United States Prevention, Pesticides EPA 738-R-96-006
Environmental Protection And Toxic Substances March 1996
Agency (7508W)
4»EPA Re registration
Eligibility Decision (RED)
Desmedipham
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, B.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case desmedipham
which includes the active ingredient ethyl m-hydroxycarbanilate carbanilate. The enclosed
Reregistration Eligibility Decision (RED) contains the Agency's evaluation of the data base of
these chemicals, its conclusions of the potential human health and environmental risks of the
current product uses, and its decisions and conditions under which these uses and products will
be eligible for reregistration. The RED includes the data and labeling requirements for
products for reregistration. It may also include requirements for additional data (generic) on
the active ingredients to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED." This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses is due 90 days from the
receipt of this letter. The second set of required responses is due 8 months from the date
of this letter. Complete and timely responses will avoid the Agency taking the enforcement
action of suspension against your products.
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
Jeffrey Billingslea at (703) 308-8004.
Sincerely yours,
Lois Rossi, Division Director
Special Review
and Reregistration Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1. DATA CALL-IN (PCI) OR "90-DAY RESPONSE" If generic data are required for
reregistration, a DCI letter will be enclosed describing such data. If product specific data
are required, a DCI letter will be enclosed listing such requirements. If both generic and
product specific data are required, a combined Generic and Product Specific DCI letter will
be enclosed describing such data. However, if you are an end-use product registrant only and
have been granted a generic data exemption (GDE) by EPA, you are being sent only the
product specific response forms (2 forms) with the RED. Registrants responsible for generic
data are being sent response forms for both generic and product specific data requirements (4
forms). You must submit the appropriate response forms (following the instructions
provided) within 90 days of the receipt of this RED/DCI letter; otherwise, your product
may be suspended.
2. TIME EXTENSIONS AND DATA WAIVER REQUESTS No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data
should be submitted in the 90-day response. Requests for data waivers must be submitted as
part of the 90-day response. All data waiver and time extension requests must be accompanied
by a full justification. All waivers and time extensions must be granted by EPA in order to go
into effect.
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE" You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original
application form. Mark it "Application for Reregistration." Send your Application for
Reregistration (along with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregistration) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration. For further
labeling guidance, refer to the labeling section of the EPA publication "General Information
on Applying for Registration in the U.S., Second Edition, August 1992" (available from the
National Technical Information Service, publication #PB92-221811; telephone number 703-
487-4650).
c. Generic or Product Specific Data. Submit all data in a format which complies
with PR Notice 86-5, and/or submit citations of data already submitted and give the EPA
identifier (MRID) numbers. Before citing these studies, you must make sure that they meet
the Agency's acceptance criteria (attached to the DCI).
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d. Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal
concentration. You have two options for submitting a CSF: (1) accept the standard certified
limits (see 40 CFR §158.175) or (2) provide certified limits that are supported by the analysis
of five batches. If you choose the second option, you must submit or cite the data for the five
batches along with a certification statement as described in 40 CFR §158.175(e). A copy of
the CSF is enclosed; follow the instructions on its back.
e. Certification With Respect to Data Compensation Requirements. Complete and
sign EPA form 8570-31 for each product.
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
By U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data
waiver and time extension requests within 60 days. EPA will also try to respond to all 8-
month submissions with a final reregistration determination within 14 months after the RED
has been issued.
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REREGISTRATION ELIGIBILITY DECISION
Desmedipham
LISTB
CASE 2150
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TABLE OF CONTENTS
DESMEDIPHAM REREGISTRATION ELIGIBILITY DECISION TEAM
EXECUTIVE SUMMARY
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 2
C. Data Requirements 3
D. Regulatory History 4
III. SCIENCE ASSESSMENT 4
A. Physical Chemistry Assessment 4
B. Human Health Assessment 5
1. Toxicology Assessment 5
a. Acute Toxicity 5
b. Subchronic Toxicity 5
c. Chronic and Carcinogenicity 8
d. Developmental Toxicity 11
e. Reproductive Toxicity 12
f. Mutagenicity 12
g. Metabolism 13
h. Reference Dose 15
i. Cancer Classification 15
j. Dermal Absorption 15
2. Exposure Assessment 16
a. Dietary Exposure 16
b. Magnitude of the Residue in Drinking Water 19
c. Occupational and Residential Exposure 20
3. Risk Assessment 21
a. Dietary 21
b. Occupational and Residential 22
C. Environmental Assessment 28
1. Ecological Toxicity Data 28
a. Toxicity to Terrestrial Animals 28
b. Toxicity to Aquatic Animals 30
c. Toxicity to Plants 31
2. Environmental Fate 34
a. Environmental Fate Assessment 34
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b. Environmental Fate and Transport 35
c. Water Resources 41
3. Exposure and Risk Characterization 42
4. Water Resources Risk Implications for Human Health 56
5. Environmental Risk Characterization 57
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 61
A. Determination of Eligibility 61
B. Determination of Eligibility Decision 62
1. Eligibility Decision 62
2. Eligible and Ineligible Uses 62
C. Regulatory Position 62
1. Worker Protection 62
2. Scope of the WPS 62
3. Post-Application/Entry Restrictions 65
4. WPS Notification Statement 66
5. Other Labeling Requirements 66
6. Dietary Exposure Assessment 67
7. Tolerance Reassessment 67
8. Restricted Use Classification 67
9. Reference Dose 68
10. Endangered Species Statement 68
11. Spray Drift Advisory 68
V. ACTIONS REQUIRED OF REGISTRANTS 68
A. Manufacturing-Use Products 68
1. Additional Generic Data Requirements 68
2. Labeling Requirements for Manufacturing-Use Products 69
B. End-Use Products 70
1. Additional Product-Specific Data Requirements 70
2. Labeling Requirements for End-Use Products 73
C. Existing Stocks 76
VI. APPENDICES 77
APPENDIX A. Table of Use Patterns Subject to Reregistration 78
APPENDIX B. Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision 83
APPENDIX C. Citations Considered to be Part of the Data Base Supporting the
Reregistration of desmedipham 91
APPENDIX D. Product Specific Data Call-In 105
Attachment 1. Chemical Status Sheets 117
Attachment 2. Product Specific Data Call-In Response Forms (Form A
inserts) Plus Instructions 118
Attachment 3. Product Specific Requirement Status and Registrant's
Response Forms (Form B inserts) and Instructions 120
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Attachment 4. EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration 127
Attachment 5. List of All Registrants Sent This Data Call-in (insert)
Notice 129
Attachment 6. Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions 131
APPENDIX E. List of Available Related Documents 138
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DESMEDIPHAM REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Alan Halvorson
James Saulman
Thomas Harris
Economic Analysis Branch
Biological Analysis Branch
LUIS
Environmental Fate and Effects Risk Assessment
Stephanie Syslo
Gail Maske
Nick Mastrota
William Effland
David Wells
Health Effects Risk Assessment
Arliene Aikens
Stephen Dapson
David Miller
Carol Lang
Brian Steinwand
Registration Support Risk Assessment
Karen Hicks
Robert Taylor
Risk Management
Richard Gebken
Office of Enforcement and Compliance:
Rick Colbert
Environmental Risk Characterization Branch
Environmental Fate and Groundwater Branch
Environmental Risk Characterization Branch
Environmental Risk Characterization Branch
Environmental Risk Characterization Branch
Risk Characterization and Analysis Branch
Toxicology Branch II
Reregi strati on Support Chemistry Branch
Occupational and Residential Exposure Branch
Science Analysis Branch
Registration Division Fungicide-herbicide Branch
Registration Division Fungicide-herbicide Branch
Accelerated Reregi strati on Branch
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific (i.e. drinkin g
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to occur.
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment, such
as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FOB Functional Observation Battery
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected
to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or
volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50% of
the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as
a weight of substance per unit weight of animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOG Level of Concern
L OD L imit of Detection
LOEC Lowest Observed Effect Concentration
LOEL Lowest Observed Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
pg/g Micrograms Per Gram
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
N/A Not Applicable
NOEC No effect concentration
NPDES National Pollutant Discharge Elimination System
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GLOSSARY OF TERMS AND ABBREVIATIONS
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRN Pesticide Registration Notice
Q*j The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RS Registration Standard
SLN Special Local Need (Registrations Under Section 24 © of FIFRA)
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
FAO/WHO Food and Agriculture Organization/World Health Organization
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
This Reregistration Eligibility Decision (RED) addresses the pesticide ethyl m-hydroxy-
carbanilate carbanilate (desmedipham) and the potential risks posed by the uses of all the currently
registered products. Desmedipham, produced by AgrEvo USA Co., is a selective postemergence
herbicide used to control various weeds in sugarbeets. It is also currently registered for special
local need in one state for use on table beets and swiss chard for seed production.
The Agency has completed its review of the target database for desmedipham and has
concluded that all currently registered uses as labeled and used as specified in this document will
not pose unreasonable risks or adverse effects to humans or the environment. All currently
registered pesticide uses of desmedipham are eligible for reregistration. However, the Agency
is requiring additional data in the physical chemistry, residue chemistry, toxicology,
environmental fate, and ecological effects disciplines to confirm this eligibility decision.
Additionally, the Agency is requiring certain risk mitigation measures, including the use of
personal protective equipment and aerial application drift management.
The Agency has determined that a preliminary classification of desmedipham as a group
E chemical (non-carcinogenicity in humans) is appropriate. A Reference Dose (RfD) was
established for chronic dietary exposure based on a parental toxicity endopont of concern in a rat
reproduction study. The endpoint of concern for 1-day dietary exposure was based on
developmental toxicity in rabbits. The Agency concludes that chronic and acute risks from dietary
exposure to desmedipham are minimal.
Desmedipham has low to moderate acute mammalian toxicity. The short-term (1-7 days)
occupational exposure endpoint of concern is based on developmental toxicity in rabbits. The
intermediate-term (1 week to several months) occupational exposure endpoint of concern is based
on parental toxicity in a rat reproduction study. Based on a dermal absorption study, dermal
absorption is considered to be relatively low. The Agency concludes that occupational risks from
exposure to desmedipham, mitigated by the use of personal protective equipment, are minimal.
The Agency has concluded that the risk to non target terrestrial and semiaquatic plants could
not be fully assessed because of lack of testing using the typical end-use product (TEP). To be
conservative, desmedipham should tentatively be assumed to pose risk to these plants through
exposure from drift. The Agency is imposing additional Tier II studies for plant effects using a TEP
and issuing guidance for aerial applications of desmedipham to reduce off-target spray drift and the
potential environmental risks. The Agency has concluded that the use of desmedipham poses minimal
risk of contamination of ground and surface water and to aquatic plants and animals. Also, acute
risks to insects, birds and mammals are minimal. The chronic risk to birds is low to moderate and any
effects are expected to be limited to local areas. The Agency also concludes that chronic risk to
mammals is minimal.
Before reregistering the products containing desmedipham, the Agency is requiring that
product specific data, revised Confidential Statements of Formula and revised labeling be
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submitted within eight months of the issuance of this document. These data include product
chemistry for each registration and acute toxicity testing. After reviewing these data and any
revised labels and finding them acceptable in accordance with Section 3(c)(5) of FIFRA, the
Agency will reregister a product. Those products which contain other active ingredients will be
eligible for reregistration only when the other active ingredients are determined to be eligible for
reregistration.
VI
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984. The amended Act provides a schedule for the reregistration process to be completed in
nine years. There are five phases to the reregistration process. The first four phases of the process
focus on identification of data requirements to support the reregistration of an active ingredient
and the generation and submission of data to fulfill the requirements. The fifth phase is a review
by the U.S. Environmental Protection Agency (referred to as "the Agency") of all data submitted
to support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for reregistration" before calling
in data on products and either reregistering products or taking "other appropriate regulatory
action." Thus, reregistration involves a thorough review of the scientific data base underlying a
pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards
arising from the currently registered uses of the pesticide; to determine the need for additional
data on health and environmental effects; and to determine whether the pesticide meets the "no
unreasonable adverse effects" criterion of FIFRA.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of desmedipham. The document consists of six sections. Section I is the
introduction. Section II describes desmedipham, its uses, data requirements and regulatory
history. Section III discusses the human health and environmental assessment based on the data
available to the Agency. Section IV presents the reregistration decision for desmedipham . Section
V discusses the reregistration requirements for desmedipham. Finally, Section VI is the
Appendices which support this Reregistration Eligibility Decision. Additional details concerning
the Agency's review of applicable data are available on request.
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II. CASE OVERVIEW
A. Chemical Overview
The following active ingredient is covered by this Reregistration Eligibility
Decision:
B.
Common Name:
Chemical Name:
Chemical Family:
CAS Registry Number:
OPP Chemical Code:
Empirical Formula:
Desmedipham
Ethyl m-hydroxycarbanilate carbanilate
Carbanilate
CAS Reg. No. 13684-56-5
104801
C16H16N204
Trade and Other Names:
3-((Ethoxycarbonyl)amino)phenyl N-phenylcarbamate,
Carbamic acid, N-phenyl-, 3-((ethoxycarbonyl)amino)phenyl ester,
Betanal-475,
Betanex,
EP 475,
SN-475,
SN-38107,
Betamix 70 WP,
Betanex 70 WP
Basic Manufacturer:
AgrEvo USA Co.
Little Falls Centre One
2711 Centerville Rd.
Wilmington DE, 19808
Use Profile
Desmedipham is notable in that the area and distribution of its use is well defined. There
is a Special Local Need registration in Washington for Swiss chard and table beets grown for seed
which comprises an area of only 100 acres. The Federal registration is for sugar beet production.
This is concentrated in relatively small areas of the country, mostly in the northern Great Plains,
Great Lakes region, Pacific Northwest, and California. About 150,000 to 200,000 acres are
treated annually with desmedipham.
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Type of Pesticide for Single Active Ingredient: HERBICIDE
Use Sites: TERRESTRIAL NON-FOOD CROP
Leafy and Stem Vegetables
* CHARD, SWISS (grown for seed)
Root Crop Vegetables
* TABLE BEETS (grown for seed)
TERRESTRIAL FOOD + FEED CROP
Sugar Crops
* SUGAR BEET
Target Pests for Desmedipham:
Weeds: Annual Sowthistle, Black Nightshade, Coast Fiddleneck, Common
Chickweed, Common Lambsquarters, Common Ragweed, Groundcherry,
London Rocket, Nettleleaf Goosefoot, Prostrate Pigweed, Purslane,
Redroot Pigweed, Shepherdspurse, Wild Buckwheat, Wild Mustard.
Types/Formulations Registered:
TECHNICAL GRADE ACTIVE INGREDIENT: 97%
END USE PRODUCT FORMULATIONS
EMULSIFIABLE CONCENTRATE: 6%, 7%, 8%, 16%
WETTABLE POWDER: 35%, 70%
Methods and Rates of Application:
Types of Treatment: Band treatment; Broadcast
Equipment: Aircraft; Ground; Sprayer
Timing: Evening (for foliar applications)
C. Data Requirements
Data required to satisfy the reregistration database for desmedipham include studies on
chemistry, ecological effects, environmental fate, toxicology, worker exposure, and residue chemistry.
Appendix B includes all data requirements identified by the Agency for currently registered uses
needed to support reregistration.
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A Data Call-In under reregistration Phase IV was issued in April 1991, for desmedipham
requiring additional chemistry, residue chemistry, toxicology, and ecological effects data to assess
the potential for toxicity as a result of exposure to desmedipham. An additional Data Call-In was
issued in September 1992, requiring data for the following guidelines based on the evaluation of
submitted environmental fate data, persistence, use pattern and formulations of desmedipham:
71-4(a) Avian Reproduction-quail,
71-4(b) Avian Reproduction-duck.
This Reregistration Eligibility Decision reflects an assessment of all data and other available
information before the Agency.
A Data Call-In was issued for desmedipham and many other pesticides in October 1995, as
part of a post-application/reentry exposure requirement to satisfy the following guidelines:
132-l(a) Foliar residue dissipation,
133-3 Dermal passive dosimetry exposure,
133-4 Inhalation passive dosimetry exposure.
These studies are considered outside of the target data requirements for reregistration. Once
these data are submitted (due October 1997) the Agency will determine whether additional risk
mitigation measures are appropriate for post-application exposures.
D. Regulatory History
Desmedipham was initially registered in the United States in November 1974, for use as a
post-emergence herbicide. Currently there are 10 registered products containing desmedipham.
There is also one Special Local Needs registration granted to the State of Washington (SLN
WA95001900) for the table beet and Swiss chard seed production uses.
III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
Desmedipham (ethyl-m-hydroxycarbanilate carbanilate) is a colorless to off-white crystalline
solid with a melting point of 120° C. Technical desmedipham is nearly insoluble in water at 25° C,
but is soluble in dichloromethane, ethyl acetate, methanol, and acetone. The molecular structure of
desmedipham is:
H H
/\ ^]sr o /-, N n
O ^ /^ O
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Empirical Formula: C16H16N2O4
Molecular Weight: 300.31
CAS Registry No.: 13684-56-5
Chemical Code: 104801
B. Human Health Assessment
1. Toxicology Assessment
The toxicological data base for desmedipham is adequate to support the reregistration
eligibility decision document.
a. Acute Toxicity
Table 1. Desmedipham Acute Toxicity
TEST (MRID)
Oral LD50-Rat (00155581)
Dermal LD50-Rat (00155582)
Inhalation LC50-Rat (41957102)
Eye irritation-Rabbit* (00155584)
Dermal irritation-Rabbit* (00155583)
Dermal sensitization-Guinea Pig* (40312901)
RESULTS
LD50 > 5000 mg/kg
LD50 > 4000 mg/kg
LC50 > 7.4 mg/L
Opacity and conjunctival
irritation cleared by 72 hours
No irritation
A dermal sensitizer
CATEGORY
IV
III
IV
II
IV
N/A
ACTIVE INGREDIENT
(%)
97.0
97.0
98.0
97.0
97.0
98.0
! Not required for TGAI.
b. Subchronic Toxicity
1. In a 13-week oral toxicity study (MRID 40387102), technical grade desmedipham was
fed to groups of 10 rats per sex at dose levels of 0, 300, 1200, or 4800 ppm in the diet for 13
weeks (equal to 0, 24, 97, and 415 mg/kg/day for males and 0, 27, 109, and 378 mg/kg/day for
females, respectively).
Systemic toxicity was noted as lower body weight and body weight gains in males and
females receiving the high dose as compared to the control during the 13-week test period. Body
weights were also lower than control in the mid dose males during weeks 10 through 13. Food
and water consumption were decreased in the high dose females. No effect was noted on
mortality, clinical signs or on ophthalmologic examinations.
Absolute organ weights of the brain, heart, liver, kidneys, ovaries and adrenal glands were
statistically significantly reduced in the high dose females. Absolute kidney weights were slightly
decreased in the low and high dose males. Relative organ weights (to body weight) of the brain,
heart, liver and kidney were slightly to moderately increased in both sexes in the high dose and
mid dose females. Relative adrenal weights were slightly to moderately increased in both sexes
in the high dose. Relative testes' weights were moderately increased in high dose males. The
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toxicological significance of these organ weight changes is unknown, since there was no
correlation between organ weight changes and histopathological observations.
Treatment related histopathological observations were noted in the spleen (hematopoiesis),
thyroid glands (follicular hyperplasia), liver (hematopoiesis and pigmentation) and kidneys
(pigmentation). The spleen was enlarged and dark red to black in color in all but one high dose
male. Macrocytic normochromic anemia was observed in all treated animals. Dose related
effects included methemoglobin formation, decreased erythrocyte counts, decreased hematocrit
and hemoglobin concentration, and reticulocytosis. Hematological effects were seen in platelet
and total leukocyte counts, mean corpuscular volume, mean corpuscular hemoglobin
concentration, and Heinz body formation.
Treatment related effects on clinical chemistry parameters consisted of increased activities
of aspartate and alanine aminotransferases, alkaline phosphatase and gamma-glutamyl transferase.
Brain and plasma cholinesterase activities were reduced in mid and high dose females. Some
minor effects were noted in levels of cholesterol, phosphorus, bilirubin and potassium. Dose
related alterations in the plasma protein electrophoretic pattern in mid and high dose animals also
occurred. The systemic toxicity LOEL is 24 mg/kg/day in males and 27 mg/kg/day in females
based on effects on hematology and clinical chemistry parameters. The systemic toxicity NOEL
is less than 24 mg/kg/day in males and less than 27 mg/kg/day in females.
2. In a 13-week oral (feeding) toxicity study (MRID 40387103), technical grade
desmedipham was fed to groups of 25 male and female rats at dose levels of 0, 6, 30, 60 and 300
ppm in the diet for 13 weeks (equal to 0, 0.5, 2.6, 5.2 and 26.0 mg/kg/day for males and 0, 0.5,
2.7, 5.6 and 27.0 mg/kg/day for females, respectively).
Ten rats per sex per dose group were observed for an additional period (recovery) of 4
weeks to determine the reversibility of any parameter affected by treatment with the test
compound. There was no effect of treatment on organ weights, body weight, food or water
consumption, mortality, ophthalmologic examinations, gross pathology or histopathology.
Treatment related effects included increased methemoglobin formation throughout the
treatment period in the high dose males and females. At weeks 16 or 17 of the recovery period,
methemoglobin levels in the high dose females were similar to control but remained elevated in
high dose males. Reticulocyte counts were increased at week 9 in high dose animals and at week
12 or 13 in high dose males. In addition, reticulocyte counts were slightly increased at week 16
or 17 of the recovery period in high dose animals. According to the investigators, the
hematological effects of desmedipham reflected a slight oxidative injury to red blood cells, an
effect that was reversible. Total thyroxine levels were slightly lower at week 12 or 13 for high
dose animals and at week 16 or 17 of the recovery period in high dose males.
The systemic toxicity LOEL is 26 mg/kg/day in males and 27 mg/kg/day for females
based on effects on hematology (increases in methemoglobin formation and reticulocyte counts)
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and clinical chemistry (total thyroxine levels) parameters. The systemic toxicity NOEL is 5.2
mg/kg/day for males and 5.6 mg/kg/day for females.
In a 90-day dietary study (MRID 40387104), technical desmedipham was fed to groups
of 4 beagle dogs per sex at dose levels of 0, 1, 5 or 150 ppm in the diet (equal to 0, 0.035, 0.17
and 4.97 mg/kg/day for males and 0, 0.035, 0.19 and 5.50 mg/kg/day for females respectively).
Treatment related increases in serum methemoglobin levels were observed at the high dose
level. Pituitary cysts were found in 3 out of 4 high dose females. No other compound related
effects were observed. The systemic toxicity LOEL is 4.97 mg/kg/day for males and 5.50
mg/kg/day for females and the systemic toxicity NOEL is 0.17 mg/kg/day for males and 0.19
mg/kg/day for females based on increases in serum methemoglobin levels.
3. In a 28-day feeding study (MRID 42045701) SPF-bred mice of the NMRI KFM-Han.,
outbred strain received 0, 100, 400, or 1600 ppm (equal to 0, 22, 91, and 416 mg/kg/day for
males and 0, 26, 108, and 519 mg/kg/day for females, respectively) in the diet as a range finding
study for the mouse carcinogenicity study.
No treatment related mortality or clinical observations were noted. There were slight
differences in body weight gain in the mid and high dose males (9% and 13%, respectively)
compared to control. There was an increase in food consumption and food efficiency in the high
dose group during weeks 3 and 4 and overall in both sexes. The biological relevance of this
observation is unclear.
Hematological observations were a dose related increase in Heinz body and methemoglobin
formation in the mid and high dose groups. Other observations were a slight decrease in the
erythrocyte count, hemoglobin concentration and hematocrit values in high dose males along with
a slight reticulocytosis in high dose animals. Also observed were morphological changes in the
erythrocytes as increased anisocytosis in mid dose males and high dose males and females and as
increased polychromatophilia in high dose animals. The effects were referred to by the
investigators as toxic hemolytic anemia. Further, spleen weights were increased in both males
and females in the high dose group, supportive of the hematological observations.
The heart weights were increased in high dose animals (not absolute in males) and kidney
weights were increased in high dose females only, probably not related to treatment. No treatment
related macroscopic observations were noted. Microscopically there was a dose related increase
in extra medullary hemopoiesis in the spleen, mainly in mid and high dose animals and bone
marrow hyperplasia in high dose males. These observations were referred to by the investigators
as reactive and compensatory processes in response to the hemolysis caused by the test compound.
Other observations were singular in nature and not related to treatment.
The systemic toxicity LOEL is 91 mg/kg/day for males and 108 mg/kg/day for females
based on hematological and related histopathological findings. The systemic toxicity NOEL is
22 mg/kg/day for males and 26 mg/kg/day for females.
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4. In a 21-day dermal toxicity study (MRID 42124201), Betanex (16% desmedipham) was
applied to the shaved skin of four groups of 10 male and 10 female rabbits each for 6 hours per
day for 21 days at dosages of either 0, 60, 180, or 540 mg/kg body weight. A recovery group
consisting of one-half of the animals from each group was treated an additional 2 days and was
then observed treatment-free for 23 days.
No treatment related mortalities or clinical signs of toxicity occurred during the study.
There was a dose-related increase in the incidence and severity of dermal lesions at the application
site in the highest two dosage groups. No alterations in food consumption or body weight resulted
from treatment. Hematology and clinical chemistry evaluations were not affected except for
statistically significant decreases in thyroxine levels in the female rabbits in the highest two dosage
groups.
The findings on gross necropsy and histopathology involved the dermal lesions. On gross
examination, the lesions consisted of thickening of the skin, necroses, brown and red foci and
nodules and eschar formation. Microscopically, there was a dose-related incidence of acanthosis,
hyperkeratosis, dermal inflammatory cell infiltrates and epidermal ulceration (in the highest group
only). The systemic toxicity LOEL is 180 mg/kg/day based on dermal lesions (gross and
microscopic observations) and decreases in thyroxine levels. The systemic toxicity NOEL is 60
mg/kg/day.
c. Chronic and Carcinogenicity Toxicity
1. In a 2-year combined chronic toxicity/carcinogenicity study (MRID 40387107),
desmedipham technical was administered to Wistar rats at dietary levels of 0, 60, 300, or 1500
ppm (equal to 0, 3.18, 15.71, and 79.90 mg/kg/day for males and 0, 3.86, 19.84, and 100.46
mg/kg/day for females, respectively). There were no effects of dosing on clinical signs or
mortality. The mean body weights were persistently decreased in high-dose males and females
with significant (p<0.05) decreases at several study intervals; at study termination, the mean
body weights in high-dose males and females were 4% and 13% lower than in controls,
respectively. A dose-related hemolytic anemia was seen in both sexes. Methemoglobin formation
was increased (p < 0.05) throughout the study in male and female mid and high dose groups. This
was accompanied by an increase in Heinz bodies (p < 0.05) at all intervals of sampling in high-
dose males and females.
Significant (p<0.05) decreases were observed in erythrocyte counts, hemoglobin
concentration, and hematocrit values in mid and high dose males and in high dose females.
Reticulocyte counts were markedly increased in high-dose males and females throughout the
study; slight but significant (p< 0.05) increases in reticulocyte counts were seen in most intervals
in mid-dose males and females. Total bilirubin was slightly increased in high-dose groups at most
intervals; the increases were significant (p< 0.05) in high-dose males at 12 months and in high-
dose females at 12 and 24 months.
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Mild effects on thyroid function were characterized by a decreased level of T4 in high-dose
males and in mid- and high-dose females at both 12 and 24 months, as well as a slight decrease
of T3 in mid- and high-dose females. Spleen weights (absolute and relative) were increased in
high-dose males and females at 12 and 24 months. No increases were seen in the incidence of
erythropoiesis and hemosiderosis in the spleen, but the severity increased with dosing. The
incidence of hyperplastic changes in the thyroid was increased in dosed males, particularly at the
high dose. Other histologic findings were considered to be spontaneous in origin. There was no
increase in tumors noted.
The systemic toxicity LOEL is 15.71 mg/kg/day for males and 19.84 mg/kg/day for
females based primarily on the anemia. The systemic toxicity NOEL is 3.18 mg/kg/day for males
and 3.86 mg/kg/day in females.
2. In a 12-month oral toxicity study (feeding) (MRID 00156889), desmedipham was
administered to beagle dogs for 1 year at dietary levels of 0, 300, 1500, and 5000 ppm (equal to
0, 9.6, 52.5, and 167.7 mg/kg/day for males and 0, 10.4, 57.4, and 200.7 mg/kg/day for
females, respectively). For the first 28 days, the high-dose level was 7500 ppm and this was
reduced to 5000 ppm because of weight loss and marked toxicity. Two dogs at the high dose
were sacrificed moribund and one died. Mean weights in high-dose males recovered to the
control level but mean weights in mid- and high-dose females were slightly decreased throughout
the study.
There was a dose-related increase in methemoglobin in males and females which was
significant (p < 0.01) in mid- and high-dose groups and an increase in Heinz bodies in the high-
dose group. Red cell counts, hematocrit, and hemoglobin were decreased and mean corpuscular
hemoglobin increased primarily in the high-dose groups. There was an erythrogenic response
indicated by an increase in reticulocyte counts and morphologic changes of erythrocytes as well
as an increase in erythrocyte precursors in the bone marrow of high-dose dogs. Several clinical
chemistry parameters such as total bilirubin, cholesterol, alkaline phosphatase, lactic
dehydrogenase and albumin/globulin ratio were affected in mid- and high-dose females. There
was a decrease in serum triiodothyronine (T3) in dosed dogs and a decrease in thyroxine (T4) in
mid- and high-dose females. This was accompanied by an increase in thyroid weights. There
were increases in hematopoiesis in the spleen in high-dose dogs and accompanying increases in
spleen weights. Hemosiderosis and cholestasis were increased in livers of high-dose dogs and
liver weights were also increased. (See special study below).
The Systemic Toxicity LOEL is equal to or less than 9.6 mg/kg/day for males and equal
to or less than 10.4 mg/kg/day for females based on moderate increases in methemoglobin in both
sexes and an increase in hemosiderin deposition in the liver in low-dose females. The System
Toxicity NOEL is less than 9.6 mg/kg/day for males and less than 10.4 mg/kg/day for females.
Based on the results from a special study in dogs (MRID 42045702; see discussion below), the
Agency RfD/QA Peer Review Committee (11/14/95) considered the threshold NOEL to be 150
ppm (equal to 5.1 mg/kg/day for males and 4.3 mg/kg/day for females) in the dog.
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3. In a special study entitled Determination of the No-Effect Level for Methemoglobin
Production Following Desmedipham Technical Administration in the Dog (oral/feeding route)
(MRID 42045702), desmedipham technical was administered to beagle dogs at varying dose levels
(150 to 500 ppm in one group; 75 ppm then 300 ppm then 0 ppm followed by 1500 ppm in
another group). Higher dose levels of desmedipham technical, 500 and 1500 ppm, produced a
"grey" urine. No other dose related clinical signs were noted. There was no apparent effect of
treatment on the body weight gains or food consumption. Hematological parameters other than
methemoglobin formation were unaffected by treatment. Some pathology was noted in the "high"
dose group. The LOEL for the increase in methemoglobinemia in male dogs is 15.5 mg/kg/day
(500 ppm) and in female dogs is 1.1 mg/kg/day (300 ppm) with the NOEL at 5.1 mg/kg/day (150
ppm) in males and 4.3 mg/kg/day (150 ppm) in females. This study must be considered with the
chronic feeding study in the dog.
4. In a 104-week carcinogenicity study (MRID 40387106), desmedipham technical was
fed to NMRI mice at dietary levels of 0, 30, 150, or 750 ppm (equal to 0, 4.2, 21.68, and 109.0
mg/kg/day for males and 0, 5.8, 30.75, and 145.0 mg/kg/day for females, respectively).
Treatment-related signs of toxicity or clinical symptoms were not observed in the treated animals
and the mortality incidence in males and females at all dietary levels was essentially similar.
