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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLLUTION PREVENTION 

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)

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

Registration Division (RD 7505P)
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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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-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime and its Zisomer (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dihydro-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 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 §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 
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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

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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-fluoro4-pyrimidinyl]oxy]phenyl](5,6-dihydro-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-

dihydro-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-dihydro-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-

dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, and the phenoxyhydroxypyrimidine 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”.
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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 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 phenoxyhydroxypyrimidine metabolite are presented in Table 1. The physicochemical properties of the 

technical grade of fluoxastrobin are presented in Table 2.

Table 1. Test Compound Nomenclature.

Compound

Cl

O

N N

F

O

O

O

N

N

O

CH3

Common name Fluoxastrobin

Company experimental name HEC 5725

IUPAC name (E)-{2-[6-(2-chlorophenoxy)-5-fluoropyrimidin-4-yloxy]phenyl}(5,6-dihydro1,4,2-dioxazin-3-yl)methanone O-methyloxime

CAS name (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone O-methyloxime

CAS registry number 361377-29-9

Formula C21H16ClFN4O5 

End-use product (EP) 4 lb ai/gal SC formulation (Fluoxastrobin 480 SC/EvitoTM 480 SC Fungicide1; 

EPA Reg. No. 66330-64) 
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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Table 1. Test Compound Nomenclature.

Compound

Cl

O

N N

F

O

O

O

N

N

O

CH3

Common name Fluoxastrobin Z-isomer

Chemical name (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone O-methyloxime

Compound Cl

O

N N

F

OH

Common name HEC 7154

Chemical name 6-(2-chlorophenoxy)-5-fluoro-pyrimidinol

1 The current label for Fluoxastrobin 480 SC Fungicide (EPA Reg. No. 66330-64) indicates that the master 

label is the basis for three different labels, including EvitoTM 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
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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

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

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

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

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

Page 12 of 22

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

N

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

Page 13 of 22

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.

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

Page 14 of 22

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

Page 15 of 22

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

Page 16 of 22

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

Attachments: 

International Residue Limit Status sheet

Appendix I - Tolerance Assessment Calculations

Template Version April 2008
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

Page 17 of 22

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-dihydro-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-dihydro1,4,2-dioxazin-3-yl)methanone O-methyloxime

Livestock: fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro4-pyrimidinyl]oxy]phenyl](5,6-dihydro-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-dihydro1,4,2-dioxazin-3-yl)methanone O-methyloxime, and its phenoxyhydroxypyrimidine, 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.
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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

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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)

0.16 0.78 0.04

0.11 0.33 0.01

0.06 0.27 0.12

0.07 0.41

0.07 0.42

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

Lognormal Probability Plot

0.1 1 2 5 10 20 30 50 70 80 90 95 98 99 99.9

1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

y = 0.466x - 2.5126

R

2 = 0.973

Percentiles

Concentrations

EPA Fluoxastrobin Cucumber 1 0.68-0.71 lb ai/A Arysta LifeScience
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

Page 20 of 22

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

Regulator: EPA

Chemical: Fluoxastrobin

Crop: Cucumber

PHI: 1

App. Rate: 0.68-0.71 lb ai/A

Submitter: Arysta LifeScience

n: 12

min: 0.04

max: 0.18

median: 0.08

average: 0.09

95th Percentile 99th Percentile 99.9th Percentile

0.20 0.20 0.25

(0.25) (0.30) (--)

0.20 0.25 0.35

(0.30) (0.45) (--)

0.25

0.25

0.50

0.9730

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

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

Lognormal Probability Plot

0.1 1 2 5 10 20 30 50 70 80 90 95 98 99 99.9

1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156

0.0078

y = 0.8331x - 2.7163

R

2 = 0.8769

Percentiles

Concentrations

EPA Fluoxastrobin Summer squash 1 0.68-0.71 lb ai/A Arysta LifeScience
Fluoxastrobin Summary of Analytical Chemistry and Residue Data DP#: 380846

Page 22 of 22

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

Regulator: EPA

Chemical: Fluoxastrobin

Crop: Summer squash

PHI: 1

App. Rate: 0.68-0.71 lb ai/A

Submitter: Arysta LifeScience

n: 10

min: 0.01

max: 0.18

median: 0.09

average: 0.08

95th Percentile 99th Percentile 99.9th Percentile

0.20 0.25 0.25

(0.25) (0.30) (--)

0.30 0.50 0.90

(0.80) (1.9) (--)

0.25

0.25

0.60

0.8769

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD