UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF CHEMICAL SAFETY

	AND POLLLUTION PREVENTION 

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  11/17/10

SUBJECT:	Fluoxastrobin.  Petition for the Establishment of Permanent
Tolerances for Uses on Squash/Cucumber Subgroup 9B.  Summary of
Analytical Chemistry and Residue Data.

PC Code:  028869	DP Barcode:  380846

Decision No.:  433137 	Registration No.:  66330-64

Petition No.:  NA	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  361377-29-9

MRID No.:  48088301	40 CFR:  180.609

		              									

FROM:	Meheret Negussie, Chemist			

		Risk Assessment Branch III

		Health Effects Division (HED 7509P)  SEQ CHAPTER \h \r 1 

		

		

THROUGH:	Leung Cheng, Senior Chemist

		Risk Assessment Branch III

		Health Effects Division (HED 7509P)	

		

			

TO:		Nancy Tsaur, Risk Assessor

		RAB III/HED (HED 7509P)

			and

			

		Tony Kish, RM# 22

		Fungicide Branch		  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 

		Registration Division (RD 7505P)

  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 

		

Executive Summary

Fluoxastrobin is a fungicide used for the control of fungal diseases in
tuberous and corm vegetables, fruiting vegetables, the leaf petiole
vegetables, peanuts, low growing berries, field corn, wheat, soybeans,
peanuts, and as a seed treatment for potato and peanut, and as a
soilborne/seedling disease control.  It works by interfering with
respiration in plant-pathogenic fungi and is a potent inhibitor of spore
germination and mycelial growth.  It belongs to the strobilurin class of
fungicides (Group 11), also termed methoxyacrylates.  Fluoxastrobin is
the accepted common name for the pesticidally active E isomer of
[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dihydro-
1,4,2-dioxazin-3-yl)methanone O-methyloxime.  The Z-isomer of
fluoxastrobin is typically present at much lower levels (E:Z ratio of
approximately 90:10).  The petitioner has requested that fluoxastrobin
(E-isomer only) be designated as the active ingredient. 

Arysta LifeScience North America (Arysta) is proposing the establishment
of tolerances for combined residues of the fungicide fluoxastrobin
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime and its Z-isomer
(1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime in/on the following raw
agricultural commodities:

Crop subgroup 9B Squash/Cucumbers	0.50 ppm

In conjunction with this petition, Arysta is requesting amended
registration of the 4 lb ai/gal suspension concentrate (SC) formulation
of fluoxastrobin, Fluoxastrobin 480 SC Fungicide (EPA Reg. No.
66330-64), to add uses on squash/cucumber subgroup 9B.  The product is
proposed for up to four foliar applications to squash/cucumber subgroup
9B at up to 0.16 lb ai/A/application for a total application rate of
0.68 lb ai/A; a 1-day preharvest interval (PHI) is proposed.  For
soilborne disease control, a rate of 0.16-0.24 fl. oz./1000 row feet (
0.005-0.075 lb ai/A) is proposed.

Tolerances for combined residues of fluoxastrobin and its Z-isomer in/on
primary crop 

commodities are established under 40 CFR §180.609(a)(1) at levels
ranging from 0.010 ppm (peanut and the tuberous and corm vegetable
subgroup 1C) to 20.0 ppm (peanut hay).  Tolerances are established under
 SEQ CHAPTER \h \r 1  40 CFR §180.609(a)(2) for the combined residues
of fluoxastrobin, its Z-isomer, and its phenoxy-hydroxypyrimidine
metabolite, 6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol, in cattle, goat,
horse, and sheep commodities at levels ranging from 0.02 ppm (milk) to
0.50 ppm (milk fat); no tolerances are currently established for poultry
commodities.  Tolerances for indirect or inadvertent combined residues
of fluoxastrobin and its Z-isomer are established under 40 CFR   SEQ
CHAPTER \h \r 1 §180.609(d) for rotated crop commodities [alfalfa
forage and hay; cotton gin byproducts; forage, fodder, and straw of
cereal grains except corn (crop group 16); grass forage and hay; and
foliage of legume vegetables (crop group 7)] at 0.020-0.50 ppm.

The nature of the residue in plants and livestock is adequately
understood.  In plants, the results of metabolism studies conducted on
wheat, peanut, and tomato indicate that metabolism of fluoxastrobin is
similar in dissimilar crops.  HED has concluded that the residues of
concern for risk assessment and tolerance setting purposes are
fluoxastrobin and its Z-isomer.  Acceptable metabolism studies on goats
and laying hens are also available.  The available data indicate that
the metabolism in goats and hens is similar.  Metabolism of
fluoxastrobin was found to be more extensive in livestock than in
plants, and metabolites consisting of single rings (e.g., 2-chlorophenol
and 2-cyanophenol) were observed in each of the livestock metabolism
studies.  HED has concluded that in livestock commodities, the residues
of concern are fluoxastrobin, its Z-isomer, and the
phenoxy-hydroxypyrimidine metabolite (HEC 7154) for risk assessment and
tolerance setting purposes.  

Acceptable high performance liquid chromatography methods with tandem
mass spectroscopic detection (LC/MS/MS) are available for tolerance
enforcement for plant and livestock commodities.  Bayer AG method 00604
and confirmatory method 00946 have been adequately validated for the
determination of residues of fluoxastrobin and its Z-isomer in plant
commodities, and Bayer AG method 00691 and confirmatory method 00945
have been adequately validated for determination of fluoxastrobin, its
Z-isomer, and HEC 7154 in ruminant commodities.