Males of both the interim sacrifice (12 months) and the high dose showed slightly reduced mean
body weights. These reductions were not consistent and were not seen in females. Food
consumption values in the interim sacrifice mid and high dose animals tended to be slightly
increased during the treatment period. Hematology results revealed treatment-related Heinz body
anemia in high dose males and females at weeks 52 and 104 accompanied by slight to moderate
methemoglobin formation in high dose males and females at week 52. Other hematology
parameters that differ significantly from controls were not considered of toxicological importance
since they were not consistent over the intervals of sampling and were generally within the normal
reference range.
Absolute and relative spleen weights were significantly increased (p < 0.05) in comparison
with controls in high dose females after 52 weeks. Gross and histopathological findings did not
indicate any toxic or carcinogenic significance. The systemic toxicity LOEL is 109 mg/kg/day
for males and 145 mg/kg/day for females and the systemic toxicity NOEL 21.68 mg/kg/day for
males and 30.75 mg/kg/day for females based on Heinz body anemia accompanied by
methemoglobin formation in both sexes and an increase in absolute and relative (to body weight)
spleen weights in females.
Desmedipham is classified as a Group E chemical (evidence of non-carcinogenity for
humans). After submittal and review of additional requested confirmatory data regarding the
historical incidence of the tumors noted and the number of animals examined, the group
classification for desmedipham will be reevaluated.
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d. Developmental Toxicity
1. In a developmental toxicity study (MRID 42045704 and 00156724), mated female
Wistar rats were administered desmedipham technical via gavage at 0, 10, 100, or 1000
mg/kg/day during days 6-15 of gestation. Maternal toxicity was noted as reduced body weight
gain and corrected body weight gain during the dosing and gestational periods and reduced food
consumption during the dosing period in rats administered 1000 mg/kg/day. The maternal
toxicity LOEL is 1000 mg/kg/day based on reduced body weight gains and corrected body weight
gains and reduced food consumption. The maternal toxicity NOEL is 100 mg/kg/day.
Developmental toxicity was manifested as reduced fetal body weight and an increased incidence
of external (palatoschisis) and skeletal (sternebrae and vertebrae) anomalies in fetuses from
animals administered 1000 mg/kg/day. The developmental toxicity LOEL is 1000 mg/kg/day
based on the increased incidence of skeletal anomalies. The developmental toxicity NOEL is 100
mg/kg/day.
2. In a developmental toxicity study (MRID 00156725) Wistar/HAN albino rats (source:
KFM) received by oral gavage either 0, 10, 100 or 500 mg/kg/day for gestation days 6 through
15. This study was conducted subsequent to study MRID 00156724 (above). Maternal toxicity
was manifested as a reduction in body weight gain during the dosing period (gestation days 6-16)
with a rebound in body weight gain following dosing (gestation day 16-21); a reduction in body
weight gain for the overall treatment period (dosing plus post dosing period) and for corrected
body weight gain. A reduction in food consumption was noted in the high dose group during the
dosing period. There was an increase in methemoglobin formation on gestation day 16 in the
treated groups (1.3, 1.6, 3.7, and 9.3% for the control, low, mid, and high dose groups,
respectively). These values were statistically significant in the mid and high dose groups with an
increasing trend noted at the low dose. There was also an increase in Heinz body formation in
the high dose group.
The maternal toxicity LOEL is 100 mg/kg/day based on hematological findings. The
maternal toxicity NOEL is 10 mg/kg day. The high dose fetuses had slightly reduced body
weights as compared to the control. There was an increase in incompletely ossified sternebrae,
and absent ossification of phalangeal nuclei, calcanea and cervical vertebrae in the high dose
group. The developmental toxicity LOEL is 500 mg/kg/day and the developmental toxicity
NOEL is 100 mg/kg/day based on the increase in fetal incidence of skeletal anomalies.
3. In a developmental toxicity study (MRID 41214706) Wistar/HAN albino rats (source:
KFM) were exposed by the dermal route to either 0 or 1000 mg/kg/day (limit dose) of
desmedipham for gestation days 6 through 15. Maternal toxicity was manifested as a slight
reduction in body weight gain during the dosing period (gestation days 6-16), for the overall
treatment period (dosing plus post dosing period) and for corrected body weight gain. No other
treatment related observations were noted. The maternal toxicity LOEL is equal to 1000
mg/kg/day and the maternal toxicity NOEL is less than 1000 mg/kg day based on reduced body
weight gain. No developmental toxicity was noted. The developmental toxicity LOEL is greater
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than 1000 mg/kg/day and the developmental toxicity NOEL is equal to or greater than 1000
mg/kg/day.
4. In a developmental toxicity study (MRID 42045703 and 00132360), female rabbits
were administered desmedipham technical via oral gavage at 0, 50, 150 or 450 mg/kg/day during
days 6 through 27 of gestation. Maternal toxicity was evidenced by decreased body weight gain
during the dosing and gestation periods and reduced corrected body weight gain during the dosing
period in the 450 mg/kg/day dose group. The maternal toxicity LOEL is 450 mg/kg/day and the
maternal toxicity NOEL is 150 mg/kg/day based on decreased body weight gain. Developmental
toxicity was noted as a slight increase in litter and increased fetal incidence of left and right
forelimb proximal phalangeal digit # 1 and medial phalangeal digit #1 and #4, and the increased
litter and fetal incidence of left and right hindlimb medial phalangeal toe # 1, # 2, and #3 and
reduced fetal body weights in litters from the 450 mg/kg/day dose group. The developmental
toxicity LOEL is 450 mg/kg/day and the developmental toxicity NOEL is 150 mg/kg/day based
on increased incidence of skeletal anomalies and reduced fetal body weights.
e. Reproductive Toxicity
In a 2-generation reproduction study (MRID 40387105), Wistar rats were fed diets
containing desmedipham technical at levels ofO, 50, 250, or 1250 ppm (approximately 0, 4, 20,
or 110 mg/kg/day, respectively) for two consecutive generations. Significant reductions in
parental body weights at the high-dose level and hemolytic anemia accompanied by significant
increases in splenic weights and compensatory functioning of the thyroid at the mid- and high-dose
levels were observed. The LOEL for parental systemic toxicity is 20 mg/kg/day and the NOEL
for parental systemic toxicity is 4 mg/kg/day based on hemolytic anemia accompanied by
significant increases in splenic weights and compensatory functioning of the thyroid.
No specific reproductive toxicity was noted; however, developmental toxicity was noted
as reductions in lactational body weights of pups at the high dose level. The developmental/ off-
spring systemic toxicity LOEL is 110 mg/kg/day and the developmental/offspring systemic
toxicity NOEL is 20 mg/kg/day. The LOEL for reproductive toxicity is greater than 110
mg/kg/day and the NOEL for reproductive toxicity NOEL is equal to or greater than 110
mg/kg/day.
f. Mutagenicity
In a Salmonella typhimurium and Escherichia coli reverse mutation assay (MRID
41607005), the mutagenic potential of eight concentrations of desmedipham, ranging from 10.0
to 5000.0 //g/plate, was tested in the plate incorporation test using the Salmonella typhimurium
strains TA 1535, TA 1537, TA 98 and TA 100 along with Escherichia coli strain WP2. Two
separate experiments were performed with triplicate plates, with and without activation, and with
negative, solvent and positive controls. Evidence of toxicity in the number of revertants was seen
at the higher concentrations of the test substance. There was no significant, reproducible and/or
dose-dependent increase in the number of revertants observed in any of the strains, with or
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without metabolic activation. In an unscheduled DNA synthesis assay (UDS) in primary rat
hepatocytes (MRID 41214707), desmedipham technical (98% a.i., Batch 320033) was negative
for UDS in primary rat hepatocytes treated with the test material at doses up to 25.2 //g/mL. At
50.4 //g/mL, hepatocytes were not scored because of poor cell morphology. Higher
concentrations (>101 //g/mL) were excessively cytotoxic.
In a mouse micronucleus assay (MRID 00156886), Desmedipham Technical (98.3% a.i.,
Batch 320033) was negative for micronucleus induction in the bone marrow cells of male or
female NMRI mice at 24, 487, or 72 hours after oral gavage administration of 5000 mg/kg (the
limit dose) desmedipham technical. No deaths or signs of target organ toxicity were seen at any
harvest time; sedation was the only clinical sign observed. In view of the negative results, the
response of the positive control validated the experiment. It was, therefore, concluded that
desmedipham technical did not induce a genotoxic effect.
In a mouse lymphoma assay (MRID 00156887), Desmedipham Technical (98% a.i., Batch
320033) was positive in two independent mouse lymphoma forward mutation assays conducted
with 6.3-200 //g/mL (initial assay) and 20-120 //g/mL assay (confirmatory assay) in the presence
and absence of S9 activation. In the initial assay, increases in the mutation frequency (MF) and
in the number of mutants per plate were observed at the highest clonable level (100 //g/mL +/-
S9) and also at 50 //g/mL +S9. In the confirmatory assay, desmedipham technical induced dose-
related increases in the MF that ranged from 1.5 to 5.4 fold higher than controls at 80 and 100
//g/mL -S9, respectively. By contrast, mutagenic activity was detected over the entire range of
assayed concentrations in the presence of S9 with fold-increases of 1.4 at the low dose (20
//g/mL) and 9.5 at the highest cloned level (100 //g/mL).
In an in vitro human lymphocytes assay (MRID 00156888), Desmedipham Technical (98%
a.i., Batch 320033) was negative for the induction of structural aberrations in human lymphocytes
treated in vitro with 10, 50, or 100 //g/mL ( + /- S9) desmedipham technical. The test material
was not cytotoxic at any dose but was insoluble at 125 //g/mL +/- S9.
g. Metabolism
In a metabolism study in the rat (MRID 41607006), disposition and metabolism of phenyl
carbamate 14C-desmedipham and ethyl phenyl carbamate14 C-desmedipham was investigated in
male and female rats at a low oral dose (5 mg/kg). Absorption of desmedipham appeared rapid
but incomplete. Urine represented the major route for excretion of desmedipham derived
radioactivity, with 68-84% excreted in 24 hours by this route for both labeled compounds. In
feces, between 10-15% was excreted in the first 24 hours for both labels. Tissue levels at study
termination (96 hours post-dose) were negligible for both phenyl-labeled and ethyl phenyl
carbamate labeled desmedipham, except for blood and plasma in rats treated with phenyl-labeled
desmedipham, where measurable amounts of radioactivity were found.
In rats administered phenyl labeled desmedipham (14C-desmedipham (phenyl carbamate
label), Radiochemical Purity: > 97.0%, Specific Activity: 59.1 //Ci/mg), the major metabolite
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identified in urine by TLC and HPLC was 4-acetamidophenol, with minor amounts of
4-aminophenol, 2-aminophenol, 2-acetamidophenol, and parent desmedipham. The major fecal
metabolite detected from administration of phenyl labeled desmedipham was 4-acetamidophenol,
with smaller amounts of 4-aminophenol and unchanged desmedipham. Several polar compounds
were also detected which were not resolved by the separation techniques employed.
In rats given ethyl phenyl carbamate labeled desmedipham (14C-desmedipham (ethyl phenyl
carbamate label), Radiochemical Purity: > 99.7%, Specific Activity: 61.6 //Ci/mg), the major
urinary metabolite detected was ethyl-N-(S-hydroxyphenyl) carbamate, with smaller amounts of
3-acetamidophenol and 3-aminophenol. Analysis of fecal homogenates showed a similar pattern
of metabolites as for urine. For both the phenyl labeled and ethyl phenyl carbamate labeled test
material, there did not appear to be any sex differences in urinary metabolites from administration
of phenyl labeled desmedipham. However, this cannot be stated with certainty as the metabolite
data were not presented in quantitative fashion (i.e. percent administered dose). A scheme for
metabolism of desmedipham was proposed based on the data presented in this study. This study
was classified as supplemental.
In a second metabolism study in the rat (MRID 42880001; 42880002), disposition and
metabolism of phenyl carbamate (PC) labeled 14C-desmedipham and ethyl phenyl carbamate (EPC)
labelled 14C-desmedipham was investigated in male and female rats at a low oral dose (5 mg/kg,
EPC labelled desmedipham only), repeated low oral dose (5 mg/kg x 14 days), and a single high
dose (1000 mg/kg). Absorption of desmedipham appeared rapid but incomplete, and was
decreased at the high dose level. Urine represented the major route for excretion of both PC and
EPC labelled desmedipham derived radioactivity, with between 67-83% excreted by 30 hours
post-dose. In feces, between 7-20% was excreted in the first 30 hours for both labels at the low
dose. At the 1000 mg/kg dose, urinary excretion was decreased to between 32-44% of the
administered dose, while fecal excretion of radioactivity was significantly increased for both labels
(between 50-56% of administered dose). Distribution data showed significant amounts of residual
radioactivity in several tissues for both PC and EPC labelled desmedipham at the 1000 mg/kg
dose level. Blood and well-perfused tissues showed the highest levels of residual radioactivity,
and values were higher for PC labelled desmedipham vs EPC labelled desmedipham.
In rats administered phenyl labeled desmedipham (14C-desmedipham (phenyl carbamate
label), Radiochemical Purity: > 98.0%, Specific Activity: 59.1 //Ci/mg), the major metabolite
detected in urine at both the 5 mg/kg and 1000 mg/kg dose level and identified by TLC and
HPLC analysis was 4-acetamidophenol, with minor amounts of 4-aminophenol, 3-aminophenol
and 3-acetamidophenol. The major fecal metabolite detected from administration of PC labelled
desmedipham at 5 mg/kg and 1000 mg/kg was phenylmethyl carbamate in both male and female
rats. Parent desmedipham was also present in significant percentage at the 1000 mg/kg dose level.
In rats given EPC labelled desmedipham (14C-desmedipham (ethyl phenyl carbamate label),
Radiochemical Purity: > 98.0%, Specific Activity: 17.2 //Ci/mg), the major urinary metabolite
detected at 5 mg/kg and 1000 mg/kg was ethyl-N-(3-hydroxyphenyl) carbamate, with smaller
amounts of 3-acetamidophenol and 3-aminophenol. An unknown metabolite comprising between
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4.2-6.2% of the administered radioactivity in EPC dosed rats was identified as N-(3-hydroxy-
phenyl) 1-hydroxyethyl carbamate. Analysis of fecal fiber extracts showed the presence of both
ethyl-N-(S-hydroxyphenyl) carbamate and parent desmedipham, while aqueous supernatants of
fecal extracts showed minor amounts (< 1% of the dose) of several previously identified
metabolites. For both the phenyl labeled and ethyl phenyl carbamate labeled test material, sex
differences in metabolism appeared to be minor. From the data presented, a revised scheme for
metabolism of desmedipham was provided. Metabolite data for the single low dose of PC labelled
desmedipham was not provided, although the Agency had requested additional data before
upgrading this study to satisfy the §85-1 data requirement. The data in this study partially satisfy
the data requirements for §85-1.
h. Reference Dose
The Agency RfD Committee recommended that a RfD for this chemical be based on a
reproductive toxicity study in rats with a parental toxicity NOEL of 4 mg/kg/day (50 ppm).
Effects seen were significant reduction of body weight, hemolytic anemia accompanied by
significant increase in spleen weights and thyroid compensatory function at the next higher dose
of 20 mg/kg/day (250 ppm), the middle dose level tested, and higher dose levels. An uncertainty
factor (UF) of 100 was applied to account for the inter-species extrapolation and intra-species
variability. On this basis, the RfD is 0.04 mg/kg/day.
i. Cancer Classification
The Cancer Classification assigned to desmedipham is tentatively classified as a "Group
E" chemical, based on evidence of noncarcinogenicity. Confirmation of this classification will
be made upon receipt and evaluation of requested confirmatory data addressing historical control
data on the background incidence of tumors seen and the registrant's response to other issues with
respect to the number of animals examined in the rat study. (MRID 40387107)
WHO/JMPR Status
Desmedipham has not been reviewed by the Food and Agriculture/World Health
Organization (FAO/WHO) joint meeting on pesticide residues (JMPR).
j. Dermal Absorption
In a dermal absorption study (MRID 41957101), groups of male Wistar rats were exposed
to single dermal doses of 0.01, 0.1, 1.0, 10.0 mg/kg 14C desmedipham for 0.5, 1,2,4, and 10
hours. Urine, feces, and blood were collected up to 120 hours post dosing. Elimination of 14C
desmedipham derived radioactivity was minor via urine and feces. The percentage of an
administered dose of desmedipham absorbed decreased with increasing dose, but the absolute
amount of desmedipham absorbed increased in a linear fashion with increasing dose. Levels of
desmedipham derived radioactivity in the carcass and blood were insignificant at all doses tested,
but the amount of radioactivity found at the application site was increased at the highest dose,
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indicating retention of desmedipham in the dermis or viable epidermis. The level of dermal
absorption was considered to be 5.4 % at 10 hours.
k. Toxicological Endpoints of Concern
The Toxicological Endpoint Selection Committee (8/24/95) of the Agency's Office of
Pesticide Programs determined the following:
• An acute (1 day) dietary risk assessment and a short term (1 to 7 days)
occupational/residential risk assessment are required. The developmental NOEL is 150
mg/kg/day based on developmental toxicity in rabbits; the developmental LOEL is 450
mg/kg/day based on incidences of skeletal anomalies and reduced fetal body weights
observed in a rabbit study. (MRIDs 42045703 and 00132360)
Discussion: The developmental NOEL is 150 mg/kg/day and the developmental LOEL is 450
mg/kg/day based on incidences of skeletal anomalies and reduced fetal body
weights. Although a developmental study in Wistar rats demonstrated a NOEL of
100 mg/kg/day, the LOEL was 1000 mg/kg/day based on external and skeletal
anomalies in fetuses. This rat study was not chosen as the primary study for
endpoint selection, since the large spacing between the doses makes it difficult to
extrapolate to meaningful results. The NOEL, although lower than that seen in the
rabbit developmental study selected, is considered to be an artifact of dose
selection and probably underestimates the actual threshold for adverse effects
significantly. It does, however, support the observations in the rabbit study above.
• An intermediate term (1 week to several months) occupational/residential risk assessment
is required. The NOEL is 4 mg/kg/day based on multi-generation reproduction study data
in the rat. The LOEL is 20 mg/kg/day, based on reduced body weight, hemolytic anemia,
significant increases in spleen weights and compensatory thyroid function in the rat.
(MRID 40387105)
2. Exposure Assessment
a. Dietary Exposure
Tolerances for residues of desmedipham per se have been established at 0.2 ppm in/on
sugar beet roots and tops [Source: 40 CFR § 180.353', no tolerances exist for residues of
desmedipham in animal commodities and no food/feed additive tolerances have been established.
A tolerance for the use on table beets and Swiss chard grown for seed is not required. The
Agency has determined that the residue to be regulated in plants and animals is desmedipham per
se.
The current analytical method in PAM, Vol. II may not be adequate for the enforcement
of tolerances for residues of desmedipham. AgrEvo has proposed an HPLC UV/VIS method to
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be the primary enforcement method used for the determination of residues of desmedipham in or
on sugar beets. Additional data have been required before this method can be incorporated into
PAM, Vol II as an enforcement method.
Plant Metabolism GLN 171-4 (a):
The qualitative nature of the residue in plants is adequately understood. The metabolism
of desmedipham in plants mirrors that of phenmedipham as the two compounds are structurally
similar. The sugar beet metabolism study conducted with phenmedipham is considered adequate:
sugar beet leaves from plants grown in nutrient solution were treated with radiolabeled
phenmedipham by foliar application or hypocotyl injection. Phenmedipham and its methyl-N-(3-
hydroxy-phenyl)carbamate hydrolysis product (MHPC) in the leaves comprised ~ 18% and 3%
of the total applied radioactivity, respectively. In addition, conjugated 0- and N-glucosides of
the MHPC metabolite and phenmedipham represented -32% and 24% of the applied activity,
respectively. (MRIDs 00041862, 40274901, 41214710)
The Agency has concluded that the AgrEvo submitted metabolism study for phenmedipham
is adequate for desmedipham, and that phenmedipham and desmedipham should be regulated in
the same manner and that the residue of concern is desmedipham per se.
Animal Metabolism GLN 171-4 (b):
The nature of the residue in animals is adequately understood based on acceptable poultry
and ruminant metabolism studies reflecting oral dosing. The Agency has determined that the
residue to be regulated in animals is desmedipham per se. (MRIDs 00098591, 41998603,
42371301, 42687401, 42822701)
Residue Analytical Methods - Plants and Animals GLN 171-4 and (d):
The residue analytical methods requirement is not fulfilled. However, for the purposes
of the risk assessment, the current analytical method discussed below is adequate for data
collection on residues of desmedipham in/on sugar beets.
The Agency will consider the HPLC UV/VIS method (Method Desmedipham/R75, also
referred to as the "desmedipham-specific method") used for the determination of residues of
desmedipham in or on sugar beets to be the proposed primary analytical enforcement method.
Submitted method validation data from AgrEvo and an independent laboratory validation indicated
that recoveries of desmedipham from sugar beet roots and tops using this method were adequate.
The Agency tentatively accepts the proposed analytical method as a primary enforcement method,
provided data pertaining to the potential interferences from the related propham (IPC) and
phenmedipham pesticides, as well as additional raw data are submitted. If this data for the
primary method is determined to be adequate, after submission of acceptable data and a successful
EPA method validation trial, then the Agency will not require the submission of a confirmatory
method. Radiovalidation of the desmedipham-specific method is still outstanding.
17
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The FDA multi-residue testing data has been forwarded to FDA for evaluation. The FDA
PESTDATA database dated 1/94 (Pam Vol. I, Appendix I) does not report recoveries for
desmedipham using any of the PAM I multiresidue methods.
Enforcement analytical methods for residues in animal commodities are not required since
tolerances are not needed (see GDLN 171-4(j)). (MRIDs 00076669, 41998604, 42921801,
42921802, 42921803, 00041859)
Storage Stability GLN 171-4 (e):
Adequate storage stability data are required to support any required field trials (see GLN
171-4(k). The available data indicate that residues of desmedipham are stable in/on sugar beet
tops and roots stored at -21°C for up to 8 months. An outstanding study which appreciably
exceeds the storage period would require that concurrent storage stability studies be performed.
(MRID 00041860)
Magnitude of the Residue in Meat, Milk, Poultry, and Eggs GLN 171-4 (j):
Sugar beet commodities are not listed as poultry feed items on the Updated Livestock
Feeds Table for Subdivision "0" dated 4/26/94. Therefore, tolerances for residues in poultry and
eggs are not required.
The administered dose in the submitted ruminant metabolism study represented ~ Ix the
maximum expected dietary burden (including the proposed 15 ppm tolerance for sugar beet tops),
and desmedipham residues in all tissues were < 0.01 ppm. Therefore, the Agency considers a
cattle feeding study is not required, and no tolerances for residues in meat and milk need be
established (see CFR §180.6(a) (3).
Magnitude of the Residue in Plants GLN 171-4 (k):
Review of available data indicates that residue trials were conducted in nine states using
application rates that exceeded the single and seasonal application rates registered at that time.
In addition, samples were collected at a 90 day PHI. The current PHI is 75 days. Treated tops
and roots bore desmedipham residues at <0.2 ppm. The residue data were supported by
submitted storage stability data. Additional data reviews indicated that after single applications
of desmedipham (at 0.5 to 4 Ib ai/A and PHIs of 60-152 days) in the major sugar beet producing
states, apparent residues ranged from 0.01-0.12 ppm in the roots and 0.02-0.15 ppm in the tops.
Following correction for control samples, net residues were typically < 0.02 ppm. The Agency
concluded that the proposed use will result in, at most, trace residues of desmedipham on sugar
beet roots and tops. However, as control values occasionally exceed 0.1 ppm, the existing
tolerance of 0.2 ppm (sugarbeet roots) was determined to be appropriate.
18
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Samples were analyzed using a method similar to the current PAM II enforcement method.
Subsequently, additional 6 (a) (2) field trial data submitted by the registrant indicated higher than
expected desmedipham residues in sugar beet tops harvested 75 days after the last of two
applications. In this submission, applications were made one week apart, each at 0.975 Ib ai/A.
The field trials were conducted in MI, MN, ND and CA using the EC and WP formulations.
Desmedipham residues were determined to be < 0.05-13.86 ppm in/on eight sugar beet top
samples, by using the desmedipham specific method. The registrant submitted a petition for a
desmedipham tolerance amendment for residues in/on sugar beet tops at 15 ppm (AgrEvo letter
12/3/92). The established 0.2 ppm tolerance for sugar beet roots appears to be acceptable at this
time. (MRIDs PP# 4F1459, 00116379, 00076668, 00041865, 00066110, 00070105, 00116710,
00049456, 42516501, 42921801, 42921802, 42921803) However, additional confirmatory field
crop data for sugar beet tops has been requested from the registrant to substantiate the residue
tolerances for sugar beet tops at 15 ppm for desmedipham. Upon receipt of these data EPA will
determine whether the current tolerance is adequate or needs to be revised.
Magnitude of the Residue in Processed Food/Feed GLN 171-4 (1):
The reregistration requirements for magnitude of the residue in processed food/feed
commodities are fulfilled for sugar beets. The submitted processing study is adequate: no
food/feed additive tolerances or Section 701 (maximum residue limits) as necessary. (MRID
42112301)
Confined Rotational Crops GLN 165-1:
For the purposes of risk assessment, the nature of the residues in rotational crops is
adequately understood. The available confined rotational crop study is adequate, provided the
dates of sample extraction and analysis for each crop matrix as well as supporting storage stability
data reflecting the storage intervals and conditions of samples from the study are submitted.
Limited and/or extensive field rotational crop studies are not required because residues of
the regulated parent were predominately found at < 0.01 ppm in/on rotational crop commodities.
Therefore, rotational crop restrictions are not necessary and no plant-back intervals need be
prescribed. (MRID 42909601)
b. Magnitude of the Residue in Drinking Water
A Maximum Contaminant Level (MCL) or a Drinking Water Lifetime Health Advisory
Level (HAL) has not been established for desmedipham (EPA, Office of Water). Desmedipham
is currently not regulated under the Safe Drinking Water Act (SDWA). Rapid environmental
degradation of desmedipham in surface water is expected to occur from hydrolysis and microbial
processes. Desmedipham residues in surface water were not detected in sugar beet agricultural
production areas (CA, WA, MN), when monitored by multi-residue test methods (see Sec.
II.C.2.C. (2)). Based on these results and because desmedipham has a low potential to leach from
19
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soil to ground water, the Agency does not expect the current registered uses of desmedipham
result in residues of desmedipham in drinking water.
c. Occupational and Residential Exposure
An occupational and/or residential exposure assessment is required for an active ingredient
if certain toxicological criteria are triggered and there is potential exposure to handlers (mixers,
loaders, applicators, etc.) during use of desmedipham or to persons entering treated sites after
application is complete.
(1) Handler Exposure
There is potential short and intermediate-term occupational exposure to mixers, loaders,
applicators, and flaggers associated with application of desmedipham products to sugar beets.
These potential exposure scenarios are: (1) mixer/loader exposure for mixing liquid aerial
application; (2) mixer/loader exposure for mixing liquid ground boom treatment application; (3)
mixer/loader exposure for mixing wettable powder for aerial application; (4) mixer/loader
exposure for mixing wettable powder for ground boom treatment application; (5) applicator
exposure for aerial (liquid application); (6) applicator exposure for ground boom tractor
equipment; and (7) flagger exposure during flagging (liquid applications). There are no
residential uses of desmedipham, therefore a residential exposure/risk assessment is not required.
Some of these workers are exposed to desmedipham more than 7 days per year (reasonable
worst-case estimate). Therefore, the exposure and risk assessments must include both short-term
(less than 7 days per year) and intermediate-term (7 or more days per year) exposure scenarios.
Short-term and intermediate-term exposure scenarios descriptions are presented in
Table 2. The Agency relied on exposure data from its Pesticide Handlers Exposure Database
(PHED). The limits of this database are defined in Table 5.
In accordance with the existing use patterns, it is not expected that occupational exposures
would occur for more than 90 days, resulting in chronic worker exposure. A chronic exposure
assessment is not required since chronic exposure is not expected.
(2) Post Application Exposure
Post-application exposures may occur to agricultural workers following applications to
sugar beets during routine crop-production tasks, such as hoeing and thinning. No desmedipham
specific data are available for assessment of post-application handler exposures to desmedipham
containing registered products.
20
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3. Risk Assessment
a. Dietary
A desmedipham tolerance of 0.2 ppm in/on the raw agricultural commodity(RAC) sugar
beets (roots and tops) is published in 40 CFR 180.353. The Agency has determined that an acute
(1 day) dietary risk assessment is appropriate for desmedipham because the toxicology endpoints
for desmedipham include developmental toxicity discussed above.
The RfD used in the analysis of dietary exposure is 0.04 mg/kg/bwt/day, based on a
NOEL of 4.0 mg/kg/day (LOEL 20 mg/kg/day) from a 2-generation rat reproduction study
(MRID 40387105) which demonstrated a significant increase in spleen weights and compensatory
thyroid function as an endpoint. An uncertainty factor of 100 was applied.
This dietary risk assessment assumes tolerance level desmedipham residues of 0.2 ppm
tolerance in sugar beets (roots) and 100 percent crop treatment, as the worst case assumption.
Anticipated residue data were not needed for this risk assessment. Although the registrant has
proposed to raise the tolerance for sugarbeet tops to 15 ppm, sugar beet tops are not a human food
item. This is because humans do not eat sugarbeet tops, and sugarbeet tops fed to animals do not
result in residues of concern in meat or milk. Therefore, this was not included in the dietary
analysis.
Acute Dietary Risk
An acute dietary risk analysis was conducted for the dietary subgroup, females
(13 + years), as this group represents women of child bearing age. The computed MOE is 50,000
for this subgroup. When the MOE is determined to be 100 or higher, the Agency does not regard
there to be human health risks of concern. Therefore, from an acute dietary exposure to residues
of desmedipham in sugar beets (0.2 ppm) the Agency believes there is an adequate margin of
exposure to the toxicological endpoint of concern (developmental effects).
Chronic Dietary Risk
A chronic dietary risk assessment of exposures to residues of desmedipham is also
appropriate, since the toxicological endpoint of concern is reproduction effects. This chronic risk
analysis was performed using the present tolerance level of 0.2 ppm desmedipham in/on sugar
beet (roots) and 100 percent crop treated, to estimate the TMRC for the general population and
22 subgroups (age, sex, ethnicity, season, and region of the U.S.).
The TMRC is 0.000066 mg/kg/day for the general population using the established
tolerance of 0.2 ppm for the RAC sugar beets. The subgroup with the highest TMRC is children
(1-6 years) with a TMRC of 0.000164 mg/kg/day or 0.41% of the RfD. The Agency concludes
this level of risk does not represent a potential level of concern for any exposed population, either
general or subgroup.
21
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b. Occupational and Residential
Desmedipham is classified as acute toxicity category II for eye irritation, category III for
dermal toxicity and is a dermal sensitizer. Acute oral, inhalation and dermal irritation are toxicity
category IV. The toxicity endpoint for short term (1 to 7 days) occupational risk assessment is
a NOEL of 150 mg/kg/day, based on the developmental toxicity study in rabbits (acute toxicity
endpoint) with correction for dermal absorption. The endpoint for intermediate term (1 week to
several months) occupational exposure risk assessment is a multi-generation reproduction study
in rats with a NOEL of 4 mg/kg/day and a LOEL of 20 mg/kg/day. The dermal absorption rate
for desmedipham is 5.4 percent at 10 hours. (MRID 40387105, 42045703, 00132360)
Handler Risk
For short and intermediate term risk from occupational exposure, the Agency estimates
risk in terms of the margin of exposure (MOE). The following equations were used to compute
the desmedipham MOEs:
,,_ NOEL
MOE =
Short- Term MOE =
Maximum Daily Exposure
15°
Maximum Daily Dose
Intermediate- Term MOE = - s-JL — L -
Maximum Daily Dose
Risk from Short-Term Exposure
Short-term exposures under the scenarios cited in Table 2, assuming workers wear
baseline PPE protection (long-sleeved shirt, long pants, shoes and socks), result in MOEs above
100 except for mixers and loaders of wettable powder formulations for aerial applications. The
MOE for this exposure scenario is 83. See Table 3, column titled "Baseline Total MOE." The
addition of chemical resistant gloves to the PPE requirements for this scenario results in an MOE
of 375.
