Document ID: EPA-HQ-OPP-2008-0854-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-09-23T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF PREVENTION, PESTICIDES

	AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:		25-Febuary-2009

Subject:	Meptyldinocap; Petition for Tolerances on Imported Grape
Commodities.  Summary of Analytical Chemistry and Residue Data.

PC Code:  036000	DP Barcode:  D355561 and D349641

Decision No.:  386467	Registration No.:  not applicable

Petition No.:  7E7294	Regulatory Action:  not applicable

Risk Assessment Type:  not applicable	Case No.:  not applicable

TXR No.:  not applicable	CAS No.:  131-72-6

MRID No.:  47289103,47289104, 47289105, 47289106, 47289107, 47289108,
47289109, 47289112, 47289115, 47304902, 47304903, 47304904, 47304905,
47602200	40 CFR:  180.###

From:		Tom Bloem

		Risk Assessment Branch 1/Health Effects Division (RAB1/HED; 7509P)

Through:		George F. Kramer, Ph.D., Senior Chemist

				RAB1/HED (7509P)

To:		Mary Waller/Tamue Gibson (RM21)

		Registration Division (RD; 7505P)

  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (1910 Sedwick Road, Building 100, Suite
B; Durham, NC 27713).  The document has been reviewed by HED and revised
to reflect current Office of Pesticide Programs (OPP) policies.

Executive Summary

Background:  Meptyldinocap (2-(1-methylheptyl)-4,6-dinitrophenyl
(2E)-2-butenoate) is a dinitrophenol fungicide which interferes with
fungal respiration by acting as an uncoupler of oxidative
phosphorylation (Fungicide Resistance Action Committee (FRAC) Group 29).
 Meptyldinocap is one of the six isomers found in the older fungicide
dinocap (see Appendix 1 for structure); dinocap contains three isomers
of 2,4-dinitro-6-octylphenyl crotonate (2,4-DNOPC) and three isomers of
2,6-dinitro-4-octylphenyl crotonate (2,6-DNOPC).  In dinocap, the octyl
groups for both the 2,4-DNOPC and 2,6-DNOPC isomers are a mixture of
1-methylheptyl, 1-ethylhexyl, and 1-propylpentyl isomers.  Meptyldinocap
consists of >90% w/w of the 2,4-dinitro-6-(1-methylheptyl) isomer, with
the remaining five isomers each being present at <1% w/w.  Dow
AgroSciences (Indianapolis, IN) proposed the establishment of a 0.3-ppm
grape tolerance for residues of meptyldinocap per se.  Note that
mepytldinocap and dinocap are not proposed/registered for application in
the U.S.  

Directions for Use:  A 350 g/L emulsifiable concentrate (EC)
meptyldinocap formulation is currently registered for control of powdery
mildew on grapevines in the UK, Italy, Romania, Hungry, Tunisia, and
Chile.  The petitioner indicated that additional registrations on grapes
are pending for other countries in Europe, Africa, and Asia (the
following countries were listed:  Austria, Czech Republic, France,
Germany, Portugal, Republic of South Africa, Slovenia, Spain, and
Slovakia).  The petition included examples of labels from the U.K.,
France, and Chile, and a summary of the use directions from current and
pending registrations.  Although there are slight regional variations in
timing and application volume, the petitioner indicated that all uses
are standardized on the following parameters:  preharvest interval (PHI)
of ≥21 days, a maximum application rate of 0.21 kg ai/ha (excluding
post-harvest application in Chile), and a maximum of 4 applications per
season.  Table 3 is a summary of the registered/pending meptyldinocap
grape application scenarios.  The submitted information concerning the
proposed/registered application scenarios are adequate.  

Residues of Concern - Plants:  The petitioner submitted apple (two
studies), cucumber, and squash metabolism studies.  All of the studies
were conducted with [14C-U-phenyl]-meptyldinocap except for one of the
apple studies which was conducted with [14C-U-phenyl]
2,6-dinitro-4-(1-methylheptyl)phenyl crotonate.  The apple metabolism
studies indicate that following a single foliar application 0-21 days
prior to harvest, the majority of the residues were in/on the fruit
surface or peel and were degraded via photolysis and/or metabolism to a
large number of low-concentration metabolites.  Meptyldinocap was the
only compound found at greater than 10% of the total radioactive residue
(TRR; 12-75% TRR); 2,4-DNOP (2-6% TRR) and several benzoxazole compounds
(<1% TRR) were also identified (see Appendix 3 for petitioner proposed
metabolic pathway).  The squash and cucumber studies are considered
scientifically unacceptable.  These studies contain a number of
deficiencies relating to the lack of adequate information on the test
substance, field trial procedures, and sample storage conditions.  In
addition, substantial proportions of the TRR in both the cucumber and
squash samples were not adequately characterized/identified, and the
identities of meptyldinocap and 2,4-DNOP were not confirmed using a
second analytical method.  While the squash and cucumber studies are
inadequate, they do support the identification of 2,4-DNOP as a minor
metabolite of meptyldinocap.

The HED Residues of Concern Knowledge-Base Subcommittee (ROCKS)
determined that the available apple metabolism data are acceptable for
purposes of this petition.  Based on these data, the ROCKS concluded
that the residues of concern in grapes for tolerance enforcement and
risk assessment are meptyldinocap and 2,4-DNOP (D362393, B. Daiss,
25-Feb-2009).  

Nature/Magnitude of the Residue - Livestock/Rotational Crops: 
Information concerning the nature and magnitude of the residue in
livestock and rotational crops were not submitted.  Since there are no
proposed/registered domestic uses and since there are no significant
feedstuffs associated with the proposed use (see Organization of
Economic Cooperation and Development (OECD) guidance document -  
HYPERLINK "http://www.oecd.org/dataoecd/60/9/41808585.pdf" 
http://www.oecd.org/dataoecd/60/9/41808585.pdf ), these data are
unnecessary.  

