntary cancellation, indicate in Item 5 the date of
that request. Since this Data Call-In requires both generic and product specific
data, you must complete item 5 on both Data Call-in response forms. You do
not need to complete any item on the Requirements Status^nd Registrant's
Response Forms.
Item 6a. ON THE GENERIC DATA FORM: Check this Item if the Data Call-in is
for generic data as indicated in Item 3 and you are eligible for a Generic Data
Exemption for the chemical listed in Item 2 and used in the subject product.
By electing this exemption, you agree to the terms and conditions of a Generic
Data Exemption as explained in the Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the MPA
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
146
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INSTRUCTIONS FOR COMPLETING THE DATA CALI^IN RESPONSE FORMS
Generic and Product Specific Data Call-In
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. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is
for generic data as indicated in Item 3 and if you are agreeing to satisfy the
generic data requirements of this Data Call-in. Attach the Requirements Status
and Registrant's Response Form that indicates how you will satisfy those
requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data,
Item 7a. ON THE PRODUCT SPECIFIC DATA FORM: For each manufecturing
use product (MUP) for which you wish to maintain registration, you must
agree to satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration,
you must agree to satisfy the data requirements by responding "yes."
FOR BOTH MUP and EUP products
You should also respond "yes* to this item (7a for MUP's and 7b for EUFs)
if your product is identical to another product and you qualify for a data
exemption. You must provide the EPA registration numbers of your
sources); do not complete the Requirements Status and Registrant's Response
form. Examples of such products include repackaged products and Special
Local Needs (Section 24c) products which are identical to federally registered
products.
If you are requesting a data waiver, answer "yes" here; in addition, on the
"Requirements Status and Registrant's Response" form under Item 9, you must
respond with option 7 (Waiver Request) for each study for which you are
requesting a waiver.
NOTE: Item 7a and 7b are not applicable for Generic Data.
147
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-In
Item 8. ON BOTH FORMS: This certification statement must be signed by an
authorized representative of your company and the person signing must include
Ms/her title. Additional pages used in your response must be initialled and
dated in the space provided for the certification.
Item 9. ON BOTH FORMS; Enter the date of signature.
Item 10. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. ON BOTH FORMS; Enter the phone number of your company contact.
Note: You may provide additional information that does not fit on this form in a signed
letter that accompanies your response. For example, you may wish to report that
your product has already been transferred to another company or that you have
already voluntarily cancelled this product. For these cases, please supply all relevant
details so that EPA can ensure that its records are correct.
148
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DRAFT COP¥
Page 1 of 1
United States Environmental Protection Agency
•* •* form Approved
Washington, D.c. 20460
^ OMB Ho. 2070-0107
DATA CALL-IN RESPONSE 2070-0057
Approval Expires 03-31-96
INSTRUCTIONS: Please type or print In ink. Please read carefully the attached instructions and supply the information requested on this form.
Use additional sheet (s) tf necessary
1. Coneanv name and Address 2. Case f and Han* 3. Date and Type of OCI
SAMPLE COMPANY 0082 J«>«-"« GENERIC
NO STEEET ADDRESS Chemical f and iame 1U1/U1
NO CITY, XX 00000 Propyzamide
*. EPA Product
Registration
NNNNNN-NNNNN
S. I wish to
cancel this
product regis-
tration voluv
tari ly
lliliillililll
:3i£:p$:;;^
:M-:-;<-?,:H::^-;:^::S vS;^^:';^: 'i1:": "*;
,::^;:§:;:^:;:v:;:^;:>v:;;^^:;:;:,>;::gc;;;:v;:
KrtWWAWWMZ&&y&&™.
£^;i;^i:$i^^;§^:^i?^^^:^v!
6. Generic Data
6a. 1 am claiming • Generic
Data Exemption because I
obtain the active ingredient
from the source EPA regis-
tration number listed below.
N.A.
ill 1
-;:%::>:x^ wtfrtf; ~y&
;:::?:::?£:-:'#^^ <•:•••<:'.•>.< >*:;
fib, 1 agree to satisfy Generic
Data requirement s as indicated
on the attached form entitled
"Requirements Status and
Registrant's Response."
N.A.
¥lliils|l|Ii:liilli;l|-:llll:illi:;il;;::i
!;llSlililS^!li!|:;;Si^;|y;^.liJi;
.:.h-;.,|-,.:.|,:.v.--XW.-j:.^X,:::,Jv.5X:,,:v.i:j:.J.._.:.:. :„.:;,,:„.;„,.:„„.;„.
il i IllllllfiiiiilillljillSISIiiii'
i^i^K^sS^B^^^'M'I'SKffillfiJMsSSSiS^f'i'
7. Product Specific Data
7a. Hy product Is an HUP and
I agree to satisfy the HUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
'f&£&&&%x%&^'&ttttW&;Mi3&$9i&8i>^i;ii
•;•:•:•:;•:•:• v :•;•,•;-:•;.,«••:«>:-••:.••;••.• :>:•• v.v.w. ,..•..--......-....-....•-....•- .. •.-.:•.•.-.-,.•,-.:
9M^W'ffx:^^f^mm^^i^^i^i^
WK«>w:^^^S:M*!S*S3SSSS«^S^.;^W;;:S:Kfe
7b. Ny product is an EUP and
I agree to satisfy the EUP
requirements on the attached
form entitled "Retirements
status and Registrant's
Response,11
•;•; »;-,»:,.»;. «:•: «. H.y v.:vK.v.v-i:*.s.:.x™.ir-w ««««;«.:.
8. Certification 9. Date
I certify that the statements made on thfs form and all attachments are true, accurate, and conplete.
] acknowledge thtt any knowingly false or misleading statement may foe punishable by fine, imprisonment
or both under applicable lax.
Signature and Title of Company's Authorized Representative
10. Mama of Conpeny Contact 11. Phone Hunter
-------
DRAFT COPY
Page 1 of 1
United States Environmental Protection Agency
Washington, D. C. 20460
DATA CALL-IN RESPONSE
INSTRUCTIONS: Please type or print in Ink. Please read carefully the attached instructions and supply the information requested
Use additional sheet(s) if necessary.
1. Company name and Address 2. Case # end Name
SAMPLE COMPANY 0082 Pronamide
NO STREET ADDRESS
NO CITY, XX 00000
4. EPA Product
Registration
NNNNNN-NNNNN
5. I wish to
cancel this
product regis-
tration volun-
tarily.
6. Generic Data
6a. 1 MI claiming a Generic
Data Exemption because I
obtain the active ingredient
from the source EPA regis-
tration number listed below.
N.A.
6b. I agree to satisfy Generic
Data requirements BB indicated
on the attached form entftled
"Requirements Status and
Re§istre.nt*s Response."
N.A.
7. Product Specific
Form Approved
OHB No. 2070-0107
2070-0057
Approval Expires 03-31-96
on this form.
3, Date and Type of DCt
PRODUCT SPECIFIC
Data
7a, My product is a HUP and
1 agree to satisfy the HUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
8. Certification
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement nay be punishable by fine, Imprisonment
or both under applicable law.
Signature and Title «f Company's Authorized Representative
10. Name of Conpany Contact
7b. My product Is an EUP and
I agree to satisfy the EUP
requirements on the attached
form entitled "Retirements
Status and Registrant's
Response."
9. Date
11.
Phone Number
-------
Attachment 3. Generic and Product Specific Requirement
Status and Registrant's Response Forms (Form B inserts)
and Instructions
151
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Instructions For Completing
The
"Requirements Status and Registrant's Response Forms"
For The Generic and Product Specific Data Call-In
INTRODUCTION
These instructions apply to the Generic and Product Specific "Requirements Status
and Registrant's Response Forms" and are to be used by registrants to respond to generic and
product specific Data Call-in's as part of EPA's reregistration program under the Federal
Insecticide, Fungicide, and Rodenticide Act. The type of Data Call-in (generic or product
specific) is indicated in item number 3 ("Date and Type of DCI") on each form. Both
"Requirements Status and Registrant's Response* forms must be completed.
Although the form is the same for both product specific and generic data, instruction!
for completing the forms differ slightly. Specifically, options for satisfying product specific
data requirements do not include (1) deletion of uses or (2) request for a low volume/minor
use waiver. Please read these instructions carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted
these forms to include certain information unique to this chemical. DQ NOT use these forms
for any other active ingredient.
Items 1 through 8 have been preprinted on the form. Item 9 must be completed by
the registrant as appropriate. Items 10 through 13 must be completed by the registrant
before submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average
30 minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggestions for reducing this burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget,
Paperwork Reduction Project 2070-0107, Washington, D.C. 20503.
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-in
Item 1, ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON THE GENERIC DATA FORM: This item identifies the case number,
case name, EPA chemical number and chemical name.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
case number, case name, and the EPA Registration Number of the product for
which the Agency is requesting product specific data.
Item 3, ON THE GENERIC DATA FORM: This item identifies the type of Data
Call-In. The date of issuance is date stamped.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
type of Data Call-In. The date of issuance is also date stamped. Note the
unique identifier number (ID#) assigned by the Agency. This ID number must
be used in the transmitted document for any data submissions in response to
this Data Call-In Notice.
Item 4. ON BOTH FORMS: This item identifies the guideline reference number of
studies required. These guidelines, in addition to the requirements specified in
the Data Call-In Notice, govern the conduct of the required studies. Note that
series 61 and 62 in product chemistry are now listed under 40 CFR 158.155
through 158.180, Subpart c.