Risk from Intermediate-Term Exposure
a.) Intermediate term exposures for handlers and flaggers are presented in Table 4.
The applicator and fogger risks are acceptable with MOEs greater than 100.
However all of the mixer/loader scenarios for exposures with baseline protection
result in MOEs below 100 (column titled "Baseline Total MOE"). The risk
22
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associated with mixer/loader exposure scenarios (except mixers and loaders for
wettable powder formulations supporting aerial applications) may be adequately
reduced (i.e., result in MOEs above 100; see column titled "Total MOE") with the
addition of personal protective equipment as follows.
• Mixers/loaders of emulsifiable concentrate formulations (see
scenarios la and Ib, Table 4) - wear chemical-resistant
gloves in addition to baseline protection;
• Mixers/loaders of wettable powder formulations who are
supporting ground applications (see scenario 2b, Table 4) -
wear dust/mist filtering respirator and chemical-resistant
gloves in addition to baseline protection;
b.) For mixers/loaders of wettable powder formulations who are supporting aerial
applications, scenario 2a, the use of double layer clothing, chemical resistant
gloves, and a dust/mist respirator would only raise the MOE to 40 (Table 4,
column "Total MOE"). The Agency estimates the use of engineering controls in
the form of water-soluble product packaging and single layer clothing will result
in an MOE of 444. Reduction of the application rates to 0.5 pound active
ingredient per acre, assuming aerial applications of up to 350 acres per day, would
negate the need for engineering controls. Other risk mitigation measures were
considered, such as limiting product users to no more than five days of exposure
per growing season. However, the Agency believes such use-limitations would not
be practical or enforceable.
Post-Application Risk
Specific desmedipham post-application exposure data are not available. However, the
Agency notes the toxicology endpoint of most concern is an intermediate-term (1 week to several
months) endpoint and that the current desmedipham registration is for early-season use on sugar
beets. Early season use should present minimal risk because foliar contact would be low. Foliage
area would be small at this time. The Agency therefore concludes that health risks to handlers
from post-application exposures will not pose a significant risk. The current REI (restricted entry
interval) is 24 hours, and PPE is required for workers who enter the treated area before 24 hours.
23
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Table 2. Short-Term and Intermediate-Term Occupational Exposure Scenarios
Exposure Scenario (Seen. #)
Baseline Dermal
Unit Exposure3
(mg/lb ai)
Baseline Inhalation
Unit Exposure1"
(ug/lb ai)
Maximum Label
Application Ratec
(Ib ai/acre)
Daily
Max.
Treated"1
(acres)
Daily Dermal
Exposure6
(mg/day)
Daily
Inhalation
Exposure'
(mg/day)
Daily Total
Exposure8
(mg/day)
Mixer/Loader Exposure
Mixing Liquid Aerial Application (la)
Mixing Liquid Ground boom Treatment
Application (Ib)
Mixing Wettable Powder for Aerial
Application (2 a)
Mixing Wettable Powder for Ground
boom Treatment Application (2b)
2.9
3.7
1.2
43.4
1.26
1.26
350
80
350
80
1278.9
292.3
1631.7
373.0
0.53
0.12
19.1
4.37
1279.4
292.42
1650.8
377.37
Applicator Exposure
Aerial (liquid application) (3)
Ground boom Tractor (4)
0.05
0.01
0.3
0.7
1.26
1.26
350
80
22.1
1.01
0.13
0.07
22.2
1.08
Flagger
Flagging (liquid applications) (5)
0.01
0.2
1.26
350
4.4
0.09
4.5
Long pants, long sleeve shirts, no gloves, open mixing/loading, open cockpit, open cab tractor.
No respirator
Label Reg Nos. 45639-160, 45639-86, 45639-155
Values represent the maximum area or the maximum volume of spray solution which can be used in a single day to complete treatments for each exposure scenario of concern.
Daily dermal exposure (mg/day) = Exposure (mg/lb ai) * Max. Appl. Rate (Ib ai/acre) * Max. Treated
Daily inhalation exposure (mg/day) = Exposure (ug/lb ai) * (Img/lOOOug) conversion * Max. Appl Rate (Ib ai/A) * Max. Treated
Daily total exposure (mg/day) = Daily dermal exposure + Daily inhalation exposure
24
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Table 3. Short-Term Handler Exposure, Mitigation, and Risk
Exposure Scenario (Seen. #)
Baseline Daily
Absorbed
Dermal Dose
(mg/kg/day)a
Baseline Total
Absorbed
Dose
(mg/kg/day)b
Baseline
Dermal
MOEC
Baseline
Total
MOE"
Risk Mitigation Measure
Additional PPEe
Dermal
Unit
Exposure
(mg/lb ai)
Inhalation
Unit
Exposure
(ug/lb ai)
Daily Dermal
Absorbed
Dose
(mg/kg/day) a
Daily Total
Absorbed
Dose
(mg/kg/day)b
Dermal
MOE
Total
MOE
Mixer/Loader Risk
Mixing Liquid Aerial Application (la)
Mixing Liquid Ground boom Treatment
Application (Ib)
Mixing Wettable Powder for Aerial
Application (2a)
Mixing Wettable Powder for Ground-
boom Treatment Application (2b)
1.2
0.263
1.5
0.336
1.2
0.265
1.8
0.409
125
570
100
446
125
566
83
370
N/A
N/A
0.2
N/A
N/A
N/A
43.4 (no
respirator)
N/A
N/A
N/A
0.08
N/A
N/A
N/A
0.40
N/A
N/A
N/A
1,875
N/A
N/A
N/A
375
N/A
Applicator Risk
Aerial (liquid Application) (3)
Ground boom Tractor (4)
0.02
0.0009
0.02
0.002
7,500
166,667
7,500
75,000
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Flagger Risk
Flagging (liquid applications) (5)
0.004
0.006
37,500
25,000
N/A
N/A
N/A
N/A
N/A
N/A
* Daily absorbed dermal dose = (daily dermal exposure * dermal absorption rate 0.054)/60 kg
b Baseline absorbed total dose = [(daily dermal exposure * dermal absorption rate 0.054) + (daily inhalation exposure)]/60 kg
Dermal MOE = NOEL (short-term NOEL = 150 mg/kg/day) / absorbed daily dermal dose
d Total MOE = NOEL (short-term NOEL =150 mg/kg/day) / absorbed daily total dose
" Scenario 2a: Additional PPE = Single layer clothing and chemical resistant gloves.
N/A Not applicable since previous MOE was over 100.
25
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Table 4. Intermediate-Term Handler Exposure, Mitigation, and Risk (Maximum PPE Used)
Exposure Scenario (Seen. #)
Baseline Daily
Dermal
Absorbed
Dose
(mg/kg/day)a
Baseline Total
Absorbed
Dose
(mg/kg/day)b
Baseline
Dermal
MOEC
Baseline
Total
MOE"
Risk Mitigation Measure
Additional PPEe
Dermal Unit
Exposure
(mg/lb ai)
Inhalation
Unit
Exposure
(ug/lb ai)
Daily Dermal
Absorbed Dose
(mg/kg/day)a
Daily Total
Absorbed Dose
(mg/kg/day)b
Dermal
MOEC
Total
MOE"
Mixer/Loader Risk
Mixing Liquid Aerial Application (la)
Mixing Liquid Ground boom Treatment
Application (Ib)
Mixing Wettable Powder for Aerial
Application (2a)
Mixing Wettable Powder for Ground
boom Treatment Application (2b)
1.2
0.263
1.5
0.336
1.2
0.265
1.8
0.409
3
15
3
12
3
15
2
10
0.04
0.04
0.1
0.2
1.2 (no
respirator)
1.2 (no
respirator)
8.7
(dust/mist
respirator)
8.7
(dust/mist
respirator)
0.02
0.0036
0.04
0.018
0.0288
0.0056
0.1
0.033
200
1111
100
222
139
714
40
121
Applicator Risk
Aerial (liquid Application) (3)
Ground boom Tractor (4)
0.02
0.0009
0.02
0.002
200
4444
200
2000
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Flagger Risk
Flagging (liquid applications) (5)
0.004
0.006
1000
667
N/A
N/A
N/A
N/A
N/A
N/A
a Daily dermal absorbed dose = (daily dermal exposure * dermal absorption rate 0.054) / 60 kg
b Baseline Total Absorbed Dose = [(daily dermal exposure * dermal absorption rate 0.054) + (daily inhalation exposure)]/60 kg
c Dermal MOE = NOEL (intermediate-term NOEL = 4 mg/kg/day)/ daily dermal absorbed dose
d Total MOE = NOEL (intermediate-term NOEL = 4 mg/kg/day) / daily total absorbed dose
Additional PPE:
Scenario la = single layer clothing and chemical-resistant gloves ;
Scenario Ib = single layer clothing and chemical resistant gloves;
Scenario 2a = double layer clothing, chemical-resistant gloves and a dust/mist respirator;
Scenario 2b = single layer clothing, chemical-resistant gloves and a dust/mist respirator.
N/A Not applicable since previous MOE was over 100.
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Table 5. Description of Desmedipham Exposure Scenarios for Risk Calculations (Tables 2, 3,and 4)
Exposure Scenario
(Number)
Data Source PHED VI. 1
PPEa
Clothing
Equipment
Engineering
Controls'1
Standard
work day)
Comments'1
Mixer/Loader Exposure
Mixing Liquid (la and
Ib)
Mixing Wettable Powder
(2a and 2b)
Single layer clothing, chemical
resistant gloves.
2a) short-term risk: single layer
clothing, chemical resistant
gloves, and for intermediate-term
risk: coveralls over single layer
clothing, chemical resistant
gloves, and a dust/mist respirator
2b) single layer clothing,
chemical resistant gloves , and a
dust/mist respirator
Open mixing
liquids
Open mixing
wettable
powder
N/A
For aerial
mixing/loading
, intermed-term
risk: Water
soluble
packets, single
layer clothing,
no gloves.
80 to 350 acres
2a) 350 acres
2b) 80 acre
Baseline: Dermal and inhalation acceptable grades. Dermal = 53 to 122
replicates; Inhalation = 85 replicates; High confidence in dermal and inhalation
data.
PPE: Dermal and inhalation acceptable grades.
Dermal = 59 to 122 replicates; Inhalation = 85 replicates; High confidence in
dermal and inhalation data.
PHED data used for baseline and Max PPE , no PFs (protection factor) were
necessary.
Baseline: Dermal and inhalation acceptable grades. Dermal = 7 to 45
replicates; Inhalation = 44 replicates; Low confidence in dermal data; Medium
confidence inhalation data.
PPE: Dermal and inhalation acceptable grades.
Dermal = 22 to 45 replicates; Inhalation = 44 replicates; Medium confidence in
dermal and inhalation data.
Engineering Control: Dermal grades acceptable; inhalation all grades. Dermal
= 5 to 15 replicates. Inhalation =15 replicates.
PHED data used for baseline and engineering controls no PFs were necessary.
Maximum PPE values calculated from PHED data using 50% PF for the addition
of coveralls. 80% PF for the addition of dust/mist respirator.
Applicator Exposure
Aerial equipment
(liquids) (3)
Ground boom (4)
Coveralls over long sleeved shirt
and long pants; no gloves.
N/A
Aircraft;
open cockpit
N/A
N/A
N/A
800 acres
80 acres
Baseline: Dermal grades A, B, C; inhalation all grades. Dermal = 1 to 17
replicates; Inhalation =17 replicates. Low confidence for dermal and inhalation
data.
PHED data used for baseline, no PFs were necessary.
Baseline: Dermal and inhalation acceptable grades. Dermal = 23 to 33
replicates; Inhalation = 22 replicates; High confidence in dermal and inhalation
data.
PHED data used for baseline, no PFs were necessary.
Flagger
Liquids (5)
N/A
N/A
N/A
800 acres
Baseline: Dermal and inhalation grades acceptable. Dermal = 16 to 18
replicates; Inhalation =18 replicates. High confidence in dermal data and
inhalation data.
PHED data used for baseline values, no PFs were necessary.
Clothing represents the baseline exposure estimates used in Tables 2, 3, and 4. Single layer clothing is long sleeved shirt, long pants, shoes and socks.
Engineering Controls: water -soluble packets, single layer clothing, no gloves.
Standard Assumptions based on an 8-hour work day as estimated by the Agency.
"Acceptable grades," as defined by Agency guidance for meeting Subdivision U Guidelines are grades A and B. All grades that do not meet Agency's criteria are listed individually. PF is protection factor.
27
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C. Environmental Assessment
1. Ecological Toxicity Data
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
In order to establish the toxicity of desmedipham to birds, the following tests are required
using the technical grade material: one avian single-dose oral (LD50) study on one species
(preferably mallard or bobwhite quail); two subacute dietary studies (LC50) on one species of
waterfowl (preferably the mallard duck) and one species of upland game bird (preferably bobwhite
quail).
Table 6. Avian Acute Oral Toxicity Findings
Species
Northern Bobwhite
% A.I.
98.3
LD50 (mg/kg)
> 2,000
MRID No.
41607004
Toxicity
Category
Practically
nontoxic
Fulfills
Guideline
Requirement
Yes
Table 7. Avian Subacute Dietary Toxicity Findings
Species
Northern Bobwhite
Mallard
Northern Bobwhite
% A.I.
98.2
98.2
"Technical"
LC50 (ppm)
> 5,000
> 5,000
> 10,000
MRID No.
00114112
00114111
00159177
Toxicity Category
Practically nontoxic
Practically nontoxic
Practically nontoxic
Fulfills
Guideline
Requirement
Yes
Yes
No,
Supplemental
These findings indicate that desmedipham is practically nontoxic to avian species on an
acute oral and subacute dietary basis. The guideline requirements are fulfilled (GLN 71-1, MRID
41607004; GLN 71-2, 00114111 and 00114112).
(2) Birds, Chronic
Avian reproduction studies are required when the persistence, bioaccumulation, or multiple
applications of the pesticide indicate that birds may be exposed repeatedly or continuously, or the
mammalian reproduction tests indicate a reproductive hazard. Avian reproduction studies are
required for desmedipham because it may be applied more than once per growing season.
28
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Table 8. Avian Reproduction Findings
Species
Northern
Bobwhite
Mallard
Duck
%
A.I.
97.8
97.8
NOEC
(ppm)
450
90
LOEC
(ppm)
2500
450
Endpoints Affected
Number of eggs laid and male
body weight
Egg shell thickness, viable
embryos per eggs set, male
body weight
MRID
43544901
43544902
Fulfills
Guideline
Requirement
Yes
Yes
Avian reproductive studies indicate that eggshell thinning could occur at dietary
concentrations above 90 ppm. A 7.5% reduction in egg shell thickness was observed in mallard
ducks fed a diet of 450 ppm desmedipham compared to ducks fed a control diet. This represents
a statistically significant difference. Also, the percent of viable embryos was slightly reduced
from 93% in the control group to 86% in the 450 ppm group. Even though this reduction was
not statistically significant, it was thought to be treatment related. The guideline requirements are
fulfilled (GLN 72-4, MRIDs 43544901 and 43544902).
(3)
Mammals
Wild mammal testing is required on a case-by-case basis, depending on the results of the
lower tier studies (including acute and subacute testing) and such factors as intended use pattern
and pertinent environmental fate characteristics. In most cases, including desmedipham, data
from the available mammalian studies which are used for human health risk assessment and are
discussed above in Section B.I. can be used to estimate the toxicity to wild mammalian species.
The Agency concluded from the available mammalian data that the technical grade active
ingredient (TGAI) of desmedipham is practically nontoxic to the rat (LD50 of > 5000 mg/kg) on
an acute oral basis (MRID 00155581). Typical end-use products (TEPs) also are practically
nontoxic to the rat (LD50 of > 5000 mg/kg for 70% and 35% desmedipham) mammals (MRIDs
42032004 and 42032404). The Agency infers from these conclusions that desmedipham may also
be practically non-toxic to wild mammalian species.
Chronic and subchronic feeding studies indicated that dietary concentrations of
desmedipham of 60 ppm (approximately 5.4 mg/kg/day) or less caused no significant effects.
Concentrations between 250 and 300 ppm (approximately 20 and 26 mg/kg/day) caused effects
on the blood, including increased levels of methemoglobin and hemolytic anemia (MRID
40387103 and 40387105). A decrease in splenic weight was also observed at the 250 ppm level
in rats (MRID 40387105). The ecological significance of these effects on wild mammals is not
known. In a 2-generation rat reproduction study (MRID 40387105), reductions in body weights
of adults and pups were observed at a concentration of 1250 ppm (approximately 100 mg/kg/d).
The NOEL for these gross effects, which are more likely to be ecologically significant, is 250
ppm or 20 mg/kg/day.
29
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Several studies with mammals have shown that desmedipham causes decreased levels of
thyroid hormones. This appears to be due to compensatory function of the thyroid in response
to effects on the blood. This effect is reversible and is not judged to be of significance to wild
mammals. Desmedipham does not appear to have a direct toxic effect on the thyroid gland.
(4)
Insects
A honey bee acute contact LD50 study is required if the proposed use will result in honey
bee exposure. Because sugar beets is not a crop that is normally associated with high exposure
to bees, it is not expected that honey bees will be exposed to desmedipham. However, the
following nontarget insect toxicity data are available.
Table 9. Nontarget Insect Acute Contact Toxicity Findings
Species
Honey Bee
% A.I.
97.5
LD50
(ug a.i./bee)
> 50a
MRID No.
41711402
Toxicity Category
Practically nontoxic
Fulfills Guideline
Requirement
Yes
* This study also found that the acute oral toxicity of desmedipham to the honey bee is > 50 ug a.i./bee.
There is sufficient information to characterize desmedipham as practically nontoxic to
bees. The guideline requirement is fulfilled (GLN 141-1, MRID 41711402).
b. Toxicity to Aquatic Animals
(1) Freshwater Fish
In order to establish the toxicity of desmedipham to freshwater fish, the minimum data
required on the technical grade of the active ingredient are two freshwater fish toxicity studies;
one study with a coldwater species (preferably the rainbow trout), and the other with a warm
water species (preferably the bluegill sunfish).
Table 10. Freshwater Fish Acute Toxicity Findings (96 hr)
Species
Rainbow trout
Bluegill sunfish
% A.I.
98.4
98.4
LC50
(ppm)
1.7
6.0
MRID No.
00116714
00116713
Toxicity Category
Moderately toxic
Moderately toxic
Fulfills
Guideline
Requirement
Yes
Yes
The results of the 96-hour acute toxicity studies indicate that desmedipham is moderately
toxic to fish. The guideline requirements are fulfilled (GLN 72-1, 00116713, 00116714).
Fish early life-stage, fish life-cycle or aquatic invertebrate studies have not been required
for desmedipham because it appears to have low toxicity to aquatic organisms, it is not expected
30
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to be continuously or recurrently present in water, and it is generally not very persistent in water
(see Section C.2. below).
(2)
Freshwater Invertebrates
The minimum testing required to assess the toxicity of desmedipham to freshwater
invertebrates is a freshwater aquatic invertebrate acute toxicity test, preferably using first instar
Daphnia magna or early instar amphipods, stoneflies, mayflies, or midges.
Table 11.
Species
Daphnia magna
% A.I.
96
FT
f^so
(mg a.i./L)
1.88
MRID NO.
00116712
Toxicity Category
Moderately Toxic
Fulfills
Guideline
Requirement
Yes
There is sufficient information to characterize desmedipham as moderately toxic on an
acute basis to aquatic invertebrates. The guideline requirement is fulfilled (GLN 72-2, MRID No.
00116712).
Aquatic invertebrate life-cycle studies have not been required for desmedipham because
it appears to have low toxicity to aquatic organisms, it is not expected to be continuously or
recurrently present in water, and it is generally not very persistent in water.
(3)
Estuarine and Marine Animals
Acute toxicity testing with estuarine and marine organisms is required when an end-use
product is intended for direct application to the marine/estuarine environment or is expected to
reach this environment in significant concentrations. Use of desmedipham on sugar beets and
Swiss chard is not expected to result in significant exposure to marine or estuarine environments.
There are therefore no data requirements under this category.
c. Toxicity to Plants
(1) Terrestrial
Terrestrial plant testing (seedling emergence and vegetative vigor) are generally required
for herbicides with terrestrial non-residential use patterns to assess risk to nontarget plants. The
vegetative vigor study is specifically required for chemicals which may move off-site through
volatilization (vapor pressure >105 mm Hg at 25°C) or drift (applied aerially or through
irrigation), and/or which may have endangered or threatened plant species associated with the site
of application. The seedling emergence study is required for chemicals with a solubility greater
than 10 ppm, or when it is applied aerially or through irrigation. These tests are required for
31
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desmedipham because it is an agricultural herbicide that can be aerially applied and because it may
affect endangered plant species which are associated with the areas where sugar beets are grown.
Tier I plant tests are screening tests to evaluate the affects of the maximum application rate
on plants. If the maximum rate results in greater than a 25% effect compared to the control
plants, Tier II plant tests are required. Tier II tests use a series of test levels to measure the dose
response. Regression analysis is used to derive EC25 values, which are defined as the estimated
levels at which 25% effects, compared to control plants, are anticipated.
Results of reviewed terrestrial plant toxicity data (Tier I) on technical desmedipham are
listed below:
Table 12. Tier I Nontarget Terrestrial Plant Toxicity Findings (Exposure = 1.26 Ib a.i./A)
Study Type
Seed Germination
Seedling
Emergence
Vegetative Vigor
MRID No.
41711401
41774101
41816401
Species
Soybean, lettuce, carrot, tomato,
cucumber, radish, corn, oat, wheat, and
onion
Soybean, carrot, cucumber, corn, oat,
and wheat
Lettuce
Tomato
Radish
Onion
Soybean, carrot, corn, oat, wheat, and
onion
Radish
Lettuce
Tomato
Cucumber
% A.I
98
98
98
98
98
98
98
98
98
98
98
Response
Not significant
Not significant
60% reduction in fresh wt.
25% reduction in fresh wt.
20% reduction in fresh wt.
40% reduction in fresh wt.
Not significant
20% reduction in fresh wt.
39% reduction in fresh wt.
Chlorosis
Chlorosis
Fulfills
Guideline
Requirement
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Based on responses in the above tier I data, a tier II vegetative vigor study using technical
grade desmedipham (TGAI) was required for lettuce and a tier II seedling emergence study with
TGAI was required for tomato, onion, and lettuce. Tier II seedling emergence and vegetative
vigor tests with a typical end-use product (TEP) were also required for tomato, onion, lettuce,
corn, soybean, and radish along with four of the most sensitive species listed on the label. Results
of reviewed tier II terrestrial plant toxicity data on technical desmedipham for the most sensitive
species are listed below:
32
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Table 13. Tier II Nontarget Terrestrial Plant Toxicity Findings
Study Type
Seedling Emergence
(TGAI)
Vegetative Vigor
(TGAI)
MRID No.
Author/Year
42366302
42366301
%
A.I.
98
98
Plant
Type
Monocot
Dicot
Dicot
Dicot
Species
Onion
Lettuce
Tomato
Lettuce
NOEL
(Ib a.i./A)
0.30
0.30
0.15
1.22
EC25
(Ib
a.i./A)
0.58
0.40
0.31
>1.22
Fulfills
Guideline
Requirement
Partially1
Partially1
1 Seedling emergence and vegetative vigor testing with a TEP is required to fulfill these guidelines.
The results in Table 13 show that when desmedipham is applied without adjuvants,
exposure levels of 0.31 Ib a.i./A or greater can cause significant detrimental effects on the
germination and emergence of certain plants. The results from the vegetative vigor test indicate
that desmedipham applied as the TGAI is not toxic at normal use rates. (NOEL of 1.22 Ib/A,
compared to the maximum label rate of 1.26 Ib ai/A). The Agency believes that the adjutants
normally present in the TEPs must be present for desmedipham to express toxicity to plants.
Therefore, testing with a TEP is needed to estimate the toxicity during normal use of
desmedipham on the foliage of nontarget terrestrial and semi-aquatic plants. The guideline
requirements are only partially fulfilled (GLN 123-1 (a), 123-1 (b), MRIDs 42366301 and
42366302).
(2) Aquatic
Aquatic plant testing is required for any herbicide which has terrestrial non-residential uses
and may move off-site by runoff (solubility > 10 ppm in water) or by drift (aerial or irrigation
applications), is applied directly to aquatic use sites, or may affect endangered plant species. This
testing is required for desmedipham because it is an agricultural herbicide which may be applied
aerially and may effect endangered plant species which are associated with the sugar beet site.
Testing is required with the following species: Kirchneria subcapitata, Lemna gibba,
Skeletonema costatum, Anabaena flos-aquae, and a freshwater diatom.
Results of reviewed tier I and II aquatic plant toxicity data on technical desmedipham are
listed below:
Table 14. Nontarget Aquatic Plant Toxicity Findings
Species
Navicula pelliculosa (Freshwater diatom) , Tier 2
Lemna gibba, Tier 1
Kirchneria subcapitata, Tier 2
Skeletonema costatum, Tier 1
Anabaena flos-aquae, Tier 1
% A.I.
98
98
98
98
98
EC50
(mg a.i./L)
0.044a
>0.33a
0.19a
>0.3a
>0.22a
MRID No.
43053503
43053505
43053501
43053504
43053502
Fulfills Guideline Requirement
Yes
Yes
Yes
Yes
Yes
aBased on estimated 5-day mean concentrations.
33
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The results also indicate that mean 5-day exposure levels of desmedipham at 0.044 mg
a.i./L or greater concentrations can cause significant detrimental effects on the growth and
reproduction of certain single-celled aquatic plants. The guideline requirements are fulfilled
(GLN 122-2, MRIDs 43053502, 43053504, and 43053505; GLN 123-2, MRIDs 43053501 and
43053503).
2. Environmental Fate
Although the environmental fate database is not complete, there is sufficient acceptable and
supplemental environmental fate information for the Agency to conclude that desmedipham will
not persist in the environment. The primary degradation pathway for desmedipham is hydrolysis
to ethyl-(3-hydroxyphenyl) carbamate (EHPC) and aniline, with further degradation by microbial
processes to C02. Photodegradation, volatilization, and bioaccumulation in fish do not appear to
contribute significantly to the dissipation of desmedipham. Desmedipham and EHPC have a low
potential to leach to ground water in most soils. It is expected that desmedipham residues which
reach surface water by either spray drift or runoff will be rapidly degraded.
The following additional confirmatory information has been requested to perform a more
comprehensive environmental fate assessment:
• The material balances during hydrolysis of desmedipham at pHs 5 and 7 (GLN 161-1);
• Pedological characteristics of the test soils used during the aerobic soil metabolism (GLN
162-1), anaerobic aquatic metabolism (GLN 162-3), and the column leaching (GDLN
163-1) studies.
• Stability during frozen storage of the field samples of the terrestrial field dissipation study
(GLN 164-1).
If the confirmatory information is acceptable, these studies can be upgraded to acceptable
and the data requirements will be fulfilled. Data to characterize desmedipham's spray drift
potential from aerial and ground applications have been recently submitted by the industry Spray
Drift Task Force. The Agency has not evaluated these data at the drafting of this document, but
will do so in the near future.
a. Environmental Fate Assessment
The primary degradation pathway for desmedipham is hydrolysis to ethyl-(3-
hydroxyphenyl) carbamate (EHPC) and aniline, with a half-life at pH 7 of 17-20 hours; at pH 9,
the half-life is 7-10 minutes. Hydrolysis of desmedipham is slower at lower pH, which is
characteristic of chemicals containing ester linkages. EHPC is then further degraded by microbial
processes to C02. Information available in the open literature indicates that aniline is rapidly
degraded by microorganisms to C02 and is also directly incorporated into bound residues
(Verschueren, 1977; Government of Canada, 1994). Desmedipham photodegrades slowly in
34
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water and on soil (half-lives > 100 hours), which indicates that, in comparison to hydrolysis,
photodegradation will not be a major degradation process in neutral to alkaline environments.
Adsorption/desorption data for desmedipham could not be obtained using batch equilibrium
methods due to the rapid hydrolysis of desmedipham to EHPC at pHs >5. Column leaching
studies indicated that desmedipham and its transformation product EHPC do not leach readily.
Following 45 days of continuous irrigation, <3% of the applied radioactivity was detected in the
leachate of treated soil columns. In addition, greater than 95% of the radioactivity applied
remained in the top 5-6 cm of the columns. In laboratory studies, desmedipham was seen to
bioaccumulate to a small extent in bluegill sunfish (maximum bioconcentration factors of 2OX,
98X, and 159X for fillet, whole fish, and viscera, respectively); however, residues were
depurated rapidly (> 90% by 7 days). Supplemental information from field dissipation studies
indicates that the DT50 (the time it takes for 50% of the applied material to dissipate) of
desmedipham when applied to sugar beets in California was 7 days; supplemental information
from a North Dakota study site indicates an even shorter half-life on alkaline soils (estimated <
1 day on soil of pH > 7.3).
Based on these data, the Agency concludes that desmedipham has a low potential to leach
to ground water in most soils. Data support a finding that desmedipham would not persist in
neutral to alkaline surface waters which would typically be found in areas of sugar beet
production. It may contaminate surface water from spray drift associated with ground or aerial
application. Desmedipham will adsorb to soil particles and may be transported by surface runoff
to surface water bodies on entrained sediment. However, rapid degradation by abiotic hydrolysis
and microbial-mediated metabolism should result in low concentrations in surface waters. Multi-
residue monitoring data in several states with sugar beet production (California, Washington, and
Minnesota) did not report the presence of desmedipham in surface waters.
b. Environmental Fate and Transport
(1) Degradation
Abiotic Hydrolysis
The rate of hydrolysis of desmedipham is pH dependent, with rapid hydrolysis occurring
under alkaline conditions. A confirmed half-life of 7-10 minutes was reported for pH 9 buffered
aqueous solutions; supplemental information from unacceptable hydrolysis studies provided half-
lives of 1417 to 1897 hours (59 to 79 days) at pH 5 and 17 to 20 hours at pH 7. The hydrolysis
products, aniline and ethyl N-(S-hydroxyphenyl) carbamate (EHPC), formed in equimolar
amounts at pH 9. After 50 minutes at pH 9 (at which time hydrolysis of desmedipham was
essentially complete), aniline and EHPC did not appear to degrade. The guideline requirement
is partially fulfilled (GLN 161-1 [pH 9], MRID 00142740).
The unacceptable hydrolysis studies conducted at pHs 5 and 7 may be upgradeable if the
registrant provides acceptable material balances for those studies.
35
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Photodegradation
Photodegradation in water: Desmedipham, at a concentration of 8 ppm in pH 3.8
buffered aqueous solution, photodegraded with a half-life of 10 hours when irradiated for 355
hours with a Hg-arc vapor lamp which had a light intensity approximately an order of magnitude
greater than that of sunlight in the 290 to 320 nm wavelength range. Desmedipham did not
degrade in the dark control (no light exposure) samples, indicating that desmedipham was stable
to hydrolysis at pH 3.8. The transformation product EHPC was present at approximately 10%
of the applied after 10 hours of irradiation; other minor photoproducts were ethyl N-(3-hydroxy-
4-phenyl carbamylphenyl) carbamate, and ethyl N-(2-phenylcarbamyl-5-hydroxyphenyl)
carbamate, each at less than 1%. Concentrations of EHPC increased with increasing time of
exposure; it did not appear to photodegrade (radioactivity in other HPLC fractions did not
increase).
