Document ID: EPA-HQ-OPP-2006-0332-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-05-23T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	11/29/06

	Subject:	Famoxadone.  IR-4’s Request for New Uses on Grapes Grown
East of the Rocky Mountains, Hops, and Caneberries.  Summary of
Analytical Chemistry and Residue Data.  PP#s 5E7001 and 6E7099.

DP Num:	323682 & 333260	Decision Number:	361957 & 369719

PC Code:	113202	MRID Nos.:	46670201, -02, and 46905801

40 CFR §180.	587(a)

Chemical Class:	Oxazolidinedione fungicide

	From:	W. Cutchin, Acting Branch Senior Scientist

		Alternative Risk Integration Assessment Team (ARIA)

		Technical Review Branch (TRB)

		Registration Division (RD) (7505P)

	Through:	C. Swartz, Branch Chief

		Registration Action Branch 2 (RAB2)

		Health Effects Division (HED) (7509P)

	To:	S. Brothers/D. Rosenblatt RM 5

			Risk Integration Minor Use and Emergency Response Branch (RIMUIERB)

		RD (7505P)

This document was originally prepared under contract by Dynamac
Corporation.  The document has been reviewed by ARIA and revised to
reflect current Office of Pesticide Programs (OPP) policies.

Executive Summary

  SEQ CHAPTER \h \r 1 Famoxadone is an oxazolidinedione fungicide.  It
inhibits oxidative phosphorylation in the fungal mitochondria and is
highly active against spore germination and mycelial growth of sensitive
fungi.  Famoxadone is presently registered for food/feed uses on   SEQ
CHAPTER \h \r 1 fruiting vegetables, group 8; cucurbit vegetables, group
9; potatoes; and head lettuce.  These uses were first registered in
connection with PP#0F6070 along with the petitioner’s (DuPont) request
for a Section 3 registration of Tanos® DF fungicide (EPA Reg. No.
352-604), a mixed active ingredient formulation containing 25%
famoxadone and 25% cymoxanil.  Although there are no U.S. registrations
for grapes, import tolerances are currently established for grape and
raisin.

Tolerances for residues of famoxadone are listed in   SEQ CHAPTER \h \r
1 40 CFR §180.587 and are expressed in terms of famoxadone per se.  The
established tolerances for plant commodities range from 0.02 ppm on
potato to 10.0 ppm on head lettuce, and the established tolerances for
animal commodities range from 0.02 ppm in cattle fat to 0.05 ppm in
cattle liver.

The   SEQ CHAPTER \h \r 1 Interregional Research Project No. 4 (IR-4)
has submitted a request for an amended registration of the end-use
product Tanos® DF to include new domestic uses of famoxadone on grapes
grown east of the Rocky Mountains, hops, and caneberries.  Concurrently,
IR-4 requests the establishment of permanent tolerances for residues of
famoxadone  SEQ CHAPTER \h \r 1  in/on the raw agricultural commodities
listed below:

	Hops, dried	60 ppm

	Grape	2.5 ppm

	Caneberry	11 ppm

IR-4’s submission of supporting field trial data for grapes, hops, and
caneberries contain residue data for both active ingredients (cymoxanil
and famoxadone).  This summary document addresses only the residue
chemistry data for famoxadone; the residue chemistry data for cymoxanil
will be discussed in a separate document.

The proposed use pattern on grapes is also inadequately delineated
because of discrepancies regarding the maximum single and seasonal rates
listed in Section B and the submitted specimen label.  Since no residue
data from field trials on grapes grown east of the Rocky Mountains were
included in the current petition and the petitioner is relying on data
generated from Europe, a label revision is required for Tanos® DF to
comply with a previous regulatory conclusion made by HED’s Chemistry
Science Advisory Council (ChemSAC) regarding translation of data. 
According to the Minutes of the 4/7/04 HED’s ChemSAC meeting,   SEQ
CHAPTER \h \r 1 residue data generated in Europe (France, Germany,
Greece, and Spain) for use of cymoxanil plus famoxadone on grapes could
be translated to support use on grapes east of the Rocky Mountains. 
This determination was made following ChemSAC’s discussions of
climatic differences between Europe and regions east of the Rockies,
formulation differences (the European product contained 30% cymoxanil
and 22.5% famoxadone whereas the US formulation contains 25% of each
fungicide), and grape production statistics.  The ChemSAC concluded that
translation of data is reasonable with the following caveats: (i) since
the ratio of actives differs in the U.S. product, the label directions
need to ensure that the maximum application rate of each fungicide is
less than or equal to the corresponding rate in the European trials;
(ii) other use parameters such as the preharvest and reapplication
intervals also need to match the data; and (iii) the petition needs to
address any significant differences in the inert ingredients of the two
formulations.  If the US product contains an inert, which can
significantly increase the adherence or stability of the residues, the
data translation is not likely to be accepted.  The ChemSAC confirmed
the use of European data to support uses on grapes east of the Rocky
Mountains for other active ingredients (7/12/06).

The proposed use pattern on hops is inadequately delineated because of
discrepancies regarding the maximum single and seasonal rates listed in
Section B and the submitted specimen label.  ARIA recommends a label
revision of Tanos® DF to reflect the application rates (single and
seasonal), retreatment interval, and preharvest interval that were used
in the hop field trials.

The proposed use pattern on caneberries is adequate.  The proposed use
is for six foliar applications of DPX-KP481 50WG (25% famoxadone)
applied at a rate of 0.75 lb ai/A (0.188 lb/A famoxadone) at 4-7 day
intervals (4.5 lb ai/A/season, 1.125 lb famoxadone/A/season) with a
0-day PHI.  

The nature of the residue in grapes, potatoes, and tomatoes is
adequately understood based on acceptable metabolism studies.  The HED
Metabolism Assessment Review Committee (MARC) has determined that the
residue of concern in plant commodities is famoxadone per se.  However, 
 SEQ CHAPTER \h \r 1 HED believes that a metabolism study with an
oilseed or grain crop is needed to complete a general understanding of
the nature of the residue in all target crops. Based on crops which are
currently registered, the residue of concern for risk assessments and
tolerance enforcement is famoxadone per se.  The metabolic profiles in
the tested primary crops (grapes, potato, and tomato) were similar in
that the majority (90+ %TRR) of the residue consisted of surface
residues of famoxadone.  However, the pathways and metabolites in each
crop differed slightly.  For the purposes of the current submissions,
the nature of the residues of famoxadone is adequately understood: the
residue of concern for risk assessments and tolerance enforcement is
famoxadone per se.  

There are no livestock feedstuffs associated with the proposed use on
grapes, hops, and caneberries.  Therefore, data requirements for animal
metabolism, residue analytical methods for animal commodities, storage
stability data for animal commodities, and animal feeding studies are
not relevant to this tolerance petition.