Item 5. ON BOTH FORMS: This item identifies the study title associated with the
guideline reference number and whether protocols and 1, 2, or 3-year progress
reports are required to be submitted in connection with the study. As noted in
Section in 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.
154
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-In
Item 6. ON BOTH FORMS; This item identifies the code associated with the use
pattern of the pesticide. In the case of efficacy data (product specific
requirement), the required study only pertains to products which have the use
sites and/or pests indicated. A brief description of each code follows:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food crop
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
Item 7. ON BOTH FORMS: This item identifies the code assigned to the substance
that must be used for testing, A brief description of each code follows:
EUP End-Use Product
MP Manufacturing-Use Product
MP/TGAI Manufacturing-Use Product and Technical
Grade Active Ingredient
PAI Pure Active Ingredient
PAI/M Pure Active Ingredient and Metabolites
PA1/PAHLA Pure Active Indredient or Puts Active
Ingredient Radiolabelled
PAIRA Pure Active Ingredient ladiolabelled
PAIRA/M Pure Active Ingredient Radiolabelled
and Metabolites
PAIRA/PM Pure Active Ingredient ladiolabelled
and Plant Metabolites
TEP Typical End-Use Product
TEP % Typical End-Use Product, Percent
Active Ingredient Specified
155
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INSTRUCTIONS EOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
generic and Product Specific Data Call-in
TEP/MET Typical End-Use Product and Metabolites
TEP/PAI/M Typical End-Use Product or Pure Active
Ingredient and Metabolites
TGAI Technical Grade Active Ingredient
TGAI/PAI Technical Grade Active Ingredient or
Pure Active Ingredient
TGAI/PAIRA Technical Grade Active Ingredient or
Pure Active Ingredient
Radiolabelled
TGAI/TEP Technical Grade Active Ingredient or
Typical End-Use Product
MET Metabolites
IMP Impurities
DEGR Degradates
* See; guideline comment
Item 8. This item completed by the Agency identifies the time frame allowed for
submission of the study or protocol identified in item 5.
ON THE GENERIC DATA FORM: The time frame runs from the date of
your receipt of the Data Call-In notice,
ON THE PRODUCT SPECIFIC DATA FORM: The due date for
submission of product specific studies begins from the date stamped on the
letter transmitting the Reregistration Eligibility Decision document, and not
from the date of receipt. However, your response to the Data Call-In itself is
due 90 days from the date of receipt.
Item 9. ON BOTH FORMS; Enter the appropriate Response Code or Codes to show
how you intend to comply with each data requirement. Brief descriptions of
each code follow. The Data Call-In Notice contains a fuller description of each
of these options.
Option 1. ON BOTH FORMS* ^Developing Data^ I will conduct a new study
and submit it within the time frames specified in item 8 above. By
indicating that I have chosen this option, I certify that I will comply
with all the requirements pertaining to the conditions for submittal of
this study as outlined in the Data Call-In Notice and that I will provide
the protocols and progress reports required in item 5 above.
156
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific; Data Call-In
Option 2. ON BOTH FORMS: (Agreement to Cost Shared 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.
However, for Product Specific Data, I understand that this
option is available for acute toxicity or certain efficacy data ONLY if
the Agency indicates in an attachment to this notice that my product is
similar enough to another product to qualify for this option. I certify
that another party in the agreement is committing to submit or provide
the required data; if the required study is not submitted on time, my
product may be subject to suspension.
Option 3. ON BOTH FORMS; (Offer to Cost Share1) I have made an offer to
enter into an agreement with one or more registrants to develop data
jointly. I am also submitting a completed "Certification of offer to
Cost Share in the Development of Data" form. I am submitting
evidence that I have made an offer to another registrant (who has an
obligation to submit data) to share in the cost of that data. I am
including a copy of my offer and proof of the other registrant's receipt
of that offer, I am identifying the party which is committing to submit
or provide the required data; if the required study is not submitted on
time, my product may be subject to suspension. I understand that other
terms under Option 3 in the Data Call-in Notice apply as well.
However, for Product Specific Data, I understand that this
option is available only for acute toxicity or certain efficacy data and
only if the Agency indicates in an attachment to this Data Call-in
Notice that my product is similar enough to another product to qualify
for this option.
Option 4, ON BOTH FORMS; (Submitting Existing Data> I will submit an
existing study by the specified due date that has never before been
submitted to EPA. By indicating that I have chosen this option, I
certify that this study meets all the requirements pertaining to the
conditions for submittal of existing data outlined in the Data Call-In
Notice and I have attached the needed supporting information along
with this response.
157
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call4n
Option 5. ON BOTH FORMS: (Upgrading a Study) I will submit by the
specified due date, or will cite data to upgrade a study that EPA has
classified as partially acceptable and potentially upgradeable. By
indicating that I have chosen this option, I certify that I have met all
the requirements pertaining to the conditions for submitting or citing
existing data to upgrade a study described in the Data Call-in Notice. I
am indicating on attached correspondence the Master Record
Identification Number (MKED) that EPA has assigned to the data that I
am citing as well as the MRH> of the study I am attempting to upgrade,
Option 6, ON BOTH FORMS: fCiting a Studyl 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. If
reviewed, I am providing the Agency's classification of the study.
However, for Product Specific Data, I am citing another
registrant's study. I understand that this option is available ONLY for
acute toxicity or certain efficacy data and ONLY if the cited study was
conducted on my product, an identical product or a product which the
Agency has "grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option if I am
citing my own data. In either case, I will provide the MRID or
Accession number (s). If I cite another registrant's data, I will submit
a completed "Certification With Respect To Data Compensation
Requirements" form.
FOR THE GENERIC DATA FORM ONLY: The following three options
(Numbers 7, 8, and 9) are responses that apply only to the "Requirements Status
and Registrant's Response Form" for generic data.
Option 7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
158
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-in
Option 8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-in
Notice and I request a low-volume minor use waiver of the data
requirement. I am attaching a detailed justification to support this
waiver request including, among other things, all information required
to support the request. I understand that, unless modified by the
Agency in writing, the data requirement as stated in the Notice
governs.
Option 9. (Request for Waiver of Data) I have read the statements concerning
data waivers other than lowvolume minor-use data waivers in the Data
Call-in Notice and I request a waiver of the data requirement I am
attaching a rationale explaining why I believe the data requirements do
not apply. I am also submitting a copy of my current labels. (You must
also submit a copy of your Confidential Statement of Formula if not
already on file with EPA). I understand that, unless modified by the
Agency in writing, the data requirement as stated in the Notice
governs.
FOR PRODUCT gPECIFIC DATA; The following option (number 7) is a
response that applies to the "Requirements Status and Registrant's Response
Form" for product specific data.
Option 1. (Waiver Request) I request a waiver for this study because it is
inappropriate for my product. I am attaching a complete justification
for this request, including technical reasons, data and references to
relevant 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 niy 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 HFRA. If the Agency denies my
waiver request, I must choose a method of meeting the data
requirements of this Notice by the due date stated by this Notice. In
this case, I must, within 30 days-of my receipt of the Agency's written
decision, submit a revised "Requirements Status" form specifying the
159
-------
INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Da
option chosen. I also understand that the deadline for submission of
data as specified by the original Data Call-In notice will not change.
Item 10.
ON BOTH FORMS:
Item 11.
Item 12,
Item 13.
ON BOTH FORMS!
ON BOTH FORMS:
ON BOTH FORMS:
This item must be signed by an authorized
representative of your company. The person
signing must include Ms/her title, and must initial
and date all other pages of this form.
Enter the date of signature.
Enter the name of the person EPA should contact
with questions regarding your response.
Enter the phone number of your company contact.
NOTE: You may provide additional information that does not fit on this form in a
signed letter that accompanies this your response. For example, you may wish
to report that your product has already been transferred to another company or
that you have already voluntarily cancelled this product. For these cases,
please supply all relevant details so that the Agency can ensure that its records
are correct.
160
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COPY
Page 1 of 2
United States Environmental Protection Agency
Washington, D,C« 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPQHSE
Form Approved
OK8 No. 2Q7Q-Q107
20TO-0057
Approval Ixplres 03-51-96
INSTRUCTIONS: Pleas* type or print in Ink. Please read carefully the attached instructions end supply the Information requested on this form.
Use additional sheet (s) if necessary
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0082 Pronamide GENERIC
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I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that eny knowingly false; or Misleading statement may be punishable by fine, imprisonment
or both under applicable law.
Signature and Title of Conpany's Authorized Representative
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DRAFT COPY
Page 2 of 2
United States Environmental Protection Agency
Washington, D.C. 20460
RBQ01RBMBHTS BTATOB AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print in ink. PI else read carefully the attached instructions and supply th* Information requested
Use additional eheet(s) if necessary
1. Conpany name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
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Page 1 of 9
United States Environmental Protection Agency
Washington, B.C. 20460
* COMMENTS FOR GOIDBLIMB REQUIREMENTS
Case # and Name
0082 Pronamide
Chwnfcal # and Name
101701 Propyzamide
GUIDELINE
COMMENT
61-1 The submitted data (MRID 40211101) does not fulfill the guideline requirement for
product identity because the CAS Registry Numbers and purpose of all of the ingredients
must be provided. The Agency is requiring a new Confidential Statement of Formula (CSF,
1PA Form 8570-4) for the 92% Technical Pronamide.