Samples from the submitted crop field trials were analyzed for residues
of fluoxastrobin and its Z-isomer using an acceptable LC/MS/MS method. 
Samples of cucumber and squash were analyzed using Bayer AG Method
00668.  The method was adequately validated prior to and/or in
conjunction with the analysis of the field trial.  The validated limit
of quantitation (LOQ) was 0.01 ppm for combined residues of
fluoxastrobin and its Z-isomer in/on all crop commodities.  

Adequate multiresidue methods testing data have been submitted.  The
data indicate that the multiresidue methods are not adequate for
enforcement of tolerances for fluoxastrobin.

Adequate storage stability data are available to support storage
conditions and intervals of samples from the cucumber and squash field
trials. 

There are no livestock feedstuffs associated with the proposed uses on
squash/cucumber subgroup 9B.  

The submitted crop field trial data for cucumbers and summer squash
reflect the proposed use patterns and are acceptable pending submission
of a revised label and an additional field trial data for cucumber in
region 2.  The submitted data will support the proposed tolerances for
Squash/cucumber subgroup 9B at 0.5 ppm. 

The nature of the residue in rotational crops is understood based on an
adequate confined rotational crop study.  HED has concluded that the
residues of concern for rotational crops for risk assessment and
tolerance setting purposes are fluoxastrobin and its Z-isomer.  Adequate
field rotational crop data are available which indicate that residues of
fluoxastrobin and its Z-isomer may accumulate in rotated crops.  The
available data support the established tolerances for indirect or
inadvertent residues established under 40 CFR 180.609(d), and indicate
that the following rotational crop restrictions are appropriate for
fluoxastrobin:  a 0-day plantback interval (PBI) for any crop listed on
the label; a 30-day PBI for the root vegetables subgroup (e.g., carrot,
radish, sugar beet, and turnip), bulb vegetables (e.g., onion and
garlic), leafy greens subgroup (e.g., lettuce and spinach), Brassica
vegetables (e.g., broccoli, cauliflower, cabbage, and mustard greens),
alfalfa, cotton, legume vegetables (dry and succulent peas and beans),
cereal grains, and forage grasses; and a 12-month PBI for all other
crops.

There are no Codex, Canadian, or Mexican maximum residue limits (MRLs)
established for fluoxastrobin. 

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for fluoxastrobin. 
Pending submission of revised Sections B, F, and resolution of the
deficiencies identified below, there are no residue chemistry issues
that would preclude granting conditional registration for the requested
uses of fluoxastrobin on squash/cucumber subgroup 9B or establishment of
the following tolerances for combined residues of fluoxastrobin and its
Z-isomer:

Squash/cucumber subgroup 9B	0.50 ppm

A human health risk assessment is forthcoming.

Note to PM:  According to HED’s Interim Guidance on Tolerance
Expressions (5/27/09, S. Knizner), the tolerance expressions for
fluoxastrobin should be revised as follow:

Under 40 CFR §180.609(a)(1) and §180.609(d):  “Tolerances are
established for residues of fluoxastrobin, including is metabolites and
degradates, in or on the commodities in the table below.  Compliance
with the tolerance levels specified below is to be determined by
measuring only the sum of
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime and its Z-isomer,
(1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime.

Under 40 CFR §180.609(a)(2):  “Tolerances are established for
residues of fluoxastrobin, including is metabolites and degradates, in
or on the commodities in the table below.  Compliance with the tolerance
levels specified below is to be determined by measuring only the sum
of(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-d
ihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, its Z-isomer,
(1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, and the
phenoxy-hydroxypyrimidine metabolite,
6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol, calculated as the
stoichiometric equivalent of fluoxastrobin.

860.1200  Directions for Use

The proposed use directions for squash/cucumber subgroup 9B should be
revised to correct the application rate from a range of 0.09 to 0.16 lbs
ai/A to a range of 0.09 to 0.18 lb ai/A.

The statement “Do not apply more than 21.8 fl oz (0.68 lbs ai) of
EVITO 480 SC per acre per year” should be revised to “Do not apply
more than 22.8 fl oz (0.72 lbs ai/A ) of EVITO 480 SC per acre per
year”.

The proposed use directions for squash/cucumber subgroup 9B should be
revised to include use of a non-ionic surfactant (NIS).

860.1500 Crop Field Trials

To fulfill geographic distribution requirements, an additional cucumber
field trial must be conducted in region 2. 

 

860.1550 Proposed Tolerances

A revised Section F is needed that reflect correct commodity definition
(Table 10).

860.1650 Submittal of Analytical Reference Standards

Arysta must provide an analytical reference standard of the metabolite
HEC 7154 to the EPA National Pesticide Standards Repository.  

Background

The chemical structure and nomenclature of fluoxastrobin, its Z-isomer,
and the phenoxy-hydroxypyrimidine metabolite are presented in Table 1. 
The physicochemical properties of the technical grade of fluoxastrobin
are presented in Table 2.

. No. 66330-64) indicates that the master label is the basis for three
different labels, including Evito™ 480 SC Fungicide.

Table 2.          Physicochemical Properties of Technical Grade
Fluoxastrobin.