  SEQ CHAPTER \h \r 1 An analytical method [AMR 3705-95; gas
chromatography with nitrogen/phosphorus detector (GC/NPD)] for plants
was developed for data gathering and enforcement purposes to quantitate
famoxadone.  The method has undergone a successful independent
laboratory validation (ILV) and Agency petition method validation (PMV).
 The limit of quantitation (LOQ) for famoxadone was reported to be 0.02
ppm for grapes, tomatoes, barley and wheat grain, and 0.05 ppm for
barley/wheat straw and green forage.  Also, Protocol D from the FDA
Multiresidue Methods recovers famoxadone for wine, grapes, and tomatoes.

Samples of grapes addressed in this document were analyzed for residues
of famoxadone using a GC electron capture detector (GC/ECD) method
[referenced as a multi-residue enforcement method (DFG S 19 Modified)
for the determination of famoxadone in dry, high water, and oil crops]. 
Adequate concurrent method recovery data have been submitted for this
method.  The validated method LOQ is 0.02 ppm and the limit of detection
(LOD) was not reported.

Samples of dried hop cones were analyzed for residues of famoxadone
using the enforcement method (AMR 3705-95, Revision No. 2) with
modifications.  The petitioner stated that a major change to the method
is that both famoxadone and cymoxanil are analyzed by liquid
chromatography with mass spectroscopy (LC/MS).  In the original method
famoxadone was analyzed by GC/NPD and cymoxanil by LC with ultraviolet
detector (LC/UV).  Adequate method validation and concurrent method
recovery data have been submitted for this method.  The lowest limit for
method validation (LLMV) is 0.5 ppm for famoxadone and the calculated
LOQ and LOD are 0.34 and 0.11 ppm, respectively, for residues of
famoxadone.

Caneberry samples were analyzed for famoxadone using an analytical
method entitled Residue Analysis of Famoxadone on Caneberry by GC/EC
Detection, Version #1.  Method validation was accomplished by spiking
untreated control samples of caneberry RAC at famoxadone levels of 0.02,
0.50, and 5.0 ppm.  The famoxadone recoveries were all in the acceptable
range of 70-120% except for one recovery value at 0.02 ppm (125%).  The
mean concurrent method recovery of famoxadone at the lowest level of
method validation (0.02 ppm) was 125% ± 5.0 (n = 3).  The mean
concurrent recovery of famoxadone at all fortification levels was 93% ±
22.3 (n = 15).  An LOQ of 0.028 ppm and an LOD of 0.0092 ppm was
reported for caneberries.  

There are adequate storage stability data to support the storage
conditions and intervals of samples collected from the crop field trials
and processing study.  

The results from the grape field trials show that residues of famoxadone
were 0.21-0.75 ppm in/on wine grapes harvested 28 days following the
last of ten foliar spray applications at a total rate of 0.899-1.099 lb
famoxadone ai/A.  Residue decline data show that famoxadone residues
generally decrease slightly in wine grapes with increasing preharvest
intervals.  The current tolerance of 2.50 ppm for grapes is appropriate
to support the proposed use.  

The residue data from the hop field trials indicate that residues of
famoxadone ranged from 14.70 ppm to 46.85 ppm in/on dried hops harvested
7-8 days after the last of six applications at a total rate of ~1.50 lb
ai/A.  Statistical analysis of the data show that a tolerance level of
80 ppm will be appropriate for hops.  A revised Section F for hops,
dried at 80 ppm is required.  

The results from the cranberry trials show that famoxadone residues
ranged from 0.40 ppm to 6.7 ppm on/in treated cranberries when the test
substance was applied at the proposed seasonal application rate of 1.125
lb ai/A using a 0-day PHI.  A residue decline study was not conducted by
the applicant.  Statistical analysis of the data show that a tolerance
level of 10 ppm will be appropriate for caneberries.  In addition, the
correct commodity definition is caneberries, subgroup 13A.  A revised
Section F for caneberries, subgroup 13A at 10 ppm is required.

The HED’s ChemSAC   SEQ CHAPTER \h \r 1 has determined that a grape
processing study is required to determine whether famoxadone residues
concentrate in juice.  An acceptable European processing study is
available for grape.  The processing data show that famoxadone residues
do not concentrate in grape juice.  The ChemSAC has also determined that
data are not required for raisins for a use limited to east of the Rocky
Mountains.  

The requirements for data pertaining to confined/field accumulation in
crops are not germane to this petition because grapes, hops, and
caneberries   SEQ CHAPTER \h \r 1 are crops not typically rotated.

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

Pending receipt of the revised Section F and label revisions as
recommended below, ARIA  SEQ CHAPTER \h \r 1  concludes that there are
no major residue chemistry data requirements that would preclude
IR-4’s amended registration request for Tanos® DF (EPA Reg. No.
352-604) to add new uses on hops and grapes grown east of the Rocky
Mountains.

A human health risk assessment will be prepared as a separate document.

860.1200 Directions for Use

Label amendments are required for Tanos® DF (EPA Reg. No. 352-604) to
reflect the parameters of field trial data for hops and to be consistent
with the HED’s ChemSAC determination regarding translation of residue
data for grapes.  

For hops, the label should be revised to specify a maximum foliar
application rate of 0.25 lb ai/A, with a 6-8 day retreatment interval
(RTI), a maximum seasonal rate of ~1.50 lb ai/A, and 7-day preharvest
interval (PHI). 

For grapes grown east of the Rocky Mountains, the label should be
revised to be consistent with the ChemSAC’s determination that   SEQ
CHAPTER \h \r 1 residue data generated in Europe (France, Germany,
Greece, and Spain) for use of cymoxanil plus famoxadone on grapes could
be translated to support use on grapes east of the Rockies provided the
use patterns are identical or the use pattern is more restrictive (i.e.,
lower application rates and longer PHI).  Therefore, based on the
European field trial data, the proposed use on grapes grown east of the
Rocky Mountains should be revised to specify a maximum seasonal rate of
~1.1 lb ai/A and a 28-day PHI.

860.1500 Crop Field Trials

Statistical analysis of the data show that a tolerance level of 80 ppm
will be appropriate for hops. A revised Section F for hops, dried at 80
ppm is required.  

Statistical analysis of the data show that a tolerance level of 10 ppm
will be appropriate for caneberries.  In addition, the correct commodity
definition is caneberries, subgroup 13A.  A revised Section F for
caneberries, subgroup 13A at 10 ppm is required.  

Note to PM:  ARIA defers to RD for examination of inert ingredients
listed on Tanos® DF.    SEQ CHAPTER \h \r 1 If Tanos® DF contains an
inert which can significantly increase the adherence or stability of the
residues, the residue data generated in Europe for use of cymoxanil plus
famoxadone on grapes could not be translated to support use on grapes
east of the Rockies.

Background

Famoxadone   SEQ CHAPTER \h \r 1 is one of the active ingredients
included in the fungicide Tanos® DF, a dry flowable formulation
containing 25% ai famoxadone + 25% ai cymoxanil.  Famoxadone is known to
inhibit the oxidative phosphorylation in the fungal mitochondria and is
highly active against spore germination and mycelial growth of sensitive
fungi.  The chemical structure and nomenclature of famoxadone are
presented in Table 1.  The physicochemical properties of famoxadone are
presented in Table 2.