The Agency does not currently accept photodegradation studies performed using a Hg
vapor lamp because the emission spectrum is not similar to that of natural sunlight. In this study,
samples at pH 3.8 were irradiated continuously with light of at least an order of magnitude greater
intensity than natural sunlight at the wavelengths (< 300 nm) at which desmedipham can
photodegrade. Although the conditions of the study show that desmedipham can photodegrade
in water, the rate of photodegradation is expected to be much slower than that of the primary
mechanism of degradation (hydrolysis) under natural conditions. It is not expected that
photodegradation in water will contribute significantly to the dissipation of desmedipham in the
environment. The guideline requirement is fulfilled (GLN 161-2, MRIDs 00098607 and
41446101).
Photodegradation on soil: Aminophenyl ring-labelled 14C-desmedipham and aniline ring-
labelled 14C-desmedipham photodegraded under a xenon arc lamp with calculated half-lives
ranging from 110 to 160 hours. Sandy loam soil films were exposed to light of an intensity
approximately 3 times that of summer solar irradiation at noon at 50°N. In the dark control
samples, desmedipham degraded with a half-life of greater than 500 hours in the aminophenol
ring-labelled samples; degradation in the aniline ring-labelled samples was < 10% after 238 hours
of irradiation. The major non-volatile transformation product identified in extracts of irradiated
soil samples was EHPC, which is a known hydrolysis product. Maximum concentrations of
EHPC were 7.4% after 488 hours of irradiation of aminophenyl labelled 14C-desmedipham and
2.9% after 238 hours of irradiation of aniline ring-labelled 14C-desmedipham. The only volatile
transformation product was carbon dioxide; maximum concentrations were 26.4 to 28.8%. The
guideline requirement is fulfilled (GLN 161-3, MRID 00098608).
Volatilization into the Atmosphere and subsequent photodegradation: No data were
reviewed for photodegradation in air (GLN 161-4). The requirement for this environmental fate
study was waived due to the low vapor pressure (3 x 109 Torr) of technical desmedipham (GLN
63-9, MRID 41937501). The low vapor pressure and the small Henry's Law constant (which is
an indication of the low tendency for the material to volatilize from water; estimated to be 1.69
x 1010 atm-m3 mol4) indicate that would not be a significant route of dissipation for desmedipham.
36
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Aerobic Soil Metabolism
Supplemental information indicates that desmedipham degraded with a calculated half-life
of 7.7 days when applied at a rate of 2.9 ppm to German Standard Soil 2.3 (described by the
study author as a sandy loam soil) which was incubated aerobically at 21 °C. The estimated DT90
(the time required from 90% of the applied material to degrade) was 29.1 days. The
transformation product EHPC reached a maximum of 4.5% (»0.09 ppm) of applied radioactivity
at day 14 post-treatment, and decreased to 0.9% of the applied by 100 days post-treatment.
Several other non-volatile transformation products were detected by TLC during the testing
period; however, none were present at >2.7% of the applied. The level of evolved 14C02
steadily increased during the testing period. The percentage of evolved 14C02 reached 15.4% by
day 30 post-treatment and a maximum of 29.1% by day 100 post-treatment. Other volatiles were
not discernible in any of the volatile traps during the testing period. Bound residues increased
from 1.1% of applied radioactivity at day 0 to a maximum of 61.7% of applied radioactivity at
day 71 post-treatment. There was a slight decrease to 59.1% by day 100. The bound soil
residues were further characterized into fulvic acid, humic acid, and humin fractions; the amounts
of applied radioactivity in the various fractions stabilized between days 30 and 100, and were 14-
17%, 19-23%, and 21-26% of the applied, respectively.
It is recommended that soils typical of the use sites in the U.S. be used in aerobic soil
metabolism studies. If other non-domestic soils are used, those soils must be comparable to U.S.
soils. The soil used in this study was a German soil (Standard soil 2.3), but the registrant did not
provide pedological characteristics for that soil (including but not limited to clay mineralogy,
Great Soil Group classification, vegetation, climatological conditions, etc.). Because the Agency
cannot evaluate whether this soil is comparable to a U.S. soil, the study is not acceptable at this
time. However, the study may be upgradeable to acceptable if the registrant provides adequate
information on the pedological characteristics of the German Standard soil and its characteristics
are substantially similar to a U.S. soil in which sugar beets are grown. The guideline requirement
is not fulfilled (GLN 162-1, MRID 41998601).
Anaerobic aquatic metabolism
Supplemental information from an unacceptable study indicates that desmedipham
hydrolyzed rapidly (< 2 hours) to EHPC when added to an anaerobic aquatic system. Therefore,
the study authors were unable to determine an exact half-life for desmedipham under anaerobic
conditions. The observed rapid hydrolysis of desmedipham under the conditions of the study is
consistent with other information reviewed by the Agency (MRID 00142740) and reported above.
Supplemental information from an unacceptable study indicates that EHPC degraded with
a half-life of 211.9 days when applied as desmedipham to an anaerobic German sediment. At 2
hours and 2 days post-treatment, 15.3% and 8.9% of applied radioactivity, respectively, remained
as desmedipham. EHPC increased to concentrations of 74.7% and 87.7% at days 2 and 15 post-
treatment, respectively, and decreased to 50% by the termination of the study (100 days post-
treatment). No further breakdown products and very little C02 (total = 4.1% of applied
37
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radioactivity) were discernible during the testing period. Therefore EHPC is assumed to be stable
to degradation under anaerobic conditions.
This study is not acceptable at this time due to deficiencies in the study, but may be
upgradeable to acceptable if confirmatory data are submitted by the registrant. The guideline
requirement is not fulfilled. (GDLN 162-3, MRID 41998601)
(2) Mobility
Adsorption/desorption studies
Adsorption/desorption data for desmedipham could not be obtained using the batch
equilibrium method due to the rapid hydrolysis of desmedipham to EHPC at pHs >5. However,
information on the mobility of desmedipham could be obtained from column leaching studies.
Aged/unaged column leaching studies
Supplemental information indicates that desmedipham and its transformation product
EHPC were relatively immobile when 14C-desmedipham (labelled in each ring) was applied to
German soil columns irrigated with water at a rate of 25 mL/day (total of 1125 mL over 45 days).
Following the 45 days of continuous irrigation, <3% of applied radioactivity was detected in the
leachate of the treated soil columns. In addition, greater than 95% of the radioactivity applied
remained in the top 5-6 cm of the columns; roughly half of this was extractable with methanol and
was comprised of both desmedipham and EHPC. 14C02 produced during the 30-day aging period
prior to leaching reached 15.4% and 4.1% of applied radioactive in the aminophenoxy- and
phenyl-labelled desmedipham treated columns, respectively.
Supplemental mobility data have shown similar results. In unacceptable aged soil column
studies using German soils, desmedipham residues did not leach. Soil TLC mobility studies are
not acceptable at this time but do provide some supplemental data. The mobility of desmedipham
applied to thin layers of soil on glass plates that were then eluted with water was compared to
pesticides of known mobility applied to the same plates. Kds were then calculated from the Rf's
and the soil/water partition coefficients for selected pesticides; these calculated Kds ranged from
100 to 158 ml/g, which would indicate that desmedipham was immobile. The USDA/Soil
Conservation Service (SCS) database reports a Koc for desmedipham of 1500 (Wauchope et al.,
1992).
At this time, soils information to upgrade the column leaching study is still required. The
guideline requirement is not fulfilled. (GLN 163-1; MRIDs 41214709, 42281403, 42124202,
41214708).
38
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Volatility studies
No laboratory volatility (GLN 163-2) or field volatility (GLN 163-1) studies were
reviewed for desmedipham. The requirement for these environmental fate studies was waived due
to the low vapor pressure (3 x 109 Torr) of technical desmedipham (GLN 63-9, MRID
41937501). The low vapor pressure and the small Henry's Law constant (which is an indication
of the tendency for the material to volatilize from water; estimated to be 1.69 x 10 10 atm-m3 mol"1)
indicate that volatilization from soil or water would not be a significant route of dissipation for
desmedipham.
(3) Accumulation
Bioaccumulation in Fish:
Results from accumulation in fish studies are used to estimate the bioconcentration
potential of the parent pesticide under controlled laboratory conditions. Bluegill sunfish exposed
to 14C-desmedipham (labelled in the aminophenol ring only) at a concentration of 0.056 mg/L for
10 days, reached maximum bioconcentration factors of 20X, 98X, and 159X for fillet, whole fish,
and viscera, respectively. During a 7-day depuration period 90%, 91%, and 93% depuration was
reported for fillet, whole fish, and viscera, respectively. During the testing period the test fish
showed no ill effects from the desmedipham-treated water. Very little parent desmedipham was
detected in fish tissues (< 1%); approximately 80% of the residues found in the fish tissues were
EHPC and N-(3-hydroxyphenyl) acetamide, both free and as conjugates (probably glucuronides).
It is recommended that each ring of a double ring compound be radiolabelled and be used in
separate bioaccumulation in fish studies in order to fully understand a pesticide's metabolic
pathway.
Desmedipham contains an aminophenol ring and an aniline ring; acceptable
bioaccumulation data for desmedipham labelled in the aminophenol ring were reported in this
study. The potential for the aniline ring to bioaccumulate in fish tissues can be inferred from its
solubility and its octanol-water partition coefficient. A combination of a high water solubility
(34,000 mg/L; Verschueren, 1977) and a low tendency to partition into organic solvents (0.8:1.0,
n-octanol:water; Chiou, et al., 1982) would predict little or no bioaccumulation in fish. In
laboratory tests, aniline does not appear to accumulate in aquatic biota (Government of Canada,
1994). Therefore, no further data for the bioaccumulation in fish of desmedipham radiolabelled
in the aniline ring are needed at this time. The guideline requirement is fulfilled (GLN 164-5;
MRID 42710101).
(4) Field Dissipation
Supplemental information from an unacceptable field dissipation study conducted in 1989
indicates that desmedipham dissipated with a registrant-calculated half-life of 30 days when
applied twice in 7 days (total application 2.19 Ib a.i./A as Betanex EC) to sugar beets planted on
loamy sand soil in the spring of 1989 in Fresno, California. The maximum mean concentration
39
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of desmedipham in the 0- to 3-inch depth was 0.95 ppm at 1 day post-treatment (the second
application date was designated by the study author as time 0); mean concentrations decreased to
0.22 and 0.07 ppm by 28 days and 2 months post-treatment, respectively.
Data were also reported for a second site in Northwood, North Dakota treated in 1989;
however, the data from this site were variable and inconsistent. This may have been due to
contamination of the test site, which was indicated by the presence of apparent residues of
desmedipham and EHPC in soil samples taken from the untreated control plots at that site. In
addition, since no samples were taken from the treatment plots prior to application, it could not
be determined if those plots also contained apparent residues. Therefore, a detailed conclusion
as to the dissipation or potential for leaching of desmedipham under field conditions at this site
was not possible. The study author estimated an apparent DT50 of 0.7 days; however, the
registrant did not calculate a half-life because the data were too variable. At soil depths down to
18 inches, reported levels of both desmedipham and EHPC were greater than the detection limit
(0.005 ppm) at all sampling intervals up to 7 days following the second application; however,
levels in the control samples were also greater than above the detection limit for that time interval.
It is therefore not possible to determine whether detections of desmedipham at those depths were
due to movement of residues or contamination of the site. The rapid disappearance of
desmedipham in North Dakota compared to that observed in California could be due to differences
in soil pH; pHs were 7.3 and 6.4 at the North Dakota and California sites, respectively.
The portion of the study conducted in North Dakota is unacceptable because of the
apparent contamination of the test soils and cannot be upgraded with the submission of additional
data.
The portion of the study conducted in California is not acceptable at this time because the
stability of desmedipham residues during frozen storage was not provided. Soil samples were
stored for up to 18 months before analysis. Because desmedipham hydrolyzes rapidly at neutral
to alkaline pHs, there is a possibility that any desmedipham residues in the test soils at time of
sampling may have degraded during storage.
However, the study may be upgradeable to acceptable if the registrant provides
information that shows that desmedipham is stable during a period of frozen storage of up to 18
months. The guideline requirement is not fulfilled (GLN 164-1, 42180501).
(5) Spray Drift
No desmedipham-specific studies were reviewed. Droplet size spectrum (GLN 201-1) and
drift field evaluation (GLN 202-1) studies were required for desmedipham, since the different
products may be applied by aircraft and it is estimated that there will be detrimental effects to
non-target organisms due to drift. However, to satisfy these requirements the registrant in
conjunction with other registrants of other pesticide active ingredients formed the Spray Drift
Task Force (SDTF). The SDTF has completed and submitted to the Agency its series of studies
which are intended to characterize spray droplet drift potential due to various factors, including
40
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application methods, application equipment, meteorological conditions, crop geometry, and
droplet characteristics. During 1996 EPA plans to evaluate these studies. In the interim and for
this assessment of desmedipham the Agency is relying on previously submitted spray drift data
and the open literature for off-target drift rates. The estimated drift rates at 100 feet down wind
of the treated sites are 1% of the applied spray volume from ground applications and 5% from
aerial applications. After its review of the new studies the Agency will determine whether a
reassessment is warranted of the potential risks from the application of desmedipham products to
sugar beets.
c. Water Resources
(1) Ground Water
The Agency found no indication that desmedipham would exceed any ground water LOG
endpoints. Although desmedipham exceeded one of the persistence triggers (calculated field
dissipation half-life), hydrolysis data indicate that desmedipham will hydrolyze rapidly in neutral
to alkaline pH soils. In addition, the high Kd and Koc values demonstrate that desmedipham will
bind strongly to soil organic matter and is not mobile. Based on the data available, desmedipham
does not meet sufficient ground water triggers. The Agency has no reports of sampling for
desmedipham in ground water (Hoheisel, et al., 1992). The Agency concludes that desmedipham
has a low potential to leach to ground water in most soils.
(2) Surface Water
Transport of desmedipham would be limited in surface runoff events for alkaline (pH 8-9)
aqueous environments due to its rapid hydrolysis (Section C.2.). However, if surface runoff from
acidic (< pH 7) environments should occur within a few days of the time of application, an
undetermined fraction of the applied may be available to runoff. The solubility (7 ppm) and the
intermediate Koc (1500 from (United States Department of Agriculture/ Agricultural Research
Service) database; and estimated Kds of 100-150 ml/g) of desmedipham indicate it could move
both in the dissolved phase and as sorbed residues to eroding soil. The soil may be transported
and deposited as sediment in streams, rivers, lakes and ponds during runoff events.
In neutral to alkaline receiving surface water bodies (rivers, streams, lakes, etc.),
desmedipham will hydrolyze fairly rapidly. However, in acidic waters, desmedipham may persist
and distribute itself between the dissolved phase and that sorbed on suspended sediments. The
transformation product EHPC may persist in the anaerobic water/sediment environment associated
with bottom sediments. Volatilization of desmedipham from surface waters is not considered an
important route of dissipation based on the low Henry's Law constant (1.69 x 10 10 atm-m3 mol"1,
estimated). Based on the bioconcentration factors, which ranged from 20X to 159X, and
depuration of > 90% in 7 days, desmedipham should not significantly bioaccumulate.
41
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3. Exposure and Risk Characterization
Explanation of the Risk Quotient (RQ) and the Level of Concern (LOG): The Levels
of Concern are criteria used to indicate potential risk to nontarget organisms. When an LOC is
exceeded by the RQ, it indicates that a chemical, when used as directed, has the potential to cause
undesirable effects on nontarget organisms. There are two general categories of LOC (acute and
chronic) for each of the four nontarget faunal groups and one category (acute) for each of two
nontarget floral groups. In order to determine if a particular LOC has been exceeded, a risk
quotient must be derived and compared to that LOC. A risk quotient is calculated by dividing an
appropriate exposure estimate, e.g. the estimated environmental concentration (EEC), by an
appropriate toxicity test effect level, e.g. the LC50. The acute effect levels typically are:
• EC25 for terrestrial plants,
• EC50 for aquatic plants and invertebrates,
• LC50 for fish and birds, and
• LD50 for birds and mammals.
The chronic test results are the NOEL (sometimes referred to as the no-observed-effect
concentration or NOEC) for avian and mammal reproduction studies, and either the NOEL or the
MATC (maximum allowable toxicant concentration) for chronic aquatic studies. The MATC is
defined as the geometric mean of the NOEL and the LOEL (sometimes referred to as the low-
observed-effect concentration or LOEC).
When the risk quotient exceeds the LOC for a particular category, potential risk to that
particular category is presumed to exist. Risk presumptions are presented along with the
corresponding LOCs.
Table 15. Levels of Concern (LOC) and associated Risk Presumption
IF THE
LOC
PRESUMPTION
Mammals, Birds
acute RQ >
acute RQ >
acute RQ >
chronic RQ >
0.5
0.2
0.1
1
Acute risk
Risk that may be mitigated through restricted use
Endangered species may be affected acutely
Chronic risk, endangered species may be affected chronically,
Fish, Aquatic invertebrates
acute RQ >
acute RQ >
acute RQ >
chronic RQ >
0.5
0.1
0.05
1
Acute risk
Risk that may be mitigated through restricted use
Endangered species may be affected acutely
Chronic risk, endangered species may be affected chronically
Plants
RQ>
RQ>
1
1
Risk
Endangered plants may be affected
Currently, no separate criteria for restricted use or chronic effects for plants exist.
42
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(1) Exposure and Risk to Nontarget Terrestrial Animals
(a) Birds
Pesticide residues found on avian dietary food items following application were compared
to LC50 values to predict hazard for birds. The Agency estimated the day 0 residues on vegetation
based on the work of Hoerger and Kenaga (1972) as modified by Fletcher et al. (1994).
Maximum residues on vegetative food items were estimated using a program for calculating daily
estimated residues based on repeated applications and first-order kinetics at an assumed rate (Lee,
n.d.). For the purpose of determining acute exposure, the maximum residues of desmedipham
are expected to occur immediately after the second of two applications. Based on label
information, the use rate per application was assumed to be 0.98 Ib ai/A, one-half of the
maximum per growing season rate of 1.96 Ib ai/A. The interapplication interval is assumed to
be 7 days, during which time the residues from the first application would partially degrade.
Based on the half-life for aerobic soil metabolism (7.7 days) and soil photolysis (6.6 days), the
half-life of the overall degradation of desmedipham on vegetation was estimated to be
approximately 7 days. This half-life may over-estimate persistence since a supplemental study
of hydrolysis at pH 7.0 suggested a half-life of only 17-22 h. The estimated peak residues (i.e.
EECs) on selected avian dietary food items, and their corresponding RQs, are given in the table
below:
Table 16. Estimated Environmental Concentrations and Dietary Risk Quotients for Birds
(Based on LC50 > 5000 ppm)
Food items
Short Grasses
Tall Grasses
Broadleaved Plants and Insects
Fruits and Pods
EEC (ppm)
353
162
198
22.1
RQ
< 0.071
< 0.032
< 0.040
< 0.0044
Because of the low acute toxicity of desmedipham to birds, the risk quotients for use of
desmedipham are very low. No RQ exceeds the LOG for high risk to birds (1) or the LOG for
possible effects to endangered species (0.1). Therefore, the use of desmedipham is expected to
pose negligible acute risk to endangered and nonendangered species of birds.
43
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Expected Residues on Wildlife Food
Single Applications at 1.26 Ib ai/A
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Time After Application (Days)
The chronic toxicity of desmedipham is considerably greater than the acute toxicity. The
NOEL for egg shell thinning in birds is 90 ppm. The same program (Lee, n.d.) was used to
estimate expected residues on wildlife food items over time following a single and two repeated
applications. As for acute exposure, desmedipham was assumed to degrade on vegetation with
a half-life of 7 days. The graph above depicts the predicted residues on plants, relative to the
NOEL, following a single application. When the residue levels exceed the NOEL, the RQ is
greater than the LOG of 1, indicating risk of reproduction impairment. The predicted plant
residues exceed the NOEL for 4, 6, and 12 days on tall grass, broadleafs, and short grass,
respectively. Predicted residue levels are always less than the LOEL of 450 ppm. Thus, a single
application of desmedipham at the maximum label rate is predicted to result in exposures to birds
for 4 to 12 days that are between the level demonstrated to cause egg shell thinning (the LOEL)
and the level demonstrated to be safe (the NOEL). The Agency concludes that desmedipham may
pose a chronic risk to birds at this application rate.
44
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Expected Residues on Wildlife Food
Two Applications at 0.98 Ib ai/A Each
400^
350-
300-
6. 250-
ffl 200-
"D
'55
v>^ "•-,.
6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Time After First Application (days)
A similar situation occurs when desmedipham is applied twice at a rate of 0.98 Ib ai/A
each application, with an inter application interval of 7 days. This rate is one-half the maximum
rate allowed per growing season. The following graph shows the expected residues on wildlife
food relative to the NOEL. The residues on short grass exceed the NOEL for a full 21 days, and
residues on tall grass and broadleafs exceed the NOEL for two short intervals that range from
approximately 2 to 9 days. Residues never exceed the LOEL of 450 ppm. As before, the Agency
concludes that desmedipham may pose a chronic risk to birds at this application rate.
(b) Mammals
Small mammal acute hazard is addressed using the acute oral LD50 value from the rat study
described above (Section III.B), converted to estimate a LC50 value for dietary exposure. The
estimated LC50 is derived using the following formula:
LD5Q X body weight (g)
food consumed per day (g)
45
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Estimated mammalian LC50 values for three species of small mammals are presented below:
Table 17. Estimated Small Mammal Dietary Exposure in PPMs (Based on an LD50 > 5000 mg/kg)
Small Mammal
Meadow vole
Adult field mouse
Least shrew
Body Weight
(s)
46
13
5
Percent of Weight
Eaten Per Day
61 %
16%
110%
Food Consumed
Per Day (g)
28.1
2.1
5.5
Estimated LC50
(ppm)
> 8200
> 31,000
> 4550
The above table is based on information contained in Principles of Mammalogy by D. E. Davis and F. Golly, published by Reinhold Corporation,
1963.
The risk quotients are calculated by dividing the EECs residues by the estimated LC50s.
The table below shows the risk quotients for peak exposures following single and multiple
application:
Table 18. Mammalian Dietary Risk Quotients
Species and Diet
Meadow vole consuming
short grasses
Adult field mouse
consuming seeds
Least shrew consuming
insects
Application Rate (Ib ai/A)
1.26 (single application)
0.98 (two applications)
1.26 (single application)
0.98 (two applications)
1.26 (single application)
0.98 (two applications)
Maximum EEC1 in food item (ppm)
302
348
18.9
21.7
170
194
Risk Quotient
< 0.037
< 0.043
< 0.00061
< 0.00070
< 0.037
< 0.043
Based on Hoeger and Kenaga (1972) with modifications by Fletcher et al. (1994).
The acute mammalian risk quotients for use of desmedipham are very low. None exceed
the LOG for risk to mammals (1) or the LOG for possible effects to endangered species (0.1).
Therefore, the use of desmedipham at the above application rate and based on the acute oral
toxicity of desmedipham to the rat is expected to pose negligible acute risk to endangered and
nonendanged species of mammals.
Mammals also may suffer subchronic or chronic effects, depending on the chronic toxicity
of the chemical and the degree and duration of exposure to the organism. The toxicity to wild
mammals is probably best represented by subchronic and reproductive toxicity studies with the
laboratory rat, as described in sections B.l.b. and B.l.e.) respectively. A subchronic feeding
study yielded a NOEL of 60 ppm and an LOEL of 300 ppm (MRID 40387102). These values
are based on changes observed in the blood which may or may not have ecological significance
to the survival and reproduction of wild mammals. A 2-generation reproduction study found
similar blood effects at similar dietary concentrations (NOEL = 50 ppm, LOEL = 250
ppm).(MRID 40387105) Gross effects which are likely to have ecological significance (e.g.
decreased weight of parents and pups) were only observed at a dietary concentration of 1250 ppm.
The NOEL for these gross effects was 250 ppm.
Estimates of desmedipham residues in mammalian food are identical to those estimated
previously for avian food. Day 0 estimates were based on the work of Hoerger and Kenaga
(1972) as modified by Fletcher et al. (1994), and the change in residues over time was estimated
46
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using the program described above [Section 3.a.(l)(a)]. The graph below shows the estimated
residues after a single application at the rate of 1.26 Ib ai/A, relative to the two NOEL values
discussed above (60 ppm and 250 ppm).
Expected Residues on Wildlife Food
Single Applications at 1.26 Ib ai/A
300-
Q.
-£=200-
lf>
<0
..
\
*>.
'X.
Legend
Tall Grass
NOEL-Blood Effects
1234567
9 10 11 12 13 14 15 16 17 18 19 20 21
Time After Application (Days)
Residues exceed the NOEL for minor blood effects (60 ppm) for 8 to 16 days. The
residues do not exceed the higher NOEL of 250 ppm except for the first two days of residues on
short grass.
Predicted residues on plants for two repeated applications of 0.98 Ib ai/A, separated by
an interval of 7 days, are depicted in the graph below.
47
-------
Expected Residues on Wildlife Food
Two Applications at 0.98 Ib ai/A Each
CD 150-
CL
Legend
Short Grass
Tall Grass
Broadleaf
NOEL-Blood Effects
NOEL-Gross Effects
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time After First Application (days)
Plant residues are generally greater than the NOEL for minor blood effects for 17 days
or longer. Furthermore, the residues on short grass also exceed the LOEL of 250 ppm for
approximately 4 days. The NOEL for gross effects is exceeded only by residues on short grass
for a duration of approximately 4 days. These residues remain well below the LOEL for gross
effects (1250 ppm). Two applications result in a higher exposure than a single application.
The overall risk of significant chronic effects to mammals from the current use of
desmedipham is presumed to be minimal, as described in the risk characterization section
(C.S.c.).
(c) Insects
Since desmedipham was found to be practically nontoxic to honey bees, no detrimental
effects on honey bees are expected.
(2) Exposure and Risk to Nontarget Aquatic Animals
Expected Aquatic Concentrations: The Agency calculated generic EECs using the
GENeric Expected Environmental Concentration Program (GENEEC). These generic EECs are
designed as a coarse screen and estimate expected concentrations from a few basic chemical
parameters and pesticide product label application information.
48
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GENEEC is a model designed to mimic a PRZM-EXAMS simulation. It uses a chemical's
soil/water partition coefficient and various degradation and metabolic half-life values to estimate
runoff from a 10-hectare field into a 1-hectare by 2-meter deep pond. GENEEC calculates
generic estimated environmental concentration (GEEC) values that are used for both acute and
chronic risk assessments. It considers reduction in dissolved pesticide concentration due to
adsorption of pesticide to soil or sediment, incorporation, degradation in soil before washoff to
a water body, and degradation of the pesticide within the water body. It also accounts for direct
deposition of spray drift onto the water body.
Table 19. The following values were used for input into the GENEEC Program:
Chemical Characteristic
Soil Organic Carbon Partitioning Coefficient
Soil Aerobic Metabolic Half-life
Hydrolysis Half-life
Photolysis Half-life (at pH 7)
Water Solubility
Value
1500
7.7 days
22 h
10 h
7 ppm
The soil organic carbon partitioning coefficient was obtained from the USDA/SCS
database. Other values were obtained from studies submitted to the Agency and are discussed in
the Environmental Fate section of this chapter (section C.2). The hydrolysis and photolysis half-
lives are based on supplemental data. For scenarios with two applications, the interval between
applications was assumed to be 7 days. Spray drift at 100 feet downwind is assumed to be 1%
of the application rate for ground applications and 5% of the application rate for aerial
applications. (A. Jones, pers. comm.)
Table 20. Estimated Environmental Concentrations (Eecs) for
Crop
Sugar Beet
Sugar Beet
Sugar Beet
Sugar Beet
Application
Method
Aerial
Ground
Aerial
Ground
Application
Rate (Ibs
a.i./A)
0.98a
0.98a
1.26
1.26
Number of
Applications
(Interval)
2 (7 days)
2 (7 days)
1
1
Peak
GEEC
(ppb)
14.5
14.1
9.64
9.77
4-day
GEEC
(ppb)
6.65
6.23
4.26
4.29
21-day
EEC
(ppb)
1.32
1.24
0.85
0.85
56-day
EEC
(P.B.)
0.50
0.46
0.32
0.32
This rate is one half of the maximum rate allowed per growing season.
The greatest aquatic environmental concentration of desmedipham is predicted to be 14.5
ppb.. This is the concentration predicted after the second of two aerial applications at 0.98 Ib
ai/A.. Concentrations are predicted to dissipate fairly rapidly. Less than half of the peak
concentration should remain after 4 days, and less than one-tenth should remain after 21 days.
(a)
Freshwater Fish
Using the highest peak EECs (aerial and ground applications, two per year), acute RQs
were calculated for the bluegill and rainbow trout, based on their respective 96-hr LC50s.
49
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Table 21. Acute Risk Quotients (RQ) for Freshwater Fish
Crop and
Application
Method
Sugar Beets,
Aerial
Sugar Beets,
Ground
Application
Rate (Ib ai/A
per application)
0.98
0.98
Peak GEECa
(ppb)
14.5
14.1
Species
Bluegill
Rainbow trout
Bluegill
Rainbow trout
96-hr LC50
(ppb)
6000
1700
6000
1700
Acute RQ
0.0024
0.0086
0.0024
0.0083
The peak GEEC is the highest expected concentration after two equal applications of desmedipham separated by an interval of
7 days.
The RQs for acute risk are all well below the LOCs for presuming risk and possible effects
on endangered species. Use of desmedipham is thus predicted to have little or no acute effects
on freshwater fish.
Due to desmedipham's relatively low acute toxicity to fish and its low persistence in water
(Section C.2.), testing for chronic effects on fish have not been required. The Agency presumes
the chronic risk to freshwater fish is minimal.
(b)
Freshwater Invertebrates
Acute RQs for Daphnia magna were calculated using the same peak EECs as above and
the Daphnia magna 96-hr LC50.
Table 22. Acute Risk Quotients (RQ) for Freshwater Invertebrates
Crop and
Application
Method
Sugar Beets,
Aerial
Sugar Beets,
Ground
Application Rate
(Ib ai/A per
application)
0.98
0.98
Peak
GEEC3
fppb)
14.5
14.1
Species
Daphnia magna
Daphnia magna
96-hr LC50
(ppb)
1880
1880
Acute
RQ
0.0077
0.0075
The peak GEEC is the highest expected concentration after two applications of desmedipham separated by an interval of 7 days.
The RQs for acute risk are all well below the LOCs for presuming risk and possible effects
on endangered species. Use of desmedipham is thus predicted to have little or no acute effects
on freshwater invertebrates.
Due to desmedipham's relatively low acute toxicity and its low persistence in water
(Section C.2.), testing for chronic effects on invertebrates has not been required. The Agency
presumes the chronic risk to freshwater invertebrates is minimal.
(c)
Estuarine and Marine Animals
Use of desmedipham is not expected to pose a risk to estuarine and marine habitats because
it is not generally used in areas associated with marine and estuarine habitats.
50
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(3) Exposure and Risk to Nontarget Plants
(a) Terrestrial and Semi-aquatic
The Agency performs separate risk assessments for two categories of nontarget plants,
terrestrial and semi-aquatic. Non-target terrestrial plants inhabit non-aquatic areas which are
generally well drained. Non-target semi-aquatic plants inhabit low-lying areas that are usually
wet, although they may be dry during certain times of the year. These plants are not obligatory
aquatic plants in that they do not live in a continuously aquatic environment.
To estimate the exposure to non-target terrestrial and semi-aquatic plants, the Agency must
calculate pesticide loading from runoff, spray drift, and volatilization. Exposure from runoff
differs between plant types, in that terrestrial plants are assumed to be subjected to sheet runoff,
whereas semi-aquatic plants are assumed to be subjected to channelized runoff. Because of the
low vapor pressure (3 x 109 Torr) of technical desmedipham (GLN 63-9, MRID 41937501),
volatilization is not considered to significantly contribute to exposure.
Ground Applications
Runoff: The Agency assumes that runoff will expose nontarget plants to a fixed
percentage of the application rate. Since the water solubility of desmedipham at 20°C is 7.0 ppm,
the percent runoff is assumed to be 1% based on the water solubility of the active ingredient.
(Table 25.)
Table 23. Assumed percentages of application rate that may expose nontarget plants through
runoff.