Parameter	Value	Reference (MRID)

Melting range	103 -105 ºC	45865525

pH	6.3 (1% in CIPAC-D water)	45865520

Density	1.4216 ±  0.0025 g/mL	45865303

Water solubility	at 20 ºC: 

0.0019 g/L;

0.0024 g/L at pH 4

0.0023 g/L at pH 7

0.00227 g/L at pH 9	45865520, 45865525

Solvent solubility		at 20 ºC:

n-heptane	0.05 g/L

xylene	38 g/L

dichloromethane	>250 g/L

2-propanol	6.7 g/L

1-octanol	1.1 g/L

polyethylene glycol 400	100-250 g/L

acetone	>250 g/L

ethyl acetate	>250 g/L

acetonitrile	>250 g/L

dimethylsulfoxide	>250 g/L	45865520, 45865525

Vapor pressure 	<1x10-5  hPa (20 ºC) 	45865525

Dissociation constant, pKa	No acidic or  basic properties in the pH
range between 4 and 9; estimated to be -2.1 ± 0.3	45865303

Octanol/water partition coefficient, Log(POW)	2.85 (20 ºC); POW = 708
45865525

UV/visible absorption spectrum	Peak maxima (nm) 250; molar absorptivity
(1000 cm²/mol) 19358; sample melting point 103.1-107.7 ºC	45865303

860.1200  Directions for Use

Arysta has submitted proposed use directions (Section B) for the 4 lb
ai/gal SC formulation of fluoxastrobin (Fluoxastrobin 480 SC Fungicide;
EPA Reg. No. 66330-64) in/on squash/cucumber subgroup 9B.  

The proposed use directions for squash/cucumber subgroup 9B are
presented in Table 3.

Table 3.	Summary of Directions for Use of Fluoxastrobin.

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

Squash/Cucumber subgroup 9B:  Chayote (fruit); Chinese waxgourd (Chinese
preserving melon);  cucumber; gherkin; gourd, edible (includes hyotan,
cucuzza, hechima, Chinese okra); Momordica spp (includes balsam apple,
balsam pear, bitter melon, Chinese cucumber); pumpkin; squash, summer
(includes crookneck squash, scallop squash, straightneck squash,
vegetable marrow, and zucchini); and squash, winter (includes butternut
squash, calabaza, hubbard squash, acorn squash, and spaghetti squash) 

Broadcast, Foliar, 

Ground, Chemigation	4 lb ai/gal SC

[66330-64]	0.09-0.16

(3-5.7 fl. oz/A)	4	0.68

(21.8 fl. oz/A)	1	Applications are to begin preventatively and continue
as needed on a minimum 7-14 day interval.  Use higher rates when disease
is severe.  

For belly-rot control, the first application should me made at the 1-3
leaf crop stage, and the second application 10-14 days later, or at vine
tip-over, whichever occurs first.  

Soilborne Disease Control (Root rot)



0.005-0.0075 lb/1000 row feet (0.16-0.24 fl. oz/1000 row feet)





Do not use the 0.24 fl oz/1000 row feet rate on rows spaced narrower
than 22 inches. 

Do not use the 0.16 fl oz/1000 row feet rate on rows spaced less than 15
inches. 

For twin rows spaced 7.5-8” apart on 30 inch centers, use the 0.16 fl
oz/1000 row feet rate for 15” rows only. 





The proposed use directions for squash/cucumbers include the following
resistance management restriction: Alternate every application of the
product with at least one application of another registered, non-Group
11 fungicide.  Do not make more than 4 applications of EVITO 480 SC
fungicide and or a Group 11 fungicide per season.  Do not use EVITO 480
SC for control of gummy stem blight where resistance to Group 11 (Qol)
fungicides exists.

The use directions submitted in Section B do not include application
spray volumes, specifications for application via chemigation and
adjuvant use.  The registered label recommends a minimum spray volume of
10 gal/A for ground equipment.  The registered label states that
chemigation applications are to be made through sprinkler-type
irrigation systems only.  The registered label does not specify adjuvant
use in any tank-mix partner.

The use directions submitted in Section B prohibits use of EVITO 480 SC
to squash/cucumber subgroup 9B crops grown in a greenhouse.  In
addition, it prohibits tank mix with emulsifiable concentrate (EC)-based
insecticides, or the following products: malathion, Kelthane®,
Thiodan®, Phaser®, Lannate®, Lorsban®, M-Pede®, or Botran®.

 

The use directions submitted in Section B do not include rotational crop
restrictions.  The following crop restrictions appear on the registered
label:  0-day PBI for any crop listed on the label; 30-day PBI for root
vegetables (e.g., carrot, radish, sugar beet, and turnips), bulb
vegetables (e.g., onion and garlic), leafy greens subgroup (e.g.,
lettuce and spinach), Brassica vegetables (e.g., broccoli, cauliflower,
cabbage, and mustard greens), alfalfa, cotton, legume vegetables (dry
and succulent peas and beans), cereal grains, and forage grasses; and a
12-month PBI for all other crops.

Conclusions.  The submitted use directions are adequate to allow
evaluation of the residue data relative to the proposed use.  With the
changes to the proposed use noted below, the submitted field trial data
for cucumbers and squash reflect the maximum proposed use rates, the
minimum retreatment intervals (RTIs), and the proposed PHIs:

The proposed use directions for squash/cucumber subgroup 9B should be
revised to correct the application rate from 0.09 to 0.16 lbs ai/A to
0.09 to 0.18 lbs ai/A.