Magnitude of the Residue - Crops:  The petitioner submitted adequate
meptyldinocap grape field trial studies (see below for summary).  All of
the field trials were conducted in Europe; additional data in Chile,
Africa, and/or Asia are not being requested for the following reasons: 
(1) based on the Chilean application scenario (3 x 0.21 kg ai/ha; PHI =
60 days) and that performed in the field trials (4 x 0.21 kg ai/ha; PHI
= 21 days), HED concludes that the European field trial data are
sufficient (Chemistry Science Advisory Committee (ChemSAC) minutes -
17-Sep-2008) and (2) the U.S. does not import a significant quantity of
table grapes, wine, or raisins from the relevant African and Asian
countries (see Appendix 4).  

The European field trial data indicated that following four applications
at 0.19-0.24 kg ai/ha (1x single/seasonal rate; retreatment interval
(RTI) = 5-32 days), combined meptyldinocap and 2,4-DNOP residues ranged
from <0.025 ppm to 0.12 ppm.  HED notes that the proposed minimum RTI
for the final two application is 5 days (studies employed RTIs of 5-32
days), only single samples were collected at 11 of the 16 trials rather
than duplicates as requested in the OPPTS 860.1500 guidelines, and the
studies employed only wine grape varieties.  For the following reasons,
HED concludes that additional data are unnecessary:  (1) RTIs - based on
the residue decline data which indicated a rapid decrease in residues as
the PHI increased from 0 to 14 days and then a more slow decline
thereafter and the proposed 21-day PHI, HED concludes that the employed
RTIs are acceptable; (2) single sample - the number of field trials
conducted in Europe (n=16) exceeds the number required for establishment
of a U.S. tolerance (n=12) and they were conducted over two years (2005
and 2006); and (3) wine grape varieties - the U.S. does not import a
significant quantity of table grapes from Europe (see Appendix 4) and
table grapes have larger berries than wine or raisin grapes and would,
therefore, have a smaller surface area per unit volume ratio than wine
or raisin grapes (most likely resulting in lower residues).  

Since 65% of the residues were <LOQ (limit of quantitation), employment
of the North American Free Trade Act (NAFTA) maximum residue limit (MRL)
calculator is inappropriate.  Based on the submitted data, HED concludes
that a grape tolerance of 0.20 ppm, for the combined residues of
meptyldinocap and 2,4-DNOP, is appropriate.  A revised Section F is
requested.  

The dinocap grape processing studies indicated that residues reduced in
juice (<0.15x) and wine (<0.15x); due to structural similarities, HED
concludes that dinocap and meptyldinocap will partition in a similar
manner during processing.  Therefore, separate grape juice and wine
tolerances are unnecessary.  The petitioner has not submitted
raisin-processing data.  Approximately 10% of the U.S. raisin
consumption is derived from imports with Chile and the Republic of South
Africa occupying 52% (5% of U.S. consumption) and 13% (1% of U.S.
consumption), respectively, of the total imported (see Appendix 4;
remaining imported raisins derived from countries where meptyldinocap is
not registered/proposed for application to grapes).  The petitioner
indicated that preliminary residue data are available which indicate
only a slight concentration of residues in raisin (concentration factor
was not provided).  Based on this information and the limited amount of
raisins imported from the relevant countries (note that Chile has a
lower application rate and longer PHI than Europe), HED concludes that a
tolerance is unnecessary.  However, the raisin processing data should be
submitted to HED when finalized; pending the submission of these data,
the risk assessment should assume a default raisin processing factor.  

Enforcement Method:  The petitioner has submitted adequate validation
and independent laboratory validation (ILV) data for a liquid
chromatography/mass spectrometry/mass spectrometry method (LC/MS/MS;
Method No. DOS/220-01R).  For this method, residues are extracted with
acetone:methanol:4 N HCl (100:10:5, v:v:v) followed by base hydrolysis
of meptyldinocap residues to 2,4-DNOP.  Residues of 2,4-DNOP are
quantified by summing the m/z 295.1→208.9 and 295.1→193.1
transitions (residues expressed in parent equivalents).  Radiovalidation
data were not submitted for this method; based on the extraction solvent
employed in this method and the results from the meptyldinocap apple
metabolism study (meptyldinocap and 2,4-DNOP only identified in the
methanol (MeOH) extract), radiovalidation is unnecessary.  HED has
determined that this method is adequate for tolerance enforcement and
forwarded the method to the Food and Drug Administration (FDA) for
publication in the Pesticide Analytical Manual (PAM; D361115, T. Bloem,
25-Feb-2009).  

FDA Multiresidue Methods:  Multiresidue method testing data are not
specifically available for meptyldinocap.  However, the 1/99 FDA
PESTDATA database (PAM Volume I) indicates that residues of dinocap are
completely recovered (>80%) using Multiresidue Methods Section 302 (Luke
Method) but are only partially recovered (50-80%) using Multiresidue
Methods Sections 303 (Mills, Onley, and Gaither, nonfatty) and 304
(Mills, fatty food).  As meptyldinocap is a major component (22%) of
dinocap and is expected to be recovered in a manner similar to the
mixture of isomers in dinocap, the available multiresidue method testing
data for dinocap will also cover meptyldinocap.

In addition to the existing FDA multiresidue testing data on dinocap,
the petitioner has also submitted data on the recovery of dinocap using
a European multiresidue method DFG S19 (Modular Multi Method L 00.00-34
of the Official Collection of Test Methods, German §35 LMBG, November
1999).  The recovery of dinocap (2,4-DNOPC and 2,6-DNOPC, 7:3) using
this multiresidue method was assessed using grapes, barley grain,
apples, and soybean flour.  Recoveries of dinocap were 69-108% from all
commodities (average from each commodity were 80-90% ± 6-12%; residues
in control samples were <30% of the LOQ for each commodity).  