™ Tanos® Fungicide; EPA Reg. No. 352-604) contains 25% famoxadone and
25% cymoxanil

Table 2.	Physicochemical Properties of Famoxadone.

Parameter	Value	Reference

Melting point/range	  SEQ CHAPTER \h \r 1 140.3- 141.8°C	PP#0F06070 and
PP#7E04847; DP Num:271377 and 287253, M. Doherty, 4/18/03

pH	  SEQ CHAPTER \h \r 1 6.56 at 20°C

	Density	  SEQ CHAPTER \h \r 1 D204 = 1.310 g/mL

	Water solubility	  SEQ CHAPTER \h \r 1 pH		g/L

unbuffered	  52

2		143

3		191

5		243

7		111

9		  38

	Solvent solubility	  SEQ CHAPTER \h \r 1 Solvent		g/L

acetone		274

acetonitrile	125

dichloromethane	239

ethyl acetate	125

hexane		    0.0476

methanol		  10.0

1-octanol		    1.87

toluene		  13.3

	Vapor pressure	  SEQ CHAPTER \h \r 1 6.4×10-4  mPa (4.8×10-9 mm Hg)

	Dissociation constant, pKa	  SEQ CHAPTER \h \r 1 Expected to be weakly
basic.  The dissociation constant could not be measured or inferred from
solubility or octanol water partition coefficient.

	Octanol/water partition coefficient, Log(KOW)	  SEQ CHAPTER \h \r 1 pH
Log Kow ± SD

3.0	4.59 ± 0.06

5.0	4.80 ± 0.13

7.0	4.65 ± 0.40

9.0	5.55 ± 0.26

	UV/visible absorption spectrum	NA

	

860.1200  Directions for Use

The petitioner submitted an undated draft specimen label for a 50% dry
flowable (DF) multiple active ingredient (MAI) formulation (Tanos®
fungicide; EPA Reg. No. 352-604) containing 25% cymoxanil and 25%
famoxadone.  In addition, the petitioner included the current accepted
registered label for the same formulation (dated 6/24/05) along with the
proposed use pattern for grapes (east of the Rocky Mountains) and hops
in Sections A and B of the petition, respectively. The product proposed
for amended use is presented in Table 3.  A summary of the proposed uses
on grapes (east of the Rocky Mountains) and hops is presented in Table
4.  We note that the use pattern from the undated draft label differs
from the use pattern proposed in Section B.

Table 3.  Summary of Proposed End-Use Products.

Trade Name	Reg. No.	ai (% of formulation)	Formulation Type	Target Crops
Target Pests	Label Date

Tanos® DF Fungicide	352-604	25% cymoxanil

25% famoxadone	Dry flowable (DF)	Grapes (east of the Rocky Mountains)

Hops	Downy mildew

Late blight	undated draft label

Table 4.  Summary of Directions for Use of Famoxadone.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Grapes (East of the Rocky Mountains)

Foliar spray

Ground, aerial, or chemigation	Section B;

[352-604]	0.25	Not specified (NS)	2.5	30

Undated specimen label;

[352-604]	0.094-0.125	3 per crop cycle	0.375 per crop cycle

1.125 per year	30	Applications may be made in a minimum of 20 gal/A
using ground equipment or 5 gal/A using aerial equipment with a 5- to
7-day retreatment interval.

Hops

Foliar spray

Ground, aerial, or chemigation	Section B; [352-604]	0.125-0.25	NS	1.5	7

Undated specimen label;

[352-604]	0.125-0.156	3 per crop cycle	0.469 per crop cycle

1.125 per year	7	Applications may be made in a minimum of 20 gal/A using
ground equipment or 10 gal/A using aerial equipment with a 5- to 7-day
retreatment interval.

Caneberries

Foliar spray

Ground or aerial	Tanos®

[352-604]	0.188	6	1.125	0	Applications may be made in a minimum of 20
gal/A using ground equipment or 5 gal/A using aerial equipment with 5-
to 7-day retreatment interval.

  SEQ CHAPTER \h \r 1 The following general use directions are also
specified for the 50% DF formulation containing 25% cymoxanil and 25%
famoxadone.    SEQ CHAPTER \h \r 1 Famoxadone, one of the active
ingredients, is a Group 11 (Qol-containing) fungicide, which also
includes all strobilurins and fenamidone.  The following recommendations
were made regarding resistance management.  Do not make more than one
application of Tanos® before alternating with a fungicide that has a
different mode of action, such as maneb, copper, captan, fosetyl-Al, or
dimethomorph.  Do not make more than three applications of Tanos® or
other Group 11 fungicides (all strobilurins or fenamidone) per cropping
cycle.  Do not alternate or tank mix with fungicides to which resistance
has developed.  A reentry interval (REI) of 12 hours is proposed.

The following rotational crop restrictions are specified on the undated
draft specimen label.  Crops listed on the label [cucurbits, grapes
(east of the Rocky Mountains), head lettuce, hops, peppers, potatoes,
and tomatoes] may be planted back at any time and all other crops may be
planted back following a minimum plantback interval of 30 days.

Conclusions:  The proposed uses of   SEQ CHAPTER \h \r 1 Tanos® DF on
hops and grapes grown east of the Rockies are inadequately delineated
because of discrepancies regarding the maximum single and seasonal rates
listed in Section B and the submitted specimen label.  For hops, label
revision is required to allow consistency of use pattern with the field
trial data; the label must be revised to specify a maximum of six foliar
directed applications with a 6- to 8-day RTIs at 0.25 lb famoxadone
ai/A/application for a total seasonal rate of 1.5 lb famoxadone ai/A and
a 7-day PHI.  For grapes, the label must be revised to comply with the
HED ChemSAC’s determination that   SEQ CHAPTER \h \r 1 residue data
generated in Europe (France, Germany, Greece, and Spain) for use of
cymoxanil plus famoxadone on grapes could be translated to support use
on grapes grown east of the Rockies provided the use patterns are
identical or the use pattern is more restrictive (i.e., lower
application rates and longer PHI).  The proposed use on grapes east of
the Rockies should be revised to specify a maximum seasonal rate of 1.07
lb famoxadone ai/A and a 28-day PHI.

The proposed use pattern on caneberries is adequate.  

860.1300 Nature of the Residue - Plants

44946415.der.wpd  (Tomato DER, L. Croteau, 4/7/03; DP Num: 271377, M.
Doherty, 4/18/03)

44302446.der.wpd (Grape DER, L. Croteau, 4/7/03; DP Num: 271377, M.
Doherty, 4/18/03)

44302448.der.wpd (Potato DER, L. Croteau, 4/7/03; DP Num: 271377, M.
Doherty, 4/18/03)

MARC Decision Memo (DP Num: 288134, M. Doherty, 3/12/03)

Plant metabolism studies with famoxadone have been conducted on tomato,
grape, and potato.  The results from each study are summarized below.

