SEPA
United States Prevention, Pesticides EPA 738-R-03-002
Environmental Protection and Toxic Substances May 29, 2003
Agency (7508C)
Reregistration
Eligibility Decision (RED)
Dinocap
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Reregistration Eligibility Decision
for
Dinocap
ListB
Case 2200
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May 29, 2003
This document explains the U.S. Environmental Protection Agency's (hereafter referred to as
EPA or "the Agency") reregistration eligibility decision (RED) for dinocap which consists of a
voluntary cancellation of all products registered in the U.S. Because the registrant, Dow
AgroSciences, LLC (DAS) has expressed interest in retaining existing tolerances for apples and
grapes for import purposes, this document presents only a dietary risk assessment for those uses and
specifically addresses the data requirements for support of the import tolerances. The following RED
document provides background information on the pesticide registration, reregistration and tolerance
reassessment, an overview of the uses and health effects associated with dinocap and a summary of
what data are required to support the tolerances on apples and grapes imported into the U.S., in the
absence of a U.S. registration.
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. 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 of all data submitted to support
reregistration.
FIFRA requires the Agency to determine whether pesticides containing an 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 or not the
pesticide meets the "no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.
This Act amends FIFRA to require that by 2006 EPA must review all tolerances in effect at the time
of enactment. FQPA also amends the Federal Food, Drug and Cosmetic Act (FFDCA) to require a
safety finding in tolerance reassessment based on factors including an assessment of cumulative
effects of chemicals with a common mechanism of toxicity. At this time, the Agency does not have
sufficient reliable information concerning common mechanism to determine whether or not dinocap
shares a common mechanism of toxicity with other chemicals. Therefore, for the purpose of this risk
assessment, the Agency has assumed that dinocap does not share a common mechanism with any
other chemical.
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n. Regulatory Background
Dinocap was the subject of a Special Review because of Agency concerns about
developmental toxicity. The Position Document (PD) 1 was published on January 9, 1985 (50 FR
1119) and the PD 2/3 on October 29, 1986 (51 FR 39577). Special Review was concluded with the
publication of the PD 4 on February 6, 1989 (54 FR 5908). In the PD 4, the Agency required that all
dinocap labels be revised to include appropriate health hazard statements and to require the use of
additional protective clothing and equipment for mixer/loaders and applicators.
Dinocap, a List B chemical, was the subject of a Phase 4 Review dated January 30, 1991 and
a Data-Call-in Notice (DCI) issued on September 10, 1991. At that time, the current registrant Rohm
and Haas Company (R&H) had indicated that they intended to amend registrations to drop all
food/feed uses for end-use products (EPs). In the Phase 4 Review, data were required under residue
chemistry guidelines pending submission of the required amendment forms and revised labels for all
EPs confirming that food/feed uses had been removed. In their 90-day response to the Phase 4 DCI,
R&H requested a waiver of residue chemistry data requirements based on their intention to delete all
food/feed uses from their product labels. The registrant subsequently requested that the Agency
retain dinocap tolerances for apples and grapes as import tolerances. Following cancellation by R&H
of all dinocap food/feed uses registered in the U.S., the Agency revoked all dinocap tolerances, except
those for apples and grapes (63 FR 206, October 26, 1998).
The registration for dinocap was transferred from R&H to DAS on September 21, 2001. On
February 12, 2002, DAS requested voluntary cancellation pursuant to Section 6(f) of FIFRA of their
U.S. product registrations for dinocap for the products Karathane WD Ag Fungicide and Miticide
(EPA Registration No. 62719-384), Karathane Liquid Concentrate Ag Fungicide and Miticide (EPA
Registration No. 62719-385) and Karathane Technical Ag Fungicide and Miticide (EPA Registration
No. 62719-390). The Agency announced its receipt of the above-mentioned cancellation requests in
the Federal Register on April 26, 2002 [OPP-2002-0013; FRL-6833-8]. The Agency did not receive
any comments specific to these cancellations; therefore, the cancellation order was effective on
October 24, 2002. Because dinocap products have not been marketed in the U.S. for several years,
existing stocks are expected to be negligible.
m. Uses
Dinocap is a foliar fungicide/miticide used to control powdery mildew. Dinocap is applied to
apples and grapes outside of the U.S., mainly in Europe, the Middle East and northern Africa. There
are currently no registered dinocap products in the U.S. DAS, the registrant of dinocap, intends to
support tolerances for dinocap residues in/on apples and grapes to permit legal importation of these
commodities into the U.S.