72-3(b) Estuarine studies are required because of pronamide use on sites adjacent to estuaries,
including turf, hay, clover, alfalfa and pasture land. Turf, hay, clover, and pastures
may exposure estuarine species to the pesticide. The value added of requesting testing
with the estuarine shrimp is much higher than with the estuarine fish species, since
there is some certainty that pronamide is practically non-toxic to fish, the value added
of obtaining molluscs data would be to confirm the Agency's presumption of minimal
hazard and to ensure that pronamide is not toxic to molluscs while having low tpxicity
to fish. The Agency is requiring that confirmatory data on the molluscs and shrimp
species be submitted.
72-3(c) See comment for guideline 72-3(b).
72-4 (b) The aquatic invertebrate life cycle study is required due to persistence of pronamide in
aquatic environments. Also, the
solubility and aerial application would allow pronamide into the aquatic environment and
the aquatic EEC is greater than or equal to 0.01 of the LC50 (5.6/100 - 0.056 ppm) for
aquatic invertebrates. Since aquatic invertebrates are more sensitive than fish, the
Agency is requiring that confirmatory data on aquatic invertebrate life cycle study be
submitted.
123-1(a) The Agency has classified the submitted data (MRID 42176801} as supplemental because a
NOEC was not determined for the seed germination study. However, the study is
sufficient to use for risk assessment purposes. Therefore, no further testing is
required for seed germination. However, the Agency has also classified the submitted
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Page 2 of 9
United States Environmental Protection Agency
Washington, D.c. 20460
* COHMEMTS FOR GUIDELINE RBQDIRKKBNT8
Case 0 and Name
0082 Pronamide
Chemical * and Name
101701 Propyzamide
GUIDELINE
COMMENT
data (MRID 42176801) as supplemental due to invalid cucumber results for the seedling
emergence study. Since cucumber and tomato are the two most sensitive dicots, the Agency
is requiring that cucumber test be repeated. The tomato test is recommended to be
performed with the cucumber for comparative purposes.
123-2 Aquatic plant toxicity study is required for five species - Lemna gibba, Skele^onema
costatum, Anabaena flos-aquae, Selenastrum capricornuturn, and freshwater diatoi because
pronamide can be applied by aerial application and the solubility (15 ppm> is greater
than 10 ppm. Selenastrum capricornuturn is the only species tested (MRID 42176802) and
is classified as core minimum. Therefore, the Agency is requiring additional <|ata on
the other four species of aquatic plants.
132-1(a) The Agency is requiring confirmatory postapplication/reentry data derived from the
foliar dislodgeable residue dissipation and dermal passive dosimetry (133-3) studies to
commercial turf to support the use of pronamide on commercial turf. This same
confirmatory data is also being required for use on lettuce based on the potential for
significant hand contact associated with this use.
The Agency does not have data to make a reregistration decision of pronamide for use on
residential lawns/turf. An estimate of risk is not feasible because of numerous
uncertainties in potential exposure levels, especially for children, and a recognition
that a reentry interval is not practical or enforceable in residential situations. The
postapplication/reentry data derived from the foliar dislodgeable residue dissipation
and (133-3) dermal passive dosimetry studies to commercial turfgrass can be used to
support the use of pronamide on residential lawns/turf.
133-3
See comment for guideline 132-1(a).
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Page 3 of 9
United States Environmental Protection Agency
Washington, D.C. 20460
* COHHINTS FOR QUIDBLINB REQUIREMENTS
Cise # and Mane
0082 Pronamide
Chemical # and Name
101701 Propyzamide
GUIDELINE
COMMENT
164-1 The submitted field dissipation study (MRID 40925401) was found unacceptable, but
upgradable. In response to concerns raised by the Agency, the registrant submitted a
supplemental report (MRID 41913503). This supplemental report did not provide any
useful information to upgrade the study. Information were either incorrect (such as "no
mention of having to isolate and/or identify degradation products in the Pesticide
Assessment Guidelines: Subdivision N - Chemistry - Environmental Fate") or misleading
(such as "overemphasizing TLC technique and ignoring other relatively-advanced
identification technology GC/MS, GC, and HPLC mentioned in the SEP for the terrestrial
field dissipation study"). Furthermore, the study sites are not representative of the
areas where the pesticide is expected to be used because they are located in two
counties (approximately 100 miles apart) in central California. Pronamide is primarily
used for lettuce, and secondarily for turf and forage (including alfalfa and seed
clover). Although lettuce is mainly grown in CAr other states (such as AZ and FL) have
significant acreage for lettuce. In addition, the total acreages for alfalfa in CA is
only half of those in WI. The relatively short dissipation rate for pronamide in the
field, resulting in high percentage of residues as unidentified degradation products, is
in contradiction to the persistence suggested by the environmental fate laboratory
studies. For the above reasons, the Agency is requiring a new field dissipation study.
The field dissipation study should be designed to allow additional samplings in order to
define the long-term dissipation if pronamide or its major degradation products were
found to be persistent during the conduction of the study. The Agency is requiring that
the parent compound and its major degradation products be analyzed separately.
165-2 Based on the metabolites identified in lettuce sampled at various intervals and the
metabolites found in carrot greens and wheat forage and straw, the Agency concluded that
residues of concern in rotated crops following treatment of pronamide consist of
pronamide and itB metabolites bearing the 3f5-dichlorobenzoyl group. Therefore, the
Agency is requiring a field rotation crop study. The registrant is required to revise
the current rotational crop restrictions for pronamide. For leafy vegetables and
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Page 4 of 9
United states Environmental Protection Agency
Washington, D.C. 20460
* COMMENTS TOE GUIDELINE REQUIREMENTS
Case i and Name
0082 Pronamide
Chemical I and Name
101701 Propyzamide
GUIDELINE
COMMENT
carrots, the pi ant back intervals should be expanded. In order to determine the
plantback intervals, field rotational crop studies are to be conducted on lettuce and
carrots. In the meantime, the plantback interval for lettuce should be changed to 6
months. Rotation to cereal grain crops following treatment of pronamide could lead to
detectable residues in grain crops. In order to determine the plantback interval or
whether tolerances are needed for rotational grain crops, field rotational crop studies
are to be conducted on wheat.
According to "Guidance on How to Conduct Studies on Rotational crops" issued
2/23/93, lettuce, carrots, and wheat should be planted after the minimum aging interval
at two sites in which the soil had been treated with pronamide at the maximum label rate
and the maximum number of applications [165-2]. The crops should be harvested and all
the plant parts prescribed in the Table II of Subdivision 0 should be analyzed for
pronamide and its metabolites containing the 3,5-dichlorobenzoyl group. If these
limited field studies show finite residues of pronamide within the 12-month plantback
period, then additional field trials will be required in order to establish rotational
crop tolerances.
171-4(c) A revised version of the PAM II method, which includes an alkaline hydrolysis to release
bound residues, resulted in increased method efficiency and has been submitted for the
enforcement of tolerances in animal commodities. The revised method remains to be
validated by an independent laboratory. For FDA enforcement monitoring purposes, the
Agency requires that representative plant and animal tissue samples bearing metabolites
of pronamide be subjected to analysis by FDA multi-residue protocols C, D, and E from
PAM Vol. I.
171-4(d) See comment for guideline 171-4(c).
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Page 5 of 9
United States Environmental Protection Agency
Washington, D.C. 20460
* COMMENTS TOR GUIDBLINB RBQOIRKMKHTfl
Cise 0 and None
0082 Pronamide
Chemical # and Nam
101701 Propyzamide
GUIDELINE COMMENT
171-4(e) The storage stability data for alfalfa, apples, and lettuce (MRID No. 41570101)
submitted by Rohm and Haas vere generated by Craven Laboratories and no storage
stability data for other crops are available. The Agency has determined that these data
are insufficient to support reregistration of pronamide and must be repeated. The
Agency is requiring storage stability data on milk, alfalfa, apples, grapes, lettuce and
plums and the processed commodities of apples, grapes and plums. These data are
considered conf irmatory.
171-4(k) ALFALFA
(ALFALFA SEED) - Samples from an alfalfa study (meal and seed) were analyzed by Craven
Laboratories (MRID Mo. 40593103). Residues did not concentrate (5X label application
rate) in the processed commodities, and it was concluded that no food/feed additive
tolerances were required for meal. Data is not required for alfalfa meal because the
Agency will translate alfalfa hay data to alfalfa meal. The Agency has determined that
the data on alfalfa seed are insufficient to support reregistration and must be
repeated. However, the Agency has concluded that enough magnitude of the residue data
are available to support the extension of the existing tolerance on alfalfa on an
interim basis until the field trial data are replaced. A new cropfieId trial study on
alfalfa seed is required. The registrant nay need to perform a processing study to
extract the seed from the plant in order to obtain residue data on alfalfa. These data
are considered confirmatory.