The statement “Do not apply more than 21.8 fl oz (0.68 lbs ai) of
EVITO 480 SC per acre per year” should be revised to “Do not apply
more than 22.8 fl oz (0.72 lbs ai/A ) of EVITO 480 SC per acre per
year”.

The proposed use directions for squash/cucumber subgroup 9B should be
revised to include use of a NIS. 

860.1300 Nature of the Residue - Plants

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

The nature of the residue in plants is adequately understood based on
acceptable metabolism studies in wheat, peanuts, and tomatoes.  The data
indicate that metabolism is similar in three dissimilar crops.  HED
previously concluded that the residues of concern in primary crops for
risk assessment and tolerance setting purposes are fluoxastrobin and its
Z-isomer.

860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo DP# 334234, 10/30/08, A. Acierto (PP#3F6556)

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

The nature of the residue in ruminants and poultry is adequately
understood based on acceptable metabolism studies with goats and hens. 
The data indicate that metabolism is similar in ruminants and poultry. 
Metabolism of fluoxastrobin was found to be more extensive in livestock
than in plants; metabolites consisting of single rings (e.g.,
2-chlorophenol and 2-cyanophenol) were observed in each of the livestock
metabolism studies.  HED previously concluded that the residues of
concern for livestock commodities for risk assessment and tolerance
setting purposes are fluoxastrobin, its Z-isomer, and HEC 7154. 

860.1340 Residue Analytical Methods

Residue Chemistry Memo DP# 334234, 10/30/08, A. Acierto (PP#3F6556)

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

Plant commodity methods

Enforcement method:  Acceptable LC/MS/MS methods are available for
tolerance enforcement for plant commodities.  Bayer AG Method 00604 and
the confirmatory Method 00946 have been adequately validated for the
determination of residues of fluoxastrobin and its Z-isomer in/on plant
commodities.

Data collection methods:  Samples of cucumber, cantaloupe, and squash
from the submitted crop field trials were analyzed for residues of
fluoxastrobin and its Z-isomer using an acceptable LC/MS/MS method.  All
samples from the cucurbit vegetable crop field trials were analyzed
using Bayer AG Method 00668.  The methods were adequately validated
prior to and/or in conjunction with the analysis of the field trial. 
The validated LOQs were 0.01 ppm for combined residues of fluoxastrobin
and its Z-isomer in/on cucumber, cantaloupe, and squash samples.

For Method 00668, samples (~ 1g) were soaked in acetone:water (75:25,
v:v) for 30 minutes, then subjected to microwave extraction for 1.5
minutes at 40 °C and centrifuged.  The residues were extracted twice
more, once with microwave extraction and once at ambient temperature,
and the resulting supernatants were combined.  The combined extracts
were evaporated under nitrogen to aqueous remainder, then subjected to
cleanup via solid phase extraction on a Bond-Elut ENV cartridge. 
Residues were eluted with ethyl acetate, evaporated to dryness, then
redissolved in acetonitrile:water (60:40, v:v) for analysis by
HPLC/MS/MS.  

Livestock commodity methods

Acceptable LC/MS/MS methods are available for tolerance enforcement for
livestock commodities.  Bayer AG Method 00691 and the confirmatory
Method 00945 have been adequately validated for determination of
fluoxastrobin, its Z-isomer, and HEC 7154 in ruminant commodities.  The
method LOQs for fluoxastrobin (E+Z isomers) and HEC 7154 are 0.01 ppm
for each analyte in milk, muscle, and fat, and 0.02 ppm for each analyte
in liver and kidney.

Conclusions.  The residue analytical methods data are adequate. 
Acceptable methods are available for tolerance enforcement purposes for
the residues of concern in/on plant and livestock commodities, and
samples of cucumber, cantaloupe, and squash from the submitted crop
field trials were analyzed for residues of fluoxastrobin and its
Z-isomer using acceptable data collection methods.

860.1360 Multiresidue Methods

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

Acceptable multiresidue methods test data were previously submitted for
fluoxastrobin, its Z-isomer, and HEC 7154.  The data indicate that the
multiresidue methods are not adequate for tolerance enforcement of
fluoxastrobin residues in/on plant or livestock commodities. The results
were forwarded to FDA.  

860.1380 Storage Stability

Residue Chemistry Memo DP# 334234, 10/30/08, A. Acierto (PP#3F6556)

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

Sufficient storage stability data are available to demonstrate that
combined residues of fluoxastrobin and its Z-isomer are stable during
frozen storage (≤-15 °C) in/on raw agricultural crop commodities for
up to ~20-23 months.  The data reflect five representative crops:  an
oilseed (soybean), a non-oily grain (wheat), a leafy vegetable (mustard
greens), a tuber crop (potato), and an acidic fruiting vegetable
(tomato), and demonstrate that residues of fluoxastrobin and its
Z-isomer are stable during frozen storage in/on soybean seed for ~21
months, mustard greens, tomato, wheat grain, hay, and straw for ~22
months, peanut and potato for ~23 months, and wheat forage for ~20
months.  

The storage durations and conditions of samples from the submitted crop
field trials and processing studies are presented in Table 4.