IV. Health Effects
The doses and endpoints for dietary risk assessment were selected by the Hazard
Identification Assessment Review Committee (HIARC) (memo dated February 23, 2000). The
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HIARC established an acute toxicity endpoint for females of reproductive age (females 13+ years
old) and determined that a risk assessment for acute dietary exposure is not necessary for the general
population. The acute endpoint was derived from a mouse developmental study (MRID 41313 001)
based on a slight (nonsignificant) increase in incidences of cleft palate and eyelids-open relative to
controls that occurred in the absence of maternal toxicity. The No Observed Adverse Effect Level
(NOAEL) was 4 mg/kg/day and the Lowest Observed Adverse Effect Level (LOAEL) was 10
mg/kg/day.
The chronic dietary endpoint was selected from a chronic feeding study in dogs (MRID
41065401, Ace. Nos. 247957 & 247959). The NOAEL for systemic toxicity was 0.375 mg/kg/day
and the LOAEL was 1.5 mg/kg/day based on effects on the eye.
The FQPA committee recommended that the FQPA safety factor for the protection of infants
and children be retained at lOx for all population subgroups when assessing acute and chronic
exposure. The reasons are: (1) there is concern for the quantitative and qualitative increase in
susceptibility observed in fetuses following in utero exposure in the prenatal developmental studies in
mice and rabbits; and (2) there is a data gap for the developmental neurotoxicity study in the rat.
The acute reference dose (aRfD) is 0.04 mg/kg/day and the acute population adjusted dose
(aPAD) is 0.004 mg/kg/day. The chronic reference dose (cRfD) is 0.0038 mg/kg/day and the chronic
population adjusted dose (cPAD) is 0.00038 mg/kg/day. The population adjusted dose is the
reference dose divided by the FQPA safety factor.
The Agency has classified dinocap as a Group E "not likely" carcinogen. It was negative for
inducing mutations in all studies of the standard mutagenicity battery except the Ames test. In Ames
studies, dinocap was weakly positive at best and only at high doses.
For more detailed information on the potential health effects associated with dinocap, please
refer to the "Dinocap Toxicology Chapter for the RED," dated April 18, 2000, which is available on
the Agency's web page at http:/Avww.cfpub.epa.gov/oppref/rereg/status.cfm?show =rereg and in the
Public Docket.
V. Dietary Risk Assessment
Acute and chronic dietary exposure assessments were conducted to determine the dietary
exposure estimates associated with the use of dinocap in/on apples and grapes to support the RED.
The qualitative nature of the residue in plants and animals are not adequately understood and no
acceptable magnitude of the residue or processing data in/on imported apples or grapes are currently
available. Therefore, the dietary risk assessment was conducted two ways, using the current
tolerances of 0.1 ppm and using Maximum Residue Limits (MRLs) recommended by the Joint
FAO/WHO Meeting on Pesticide Residues (JMPR). There are European data which have been
reviewed by the JMPR. The JMPR proposes MRLs for individual pesticides in different food and
feed items, and provides advice on the acceptable levels of pesticide residues in food moving in
international trade. Residues of dinocap in the European trials were <0.05 (ND) to 0.09 ppm in
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apples and <0.05 to 0.67 ppm in grapes. In 1988, JMPR recommended MRLs of 0.2 for apples and 1
ppm for grapes.
No processing data are available; therefore, default processing factors were used. Information
is available to estimate the percent of the import apple and grape crops that are treated with dinocap.
Less than 5% of the apples and grapes consumed in the U.S. are imported and less than 1% of those
are treated with dinocap. Thus, the calculated percent crop treated (% CT) for dinocap is 0.05%
which has been rounded up to 0.1% in the chronic dietary risk assessment.
Dinocap acute and chronic dietary exposure assessments were conducted using the Dietary
Exposure Evaluation Model (DEEM™) software Version 7.73, which incorporates consumption data
from USDA's Continuing Survey of Food Intake by Individuals (CSFII), 1989-1992. The 1989-1992
data are based on the reported consumption of more than 10,000 individuals over 3 consecutive days
and therefore represent more than 30,000 unique "person days" of data.
Irrespective of the residue data used (i.e., current U.S. tolerances or MRLs), acute and chronic
dietary risk estimates are well below the Agency's level of concern for all supported dinocap food
uses. Acute dietary risk is <1% of the aPAD for the only subpopulation of concern, females, 13-50
years old. Chronic dietary risk is <1% of the cPAD for the U.S. general population and all
subpopulations.
For more detailed information on the dietary risk assessment for dinocap, please refer to the
"Dinocap Acute and Chronic Dietary Exposure Assessment," dated November 7, 2001, which is
available on the Agency's web page at
http://\vww.cfpub. epa.gov/oppref/rereg/status. cfm ?show =rereg and in the Public Docket.