171-4 fk) ARTICHOKE
Residue data are not available for the Agency to determine whether the existing
tolerance is adequate for the labeled use (1 day PHI). The use after ditching with a 1
day PHI relies solely on Craven Laboratories, Inc. data. The Agency has determined that
these data are insufficient to support reregistration and must be repeated. The Agency
has also concluded that enough magnitude of the residue data are available to support an
extension of the existing tolerance on artichokes on an interim basis until the field
-------
Page 6 of 9
United States Environmental Protection Agency
Washington, D.C. 20460
* COMMENTS FOR QUIDEHNB RB^OIRKMEHTB
Case # and Name
0082 Pronawide
Ch«mlcal f and Name
101701 Propyzainide
GUIDELINE
COMMENT
trial data are replaced. The existing non-Craven artichoke field trial data will not
support all of the current use patterns. Additionally, there are no other crop field
trial data that might be translated to this particular use of artichokes. The
over-the-plant row application with a 60 day PHI is not affected. The Agency is
requiring a label amendment to delete the 1 day PHI use or replacement of artichoke
field trial data.
171-4(k) PEAS, DRIED
(AUSTRIAN WINTER PEAS) REGIONAL - Rohm and Haas has identified Craven Laboratories as
the source of the analytical field trial data submitted in the IR-4 tolerance petition
(PP#6E3457J to support the tolerance for Austrian winter peas. The Agency has
. determined that these data are insufficient and must be repeated. The Agency has also
concluded that enough magnitude of residue data are available to support an extension of
the existing tolerance on winter peas on an interim basis until the field trial data are
replaced. Summary data from Europe have been submitted to support the pea tolerance.
The Agency has determined that these data are also insufficient to support this use.
The Agency is requiring confirmatory crop field trial data on dried winter peas. This
study is to be conducted in the U.S. (Idaho? Oregon or Washington). These states
represent about 99% of domestic Austrian winter pea production, IR-4 or other parties
interested in developing the data are advised to consult the Agency before pursuing the
trials.
171-4(1) APPLE
Craven Laboratories was identified as the analytical services laboratory for an apple
processing study (MRID No, 41034301). No detectable residues of pronanide (5X label
rate) were found in juice and dry pomace. It was determined that no food/feed additive
tolerances were necessary. The Agency has determined that these data are insufficient
to Bupport reregistration and must be repeated. The Agency has also concluded that
enough magnitude of the residue data are available to support an extension of the
-------
Page 7 of 9
United States Environmental Protection Agency
Washington, D.C. 20460
* COMMENTS FOR GUIDELINE REQUIREMENTS
Case f and Name
0082 Pronamide
Chemical # and Name
101701 Propyzamide
GUIDELINE COMMENT
existing tolerance on apples on an interim basis until the processing data are replaced.
The Agency is requiring a new processing study to determine if pronamide and/or its
regulated metabolites concentrate in the processed apple products (juice, wet pomace,
and dry pomace) . These data are considered confirmatory.
171-4(1) GBAPES
Rohm and Haas identified a grape processing study {MRID No. 40593101) as containing
Craven data. Residues of pronamide were detected below the established o.l ppm
tolerance for grapes (IX application rate) in juice, raisins, raisin waste, wet pomace,
and dry pomace. Food/feed additive tolerances were not required. The Agency has
determined that these data are insufficient to support reregistration and must be
repeated. The Agency has also concluded that enough magnitude of the residue data are
available to support an extension of the existing tolerance on grapes on an interim
basis until the processing data are replaced. The Agency is requiring a new processing
study to determine if pronamide and/or its regulated metabolites concentrate in the
grape processed commodities. These data are considered confirmatory.
171-4(1) PLUM
Rohm and Haas identified Craven Laboratories as the source of the processing study for
plums (MRID No. 40593102). Ho measurable residues of pronamide were detected in/on
fresh plums and prunes from a 5X label rate treatment. It was concluded that no
food/feed additive tolerances were necessary. The Agency has determined that these data
are insufficient to support reregistration and must be repeated. The Agency has also
concluded that enough magnitude of the residue data are available to support an
extensioon of the existing tolerance on plums on an interim basis until the processing
data are replaced. The Agency is requiring a new processing study to determine if
pronamide and/or its regulated metabolites concentrate in prunes (plums). These data
are considered confirmatory.
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Page 8 of 9
United States Environmental Protection Agency
Washington, D.C, 20460
* COMMENTS FOR GUIDELINE RBQUIREHEHT8
Case 0 and Name
0082 Pronaraide
Chemical f and Name
101701 Propyzamlde
GUIDELINE
COMMENT
201-1 Data must be submitted to support the spray drift data requirements [Droplet size
spectrum (2O1-1) and Drift Field Evaluation (202-2)]. The Agency is requiring these
studies because: (a) pronamide can be applied by aerial equipnent to lettuce (AZ790036
and CA7900O2), artichoke (Reg. No. 707-159 and CA870078J, endive (AZ790036), Christmas
tree plantations (QR830013 and WA91Q043), and fallow lands (Reg. No. 707-159); and (2)
the Agency is concerned about the off-target damage drift of a toxic substance. The
registrant is not currently a member of the Spray Drift Task Force, therefore these
studies are required. However, if the registrant joins the Spray Drift Task Force and
provides the Agency with documentation, these data requirements will be held in reserve
status pending the submission of the final Task Force report. If the findings of the
Task Force are inconclusive, then new studies may be required.
202-1 See comment for guideline 201-1.
231 Mixer/loader/applicator exposure data are required when both the exposure and toxicity
criteria are met. The potential for dermal and inhalation exposure exists during the
mixing and loading of pronamide products and during the ground boom, aerial, and
hand-spray applications of the wettable powder formulation of pronamide. Data are
available for the wettable powder formulation of pronamide, but data are needed to
confirm that the potential worker exposure when using the granular formulation does not
result in an unacceptable risk to workers, especially the mixer/loaders. Pronamide has
been classified as a B2 carcinogen. Therefore, the Agency is requiring confirmatory
mixer/loader/applicator exposure data for the granular formulations of pronamide.
In lieu of conducting a study, the registrant may submit surrogate data in support
of the reregistration requirements. Engineering controls, protective clothing and
equipment, and risk mitigation procedures as appropriate for the current label should be
discussed. Additional worker activity/use information which would clarify the actual
exposure may also be submitted for evaluation.
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Page 9 of 9
United States Environmental Protection ftgency
Washington, D.C. 20460
* COMMENTS FOR GUIDELINE REQUIREMENTS
Case # end Name
0082 Pronamide
Chemical f and Heine
101701 Propyzamide
GUIDELINE COMMENT
232 See comment for guideline 231,
-------
DRAFT COPY
Page 1 of 3
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print frt ink. Please read carefully
Use additional sheet(s) ff necessary.
1 . Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
Nunfcer
61-1
61-2 (b) w^_
lliltliil Jll^f; 5§lillill
62— 1
iiiiliiiiiiiii
62-3
63-3
63-5
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5. Study Title
Prod Chen - Regular Chemical
the attached Instructions and supply tlie information requested
2. Case f and Name
0082 Pronamide
EPA Reg. No. NNNNNN-NNNNN
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Product Identity & composition (1)
productn & fornulatn
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Form Approved
MB do. Z070-0107
2070-0057
Approval fxpires 03-31-96
on this form.
3. Date and Type of DC!
PRODUCT SPECIFIC
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I acknowledge that any knowingly false or misleading statement may
or both under applicable law.
Signature and Title of Company's Authorized Representative
be punishable by fine, Imprisonment
12. Name of Company Contact
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-------
DRAFT COP¥
Page 2 of3
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS; Please type or print in ink. Please read carefully
Use additional sheet (s) ff necessary.
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
Number
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the attached instructions and supply the information requested
2. Case # and Name
0082 Pronamide
EPA Reg. No. NNNNNN-NNNNN
Vapor pressure
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Form Approved
OMB DO. 2070-0107
2070-0057
Approval Expires 03-31-96
on this form.
3. Date and Type of DG1
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
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Date
-------
DRAFT COPY
Fage 3 of
United States Environmental Protection Agency
Washington, D, c. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print In ink. Please read carefully
Use additional sheet (s) ff necessary.
1. Conpany name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4, Guideline
Requirement
Number
iiiillillliilll
81-5
5. Study Title
Primary dermal irritation (1,1)
^^s|j|^;§li§^||(^i^^^^Jil|^|||;§i
the attached Instructions and supply the information requested
2. Case tf and Name
0082 Pronamide
EPA Reg. No. NNNNNN-NNNNN
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Reports
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Initial to indicate certification as to Information on this page
(full text of certification is on page one).
7. Teat
Form Approved
OMB No. 2070-0107
2070-0057
Approval Expires 01-31-96
on this form.
3. Date and Type of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
Substance
MP/EP
8. Time
Frame
8 raos.
9, Registrant
Response
'mfmmmmm
Date
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DRAFT COPY Page 1 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
FOOTNOTES AND KEX DEFINATIONS FOR GUIDELINE REQUIREMENTS
Case / and Name: 0082 Pronamide
Key: MP « manufacturing-use product; EP • end-use product; provided formulators purchase their active ingredient(s) from a registered source, they need not submit or cfte
(fata pertaining to the purchased product.[MOTE: If a product Is a 100 percent repackage of another registered product that fa purchased, and any use for the product does
not differ from those of the purchased and registered source, users are not subject to any data requirements identified in the tables.]; T6P = typical end-use product;
TCAl • technical grade of the active ingredient; PA I = "pure" active ingredient; PAIRA = "pure11 active ingredient, radiolabeled.
UB« Categories Key;
A - Terrestrial food crop B - Terrestrial food feed crop C - Terrestrial nonfood crop D - Aquatic food crop E - Aquatic nonfood outdoor
f - Aquatic nonfood Industrial 0 - Aquatic nonfood residential H • Greenhouse food crop 1 - Greenhouse nonfood crop J - Forestry
K * Residential outdoor L - Indoor food N - Indoor nonfood M - Indoor Medical o - Indoor residential
Footnotes: IThe following notes are referenced in column t*ro (5. Study Title) of the REQUIREMENTS STATUS ANO REGISTRANT'S RESPONSE form.l
Prod diea - Regular Chancel
1 Requirements pertaining to product identity, conposftion, analysis, and certification of ingredients are detailed further in the following sections: "158.155 for
product identity and composition (61-15; "158.160, 1M.162, and 158.165 for description of starting materials and manufacturing process <61-2>j *!58.167 for
discussion of formation of impurities (el-I); *158.1fO for preliminary analysis (62-1); *158.175 for certification of limits <62-2>; and "158.1SQ for enforcement
analytical methods <62-B). '
2 A schematic diagram end/or brief description of the production process will suffice if the pesticide is not already under full scale production and an experimental
use permit is being sought. .
3 If the pesticide Is not already under full scale production and an experimental use permit is sought, a discussion of unintentional ingredients shall be submitted to
the extent this information Is available.
4 To support registration of an HP or EP, whether produced by an integrated system or not, the technical grade of Active Ingredient must be analyzed, tf the technical
grade of Active Ingredient cannot be isolated, m statement of conposition of the practical equivalent of the technical grade of Active Ingredient must be submitted.
Data on EPs or HPa Mill be required on a case-by-case basis.
5 Certified limits are not required for inert ingredients in products proposed for experimental use.
6 Required If technical chemical Is solid at room tegperature.
7 Required if technical chemical is liquid at room temperature,
8 Required if technical chemical is organic and non-polar.
9 Required if test substances are dfspersible with water.
10 Required if product contains an oxidizing or reducing agent,
11 Required if product contains combustible liquids.
12 Required if product is potentially explosive.
13 Required if product is a liquid.
14 Required if product is an emulsifiable liquid and is to be diluted with petroleum solvents.
15 Required if end-use product is liquid and is to be used around electrical equipment.
Acute Toxic - Regular Chevical
1 Hot required If test material is a gaa or highly volatile.
2 Mot required if test materfal is corrosive to skin or has pH less then 2 or greater than 11.5; such a product will be classified as Toxfcity Category 1 on the basis
of potential eye and dermal irritation effects.
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DRAFT COPY Page 2 of 2
United States Environmental Protection Agency
Washington, D. c, 20460
FOOTNOTES AND KEY DEFINATIONS FOR GUIDELINE REQUIREMENTS
Case t and Name: 0082 Pronamide
Footnotes (cont.):
3 Required if the product consists of, or infer conditions of use Mill result in, an inhaUble material (1>.
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Attachment 4. EPA Grouping of End-Use Products for
Meeting Data Requirements for Reregistration
177
-------
-------
EPAS DECISION ON BATCHING PRODUCTS CONTAINING ERONAMIDE FOR PURPOSES OF
MEETING ACUTE TOXICITY DATA REQUIREMENTS FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the acute toxicity
data requirements for reregistration of products containing the active ingredient pronamide, the Agency
considered batching products. This process involves grouping similar products for purposes of acute
toxicity. Factors considered in the sorting process include each product's active and inert ingredients
(identity, percent composition and biological activity), type of formulation (e.g,,emulsifiable concentrate,
aerosol, wettable powder, granular, etc.), and labeling (e.g.,signal word, use classification, precautionary
labeling, etc.). Note that the Agency is not describing batched products as "substantially similar" since
some products within a batch may not be considered chemically similar or have identical use patterns,
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Acute toxicity data on individual products has frequently been found to be
incomplete. Notwithstanding the batching process, the Agency reserves the right to require, at any time,
acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite a single
battery of six acute lexicological studies to represent all the products within that batch. It is the
registrants' option to participate in the process with all other registrants, only some of the other registrants,
or only their own products within a batch, or to generate all the required acute toxicological studies for
each of their own products. If a registrant chooses to rely upon previously submitted acute toxicity data,
he/she may do so provided that the data base is complete and valid by today's standards (see acceptance
criteria attached), the formulation tested is considered by EPA to be similar for acute toxicity, and the
formulation has not been significantly altered since submission and acceptance of the acute toxicity data.
Regardless of whether new data is generated or existing data is cited, the registrant must clearly identify
the material tested by its EPA registration number. If more than one Confidential Statement of Formula
(CSF) exists for a product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI Notice
contains two response forms which are to be completed and submitted to the Agency within 90 days of
receipt. The first form, "Data Call-In Response", asks whether the registrant will meet the data
requirements for each product. The second form, "Requirements Status and Registrant's Response", lists
the product specific data required for each product, including the standard six acute toxicity tests. A
registrant who wishes to participate in a batch must decide whether he/she will provide the data or depend
on someone else to do so* If a registrant supplies the data to support a batch of products, he/she must
select one of the following options: Developing Data (Option 1), Submitting an Existing Study (Option
4), Upgrading an Existing Study (Option 5), or Citing an Existing Study (Option 6). If a registrant depends
on another's data, he/she must choose among: Cost Sharing (Option 2), Offers to Cost Share (Option
3) or Citing an Existing Study (Option 6). If a registrant does not want to participate in a batch, the
choices are Options 1, 4, 5 or 6. However, a registrant should know that choosing not to participate in
a batch does not preclude other registrants in the batch from citing his/her studies and offering to cost
share (Option 3) those studies.
179
-------
Table I identifies 1 batch.
Table I.
Batch
No.
1
EPA Reg. No.
707-159
707-98
8660-85
CA79000200
CA86006500
CA9 1000700
FL91QOQ70G
OR983001300
OR9000400
OR9000400
WA91004300
% of pronamide
& other Active ingredients
50
50
50
50
50
50
50
50
50
50
50
Formulation Type
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
wettable powder
Table n lists the products which could not be batched. For the purposes of acute toxicity batching,
these products were not considered similar, or their similarity could not be determined with the
information available. The registrants of these products are responsible for meeting the acute toxicity data
requirements specified in the data matrix for end-use products.
Table H,
EPA Reg. No.
707-113
5481-170
8660-132
8660-134
% of pronamide
& other Active Ingredients
92.0
1.0
0.57
0.57
Formulation Type
technical
granular
granular
granular
180
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Attachment 5. EPA Acceptance Criteria
181
-------
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SUBDIVISION D
Guideline Study Title
Series 61 Product Identity and Composition
Series 62 Analysis and Certification of Product Ingredients
Series 63 Physical and Chemical Characteristics
183
-------
61 Product Identity and Composition
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Name of technical material tested (include product name mad trade name, if appropriate).
2 , _ Name, nominal concentration, and certified limits (upper and lower) for each active ingredient and each intentionally -added
inert ingredient.
3. _ Name and upper certified limit for each impurity or each group of impurities present at _>, 0. 1 % by weight and for certain
lexicologically significant impurities (e.g., dioxias, m'trosamines) present at <0.1%,
4. _ Purpose of each active ingredient and each intentionally-added inert
5. _ Chemical name from Chemical Abstracts index of Nomenclature and Chemical Abstracts Service (CAS) Registry Number
for each active ingredient and, if available, for each intentionally-added inert.
6, _ _ Molecular, structural, and empirical formulas, molecular weight or weight range, and any company assigned experimental
or internal code numbers for each active ingredient.
7. _ Description of each beginning material in the manufacturing process.
_ EPA Registration Number if registered;
for other beginning materials, the following:
_ Name and address of manufacturer or supplier.
_ Brand name, trade name or commercial designation.
_ Technical specifications or data sheets by which manufacturer or supplier describes composition, properties or
toxicity.
8. _ Description of manufacturing process.
Statement of whether batch or continuous process.
_ Relative amounts of beginning materials and order in which they are added.
Description of equipment.
_ Description of physical conditions (temperature, pressure, humidity) controlled in each step and the parameters that
are
Statement of whether process involves intended chamical reactions.
Flow chart with chemical equations for each intended chemical reaction.
Duration of each step of process.
Description of purification procedures.
Description of measures taken to assure quality of final product.
9, _ Discussion of formation of impurities based on established chemical theory addressing (1) each impurity which may be
present at _>_ 0. 1 % or was found at >_ 0. 1 % by product analyses and (2) certain lexicologically significant impurities (see
#3).
184
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62 Analysis and Certification of Product Ingredients
ACCEPTANCE CRITERIA
The following criteria apply to the technical grade of the active ingredient being reregistered. Use a table to present the information
in items 6, "7, and 8,
Does your study meet the following acceptance criteria?
1. Five or more representative samples (batches in case of batch process) analyzed for each active ingredient and all impurities
present at _>_0.1%.
2. Degree of accountability or closure > ca 98%.
3, Analyses conducted for certain trace toxic impurities at lower than 0.1 % (examples, nitrosamines in tfae case of products
containing dimtroanilines or containing secondary or tertiary amines/alkanoJamines plus nitrites; polyhalogentted
dibenzodioxins and dibenzofurans). [Note that in the case of nitrosamines both fresh and stored samples must be analyzed.].
4. Complete and detailed description of each step in analytical method used to analyze above samples,
5. Statement of precision and accuracy of analytical method used to analyze above samples.
6. Identities and quantities (including mean and standard deviation) provided for each analyzed ingredient.
7. Upper and lower certified limits proposed for each active ingredient and intentionally added inert along with explanation
of how the limits were determined.