TABLE 4.	Summary of Storage Conditions and Durations of Samples from
Crop Field Trials.

Matrix 	Storage Temperature

(°C)	Actual Storage Duration1	Interval of Demonstrated Storage
Stability



Cucumber	~-20	196-227 days (6.5-7.5 months)	Residues of fluoxastrobin
and its Z-isomer are stable during frozen storage in/on five diverse
crops for up to 20-23 months.2

Cantaloupe

117-218 days (3.9-7.2 months)

	Summer Squash

123-225 days (4-7.5 months)

	1  Interval from harvest to completion of analysis.  Method extraction
and analysis procedures were conducted over several days; the durations
from initial to final extraction were 2-7 days, and analyses were
conducted over 0-2 days; analysis of final extracts was completed within
0-1 day of extraction.

2  Refer to DP# 289106, 01/25/05, W. Wassell.

Conclusions.  The available storage stability data for fluoxastrobin on
representative crops are adequate to support the storage durations and
conditions of samples of cucumber, cantaloupe, and summer squash from
the submitted crop field trials.  

860.1400 Water, Fish, and Irrigated Crops

This guideline requirement is not relevant to the current petition as
there are no aquatic uses currently proposed for fluoxastrobin.

860.1460 Food Handling

This guideline requirement is not relevant to the current petition as
there are no food handling uses being proposed for fluoxastrobin.

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with the proposed uses on
squash/cucumber subgroup 9B.  The dietary burdens for fluoxastrobin
residues in livestock diets will not be affected by the subject action;
therefore, data requirements pertaining to meat, milk, poultry, and eggs
are not relevant to the proposed uses. 

860.1500 Crop Field Trials

DER Reference:	48088301.der.doc (Squash/cucumber subgroup 9B)

Arysta has submitted field trial data for fluoxastrobin on cucumber,
cantaloupe, and summer squash as the representative crops of the
cucurbit vegetable, crop group 9.  Seventeen field trials were conducted
in the U.S. during the 2008 growing season.  Six cucumber trials were
conducted in region 2 (GA; 2 trials), 3 (FL; 1 trial), 5 (MI; 2 trials),
and 6 (OK; 1 trial).  Six cantaloupe trials were conducted in region 10
(CA; 3 trials) and region 2 (GA; 1 trial), 5 (MI; 1 trial), 6 (TX; 1
trial).  Five summer squash trials were conducted in region 1 (PA; 1
trial), 2 (GA; 1 trial), 3 (FL; 1 trial), 5 (MI; 1 trial) and 10 (CA; 1
trial). 

At each test location, four foliar broadcast applications of a 4 lb
ai/gal SC formulation of fluoxastrobin were made at 0.17-0.19 lb
ai/A/application, with a 6- to 8-day RTI, for a total rate of 0.68-0.73
lb ai/A.  Applications were made at BBCH 19-BBCH 90 growth stages using
ground equipment in spray volumes of 14-29 gal/A.  For some trials,
growth stages were not specified as BBCH growth stages.  A NIS was added
to the spray mixtures in some trials.  In the cantaloupe trials,
adjuvant was used at one location only.  In the squash trials, adjuvant
was used at all locations except one.  In the cucumber trials, adjuvant
was used at 2 of the 5 trial locations.  Samples of mature cucumber,
cantaloupe, and summer squash fruits were collected 1 day after the last
application.  Samples of cucumber, cantaloupe, and summer squash were
harvested at 0-, 1-, 3-, 7-, and 10-day PHIs to evaluate residue
decline.

Samples of cucumber, cantaloupe, and summer squash were analyzed for
residues of fluoxastrobin (E-isomer) and its Z-isomer using an LC/MS/MS
method, Bayer AG Method 00668.  The method LOQ was 0.01 ppm for combined
residues of fluoxastrobin and its Z-isomer in cucurbit vegetables. 
Quantifiable residues (0.01-0.88) were observed in treated cucumber,
cantaloupe, and squash samples.  The method is adequate based on
acceptable method validation and concurrent recovery data.  The
fortification levels used in concurrent method validation were adequate
to bracket field trial residue results.  

Samples of cucurbit vegetables were stored frozen for up to 7.5 months
prior to analysis.  Acceptable storage stability data were previously
submitted which indicate that residues of fluoxastrobin and its Z-isomer
are stable during frozen storage in/on various representative crops for
up to 23 months.  These data are adequate to support the storage
conditions and durations of samples from the cucurbit vegetables crop
field trial study.

Combined residues of fluoxastrobin and its Z-isomer were 0.04-0.18 ppm
in/on cucumber, 0.08-0.88 ppm, in/on cantaloupe, and 0.01-0.18 ppm in/on
summer squash samples.  In the cantaloupe trials, adjuvant was used at
one location only.  The residue for the trial with adjuvant was 0.09
ppm; the range for trials without adjuvant was 0.14 – 0.83 ppm.  In
the squash trials, adjuvant was used at all locations except one.  The
residue was 0.04 ppm where adjuvant was not used, and ranged from 0.06
to 0.15 ppm where adjuvant was used.  In the cucumber trials, adjuvant
was used at 2 of the 5 trial locations.   Residues ranged from 0.04 to
0.09 ppm where adjuvant was used and from 0.07 to 0.17 ppm where
adjuvant was not used.   For all crops, no side-by-side trials were
conducted with and without adjuvant, and therefore it is impossible to
separate the effect of adjuvant use from the effects of trial location  
 . 