Tomato

Famoxadone, as a suspension concentrate (SC), was radiolabeled in either
the phenylamino [14C-PA] or phenoxyphenyl [14C-POP] moiety and applied
to tomato plants (variety: “Heinz 1370") at 1,260 g ai/ha/season (1.12
lb ai/A; 18 oz/A) as two over-the-top foliar sprays.  Tomato samples
were homogenized, combusted and radioassayed by liquid scintillation
counting (LSC).  Identification and characterization of 14C-residues was
achieved by high-performance chromatography (HPLC) with a diode array
detector/radiodetector.  Mass spectroscopy (MS) was used to confirm the
identity of the parent compound.  The storage stability of famoxadone in
tomato samples was adequately demonstrated under the storage conditions
of the nature of the residue study.  

The total radioactive residues (TRRs) were 0.2 ppm (POP) and 0.17 ppm
(PA) in the first immature tomato fruit sample collected immediately
after the 1st application.  The TRRs for samples collected immediately
prior to the 2nd application (Day 14) were 0.08 ppm for both the POP and
PA-labelled samples.  The concentration of the TRRs in mature fruit
collected 3 days after the 2nd application was 0.1 ppm (POP) and 0.06
ppm (PA).  The majority of the radioactive residues were extractable
(89-95% of the TRRs), with acetone extraction removing 78-88% of the
total radioactive residues.  Phosphate buffer extracts contained smaller
quantities (6-14% of the TRRs) with the highest buffer concentration
representing 0.02 ppm (Day 0 samples).  The concentration of
unextractable [14C]residues was <10% of the TRRs (<0.01 ppm) for all
samples.  The predominant residue extracted was famoxadone with
concentrations of 0.07 ppm (POP) and 0.05 ppm (PA) in the final harvest
mature fruit collected 3 days after the 2nd treatment.  No significant
metabolites were detectable in any tomato fruit extract.

Grape

Famoxadone, as a suspension concentrate (SC), was radiolabeled in either
the phenylamino [14C-PA] or phenoxyphenyl [14C-POP] moiety and applied
twice to grape vines (variety: “Seyval Blanc”) at 300 g ai/ha per
application for a total of 600 g ai/ha/season (8.6 oz/A) with a 7-day
interval between spraying.  Grape cuttings were transplanted in a
greenhouse and grown until approximately three weeks before the
anticipated grape harvest, when individual vines were each pruned to
12-14 leaves and one grape cluster.  Leaves and grapes were sampled
immediately after each application, and one and two weeks after the
second application.  Grape samples (fruit and foliage) were homogenized,
combusted and radioassayed by LSC.  Identification and characterization
of 14C-residues was achieved by HPLC with a diode array
detector/radiodetector.  MS was used to confirm the identity of the
parent compound and metabolites.  The storage stability of famoxadone in
grape samples was adequately demonstrated under the storage conditions
of the nature of the residue study.

The majority of the 14C-residues in the leaves were characterized as
surface residues, accounting for more than 93% (range 88-98%) of the
total radioactivity from the [14C-POP]famoxadone and [14C-PA]famoxadone
treatments averaged over the four sampling intervals.  An average of
less than 7% (range 2-12%) of the radioactivity was incorporated into
the leaf tissue.  Surface residues on [14C-POP] famoxadone- and [14C-PA]
famoxadone-treated grape berries also averaged greater than 92% (range
87-98%) of the total radioactivity over the four sampling intervals.  An
average of less than 10% (range 2-21%) of the radioactivity was
incorporated into the grape tissue.

Famoxadone was the major radioactive component in grape leaves and
berries from both label treatments.  Greater than 98% (range 94-100%) of
the surface 14C-residues were identified as famoxadone.  IN-H3310 was
isolated from the surface residues of [14C-POP] famoxadone treated
leaves immediately after the second application.  This metabolite
accounted for less than 2% (range <0.1-1.4%) of the surface residues at
Days 7 and 14 in the study.

Approximately 84% of the radioactivity incorporated in the leaf tissue
from both label treatments was extractable with ethyl acetate, and
chromatographic analyses indicated that an average of 72% of the
extractable radioactivity co-eluted with famoxadone.  Approximately 59%
of the radioactivity in grape tissue was solvent extractable and an
average of 73% of the extractable radioactivity co-eluted with
famoxadone.

The majority of the applied [14C] famoxadone on the grape leaves and
berries was deposited as surface residues and recovered as undegraded
famoxadone.  Cleavage of the parent molecule to yield the corresponding
1-(4-phenoxyphenyl)ethanone (IN-H3310) is the primary metabolic pathway.

Potato

Famoxadone, as a suspension concentrate (SC), was radiolabeled in either
the phenylamino [14C-PA] or phenoxyphenyl [14C-POP] moiety and applied
three times to groups of four potato plants (“Maine Certified Seed
Potatoes”) at a rate of 300 g ai/ha (0.267 lb ai/A) for a total of 900
g ai/ha/season (0.801 lb ai/A), with 30 days between the first and
second application and 7 days between the second and third application. 
Potato plants were maintained in the greenhouse.

Treated and control leaves/seed potatoes were harvested within 2 hours
after the first application, at 1 hour before the second and third
application and at 14 days after the third application.  Radiolabeled
residues in the leaves and tubers were characterised as surface-
washable residues (recovered using acetone/water washing) and plant
residues (solvent extractable and unextractable residues).  Potato
foliage and tuber samples were homogenized, combusted and radioassayed
by LSC.  Identification and characterization of 14C-residues was
achieved by HPLC with a diode array detector/radiodetector.  [14C]
Residues associated with the residual extracted plant tissues were
subjected to enzyme (cellulase) digestion (pH 5) in an attempt to
release any bound residue for characterization.  MS was used to confirm
the identity of the parent and the metabolites.  The storage stability
of famoxadone in potato samples was adequately demonstrated under the
storage conditions used in this nature of the residue study.

Greater than 50% (range 52-97%) of the total radiolabeled residues from
both the [ 14C-POP]- and [14C-PA] famoxadone treatment groups were
recovered as surface residues from the treated leaves.  No detectable
radiolabeled residues were found in either immature or mature tubers
(<0.01 mg/kg equivalent).  On average, greater than 90% (range 76(100%)
of the surface residues were identified as famoxadone. 
1-(4-phenoxyphenyl)ethanone (IN-H3310) was isolated as a minor
degradation product from the [14C-POP] famoxadone treated leaves (less
than 5% of the total plant residues).  No significant degradation
product was observed from the [14C-PA] famoxadone treated samples.

The isomeric ratio of famoxadone in the treatment solutions and in the
undegraded materials recovered from the leaf surfaces and leaf extracts
remained at approximately 50/50, indicating that no stereoselective
metabolism/degradation of famoxadone occurred in/on potato leaf
surfaces.

Conclusions:  The available plant metabolism studies with famoxadone on
tomato, grape, and potato have been deemed scientifically acceptable and
adequate to delineate the nature of famoxadone-related residues in those
crops.  In a meeting held on 12/16/02, the HED MARC determined that for
the petitioned crops, the residue of concern for both tolerance
enforcement and risk assessment is famoxadone, per se.  Although all the
studies show famoxadone to be the predominant residue in examined crops,
there are slight differences in the metabolic profile for each.  In
order for the Agency to conclude that the metabolism of famoxadone is
adequately delineated in all crops, a metabolism study in an oilseed or
grain crop will need to be submitted.  However, the nature of the
residue studies are adequate for the determination of famoxadone
residues on grapes, hops, and caneberries.  The residue of concern for
both tolerance enforcement and risk assessment for the purposes of this
petition is famoxadone, per se

860.1300 Nature of the Residue - Livestock

There are no livestock feedstuffs associated with the proposed use on
grapes and hops.  Therefore, data requirements for livestock metabolism
are not relevant to this tolerance petition.

860.1340 Residue Analytical Methods

MRIDs 44579102, 449464419, 44331201, 44302451, 44946421, 449464418 (DP
Num: 287253 and 271377, M. Doherty, 4/18/03)

Enforcement methods:  In conjunction with PP#0F6070 and PP#7E4847, a 
SEQ CHAPTER \h \r 1 n analytical method  (AMR 3705-95; GC/NPD) was
developed for data gathering and enforcement purposes to quantitate
famoxadone and its co-formulated active ingredient cymoxanil.  The
principle of the method is homogenization/extraction of sample matrices
with aqueous acetonitrile, cleanup by solvent partitioning into hexane
followed by passage through a Florisil column or various solid-phase
extraction (SPE) cartridges, and analysis/quantitation by GC/NPD or
column switching HPLC/UV (tomato paste).  The enforcement method for
plant matrices has undergone adequate ILV.

range of 0.01-3.0 μg/mL.  Percent recoveries ranged from 73-112% (SD
<15%) for grapes, tomatoes, grain, and straw over a spiking range of
0.02-15 ppm.  Confirmation was provided by HPLC/MS, GC/MS or GC/MS/MS. 
The method was adequately radiovalidated using bioincurred residues from
plant metabolism studies.

Data-collection methods:  Samples of grapes addressed in this document
were analyzed for residues of famoxadone using a GC electron capture
detector (GC/ECD) method [referenced as a multi-residue enforcement
method (DFG S 19 Modified) for the determination of famoxadone in dry,
high water, and oil crops].  Adequate concurrent method recovery data
have been submitted for this method.  The validated method LOQ is 0.02
ppm and the LOD was not reported.

Samples of dried hop cones were analyzed for residues of famoxadone
using the enforcement method (AMR 3705-95, Revision No. 2) with
modifications.  The petitioner stated that a major change to the method
is that both famoxadone and cymoxanil are analyzed by liquid
chromatography (LC/MS).  In the original method famoxadone was analyzed
by GC/NPD and cymoxanil by LC/UV.  Adequate method validation and
concurrent method recovery data have been submitted for this method. 
The lowest limit for method validation (LLMV) is 0.5 ppm for famoxadone
and the calculated LOQ and limit of detection (LOD) are 0.34 and 0.11
ppm, respectively, for residues of famoxadone.

Caneberry samples were analyzed for famoxadone using an analytical
method entitled Residue Analysis of Famoxadone on Caneberry by GC/EC
Detection, Version #1.  Method validation was accomplished by spiking
untreated control samples of caneberry RAC at famoxadone levels of 0.02,
0.50, and 5.0 ppm.  The famoxadone recoveries were all in the acceptable
range of 70-120% except for one recovery value at 0.02 ppm (125%).  The
mean concurrent method recovery of famoxadone at the lowest level of
method validation (0.02 ppm) was 125% ± 5.0 (n = 3).  The mean
concurrent recovery of famoxadone at all fortification levels was 93% ±
22.3 (n = 15).  An LOQ of 0.028 ppm and an LOD of 0.0092 ppm was
reported for caneberries.  

Conclusions.  The methods used in these studies are acceptable for data
collection purposes.

860.1360 Multiresidue Methods

MRID 44302452 (DP Num: 287253 and 271377, M. Doherty, 4/18/2003)

  SEQ CHAPTER \h \r 1 Famoxadone was screened through multiresidue
methods listed in the Pesticide Analytical Manual Volume I (PAM Vol. I),
Third Edition (January 1994), using Protocols C to E.  Protocols A and B
were not used because famoxadone does not have an n-methyl carbamate
structure (Protocol A), nor is it an acid or phenol (Protocol B). 
Protocol C showed good analytical response using ECD and NPD.  Good
recoveries were obtained for the analysis of wine, grapes, and tomatoes
(92-138%) using Protocol D.  Grapes (red seedless) can be analyzed for
famoxadone residues using Protocol E involving extraction with the mixed
ether elution system, resulting in recovery values of 92 to 108%.

Conclusions:  The multiresidue methods testing appears to be
scientifically acceptable and has been sent to the FDA for further
evaluation.  Preliminary analysis suggests that Protocol D may be
appropriate for analysis of famoxadone in plant matrices and has the
potential to be the primary enforcement method.

860.1380 Storage Stability

Samples collected from the field and processing studies were stored
frozen prior to residue analysis.  The storage intervals and conditions
of samples are presented in Table 5.

Table 5.   Storage Conditions and Intervals of Samples from Field Trial
Studies.

Matrix 

[MRID]	Storage Temperature

(°C)	Actual Storage Duration	Interval of Demonstrated Storage Stability

Grape, fruit

[46670202]	-18	55-84 days

(1.8-2.8 months)	18 months 1

Grape, fruit

[44302458-44302464]	-10	5-13 months

	Hops, dried cones

[46670201]	-20	195-206 days

(6.4-6.8 months)	253 days (8.3 months)

Raspberries

 [46905801]  	-21	181 days (6 months)	215-216 days (7.2 months)

1  Data (MRID 44302453) submitted in a previous petition review; refer
to PP#7E4847; DP Num: 287253 and 271377, M. Doherty, 4/18/03.

Conclusions:  There are adequate storage stability data to support the
integrity of samples collected from field and processing studies. 
Residues of famoxadone are stable under frozen storage conditions for up
to 18 months in/on grapes, 8.3 months in/on dried hops, and 7.2 months
on caneberries.  There are no storage stability issues or corrections
that may need to be applied to the various residue studies.

860.1400 Water, Fish, and Irrigated Crops

There are no proposed/registered uses that are relevant to this
guideline.

860.1460 Food Handling

There are no proposed/registered uses that are relevant to this
guideline.

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with the proposed use on
grapes, hops and caneberries.  Therefore, data requirements pertaining
to meat, milk, poultry, and eggs are not relevant to this tolerance
petition.

860.1500 Crop Field Trials

IR-4 has submitted magnitude of the residue studies in support of
tolerances discussed in this document.  These studies have been
reviewed, and the Executive Summaries of study DERs are reproduced below
followed by a crop conclusion.

