Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 1 of 17 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date: 05

- December

- 2013

Subject: Fenoxaprop

- p - ethyl

. Petition for the Estab lishment of a Permanent Tolerance and Registration for Use on Grass Grown for Seed ( Grass Hay )

. Summary of Analyt ical Chemistry and Residue Data for Registration Review.

PC Code: 129092 DP Barcode: D 4 15999, D41600 1 Decision No.: 466648, 477911 Registration No. : 264

- 666, 264

- 1073, 264

- 653 Petition No.: 2 E8051 Regulatory Action: Section 3 Registration

, Registration Review Risk Assessment Type: NA Case No.: NA T XR No.: N A CAS No.: 71283

- 80

- 2 MRID No.: 48834301 40 CFR : 180.430

From: Donald Wilbur, Chemist Risk Assessment Branch VI Health Effects Division ( 7509P)

Through: Sheila Piper, Senior Chemist Risk Assessment Branch VI Health Effects Division (7509P)

To: Shalu Shelat , Risk Assessor Risk Assessment Branch VI Health Effects Division (7509P)

Andrew Ertman/ Barbara Madden, Risk Managers Risk Integration Minor Use, and Emergency Response Branch Registration Division (7505C)

Molly Clayton, Chemical Review Manager Risk Manag ement and Implementation Branch III Pesticide Re

- evaluation Division (7508P)Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 2 of 17 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............ 3 2.0 Regulatory Recommendations

................................ ................................ ............................ 3 2. 1 Data Deficiencies/Data Needs

................................ ................................ .......................... 4 2.2 Tolerance Considerations

................................ ................................ ................................ . 4 2.2.1 Enforcement Analytical Method

................................ ................................ ............... 4 2.2.2 Established Tolerances

................................ ................................ .............................. 4 2.2. 2.1 Revisions to Established Tolerances

................................ ................................ . 5 2.2.3 Petitioned

- For Tolerances

................................ ................................ ......................... 5 2.2.3.1 Revisions to Petitioned

- For Tolerances

................................ ............................. 5 2.2.4 International Harmonization

................................ ................................ ..................... 6 3.0 Introduction

................................ ................................ ................................ ......................... 6 3.1 Chemical Identity

................................ ................................ ................................ ............. 6 3.2 Physical/Chemical Characteristics

................................ ................................ ................... 6 3.3 Pesticide Use Pattern/Directions for Use (860.1200)

................................ ....................... 7 4.0 Metabolite/Degradate Residue Profile

................................ ................................ ................ 9 4.1 Nature of the Residue

................................ ................................ ................................ ....... 9 4.1.1 Summary of Plant Metabolism (860.1300)

................................ ............................... 9 4.1.2 Summary of Livestock Metabolism (860.1300)

................................ ....................... 9 4.1.3 Summary of Confined Rotational Crops (860.l850)

................................ ............... 10 4.2 Comparison of Metabolic Pathways

................................ ................................ .............. 10 4.3 Residues of Concern Summary

................................ ................................ ...................... 11 5.0 Residue Profile

................................ ................................ ................................ .................. 11 5.1 Residue Analytical Methods (860.1340)

................................ ................................ ........ 11 5.1.1 Data Collection Method (Grass Hay)

................................ ................................ ..... 11 5.1.2 Tolerance Enforcement Method

................................ ................................ ............. 12 5.1.3 Multi

- Residue Methods (860.1360)

................................ ................................ ........ 12 5.1.4 Submittal of Analytical Reference Standards (860.1650)

................................ ...... 12 5.2 Storage Stability (860.1380)

................................ ................................ .......................... 12 5.3 Residue Data

................................ ................................ ................................ .................. 13 5.3.1 Crop Fie ld Trials (860.1500)

................................ ................................ .................. 13 5.3.2 Field Rotational Crops (860.1900)

................................ ................................ ......... 13 5.3.3 Processed Food and Feed (860.1520)

................................ ................................ ..... 14 5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

................................ .............................. 14 5.3.5. Food Handling (860.1460)

................................ ................................ ...................... 14 5.3.6 Water, Fish, and Irrigated Crops (860.1400)

................................ .......................... 14 5.4 Food Residue Profile

................................ ................................ ................................ ...... 14 6.0 Tolerance Derivation

................................ ................................ ................................ ........ 15 7.0 Chem SAC Reference

................................ ................................ ................................ ........ 15 Appendix A. International Residue Limits Table

................................ ................................ ........ 16Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 3 of 17 1.0 Executive Summary

Fenoxaprop

- p

- ethyl [FPE; (+)