Water Solubility
< 10 ppm
10 - 100 ppm
> 100 ppm
% Runoff Assumed
1%
2%
5%
The Agency recognizes that runoff potential is not strictly a function of solubility. Because
of the rapid hydrolysis of desmedipham in neutral to alkaline water, exposure to plants from
runoff will probably be less than that predicted by this model. The conclusions of this model will
therefore be conservative (i.e., over-protective).
For non-target terrestrial plants, the Agency assumes a scenario in which plants are
exposed from sheet runoff. A treated site of 1 acre is assumed to drain into an adjacent area of
1 acre where terrestrial plants may be impacted. The runoff loading (Ib ai) for sheet runoff is
calculated with the following formula:
Runoff Loading (Ib ai) = max. appl. rate (Ib ai/A) X \% runoff X 1 acre
51
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In the scenario used for non-target semi-aquatic plants, exposure from runoff is assumed
to be from channelized runoff. A treated site of 10 acres is assumed to drain into a low lying area
of 1 acre where semi-aquatic plants may be impacted. Like terrestrial nontarget plants, the
percentage of runoff is based upon water solubility. The runoff loading (Ib ai) for channelized
runoff is calculated with the following formula:
Runoff Loading (Ib ai) = max. appl. rate (Ib ai/A) X \% runoff X 10 acre
Spray drift: For application with ground equipment, exposure from spray drift is
assumed to be 1% of the application rate. The drift loading (Ib ai) impacting a 1-acre site adjacent
to a 1-acre treated site is calculated as follows:
Drift Loading (Ib ai) = max. appl. rate (Ib ai/A) X 1% runoff X 1 acre
The drift loading rate is divided by the vegetative vigor EC25 to calculate a risk quotient
for spray drift on vegetation. In addition, the total loading rate is divided by the seedling
emergence EC25 to calculate risk quotients for exposure to emerging seedling of terrestrial and
semi-aquatic plants. The total loading rate, or the total Ib ai potentially impacting a 1-acre site,
is the sum of the runoff loading and drift loading. Because of the greater assumed drainage area,
the runoff loading from channelized runoff (for semi-aquatic plants) will be ten times greater than
that from sheet runoff (for terrestrial plants).
The predicted loading rates from ground applications of desmedipham at the maximum use
rate of 1.26 Ib ai/A are summarized in Table 26.
Table 24. Predicted loading rates from ground applications.
Type of Exposure
Sheet runoff
Channelized runoff
Spray drift
Loading Rate (Ib ai/A)
0.0126
0.126
0.0126
Aerial Applications
Runoff: Exposure due to runoff following aerial applications is calculated in the same
manner as for unincorporated ground applications, except that a correction for application
efficiency is required. Application efficiency, that is, how much of what is applied actually hits
the target site, is less for aerial application since much of what is sprayed drifts away from the
site. The Agency assumes the application efficiency to the treated site to be 60%. The runoff
loading (Ib ai) for sheet runoff is calculated as follows:
Runoff loading (Ib ai) = max. appl. rate (Ib ai/A) X 60% appl. efficiency X 1% runoff X 1 acre
52
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The runoff loading (Ib ai) for channelized runoff is calculated as follows:
Runoff loading (Ib ai) = max. appl. rate (Ib ai/A) X 60% appl. efficiency X 1% runoff X 10 acre
Spray drift: Some of what drifts from the site following aerial application settles
relatively quickly in immediately adjacent areas; the Agency estimates the drift at 100 feet
downwind of the site will be 5% of the application rate. The loading from spray drift from aerial
application is calculated as follows:
Drift loading (Ib ai) = max. appl. rate (Ib ai/A) X 60% appl. efficiency X 5% runoff X 1 acre
As with ground applications, the total loading rate for aerial applications is the sum of the
runoff loading and drift loading. The runoff loading rate for sheet runoff is used in the sum for
terrestrial plants whereas the runoff loading rate for channelized runoff is used in the sum for
semi-aquatic plants.
The predicted loading rates from aerial applications of desmedipham at the maximum use
rate of 1.26 Ib ai/A are summarized in Table 27.
Table 25. Predicted loading rates from aerial applications
Type of Exposure
Sheet runoff
Channelized runoff
Spray drift
Loading Rate (Ib ai/A)
0.00756
0.0756
0.0630
Risk Quotients
Risk quotients for terrestrial and semi-aquatic plants are derived by dividing an exposure
estimate, in terms of a loading rate (Ib ai/A), by an EC25, also expressed in terms of Ib ai/A. The
total loading rate (runoff plus spray drift) is used with the EC25 of the most sensitive species in
the seedling emergence study to determine the risk quotient for exposure to seedlings. The
loading from spray drift alone is used with the EC25 value of the most sensitive species in the
vegetative vigor study to determine the risk quotient for exposure to foliage.
53
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The summarized information for terrestrial and semi-aquatic non-target plants is presented
in Table 26.
Table 26. Exposure and Risk Quotients for Terrestrial and Semi-aquatic Plants
Use Site & Rate
Ground, 1.26 Ib ai/A
Aerial, 1.26 Ib ai/A
Type of Plants
Terrestrial
Semi-aquatic
Terrestrial and
semi-aquatic
Terrestrial
Semi-aquatic
Terrestrial and
semi-aquatic
Exposure Scenario
Sheet runoff + spray
drift (1%)
Channelized runoff +
spray drift (1%)
Spray drift (1%)
Sheet runoff + spray
drift (5%)
Channelized runoff +
spray drift (5%)
Spray drift (5%)
Exposure
(Ib ai/A)
0.025
0.14
0.013
0.071
0.14
0.063
EC25
(Ib ai/A)
0.31
(Seedling
emergence)
0.31
(Seedling
emergence)
(Vegetative
vigor)
0.31
(Seedling
emergence)
0.31
(Seedling
emergence)
(Vegetative
vigor)
Risk Quotient
0.081
0.45
0.23
0.45
* The Agency does not believe that the toxicity values determined from the vegetative vigor tests with the TGAI represent the toxicity
of desmedipham when plants are exposed to spray drift of formulated product. This toxicity value should be derived from a TEP
vegetative vigor study, which has not yet been submitted to the Agency.
As shown in the above table, the risk assessment for terrestrial and semi-aquatic plants is
incomplete (i.e., missing spray drift component) because data from TEP studies are lacking. TEP
studies are needed because desmedipham end-use products are expected to show enhanced activity
on plant foliage due to the addition of adjuvants. These adjuvants are important for the proper
wetting of foliage and absorption of the active ingredient into plant tissue. Risk resulting from
exposure of spray drift on foliage cannot be quantitatively assessed until these TEP data are
obtained. Since desmedipham is used to control emerged weeds, it is assumed that exposure from
spray drift poses some risk to nontarget plants.
Risk for exposure to emerging seedlings resulting from a combination of runoff and spray
drift were assessed using data from TGAI studies. The Agency has more confidence in using
desmedipham TGAI data for assessing risk to seedlings than for emerged vegetative because
adjuvants are expected to affect the activity of desmedipham less when it is applied to soil than
when it is applied to foliage. Nevertheless, the certainty of the risk assessment is still reduced by
not having TEP data.
None of the risk quotients for emerging seedlings exceed 1, the LOG for presuming risk.
This indicates that exposure of desmedipham from runoff and spray drift will have minimal risk
to the germination and emergence of seedlings.
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Threatened and endangered plants: Risk quotients for threatened and endangered plants
are calculated using NOELs rather than EC25s.
Table 27. Exposure and Risk Quotients for Endangered Terrestrial and Semi-aquatic Plants
Use Site & Rate
Ground, 1.26 Ib ai/A
Aerial, 1.26 Ib ai/A
Type of Plants
Terrestrial
Semi-aquatic
Terrestrial and
semi-aquatic
Terrestrial
Semi-aquatic
Terrestrial and
semi-aquatic
Exposure Scenario
Sheet runoff
+ spray drift (1%)
Channelized runoff
+ spray drift (1%)
Spray drift (1%)
Sheet runoff
+ spray drift (5%)
Channelized runoff
+ spray drift (5%)
Spray drift (5%)
Exposure
(Ib ai/A)
0.025
0.14
0.013
0.071
0.14
0.063
NOEC
(Ib ai/A)
0.15
(Seedling
emergence)
0.15
(Seedling
emergence)
(Vegetative
vigor)
0.15
(Seedling
emergence)
0.15
(Seedling
emergence)
(Vegetative
vigor)
Risk Quotient
0.17
0.93
-
0.47
0.93
-
* The Agency does not have confidence that the toxicity value determined from the vegetative vigor tests with the TGAI represent the
toxicity of desmedipham in formulations when plants are exposed via spray drift. This toxicity value should be derived from a TEP
vegetative vigor study, which has not yet been submitted to the Agency.
None of risk quotients for emerging seedlings exceed the LOG of 1. This assessment
indicates that exposure to desmedipham from runoff and spray drift will not effect seedlings of
endangered or threatened plants. However, as explained above, this risk assessment is incomplete
because of the lack of TEP toxicity data. The potential for desmedipham to effect endangered or
threatened plants via spray drift cannot be quantitatively assessed at this time. However, since
desmedipham is used to control emerged weeds, it is assumed that spray drift from aerial
applications could harm endangered or threatened plants.
(b) Aquatic Plants
The scenario used to estimate exposure to nontarget aquatic plants assumes a 1-ha by
2-meter deep pond that receives drainage from a 10-ha treated site. Exposure is assumed to occur
through both runoff and spray drift from the treated site. Generic EEC's (GEEC's) were
estimated by the GENEEC Program (see section C.3.a.2).
Risk quotients are calculated for aquatic plants by dividing the peak GEEC by the aquatic
plant EC50 values. A risk quotient for aquatic vascular plants is based on the EC50 for duckweed
(Lemna gibba). A risk quotient for nonvascular aquatic plants is based on the EC50 of the most
sensitive algal or diatom species tested. For desmedipham, the most sensitive nonvascular plant
tested was a freshwater diatom (Navicula pelliculosa).
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Table 28. Acute Risk Quotients (RQ) for Aquatic Plants
Crop and
Application Method
Sugar Beets, Aerial
Sugar Beets, Ground
Application
Rate (Ib ai/A
per application)
0.98
0.98
Peak
GEEC1 (ppb)
14.5
14.1
Type of Plant
Vascular (Lemna gibba)
Algae or Diatom
Vascular (Lemna gibba)
Algae or Diatom
EC50 (ppb)
>330
44
>330
44
Acute RQ
< 0.044
0.33
< 0.042
0.32
* The peak GEEC is the highest expected concentration after two applications of desmedipham separated by an interval of 7 days.
None of the risk quotients exceed 1, the LOG for presuming risk. Thus, concentrations
of desmedipham in water are predicted to have minimal effects of nontarget aquatic plants. Also,
desmedipham concentrations in water are not expected to affect endangered species of aquatic
plants. As with terrestrial plants, drift of TEP possibly may have adverse effects to aquatic plants
if it contacts foliage above the water.
(4) Endangered Species
The risk assessment indicates that use of desmedipham may affect endangered species of
terrestrial vertebrates (birds, mammals, reptiles, and amphibians). (Birds and mammals are used
as surrogates for reptiles and amphibians). Chronic effects on these species are possible. Foliar
contact of spray drift of desmedipham may also affect nontarget terrestrial plants, as well as
macrophytes and emerged aquatic plants. Use of desmedipham should not cause effects on
endangered fish, insects, or aquatic invertebrates.
When the Endangered Species Protection Program becomes final, limitations in the use
of desmedipham may be required to protect endangered and threatened species, but these
limitations have not been defined and may be formulation specific. EPA anticipates that a
consultation with the Fish and Wildlife Service may be conducted in accordance with the species-
based priority approach described in the Program. After completion of consultation, registrants
will be informed if any required label modifications are necessary. Such modifications would
most likely consist of the generic label statement referring pesticide users to use limitations
contained in county Bulletins.
4. Water Resources Risk Implications for Human Health
Desmedipham is currently not regulated under the Safe Drinking Water Act (SDWA). The
Agency's Office of Water has not established a Maximum Contaminanant Level (MCL) for a
Drinking Water Lifetime Health Advisory Level (HAL) for desmedipham.
a.
Ground Water
The Agency has no reports of sampling for desmedipham in ground water. Chemical and
physical data indicate that desmedipham will hydrolyze rapidly in neutral to alkaline soils. In
addition, the high estimated Kd and Koc values demonstrate that desmedipham will bind strongly
to soil organic matter and is not mobile. The Agency concludes that desmedipham has a low
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potential to leach to ground water on most soils and there is a low human health risk in regard to
ground water resources.
b. Surface Water
Desmedipham degrades rapidly via neutral to alkaline hydrolysis; therefore, it is non-
persistent in neutral to alkaline surface waters which would be typically occur in most areas of
sugar beet production. Desmedipham could be transported to surface water bodies during
application by means of spray drift. Desmedipham will adsorb to soil particles and could be
transported by surface runoff to surface water bodies on entrained sediment. However, rapid
degradation by abiotic hydrolysis and microbial-mediated metabolism will result in low
concentrations in surface waters. Currently available multi-residue monitoring data for states
associated with sugar beet production (CA, WA, MN) did not report the presence of desmedipham
in surface waters.
Desmedipham is tentatively classified as a Group E chemical (evidence of non-
carcinogenicity for humans; Section B.l.c.) and also does not have Acute Toxicity concerns with
regard to human health (Table 2, section B.I.a.). The RfD for desmedipham is 0.04 mg/kg/day
(section B.l.i.).
5. Environmental Risk Characterization
Based on available data, desmedipham is expected to have minimal effects on the quality
of ground water. The Agency has no reports of sampling for desmedipham in ground water.
Chemical and physical data indicate that desmedipham binds strongly to soil organic matter and
is not mobile. The Agency concluded that desmedipham has a low potential to leach to ground
water in most soils.
The environmental impact from residues of desmedipham on surface water is expected to
be negligible. Desmedipham may reach surface water, primarily via spray drift and suspended
particles in runoff to which desmedipham is absorbed. However, in most areas where sugar beets
are grown, rapid degradation by abiotic hydrolysis and microbial-mediated metabolism should
result in relatively low concentrations in surface water. Also, the toxicity of desmedipham to
aquatic organisms is relatively low. The Agency concluded from its risk assessment negligible
risk to endangered and nonendangered aquatic organisms (fish, invertebrates, and plants), with
the exception of aquatic plants with foliage above the water which may be affected by spray drift.
The Agency concluded negligible risk from the risk assessment for desmedipham exposure
to seeds and to emerging seedlings from the chemical in the soil, but this assessment was
incomplete because testing with a TEP was lacking. Without a complete risk assessment, a
tentative conclusion was made that desmedipham could harm terrestrial and semiaquatic plants that
are exposed to drift.
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Because desmedipham was shown to be practically nontoxic to honey bees, the Agency
concludes that the risk to honey bees will be minimal. The risk characterization for other
terrestrial animals is less certain. Acute risk screens indicated that acute exposure to residues of
desmedipham will result in little or no mortality to birds or mammals. With high confidence, the
Agency can conclude that the acute risk of desmedipham to endangered and nonendangered
terrestrial animals is minimal.
However, the chronic risk screens indicated that chronic risks may exist in that exposure
to desmedipham has the potential to cause some minor blood effects in mammals (MRID
40387103). Whether these blood effects are of ecological significance to wild mammals is not
known. Exposure appears to be too little and for too short of duration to cause gross effects in
the survival and reproduction of wild mammals. The risk from exposure to desmedipham
residues should be limited to minor sublethal effects that are temporary and may not be
ecologically significant. The risk of serious chronic effects on the reproduction and survival of
mammals is minimal.
For birds, the risk screen indicated a possible risk of reproductive effects, but as discussed
below, the Agency concludes that this risk is low to moderate. Because the chronic RQ for birds
exceeded the LOG, an analysis of the certainties and uncertainties in the risk assessment and of
the extent and significance of the risk was conducted. One uncertainty is due to the fact that only
two species were tested. The risk assessment used the results from the more sensitive of the two
species tested. However, because variation in sensitivity between species to pesticides tends to
be great, it is likely that other species are more sensitive. The risk to these other species could
be greater than that predicted.
Furthermore, on a per weight basis, food consumed by birds in the wild generally contains
more water, fewer calories, and less nutrition than does the feed consumed by birds in laboratory
tests. Therefore, birds in the wild must consume a greater quantity of food to meet their
nutritional requirements. For the same concentration of active ingredient in the diet, birds in the
field will ingest a larger dose (mass per body weight) than the birds in the laboratory tests. If
these factors were known and taken into account, the predicted risk may have been greater.
On the other hand, conservative assumptions were made in estimating residue levels. For
example, residues are based on maximum application rates, which may be greater than those
typically used. Residue on each type of food item was assumed to be equal to the highest level
of the possible range of levels predicted from field trials. That is, the estimated residues approach
the maximum likely to occur (Hoerger and Kenaga, 1972; Fletcher et al, 1994).
Also, it is uncertain where the threshold is at which significant reproductive effects begin
to occur. Based on chronic test results from the most sensitive species, this threshold is predicted
to lie somewhere between the NOEL (90 ppm) and LOEL (450 ppm), but the precise level is
unknown. Estimated environmental concentrations of desmedipham lie between the LOEL and
the NOEL. Even if the environmental concentrations of desmedipham were precisely known, all
that can be concluded is that the environmental concentrations probably are near the threshold.
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The duration of the exposure is also in question. Greater durations of exposure correspond
with a greater risk and extent of detrimental effects. The longer residues remain at levels that
may cause effects (i.e. levels greater than the NOEL), the greater the likelihood that wild
organisms will move into the treated areas and be exposed. For desmedipham, the duration of
exposure that exceeds the NOEL is predicted to be 21 days for short grass that receives two
applications of desmedipham spaced seven days apart. For other types of foliage with two
applications, and for all foliage types with a single application, the durations of exposure was
characterized as 4 to 12 days. Overall, the estimated duration of exposure is relatively short
compared to the duration of the avian reproductive tests.
The assumed persistence of residues on wildlife food was conservative, i.e. at the upper
end of the range of the different degradation rates reported in the environmental fate studies. The
half-life selected for estimating dissipation of residues on food items (approximately 7 days) was
consistent with the half-lives determined in the field dissipation and aerobic soil metabolism
studies (Section 2.b.). Under some conditions, the rate of degradation may be faster (hydrolysis
half-life at pH 7 was 17-22 hours), which would result in a quicker decline of residues, and risk,
to levels below the LOG for chronic effects.
In the statements concerning the duration of exposure, birds were assumed to consume
only those food items containing the maximum predicted concentration of desmedipham during
the entire period. While the test organisms were fed only on the contaminated food, wild
organisms, and especially birds, may move about, feeding in an opportunistic manner from a
variety of sites. In the chronic risk assessment, the assumption is made that birds would be
returning to the treated fields every day to feed. This is considered unlikely because sugar beet
fields are not believed to be favorable feeding areas for birds. Most birds will likely feed part
of the time in uncontaminated areas, thereby reducing the level of chronic risk.
Another consideration is the extent of exposure. The EECs used to assess risk to birds
were based on direct application to the food items in the treated field. Therefore, the birds would
have to be feeding in the treated field itself to be exposed to these levels. Residues on avian food
items off the treated site generally result from drift from the treatment area. Residues on food
items would only be a small percentage of those that occur within the treated field (currently
assumed to be 1% if treatment is by ground equipment and 5% if by aerial equipment). Chronic
risk to birds feeding in this area would be negligible. Although these marginal regions probably
comprise less area than the fields themselves, they probably comprise a more favorable habitat
that will be used more extensively for feeding. These regions would likely contain more plant
foods than areas in the field where weeds are controlled by tilling. Also, most of the weeds in
the field should be killed by action of desmedipham and other herbicides that are applied. This
dead and dying vegetation may be less attractive to birds than the green vegetation that would
occur in the field margins.
Finally, the timing of exposure is important in considering the potential for desmedipham
to cause reproductive effects in birds. The reproductive effects observed in laboratory tests
(eggshell thinning and reduced viability of embryos) would be expected only in wild birds that are
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exposed during the period of breeding and egg laying. The field dissipation tests give an
indication of the typical timing application of, and hence exposure to, desmedipham on sugar beet
fields. These studies were done in actual fields of sugar beets under typical growing conditions.
Applications in these tests were made in May and mid-June in California and North Dakota,
respectively. Timing of the breeding and egg laying of some relevant species are reported below:
Table 29. Timing of Breeding in Selected Bird Species
Species
Canada Goose
Mallard Duck
Northern Bobwhite
American Robin
Begin
Early March
Mid-March
Early April
Early April
April
Early April
Peak
Late March
Late March - April
Mid- April
May
Early May
Mid- May - July
Mid- April
End
May
Early May
Mid- July
September
Late April
Location
Oregon, Washington, California,
Montana
Idaho
California, Utah, Montana, South Dakota,
New York, Vermont
North Dakota
Illinois
Illinois
Source: Environmental Protection Agency, 1993. Wildlife Exposure Factors Handbook, Volume I of II. Document number EPA/600/R-
93/187a. Washington, DC 20460.
Reproduction of Canada geese should not be affected since applications of desmedipham
are made in areas where sugar beets are grown after the end of the breeding season. For the
mallard, applications generally occur after the peak of breeding, but the period of exposure does
overlap with the later part of the breeding season. There will also be overlap for species whose
breeding season continues into the summer, such as the northern bobwhite and passerines that
have multiple clutches. However, unlike ducks and geese, these species generally do not feed
extensively on grass. Their diet is usually composed of some combination of seeds, fruit, or
invertebrates, which are food items predicted to contain considerably less residues than short
grass. This reduces the level of risk to these species.
The Agency concludes that the use of desmedipham poses some risk to birds in that it may
cause impairment of reproduction of some species. The risk characterization suggests that the
level of risk is moderate to low. Risk appears to be limited to situations of exceptionally high
exposure. At the local level, some effects may be possible in a few cases when sensitive birds
feed heavily for a continued time within treated fields. The mallard duck is an example of a
species which may be susceptible. Chronic effects, however, are not expected to be widespread
or extensive. Also, as the use of desmedipham is concentrated in a few relatively small areas of
the country, the impact to the environment will be limited to the local level. The impact on the
overall environment on national or regional scales is not likely to be significant.
Risk Characterization Conclusions
The Agency's following risk characterization conclusions are based on the weight-of-the-
evidence after consideration of all the information reviewed by the Agency on desmedipham and
wildlife behavior. It also takes into account the assumptions made during the risk assessment
process.
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The following are concluded with relatively high certainty:
• Ground water and surface water contamination is of minimal concern.
• Risk to aquatic plants and animals is minimal.
• Acute risk to insects, birds, and mammals is minimal.
Certainty is not as high in the following conclusions:
• The chronic risk to mammals is minimal.
• A chronic risk to birds exists but is characterized as low to moderate. Effects are expected
to be limited in extent, and the impact to the environment should be significant only on the
local level.
Risk to terrestrial and semiaquatic plants could not be assessed because of lack of testing
using the TEP. To be conservative, desmedipham should tentatively be assumed to pose risk to
these plants through exposure from drift.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active ingredients
are eligible for reregistration. The Agency has previously identified and required the submission
of the generic (i.e. active ingredient specific) data required to support reregistration of products
containing desmedipham as an active ingredient. The Agency has completed its review of these
generic data, and has determined that the data are sufficient to support reregistration of all
products containing desmedipham. Appendix B identifies the generic data requirements that the
Agency reviewed as part of its determination of reregistration eligibility of desmedipham, 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 desmedipham and to determine that desmedipham can be used without resulting
in unreasonable adverse effects to humans and the environment. The Agency therefore finds that
all currently registered products containing desmedipham as the active ingredient are eligible for
reregistration. The reregistration of these 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, published scientific literature, etc. and the data identified in Appendix B.
Although the Agency has found that all uses of desmedipham 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 desmedipham, if
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new information comes to the Agency's attention or if the data requirements for registration (or
the guidelines for generating such data) change.
B. Determination of Eligibility Decision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient desmedipham, the
Agency has sufficient information on the health effects of desmedipham and on its potential for
causing adverse effects in fish and wildlife and the environment. The Agency has determined that
desmedipham products, labeled and used as specified in this Reregistration Eligibility Decision,
will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the
Agency concludes that products containing desmedipham for all uses are eligible for
reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all current uses of desmedipham are eligible for
reregistration.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for desmedipham.
Where labeling revisions are imposed, specific language is set forth in Section V of this
document.
1. Worker Protection
The Worker Protection Standard (WPS)
2. Scope of the WPS
The 1992 Worker Protection Standard for Agricultural Pesticides (WPS) established
certain worker-protection requirements (personal protective equipment, restricted-entry intervals,
etc.) to be specified on the label of all products that contain uses within the scope of the WPS.
Uses within the scope of the WPS include all commercial (non-homeowner) and research uses on
farms, forests, nurseries, and greenhouses to produce agricultural plants (including food, feed,
and fiber plants, trees, turf grass, flowers, shrubs, ornamentals, and seedlings). Uses within the
scope include not only uses on plants, but also uses on the soil or planting medium the plants are
(or will be) grown in.
At this time all registered uses of desmedipham are within the scope of the Worker
Protection Standard for Agricultural Pesticides (WPS).
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a. Compliance With the WPS
Any product whose labeling can be reasonably interpreted to permit use in the production
of an agricultural plant on any farm, forest, nursery, or greenhouse must comply with the labeling
requirements of PR Notice 93-7, "Labeling Revisions Required by the Worker Protection
Standard (WPS)," and PR Notice 93-11, "Supplemental Guidance for PR Notice 93-7," which
reflect the requirements of EPA's labeling regulations for worker protection statements (40 CFR
part 156, subpart K). These labeling revisions are necessary to implement the Worker Protection
Standard for Agricultural Pesticides (40 CFR part 170) and must be completed in accordance
with, and within the deadlines specified in, PR Notices 93-7 and 93-11. Unless otherwise
specifically directed in this RED, all statements required by PR Notices 93-7 and 93-11 are to be
on the product label exactly as instructed in those notices.
• After April 21, 1994, except as otherwise provided in PR Notices 93-7 and 93-11,
the labeling of all products within the scope of those notices must meet the
requirements of the notices when the products are distributed or sold by the
primary registrant or any supplementally registered distributor.
• After October 23, 1995, except as otherwise provided in PR Notices 93-7 and
93-11, the labeling of all products within the scope of those notices must meet the
requirements of the notices when the products are distributed or sold by any
person.
b. Personal Protective Equipment/Engineering Controls for
Handlers
For each end-use product, PPE requirements for pesticide handlers are set during
reregistration in one of two ways:
1. If EPA determines that no regulatory action must be taken as the result of the acute
effects or other adverse effects of an active ingredient, the PPE for pesticide
handlers will be based on the acute toxicity of the end-use product. For
occupational-use products, PPE must be established using the process described in
PR Notice 93-7 or more recent EPA guidelines.
2. If EPA determines that regulatory action on an active ingredient must be taken as
the result of very high acute toxicity or to certain other adverse effects, such as
allergic effects or delayed effects (cancer, developmental toxicity, reproductive
effects, etc.):
• In the RED for that active ingredient, EPA may establish minimum or
"baseline" handler PPE requirements that pertain to all or most end-use
products containing that active ingredient.
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• These minimum PPE requirements must be compared with the PPE that
would be designated on the basis of the acute toxicity of the end-use
product.
• The more stringent choice for each type of PPE (i.e., bodywear, hand
protection, footwear, eyewear, etc.) must be placed on the label of the end-
use product.
Personal protective equipment requirements usually are set by specifying one or more pre-
established PPE units — sets of items that are almost always required together. For example, if
chemical-resistant gloves are required to mitigate risk, then long-sleeve shirts, long pants, socks,
and shoes are also included in the required minimum attire. If the requirement is for two layers
of body protection (coveralls over a long- or short-sleeve shirt and long or short pants), the
minimum must also include (for all handlers) chemical-resistant footwear and chemical-resistant
headgear for overhead exposures and (for mixers, loaders, and persons cleaning equipment)
chemical-resistant aprons.
c. Occupational-Use Products
EPA has determined that regulatory action on desmedipham must be taken to adequately
mitigate risks to certain handlers. EPA will establish active-ingredient-based minimum PPE
requirements for certain occupational handlers.
The MOEs for dermal exposure are of concern for occupational mixers/loaders. EPA is
requiring active-ingredient-based protection for handlers of desmedipham in these exposure
situations. Specifically, EPA is requiring chemical-resistant gloves for all mixers and loaders.
In addition, a dust/mist respirator will be required for mixers/loaders of wettable powder
formulations who are supporting groundboom applications. To adequately mitigate risks to
mixers/loaders of wettable powder formulations who are supporting aerial applications, EPA is
requiring engineering controls — the product must be formulated in water-soluble packaging, or
application rates must be limited to no more than 0.5 Ib/a.i. on no more than 350 acres/day.
d. Homeowner-Use Products
There are no homeowner uses of desmedipham.
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3. Post-Application/Entry Restrictions
a. Occupational-Use Products (WPS Uses)
(1) Restricted-Entry Interval:
Under the Worker Protection Standard (WPS), interim restricted-entry intervals (REI's)
for all uses within the scope of the WPS are based on the acute toxicity of the active ingredient.
The toxicity categories of the active ingredient for acute dermal toxicity, eye irritation potential,
and skin irritation potential are used to determine the interim WPS REI. If one or more of the
three acute toxicity effects are in toxicity category I, the interim WPS REI is established at 48
hours. If none of the acute toxicity effects are in category I, but one or more of the three is
classified as category II, the interim WPS REI is established at 24 hours. If none of the three
acute toxicity effects are in category I or II, the interim WPS REI is established at 12 hours. A
48-hour REI is increased to 72 hours when an organophosphate pesticide is applied outdoors in
arid areas. In addition, the WPS specifically retains two types of REI's established by the Agency
prior to the promulgation of the WPS: (1) product-specific REI's established on the basis of
adequate data, and (2) interim REI's that are longer than those that would be established under
the WPS.
During the reregistration process, EPA considers all relevant product-specific information
to decide whether there is reason to shorten or lengthen the previously established REI.
The WPS REI in effect until now was 24 hours. This was an interim REI placed on
desmedipham products by PR Notice 93-7 based on data which indicated that desmedipham is in
toxicity category II for eye irritation potential.
During the reregistration process, EPA determined that the 24-hour REI established under
the WPS should be retained for all occupational-use products that contain desmedipham and are
within the scope of the Worker Protection Standard for Agricultural Pesticides (WPS). The basis
for this decision is that desmedipham is categorized as toxicity category II for eye irritation
potential. EPA has determined that no additional regulatory action (beyond the 24-hour REI)
must be taken to mitigate post-application exposures/risks.
(2) Early-Entry PPE:
The WPS establishes very specific restrictions on entry by workers to areas that remain
under a restricted-entry interval, if the entry involves contact with treated surfaces. Among those
restrictions are a prohibition of routine entry to perform hand labor tasks and a requirement that
personal protective equipment be worn. Under the WPS, these personal protective equipment
requirements for persons who must enter areas that remain under a restricted-entry interval are
based on the acute toxicity category.
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During the reregistration process, EPA considers all relevant product-specific information
to decide whether there is reason to set personal protective equipment requirements that differ
from those set through the WPS.
The RED requirements for early-entry personal protective equipment are set in one of two
ways:
1. If EPA determines that no regulatory action must be taken as the result of the acute
effects or other adverse effects of an active ingredient, it establishes the early-entry
PPE requirements on the basis of the acute dermal toxicity category, skin irritation
potential category, and eye irritation potential category of the active ingredient.
In any case, the minimum early-entry PPE allowed by the WPS is coveralls,
chemical-resistant gloves, socks, and shoes.
2. If EPA determines that regulatory action on an active ingredient must be taken as
the result of very high acute toxicity or to certain other adverse effects, such as
allergic effects or delayed effects (cancer, developmental toxicity, reproductive
effects), it may establish early-entry PPE requirements that are more stringent than
would be established otherwise.
Since EPA has determined that no additional regulatory action must be taken due to the
adverse effects of desmedipham, it is establishing PPE for dermal protection on the basis of the
acute toxicity of the active ingredient. Desmedipham is classified as toxicity category III for acute
dermal toxicity and toxicity category IV for skin irritation potential, therefore, the minimum
early-entry PPE allowed by the WPS is required. Since desmedipham is classified as toxicity
category II for eye irritation potential, protective eyewear is required.
4. WPS Notification Statement
Under the WPS, the labels of some pesticide products must require employers to notify
workers about pesticide-treated areas orally as well as by posting of the treated areas. The
reregistration process also may decide that a product requires this type of "double notification."
EPA has determined that double notification is not required for desmedipham end-use
products.
5. Other Labeling Requirements
The Agency is also requiring other use and safety information to be placed on the labeling
of all end-use products containing desmedipham. See specific labeling statements are described
in the next section.
66
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6. Dietary Exposure Assessment
For the purposes of risk assessment, adequate plant metabolism and magnitude of the
residue data are available for sugar beets. The Agency used the established 0.2 ppm tolerance for
sugar beet roots for risk assessment.
The qualitative nature of the residue in animals is adequately understood. As sugar beet
commodities are not fed to poultry, no tolerances are required for poultry meat and eggs. The
Agency has determined under section 180.6(a) (3) of the Code of Federal Regulations, that there
is no reasonable expectation of finite residues for ruminant commodities and that no tolerances
on meat, milk, poultry, or eggs will be required. The Agency used the proposed 15 ppm
tolerance level for sugar beet tops when calculating the theoretical maximum dietary intake of beef
and dairy cattle for purposes of determining that tolerances for meat and milk are not needed.
7.
Tolerance Reassessment
The tolerances listed in 40 CFR § 180.353 are for residues of desmedipham per se in/on sugar
beets (roots and tops). No tolerances exist for residues of desmedipham in animal commodities, and
no food/feed additive tolerances have been established.
AgrEvo has proposed raising the established tolerance for sugar beet tops from 0.2 ppm to
15 ppm based on preliminary field trial data submitted under section 6(a)(2) of FIFRA. The Agency
is requesting that additional confirmatory field trial data for sugar beet tops be submitted to reassess
the existing 0.2 ppm tolerance for sugar beet tops and whether the proposed tolerance of 15 ppm in
sugar beet tops should be adopted.
Table 30. Tolerance Reassessment Summary for Desmedipham.
Commodity
Current Tolerance
(ppm)
Tolerance
Reassessment (ppm)
Comment/Correct Commodity
Definition
Tolerances listed under 40 CFR 180.353:
Sugar beets (roots and tops)
0.2
To be determined
Additional residue data are required for
roots and tops.
Sugar beets, roots
Sugar beets, tops
8.
Restricted Use Classification
No restricted use classification is required for desmedipham and all currently registered uses.
67
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9. Reference Dose
The Agency RfD Committee recommends that an RfD for this chemical be based on a
reproductive toxicity study in rats with a parental toxicity NOEL of 4 mg/kg/day (50 ppm).
Significant reduction of body weight, hemolytic anemia accompanied by significant increase in spleen
weights and thyroid compensatory function were seen at the next higher dose of 20 mg/kg/day (250
ppm), the middle dose level tested, and higher dose levels. An uncertainty factor (UF) of 100 was
applied to account for the inter-species extrapolation and intra-species variability. On this basis, the
RfD is 0.04 mg/kg/day.
10. Endangered Species Statement
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 restrictions to protect endangered and threatened species at the county
level. Consultations with the Fish and Wildlife Service may be necessary to assess risks to newly
listed species or from proposed new uses. In the future, the Agency plans to publish a description
of the Endangered Species Program in the Federal Register and have available voluntary county-
specific bulletins. 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 document.
Rather, any requirements for product use modifications will occur in the future under the Endangered
Species Protection Program.
11. Spray Drift Advisory
The Agency has been working with the Spray Drift Task Force, the Agency Regional
Offices and State Lead Agencies for pesticide regulation to develop the best spray drift
management practices. The Agency is now requiring interim measures that must be placed on
product labels/labeling as specified in Section V. Once the Spray Drift Task Force completes
their studies, submits data, and the Agency evaluation is completed, there may be further
refinements in spray drift management practices.
V. ACTIONS REQUIRED OF 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 desmedipham for the above eligible
uses has been reviewed and determined to be substantially complete. The following confirmatory
68
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data has been requested from AgrEvo to upgrade the following supplemental submissions to
guideline acceptable.
61-1 Product Identity and Disclosure of Ingredients
62-2 Certification of Ingredient Limits
62-3 Analytical Methods to Verify the Certified Limits
83-1 (a) Chronic Feeding Toxicity - Rodent
85-1 General Metabolism
123-1 (a) Seed Germination/Seedling Emergence
123-1 (b) Vegetative Vigor
161-1 Hydrolysis
162-1 Aerobic Soil Metabolism
162-3 Anaerobic Aquatic Metabolism
164-1 Terrestrial Field Dissipation
165-1 Rotational Crops (Confined)
171-4 (c/d) Residue Analytical Methods
171-4 (k) Magnitude of the Residue in Plants
- Sugar Beets, roots
- Sugar Beets, tops
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing use product (MP) labeling must be
revised to comply with all current EPA regulations, PR Notices and applicable policies. The MP
labeling must bear the following statement under Directions for Use:
"Only for formulation into an herbicide used for use in sugar beets."
An MP registrant may, at his/her discretion, add one of the following statements to an MP
label under
"Directions for Use" to permit the reformulation of the product for a specific use
or all additional uses supported by a formulator or user group:
(a) "This product may be used to formulate products for specific use(s) not
listed on the MP label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of
such use(s)."
(b) "This product may be used to formulate products for any additional use(s)
not listed on the MP label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of
such use(s)."
69
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B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. Registrants must
review previous data submissions to ensure that they meet current EPA acceptance criteria and
if not, commit to conduct new studies. If a registrant believes that previously submitted data meet
current testing standards, then study MRID numbers should be cited according to the instructions
in the Requirement Status and Registrants Response Form provided for each product.
Additional studies are being required for seedling emergence testing (GDLN 123-la) and
a vegetative vigbor test (GDLN 123-lb), using a typical end-use product (TEP). Results from
Tier II nontarget terrestrial plant toxicity studies utilizing the desmedipham technical (TGAI)
showed no detrimenal effects to the vegetative vigor of the most sensitive species (lettuce) when
applied at a rate near the maximum label rate. This result implies that the adjuvants normally
present in the TEPs must be present for the desmedipham to express toxicity to plants.
Confirmatory testing utilizing a TEP containing these adjuvants is thus required.
PPE/Engineering Control Requirements for Pesticide Handlers
For sole-active-ingredient end-use products that contain desmedipham, the product
labeling must be revised to adopt the handler personal protective equipment/engineering control
requirements set forth in this section. Any conflicting PPE requirements on the current labeling
must be removed.
For multiple-active-ingredient end-use products that contain desmedipham, the handler
personal protective equipment/engineering control requirements set forth in this section must be
compared to the requirements on the current labeling and the more protective must be retained.
For guidance on which requirements are considered more protective, see PR Notice 93-7.
Products Intended Primarily for Occupational Use
Minimum (Baseline) PPE/Engineering Control Requirements
The minimum (baseline) PPE for all occupational uses of desmedipham end-use products
is:
For emulsifiable concentrate formulations1^
"Mixers and loaders must wear:
For the glove statement, use the statement established for desmedipham through the instructions in Supplement Three of PR Notice 93-7.
70
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—long-sleeved shirt and long pants,
—chemical-resistant gloves,
—shoes plus socks.
For wettable powder formulations1^
"Mixers and loaders must wear:
—long-sleeved shirt and long pants,
—chemical-resistant gloves,
—shoes plus socks.
—dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC-21C)."
If the formulation is produced in water-soluble packaging, the respirator equipment may
be reduced as specified in the WPS. Also, registrants may modify the labels of their wettable
powder formulations to limit sugar beet aeriel applications to 0.5 pounds AI per acre and 350
acres per day rather than reformulating to water-soluble packets.
Determining PPE Requirements for End-use Product Labels
The PPE that will be established on the basis of the acute toxicity category of the end-use
product must be compared to the active-ingredient-based minimum (baseline) personal protective
equipment specified above. The more protective PPE must be placed on the product labeling. For
guidance on which PPE is considered more protective, see PR Notice 93-7.
Placement in Labeling
The personal protective equipment requirements must be placed on the end-use product
labeling in the location specified in PR Notice 93-7, and the format and language of the PPE
requirements must be the same as is specified in PR Notice 93-7.
Entry Restrictions
For sole-active-ingredient end-use products that contain desmedipham the product labeling
must be revised to adopt the entry restrictions set forth in this section. Any conflicting entry
restrictions on the current labeling must be removed.
For multiple-active-ingredient end-use products that contain desmedipham the entry
restrictions set forth in this section must be compared to the entry restrictions on the current
labeling and the more protective must be retained. A specific time period in hours or days is
considered more protective than "sprays have dried" or "dusts have settled."
71
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Products Intended Primarily for Occupational Use
WPS Uses
Restricted-entry interval:
A 24-hour restricted-entry interval (REI) is required for uses within the scope of the WPS
on all desmedipham end-use products.
Early-entry personal protective equipment (PPE):
The PPE required for early entry is:
— coveralls,
— chemical-resistant gloves,
— shoes plus socks,
— protective eyewear.
Other Labeling Requirements
Products Intended Primarily for Occupational Use
The Agency is requiring the following labeling statements to be located on all end-use products
containing desmedipham that are intended primarily for occupational use.
Application Restrictions
"Do not apply this product in a way that will contact workers or
other persons, either directly or through drift. Only protected
handlers may be in the area during application."
Engineering Controls
"When handlers use closed systems, enclosed cabs, or aircraft in
a manner that meets the requirements listed in the Worker
Protection Standard (WPS) for agricultural pesticides (40 CFR
170.240(d)(4-6), the handler PPE requirements may be reduced
or modified as specified in the WPS."
72
-------
User Safety Requirements
1. Registrant: select this if coveralls are required for pesticide handlers on the end-use
product label:
"Discard clothing or other absorbent materials that have been drenched or heavily
contaminated with this product's concentrate. Do not reuse them."
2. Registrant: select this always:
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no
such instructions for washables, use detergent and hot water. Keep and
wash PPE separately from other laundry."
User Safety Recommendations
• "Users should wash hands before eating, drinking, chewing
gum, using tobacco, or using the toilet."
• "Users should remove clothing immediately if pesticide gets
inside. Then wash thoroughly and put on clean clothing."
• "Users should remove PPE immediately after handling this
product. Wash the outside of gloves before removing. As
soon as possible, wash thoroughly and change into clean
clothing."
Skin Sensitizer Statement
"This product may cause skin sensitization reactions in some
people."
2. Labeling Requirements for End-Use Products
Spray Drift Labeling
The following language must be placed on each product label that can be applied aerially:
Avoiding spray drift at the application site is the responsibility of the applicator. The
interaction of many equipment-and-weather-related factors determine the potential for spray drift.
The applicator and the grower are responsible for considering all these factors when making
decisions.
73
-------
The following drift management requirements must be followed to avoid off-target drift
movement from aerial applications to agricultural field crops. These requirements do not apply
to forestry applications, public health uses or to applications using dry formulations.
1. The distance of the outer most nozzles on the boom must not exceed 3/4 the length
of the wingspan or rotor.
2. Nozzles must always point backward parallel with the air stream and never be
pointed downwards more than 45 degrees.
Where states have more stringent regulations, they should be observed.
The applicator should be familiar with and take into account the information covered in
the Aerial Drift Reduction Advisory Information.
The following aerial drift reduction advisory information must be contained in the product
labeling:
[This section is advisory in nature and does not supersede the mandatory
label requirements.]
Information on Droplet Size
The most effective way to reduce drift potential is to apply large droplets. The best drift
management strategy is to apply the largest droplets that provide sufficient coverage and control.
Applying larger droplets reduces drift potential, but will not prevent drift if applications are made
improperly, or under unfavorable environmental conditions (see Wind, Temperature and
Humidity, and Temperature Inversions).
Controlling Droplet Size
• Volume - Use high flow rate nozzles to apply the highest practical spray volume.
Nozzles with higher rated flows produce larger droplets.
• Pressure - Do not exceed the nozzle manufacturer's recommended pressures. For
many nozzle types lower pressure produces larger droplets. When higher flow rates are
needed, use higher flow rate nozzles instead of increasing pressure.
• Number of nozzles - Use the minimum number of nozzles that provide uniform
coverage.
• Nozzle Orientation - Orienting nozzles so that the spray is released parallel to the
airstream produces larger droplets than other orientations and is the recommended
74
-------
practice. Significant deflection from horizontal will reduce droplet size and increase drift
potential.
• Nozzle Type - Use a nozzle type that is designed for the intended application.
With most nozzle types, narrower spray angles produce larger droplets. Consider using
low-drift nozzles. Solid stream nozzles oriented straight back produce the largest droplets
and the lowest drift.
Boom Length
For some use patterns, reducing the effective boom length to less than 3/4 of the wingspan
or rotor length may further reduce drift without reducing swath width.
Application Height
Applications should not be made at a height greater than 10 feet above the top of the
largest plants unless a greater height is required for aircraft safety. Making applications at the
lowest height that is safe reduces exposure of droplets to evaporation and wind.
Swath Adjustment
When applications are made with a crosswind, the swath will be displaced downward.
Therefore, on the up and downwind edges of the field, the applicator must compensate for this
displacement by adjusting the path of the aircraft upwind. Swath adjustment distance should
increase, with increasing drift potential (higher wind, smaller drops, etc.)
Wind
Drift potential is lowest between wind speeds of 2-10 mph. However, many factors,
including droplet size and equipment type determine drift potential at any given speed.
Application should be avoided below 2 mph due to variable wind direction and high inversion
potential. NOTE: Local terrain can influence wind patterns. Every applicator should be familiar
with local wind patterns and how they affect spray drift.
Temperature and Humidity
When making applications in low relative humidity, set up equipment to produce larger
droplets to compensate for evaporation. Droplet evaporation is most severe when conditions are
both hot and dry.
Temperature Inversions
Avoid applications during a temperature inversion because drift potential is high.
Temperature inversions restrict vertical air mixing, which causes small suspended droplets to
75
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remain in a concentrated cloud. This cloud can move in unpredictable directions due to the light
variable winds common during inversions. Temperature inversions are characterized by
increasing temperatures with altitude and are common on nights with limited cloud cover and light
to no wind. They begin to form as the sun sets and often continue into the morning. Their
presence can be indicated by ground fog; however, if fog is not present, inversions can also be
identified by the movement of smoke from a ground source or an aircraft smoke generator.
Smoke that layers and moves laterally in a concentrated cloud (under low wind conditions)
indicates an inversion, while smoke that moves upward and rapidly dissipates indicates good
vertical air mixing.
Sensitive Areas
The pesticide should only be applied when the potential for drift to adjacent sensitive areas
(e.g. residential areas, bodies of water, known habitat for threatened or endangered species, non-
target crops) is minimal (e.g. when wind is blowing away from the sensitive areas).
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregistration Eligibility Decision (RED). Persons
other than the registrant may generally distribute or sell such products for 50 months from the
date of the issuance of this RED. However, existing stocks time frames will be established
case-by-case, depending on the number of products involved, the number of label changes, and
other factors. Refer to "Existing Stocks of Pesticide Products; Statement of Policy"; Federal
Register, Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell desmedipham products
bearing old labels/labeling for 26 months from the date of issuance of this RED. Persons other
than the registrant may distribute or sell such products for 50 months from the date of the issuance
of this RED. Registrants and persons other than registrants remain obligated to meet pre-existing
Agency imposed label changes and existing stocks requirements applicable to products they sell
or distribute.
76
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VI. APPENDICES
77
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Report Run Date: 03/14/96 ) Time 16:15
PRD Report Date: 04/19/95
LUIS 3.0- Page:
APPENDIX A REPORT
Case 2150[Desmidipham] Chemical 104801[Desmedipham (ethyl m-hydroxycarbanilate carbanilate)ester]
SITE Application Type, Application
Timing, Application Equipment )
Surface Type (Antimicrobial only) & Effica-
cy Influencing Factor (Antimicrobial only)
Form(s) Min. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Min. Restr. Geographic Limitations Use
Rate (AI un- Rate (AI Tex. ® Max. Rate unless noted Interv Entry Allowed Disallowed Limitations
less noted unless noted Max. /crop /year otherwise)/A] (days) Interv Codes
otherwise) otherwise) Dose cycle /crop /year [day(s)]
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES
SUGAR BEET
Band treatment, Foliar, Sprayer
Use Group: TERRESTRIAL FOOD+FEED CROP
Broadcast, Evening, Aircraft
EC
EC
EC
EC
EC
EC
WP
WP
EC
EC
EC
EC
EC
EC
WP
WP
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
.375
.3809
.6094
.375
.3809
1.219
.63
1.26
.05625
.2484
.08125
.24375
.2484
.1625
.315
.63
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
Ib A
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
.6525
Ib
.96 Ib
.975 Ib
.975 Ib
.99375
Ib
1.95 Ib
.98 Ib
1.96 Ib
.6525
Ib
.96 Ib
.975 Ib
.975 Ib
.99375
Ib
1.95 Ib
.98 Ib
1.96 Ib
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
7
7
5
7
7
5
7
7
7
7
5
7
7
5
7
7
1
NS
1
1
NS
1
NS
1
1 AZ, 013
NS AZ, 013
1 AZ, 013
1 AZ, 013
NS AZ, 013
1 AZ, 013
NS AZ, 013
1 AZ, 013
C46,
C46,
C46,
C46,
C46,
C92, H01(75)
CAU, HOI (75)
C92, H01(75)
C92, H01(75)
CAU, HOI (75)
C46, C92, CAG, CAU,
H01(75)
C46,
C46,
C46,
C46,
C46,
C46,
C46,
CAU, HOI (75)
C92, H01(75)
C92, H01(75)
CAU, HOI (75)
C92, H01(75)
C92, H01(75)
CAU, HOI (75)
C46, C92, CAG, CAU,
H01(75)
C46,
C46,
CAU, HOI (75)
C92, H01(75)
78
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Report Run Date: 03/14/96 ) Time 16:15
PRD Report Date: 04/19/95
LUIS 3.0- Page:
APPENDIX A REPORT
Case 2150[Desmidipham] Chemical 104801[Desmedlpham (ethyl m-hydroxycarbanilate carbanilate)ester]
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max. # Apps Max. Dose [ (AI Min. Restr. Geographic Limitations Use
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. ® Max. Rate unless noted Interv Entry Allowed Disallowed Limitations
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/A] (days) Interv Codes
otherwise) otherwise) Dose cycle /crop /year [day(s)]
cycle
cy Influencing Factor (Antimicrobial only)
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
SUGAR BEET (con't)
Broadcast, Evening, Ground
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
Broadcast, Foliar, Aircraft
EC
EC
EC
EC
EC
EC
WP
WP
EC
EC
EC
EC
EC
EC
WP
WP
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
.05625
.2484
.08125
.24375
.2484
.1625
.315
.63
.375
.3809
.6094
.375
.3809
1.219
.63
1.26
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
Ib A
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
.6525
Ib
.96 Ib
.975 Ib
.975 Ib
.99375
Ib
1.95 Ib
.98 Ib
1.96 Ib
.6525
Ib
.96 Ib
.975 Ib
.975 Ib
.99375
Ib
1.95 Ib
.98 Ib
1.96 Ib
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
7
7
5
7
7
5
7
7
7
7
5
7
7
5
7
7
1 AZ, 013
NS AZ, 013
1 AZ, 013
1 AZ, 013
NS AZ, 013
1
NS AZ, 013
1 AZ, 013
1
NS
1
1
NS
1
NS
1
C46,
C46,
C46,
C46,
C46,
C92, H01(75)
CAU, HOI (75)
C92, H01(75)
C92, H01(75)
CAU, HOI (75)
C46, C92, CAG, CAU,
H01(75)
C46,
C46,
C46,
C46,
C46,
C46,
C46,
CAU, HOI (75)
C92, H01(75)
C92, H01(75)
CAU, HOI (75)
C92, H01(75)
C92, H01(75)
CAU, HOI (75)
C46, C92, CAG, CAU,
H01(75)
C46,
C46,
CAU, HOI (75)
C92, H01(75)
79
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Report Run Date: 03/14/96 ) Time 16:15
PRD Report Date: 04/19/95
LUIS 3.0- Page:
APPENDIX A REPORT
Case 2150[Desmidipham] Chemical 104801[Desmedlpham (ethyl m-hydroxycarbanilate carbanilate)ester]
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max. # Apps Max. Dose [ (AI Min. Restr. Geographic Limitations Use
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. ® Max. Rate unless noted Interv Entry Allowed Disallowed Limitations
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/A] (days) Interv Codes
otherwise) otherwise) Dose cycle /crop /year [day(s)]
cycle
cy Influencing Factor (Antimicrobial only)
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
))))))))))))))))))))))
SUGAR BEET (con't)
Broadcast, Foliar, Ground
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
EC
EC
EC
EC
EC
EC
WP
WP
NA
NA
NA
NA
NA
NA
NA
NA
.375
.3809
.6094
.375
.3809
1.219
.63
1.26
Ib
Ib
Ib
Ib
Ib
Ib
Ib
Ib
A
A
A
A
A
A
A
A
* NS
* NS
* NS
* NS
* NS
* NS
* NS
* NS
NS
NS
NS
NS
NS
NS
NS
NS
.6525
Ib
.96
.975
.975
Ib
Ib
Ib
.99375
Ib
1.95
.98
1.96
Ib
Ib
Ib
NS
NS
NS
NS
NS
NS
NS
NS
7
7
5
7
7
5
7
7
1
NS
1
1
NS
1
NS
1
C46, C92, H01(75)
C46, CAU, HOI(75)
C46, C92, H01(75)
C46, C92, H01(75)
C46, CAU, HOI(75)
C46, C92, CAG, CAU,
H01(75)
C46, CAU, HOI(75)
C46, C92, H01(75)
NON- FOOD/NON- FEED
BEETS (for seed crop only)
Broadcast, Postemergence, Low volume
ground sprayer
CHARD, SWISS
(for seed crop only)
Broadcast, Postemergence, Low volume
ground sprayer
Use Group: TERRESTRIAL NON-FOOD CROP
.24375 Ib A
2 NS NS NS 30 NS WA, 013
Geo.013: For use only within Western Washington.
Use Group: TERRESTRIAL NON-FOOD CROP
.24375 Ib A * 2 NS NS NS
Geo.013: See above
WA, 013
C14, C92
C14, C92
80
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Report Run Date: 03/14/96 ) Time 16:15 LUIS 3.0 - Page:
PRD Report Date: 04/19/95
APPENDIX A REPORT
Case 2150 [Desmidipham] Chemical 104801[Desmedipham (ethyl m-hydroxycarbanilate carbanilate)ester]
44444444
LEGEND
444444
Sort: Uses Eligible or Ineligible for Re-registration, Food/Feed or Non-Food/Non-Feed Uses, Alpha Site Name, Use Group Name, Alpha Application Type/Timing/Equipment
Description, Formulation, Maximum Application Rate Unit/Area Quantity, Minimum Application Rate, Maximum Number of Applications at Maximum Rate, Maximum Dose per Crop
Cycle or per Year, Minimum Interval Between Applications (Days), Restricted Entry Interval (Days), Allowed/Disallowed Geographical Areas, Use Limitations Codes.
HEADER ABBREVIATIONS
Min. Appl. Rate (AI unless : Minimum dose for a single application to a single site. System calculated. Microbial claims only.
noted otherwise)
Max. Appl. Rate (AI unless : Maximum dose for a single application to a single site. System calculated.
noted otherwise)
Soil Tex. Max. Dose : Maximum dose for a single application to a single site as related to soil texture (Herbicide claims only).
Maximum number of Applications at Maximum Dosage Rate. Example: "4 applications per year" is expressed as "4/1 yr"; "4 applications per 3
years" is expressed as "4/3 yr"
Maximum dose applied to a site over a single crop cycle or year. System calculated.
Max. # Apps © Max. Rate
Max. Dose [(AI unless
noted otherwise)/A]
Min. Interv (days)
Restr. Entry Interv (days)
PRD Report Date
Minimum Interval between Applications (days)
Restricted Entry Interval (days)
LUIS contains all products that were active or suspended (and that were available from OPP Document Center) as of this date. Some products
registered after this date may have data included in this report, but LUIS does not guarantee that all products registered after this date have
data that has been captured.
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
FORMULATION CODES
EC : EMULSIFIABLE CONCENTRATE
WP : WETTABLE POWDER
ABBREVIATIONS
AN : As Needed
NA : Not Applicable
NS : Not Specified (on label)
UC : Unconverted due to lack of data (on label), or with one of following units: bag, bait, bait block, bait pack, bait station, bait station(s), block, briquet,
briquets, bursts, cake, can, canister, capsule, cartridges, coil, collar, container, dispenser, drop, eartag, grains, lure, pack, packet, packets, pad, part,
parts, pellets, piece, pieces, pill, pumps, sec, sec burst, sheet, spike, stake, stick, strip, tab, tablet, tablets, tag, tape, towelette, tray, unit, --
APPLICATION RATE
DCNC
No Calc
W
V
U
cwt
nnE-xx
Dosage Can Not be Calculated
No Calculation can be made
PPM calculated by weight
PPM Calculated by volume
Unknown whether PPM is given by weight or by volume
Hundred Weight
nn times (10 power -xx); for instance, "1.234E-04"
is equivalent to ".0001234"
81
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Report Run Date: 03/14/96 ) Time 16:15
PRD Report Date: 04/19/95
LUIS 3.0- Page:
APPENDIX A REPORT
Case 2150[Desmidipham] Chemical 104801[Desmedlpham (ethyl m-hydroxycarbanilate carbanilate)ester]
444444444444444444444444444
USE LIMITATIONS CODES
C14 Grown for seed only.
Do not apply through any type of irrigation system.
For terrestrial uses, 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 apply where runoff is likely to occur.
Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.
day(s) preharvest interval.
C46
C92
CAG
CAU
HOI
* NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
GEOGRAPHIC CODES
013 : Other
AZ : Arizona
WA : Washington
82
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active
ingredients within the case desmedipham covered by this Reregistration Eligibility Decision
Document. It contains generic data requirements that apply to desmedipham in all products,
including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in
which they appear in 40 CFR Part 158. the reference numbers accompanying each test refer
to the test protocols set in the Pesticide Assessment Guidelines, which are available from the
National Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703)
487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
0 Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files,
this column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
83
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84
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of desmedipham
REQUIREMENT
USE PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1 Chemical Identity
61-2A Start. Mat. & Mnfg. Process
61-2B Formation of Impurities
62-1 Preliminary Analysis
62-2 Certification of limits
62-3 Analytical Method
63-2 Color
63-3 Physical State
63-4 Odor
63-5 Melting Point
63-6 Boiling Point
63-7 Density
63-8 Solubility
63-9 Vapor Pressure
63-10 Dissociation Constant
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
41607001*
41607001, 42281401
41607001
41607002
41607002*
41607002*
41607003
41607003
41607003
41607003
N/A
41607003
41214701, 41607003
41937501
41607003
Studies submitted for this guideline have been classified as supplemental, and additional data is required by the registrant to upgrade these studies to guideline acceptable.
85
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Data Supporting Guideline Requirements for the Reregistration of desmedipham
REQUIREMENT
63-11
63-12
63-13
Octanol/Water Partition
pH
Stability
USE PATTERN
AB
AB
AB
CITATION(S)
41214703
N/A
41607003,42281402, 43406001
ECOLOGICAL EFFECTS
71-1A
71-2A
71-2B
71-4A
71-4B
72-1A
72-1C
72-2A
122-1A
122-1B
122-2
123-1A
123-1B
Acute Avian Oral - Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Avian Reproduction - Quail
Avian Reproduction - Duck
Fish Toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
Seed Germination/Seedling Emergence
Vegetative Vigor
Aquatic Plant Growth
Seed Germination/Seedling Emergence
Vegetative Vigor
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
41607004
00114112,00159177*
00114111
43544901
43544902
00116713
00116714
00116712
41774101,41711401
41816401,41711401
WAIVED
42366302*
42366301*
41816401
Studies submitted for this guideline have been classified as supplemental, and additional data is required by the registrant to upgrade these studies to guideline acceptable.
86
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Data Supporting Guideline Requirements for the Reregistration of desmedipham
REQUIREMENT
USE PATTERN
CITATION(S)
123-2
Aquatic Plant Growth
141-1 Honey Bee Acute Contact
TOXICOLOGY
81-1 Acute Oral Toxicity - Rat
81-2 Acute Dermal Toxicity - Rabbit/Rat
81-3 Acute Inhalation Toxicity - Rat
81-4 Primary Eye Irritation - Rabbit
81-5 Primary Dermal Irritation - Rabbit
81-6 Dermal Sensitization - Guinea Pig
82-1A 90-Day Feeding - Rodent
82-1B 90-Day Feeding - Non-rodent
82-2 21-Day Dermal - Rabbit/Rat
83-1A Chronic Feeding Toxicity - Rodent
83-1B Chronic Feeding Toxicity -Non Rodent
83-2A Oncogenicity - Rat
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
43053501,43053502,
43053503, 43053504, 43053505
41711402
00155581
00155582
41957102
00155584
00155583
41692901,41415401,
41214704, 41214705, 40312901
40387102, 40387103, 42045701
40387104
41957101,42124201
40387107*
42045702, 40387104
00156889
40387107*
Studies submitted for this guideline have been classified as supplemental, and additional data is required by the registrant to upgrade these studies to guideline acceptable.
87
-------
Data Supporting Guideline Requirements for the Reregistration of desmedipham
REQUIREMENT
USE PATTERN
CITATION(S)
83-2B Oncogenicity - Mouse
83-3A 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
ENVIRONMENTAL FATE
160-5 Chemical Identity
161-1 Hydrolysis
161-2 Photodegradation - Water
161-3 Photodegradation - Soil
161-4 Photodegradation - Air
162-1 Aerobic Soil Metabolism
162-3 Anaerobic Aquatic Metabolism
163-1 Leaching/Adsorption/Desorption
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
42045701, 40387106
42045704, 41214706
00156724, 00156725
42045703,00156889, 00132360
40387105
41607005, 41214707, 00156887
00156886, 00156888
41214707
42880001*, 42880002*, 41607006*
41607001
00148330,00148331*
41780401, 41446101, 00098607
00098608
WAIVED
41998601*
41998602*, 00142740*
42281403*, 42124202*, 41214708*, 41214709*
Studies submitted for this guideline have been classified as supplemental, and additional data is required by the registrant to upgrade these studies to guideline acceptable.
-------
Data Supporting Guideline Requirements for the Reregistration of desmedipham
REQUIREMENT
163-2 Volatility - Lab
164-1 Terrestrial Field Dissipation
165-1 Confined Rotational Crop
165-2 Field Rotational Crop
165-4 Bioaccumulation in Fish
RESIDUE CHEMISTRY
171-4A Nature of Residue - Plants
171-4B Nature of Residue - Livestock
USE PATTERN
AB
AB
AB
AB
AB
AB
AB
CITATION(S)
WAIVED
42180501*
42909601*
WAIVED
42710101
00041862, 40274901, 41214710*
00098591,41998603,
171-4C Residue Analytical Method - Plants
171-4D Residue Analytical Method - Animal
171-4E Storage Stability
AB
AB
AB
42371301,42687401, 42822701
00076669*, 41998604*, 42921801*,
42921802*, 42921803*, 00041859*
00076669*, 41998604*, 42921801*,
42921802*, 42921803*, 00041859*
00041860
Studies submitted for this guideline have been classified as supplemental, and additional data is required by the registrant to upgrade these studies to guideline acceptable.