Grape

46670202.der.doc

44302458.der.wpd (Imported Grape DER; Summarized in DP Num: 271377, M.
Doherty, 4/18/03)

IR-4 has submitted field trial data depicting the magnitude of the
residue of famoxadone in/on wine grapes.  A total of 10 field trials
were conducted in Europe on wine grapes during the 1999 growing season
in Greece (2 trials), Italy (2 trials), southern France (4 trials),
northern France (2 trials), and Germany (2 trials).  However, only
samples from northern France (2 trials) and Germany (2 trials) were
analyzed.  At each test location, a total of 10 foliar spray
applications of a water-dispersible granular (WG) formulation
(containing 22.5% famoxadone and 30% cymoxanil) were applied to wine
grapes during the growing season at progressive vine growth stages.  The
first seven applications were made at 0.060-0.107 lb famoxadone
ai/A/application followed by three applications made at 0.121-0.130 lb
famoxadone ai/A/application, for a total rate of 0.899-1.099 lb
famoxadone ai/A.  The petitioner indicated that this application
scenario was designed to incorporate high spray volume situations due to
large vines with excessive foliage.  Applications were made with a 6- to
8-day RTI, using ground equipment (knapsack or portable sprayer) in
~88-171 gal/A spray volumes; an adjuvant was not added to the spray
mixture.  Samples of mature wine grapes were harvested 28 days after the
last application (DALA).  At one location, additional immature grape
samples were collected 0, 1, 7, and 14 DALA to generate residue decline
data.

The current submission contains residue data for both active ingredients
(cymoxanil and famoxadone).  The DER reports only the residue chemistry
data for famoxadone; the residue chemistry data for cymoxanil will be
handled in a separate DER (refer to PP#5E7000; DP Num: 324447). 

The maximum storage interval of crop samples from harvest to analysis
was 84 days (2.8 months) for grapes.  The results of a storage stability
study (MRID 44302453) were submitted in conjunction with a previous
petition review (PP#7E4847; DP Num: 287253 and 271377, M. Doherty,
4/18/03) which indicate that residues of famoxadone are stable under
frozen storage conditions in/on fortified samples of grapes for up to 18
months.  These data are adequate to support the storage intervals of
samples from the grape field trials.

  SEQ CHAPTER \h \r 1 Samples of grapes were analyzed for residues of
famoxadone using a GC/ECD method, referenced as a multi-residue
enforcement method (DFG S 19 Modified) for the determination of
famoxadone in dry, high water, and oil crops.  The validated LOQ was
0.02 ppm, and the LOD was not reported.  This method is adequate for
data collection based on acceptable concurrent method recovery data.

The results from the grape field trials (Table 6) show that residues of
famoxadone were 0.21-0.75 ppm in/on wine grapes harvested 28 days
following the last of ten foliar spray applications at a total rate of
0.899-1.099 lb famoxadone ai/A.  Residue decline data show that
famoxadone generally decreases slightly in wine grapes with increasing
preharvest intervals.

  SEQ CHAPTER \h \r 1 

Table 6.   Summary of Residue Data from European Grape Field Trials with
Famoxadone Submitted

                To Support Use of Tanos® DF on Grapes Grown East of the
Rocky Mountains.

Commodity	Total Applic. Rate

(lb ai/A)

[kg ai/ha]	PHI (days)	Residue Levels  (ppm)

	n	Min.	Max.	HAFT 1	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Wine grape, fruit	0.899-1.099

[1.008-1.232]	28	12	0.21	0.75	0.62	0.43	0.44	0.15

1  HAFT = Highest average field trial result.

Conclusions:  The residue data from the current European field trial
submission (MRID 46670202) indicate that residues of famoxadone were
0.21-0.75 ppm in/on wine grapes harvested 28 days following the last of
multiple foliar spray applications at a total rate of 0.899-1.099 lb
famoxadone ai/A.  The residue data (44302458.der.wpd, M. Doherty,
4/7/03) that were previously submitted in support of the import grape
tolerance petition indicate that residues of famoxadone were 0.07-2.14
ppm in/on wine grapes harvested approximately 28 days following the last
of multiple foliar spray treatments of Tanos® DF at a total rate of
1.07 lb ai/A.

Based on the aggregate of field trial data, all of which were conducted
in Europe, the current tolerance of 2.50 ppm for grapes is appropriate
to support the proposed use of Tanos® DF on grapes grown east of the
Rocky Mountains pending label revision to conform to the HED’s ChemSAC
determination regarding data translation.  The label should be modified
to specify a maximum seasonal rate of ~1.1 lb ai/A and a 28-day PHI. 
The Agency’s tolerance spreadsheet was not used for grape because
previously submitted and reviewed European residue data were used to
establish the existing tolerance and support use in the Eastern U.S.

Hops

46670201.der.doc

IR-4 has submitted field trial data depicting the magnitude of the
residue of famoxadone in/on dried hops.  A total of three hop field
trials were conducted in the United States in Zones 11 (ID and WA) and
12 (OR) during the 2000 growing season.  At each test location, hop
plants received six foliar directed applications of the test
formulation, Tanos® DF, a dry flowable formulation containing 25% ai
famoxadone + 25% ai cymoxanil,   SEQ CHAPTER \h \r 1 at ~0.25 lb
famoxadone ai/A/application with a 6- to 8-day retreatment interval for
a total seasonal rate of ~1.5 lb ai famoxadone/A.  No adjuvant was
included in the spray mixture.  Samples of fresh hop cones were
harvested 7-8 days after the last spray application, and cones were
dried 3 to approximately 20 hours after to sampling.

The current submission contains residue data for both active ingredients
(cymoxanil and famoxadone).  The DER reports only the residue chemistry
data for famoxadone; the residue chemistry data for cymoxanil will be
handled in a separate DER (refer to PP#5E7000; DP Num:  324447).

The maximum storage interval of dried hop samples from harvest to
analysis was 206 days (6.8 months).  The storage interval is supported
by adequate storage stability data which were generated concurrently
with the field trials.    SEQ CHAPTER \h \r 1 These data indicate that
residues of famoxadone are stable in/on fortified dried hop samples
stored frozen up to 253 days.

Samples of hops were analyzed for residues of famoxadone and cymoxanil
using an LC/MS method (DuPont Report No. AMR 3705-95, Revision No. 2). 
The LLMV for this method was 0.5 ppm for famoxadone.  The calculated LOQ
and LOD were 0.34 and 0.11 ppm, respectively, for residues of
famoxadone.  This method is adequate for data collection based on
acceptable method validation and concurrent method recovery data.

The results from the hop field trials (Table 7) show that the maximum
residues of famoxadone were 46.85 ppm in/on dried hop cones harvested
7-8 days following the last of six foliar directed applications at ~0.25
lb ai/A/application for a total rate of ~1.50 lb ai/A.

Table 7.	Summary of Residue Data from Hop Field Trials with Famoxadone.

Crop matrix	Total Applic. Rate

(lb ai/A)	PHI (days)	Residue Levels (ppm)

	n	Min.	Max.	HAFT 1	Median	Mean	Std. Dev.