VI. Tolerance Reassessment Summary
There are currently no registered food/feed uses of dinocap in the U.S. The established
dinocap tolerances for food and feed commodities have been revoked except those for apples and
grapes. DAS, the basic producer, intends to support tolerances for dinocap residues in/on apples and
grapes to permit legal importation of these commodities into the U.S., in the absence of a U.S.
registration.
Tolerances for dinocap are currently expressed in terms of combined negligible residues of a
fungicide and insecticide that is a mixture of 2,4-dinitro-6-octylphenyl crotonate and 2,6-dinitro-4-
octylphenyl crotonate in/on apples and grapes at 0.1 ppm [40 CFR §180.341(a)]. Current U.S.
tolerances are 0.1 ppm (negligible) on both crops [40 CFR §180.341].
There are currently no Codex MRLs established for residues of dinocap. However, in 1988,
JMPR recommended dinocap MRLs of 0.2 for apples and 1 ppm for grapes. Harmonization of the
tolerance expression/definition and tolerances between Codex MRLs and U.S. tolerances cannot be
achieved until the outstanding metabolism and residue data have been submitted.
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Table 1.
Tolerance Reassessment Summary for Dinocap.
Commodity
Current Tolerance
(ppm)
Reassessed Tolerance
(ppm)
Comments
[Corrected Canvttodity De/atilion/
Tolerances Established Under 40 CFR §180.341(a)
Apples
Grapes
O.KIM)1
0.1(N)
To be determined2
To be determined
[Apple]
[Grape]
VH. Data Gaps
The toxicology database for dinocap is considered adequate for the current risk assessment.
Acute, subchronic and a developmental neurotoxicity study in rats are required based on concerns for
the severe effects (malformations) seen in the developmental toxicity studies in mice and rabbits, as
well as for the neurological effects demonstrated in mice and dogs.
There are several data gaps for residue chemistry. Data are required to describe the
qualitative nature of dinocap residues in plants and animals. Magnitude of the residue in/on imported
apples and grapes must be addressed with field residue data reflecting the maximum use patterns for
the representative formulations in the areas/countries where dinocap will be sold and used. DAS
may not need to conduct all new studies to fulfill these requirements, but may be able to rely on
existing studies developed for a foreign registration or Codex MRLs to support the proposed
tolerance.
Table 2 below lists the confirmatory data requirements for supporting the apple and grape
tolerances for import purposes. These requirements are consistent with EPA's "Guidance on
Pesticide Import Tolerances and Residue Data for Imported Food," 65 FR 106; 35069-350-90, June
1, 2000.
Table 2.
Data Requirements for Dinocap Import Tolerances.
Data Requirements
New OPPTS Guideline Number
Old Guideline Number
TOXICOLOGY
Acute Neurotoxicity Screening Battery, Rat
Subchronic Neurotoxicity Study, Rat
Developmental Neurotoxicity Study, Rat
870.6200
870.6300
81-8
82-7
83-6
RESIDUE CHEMISTRY
Directions for Use
860.1200
171-3
1 (N) = negligible residues; however, the Agency is removing the "(N)" designation from all entries to
conform to current Agency administrative practice.
2 These commodities were included in the dietary risk assessment for dinocap using the Current Tolerance
level. Additional confirmatory field trial residue data are required; therefore, the final tolerance may be revised.
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Data Requirements
Nature of the Residue, Plants
Nature of the Residue, Livestock
Storage Stability, Plants
Crop Field Trials (Apple & Grapes)
Processed Food (Apple & Grapes)
New OPPTS Guideline Number
870.1300
860.1380
860.1500
860.1520
Old Guideline Number
171-4A
171-4B
171-4E
171-4K
171-4L
A ruminant metabolism study is included in the above list because wet apple pomace is a
livestock feed item. In order to waive this study, registrants must convincingly document that it is
unlikely that imported apples or wet pomace would be significant feed items in the U.S. or exporting
countries and/or that there are not significant imports of livestock commodities.
Before conducting any toxicology or residue chemistry study, the registrant should submit
study protocols for EPA comment if they have any questions regarding study design and conduct.
The Agency will attempt to harmonize with international standards to the extent possible.
Regulatory Conclusion
The Agency has completed its reregistration eligibility decision for the fungicide/miticide,
dinocap, which consists of a voluntary cancellation of all U.S. product registrations. Because the
registrant has indicated their intention to retain the existing tolerances for apples and grapes for
import purposes, EPA has conducted a dietary risk assessment for dinocap. Although there are data
gaps, the Agency has used protective assumptions including a lOx safety factor and tolerance level
residue values to determine that dietary risk is minimal, less than 1% of the acute and chronic PADs
for all population subgroups. EPA finds that there is a reasonable certainty that no harm will result
from dinocap use on apples and grapes imported into the U.S. Confirmatory data are required as
outlined in the previous section.