89
-------
Data Supporting Guideline Requirements for the Reregistration of desmedipham
REQUIREMENT
USE PATTERN
CITATION(S)
171-4J Magnitude of Residues - AB
Meat/Milk/Poultry/Egg
171-4K Crop Field Trials AB
- Sugar Beets, roots
- Sugar Beets, tops
171-4L Magnitude of the Residues in Processed Food/Feed
- Sugar Beets AB
Guideline four poultry and eggs was waived,
No tolerances established
PP#4F1459, 00116379*, 00076668*,
00041865*, 00066110*, 00070105*,
00116710*, 00049456*
PP#4F145913, 00116379*, 00076668*,
00041865*, 00066110*, 00070105*,
00116710*, 00049456*, 42516501*
42112301, No tolerances established
Studies submitted for this guideline have been classified as supplemental, and additional data is required by the registrant to upgrade these studies to guideline acceptable.
90
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GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated
elsewhere in the Reregistration Eligibility Document. Primary sources for studies in
this bibliography have been the body of data submitted to EPA and its predecessor
agencies in support of past regulatory decisions. Selections from other sources
including the published literature, in those instances where they have been considered,
are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the
case of published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a
distinct title (or at least a single subject), can stand alone for purposes of review and
can be described with a conventional bibliographic citation. The Agency has also
attempted to unite basic documents and commentaries upon them, treating them as a
single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted
numerically by Master Record Identifier, or "MRID number". This number is unique
to the citation, and should be used whenever a specific reference is required. It is not
related to the six-digit "Accession Number" which has been used to identify volumes of
submitted studies (see paragraph 4 (d) (4) below for further explanation). In a few
cases, entries added to the bibliography late in the review may be preceded by a nine
character temporary identifier. These entries are listed after all MRID entries. This
temporary identifying number is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic
conventions used reflect the standard of the American National Standards Institute
(ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the
Agency has shown an identifiable laboratory or testing facility as the author.
When no author or laboratory could be identified, the Agency has shown the
first submitter as the author.
b. Document date. The date of the study is taken directly from the document.
When the date is followed by a question mark, the bibliographer has deduced
the date from the evidence contained in the document. When the date appears
91
-------
as (19??), the Agency was unable to determine or estimate the date of the
document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained
between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the
trailing parentheses include (in addition to any self-explanatory text) the
following elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received."
(2) Administrative number. The next element immediately following the
word "under" is the registration number, experimental use permit
number, petition number, or other administrative number associated
with the earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is
defaulted to the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the
trailing parentheses identifies the EPA accession number of the volume
in which the original submission of the study appears. The six-digit
accession number follows the symbol "CDL," which stands for
"Company Data Library." This accession number is in turn followed by
an alphabetic suffix which shows the relative position of the study within
the volume.
92
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BIBLIOGRAPHY
MRID CITATION
Brehm, M. 1991a. Nor-am Response to EPA Review of Guideline 161-1 -Hydrolysis .
Sponsored and submitted by NOR-AM Chemical Company, Wilmington, DE under Report
Nos. W39, W40; Received by EPA 28 August 1991. (No MRID)
Brehm, M. 1991b. Nor-am Response to EPA Review of Guideline 161-2 -
Photodegradation in Water. Sponsored and submitted by NOR-AM Chemical Company,
Wilmington, DE under Report Nos. W39, W40; Received by EPA 28 August 1991. (No
MRID)
Brehm, M. 1991c. Nor-am Response to EPA Review of Guideline 161-3 -
Photodegradation on Soil. Sponsored and submitted by NOR-AM Chemical Company,
Wilmington, DE under Report Nos. W39, W40; Received by EPA 28 August 1991. (No
MRID)
Chiou, C.T., D.W. Schmedding, and M. Manes. 1982. Partitioning of organic compounds
in octanol-water systems. Envir. Sci. Technol. 16:4-10.
Desmedipham labels.
Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger. 1994. Literature review and evaluation of
the EPA food-chain (Kenaga) nomogram, an instrument for estimating pesticide residues
on plants. Environ. Toxicol. Chem. Vol.13: pp 1383-1391.
Government of Canada. 1994. Canadian Environmental Protection Act Priority
Substances List Assessment Report - Aniline . Minister of Supply and Services Canada.
Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of
representative data as a basis for estimation of their magnitude in the environment.
Environmental Quality and Safety. Vol. 1: pp. 9-28.
Hoheisel, C., J. Karrie, et al., 1992. Pesticides in Ground Water Database -A Compilation
of Monitoring Studies: 1971 - 1991. USEPA, Office of Pesticide Programs, Washington,
D.C.
Kenaga, E.E. 1973. Factors to be considered in the evaluation of the toxicity of
pesticides to birds in their environment. Environmental Quality and Safety. Vol. 2: pp.
166-181.
Lee, R. n.d. FATE - A program for calculating daily estimated residues of pesticides on
vegetation based on first order dissipation characteristics at an assumed rate . USEPA,
Office of Pesticide Programs, Washington, D.C.
U.S. EPA, 1993. Memorandum dated 8 March 1993. Use Sites that may Require Estuarine
Tests". USEPA, Office of Pesticide Programs, EFED/EEB, Washington, D.C.
93
-------
MRID
BIBLIOGRAPHY
CITATION
U.S. EPA, 1994. Drinking Water Regulations and Health Advisories . Office of Water,
Washington, D.C., November 1994.
U. S. EPA 1995. Toxicology Endpoint Selection Document for Desmedipham.
Dated 8/24/95.
U.S. EPA, 1995. LUIS Report for Desmedipham. Dated 7/27/95.
Vershueren, K. 1977. Handbook of Environmental Data on Organic Chemicals . Van
Nostrand Reinhold Company.
00049456 Nor-Am Agricultural Products, Incorporated (1976) Residue Data: Betanex
Aerial Application; Betanax Sequential Application. (Compilation; unpublished
study received on unknown date under unknown admin, no.; CDL:226427-B)
00132360 Becker, H.; Mueller, E.; Hofer, P.; et al. (1983) Embryotoxicity (Including
Teratogenicity) Study with Desmedipham Technical in Rabbits: RCC Project
014613. (Unpublished study received Sep 6, 1983 under 2139-119; prepared
by Research and Consulting Co. Ltd., Switz., submitted by Nor-Am
Agricultural Products, Inc., Naperville, IL; CDL:251513-A)
00142740 Repenthin, W. (1982) Determination of the Rate of Hydrolysis of
Phenmedipham at 22 deg. C and pH values of 5, 7 and 9: Report
No.APC39/82. Unpublished report prepared by Schering AG. 21 p
00041859 Nor-Am Agricultural Products, Incorporated (1972) Specificity ofSN 38 107
Residue Method in the Presence of Other Pesticides: Report No. 475/25.
(Unpublished study received Apr 11, 1972 under 2G1262; CDL:095558-C)
00041860 Nor-Am Agricultural Products, Incorporated (1972) Storage Stability of Ethyl-
m-hydroxycarbanilate carbanilate (SN 38 107) in Spiked Sugar Beet Root and
Top Samples: Report No. 475/26. (Unpublished study received Apr 11, 1972
under 2G1262; CDL: 095558-D)
00041862 Knowles, C.O.; Sonawane, B.R. (1971?) Ethyl-m-hydroxycarbanilate
carbanilate (EP-475) Metabolism in Sugar Beets. (Unpublished study received
Apr 11, 1972 under 2G1262; prepared by Univ. of Missouri, Agricultural
Experiment Station, Dept. of Entomology, submitted by Nor-Am Agricultural
Products, Inc., Naperville, 111.; CDL:095558-F)
00041865 Jenny, N.A.; Feller, R.; Schweizer, E.E.; et al. (1971) Residue Reports: SN 38
107 on Sugar Beets: Residue Report 475/2. (Unpublished study including
94
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MRID
BIBLIOGRAPHY
CITATION
residue reports 475/3, 475/4, 475/9..., received Apr 11, 1972 under 2G1262;
prepared in cooperation with Colorado State Univ. and others, submitted by
Nor Am Agricultural Products, Inc., Naperville, 111.; CDL:095558-I)
00066110 Nor-Am Agricultural Products, Incorporated (1976) Residues of Desmedipham
in Sugar Beets after Repeat Applications ofBetanex. (Compilation; unpublished
study received Jan 4, 1977 under 2139119; CDL:228696-A)
00070105 Nor-Am Agricultural Products, Incorporated (1978) Residues of Desmedipham
in Sugar Beets after Aerial Application ofBetanex. (Compilation; unpublished
study received Mar 29, 1978 under 2139-119; CDL:233360-A)
00076668 Nor-Am Agricultural Products, Incorporated (1974?) Desmedipham: The
Results of Tests on the Amount of Residue Remaining, Including a Description
of the Analytical Method Used. (Unpublished study received May 21, 1981
under 2139-EX-28; CDL: 070109-A)
00076669 Jenny, N. (1971) Gas Chromatographic Residue Determination ofEthyl-
M-hydroxycarbanilate (Nor-Am SN 38 107, Sobering SN 38 107): Report No.
475/1. Method dated Apr 15, 1971. (Unpublished study received May 21,
1981 under 2139-EX-28; submitted by Nor-Am Agricultural Products, Inc.,
Naperville, 111.; CDL: 070109-B)
00098591 Herrett, R.J. (1973) Desmedipham Distribution in the Dairy Goat: Project No.
715.11.17.01. (Unpublished study received Apr 20, 1982 under 2F2673;
prepared by Morton-Norwich Products, Inc., submitted by Nor-Am
Agricultural Products, Inc., Naperville, 111.; CDL:070792-D)
00098607 Klehr, M.; Riemann, J. (1981) Photolysis of Desmedipham (DMP, SN 38 107)
in Aqueous Solution: Bericht-Nr. APC 64/81. (Unpublished study received Apr
20, 1982 under 2F2673; prepared by Schering AG, West Germany, submitted
by Nor-Am Agricultural Products, Inc., Naperville, 111.; CDL:070793-S)
00098608 Klehr, M.; Riemann, J. (1982) Photodegradation of Desmedipham (DMP, SN
38107) on Soil Surfaces: Bericht-Nr. APC 02/82. (Unpublished study received
Apr 20, 1982 under 2F2673; prepared by Schering AG, West Germany,
submitted by Nor-Am Agricultural Products, Inc., Naperville, 111.;
CDL:070793-T)
00114111 Fletcher, D. (1982) Report to Nor-Am Agricultural Products, Inc.: 8-day
Dietary LC50 Study with Desmedipham Technical in Mallard Ducklings: BLAL
No. 82 DC 13. (Unpublished study received Aug 30, 1982 under 2139-119;
95
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MRID
BIBLIOGRAPHY
CITATION
prepared by Bio-Life Assoc., Ltd., submitted by Nor-Am Agricultural
Products, Inc., Naperville, IL; CDL:248230-A)
00114112 Fletcher, D. (1982) Report to ...: 8-day Dietary LC50 Study with Desmedipham
Technical in Bobwhite Quail: BLAL No. 82 QC 13. (Unpublished study
received Aug 30, 1982 under 2139-119; prepared by Bio-Life Assoc., Ltd.,
submitted by Nor-Am Agricultural Products, Inc., Naperville, IL;
CDL:248231-A)
00116379 Nor-Am Agricultural Products, Inc. (1974) Desmedipham: The Results of Tests
on the Amount of Residue Remaining, Including a Description of the Analytical
Method Used. (Compilation; unpublished study received Jan 31, 1975 under
4F1459; CDL:093890-B)
00116710 Nor-Am Agricultural Products, Inc. (1976) Residue Data: Betanex Aerial
Application; Betanex Sequential Application. (Compilation; unpublished study
received on unknown date under unknown admin, no.; CDL:225842-A)
00116712 Morrissey, A. (1978) Acute Toxicity of Desmedipham Technical to the Water
Flea ...: UCES Project No. 11506-74-01. (Unpublished study received Aug 9,
1978 under 2139-118; prepared by Union Carbide Corp., submitted by Nor-Am
Agricultural Products, Inc., Naperville, IL; CDL:235009-A)
00116713 Schneider, C. (1979) The Acute Toxicity of Desmedipham Technical to the
Bluegill Sunfish ...: UCES Proj. No. 11506-74-03. (Unpublished study
received Mar 27, 1979 under 2139-119; prepared by Union Carbide Corp.,
submitted by Nor-Am Agricultural Products, Inc., Naperville, IL;
CDL:237908-A)
00116714 Schneider, C. (1979) The Acute Toxicity of Desmedipham Technical to the
Rainbow Trout...: UCES Proj. No. 11506-74-02. (Unpublished study received
Mar 27, 1979 under 2139-119; prepared by Union Carbide Corp., submitted by
Nor-Am Agricultural Products, Inc., Naperville, IL; CDL:237908-B) [Ace. #
237908]
00155581 Ullmann, L.; Sacher, R. (1984) Acute Oral Toxicity (LD50) Study with
Desmedipham Technical (SN 38107) in Rats: Project No. 031151.
Unpublished Schering Project No. PF-84 809 prepared by Research &
Consulting Co., AG. 26 p. [Ace. No. 261116]
00155582 Ullmann, L.; Suter,B. (1984) Acute Dermal Toxicity (LD50) Study with
Desmedipham Technical (SN 38107) in Rabbits: Project #0311162.
96
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MRID
BIBLIOGRAPHY
CITATION
Unpublished Schering Project No. PF-84.810 prepared by Research &
Consulting Co., AG. 24 p.
00155583 Ullmann, L.; Suter, B. (1984) Primary Skin Irritation Study with
Desmedipham Technical (SN 38.107) in Rabbits (4-hour Occlusive
Application): Project No. 031173. Unpublished Schering Project No.
PF-84.811 prepared by Research & Consulting Co., AG. 24 p.
00155584 Ullmann, L.; Suter, B. (1984) Primary Eye Irritation Study with Desmedipham
Technical (SN 38.107) in Rabbits: Project No. 031184. Unpublished Schering
Project No. PF-83.805 prepared by Reserach & Consulting Co., AG. 25 p.
00156724 Becker, H. (1985) Embryotoxicity (Including Teratogenicity) Study with
Desmedipham Technical in the Rat: Project No. 024996. Unpublished report
prepared by Research Consulting Co. 130 p.
00156725 Becker, H. (1985) Embryotoxicity (Including Teratogenicity) Study with
Desmedipham Technical in the Rat: Project No. 043053. Unpublished report
prepared by Research Consulting Co. 136 p.
00156886 Herbst-Guenard, J. (1985) Mouse Micronucleus Assay with Desmedipham
Technical: Project 041433. Unpublished study prepared by Research &
Consulting Company. 25 p.
00156887 Brown, A.; McGregor, D. (1984) Mouse Lymphoma Mutation Assay:
Technical Desmedipham: IRI Project No. 732433: Sponsor's Study No. TOX
84072. Unpublished study prepared by Inveresk Research International. 37 p.
00156888 Allen, J.; Brooker, P.; Howell, A.(1984) Metaphase Chromosome Analysis of
Human Lymphocytes Cultured in vitro: Technical Desmedipham: SHG
210/84986: Sponsors Study No. Tox 84073. Unpublished study prepared by
Huntingdon Research Centre pic. 16 p.
00156889 Bathe, R. (1985) 12-Month Oral Toxicity (Feeding) Study with Desmedipham
Technical in Beagle Dogs: Final Report: Project 011913. Unpublished study
prepared by Research & Consulting Company. 420 p.
00159177 Krize, K. (1978) Avian Dietary LC50 (5-day Dietary Exposure) of Desmedipham
Technical to Bobwhite Quail: Laboratory No. 8E-1527. Unpublished study
prepared by Cannon Laboratories, Inc. 12 p.
97
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MRID
BIBLIOGRAPHY
CITATION
40274901 Celerio, J. (1987) M16-Metabolism of Phenmedipham in the Sugar Beet (Beta
vulgaris L.). Unpublished study prepared by Technische Universitat Berlin.
147 p.
40312901 Ullmann, L. (1987) T58 Desmedipham: Contact Hypersensitivity to
Desmedipham Techn. in Albino Guinea Pigs—Maximization Test: Laboratory
Project ID: PF-86.836. Unpublished study prepared by Research & Consulting
Co. AG. 43 p.
40387102 Suter, P.; Horst, K.; Luetkemeier, H.; et al. (1984) T37 Desmedipham:
13-Week Oral (Feeding) Toxicity Study with Desmedipham Technical in Rats:
Laboratory Project ID: 015153. Unpublished study prepared by Research &
Consulting Co., AG. 236 p.
40387103 Suter, P. (1985) T51 Desmedipham: 13-Week Oral Toxicity (Feeding) Study
with Desmedipham Technical in the Rat: Laboratory Project ID: PF-85.814.
Unpublished study prepared by Research & Consulting Co., AG. 500 p.
40387104 Hounsell, L; Martin, P. (1986) T53-Desmedipham: Technical Desmedipham:
90 Day Dietary Study in the Dog: Laboratory Project ID:TOX/86/198-ll.
Unpublished study prepared by FBC Ltd. 313 p.
40387105 Becker, H.; et al. (1986) T54 Desmedipham: Multiple Generation Reproduction
Study with Desmedipham Technical in Rats: Laboratory Project ID: PF-82.810.
Unpublished study prepared by Research & Consulting Co., AG. 1057 p.
40387106 Suter, P.; et al. (1986) T55-Desmedipham: 104-Week Oncogenicity Study with
Desmedipham Technical in Mice—Dietary Administration: Laboratory Project
ID: PF 83.812. Unpublished study prepared by Huntingdon Research Centre.
1085 p.
40387107 NOR-AM Chemical Co. (1986) T56-Desmedipham: Final Report: 2 Year
Chronic Toxicity/Oncogenicity Study with Desmedipham Technical in Rats:
Laboratory Project ID No: 020968. Unpublished study prepared by Research
& Consulting Co., AG. 1613 p.
41214701 Miklautz, H. (1988) C39 Desmedipham Solubility in Water at 25°Degree C.:
Project ID APC 16/88. Unpublished study prepared by Scheuing AG. 12 p.
41214703 Miklautz, H. (1987) C35 Desmedipham: Determination of the Partition
Coefficient of Desmedipham: (Schering Code No. ZK 14 494): Project ID APC
49/87. Unpublished study prepared by Schering AG. 17 p.
98
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MRID
BIBLIOGRAPHY
CITATION
41214706 Allen, P. et.al. (1988) T69 Desmedipham: Limit Test of Embryotoxicity and
Teratogenicity with Desmedepham Technical in the Rat (Dermal Application):
Project ID TB 87042. Unpublished study prepared by Research & Consulting
Co. AG. 179 p.
41214707 Cifone, M. (1988) Mutagenicity Test on Desmedipham Technical in the Rat
Primary Hepatocyte Unscheduled DNA Synthesis Assay: Project ID TB 87037.
Unpublished study prepared by Hazleton Laboratories of America. 29 p.
41214708 Feyerabend, M.; Bruhl, R. (1989) W64/2 Desmedipham: TheMobilility of
3-Amino-UL14C-Phenoxy-Desmedipham in four Soils Determined by Soil TLC:
Project ID UPSR 76/88-PA 38107.7/17. Unpublished study prepared by
Schering AG. 32 p.
41214709 Bruhl, R. (1987) W59-Desmedipham: The Adsorption of Desmedipham to Soils:
Project ID UPSR 19/87-PA 38 107.7/6. Unpublished study prepared by
Schering AG. 19 p.
41214710 Bruhl, R. (1989) M10 Desmedipham: The Metabolism of Desmedipham in
Sugar Beet: Project ID UPSR 38/89. Unpublished study prepared by Schering
Ag. 206 p.
41446101 Brehm, M. (1989) Photolysis of Desmedipham (DMP, SN 38107) in Aqueous
Solution W42: Supplement 1: Lab Project I.D.: APC 39/88. Unpublished study
prepared by Schering AG. 10 p.
41607001 Steib, C. (1990) Desmedipham Technical-Product Chemistry: Lab Project
Number: 90/066; 90/095; 90/064. Unpublished study prepared by Schering
AG. 68 p.
41607002 Muller, T.; Steib, C. (1990) Desmedipham Technical-Product Chemistry: Lab
Project Number: 90/033; 90/078; 90/032. Unpublished study prepared by
Schering AG. 55 p.
41607003 Steib, C. ; Lehne, V. ; Muller, T. ; et al. (1990) Desmedipham Tech
nical-Product Chemistry: Lab Project Number: 90/019: 90/074: 90/044.
Unpublished study prepared by Schering AG. 142 p.
41607004 Hakin, B.; Johnson, A. (1990) Technical Desmedipham: Acute Oral Toxicity
(LD50) to Bobwhite Quail (W78): Lab Project Number: SMS 198/90728 (TOX
89290). Unpublished study prepared by Huntingdon Research Center, Ltd. 23
P-
99
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MRID
BIBLIOGRAPHY
CITATION
41607005 Poth, A. (1990) T79 Desmedipham: Salmonella typhimurium and escherchia
coli Reverse Mutation Assay with Desmedipham: Lab Project Number: TB 89
057. Unpublished study prepared by Cytotest Cell Research GMBH & Co,
KG. 39 p.
41607006 Challis, I.; Greedy, C. (1990) The Metabolism of Demedipham in the Rat
(Mil): Lab Project Number: TOX/90-198-16; TOX/89360. Unpublished study
prepared by Schering Agrochemicals Ltd. 102 p.
41711401 Foertsch, A. (1990) Investigation into the Phytotoxic Effects of Desmedipham
on Seed Germination (Tier I): Lab Project Number: 501 AL. Unpublished
study prepared by Nor-Am Chemical Co. 38 p.
41711402 Barrett, K. (1990) Desmedipham (W-91): The Acute Oral and Topical
Toxicities of Desmedipham to Worker Honeybees (Apis mellifera L.): Lab
Project Number: ENVIR 90/45. Unpublished study prepared by Schering
Agrochemicals Ltd. 24 p.
41774101 Downey, S. (1991) Investigation into the Phytotoxic Effects of Desmedipham on
Seedling Emergence (Tier 1): Lab Project Number: 502 AL. Unpublished
study prepared by Nor-Am Chemical Co. 61 p.
41816401 Downey, S. (1991) Investigation into the Phytotoxic Effects of
DesmediphamAV98 on Vegetative Vigor: Lab Project Number: 503 AL.
Unpublished study prepared by Nor-Am Chemical Co. 95 p.
41937501 Miklautz, H. (1990) C86 Desmedipham: The Temperature Dependence of the
Vapor Pressure of Desmedipham (ZK 14 494): Lab Project Number: APC
74/90. Unpublished study prepared by Schering AG. 19 p.
41957101 Cornelissen, K. (1991) Carbon 14-Desmedipham: Dermal Absorption in the
Rat: Lab Project Number: 6510-194/39. Unpublished study prepared by
HazletonUk. 480 p.
41957102 Thevenaz, Ph. (1990) 4-Hour Acute Inhalation Toxicity Study with
Desmedipham Technical in the Rat: Lab Project Number: 268457: TB 0019.
Unpublished study prepared by RCC, Research and Consultin Co., AG. 50 p.
41998601 Forster, V. (1991) W104 Desmedipham: The Degredation and Metabolism of
Desmedipham in German Standard Soil 2.3 (Sandy Loam) Under Aerobic
Conditions at 21 °C: Lab Project Number: UPSR 34/91. Unpublished study
prepared by Schering Ag. 43 p.
100
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BIBLIOGRAPHY
MRID
CITATION
41998602 Forster, V. (1991) W96 Desmedipham: The Anaerobic Aquatic Behavior of
Desmedipham in a Simulated Sediment/Water Ecosystem Taken from
Hubertussee, Berlin: Lab Project Number: UPSR 34/90. Unpublished study
prepared by Sobering Ag. 28 p.
41998603 Greedy, C. (1991) M14 Desmedipham: The Magnitude and Nature of
Desmedipham Residues in the Laying Hen Following Daily Oral Adminisration
of 1.5 MG Carbon14-Desmedipham Per Bird: Lab Project Number:
TOX/91/198-26. Unpublished study prepared by Schering Agr. Ltd. 64 p.
41998604 Bowman, M. (1991) Testing of Desmedipham Through US FDA Multiresidue
Methods: Lab Project Number: R342.50.90: MCB-NOR-AM/MR-1.
Unpublished study prepared by M. C. Bowman & Associates. 30 p.
42032404 Malarkey, P.; Wason, S. (1990) T76 Desmedipham: Betamix WP 70 (CQ
1232): Rat Acute Oral Toxicity Study: Lab Project Number: TOX/90/129-29.
Unpublished study prepared by Schering Agrochemicals Ltd. 24 p.
42032004 Baldrick, P.; Healing, G. (1990) T84 Desmedipham: Betanex WP 70
Formulation, CR 19520/1: Acute Oral Toxicity to Rats: Lab Project Number:
TOX 89077. Unpublished study prepared by Huntingdon Research Centre Ltd.
21 p.
42045701 Suter, P. (1984) T38 Desmedipham: 28-Day Oral Toxicity (Feeding) Study
with Desmdipham Technical in Mice: Lab Project Number: RCC 020946.
Unpublished study prepared by Research & Consulting Company AG. 175 p.
42045702 Allen, T.; Corney, S.; Frei, T.; et al. (1989) Determination of the No-Effect
Level for Methemoglobin Production Following Desmedipham Technical
Administration in the Dog (Oral/ Feeding Route): Lab Project Number:
250288: TB 89 055. Unpublished study prepared by RCC Research and
Consulting Company AG, RCC Umweltchemie AG and Patco Experimental
Pathology Consulting AG. 204 p.
42045703 Becker, H. (1984) T23 (Including Addendum) Desmedipham Technical:
Embryotoxicity (Including Teratogenicity) Study With Desmedipham
Technical: Lab Project Number: 014613. Unpublished study prepared by RCC
Research and Consulting Company AG. 254 p.
42045704 Kaiser, R. (1991) T49 Amendment 1 Desmedipham: Embryotoxicity (Including
Teratogenicity) Study With Desmedipham Technical in the Rat: Lab Project
Number: 043053. Unpublished study prepared by RCC Research & Consulting
Company Ag. 7 p.
101
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MRID
BIBLIOGRAPHY
CITATION
42112301 Brady, S. (1991) Residues of Desmedipham in Sugar Beets and Processed
Commodities Treated with Betanex: USA, 1990: Lab Project Number:
R342.01.90. Unpublished study prepared by Nor-Am Chemical Co. 50 p.
42124201 Ullmann, L.; Sacher, R.; Luetkemeier, H. et al. (1986) T57 Desmedipham:
21-Day Dermal Toxicity Study with Betanex in the Rabbit: RCC Project No.
051085; Study No. PVER 85053; PF-85.835. Unpublished study prepared by
RCC Research & Consulting Co. AG. 233p.
42124202 Bruhl, R.; Celorio, J. (1981) W32 Desmedipham: Mobility of UL 14Carbon
-aminophenoxy-desmedipham in Four Soils: Lab Project No. PA 38 107.72/6.
Unpublished study prepared by Schering AG. 13 p.
42180501 Castro, L. (1991) Dissipation of Desmedipham and Its Major Metabolites in
Soil Following the Application of Betanex EC at the Highest Label Rate in
Sugar Beet Trials in the USA, 1989: Lab Project Number: R342.03.89.
Unpublished study prepared by Nor-Am Chemical Co. 336 p.
42281401 Kruger, W. (1992) C63 Addendum 1 Desmedipham: Technical Specifications
& Safety Data Sheets for the Beginning Materials: Unpublished study prepared
by Schering AG. 61 p.
42281402 Steib, C. (1992) Cl 10 Desmedipham-Stability to Metals and Metal Ions: Lab
Project Number: 92/018. Unpublished study prepared by Schering AG. 8 p.
42281403 Forster, V. (1992) W63/3 Desmedipham: The Mobility of UL-Carbon14
Desmedipham Following Aging in Hatzenbuhl Soil: Lab Project Number: UPSR
60/91. Unpublished study prepared by Schering AG 27 p.
42366301 Willard, T. (1992) W109 Desmedipham: Study of the Effects of Desmedipham
on Plant Vegetative Vigor: A Tier 2 Terrestrial Non-target Plant Hazard
Evaluation: Lab Project Number: 505 AL. Unpublished study prepared by
American Agric. Services, Inc. 28 p.
42366302 Willard, T. (1992) WHO Desmedipham: Study of the Effects of Desmedipham
on Seedling Emergence: A Tier 2 Terrestrial Non-Target Plant Hazard
Evaluation: Lab Project Number: 506AL. Unpublished study prepared by
American Agric. Services, Inc. 50 p.
42371301 Greedy, C. (1992) M15 Desmedipham: The Magnitude and Nature of
Desmedipham Residues in the Milk and Meat of a Cow Following Oral
Administration for Four Days at 0.4 mg/kg Body Weight: Lab Project Number:
102
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MRID
BIBLIOGRAPHY
CITATION
TOX/92/198-28. Unpublished study prepared by Schering Agrochemicals Ltd.
40 p.
42516501 Brady, S. (1992) Comparison of Desmedipham-derived At-harvest Residues in
or on Sugarbeets Resulting from Application of Betanex WP with Those
Resulting from Application of Betanex EC, USA, 1991: Lab Project Number:
AL-91R-01. Unpublished study prepared by NOR-AM Chemical Co. 82 p.
42687401 Greedy, C. (1992) The Magnitude and Nature of Desmedipham Residues in the
Laying Hen following Daily Oral Administration of 1.5 mg (carbon 14) Des-
medipham per Bird: M14, Supplement 1: Response to EPA 9/30/92 Review:
Lab Project Number: 030305. Unpublished study prepared by Schering
Agrochemical Ltd. lip.
42710101 Blakemore, G.; Voney, S.; Stuerman, L. (1993) Uptake, Depuration and
Bioconcentration of C14-Desmedipham by Bluegill Sunfish (Lepomis
macrochirus): Lab Project Number: 39258: 5HAL. Unpublished study
prepared by ABC Labs, Inc. 104 p.
42822701 Greedy, C. (1993) M15 Addendum 1: Desmedipham: The Magnitude and
Nature of Desmedipham Residues in the Milk and Meat of a Cow Following
Oral Administration for 4 Days at 0.4 mg/kg Bodyweight: Lab Project Number:
TOX/92/198-28: TOX90459. Unpublished study prepared by Schering
Agrochemical Ltd. 82 p.
42880001 Greedy, C. (1993) M16 Desmedipham: Absorption Distribution and Excretion
in Rats Following Oral Administration: Lab Project Number: TOX/93/198-31.
Unpublished study prepared by Schering Agrochemical Ltd. 45 p.
42880002 Greedy, C. (1993) M17 Desmedipham: Metabolism in the Rat: Lab Project
Number: TOX/93/198-32. Unpublished study prepared by Schering
Agrochemical Ltd. 165 p.
42909601 Meyer, B.; Downey, S. (1993) Confined Accumulation Study of
(C14)-Desmedipham in Rotational Crops: Lab Project Number: 500AL.
Unpublished study prepared by NOR-AM Chemical Co. 156 p.
42921801 Straszewski, A.; Wrede-Rucker, A. (1993) R75 Desmedipham: Analytical
Method for the Determination of Residues of Desmedipham and a Major
Metabolite in Sugar Beet (Leaves/Roots) by HPLC: Lab Project Number: U/R
46/92: PA 14 494.5/16. Unpublished study prepared by Schering AG. 32 p.
103
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BIBLIOGRAPHY
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CITATION
42921802 Williams, L. (1993) Validation of an Analytical Method for the Determination
of Residues of Desmedipham and a Major Metabolite in Sugar Beet Leaves and
Roots by HPLC: Lab Project Number: AL-93R-06. Unpublished study
prepared by NOR-AM Chemical Co. 28 p.
42921803 Wrede-Rucker, A. (1993) Desmedipham: Comments on the Development of an
Analytical Method for the Determination of Desmedipham and its Major
Metabolites EHPC in Sugar Beet Roots and Leaves: Lab Project Number:
PF-RAN. Unpublished study prepared by Schering AG. 18 p.