8, Upper certified limit proposed for each impurity present at _>_ 0.1 % and for certain lexicologically significant impurities
at <€>.!% along with explanation of bow limit determined.
9, Analytical methods to verify certified limits of each active ingredient and impurities (latter not required if exempt from
requirement of tolerance or if generally recognized as safe by FDA) are fully described.
10. Analytical methods (as discussed in #9) to verify certified limits validated as to their precisian and accuracy.
185
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63 Physical and Chemical Characteristics
ACCEPTANCE CRITERIA
The following criteria apply to the technical grade of the active ingredient being reregistered.
Does your study meet the following acceptance criteria?
63-2 Color
Verbal description of coloration (or lack of it)
Amy intentional coloration also reported in terms of Munsell color system
63-3 Physical State
Verbal description of physical state provided using terms such as "solid, granular, volatile liquid*
Based on visual inspection at about 20-25° C
63-4 Odor
Verbal description of odor (or lack of it) using terms such ai 'garlic-like, characteristic of aromatic compounds"
Observed at room temperature
63-5 Melting Point
Reported in °C
Any observed decomposition reported
63-6 Boiling Point
Reported in "C
Pressure under which B,P. measured reported
Any observed decomposition reported
63-7 Density, Bulk Density, Specific Gravity
Measured at about 20-25° C
Density of technical grade active ingredient reported in g/ml or the specific gravity of liquids reported with reference to
water at 20° C. [Note: Bulk density of registered products may be reported in Iba/ft3 or Ibs/gallon.]
63-8 Solubility
Determined in distilled water and representative polar sod non-polar solvents, including those used in formulations and
analytical methods for the pesticide
Measured at about 20-25° C
Reported in g/100 ml (other units like ppm acceptable if sparingly soluble)
63-9 Vapor Pressure
Measured at 25° C (or calculated by extrapolation from measurements made at higher temperature if pressure too low to
measure at 25° C)
Experimental procedure described
Reported in nun Hg (tarr) or other conventioBal units
63-10 Dissociation Constant
Experimental method described
Temperature of measurement specified (preferably about
20-25°C)
63*11 Octanol/water Partition Coefficient
__ Measured at about 20-25" C
Experimentally determined and description of procedure provided (preferred method-45 Fed. Register 77350}
Data supporting reported value provided
186
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63-12 pH
Measured at about 20-25° C
Measured following dilution or dispersion in distilled water
63-13 Stability
Sensitivity to metal ions and metal determined
Stability at normal and elevated temperatures
Sensitivity to sunlight determined
187
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SUBDIVISION F
Guideline Study Title
81-1 Acute Oral Toxichy in the Rat
81-2 Acute Dermal Toxicily in the Rat, Rabbit or Guinea Pig
81-3 Acute Inhalation Toxicity in the Rat
81-4 Primary Eye Irritation in the Rabbit
81-5 Primaiy Dermal Irritation Study
81-6 Dermal Sensitization in the Guinea Pig
188
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81-1 Acute Oral Toxicity in the Bat
ACCEPTANCE CRITERIA
Does your study me?f the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. At least 5 young adult rats/sex/group.
3, Dosing, single oral may be administered over 24 his.
4." Vehicle control if other than water.
5. Doses tested, sufficient to determine a toirieity category or a limit dose (5000 mg/kg).
6. Individual observations at least once a day.
7. Observation period to last at least 14 days, or until all test animals appear normal whichever is longer.
8. Individual daily observations.
9. Individual body weights.
10. Gross necropsy on all animals.
Criteria marked with in * ire supplemental «nd may DC* be requited for every study.
189
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81-2 Acute Dermal tenacity in the Rat, Babbit or Guinea Pig
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. At least 5 aaimals/sex/grenip.
3.f Sate 200-300 gm, fsbbits 2.0-3.0 kg or guinea pigs 350-450 gm.
4. Dosing, single dermal.
5. Dosing duration at least 24 hours.
6.* Vehicle control, only if toxicity of ¥ehicle is unknown,
7. Doses tested, sufficient to determine a toxicity category or a limit dose (2000 mg/kg),
8. Application site clipped or sfcaved at least 24 noun before dosing.
9. Application site at least 10% of body surface area.
10, Application site covered with a porous nomiritating cover to retain test material and to prevent
ingestion.
11. Individual observations at least once a day,
12. Observation period to last at least 14 days,
13. Individual body weights,
14. Gross necropsy on all animals.
Criteria narked with in * ire supplements] uid may not be required for every study.
190
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81-3 Acute Inhalation Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify' material tested (technical, end-use product, etc).
2. Product is a gas, a solid which may produce a significant vapor hazard based on toxicity and expected use or contains
particles of inhalable size for man (aerodynamic diameter 15 jim or less),
3. At least 5 young adult rats/sex/group.
4. Dosing, at least 4 hours by inhalation.
5. Chamber air flow dynamic, at least 10 air changes/hour, at least 19% oxygen content.
6. Chamber temperature, 22° C (±2°), relative humidity 40-60%.
7. Monitor rate of air flow.
8, Monitor actual concentrations of test material in breathing zone.
9. Monitor aerodynamic particle size for aerosols.
10. Doses tested, sufficient to determine a toxicity category or a limit dose (5 mg/L actual concentration of respirable substance).
11. Individual observations at least onoe a day.
12. Observation period to last at least 14 days,
13. Individual body weights.
14. Gross necropsy on all animal.'!.
191
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81-4 Primary Eye Irritation in the Rabbit
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1, Identify material tested (technical, end-use product, etc).
2, Study not required if material is corrosive, causes severe
dermal irritation or has a pH of _<_2 or >11.S.
3. 6 adult rabbits,
4. Dosing, instillation into the conjunctiva! sac of one eye
per animal.
5. Dose, 0.1 ml if a liquid; 0.1 ml or aot more than 100 mg if a solid, paste or particulate substance.
6. Solid or granular test material ground to a fine dust.
7. Eyes not washed for at least 24 hours.
8. Eyes examined and graded for irritation before dosing and
at 1, 24, 48 and 72 hr, then daily until eyes are normal
or 21 days (whichever is shorter).
9,* Individual daily observations.
Criteria nutted with an * «it supplemental and cay not be required for every study.
192
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81-5 Primary Dermal Irritation Study
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1, Identify material tested (technical, aid-use product, etc).
2. Study not required if material is corrosive or has a pH of <2 or >11.S.
3. 6 adult animals.
4. _ Dosing, single dermal.
5. Dosing duration 4 hours.
6, Application site shaved or clipped at least 24 hours prior to dosing.
7. Application ate approximately 6 en?.
8. Application site covered with a gauze patch held in place with noninitating tape.
9, Material removed, washed with water, without trauma to application site.
10. Application site examined and graded for irritation at 1, 24, 48 and 72 hr, then daily until normal or 14 days (whichever
is shorter).
11.* Individual daily observations.
Criteria mukc4 with an * are eupplemeaUl and may not be required for every study.
193
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81-4 Dermal Scnsitization in the Guinea Fig
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. Study not required if material is corrosive or has a
pH of <2 or >I1.5.
3. One of the following methods is utilized:
Freund's complete adjuvant test
^___^ Guinea pig maximization test
Split adjuvant technique
Buckler test
Open epicutaneous lest
Mauer optimization test
Footpad technique in guinea pig.
4. Complete description of test,
5.* Reference for test.
6. Test followed essentially as described in reference document.
7. Positive control included (may provide historical data conducted within the last 6 months).
Criteria mtrfced wilh an * w« wpplemenul md may not be required for every study.
194
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Attachment 6. List of AM Registrants Sent This Data Call-in (insert) Notice
195
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List of.All Registrants Sent This Data Call-in Notice
Company Muitwr
OOOfOF
005481
003660
065147
Company Mam*
ROHM & HAAS CO
AMVAC CHEMICAL CORP
ANDERSONS, (THE), LAWH FERTILIZER
BOTANICAL RESOURCES INC
Additional Maine
ATTN: ROBERT H. LARK IN
AGENT FOR: ANDERSONS, THE
Address
100 INDEPENDENCE HALL WEST
4100 EAST WASHINGTON BLVD
BOX 119
5465 HALLS FERRY RO
City S State
PHILADELPHIA PA
LOS ANGELES CA
HAUMEE OH
INDEPENDENCE OR
Ztp
19106
90023
4S537
97351
Case i and Name
0082 Pronamide
Chemical f and Name
101701 Propyzamide
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Attachment 7. Cost Share and Data Compensation Forms and Confidential
Statement of Formula Form with Instructions
197
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Confidential Business Informttion: Dots Not Contain N»tfon*i Security
UflM SUM* Enyfron>n*nl*l Pfolnrlton Agency
_ Oft** <* PWHteMt ffowiww n, OC 304$O
v C rr-% Confidential Statement of Formula
3. Product NMM
EPA USE ONLY
Id, C«n|»n*ntt in Fwmulnwfl (Lut m »e>u*8y tmrotiuc+d
mfe tfw tottwtmtion. 6m somnentr Kctfttd ttitmiul
ntmt, trmdf nmtM, and CAS rnmt»(.)