/s /
Lois A. Rossi, Director
Special Review and Reregistration Division
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Appendix B. Data Supporting Guideline Requirements for the Establishment of Import
Tolerances for Dinocap
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the reregi strati on for active
ingredients within the chemical case covered by this RED. It contains generic data requirements
that apply in all products, including data requirements for which a "typical formulation" is the
test substance.
The data table is organized in the following formats:
1. Data Requirement (Columns 1, 2 & 3). The data requirements are listed in the order of
New Guideline Number and appear in 40 CFR §158. The reference numbers
accompanying each test refer to the test protocols set in the Pesticide Assessment
Guidance, which are available from the National Technical Information Service, 5285
Port Royal Road, Springfield, VA 22161-0002, (703) 487-4650.
2. Use Pattern (Column 4). 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 nonfood
D. Aquatic food
E. Aquatic nonfood outdoor
F. Aquatic nonfood industrial
G. Aquatic nonfood residential
H. Greenhouse food
I. Greenhouse nonfood
J. Forestry
K. Residential
L. Indoor food
M. Indoor nonfood
N. Indoor medical
O. Indoor residential
3. Bibliographical Citation (Column 5). If the Agency has acceptable data in its files, this
column lists the identification number of each study. Normally, this 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 D) for a complete citation of the study.
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Appendix B. Data Supporting Guideline Requirements for the Establishment of Import
Tolerances for Dinocap
New
Guideline
Number
Old
Guideline
Number
Requirement
Use
Pattern
Bibliographical Citation(s)
TOXICOLOGY
870.1100
870.6200
870.3100
870.3150
870.6200
870.4100
870.4200
870.3700
870.3800
870.4300
870.6300
870.5140
870.5375
870.5300
870.5500
870.7600
81-1
81-8
82-1 A
82-1B
82-7
83-1A
83-1B
83-2A
83-2B
83-3A
83-3B
83-4
83-5
83-6
84-2A
84-2B
84-2
84-4
85-2
Acute Oral Toxicity, Rat
Acute Neurotoxicity Screening Battery, Rat
90-Day Subchronic Feeding, Rodent and
Nonrodent (Dog)
Subchronic Neurotoxicity Study, Rat
Chronic Feeding Toxicity, Rodent and
Nonrodent (Dog)
Chronic Carcinogenicity (Feeding), Rat and
Mouse
Prenatal Developmental Toxicity, Rodent
and Rabbit
2-Generation Reproduction and Fertility
Effects, Rat
Combined Chronic Toxicity/
Carcinogenicity Study, Rat
Developmental Neurotoxicity Study, Rat
Gene Mutation (Ames Test)
Structural Chromosomal Aberration
Detection of Gene Mutations in Somatic
Cells in Culture, Mammalian
Other Genotoxic Effects
Dermal Absorption (Penetration), Rat
42124301
Data Gap
41065401, Ace. Nos. 247957,
247959
Data Gap
41065401, 44932601, Ace. Nos.
247957, 247959
41065401, Ace. No. 247959
40315401, 41313001, Ace. Nos.
251713, 252443, 255892, 256934,
259645
41542501, Ace. No. 254950
41065401, Ace. No. 247959
Data Gap
46002023, 47005237, Ace. Nos.
00154778, 00256483, 00264191
Ace. Nos. 00256483, 00264191
47025237, Ace. No. 00264191
00256483
Ace. Nos. 259639,260614
RESIDUE CHEMISTRY
860.1200
860.1300
860.1340
860.1360
860.1380
860.1480
171-3
171-4A
171-4B
171-4C
171-4D
171-4M
171-4E
171-4J
Directions for Use
Nature of the Residue, Plants and Animals
Residue Analytical Method, Plants and
Animals
Multiresidue Methods
Storage Stability, Plants
Storage Stability, Animals
Magnitude of Residues in Meat, Milk,
Poultry and Eggs
Data Gap
Data Gap
Reserved
Reserved
Data Gap
Reserved
Reserved
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New
Guideline
Number
Old
Guideline
Number
Requirement
Use
Pattern
Bibliographical Citation(s)
Miscellaneous Commodities Group
860.1500
171-4K
Crop Field Trials (Grapes)
Data Gap
Pome Fruits Group
860.1500
171-4K
Crop Field Trials (Apple)
Data Gap
Processed Food/Feed Group
860.1520
171-4L
Processed Food (Apple)
Processed Food (Grapes)
Data Gap
Data Gap
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