- ethyl 2

- [4

- [(6

- chloro

- 2

- benzo xazolyl)oxy]phenoxy]propanoate] is a selective aryloxy phenoxy

- propionate herbicide used to control grass weeds after emergence. FPE is currently registered for use on barley, co tton, rice, soybeans, and wheat. FPE is also registered for non

- agricultural use on conservation reserves, ornamentals, rights

- of

- way, and turf. The Interregional Research Project No. 4 (IR

- 4) has submitted a p etition requesting a new tolerance be established on grass, hay to support a new use on grass grown for seed in the states of Oregon, Washington, and Utah only

. Based on a ChemSAC’s recommendation (See Section 7.0), data were only generated for grass hay. Additionally, this updated residue chemistry summary document is being drafted to support the registration review of FPE.

The requirements for residue analytical methods are fulfilled for t he purposes of the proposed use as well as for registration review . Adequate methods are available for tolerance enforcement and data collection purposes for plant and animal commodities

. The nature of the residue is adequately understood based on submitted barley, soybean, rice, cotton, peanut, and wheat metabo lism studies . An adequate number of magnitude of the residue (MOR) field trial studies were conducted, with appropriate geographic representation and application scenarios . All samples were analyzed using a validated analytical method and were supported by sufficient storage stability data. Processing studies showed that residues of FPE do not concentrate in any regulated processed commodities

.

The nature of the residu e in livestock (poultry and ruminants) is adequately understood based on submitted goat and laying hen metabolism studies. Tolerances on ruminant livestock commodities have been established based on dietary burden calculations and the submitted ruminant f eeding study . Based on the submitted poultry metabolism study, the Agency has concluded that there is no reasonable expectation of finite residues in poultry commodities [40 CFR 180.6(a)(3)]; accordingly, no poultry tolerances are needed.

It is importa nt to note that FPE is an enriched isomer formulation ( 95% d and 5% l enantiomers ) based on the previously registered product fenoxaprop ethyl (FE

, PC Code 128701) which is a 50:50 racemic mixture of d and l enantiomers

. All current tolerances from the use of FPE are listed under FE in 40CFR

. HED has concluded that FE and FPE have comparable toxicity profiles and the toxicological databases have been bridged. Therefore, even though the tolerance s are in terms of FE, they are protective for all uses of FPE based on the comparable toxicity as well as the fact that the data

- co llection and tolerance enforcement methods are not stereo

- specific and cannot differentiate between FE and FPE ( i.e., cannot distinguish between the
two isomers or the level of enrichment of the d enantiomer ). For this reason, any discussion of tolerances with respect to FPE is described in terms of FE in this document.

2.0 R egulatory R ecommendations

HED has examined the residue chemistry database for FPE . Pending submission of a revised Section F (see requirements under Revisions to Petitioned

- For Tolerances below ) there are no residue chemistry issues that would preclude the establishment of a tolerance with regional restriction on grass, hay. Addit ionally, all regulatory requirements related to residue chemistry for FPE are considered adequate for registration review.Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 4 of 17 A human

- health risk assessment is forthcoming.

2.1 Data Deficiencies/Data Needs

There are no residue chemistry data deficiencies i dentified for FPE

.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate analytical met hod is available to enforce tolerances for F E in plant and animal commodities. A gas chromatography with electron captu re detection (GD

- ECD) method, based

on Hoechst HRAV Analytical Method HRAV

- 4B , was previously reviewed by the Agency and was incorporated into the Food and Drug Administration (FDA) Pesticide Analytical Manual, Volume II (PAM II). The method has a limit o f quantitation (LOQ) of 0.0 5 ppm in all matrix types.

The method is described as follows. Briefly, samples are refluxed with a solution of acetonitrile, concentrated HCl, and water for 6 hours and filtered through filer paper. An aliquot is transferre d onto an Extrelut column and equilibrated with the column matrix. The hydrolysis product 6

- chlorobenzoxazolone is eluted with hexane:diethyl ether and evaporated to dryness. The residue is dissolved with ethyl acetate and the ethyl acetate evaporated to dryness. The residue is then derivatized in a mixture of toluene, acetic anhydride, and pyridine for 2 hours at 130° C. The residue with reaction product acyl 6

- chlorobenzoxazolone (AE F083312) is dried, and cleaned up on a silica gel SPE cartridge. F E and its metabolites are then determined as 6

- chlorobenzoxazolone (AE F083312) by GC

- ECD. Total residue is then expressed as FE equivalents.