Recommendation:  Provided the petitioner submits analytical standards
(meptyldinocap and 2,4-DNOP) to the EPA National Pesticide Standards
Repository, submits a revised Section F, and agrees to submit a grape to
raisin processing study, HED concludes that the residue chemistry
database supports the establishment of the following tolerance for the
combined residues of meptyldinocap (2-(1-methylheptyl)-4,6-dinitrophenyl
(2E)-2-butenoate) and 2,4-DNOP (2,4-dinitro-6-(1-methyheptyl)phenol)
expressed as meptyldinocap:  grape - 0.20 ppm.  

Summary of Residue Chemistry Deficiencies

(Submission of analytical standards (meptyldinocap and 2,4-DNOP) to the
EPA National Pesticide Standards Repository.

(Revised Section F.

(Grape to raisin processing data.Background

Meptyldinocap is a dinitrophenol fungicide which interferes with fungal
respiration by acting as an uncoupler of oxidative phosphorylation (FRAC
Group 29).  Meptyldinocap is one of the six isomers found in the older
fungicide dinocap (see Appendix 1 for structure); dinocap contains three
isomers of 2,4-DNOPC and three isomers of 2,6-DNOPC.  In dinocap, the
octyl groups for both the 2,4-DNOPC and 2,6-DNOPC isomers are a mixture
of 1-methylheptyl, 1-ethylhexyl, and 1-propylpentyl isomers. 
Meptyldinocap consists of >90% w/w of the 2,4-dinitro-6-(1-methylheptyl)
isomer, with the remaining five isomers each being present at <1% w/w. 
The meptyldinocap nomenclature is summarized in Table 1; the
meptyldinocap physicochemical properties are summarized in Table 2.  

Common name	Meptyldinocap (also referred to as
2,4-dinitro-6-(1-methylheptyl) crotonate)

Company experimental name	DE-126; RH-23,163

IUPAC name	(RS)-2-(1-methylheptyl)-4,6-dinitrophenyl crotonate 1

CAS name	2-(1-methylheptyl)-4,6-dinitrophenyl (2E)-2-butenoate

CAS registry number	131-72-6

Molecular weight	364.40

End-use product (EP)	350 g/L EC (GF-1478 Fungicide; 33.2% EC)

1	Previously referred to as 2,4-dinitro-6-(1-methylheptyl)phenyl
crotonate.

Table 2:  Physicochemical Properties of Technical Grade Meptyldinocap. 

Melting point	-22.5°C	MRID 47304901

pH	not applicable

	Relative density	1.11

	Water solubility (mg/L) at 20°C	0.151

	Solvent solubility (g/L) at 25°C	Acetone	>252

Ethyl acetate	>256

1,2-Dichloroethane	>252

Xylene	>256

n-Heptane	>251

acidic: 	240 nm (ε=16727), 310 nm (ε=2155)

basic:	260 nm (ε=6376), 372 nm (ε=12980), 405 nm (ε=10969)

neutral:	240 nm (ε=16727), 310 nm (ε=2155)

	860.1200  Directions for Use

A 350 g/L EC meptyldinocap formulation is currently registered for
control of powdery mildew on grapevines in the UK, Italy, Romania,
Hungry, Tunisia, and Chile.  The petitioner indicated that additional
registrations on grapes are pending for other countries in Europe,
Africa, and Asia (the following countries were listed:  Austria, Czech
Republic, France, Germany, Portugal, Republic of South Africa, Slovenia,
Spain, and Slovakia).  The petition included examples of labels from the
U.K., France, and Chile, and a summary of the use directions from
current and pending registrations.  Although there are slight regional
variations in timing and application volume, the petitioner indicated
that all uses are standardized on the following parameters:  PHI of
≥21 days, a maximum application rate of 0.21 kg ai/ha (excluding
post-harvest application in Chile), and a maximum of 4 applications per
season.  Table 3 is a summary of the registered/pending meptyldinocap
grape application scenarios.  The submitted information concerning the
proposed/registered application scenarios are adequate.  

Table 3:  Summary of Directions for Use of Meptyldinocap on Grapes.

App. Timing, Type,

and Equip.	Formulation	App. Rate

(kg ai/ha)	Max. No. App. per Season	Max. Seasonal App. Rate

(kg ai/ha)	PHI

(days)	Use Directions and Limitations

Maximum Application Rate in Several Europe, Africa, and Asia Countries

Broadcast foliar - BBCH 13 (3 leaves unfolded) to 81 (beginning of
ripening); ground equipment	350 g/L EC	0.21	4	0.84	21	RTI = 10 days, RTI
of 5 days when used as an eradicant late in the season (only two
applications may be made as a late season eradicant )

Chile

Broadcast foliar - swollen-bud to preflower and postharvest; ground
equipment	350 g/L EC	preharvest - 

0.21 postharvest -0.41	3	not indicated	60	RTI = 7 days.