In the residue decline studies, combined residues of fluoxastrobin and
its Z-isomer generally declined with increasing sampling interval.  

		

Table C.5.   Summary of Residue Data from Cucurbit Field Trials with
Fluoxastrobin.

Crop matrix	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels (ppm) 1



	N2	Min.	Max.	HAFT3	Median	Mean	Std. Dev.

Cucurbit Vegetables (proposed use = 0.017 lb ai/A total application
rate, 1-day PHI)

Cucumber	0.68-0.71	1	12	0.04	0.18	0.17	0.08	0.09	0.04

Cantaloupe	0.68-0.73	1	12	0.08	0.88	0.83	0.34	0.35	0.25

Summer squash	0.68-0.71	1	10	0.01	0.18	0.16	0.08	0.08	0.05

1  Combined residues of fluoxastrobin and its Z-isomer.  

2 N = number of samples (includes only target PHI samples from decline
trials) 

3 HAFT = Highest average field trial

Conclusions.  The submitted cucumber and summer squash field trial
studies are acceptable and reflect the proposed use patterns.  Samples
were analyzed for residues of fluoxastrobin and its Z-isomer using
acceptable methods, and the studies are supported by adequate storage
stability data.  

For cucumbers, the number of field trials is not in accordance with
OPPTS 860.1500.  Six trials were conducted; however, the two field
trials conducted in region 2 could not be counted as independent trials
since both trials have the same address.  One additional cucumber trial
must be conducted in region 2. 

Pending revision of the proposed use patterns and submission of the
outstanding field trial data, the submitted field trial data will
support the proposed tolerance of 0.5 ppm for squash/cucumber subgroup
9B.   

The field trial data for cucumber and summer squash were separately
entered into the Agency’s tolerance spreadsheet as specified by the
Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP
to determine an appropriate tolerance level; see Appendix II.  The
tolerance spreadsheet recommends individual tolerances of 0.25 ppm for
cucumber and 0.5 ppm for summer squash.  Because the minimum and maximum
recommended tolerances differ by less than 5x, a crop group tolerance is
appropriate for squash/cucumber subgroup 9B.  The recommended value is
0.5 ppm, the maximum of the recommended individual tolerances.  The
recommended tolerance level is the same as the level proposed by the
petitioner (0.5 ppm).  

860.1520 Processed Food and Feed

HED does not require residue data for any processed commodities
associated with squash/cucumber subgroup 9B.  Therefore, data
requirements for processed food and feed are not relevant to this
tolerance petition.

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

Analytical standards for fluoxastrobin and Z-fluoxastrobin are currently
available in the EPA National Pesticide Standards Repository
(Repository) (email communication with Charles Stafford, ACB, 9/23/10),
with expiration dates of 2011-2018; the reference standard for the
metabolite HEC 7154 [6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol] has
expired and must be submitted to the Repository.

Standards were supplied by the previous registrant, Bayer CropScience. 
ACB requests that the new registrant, Arysta, provide analytical
reference standard of the metabolite HEC 7154 to the Repository 

Conclusions.  The new registrant, Arysta, must provide an analytical
reference standard of the metabolite HEC 7154 to the Repository.  

860.1850 Confined Accumulation in Rotational Crops

Residue Chemistry Memo DP# 334234, 10/30/08, A. Acierto (PP#3F6556)

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

Residue Chemistry Memo DP# 292422, 1/24/05, S. Winfield

Available confined rotational crop data are adequate to satisfy data
requirements and to delineate the nature of the residue in rotated crop
commodities.  The confined rotational crop studies indicate the
potential for quantifiable residues of fluoxastrobin in rotated crop
commodities.  HED previously concluded that the residues of concern for
rotational crops for risk assessment and tolerance setting purposes are
fluoxastrobin and its Z-isomer.  

860.1900 Field Accumulation in Rotational Crops

Residue Chemistry Memo DP# 334234, 10/30/08, A. Acierto (PP#3F6556)

Residue Chemistry Memo DP# 289106, 1/25/05, W. Wassell (PP#3F6556)

Acceptable limited field rotational crop and extensive field rotational
crop studies were previously reviewed under PP#3F6556.  Adequate field
rotational crop data are available on the representative crops of
mustard greens (leafy vegetable), turnips (root vegetable), and wheat
(cereal grain).  The primary crops each received four spray applications
of fluoxastrobin at ~0.18 lb ai/A, for total application rates of ~0.72
lb ai/A.  The limited field rotational crop data, which indicated no
quantifiable residues of fluoxastrobin and its Z-isomer in mustard
greens and turnip roots and tops at a 30-day PBI, are adequate to
support the proposed 30-day PBI for root and tuber vegetables, bulb
vegetables, leafy vegetables, and Brassica vegetables.  Extensive field
rotational crop studies reflecting a 1-month PBI support the established
indirect or inadvertent tolerances on alfalfa forage and hay; cotton gin
byproducts; forage, fodder, and straw of cereal grains; grass forage and
hay; and foliage of legume vegetables.  These data support the
established rotational crop restrictions on the master label (EPA
Registration No. 66330-64).  