43053501 Hughes, J.; Williams, T. (1993) The Toxicity of Desmedipham Technical to
Selenastrum capricornutum (Tier 2): Lab Project Number: B643/022/1: 513AL.
Unpublished study prepared by Malcolm Pirnie, Inc. 36 p.
43053502 Hughes, J.; Williams, T. (1993) The Toxicity of Desmedipham Technical to
Anabaena flos-aquae (Tier 1): Lab Project Number: B643/022/2: 515AL.
Unpublished study prepared by Malcolm Pirnie, Inc. 32 p.
43053503 Hughes, J.; Williams, T. (1993) The Toxicity of Desmedipham Technical to
Navicula pelliculosa (Tier 2): Lab Project Number: B643/022/3: 516AL.
Unpublished study prepared by Malcolm Pirnie, Inc. 36 p.
43053504 Hughes, J.; Williams, T. (1993) The Toxicity of Desmedipham Technical to
Skeletonema costatum (Tier 1): Lab Project Number: B643/022/4: 517AL.
Unpublished study prepared by Malcolm Pirnie, Inc. 33 p.
43053505 Hughes, J.; Williams, T. (1993) The Toxicity of Desmedipham Technical to
Lemna gibba G3 (Tier 1): Lab Project Number: B643/022/5: 518AL.
Unpublished study prepared by Malcolm Pirnie, Inc. 31 p.
43406001 Mueller, T. (1994) C117 Desmedipham: Stability to Ions and Metal: Lab
Project Number: 94/035. Unpublished study prepared by Hoechst Schering
AgrEvo GmbH. 30 p.
43544901 Beavers, J.; Haberlein, D.; Mitchell, L.; et al. (1995) W142 Technical
Desmedipham: Northern Bobwhite Quail Dietary One Generation Reproduction
Study: Lab Project Number: 312-105: TOX/92030/92029: TOX/92030.
Unpublished study prepared by Wildlife International Ltd. 219 p.
43544902 Beavers, J.; Haberlein, D.; Mitchell, L.; et al. (1995) W142 Technical
Desmedipham: Mallard Duck Dietary One Generation Reproduction Study: Lab
Project Number: 312-106: TOX/92032/92031: TOX/92032. Unpublished study
prepared by Wildlife International Ltd. 225 p.
104
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 1 of this Notice, the Data Call-in Chemical Status Sheet, to
submit certain product specific data as noted herein to the U.S. Environmental Protection
Agency (EPA, the Agency). These data are necessary to maintain the continued registration of
your product(s) containing this active ingredient. Within 90 days after you receive this Notice
you must respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 6; or
2. Why you believe you are exempt from the requirements listed in this Notice and
in Attachment 3, Requirements Status and Registrant's Response Form, (see
section III-B); or
3. Why you believe EPA should not require your submission of product specific
data in the manner specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list of
all of your products subject to this Notice in Attachment 2, Data Call-In Response Form, as
well as a list of all registrants who were sent this Notice (Attachment 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 03-31-96).
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This Notice is divided into six sections and six Attachments. The Notice itself contains
information and instructions applicable to all Data Call-in Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse
Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Response Form
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
6 - Cost Share and Data Compensation Forms
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the
data needed to support continued registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product specific data. No additional
generic data requirements are being imposed. You have been sent this Notice because you
have product(s) containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment 3,
Requirements Status and Registrant's Response Form. Depending on the results of the studies
required in this Notice, additional testing may be required.
II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment 3, Requirements Status and Registrant's Response Form, within the time frames
provided.
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II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD-recommended test standards conform to those specified
in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the OECD
protocols, they should be modified as appropriate so that the data generated by the study will
satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend deadlines for
complying with data requirements when the studies were not conducted in accordance with
acceptable standards. The OECD protocols are available from OECD, 2001 L Street, N.W.,
Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone number 202-785-
0350).
All new studies and proposed protocols submitted in response to this Data Call-in Notice
must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B) NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change the
requirements of any previous Data Call-In(s), or any other agreements entered into with the
Agency pertaining to such prior Notice. Registrants must comply with the requirements of all
Notices to avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for product specific data must
be submitted to the Agency within 90 days after your receipt of this Notice. Failure to adequately
respond to this Notice within 90 days of your receipt will be a basis for issuing a Notice of Intent
to Suspend (NOIS) affecting your products. This and other bases for issuance of NOIS due to
failure to comply with this Notice are presented in Section IV-A and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this notice or
(c) request a data waiver (s).
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A discussion of how to respond if you chose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product specific
data requirements of this Notice is contained in Section III-C. A discussion of options relating to
requests for data waivers is contained in Section III-D.
There are two forms that accompany this Notice of which, depending upon your response,
one or both must be used in your response to the Agency. These forms are the Data-Call-in
Response Form, and the Requirements Status and Registrant's Response Form, Attachment 2 and
Attachment 3. The Data Call-in Response Form must be submitted as part of every response to
this Notice. In addition, one copy of the Requirements Status and Registrant's Response Form
must be submitted for each product listed on the Data Call-In Response Form unless the voluntary
cancellation option is selected or unless the product is identical to another (refer to the instructions
for completing the Data Call-In Response Form in Attachment 2). Please note that the company's
authorized representative is required to sign the first page of the Data Call-In Response Form and
Requirements Status and Registrant's Response Form (if this 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.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by requesting
voluntary cancellation of your product(s) containing the active ingredient that is the subject of this
Notice. If you wish to voluntarily cancel your product, you must submit a completed Data Call-In
Response Form, indicating your election of this option. Voluntary cancellation is item number 5
on the Data Call-In Response Form. If you choose this option, this is the only form that you are
required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
2. Satisfying the Product Specific Data Requirements of this Notice There are various
options available to satisfy the product specific data requirements of this Notice. These options
are discussed in Section III-C of this Notice and comprise options 1 through 6 on the
Requirements Status and Registrant's Response Form and item numbers 7a and 7b on the Data
Call-in Response Form. Deletion of a use(s) and the low volume/minor use option are not valid
options for fulfilling product specific data requirements.
3. Request for Product Specific Data Waivers. Waivers for product specific data are
discussed in Section III-D of this Notice and are covered by option 7 on the Requirements Status
and Registrant's Response Form. If you choose one of these options, you must submit both forms
as well as any other information/data pertaining to the option chosen to address the data
requirement.
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III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form that you agree to satisfy the
product specific data requirements (i.e. you select item number 7a or 7b), then you must select
one of the six options on the Requirements Status and Registrant's Response Form related to data
production for each data requirement. Your option selection should be entered under item
number 9, "Registrant Response." The six options related to data production are the first six
options discussed under item 9 in the instructions for completing the Requirements Status and
Registrant's Response Form. These six options are listed immediately below with information in
parentheses to guide registrants to additional instructions provided in this Section. The options
are:
(1) I will generate and submit data within the specified time frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1, Developing Data — If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced herein and
in the attachments. All data generated and submitted must comply with the Good Laboratory
Practice (GLP) rule (40 CFR Part 160), be conducted according to the Pesticide Assessment
Guidelines (PAG), and be in conformance with the requirements of PR Notice 86-5.
The time frames in the Requirements Status and Registrant's Response Form are the time
frames that the Agency is allowing for the submission of completed study reports. The noted
deadlines run from the date of the receipt of this Notice by the registrant. If the data are not
submitted by the deadline, each registrant is subject to receipt of a Notice of Intent to Suspend the
affected registration(s).
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.
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Option 2, Agreement to Share in Cost to Develop Data — Registrants may only choose
this option for acute toxicity data and certain efficacy data and only if EPA has indicated in the
attached data tables that your product and at least one other product are similar for purposes of
depending on the same data. If this is the case, data may be generated for just one of the products
in the group. The registration number of the product for which data will be submitted must be
noted in the agreement to cost share by the registrant selecting this option. If you choose to enter
into an agreement to share in the cost of producing the required data but will not be submitting
the data yourself, you must provide the name of the registrant who will be submitting the data.
You must also provide EPA with documentary evidence that an agreement has been formed. Such
evidence may be your letter offering to join in an agreement and the other registrant's acceptance
of your offer, or a written statement by the parties that an agreement exists. The agreement to
produce the data need not specify all of the terms of the final arrangement between the parties or
the mechanism to resolve the terms. Section 3(c)(2)(B) provides that if the parties cannot resolve
the terms of the agreement they may resolve their differences through binding arbitration.
Option 3, Offer to Share in the Cost of Data Development — This option only applies to
acute toxicity and certain efficacy data as described in option 2 above. If you have made an offer
to pay in an attempt to enter into an agreement or amend an existing agreement to meet the
requirements of this Notice and have been unsuccessful, you may request EPA (by selecting this
option) to exercise its discretion not to suspend your registration(s), although you do not comply
with the data submission requirements of this Notice. EPA has determined that as a general
policy, absent other relevant considerations, it will not suspend the registration of a product of a
registrant who has in good faith sought and continues to seek to enter into a joint data
development/cost sharing program, but the other registrant(s) developing the data has refused to
accept your offer. To qualify for this option, you must submit documentation to the Agency
proving that you have made an offer to another registrant (who has an obligation to submit data)
to share in the burden of developing that data. You must also submit to the Agency a completed
EPA Form 8570-32, Certification of Offer to Cost Share in the Development of Data, Attachment
7. In addition, you must demonstrate that the other registrant to whom the offer was made has
not accepted your offer to enter into a cost sharing agreement by including a copy of your offer
and proof of the other registrant's receipt of that offer (such as a certified mail receipt). Your
offer must, in addition to anything else, offer to share in the burden of producing the data upon
terms to be agreed or failing agreement to be bound by binding arbitration as provided by FIFRA
section 3(c)(2)(B)(iii) and must not qualify this offer. The other registrant must also inform EPA
of its election of an option to develop and submit the data required by this Notice by submitting a
Data Call-In Response Form and a Requirements Status and Registrant's Response Form
committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your offer
to share in the burdens of developing the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this Notice. If the other registrant fails
to develop the data or for some other reason is subject to suspension, your registration as well as
that of the other registrant will normally be subject to initiation of suspension proceedings, unless
you commit to submit, and do submit the required data in the specified time frame. In such cases,
the Agency generally will not grant a time extension for submitting the data.
Option 4, Submitting an Existing Study — If you choose to submit an existing study in
response to this Notice, you must determine that the study satisfies the requirements imposed by
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this Notice. You may only submit a study that has not been previously submitted to the Agency
or previously cited by anyone. Existing studies are studies which predate issuance of this Notice.
Do not use this option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid and
needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted that the raw data
and specimens from the study are available for audit and review and you must
identify where they are available. This must be done in accordance with the
requirements of the Good Laboratory Practice (GLP) regulation, 40 CFR Part 160.
As stated in 40 CFR 160.3(j) " 'raw data' means any laboratory worksheets,
records, memoranda, notes, or exact copies thereof, that are the result of original
observations and activities of a study and are necessary for the reconstruction and
evaluation of the report of that study. In the event that exact transcripts of raw
data have been prepared (e.g., tapes which have been transcribed verbatim, dated,
and verified accurate by signature), the exact copy or exact transcript may be
substituted for the original source as raw data. 'Raw data' may include
photographs, microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated instruments."
The term "specimens", according to 40 CFR 160.3(k), means "any material
derived from a test system for examination or analysis."
b. Health and safety studies completed after May 1984 must also contain all GLP-
required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants must also certify at the time of
submitting the existing study that such GLP information is available for post-May
1984 studies by including an appropriate statement on or attached to the study
signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregistration Phase 3
Technical Guidance and that the study has been conducted according to the
Pesticide Assessment Guidelines (PAG) or meets the purpose of the PAG (both
available from NTIS). A study not conducted according to the PAG may be
submitted to the Agency for consideration if the registrant believes that the study
clearly meets the purpose of the PAG. The registrant is referred to 40 CFR 158.70
which states the Agency's policy regarding acceptable protocols. If you wish to
submit the study, you must, in addition to certifying that the purposes of the PAG
are met by the study, clearly articulate the rationale why you believe the study
meets the purpose of the PAG, including copies of any supporting information or
data. It has been the Agency's experience that studies completed prior to January
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1970 rarely satisfied the purpose of the PAG and that necessary raw data are
usually not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements of
the criteria outlined above.
If you know of a study pertaining to any requirement in this Notice which does not meet
the criteria outlined above but does contain factual information regarding unreasonable adverse
effects, you must notify the Agency of such a study. If such study is in the Agency's files, you
need only cite it along with the notification. If not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5.
Option 5, Upgrading a Study — If a study has been classified as partially acceptable and
upgradeable, you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the requirement is
not satisfied, you may still be required to submit new data normally without any time extension.
Deficient, but upgradeable studies will normally be classified as supplemental. However, it is
important to note that not all studies classified as supplemental are upgradeable. If you have
questions regarding the classification of a study or whether a study may be upgraded, call or write
the contact person listed in Attachment 1. If you submit data to upgrade an existing study you
must satisfy or supply information to correct all deficiencies in the study identified by EPA. You
must provide a clearly articulated rationale of how the deficiencies have been remedied or
corrected and why the study should be rated as acceptable to EPA. Your submission must also
specify the MRID number(s) of the study which you are attempting to upgrade and must be in
conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option should also be used to cite data that has been previously submitted to upgrade
a study, but has not yet been reviewed by the Agency. You must provide the MRID number of
the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to all
data submissions intended to upgrade studies. Additionally your submission of data intended to
upgrade studies must be accompanied by a certification that you comply with each of those
criteria as well as a certification regarding protocol compliance with Agency requirements.
Option 6, Citing Existing Studies — If you choose to cite a study that has been previously
submitted to EPA, that study must have been previously classified by EPA as acceptable or it
must be a study which has not yet been reviewed by the Agency. Acceptable toxicology studies
generally will have been classified as "core-guideline" or "core minimum." For all other
disciplines the classification would be "acceptable." With respect to any studies for which you
wish to select this option you must provide the MRID number of the study you are citing and, if
the study has been reviewed by the Agency, you must provide the Agency's classification of the
study.
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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.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-in Response Form and the Requirements
Status and Registrant's Response Form, as appropriate.
III-D REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies. (Note: any
supplemental data must be submitted in the format required by PR Notice 86-5). This will be the
only opportunity to state the reasons or provide information in support of your request. If the
Agency approves your waiver request, you will not be required to supply the data pursuant to
section 3(c)(2)(B) of FIFRA. If the Agency denies your waiver request, you must choose an
option for meeting the data requirements of this Notice within 30 days of the receipt of the
Agency's decision. You must indicate and submit the option chosen on the Requirements Status
and Registrant's Response Form. Product specific data requirements for product chemistry, acute
toxicity and efficacy (where appropriate) are required for all products and the Agency would grant
a waiver only under extraordinary circumstances. You should also be aware that submitting a
waiver request will not automatically extend the due date for the study in question. Waiver
requests submitted without adequate supporting rationale will be denied and the original due date
will remain in force.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study
as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this
Notice.
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5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration concerning
joint data development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or
failure of a registrant on whom you rely for a generic data exemption either to:
a. inform EPA of intent to develop and submit the data required by this Notice
on a Data Call-in Response Form and a Requirements Status and
Registrant's Response Form;
b. fulfill the commitment to develop and submit the data as required by this
Notice; or
c. otherwise take appropriate steps to meet the requirements stated in this
Notice, unless you commit to submit and do submit the required data in the
specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds
for suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-In Notice or other documents incorporated
by reference (including, as applicable, EPA Pesticide Assessment Guidelines, Data
Reporting Guidelines, and GeneTox Health Effects Test Guidelines) regarding the design,
conduct, and reporting of required studies. Such requirements include, but are not limited
to, those relating to test material, test procedures, selection of species, number of animals,
sex and distribution of animals, dose and effect levels to be tested or attained, duration of
test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation
of any changes required by the Agency following review.
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3. EPA requirements regarding the reporting of data, including the manner of reporting,
the completeness of results, and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or included in this Notice or
contained in PR 86-5. All studies must be submitted in the form of a final report; a
preliminary report will not be considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally not
be consistent with the Act's purposes. Accordingly, the Agency anticipates granting registrants
permission to sell, distribute, or use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your product(s) which may be
suspended for failure to comply with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be consistent with the Act. You
must also explain why an "existing stocks" provision is necessary, including a statement of the
quantity of existing stocks and your estimate of the time required for their sale, distribution, and
use. Unless you meet this burden the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice and
your product is in full compliance with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use such
existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily cancelled products containing an active ingredient for which the Agency has particular
risk concerns will be determined on case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required by
this Notice will not result in the Agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was due unless you demonstrate
to the Agency that you are in full compliance with all Agency requirements, including the
requirements of this Notice. For example, if you decide to voluntarily cancel your registration six
months before a 3 year study is scheduled to be submitted, all progress reports and other
information necessary to establish that you have been conducting the study in an acceptable and
good faith manner must have been submitted to the Agency, before EPA will consider granting an
existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE UNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6 (a) (2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
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adverse effects on the environment by the pesticide, the registrant shall submit the information to
the Agency. Registrants must notify the Agency of any factual information they have, from
whatever source, including but not limited to interim or preliminary results of studies, regarding
unreasonable adverse effects on man or the environment. This requirement continues as long as
the products are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary cancellation requests and generic data
exemption claims) must include a completed Data Call-in Response Form and a completed
Requirements Status and Registrant's Response Form (Attachment 2 and Attachment 3 for product
specific data) and any other documents required by this Notice, and should be submitted to the
contact person(s) identified in Attachment 1. If the voluntary cancellation or generic data
exemption option is chosen, only the Data Call-In Response Form need be submitted.
The Office of Compliance Monitoring (OCM) of the Office of Pesticides and Toxic
Substances (OPTS), EPA, will be monitoring the data being generated in response to this Notice.
Sincerely yours,
Lois Rossi, Division Director
Special Review and
Reregistration Division
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DESMEDIPHAM DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product (s) containing
desmedipham.
This Product Specific Data Call-In Chemical Status Sheet, contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregistration of
desmedipham. This attachment is to be used in conjunction with (1) the Product Specific Data Call-
in Notice, (2) the Product Specific Data Call-In Response Form (Attachment 2), (3) the
Requirements Status and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use
Products for Meeting Acute Toxicology Data Requirement (Attachment 4), (5) the EPA Acceptance
Criteria (Attachment 5), (6) a list of registrants receiving this DCI (Attachment 6) and (7) the Cost
Share and Data Compensation Forms in replying to this desmedipham Product Specific Data Call-In
(Attachment 7). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for desmedipham are
contained in the Requirements Status and Registrant's Response, Attachment 3. The Agency has
concluded that additional data on desmedipham are needed for specific products. These data are
required to be submitted to the Agency within the time frame listed. These data are needed to fully
complete the reregistration of all eligible desmedipham products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures
established by this Notice, please contact Jeffrey Billingslea at (703) 308-8004.
All responses to this Notice for the Product Specific data requirements should be submitted
to:
Jeffrey Billingslea
Chemical Review Manager Team 81
Product Reregistration Branch
Special Review and Reregistration Branch 7508W
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: DESMEDIPHAM
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer "yes." If you choose this
option, you will not have to provide the data required by the Data Call-In Notice and
you will not have to complete any other forms. Further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing
Stocks provision of the Data Call-In Notice (Section IV-C).
Item 6. Not applicable since this form calls in product specific data only. However, if your
product is identical to another product and you qualify for a data exemption, you
must respond with "yes" to Item 7a (MUP) or 7B (EUP) on this form, provide the
EPA registration numbers of your source(s); you would not complete the
"Requirements Status and Registrant's Response" form. Examples of such products
include repackaged products and Special Local Needs (Section 24c) products which
are identical to federally registered products.
Item 7a. For each manufacturing use product (MUP) for which you wish to maintain
registration, you must agree to satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration, you
must agree to satisfy the data requirements by responding "yes." If you are
requesting a data waiver, answer "yes" here; in addition, on the "Requirements
Status and Registrant's Response" form under Item 9, you must respond with Option
7 (Waiver Request) for each study for which you are requesting a waiver. See Item
6 with regard to identical products and data exemptions.
Items 8-11. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed
letter that accompanies this form. For example, you may wish to report that your
product has already been transferred to another company or that you have already
voluntarily canceled this product. For these cases, please supply all relevant details
so that EPA can ensure that its records are correct.
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This page is replaced with the sample DCI part A from the
Agency PSDCI module.
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INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number assigned by EPA in Item
3. This number must be used in the transmittal document for any data
submissions in response to this Data Call-In Notice.
Item 4. The guideline reference numbers of studies required to support the product's
continued registration are identified. These guidelines, in addition to the requirements
specified in the Notice, govern the conduct of the required studies. Note that series
61 and 62 in product chemistry are now listed under 40 CFR 158.155 through
158.180, SubpartC.
Item 5. The study title associated with the guideline reference number is identified.
Item 6. The use pattern(s) of the pesticide associated with the product specific requirements
is (are) identified. For most product specific data requirements, all use patterns are
covered by the data requirements. In the case of efficacy data, the required studies
only pertain to products which have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For product specific data, the
product as formulated for sale and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified. It is normally based on 8
months after issuance of the Reregistration Eligibility Document unless EPA
determines that a longer time period is necessary.
Item 9. Enter only one of the following response codes for each data requirement to show
how you intend to comply with the data requirements listed in this table. Fuller
descriptions of each option are contained in the Data Call-In Notice.
1. I will generate and submit data by the specified due date (Developing Data). By
indicating that I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of this study as outlined in the
Data Call-In Notice. By the specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation Requirements" form (EPA
Form 8570-29) and (2) two completed and signed copies of the Confidential
Statement of Formula (EPA Form 8570-4).
2. I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing). I am submitting a copy of this agreement. I understand that this
option is available only for acute toxicity or certain efficacy data and only if EPA
indicates in an attachment to this Notice that my product is similar enough to another
product to qualify for this option. I certify that another party in the agreement is
committing to submit or provide the required data; if the required study is not
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submitted on time, my product may be subject to suspension. By the specified due
date, I will also submit: (1) a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
3. I have made offers to share in the cost to develop data (Offers to Cost Share). I
understand that this option is available only for acute toxicity or certain efficacy data
and only if EPA indicates in an attachment to this Data Call-in Notice that my product
is similar enough to another product to qualify for this option. I am submitting
evidence that I have made an offer to another registrant (who has an obligation to
submit data) to share in the cost of that data. I am also submitting a completed
"Certification of Offer to Cost Share in the Development Data" form. I am
including a copy of my offer and proof of the other registrant's receipt of that offer.
I am identifying the party which is committing to submit or provide the required data;
if the required study is not submitted on time, my product may be subject to
suspension. I understand that other terms under Option 3 in the Data Call-in Notice
(Section III-C.l.) apply as well. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-29) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4).
4. By the specified due date, I will submit an existing study that has not been submitted
previously to the Agency by anyone (Submitting an Existing Study). I certify that
this study will meet all the requirements for submittal of existing data outlined in
Option 4 in the Data Call-In Notice (Section III-C.l.) and will meet the attached
acceptance criteria (for acute toxicity and product chemistry data). I will attach the
needed supporting information along with this response. I also certify that I have
determined that this study will fill the data requirement for which I have indicated this
choice. By the specified due date, I will also submit a completed "Certification With
Respect To Data Compensation Requirements" form (EPA Form 8570-29) to
show what data compensation option I have chosen. By the specified due date, I will
also submit: (1) a completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed and signed copies
of the Confidential Statement of Formula (EPA Form 8570-4).
5. By the specified due date, I will submit or cite data to upgrade a study classified by
the Agency as partially acceptable and upgradable (Upgrading a Study). I will
submit evidence of the Agency's review indicating that the study may be upgraded
and what information is required to do so. I will provide the MRID or Accession
number of the study at the due date. I understand that the conditions for this option
outlined Option 5 in the Data Call-In Notice (Section III-C.l.) apply. By the
specified due date, I will also submit: (1) a completed "Certification With Respect
To Data Compensation Requirements" form (EPA Form 8570-29) and (2) two
completed and signed copies of the Confidential Statement of Formula (EPA Form
8570-4).
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6. By the specified due date, I will cite an existing study that the Agency has classified
as acceptable or an existing study that has been submitted but not reviewed by the
Agency (Citing an Existing Study). If I am citing another registrant's study, I
understand that this option is available only for acute toxicity or certain efficacy data
and only if the cited study was conducted on my product, an identical product or a
product which EPA has "grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option if I am citing my own
data. In either case, I will provide the MRID or Accession number(s) for the cited
data on a "Product Specific Data Report" form or in a similar format. By the
specified due date, I will also submit: (1) a completed "Certification With Respect
To Data Compensation Requirements" form (EPA Form 8570-29) and (2) two
completed and signed copies of the Confidential Statement of Formula (EPA Form
8570-4).
7. I request a waiver for this study because it is inappropriate for my product (Waiver
Request). I am attaching a complete justification for this request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies.
[Note: any supplemental data must be submitted in the format required by P.R. Notice
86-5]. I understand that this is my only opportunity to state the reasons or provide
information in support of my request. If the Agency approves my waiver request, I
will not be required to supply the data pursuant to Section 3(c) (2) (B) of FIFRA. If
the Agency denies my waiver request, I must choose a method of meeting the data
requirements of this Notice by the due date stated by this Notice. In this case, I must,
within 30 days of my receipt of the Agency's written decision, submit a revised
"Requirements Status and Registrant's Response" Form indicating the option chosen.
I also understand that the deadline for submission of data as specified by the original
data call-in notice will not change. By the specified due date, I will also submit: (1)
a completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-29) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4).
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed
letter that accompanies this form. For example, you may wish to report that your
product has already been transferred to another company or that you have already
voluntarily canceled this product. For these cases, please supply all relevant details
so that EPA can ensure that its records are correct.
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This page is replaced with the Product Specific DCI Part B
page 1
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This page is replaced with the Product Specific DCI Part B
page 2
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This page is replaced with the Product Specific DCI Part B
pageS
125
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This page is replaced with the Product Specific DCI Part B
page 4
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EPA'S BATCHING OF DESMEDIPHAM PRODUCTS FOR MEETING REREGISTRATION
ACUTE TOXICITY DATA REQUIREMENTS
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 desmedipham as the active
ingredient, the Agency has batched products which can be considered similar for purposes of acute
toxicity. Factors considered in the sorting process include each product's active and inert ingredients
(identity, percent composition and biological activity), type of formulation (e.g., emulsifiable
concentrate, aerosol, wettable powder, granular, etc.), and labeling (e.g., signal word, use
classification, precautionary labeling, etc.). Note that the Agency is not describing batched products
as "substantially similar" since some products within a batch may not be considered chemically
similar or have identical use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Not with-standing the batching process, the Agency reserves the right to
require, at any time, acute toxicity data for an individual product should the need arise.
In the batching process, the Agency reviewed the following products:
Desmedipham Technical [97.0% a.i.) (Id. No. 45639-85)]
Betanex [16% a.i.) (Id. No. 45639-86)]
Betamix Herbicide [(8.0% a.i.) (Id. No. 45639-87)]
Betanex 70 WP [(70.0% a.i.) (Id. No. 45639-155)]
Betamix 70WP [(35.0% a.i.) (Id. No. 45639-156)]
NA 305 [(6.0% a.i.) (Id. No. 45639-158)]
Betamix Progress [(7.0% a.i.) (45639-159)]
CQ 1451 [(6.0% a.i.) (45639-160)]
NA 307 [(7.0% a.i.) (45639-162)]
Betamix Herbicide [(8.0% a.i.) (WA95001900)]
There are no acute tox data requirements for Desmedipham Technical (45639-85).
The following products: NA 305 (45639-158); Betamix Progress (45639-159); CQ 1451 (45639-
160); and NA 307 (45639-162) are in the same batch and there are acceptable data available within
PRS to categorize their acute toxicity.
127
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Also, there are acceptable data available within PRS to categorize the acute toxicity of Betanex 70WP
(45639-155) and Betamix 70WP (45639-156).
However, PRS requests that acute toxicity testing on Betamix (45639-87) or (45639-87 EPA SLN
Reg. No. WA-950019) be provided for review. The results should be acceptable to support Betanex
Herbicide (45639-86).
128
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Attachment 5. List of All Registrants Sent This Data Call-In (insert) Notice
129
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130
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Instructions for Completing the Confidential Statement of Formula
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible, signed
copies of the form are required. Following are basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
c. The CSF must be signed, dated and the telephone number of the responsible party
must be provided.
d. All applicable information which is on the product specific data submission must also
be reported on the CSF.
e. All weights reported under item 7 must be in pounds per gallon for liquids and pounds
per cubic feet for solids.
f. Flashpoint must be in degrees Fahrenheit and flame extension in inches.
g. For all active ingredients, the EPA Registration Numbers for the currently registered
source products must be reported under column 12.
h. The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all
common names for the trade names must be reported.
i. For the active ingredients, the percent purity of the source products must be reported
under column 10 and must be exactly the same as on the source product's 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.
131
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United States Environmental Protection Agency
^t ^™r\/\ Washington, DC 20460
^Bfc l"™KfcX CERTIFICATION OF OFFER TO COST
\F IM! *\ SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
2070-0057
Approval Expires 3-31-96
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firm(s) on the following
date(s):
Name of Firm(s)
Date of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature
Name and
of Company's Authorized Representalive
Date
Title (Please Type or Print)
EPA Form 8570-32 (5/91) Replaces EPA Form 8580, which is obsolete
135
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136
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United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
2
\
Form Approved
OMB No. 2070-0107,
2070-0057
Approval Expires
3-31-96
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including time for
reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect of this collection of information,
including suggestions for reducing this burden to, Chief Information Policy Branch, PM-233, U.S. Environmental Protection
Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of Management and Budget, Paperwork Reduction Project
(2070-0106), Washington, DC 20503.
Please fill in blanks below.
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
1. For each study cited in support of registration or reregistratiion under the Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the written permission of the original
data submitter to cite that study.
2. That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use study, I am the
original data submitter, or I have obtained the written permission of the original data submitter, or I have notified in writing the
company(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
3(c)(1 )(F) and 3(c)(2)(D) of FIFRA; and (b) Commence negotiation to determine which data are subject to the compensation
requirement of FIFRA and the amount of compensation due, if any. The companies I have notified are. (check one)
[ ] The companies who have submitted the studies listed on the back of this form or attached sheets, or indicated on the attached
"Requirements Status and Registrants' Response Form,"
3. That I have previously complied with section 3(c)(1)(F) of FIFRA for the studies I have cited in support of registration or
reregistration under FIFRA.
Signature
Date
Name and Title (Please Type or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the registration or
reregistration of my products, to the extent required by FIFRA section 3(c)(1)(F) and 3(c)(2)(D).
Signature
Date
Name and Title (Please Type or Print)
EPA Form 8570-31 (4-96)
137
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The following is a list of available documents for desmedipham that my further assist you
in responding to this Reregistration Eligibility Decision document. These documents may be
obtained by the following methods:
Electronic
File format: Portable Document Format (.PDF) Requires Adobe® Acrobat or compatible
reader. Electronic copies can be downloaded from the Pesticide Special
Review and Reregistration Information System at 703-308-7224. They also are
available on the Internet on EPA's gopher server, GOPHER.EPA.GOV, or
using ftp on FTP.EPA.GOV, or using WWW (World Wide Web) on
WWW.EPA.GOV., or contact Jeffrey Billingslea at (703)-308-8004.
1. PR Notice 86-5.
2. PR Notice 91-2 (pertains to the Label Ingredient Statement).
3. A full copy of this RED document.
4. A copy of the fact sheet for desmedipham.
The following documents are part of the Administrative Record for desmedipham and may
included in the EPA's Office of Pesticide Programs Public Docket. Copies of these
documents are not available electronically, but may be obtained by contacting the person listed
on the Chemical Status Sheet.
1.Health and Environmental Effects Science Chapters.
2.Detailed Label Usage Information System (LUIS) Report.
The following Agency reference documents are not available electronically, but may be
obtained by contacting the person listed on the Chemical Status Sheet of this RED document.
1. The Label Review Manual.
2. EPA Acceptance Criteria
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