Hops, dried cones	1.50-1.53	7-8	6	14.70	46.85	45.66	41.57	34.16	14.85

HAFT = Highest average field trial result.

Conclusions:  The residue data from the current field trial submission
indicate that residues of famoxadone ranged from 14.70 ppm to 46.85 ppm
in/on dried hops harvested 7-8 days after the last of six directed
foliar applications of Tanos® DF formulation at ~0.25 lb
ai/A/application for a total rate of ~1.50 lb ai/A.  The submitted data
are adequate pending label revision to reflect the parameters of field
trial data.  HED is recommending label revisions to specify a maximum
single foliar application rate of 0.25 lb ai/A, with a 6-8 day RTI, a
maximum seasonal rate of ~1.50 lb ai/A, and a 7-day PHI.  The hop data
were entered into the Agency’s tolerance spreadsheet (see Appendix I),
and statistical analysis of data shows that a tolerance level of 80 ppm
will be appropriate for hops.  A revised Section F for hops, dried at 80
ppm is required.

Caneberries

46905801.der.doc

The IR-4 has submitted field trial data for famoxadone on caneberries. 
Four supervised crop field trials were conducted in CA (two trials, U.S.
EPA Region 10), WA (U.S. EPA Region 12) and OR (U.S. EPA Region 12)
during the 2003 growing season.  In addition, three supervised crop
field trials were conducted in Canada, with one trial in British
Columbia (Canadian Region 12), one trial in Ontario (Canadian Region 5),
and one trial in Quebec (Canadian Region 5B).  Six foliar applications
of DPX-KP481 50WG (25% famoxadone) were applied at a rate of 0.75 lb
ai/A (0.188 lb/A famoxadone) at 6-8 day intervals (4.5 lb ai/A/season,
1.125 lb famoxadone/A/season).  Samples were collected on the day of the
last application (0-day PHI).  No adjuvants or additives were added to
the spray mixture for any of the above applications.  The number and
locations of field trials are in accordance with OPPTS Guideline
860.1500 (with some acceptable deviations).  

The analytical procedure for quantifying residues of famoxadone was the
Cornell Analytical Laboratory Method Residue Analysis of Famoxadone on
Caneberry by GC/EC Detection, Version #1.  This procedure was adapted
from a Morse Laboratories and E.I. duPont Nemours and Company method
entitled Analytical Method for the Determination of DPX-JE874 and
Famoxadone Residues in Various Matrices.  Caneberry samples were
extracted in separate steps with acetonitrile/water and hexane and
purified via activated Florisil column chromatography.  Quantitation was
accomplished by GC/NPD.  Samples of control caneberries were fortified
at levels ranging from 0.50 to 10.0 ppm.  The LOQ and LOD were
calculated to be 0.028 ppm and 0.0092 ppm, respectively for caneberries.
 The concurrent recovery of famoxadone from caneberries ranged from 80 -
125%.  The method is adequate for data collection.

Table 8.	Summary of Residue Data from Caneberry Field Trials with
Famoxadone.

Crop matrix	Total Applic. Rate

(lb ai/A)	PHI (days)	Residue Levels (ppm)

	n	Min.	Max.	HAFT 1	Median	Mean	Std. Dev.

Caneberries	1.118-1.141

(1.253–1.279)	0	14	0.41	6.65	6.05	1.38	2.01	1.91

1  HAFT = Highest average field trial result. 

Conclusions:  The results from these trials show that famoxadone
residues ranged from 0.40 ppm to 6.7 ppm on/in treated caneberries when
the test substance was applied at the proposed seasonal application rate
of 1.125 lb ai/A using a 0-day PHI.  Caneberries were stored frozen for
a maximum of 181 days at –21ºC.  Submitted storage stability studies
indicate that famoxadone residues are stable on caneberries for up to
216 days.  A residue decline study was not conducted by the applicant. 
The cranberry data were entered into the Agency’s tolerance
spreadsheet (see Appendix I), and statistical analysis of the data show
that a tolerance level of 10 ppm will be appropriate for hops.  In
addition, the correct commodity definition is caneberries, subgroup 13A.
 A revised Section F for caneberries, subgroup 13A at 10 ppm is
required.

860.1520 Processed Food and Feed

MRID 44302464 (DP Num: 287253 and 271377, M. Doherty, 4/18/03)

HED’s   SEQ CHAPTER \h \r 1 ChemSAC, in a memo dated 4/19/2004,
concluded that European grape data could be used to support the use in
the eastern U.S.  They also pointed out that a processing study was
required to determine whether famoxadone residues concentrated in juice.
 Data were not required for raisins for a use limited to east of the
Rocky Mountains.

The petitioner previously submitted a European grape processing study
(MRID 44302464) in conjunction with PP#7E4847.  These data were reviewed
by the Agency (DP Num: 287253 and 271377, M. Doherty, 4/18/03) where it
was reported that residues of famoxadone were below the LOQ of 0.02 ppm
in juice processed from grapes bearing detectable residues.  Assuming
residues at ½ the LOQ, the processing factor for juice is 0.01x.  The
empirical concentration factors are less than the theoretical
concentration factors for grape commodities.

Conclusions:  The field trials that supplied the grapes for processing
were conducted at 1x the field application rate.  Processing   SEQ
CHAPTER \h \r 1 followed typical commercial practices for grapes, and
the residue data are supported by the analytical methods and storage
stability studies.  This study indicates that residues of famoxadone per
se do not concentrate in grape juice processed from grapes bearing
detectable famoxadone residues.  Based on this determination, a
tolerance will not be required for famoxadone residues in grape juice.

The ChemSAC has also determined that data are not required for raisins
for a use limited to east of the Rocky Mountains since raisins are not
typically produced in that area.  Therefore, no change in the
established raisin tolerance is required.  

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

Analytical standards for famoxadone are currently available in the
National Pesticide Standards Repository.  

860.1850 Confined Accumulation in Rotational Crops

860.1900 Field Accumulation in Rotational Crops

Grapes, hops, and caneberries   SEQ CHAPTER \h \r 1 are crops which are
typically not rotated; therefore, the proposed uses are not relevant to
these topics.

860.1550 Proposed Tolerances

General tolerances are currently listed in 40 CFR (180.587(a) for
residues of the fungicide famoxadone
(3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione).  The
MARC had previously determined that the residue of concern for both
tolerance enforcement and risk assessment is famoxadone per se.  The
proposed tolerance expression is consistent with 40 CFR §180.587.

The aggregate of residue data for grapes indicate that the appropriate
RAC tolerance is 2.5 ppm to support the proposed use of Tanos® DF on
grapes grown east of the Rocky Mountains and the entry to the United
States of famoxadone-treated grapes imported from Europe.  The tolerance
on grapes and raisins should no longer indicate that there are no US
registrations. 

A Codex MRL (CXL) has been established for grapes at 2 mg/kg.  The MRL
for grape is below the existing tolerance of 2.5 ppm.  A Codex MRL has
also been established for dry grape pomace at 7 mg/kg.  There are
currently no established Canadian or Mexican MRLs for famoxadone.  An
International Residue Limit Status sheet is attached to this review.

Table 9. 	Tolerance Summary for Famoxadone

Commodity	Established Tolerance

[40 CFR §180.587(a)] (ppm)	Proposed Tolerance (ppm)	Recommended
Tolerance (ppm)	Comments; Correct Commodity Definition

Grape	2.50 	2.5	2.5

	Hops, dried	None	60	80

	Caneberries, subgroup 13A	None	11	10	Change from request on caneberry

References

DP Num:	288134

Subject:	MARC Decision Memo

From:		M, Doherty

To:		

Dated:		3/12/03

MRID(s):	None

DP Num:	287253 and 271377

Subject:	Famoxadone.  Summary of Analytical Chemistry and Residue Data. 
PP#0F06070:  Section 3 Registration on Fruiting Vegetables, Cucurbit
Vegetables, Head Lettuce, and Potatoes.  PP#7E04847:  Tolerance without
a U.S. Registration for Grapes and Raisins.

From:		M. Doherty

To:		J. Whitehurst/C. Giles Parker

Dated:		04/18/03

MRID(s):	44302446, 44302448, 44302451-44302453, 44302458-44302464,
44946411, 44946412, 44946415-44946425, 44946427-44946431, 44331201,
44579102, 45620301, 44967205, 45845601

DP Num:	None

Subject:	Minutes of the 4/7/04 ChemSAC Meeting

From:		HED’s Chemistry Science Advisory Council

To:		HED’s Chemistry Interest Group

Dated:		4/19/04

MRID(s):	None

  SEQ CHAPTER \h \r 1 Attachments:

International Residue Limit Status sheet

Appendix I - Tolerance Assessment Calculations

Template Version September 2005



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 
3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione	Common
Name:

Famoxadone	X Proposed tolerance

( Reevaluated tolerance

( Other	Date: 6/13/06

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

 No Codex proposal step 6 or above

  No Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#5E7001

DP Num:  323682

Other Identifier:  

Residue definition (step 8/CXL):  famoxadone	Reviewer/Branch:  C.
Swartz/RAB2

	Residue definition:  famoxadone
(3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione)  SEQ
CHAPTER \h \r 1 

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

Grape pomace, Dry	7	Hops, dried	60

Grapes	2	Grape	2.50

	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, 06/20/2006.

Appendix I.  Tolerance Assessment Calculations.

Hops

The dataset used to establish a tolerance for famoxadone on hop
consisted of field trial data representing application rates of
1.50-1.53 lb ai/A (6 applications at 0.24-0.26 lb ai/A/application) with
a 7- to 8-day PHI.  As specified by the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data SOP, the field trial application
rates and PHIs are within 25% of the maximum label application rate and
minimum label PHI, respectively.  The residues values used to calculate
the tolerance are provided in Table I-1.

All 6 field trial sample results were above the LOQ.  Since there were
no values reported below the LOQ, maximum likelihood estimation (MLE)
procedures were not needed to impute censored values.

The famoxadone-hop dataset was entered into the tolerance spreadsheet. 
The result from the approximate Shapiro-Francia test statistic (Figure
I-2) indicated that the assumption of lognormality should be rejected. 
Visual inspection of the lognormal probability plot (Figure I-1)
provided in the spreadsheet confirmed that the dataset is not lognormal.

Since the field trial data for famoxadone on hop are not lognormal, the
upper bound on the 89th percentile should be selected as the tolerance
value (distribution-free method).  Using the rounding procedure as
outlined in the Guidance for Setting Pesticide Tolerances Based on Field
Trial Data SOP, the upper bound on the 89th percentile rounds to the
value 80 ppm.  Therefore, 80 ppm is the recommended tolerance level for
famoxadone on hop.

Table I-1.	Residue data used to calculate tolerance for famoxadone on
hop.

Regulator:	  EPA

Chemical:	  Famoxadone

Crop:	  Hop

PHI:	  7-8 Days

App. Rate:	  1.50-1.53 lb ai/A

Submitter:	  IR-4

MRID Citation:	  46670201

	Residues of Famoxadone (ppm)

	14.70

	15.82

	39.22

	43.91

	44.46

	46.85

Figure I-   SEQ Figure_II- \* ARABIC  1 .  Lognormal probability plot
of famoxadone field trial data for hop.

Figure I- 2.   Tolerance spreadsheet summary of famoxadone field trial
data for hop.

                                                                        
                         

Caneberries

k

¥

©

ª

¾

¿

h

¯

¼

½

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

@

ĈĈĈĈĈ혈Fᴃἀ⼍괛$Ȇ

ĈĈ혈Fᴃἀ⼍괛$Ȇ

ĈĈ혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

@

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

Ёฃ愀϶e

愀Ĥ

@

$

Ёฃ愀϶e

Ёฃ愀϶e

Ёฃ愀϶e

$

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

Ö

̗⍪|ᘀ㥨ᩀ䌀ᑊ唀Ĉ䩡 ᘆ㥨ᩀ䌀tes and PHIs are within 25% of
the maximum label application rate and minimum label PHI, respectively. 
The residues values used to calculate the tolerance are provided in
Table I-2.

All 7 field trial sample results were above the LOQ.  Since there were
no values reported below the LOQ, maximum likelihood estimation (MLE)
procedures were not needed to impute censored values.

The famoxadone-caneberries dataset was entered into the tolerance
spreadsheet.  The result from the approximate Shapiro-Francia test
statistic (Figure I-4) indicated that the assumption of lognormality
should not be rejected.  Visual inspection of the lognormal probability
plot (Figure I-3) provided in the spreadsheet confirmed that the dataset
appears lognormal.

Since the field trial data for famoxadone on caneberries appear
lognormal, the UPL Meridiam 95th percentile should be selected as the
tolerance value.  Using the rounding procedure as outlined in the
Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP,
the upper bound on the 95th percentile rounds to the value 10 ppm. 
Therefore, 10 ppm is the recommended tolerance level for famoxadone on
caneberries.

Table I-2.	Residue data used to calculate tolerance for famoxadone on
caneberries.

Regulator:	  EPA

Chemical:	  Famoxadone

Crop:	  Caneberries

PHI:	  0-Day

App. Rate:	  2.236-2.282 lb ai/A

Submitter:	  IR-4

MRID Citation:	 4690580

	Residues of Famoxadone (ppm)

	5.50

	0.41

	2.00

	1.70

	1.04

	0.98

	0.45

	6.65

	0.48

	3.20

	2.15

	1.05

	0.69

	1.85

         Figure I- 3.  Lognormal probability plot of famoxadone field
trial data for canberries.                         

    

Figure I- 4.   Tolerance spreadsheet summary of famoxadone field trial
data for caneberries.

Page   PAGE  1  of   NUMPAGES  26 

Famoxadone	Summary of Analytical Chemistry and Residue Data	Num:  323682