860.1550 Proposed Tolerances

Residue Chemistry Memo DP#s 356953 and 357691, 7/8/09, M. Negussie
(PP#8F7406 and PP#8F7437)

Tolerances for plant commodities are established under 40 CFR
§180.609(a)(1) for the combined residues of fluoxastrobin and its
Z-isomer; tolerances for livestock commodities are established under 40
CFR §180.609(a)(2) for combined residues of fluoxastrobin, its
Z-isomer, and the phenoxy-hydroxypyrimidine metabolite.  The tolerance
expression proposed by the petitioner is appropriate for Squash/cucumber
subgroup 9B. 

The tolerance proposed by Arysta is the same as the recommended
tolerance by RAB3 and is listed in Table 10, along with the revised
commodity definition.  

Pending submission of an additional field trial for cucumber, adequate
field trial data reflecting the proposed use patterns are available for
purposes of establishing tolerances in Squash/cucumber subgroup 9B.  The
field trial data for cucumber and squash were separately entered into
the Agency’s tolerance spreadsheet as specified by the Guidance for
Setting Pesticide Tolerances Based on Field Trial Data SOP (rev. August
2009) to determine an appropriate tolerance level; see Appendix II.  The
tolerance spreadsheet recommends individual tolerances of 0.25 ppm for
cucumber and 0.5 ppm for summer squash.  Because the minimum and maximum
recommended tolerances differ by less than 5x, a crop group tolerance is
appropriate for squash/cucumber subgroup 9B.  The recommended value is
0.5 ppm, the maximum of the recommended individual tolerances.  Based on
the tolerance spreadsheet, the proposed tolerances of 0.5 ppm for
Squash/cucumber subgroup 9B is appropriate.  

Table 10. 	Tolerance Summary for Fluoxastrobin

Commodity	Tolerance (ppm)	Comments; Correct Commodity Definition

	Established	Proposed	Recommended

	40 CFR §180.609(a)(1)

Crop subgroup 9B Squash/Cucumbers	--	0.5	0.5	Squash/cucumber subgroup 9B



References

DP#s:		292422 and 303256

Subject:	Fluoxastrobin:  Human Health Risk Assessment for Proposed Uses
on Peanuts, Tuberous and Corm Vegetables (Subgroup 1C), Leaf Petiole
Vegetables (Subgroup 4B), Fruiting Vegetables (Group 8), Turf, and as a
Seed Treatment on Potato (Seed Pieces), Peanut and Turf.  PC Code: 
028889.  Petition No.: 3F6556.

From:		S. Winfield

To:		C. Giles-Parker

Dated:		1/24/05

MRIDs:	None

DP#:		289106

Subject:	PP#3F6556.  Fluoxastrobin.  Petition for the Establishment of
Permanent Tolerances for Use on Peanuts, Tuberous and Corm Vegetables
Subgroup, Leaf Petiole Vegetables Subgroup, Fruiting Vegetables Group,
and Seed Treatment of Peanut and Potato.  First Food/Feed Use.  Summary
of Analytical Chemistry and Residue Data.

From:		W. Wassell

To:		D. McNeilly

Dated:		1/25/05

MRIDs:	45865507-45865534 and 45865601-45865611

DP#:	334234

Subject:	Fluoxastrobin.  Supplemental Residue Data for Livestock
Metabolism, Residue Analytical Methods, Storage Stability, Crop Field
Trials, and Rotational Crop Field Trials, Submitted to Fulfill
Conditions of Registration for Fluoxastrobin 480 SC (EPA Reg. No.
66330-64).

From:	A. Acierto

To:	J. Bazuin/T. Kish

Dated:	10/30/08

MRIDs:	46486101-46486104 and 46925801-46925804

DP#s:		356953 and 357691

Subject:	Fluoxastrobin:  Petitions for the Establishment of Permanent
Tolerances for New Uses on Low-Growing Berry Crop Subgroup 13-07G
(PP#8F7406), Soybean and Field Corn (PP#8F7437).  Summary of Analytical
Chemistry and Residue Data.

From:		M. Negussie

To:		T. Kish

Dated:		07/08/09

MRIDs:	47494701 and 47549202-47549205

  SEQ CHAPTER \h \r 1 Attachments:  

International Residue Limit Status sheet

Appendix I - Tolerance Assessment Calculations

Template Version April 2008

International Residue Limits.

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US	Canada	Mexico2	Codex3

40 CFR 180.609

Plant: fluoxastrobin,
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime and its Z isomer,
(1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime

Livestock: fluoxastrobin,
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, its Z isomer,
(1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dih
ydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, and its
phenoxy-hydroxypyrimidine, 6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol
None

None

Commodity1	Tolerance (ppm) /Maximum Residue Limit (mg/kg)

	US	Canada	Mexico2	Codex

Squash/cucumber subgroup 9B	0.5



































































































	Completed:  M. Negussie; 09/23/2010

1 Includes only commodities of interest for this action.  Tolerance
values should be the HED recommendations and not those proposed by the
applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment,
such as treatment of stored grains.  PoP = processed postharvest treated
commodity, such as processing of treated stored wheat. (fat) = to be
measured on the fat portion of the sample. MRLs indicated as proposed
have not been finalized by the CCPR and the CAC.

Appendix I.  Tolerance Assessment Calculations.