Information (E.O. t2065f
A. ,-,
LJ Baric Farfliulaiian
O AltwrnMe Formuloiion
Fom Approved. OMB No 2070-0060. Appr««! Expires 2«a»4i
8,
Sat Inttruclioni on Back
2, N«mt »rxl Addrsu
4,B«ltor«laf,»,./fto6¥n*.l
7. Pound»/Qil gr Bu* Dtntiiy
aiwteta.>MM.
f. EPA Product Ufif/T«»m No
*•*"
12, CPARtg Na
1 6. Typed Nam* of ApprcvifiB Official
18. signature of Approving Ofticia)
in FqrmuUliijn
*. Amount (.no»wiijff
1 7. Total
«.TOMi
100%
8 Coonlry Wh»r« FotmulMMi
9. ^tath Pomi/f l«m» InMntion
1*. C«niM Lvnli
1 UW*rliiTM t Uwtf Im*
1*. PutfMIM i»
autaM «*»***» 0*1
21, Date
CPA Form 6570-4 (Raw. 12-flO) PnvloiM edition* *r» ob«o««t«. If you can photocopy M*. olaase submit an aiJdttonal copy, WWW- EPA Fife Copy (original) Yellow- Appltcani copy
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Instructions for Completing the Confidential Statement of Formula
The Confidential Statement of Formula (CSF) Form 857CM must be used. Two legible, signed
copies of the form are required. Following are basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
c. The CSF must be signed, dated and the telephone number of the responsible party
must be provided.
d. All applicable information which is on the product specific data submission must
also be reported on the CSF,
e. All weights reported under item 7 must be in pounds per gallon for liquids and
pounds per cubic feet for solids.
f. Flashpoint must be in degrees Fahrenheit and flame extension in inches.
g. For all active ingredients, the EPA Registration Numbers for the currently
registered source products must be reported under column 12.
h« The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all
common names for the trade names must be reported.
i. For the active ingredients, the percent purity of the source products must be
reported under column 10 and must be exactly the same as on the source
product's label.
j. All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or
grams. In no case will volumes be accepted. Do not mix English and metric
system units (i.e., pounds and kilograms).
k. All the items under column 13»b. must total 100 percent.
1. All items under columns 14.a. and 14.b. for the active ingredients must represent
pure active form.
m. The upper and lower certified limits for ail active and inert ingredients must
follow the 40 CFR 158.175 instructions. An explanation must be provided if the
proposed limits are different than standard certified limits,
n. When new CSFs are submitted and approved, all previously submitted CSFs
become obsolete for that specific formulation.
201
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?/EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Farm Approved
OMB No. 2070-D108
2070-0057
Approve! Explra* 3-31-96
Public repotting burden for this selection of information is estimated to average 1§ minutes per response, Including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data nestled, and
completing and reviewing the collection of Information. Send comments regarding the burden estimate or any other
aspect of this collection of Informal ton, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Compiiiy Xaifce
Product X'wnc
Company Number
F.PA Kfg.^K,
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fung'eWe and RodenMcIdi Ad (FlFflA), if necessary. However, my company would prefer to
enter Into an agreement wiih one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. Thai offer was Irrevocable and included an
offer to be bound by arbitration decision under section 3{c)(2}(B){iu) of FIFRA if final agreement on ill
terras could not be reached otherwise. This offer was made to the following flrm{s) on the following
date(s):
Nun* of FIrm(a)
Otto of Offer
Certification:
I certify that 1 am duly authorized to represent the company named above, and that the statements that I have made on
this form and a! attachments tnemn are true, accurate, and complete, t acknowledge thai any knowingly raise or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Stgn*lur*
Mini* md
of Camp*ny'« Authorized R»pr*M(}Utiv*
D»l*
TTUi (PlMit Type or Print)
EPA Form 857002
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united state* environmental Protection Ag*ney
Wuhlngton, DC 20480
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
O"> "*
a*£S£
PubBc report mo bmdcn for thte eeNctiofi of IMomtatiMi it estimated to average tS irtnutf* per rwpontt, inckidinQ
tiiiM for raviowfng Mstiuetlons, starcMnQ editing dau sowcii, o&lwrfng ind mahtairtnQ the daa rwtded. anj
compiOJng and itvitwing ih» cofltOlon of irtformaica Send coitimnu rtflarding On burden tttimati or any otter
aspect of iltis crttectton or infermaiton, induing luggesUoiis tor radudng this burden, to Chid. Information Policy
Branch. PM-223, U.S. Envlronmintai Profsdon A^*rcy. 401 M St., S.W., Wasrtngion. DC 204fO; and to Uie Oflca
of Mwa0t m»rt and Budget, Piperwortc Refludton Project (2070-0106). WtsMngion. DC 20503.
PfcsM nu In blanks below.
e^r M
rroctoct Meaw
e_M M«*T
DA, 1*9 . *>.
Roosnacifle «i {FiFfiAl rat it an txeksivt use study, 1
Federal msacfieiee, nmpteidt and
'.or I have obtained the
2.
la ubjrvner, or i
iwv«noiJile4inwitingthao9ifipafty(ie$)lh^ (a) Pty
eompentatton tor thoie data ki accordance vin tections 3(C)[1)(D) and 3{cX2)(D) of FIFHA; and |b) Commence
negotiation to deiennh* wMefi data ant sufcjtd to the conpensji^ jtqutrtmert or RFRA and tr» amouni oi
eompensaUon duf, I any. The companieU hav» notified are: (cnaenona)
[] The conpanlt* who navtsubmAtdlha ttytfe* isted on the back of thiifcxtn or attached
sheets, or fevieaJtd on tht nactud T^»quir«menu Status and flegittranis'Response Form,'
3. 7rWihavfprvfl9usJyoo{i9M«^ieetlon3{§HiX^
ftpittrition Of rengistration under F1FRA.
HUM eai Tia»
Tfte er Mnl)
GENEFWt OFFER TO PAY: I hereby offer and agree » pay eompensattan to other persons, wtft
reoatraaon or reregistratton of my predoctt.»the t3twni required ay RFnA«eeJ(ons3(cKi)(D}
Signature
NaiM Mrt tllta (PIMM T|fe tf PMM|
1
•PA Pem M70-«
205
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APPENDIX F. FACT SHEET
207
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United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508WJ
EPA-738-F-94-007
May 1934
&EBA R.E.D. FACTS
Pesticide
Reregistration
Pronamide
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered years ago be reregistered to ensure
that they meet today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks, EPA then reregisters pesticides that can be used without
posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this
and explains why in a leregistration Eligibility Decision (RED) document.
This feet sheet summarizes the mformation in the RED for pronamide, also
known by the trade name Kerb.
Use Profile
Pronamide is a selective, systemic, pre- and post-emergence
herbicide that acts by inhibiting plant cell division. It is used to control
grasses and broadleaf weeds in food and feed crops including lettuce (the
largest use site), endive, alMfe, rhubarb, pome and stone fruits,
artichokes, berries, grapes and legumes, as well as on woody ornamentals,
Christmas trees, nursery stock, lawns, turf and fellow land. Formulations
include a wettable powder and a granular. Pronamide may be applied
using ground spray equipment, by soil incorporation or by aircraft.
Regulatory
History
Pronamide was first registered as a pesticide in the U.S. in 1972.
Between 1977-1979, EPA conducted a Special Review based on a study
indicating that pronamide caused cancer in mice. In concluding this
review, the Agency required: 1) restricted use classification for the 50%
active ingredient end-use products; 2) use of protective clothing during
mixing and appEcation of the wettable powder formulations; 3) water-
soluble packaging for the wettable powders; and 4) lowering of the
tolerance on lettuce from 2 ppm to 1 ppm, to reduce dietary exposure.
209
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EPA issued a Registration Standard for pronamide in April My 1986
(NTIS JHPB87-103735), requiring additional generic data. A Data Call-In
issued in 1990 required additional product chemistry, residue chemistry,
plant protection and environmental fete data. The RED reflects EPA's
assessment of all data received, to date.
Currently, 18 products are registered which contain the active
ingredient (ai) pronamide. The 13 wettable powder products (each
containing 50% ai) are registered for food, feed and outdoor residential
uses. The 3 granular products (each containing up to 1 % ai) are registered
only for use on lawns and turf. A formulation intermediate and a technical
grade manufacturing product also are registered.
Human Health Toxicity
Assessment In acute toxicity studies, pronamide technical is practically non-toxic
by the oral route, and has been placed in Ibxicity Category IV (the lowest
of four categories) for this effect. It is slightly toxic by the dermal and
inhalation routes, and has been placed in Toxicity Category in for these
effects. In subehronic toxicity studies using rats, the liver, thyroid and
pituitary appear to be the target organs.
In chronic feeding studies, pronamide causes an increased incidence
of liver cancer in male mice, and benign testicular and thyroid tumors in
rats. EPA has classified pronamide as a Group B2 (probable human)
carcinogen.
Pronamide appears to be a toxicant to the liver and several endocrine
organs including the thyroid, testes and pituitary. Pronamide is related to
the organochlorine class of chemicals, many of which disrupt the endocrine
system. Pronamide is not mutagenic.
Dietary Exposure
Some of the residue chemistry studies on pronamide were generated
by Craven Laboratories, which has been convicted of producing fraudulent
data. EPA has extrapolated information to draw satisfactory conclusions
about pronamide residues in food. However, several confirmatory residue
studies must be provided-for example, on alfalfa seed, dried winter peas
and early season use on artichokes.