860.1300 Nature of the Residue – Plants

47289103.der.doc (apple - meptyldinocap); 47289104.der.doc (apple -
2,6-DNOPC); 47289106.der.doc (cucumber - meptyldinocap);
47304905.der.doc (squash – meptyldinocap)

The petitioner submitted apple (two studies), cucumber, and squash
metabolism studies.  All of the studies were conducted with
[14C-U-phenyl]-meptyldinocap except for one of the apple studies which
was conducted with [14C-U-phenyl] 2,6-dinitro-4-(1-methylheptyl)phenyl
crotonate.  The apple metabolism studies indicate that following a
single foliar application 0-21 days prior to harvest, the majority of
the residues were in/on the fruit surface or peel and were degraded via
photolysis and/or metabolism to a large number of low-concentration
metabolites.  Meptyldinocap was the only compound found at greater than
10% of the total radioactive residue (TRR; 12-75% TRR); 2,4-DNOP (2-6%
TRR) and several benzoxazole compounds (<1% TRR) were also identified
(see Appendix 3 for petitioner proposed metabolic pathway).  The squash
and cucumber studies are considered scientifically unacceptable.  These
studies contain a number of deficiencies relating to the lack of
adequate information on the test substance, field trial procedures, and
sample storage conditions.  In addition, substantial proportions of the
TRR in both the cucumber and squash samples were not adequately
characterized/identified, and the identities of meptyldinocap and
2,4-DNOP were not confirmed using a second analytical method.  While the
squash and cucumber studies are inadequate, they do support the
identification of 2,4-DNOP as a minor metabolite of meptyldinocap.

The ROCKS determined that the available apple metabolism data are
acceptable for purposes of this petition.  Based on these data, the
ROCKS concluded that the residues of concern in grapes for tolerance
enforcement and risk assessment are meptyldinocap and 2,4-DNOP (D362393,
B. Daiss, 25-Feb-2009).  

860.1300 Nature of the Residue - Livestock

Livestock metabolism data were not submitted.  Since there are no
significant feedstuffs associated with the proposed use (see OECD
guidance document -   HYPERLINK "http://www.oecd.org/dataoecd/60/9/
41808585.pdf"  http://www.oecd.org/dataoecd/60/9/ 41808585.pdf ), these
data are unnecessary.  

860.1340 Residue Analytical Methods

47289107.der.doc (LC/MS/MS method)

Grape samples from the field trial, processing, and storage stability
studies were analyzed for residues of dinocap (2,4-DNOPC and 2,6-DNOPC)
or meptyldinocap and their respective DNOP derivatives using an
adequately validated LC/MS/MS (Method No. DOS/220-01R) or gas
chromatograph/electron-capture detector (GC/ECD; Rohm and Haas Method
No. 34-91-19) method.  The LC/MS/MS method has also undergone a
successful ILV trial using grape and apple samples fortified with mixed
standards (2,4- and 2,6-isomers) of DNOPC and DNOP.  Neither method was
radiovalidated; based on the extraction solvent employed in the LC/MS/MS
(acetone:MeOH:4 N HCl (100:10:5, v:v:v)) and GC/ECD (MeOH) methods and
the results from the meptyldinocap apple metabolism study (meptyldinocap
and 2,4-DNOP only identified in the MeOH extract), radiovalidation is
unnecessary.  

Based on a review of the method procedure and the validation data
submitted with the field trial and ILV studies, HED forwarded the method
to the FDA for publication in PAM (D361115, T. Bloem, 25-Feb-2009).  The
following text is a brief description of these methods and the FDA
Multiresidue Method testing data.  

Method No. DOS/220-01R:  Residues are extracted twice with
acetone:MeOH:4 N HCl (100:10:5, v:v:v), centrifuged, filtered, and
concentrated.  Residues are partitioned into hexane:ethyl acetate (1:1
v:v) and concentrated to dryness.  Residues are reconstituted in MeOH:5N
NaOH (2:1 v:v) and heated at 60°C for 60 minutes hydrolyzing the DNOPC
isomers into their respective phenol derivatives (DNOP).  After cooling,
the hydrolysate is diluted with water and acidified, and the residues
are partitioned into ethyl acetate.  Residues are dried through
anhydrous sodium sulfate, concentrated to dryness, and reconstituted in
acidic MeOH:water (70:30 v:v, with 0.1% glacial acetic acid) for
analysis by LC/MS/MS.  Residues of 2,4-DNOP are quantified by summing
the m/z 295.1→208.9 and 295.1→193.1 transitions, and residues of
2,6-DNOP are quantified using the m/z 295.1→208.9 transition.  The
method does not differentiate between the individual octyl isomers of
2,4-DNOPC and 2,6-DNOPC or between 2,4-DNOPC/2,6-DNOPC and their
respective DNOP isomers.  The combined LOQ is 0.05 ppm for both groups
of isomers, or 0.025 ppm for each isomer group and the limit of
detection (LOD) is 0.01 ppm for each isomer group.  Residues are
expressed in parent equivalents.  

Method No. 34-91-19:  Residues are extracted with MeOH and base
hydrolyzed to the respective DNOP derivatives by the addition of aqueous
sodium hydroxide.  The hydrolysate is acidified and the residues are
partitioned into hexane.  The residues are dried over anhydrous sodium
sulphate, concentrated to dryness, redissolved in diethyl ether, and
methylated using diazomethane.  The methylated residues are concentrated
to dryness, redissolved in hexane, and cleaned up using a deactivated
silica-gel column.  Residues are concentrated to dryness, redissolved in
2,2,4-trimethylpentane and analyzed by GC/ECD.  The total concentration
is generated by summing the peak areas of the three 2,4-DNOPC isomers
and the three 2,6-DNOPC isomers (individual concentration of each isomer
was not provided).  The study indicated that the concentration of the
2,6-dinocap isomers were estimated by calculating a ratio of the peak
area of the 2,6 isomers to the total area and applying this ratio to the
total calculated residue; the concentration of the 2,4-dinocap isomers
were then calculated as the difference between the total residue and the
2,6-dinocap residue.  The method does not differentiate between the
individual octyl isomers of 2,4-DNOPC and 2,6-DNOPC or between
2,4-DNOPC/2,6-DNOPC and their respective DNOP isomers.  The LOQ and LOD
for total dinocap residues are 0.05 ppm and 0.01 ppm, respectively. 
Residues are expressed in parent equivalents.

860.1360 Multiresidue Methods

47304904.der.doc (European multiresidue methods testing)

Multiresidue method testing data are not specifically available for
meptyldinocap.  However, the 1/99 FDA PESTDATA database (PAM Volume I)
indicates that residues of dinocap are completely recovered (>80%) using
Multiresidue Methods Section 302 (Luke Method) but are only partially
recovered (50-80%) using Multiresidue Methods Sections 303 (Mills,
Onley, and Gaither, nonfatty) and 304 (Mills, fatty food).  As
meptyldinocap is a major component (22%) of dinocap and is expected to
be recovered in a manner similar to the mixture of isomers in dinocap,
the available multiresidue method testing data for dinocap will also
cover meptyldinocap.

In addition to the existing FDA multiresidue testing data on dinocap,
the petitioner has also submitted data on the recovery of dinocap using
a European multiresidue method DFG S19 (Modular Multi Method L 00.00-34
of the Official Collection of Test Methods, German §35 LMBG, November
1999).  The recovery of dinocap (2,4-DNOPC and 2,6-DNOPC, 7:3) using
this multiresidue method was assessed using a high-water-content
commodity (grapes), a dry commodity (barley grain), an acidic commodity
(apples), and an oily commodity (soybean flour).  Recoveries of dinocap
were 69-108% from all commodities, and average recoveries from each
commodity were 80-90%, with relative standard deviations of 6-12%. 
Apparent residues of dinocap in control samples were <30% of the LOQ for
each commodity.  

860.1380 Storage Stability

47289109.der.doc (dinocap storage stability study)

Although the current petition is for meptyldinocap, the submitted
storage stability study examines the frozen storage stability of dinocap
in various fruits and vegetables.  In the study, control samples of
cucumbers, tomatoes, peaches, apples, and strawberries were fortified
with a mixed dinocap standard containing the 1-methylheptyl,
1-ethylhexyl, and 1-propylpentyl isomers of both the 2,4-DNOPC and
2,6-DNOPC components of dinocap.  The combined fortification level for
all six isomers was 1.0 ppm.  The fortified samples were analyzed after
0 (0-days), 1, 3, 6, 9, 12, 18, and 24 months of storage at ≤-20°C
using an adequately validated GC/ECD method (34-91-19; see above for
method description). 

There were no notable decreases in total dinocap residues in any
commodity over 24 months of frozen storage at ≤-20°C.  After 24
months of frozen storage, the average corrected recoveries for total
dinocap residues were 106-118% from cucumber, tomato, peach, apple, and
strawberry.  Although levels of the individual isomers were not
reported, the available chromatographic data indicated that the relative
peak heights for the six isomers were similar over time.  Considering
the high levels of recovery of total dinocap residues and the similarity
in the chromatographic data over time, the study also indicates that the
individual isomers, including meptyldinocap, are stable during frozen
storage.  Samples from the submitted grape field trials and processing
studies were stored frozen for 16-358 days prior to analysis (see Table
4).  Therefore, the storage intervals employed in the field trial and
processing studies have been validated.

≤-20	44-127	720 

(24 months)

	47304903.de1	≤-20	221-256

47289112.der	≤-18	199-252

47289115.der	≤-18	48-88

	Grape juice and wine	47304902.de2	≤-20	16-325

47304903.de2	≤-20	221-358

	

860.1400 Water, Fish, and Irrigated Crops

There are no proposed uses that are relevant to this guideline topic.  

860.1460 Food Handling

There are no proposed uses that are relevant to this guideline topic.  

860.1480 Meat, Milk, Poultry, and Eggs

There are no significant livestock feedstuffs associated with the
proposed use on grapes (see OECD guidance document -   HYPERLINK
"http://www.oecd.org/dataoecd/60/9/41808585.pdf" 
http://www.oecd.org/dataoecd/60/9/41808585.pdf ).  Therefore, data
requirements pertaining to the magnitude of the residue in meat, milk,
poultry, and eggs are not relevant to this tolerance petition.  

860.1500 Crop Field Trials

47304902.de1.doc; 47304903.de1.doc; 47289112.der.doc; 47289115.der.doc;
476002201.der.doc

The petitioner submitted sufficient European grape field trial data (see
next paragraph); however, application of meptyldincap to grapes grown in
Africa, Asia, and Chile is also requested but no residue data have been
submitted from these areas.  For the following reasons, HED concludes
that residue data from Africa, Asia, and/or Chile are unnecessary:  (1)
based on the Chilean application scenario (3 x 0.21 kg ai/ha; PHI = 60
days) and that performed in the field trials (4 x 0.21 kg ai/ha; PHI =
21 days), HED concludes that the European field trial data are
sufficient (ChemSAC minutes - 17-Sep-2008) and (2) the U.S. does not
import a significant quantity of table grapes, wine, or raisins from the
relevant African and Asian countries (see Appendix 4).  

Sixteen European grape field trials were conducted during 2005 and 2006
in France (7 trials), Italy (4 trials), Germany (3 trials), and Spain (2
trials).  In each trial, meptyldinocap (350 g/L EC) was applied to
grapes as four broadcast foliar applications during fruit development
(BBCH 76-85) at rates of 0.19-0.24 kg ai/ha (1x single/seasonal rate;
RTIs of 5-32 days).  Grape samples were harvested 21 days after
application (single sample at each trial) and were analyzed for residues
of meptyldinocap using an adequately validated method (storage intervals
have also been validated).  Combined residues of meptyldinocap and
2,4-DNOP ranged from <0.025 ppm to 0.12 ppm.  The residue data are
summarized in Table 5 (additional submitted exaggerated rate data are
also presented in Table 5).  

HED notes that the proposed minimum RTI is 5 days while the studies
employed RTIs of 5-32 days (the proposed 5-day RTI for the last two
applications; see Table 3), only single samples were collected at 11 of
the 16 trials rather than duplicates as requested in the OPPTS 860.1500
guidelines, and the studies employed only wine grape varieties.  For the
following reasons, HED concludes that additional data are unnecessary: 
(1) RTIs - based on the residue decline data which indicated a rapid
decrease in residues as the PHI increased from 0 to 14 days and then a
more slow decline thereafter and the proposed 21-day PHI, HED concludes
that the employed RTIs are acceptable and (2) single sample - the number
of field trials conducted in Europe (n=16) exceeds the number required
for establishment of a U.S. tolerance (n=12) and they were conducted
over two years (2005 and 2006); and (3) wine grape varieties - the U.S.
does not import a significant quantity of table grapes from Europe (see
Appendix 4) and table grapes have larger berries than wine or raisin
grapes and would, therefore, have a smaller surface area per unit volume
ratio than wine or raisin grapes (most likely resulting in lower
residues).  

Since 65% of the residues were <LOQ, employment of the NAFTA MRL
calculator is inappropriate.  Based on the submitted data, HED concludes
that a grape tolerance of 0.20 ppm, for the combined residues of
meptyldinocap and 2,4-DNOP (expressed in parent equivalents), is
appropriate.  A revised Section F is requested.  

Table 5:  Summary of Residue Data from Grape Field Trials with Dinocap
and Meptyldinocap.

Field trials (country/year/DER)	AI; Formulation	Total Rate (kg ai/ha)
PHI (days)	Residues (combined meptyldinocap and 2,4-DNOP; ppm)1

n	Min.	Max.	HAFT 2	Median	Mean	Std. Dev.

Grape (Maximum proposed use for meptyldinocap = 4 x 0.21 4g ai/ha,
21-day PHI)3

Germany, 1996

47304903.de1.doc	Dinocap 4

350 g/L EC	1.95-2.31

(2.3-2.8x)	0	3	1.30	1.97	1.97	1.76	1.68	0.34

	7	3	0.82	1.52	1.52	1.02	1.12	0.36

	14	3	0.55	0.74	0.74	0.65	0.65	0.10

	21	3	0.33	0.67	0.67	0.66	0.55	0.19

	28	3	0.41	0.46	0.46	0.46	0.44	0.03

Germany and France,

1997

47304902.de1.doc	Dinocap 4

350 g/L EC	1.23-2.01

(1.5-2.4x)	0	6	0.68	2.06	2.06	1.36	1.36	0.51

	7	6	0.33	0.92	0.92	0.65	0.64	0.21

	14	6	0.32	0.68	0.68	0.38	0.43	0.14

	21	6	<0.05	0.59	0.59	0.33	0.34	0.16

	28	6	0.14	0.44	0.44	0.23	0.26	0.11

	Dinocap 4

18% WP	1.21-2.02

(1.4-2.4x)	0	6	0.93	2.02	2.02	1.21	1.34	0.44

	7	6	0.48	1.18	1.18	0.69	0.74	0.24

	14	6	0.23	0.78	0.78	0.44	0.47	0.19

	21	6	0.22	0.50	0.50	0.27	0.31	0.11

	28	6	0.19	0.44	0.44	0.28	0.31	0.11

France, 2005

47289115.der.doc5	Dinocap 4

350 g/L EC	0.84-0.86

(1x)	21	4	<0.050	<0.055	<0.055	0.050	0.051	0.003

	Meptyldinocap 350 g/L EC	0.83-0.87

(1x)	21	4	<0.025	0.030	0.030	0.025	0.026	0.003

Italy and Spain, 2005

47602201.der.doc5	Dinocap 4

350 g/L EC	0.83-0.87

(1x)	21	4	<0.050	<0.055	<0.055	0.050	0.051	0.003

	Meptyldinocap 350 g/L EC	0.85-0.87

(1x)	21	4	<0.025	<0.025	<0.025	0.025	0.025	NA

France, Germany and Italy 2006

47289112.der.doc	Meptyldinocap 350 g/L EC	0.83-0.90

(1x)	21	7	<0.025	0.12	0.12	0.04	0.05	0.03

1  Values <LOQ were estimated to be at the LOQ for calculating the
median, mean and standard deviation; the residue values for
meptyldinocap at the proposed 21 day PHI are bolded.

2  HAFT = highest-average field trial residue.

3  The maximum global use rate as indicated by the petitioner; the
Chilean application rate is lower (3 x 0.21 kg ai/ha) with a longer PHI
(61 days).

4  The residue data on dinocap are summarized here only for information
purposes; these data indicate that the EC and WP formulations
(47304902.de1.doc) and high and low spray volumes (47304903.de1.doc)
yielded similar residues.

5  These studies employed side-by-side comparison of dinocap and
meptyldinocap.  Due to meptyldinocap containing only the single
2,4-DNOPC isomer and since residue were near the LOQ for both dinocap
and meptyldinocap, residues of meptyldinocap were less than that of
dinocap.  

860.1520 Processed Food and Feed

47304902.de2.doc; 47304903.de2

The petitioner   SEQ CHAPTER \h \r 1 submitted dinocap (2,4- and
2,6-DNOPC isomers) grape processing data from two trials conducted in
Germany during 1996 (47304903.de2.doc) and two trials conducted in
France during 1997 (47304902.de2.doc).  In each trial, dinocap (350 g/L
EC) was applied to grapes as eight broadcast foliar applications from
pre-bloom through fruit maturation (BBCH 16-85) at rates of 0.06-0.34 kg
ai/ha (0.3-1.6x) for a total application rate of 1.23-2.20 kg ai/ha
(1.5-2.4x; RTIs = 10-16 days).  Bulk grape samples were harvested 21
days after application and were processed into juice, young wine, and
mature wine using standard commercial procedures.  The resulting samples
were analyzed using an adequately validated method (storage intervals
have also been validated).  In the German trials, total dinocap residues
(2,4- and 2,6-isomers) were as follows:  grape - 0.64 ppm and 0.37 ppm;
juice - <0.05 ppm; young wine - <0.05 ppm; and wine - <0.05 ppm.  In the
French trials, total dinocap residues were as follows:  grape - 0.59 ppm
and 0.35 ppm; juice - <0.05 ppm; young wine - <0.05 ppm; and wine -
<0.05 ppm.  A summary of the processing factors are present in Table 6. 
The maximum theoretical concentration factor for juice and raisin are
1.2x and 4.7x, respectively (OPPTS 860.1520 Tables 2 and 3).

Based on structural similarities, HED concludes that dinocap and
meptyldinocap will partition in a similar manner during processing. 
Since dinocap, and by extension meptyldinocap, does not concentrate in
juice or wine, separate tolerances for these commodities are
unnecessary.  HED notes that the petitioner has not submitted
raisin-processing data.  Approximately 10% of the U.S. raisin
consumption is derived from imports with Chile and the Republic of South
Africa occupying 52% (5% of U.S. consumption) and 13% (1% of U.S.
consumption), respectively, of the total imported (see Appendix 4:
remaining imported raisins derived from countries where meptyldinocap is
not registered/proposed for application to grapes).  The petitioner
indicated that preliminary residue data are available which indicate
only a slight concentration of residues in raisin (concentration factor
was not provided).  Based on this information and the limited amount of
raisins imported from the relevant countries (note that Chile has a
lower application rate and longer PHI than Europe), HED concludes that a
tolerance is unnecessary.  However, the raisin processing data should be
submitted to HED when finalized; pending the submission of these data,
the risk assessment should assume a default raisin processing factor.  

  SEQ CHAPTER \h \r 1 Table 6:  Summary of Processing Factors for
Dinocap.

RAC	Processed Commodity	Processing Factors

Grapes;

Germany 1996

(47304903.de2)	Juice	<0.07x

	Young Wine	<0.07x

	Mature Wine	<0.07x

	Juice	<0.15x

	Young Wine	<0.15x

	Mature Wine	<0.15x

Grapes;

France 1997

(47304902.de2)	Juice	<0.14x

	Young Wine	<0.14x

	Mature Wine	<0.14x

	Juice	<0.08x

	Young Wine	<0.08x

	Mature Wine	<0.08x

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

An analytical standard for meptyldinocap is currently available in the
EPA National Pesticide Standards Repository (personal communication with
Dallas Wright; Analytical Chemistry Branch (ACB); 17-Jun-2008).  As this
standard will expire on 27-Mar-2009, the registrant must either
recertify the lot in the repository and send in an updated certificate
of analysis (COA), or submit a new standard (different lot #) if the
previous lot will not be recertified.  If a new COA is being submitted,
then it should be faxed to the repository at 410-305-2999.  If a new
standard is being submitted, then it should be sent to the following
address (note that the mail will be returned if the extended zip code is
not used):

	USEPA (attn:  Theresa Cole)

	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

	701 Mapes Road

	Fort George G. Meade, MD  20755-5350

860.1850/860.1900 Confined and Field Accumulation in Rotational Crops

There are no proposed U.S. uses for meptyldinocap or dinocap. 
Therefore, data requirements pertaining to rotational crops are not
relevant to this tolerance petition.  

860.1550 Proposed Tolerances

Based on the currently available data, HED recommends for a the
establishment of the grape tolerance listed in Table 7 for the combined
residues of meptyldinocap (2-(1-methylheptyl)-4,6-dinitrophenyl
(2E)-2-butenoate) and 2,4-DNOP (2,4-dinitro-6-(1-methyheptyl)phenol)
expressed as meptyldinocap.  There are currently no established Codex,
Canadian, or Mexican MRLs for meptyldinocap on grapes (see Appendix 2). 
However, the petitioner indicated that grape MRLs of 0.5 ppm have been
set in the UK and Italy based on a combination of meptyldinocap and
dinocap residue data; the petitioner anticipates that once the European
Union reviews the meptyldinocap residue data, the MRL will be lowered. 
Since there are currently no Canadian, Codex, or Mexican meptyldinocap
grape MRLs, harmonization is irrelevant.  

Table 7:  Tolerance Summary for Meptyldinocap.

Commodity	Proposed Tolerance (ppm)	HED-Recommended Tolerance (ppm)
Comments; Correct Commodity Definition

Grape	0.3	0.20	Revised Section F is requested (revise tolerance
expression and numerical value of the tolerance).

Grape, wine	0.3	None	Adequate data are available indicating that
residues do not concentrate in grape juice or wine; therefore, separate
tolerances are not required.

Grape, juice	0.3	None

	

  SEQ CHAPTER \h \r 1 RDI: RAB1 Chemists (28-Jan-2009); ChemSAC
(4-Feb-2009)

T. Bloem:S10945:Potomac Yard 1:703-605-0217:7509P:RAB1

  SEQ CHAPTER \h \r 1 Appendix 1	Chemical Name and Structure Table

Appendix 2	International Residue Limit Status Sheet

Appendix 3	Proposed Metabolic Pathways in Plants

Appendix 4	Import Information for Grape and Grape Processed Commodities

Template Version September 2005

Appendix 1:  Chemical Names and Structures of [14C]Meptyldinocap
Residues Identified in Plant Metabolism Studies.

Chemical name	Chemical structure	Matrices (%TRR)

meptyldinocap

2,4-dinitro-6-(2-octyl)phenyl crotonate

2,4-dinitro-6-(1-methyheptyl)phenyl crotonate 

(E)-2-butenoic acid, 2-(1-methylheptyl)-4,6-dinitrophenyl ester 		Apple
fruit – 7 and 21 DAT (21.2% and 12.2%)

Squash leaves – 25 DAT (3.2% TRR)

Squash - 25 DAT

(5.9%)

Cucumbers – 48 DAT (0.6%)

2.4-DNOP

2,4-dinitro-6-(1-methyheptyl)phenol		Apple fruit – 7 and 21 DAT (3.4%
and 5.6%)

Squash leaves - 25 DAT (4.8%)

Squash - 25 DAT (1.3%)

Cucumbers – 48 DAT (0.7%)

Metabolite A

2-hydroxy-5-nitro-3-(2-octyl)-phenyl crotonamide		Apple peel – 14 DAT
(0.3%)

Metabolite B

2-methyl-5-nitro-7-(2-octyl) benzoxazole		Apple peel – 14 DAT (0.1%)

Metabolite C

5-nitro-7-(2-octyl) benzoxazole		Apple peel – 14 DAT (0.1%)

Metabolite D

2-(hydroxymethyl)-5-nitro-7-(2-octyl) benzoxazole		Apple peel – 14 DAT
(0.4%)

Metabolite E

2-(1-propenyl)-5-nitro-7-(2-octyl) benzoxazole		Apple peel – 14 DAT
(0.1%)

Dinocap	

1-methylheptyl isomer	1-ethylhexyl isomer	1-propylpentyl isomer	not
identified

Appendix 2:  International Residue Limit Status Sheet.

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 

2,4-dinitro-6-(1methyheptyl)phenyl crotonate

	Common Name:

meptyldinocap

	x Proposed tolerance

( Reevaluated tolerance

( Other - HED recommended tolerances	Date: 1/14/09

Codex Status (Maximum Residue Limits)	U. S. Tolerances

x No Codex proposal step 6 or above

(No Codex proposal step 6 or above for the crops requested	Petition
Number:  7E7294

DP Number:  

Other Identifier:

Residue definition:  n/A	Reviewer/Branch: Tom Bloem/RAB1

	Residue definition:  meptyldinocap

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

grape	0.3

	Limits for Canada	Limits for Mexico

x No Limits

( No Limits for the crops requested	x No Limits

(   No Limits for the crops requested

Residue definition: N/A	Residue definition:  N/A

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

Notes/Special Instructions: S.Funk, 01/14/2009.

Appendix 3:  Proposed Metabolic Pathways in Plants.

Proposed Metabolic Pathway for the Formation of Metabolites B, C, and D.



Proposed Metabolic Pathway for the Formation of Metabolites A and E.

Appendix 4	Import Information for Grape and Grape Processed
Commodities.

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Share of Total Imported (%)1	Share of U.S. Consumption (%)3

2007	2006	2005	2004	2003

2007	2006	2005	2004	2003	2007	2006	2005	2004	2003	Average

Fresh Grapes3

44.7	41.4	41.0	53.3	56.3	Chile 	73	80	72	79	74	34	38	34	38	35	36

	Mexico 	23	16	25	18	25	11	8	12	9	12	10

	Brazil 	2	2	1	<1	<1	1	1	1	<1	<1	1

	Peru 	1	1	1	<1	<1	1	<1	<1	<1	<1	1

	Canada 	1	1	1	1	<1	<1	<1	<1	<1	<1	1

	Others 	<1	<1	<1	1	1	<1	<1	<1	<1	<1	1

Grape Juice3

48.7	54.4	40.6	57.1	45.6	Argentina 	88	89	86	79	74	44	44	42	41	38	42

	Chile 	4	2	4	18	25	2	1	2	3	5	3

	Canada 	3	2	2	<1	<1	2	1	1	1	1	1

	Mexico 	2	2	3	<1	<1	1	1	1	1	1	1

	Brazil 	1	1	4	1	<1	1	1	2	2	2	2

	Others 	2	2	1	1	1	1	1	1	1	1	1

	total

	Wine3

30.6	29.7	23.2	25.4	25.2	Italy	30	30	30	31	35	8	8	8	8	9	8

	Australia	24	28	28	29	25	6	7	8	8	7	7

	France	15	15	14	15	16	4	4	4	4	4	4

	Argentina	8	5	4	3	2	2	1	1	1	1	1

	Chile	7	7	8	8	8	2	2	2	2	2	2

	Spain	5	5	5	5	5	1	1	1	1	1	1

	Others	11	10	10	9	8	3	3	3	2	2	3

Raisin3

11	14	11	10	6	Chile	43	55	51	53	60	5	8	6	5	4	6

	Argentina	24	11	21	5	1	3	2	2	<1	<1	2

	Repub. of South Africa	20	13	9	11	12	2	2	1	1	1	1

	Mexico	6	12	10	27	22	1	2	1	3	1	2

	Iran	3	4	3	2	3	<1	1	<1	<1	<1	<1

	Greece	1	3	3	1	<1	<1	<1	<1	<1	<1	<1

	China	1	1	2	<1	<1	<1	<1	<1	<1	<1	<1

	Others	1	1	1	2	1	<1	<1	<1	<1	<1	<1

1  Import data for fresh grapes, grape juice, and wine was attained from
the USDA Fruit and Tree Nuts Situation and Outlook Yearbook (October
2008;   HYPERLINK
"http://www.ers.usda.gov/publications/fts/Yearbook08/FTS2008.pdf" 
http://www.ers.usda.gov/publications/fts/Yearbook08/FTS2008.pdf ). 
Import data for raisins was also attained from the October 2008 summary
and from communication with Agnes Perez of the USDA.  

2  Meptyldinocap may be applied to grapes grown in the bolded countries.
 

3  share of U.S. consumption = (imports as a share of U.S. consumption
(%)) x (share of total imported (%) ÷ 100)

Meptyldinocap	Summary of Analytical Chemistry and Residue Data	DP
Barcode:  D355561

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