For each of the crops listed below, the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data (SOP), along with the tolerance
spreadsheet (August 2009 version), was used for calculating recommended
tolerances.  As specified in the SOP, the minimum of the 95% upper
confidence limit (UCL) on the 95th percentile and the point estimate of
the 99th percentile was selected as the tolerance value in cases when
the dataset was large (greater than 15 samples) and reasonably
lognormal.  For datasets that were not lognormal, the upper bound on the
89th percentile was selected as the tolerance value (distribution-free
method).  The rounding procedures specified in the SOP were also used.

Cucumber

The dataset used to establish tolerances for combined residues of
fluoxastrobin and its Z-isomer on cucumber consisted of field trial data
representing application rates of 0.68-0.73 lb ai/A (4 applications at
0.17-0.19 lb ai/A/application) with a 1-day PHI.  The field trial
application rates and PHIs are in accordance with the label application
rate and minimum label PHI, respectively.  The residue values entered
into the tolerance spreadsheet are provided in Table I-1.

All field trial sample results for cucumber and squash were above the
LOQ (LOQ = 0.01 ppm).  The datasets were small (12 and 10 samples,
respectively).  Visual inspection of the lognormal probability plots
(Figures I-1 and I-3) and the approximate Shapiro-Francia test
statistics (Figures I-2 and I-4) indicated that the datasets for
cucumber and squash were reasonably lognormal.   

Using the tolerance spreadsheet, the recommended tolerance for cucumber
is 0.25 ppm and 0.5 ppm for squash.  Because the minimum and maximum
recommended tolerances differ by less than 5x, a crop group tolerance is
appropriate for squash/cucumber subgroup 9B.  The recommended value is
0.5 ppm, the maximum of the recommended individual tolerances, which is
the same as the proposed tolerance (0. 5 ppm).

 

Table I-1.	Residue data used to calculate tolerances for fluoxastrobin
on cucumber.

Regulator:	EPA	EPA	EPA

Chemical:	Fluoxastrobin	Fluoxastrobin	Fluoxastrobin

Crop:	Cucumber	Cantaloupe	Squash

PHI:	1-day	1-day	1-day

App. Rate:	0.68-0.73 lb ai/A	0.68-0.71 lb ai/A	0.68-0.71 lb ai/A

Submitter:	Arysta LifeScience	Arysta LifeScience	Arysta LifeScience

MRID Citation:	MRID 48088301	MRID 48088301	MRID 48088301

	Combined residues of fluoxastrobin and its Z-isomer (ppm)

	0.06	0.09	0.10

	0.09	0.08	0.12

	0.04	0.19	0.07

	0.05	0.09	0.05

	0.10	0.34	0.11

	0.08	0.34	0.18

	0.18	0.88	0.04

	0.16	0.78	0.04

	0.11	0.33	0.01

	0.06	0.27	0.12

	0.07	0.41



0.07	0.42

	

逞설㇂Ĥ摧⴦Á

0

M

t

w

{

›

µ

¶

½

Á

Õ

 



!

(

/

0

2

s

v

w

y

{

€

š

 

¤

©

´

µ

¶

¼

¿

À

Á

Ã

Í

Î

Ñ

Ñ

Ò

Ô

×

á

é

ê

þ



4

@

G

Q

Z

^

hAM

h

h

 h

h

h

h

␅؁Ĥ☊଀цഀ׆Ā褐㄀Ĥ摧碩!

h

ഀ׆Ā褐ༀ梄㄁Ĥ葞Ũ摧㽞°0਀&䘋

혈Fᴃ騀褋괛$紆

ĈĈĈĈĈ혈Fᴃ騀褋괛$紆

ĈĈĈĈĈ혈Fᴃ騀褋괛$紆

ĈĈĈĈĈ혈Fᴃ騀褋괛$紆

阂H㐃ԁᣖĈĈĈĈĈĈ혈Fᴃ騀褋괛$紆

혈Fᴃ騀褋괛$紆

혈Fᴃ騀褋괛$紆

혈Fᴃ騀褋괛$紆

혈Fᴃ騀褋괛$紆

$

]

$

$

]

	ԀĤ␆㄁Ĥ摧⴦Á

h<

ùõñçàÙËÀËÀËÀËÀ¹µ±µµµµ¥µ¡ÙµËš”‹”‹”
‹”‹”ÀËÀËÀËÀËÀ„µ h<

h<

 h<

@

㄀Ĥ摧⴦Á

 h<

h<

h<

h<

h<

h<

h<

¹

ò

¹

ò

¹

ò

ò

 h

hí

hí

hí

ഀ׆Ā褐㄀Ĥ摧⴦Á	ԀĤ␆㄁Ĥ摧⴦Á

㄀Ĥ摧⴦Áༀ

 ԀĤ␆ഁ׆Ā֠ༀꂄᄅ悄ㇺĤ葞֠葠褐摧⴦Á

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

”ÿô

	Figure I-1.  Lognormal probability plot of fluoxastrobin field trial
data for cucumber.

 

Figure I-2.   Tolerance spreadsheet summary of fluoxastrobin field trial
data for cucumber.

 

Figure I-3.  Lognormal probability plot of fluoxastrobin field trial
data for summer squash.

 

Figure I-4.   Tolerance spreadsheet summary of fluoxastrobin field trial
data for summer squash.

 

 

Page   PAGE  22  of   NUMPAGES  22 

Fluoxastrobin	Summary of Analytical Chemistry and Residue Data	DP#: 
380846