Tolerances or maximum residue limits are established for residues of
pronamide in or on a number of food and feed crops, meat and milk (see
40 CFR 180.31T(a)). Crop group tolerances must be proposed for residues
in/on forage and hay of the non-grass animal feeds group, and for the stone
fruits group. The tolerance for endive must be reduced from 2.0 ppm to
1.0 ppm. Certain animal organ tolerances must be raised from 0.2 ppm to
0.4 ppm, due to improved efficiency of enforcement residue detection
methods.
210
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Based on the anticipated residue contributions of red meat and milk
(which contribute the most to anticipated residues in the diet) and
reassessed tolerances, EPA estimates that the overall U.S. population is
exposed to 0.04% of the Reference Dose (RfD) or amount believed not to
cause adverse effects if consumed daily over a 70-year lifetime. Dietary
exposure to pronamide is associated with an estimated upper bound cancer
risk of 5 x 10-7, or five extra incidences of cancer per 10,000,000. This
assessment still overestimates the actual degree of risk, which is likely to
be less.
Occupational and Residential Exposure
Pesticide handlers (mixers, loaders and applicators) may be exposed
to pronamide sprays and dusts via skin and inhalation during ground boom,
aerial and hand-spray applications. The major route of exposure is the
dermal route, and exposure is estimated for use of the wettable powder
formulation in water-soluble pouches.
TAforkers and homeowners also may be dermaliy exposed post-
application to pronamide residues on treated foliage and soil. To reduce
exposure and risk, EPA is imposing a restricted entry interval following
commercial food, feed and turf uses. However, the Agency is unable to
estimate risks associated with use of pronamide on residential lawns, and
cannot impose a reentry interval for residential situations. Therefore, EPA
is unable to make a reregistration eligibility decision about pronamide use
on residential lawns, pending the results of several exposure studies.
Similarly, post-application reentry data are required for pronamide
use on lettuce because of the potential for significant hand contact.
Human Risk Assessment
Pronamide is of relatively low acute toxieiiy, but has been
demonstrated to cause liver cancer in male mice and is classified as a B2
"probable" human carcinogen. People may be exposed to residues of
pronamide in a number of food crops, meat and milk. However, chronic
exposure to pronamide in the diet is at a very low level (only a small
fraction of the RfD), and is not a cause far concern at this time.
There is a concern for cancer associated with lifetime exposure of
mixers/loaders/applicators and homeowners to pronamide. The combined
risk for mixer/loader/applieators wearing personal protective equipment
(PPE) is estimated to be 3 x 10-5. However, this estimate is conservative
and actual risk is likely to be lower.
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Environmental
Assessment
Environmental Fate
Pronamide is stable to hydrolysis, and to photolysis in water and on
soil. It is very persistent in soil under aerobic conditions, and even more
persistent under anaerobic conditions (with an estimated half-life greater
than 13 months). Pronamide has a relatively low vapor pressure and is
relatively mobile in soil. Leaching appears to be its major route of
dissipation.
A chemical with these properties is expected to be persistent and
mobile in the field. Therefore, a study generated by Craven Laboratories
which suggests that pronamide is neither persistent nor mobile must be
replaced by a new field dissipation study.
Ecological Effects
Pronamide is practically nontoxic to birds and mammals on an acute
basis. It is slightly toxic to freshwater fish and moderately toxic to
freshwater invertebrates. Although taxicity to aquatic organisms is not
anticipated, confirmatory estuarine studies are required. Pronamide is
toxic to green algae, Testing on four other aquatic plants is required,
therefore, to assess effects on the aquatic habitat and endangered aquatic
plant species.
Ecological Effects Risk Assessment
Use of pronamide as directed by product labeling will have minimal
adverse acute effects on insects, birds and mammals. However, chronic
risk to aquatic invertebrates is possible, due to pronanuWs persistence in
water. EPA is requiring an aquatic invertebrate life cycle study to assess
this potential risk. Testing on four additional aquatic plant species is
required, as mentioned above. Risks to non-target terrestrial plants also
will be further explored.
Regarding endangered species, pronamide may not adversely effect
endangered birds or aquatic invertebrates, but risk to aquatic plants is
uncertain. Terrestrial plants may be adversely affected by pronamide
applied at maximum label rates. EPA may require additional labeling and
use modifications when implementing the Endangered Species Protection
Program.
Additional Data EPA is requiring the following additional generic data for pronamide
Required to confirm its regulatory assessments and conclusions:
Product Identity
Aquatic Invertebrate life Cycle
Estuarine and Marine Organisms (Mollusc and Shrimp)
Terrestrial Field Dissipation
Field Rotational Crop
212
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Droplet Size Spectrum and Drift Field Evaluation
Foliar Dislodgeable Dissipation
Dermal Passive Dosimetry
Estimation of Dermal/Inhalation Exposure at
Outdoor Sites
Residue Analytical Method
Storage Stability
Magnitude of Residue
Processed Food
The following studies which are not part of the target data base also are
required:
Seed Germination/Seedling Emergence
Aquatic Plant Growth
The following studies are required to support use of products on residential
lawn and turf:
Foliar Dislodgeable Dissipation
Dermal Passive Dosimetry
To support the late season use of pronamide on artichokes, registrants must
delete this use from their product labels or submit the following study:
Magnitude of Residue
The Agency also is requiring product-specific data including product
chemistry and acute dermal tenacity studies, and revised labeling for
reregistration.
Product Labeling All pronamide end-use products must comply with EPA's current
Changes Required pesticide product labeling requirements, and the following:
Worker Protection Standard (WPS) - All pronamide products within the
scope of the V^rker Protection Standard (WPS) for Agricultural Pesticides
(see PR Notice 93-7) must, within the timeftames listed in PR Notices 93-7
and 93-11, revise their labeling to be consistent with the WPS, as directed
in those notices and the requirements of the RED.
Entry Restrictions
Uses Within the Scope of the WPS - A 24-hour restricted entry
interval (REI) is required on all end-use products, except those intended
primarily for home use. The PPE for early entry must be that required for
applicators of pronamide except no apron or respirator is required.
« Labels of Sole AI Products - Revise to adopt these entry
restrictions. Remove any conflicting entry restrictions on current
labeling.
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• Labels of Multiple-AI Products - Must bear the more protective of
either the entry restrictions set forth here, or those on current
labeling.
Uses Not Within the Scope of the WPS - Do not add any entry
restrictions, but retain any on current labeling.
Personal Protective Equipment (PPE) Requirements
Uses on Products NOT Primarily Intended for Home Use The PPE
requirement for pesticide handlers on all end-use products is;
"Applicators and other handlers must wear:
—Coveralls over short sleeved-shirt and short pants
-Chemical-resistant or waterproof gloves
—Chemical-resistant footwear plus socks
-Chemical-resistant headgear for overhead exposure
-Chemical-resistant apron when cleaning equipment, mixing or
loading."
Pronamide products must bear these PPE requirements or those on current
labeling, which ever is more protective.
Lawn and Turf Uses - If a registrant chooses to support the residential
lawn uses only, he/she must add the following exclusionary statement on
the front panel of the product label near the product name, or near the
beginning of the Directions for Use section:
"Not for use on turf being grown for sale or other commercial use as
sod, or for commercial seed production, or for research purposes."
If the registrant does not support the residential lawn uses, he/she must
amend the product label to delete lawn and turf uses.
fish and Wildlife Hazard - Labels must bear the following statement in
the Precautionary Statements section under the subheading Environmental
Hazards:
"Do not apply directly to water, or to areas where surface water is
present or to intertidal areas below the mean high water mark. Do
not contaminate water when disposing of equipment washwaters."
Restricted Use Pesticide Classification - The wettable powder products
must maintain the Restricted Use Pesticide classification imposed.at the
conclusion of the Special Review.
Regulatory The use of all currently registered pesticide products containing
Conclusion pronamide in accordance with approved labeling, except residential lawn
and turf uses and late season use on artichokes, will not pose unreasonable
risks or adverse effects to humans; however, they may pose adverse effects
to terrestrial plants and perhaps to aquatic plants. Products containing
pronamide for all uses, except broadcast application on residential lawns
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and turf, and the late season use on artichokes, are eligible for
reregistration.
EPA has insufficient data at this time to make a reregistration
eligibility decision regarding the use of pronamide on residential lawns and
turf, or the late season use on artichokes. An eligibility decision cannot be
made for broadcast application to residential lawns and turf until post-
application/reentry exposure data are submitted and evaluated. A decision
cannot be made for late season use on artichokes until residue data are
submitted and evaluated.
Products that are eligible will be reregistered once the required
confirmatory generic data, product specific data and revised labeling are
received and accepted by EPA.
For More EPA is requesting public comments on the Reregistration Eligibility
information Decision (RED) document for pronamide during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register.
To obtain a copy of the RED document or to submit written comments,
please contact the Pesticide Docket, Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Following the comment period, the pronamide RED document will be
available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703^87-4650.
For more information about EPA's pesticide reregistration program,
the pronamide RJED, or reregistration of individual products containing
pronamide, please contact the Special Review and Reregistration Division
(7508W), OPP, US EPA, mshington, DC 20460, telephone
703-308-8000.
For information about the health effects of pesticides, or for
assistance in recognizing and managing pesticide poisoning symptoms,
please contact the National Pesticides THecomrmirdcations Network
(NPTN). Call toll-free 1-800-858-7378, from 8:00 am to 6:00 pm Central
Time, Monday through Friday.
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