F E has also been subjected to analysis by the Food and Drug Administration ( FDA ) multi

residue method (MRM) proto cols. Multi

- residue methods are available for residues of FE and the metabolites of concern under Protocols 1 through 4.

2.2.2 Established Tolerances

Currently there are toleranc es established for residues of FE as listed in Table 2.2.2 below

. The tolerance expression for FE is as follows:

Compliance with the tolerance levels specified is to be determined by measuring only the sum of fenoxaprop

- ethyl, (±)

- ethyl 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoate, and its metabolites, 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoic acid and 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one, calculated as the stoichiometric equivalent of fenoxaprop

- ethyl

.

Table 2.2.2 Tolerance Summary for FE Commodity Tolerance (ppm) Comments /Corrected Commodity Definition 180.430 (a) General Barley, grain 0.05 Barley, straw 0.1 Cattle, fat 0.05 Cattle, meat byproducts 0.05Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 5 of 17 Cattle, meat 0.05 Cotton, undelinted seed 0.05 Goat, fat 0.05 Goat, meat byproducts 0.05 Goat, meat 0.05 Hog, fat 0.05 Hog, meat byproducts 0.05 Hog, meat 0.05 Horse, fat 0.05 Horse, meat byproducts 0.05 Horse, meat 0.05 Milk 0.02 Peanut 0.05 Peanut, hulls 0.05 Revoke , no longer a regulated commodity Rice, grain 0.05 Sheep, fat 0.05 Sheep, meat byproducts 0.05 Sheep, meat 0.05 Soybean 0.05 Soybean, seed Wheat, grain 0.05 Wheat, s traw 0.05 180.430 (b) Section 18 emergency exemptions Grass, forage 0.05 Expires 12/31/2013 Grass, hay 0.05 Expires 12/31/2013

2.2.2.1 Revisions to Established Tolerances

HED is recommending that certain existing tolerances be amended to reflect current polices. The commodity definition for soybean should be changed from soybean to soybean, seed

. Additionally, the tolerance on peanut, hulls may be revoked since that commodity is no longer a regulated raw agricultural commodity (RAC).

2.2.3 Petitioned

- For Tolerances

For the purposes of this petition, t olerances for residues of FE in/on grass, hay were not derived using the Organization for Economic Cooperation and Development Maximum Residue Level (O ECD MRL) Calculation Procedures since all of the residue values were less than the limit of quantification (<LOQ) of the analytical method

.

Table 2.2.3 Proposed Tolerance Summary for FE Commodity P roposed Tolerance

(ppm) HED

- Recommended Tolerance (ppm) Comments

180.430 (c) Tolerances with regional restrictions Grass, hay 0.15 0.09 For the states of WA, OR, and UT only

2.2.3.1 Revisions to Petitioned

- For Tolerances

HED is recommending that a tolerance with regional restriction be set for grass, hay as requested by the petitioner with the change noted below

.Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 6 of 17 The method used for data

- collection (as well as tolerance enforcement) converts the residues of concern for FE to acyl 6

- chlorobenzoxazolone for detection. It is necessary to then convert this residue value to parent equivalents. Since the residues found on grass, hay were less than the LOQ of 0.05 ppm for acyl 6

- chlorobenzoxazolone , HED multiplied this 0.05 ppm value by t he ratio of the molecular weights (1.71) to arrive at a recommended tolerance of 0.09 ppm.

The requested change to the proposed tolerance level is shown in Table 2.2.3 above.

2.2.4 International Harmonization

There are no international harmonization issues related to the existing or proposed uses of FPE. Please see Appendix A for a summary of international maximum residue limits (MRLs).

2.3 Label Recommendations

There are no label recommendations based on residue chemistry identified for this petiti on.

3.0 Introduction

Fenoxaprop

- p

- ethyl [FPE; (+)

- ethyl 2

- [4

- [(6

- chloro

- 2

- benzo xazolyl)oxy]phenoxy]propanoate] is a selective aryloxy phenoxy

- propionate herbicide used to control grass weeds after emergence. FPE is currently registered for use on barley, co tton, rice, soybeans, and wheat. FPE is also registered for non

- agricultural use on conservation reserves, ornamentals, rights

- of

- way, and turf.

The chemical structure and nomenclature of FPE are presented in Table 3.1 , and the physico chemical properties of the technical grade of FPE are provided in Table 3

. 2.

3.1 Chemical Identity

Table 3.1

. FPE Nomenclature
Fenoxaprop

- p

- ethyl

Common Name Fenoxaprop

- p

- ethyl Company Experimental Name AE F046360
IUPAC Name ethyl ( R )

- 2

- [4

- (6

- chloro

- 1,3

- benzoxazol

- 2

- yloxy)phenoxy] propionate

or ethyl ( R )

- 2

- [4

- (6

- chlorobenzoxazol

- 2

- yloxy)phenoxy]propionate
CAS Name ethyl (2 R )

- 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoate
CAS # 71283

- 80

- 2

3.2 Physical/Chemical Characteristics

FPE has low water solubility. Its octanol/water partition coefficient suggests that it is a hydrophobic compound that is more fat soluble than water soluble, exhibiting a tendency toFenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 7 of 17 dissolve in fats, oils, lipids, and non

- polar solvents more re adily than in water. Further, FPE has a low vapor pressure. The full complement of physiochemical properties for this active ingredient is shown in Table 3.2.

Table 3.2. Physicochemical Properties of the Technical Grade FPE

Parameter Value Reference
Melting Point/Range ( ° C) 86.5 Health Canada Fenoxaprop

- p

- ethyl Proposed Re

Evaluation Decision

(PRVD2011

- 04) Density (g/cm 3 ) 1.32 Water Solubility ( 20 ° C, pH 5.8) (mg/L) 0.7 Solvent Solubility (g/L at 20 ° C) n

- hexane 7.0
acetone >400
toluene >480
dichloromethane >400
methanol 43.1 isopropanol 14.2 ethyl acetate >380 Vapor Pressure (Pa) 5.3 x 10

- 7 at 20°C 1.4 x 10

- 6 at 25°C
1.1 x 10 - 4 at 50°C Dissociation Constant (pK a ) Not possible to measure in water in the pH range 1

- 13 (no acidic or basic groups on the molecule) Octanol/Water Partition Coefficient Log (K ow ) 4.58 UV/Visible Absorption Spectrum Not expected to absorb at
λ > 300nm

3.3 Pesticide Use Pattern/ Directions for Use (860.1200)

The only FPE end

- use formulation currently registered is as a liquid formulation which may be applied post

- emergent for the use on various agricultural crops (barley, cotton, rice, soybeans, and wheat), ornamentals, turf (residential lawns and sod farms), and commercial sites (conservatio n reserve and right

- of

- way). There is also a proposed new use for grasses grown for seed in Oregon, Washington, and Utah.

A summary of the existing and proposed use patterns for FPE are shown in Table 3. 3 below.

Table 3.3 . Summary of Directions for Use of Currently Registered FPE Uses
Applic. Timing, Type,

and Equip. Formulation [EPA Reg. No.] Max Applic. Rate (lb

ai/A) Max. No. Applic. per

Season Max. Seasonal Applic. Rate

(lb ai/A) PHI (days) Use Directions and Limitations

Barley Groundboom

and Aerial applications 264

- 666* 264

- 1073* 264

- 1075 0.08 3 1 0.083 57 No chemigation 24 hour REI

Conservation Reserve
Groundboom 264

- 647* 0.1 NS 0.142 N/A No chemigationFenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 8 of 17 Table 3.3 . Summary of Directions for Use of Currently Registered FPE Uses
Applic. Timing, Type,

and Equip. Formulation [EPA Reg. No.] Max Applic. Rate (lb

ai/A) Max. No. Applic. per

Season Max. Seasonal Applic. Rate

(lb ai/A) PHI (days) Use Directions and Limitations

and Aerial applications 24 hour REI

Cotton Groundboom

and Aerial applications 100

- 1059* 0.1 0 5 1 0.105 90 No chemigation 24 hour REI

Ornamentals Groundboom and handheld applications 432

- 950* 0.173 0.002 lbs

ai/gal 3 0.531 N/A No chemigation 24 hour REI

Ornamentals (Residential)
H andheld applications 72155

- 74 0.076 NS 0.531 N/A N/A

Rice Groundboom

and Aerial applications 264

- 647 264

- 682 0.108 (SLN) 1 0.142 65 No chemigation 24 hour REI
Right of Way

Groundboom

and Aerial applications 100

- 1059 432

- 950* 0.173 0.177

(lbs ai/gal) 3 0.531 N/A No chemigation 24 hour REI

Soybean Groundboom

and Aerial applications 100

- 1059 264

- 647* 0.1 2 0.128 90 No chemigation 24 hour REI
Turf (sod/commercial) Groundboom

and Aerial applications 432

- 950* 0.173 NS 0.531 NS No chemigation 24 hour REI
Turf (residential lawns) Ready to use

Hose

- end sprayer and
concentrate

solutions through handheld equipment 228

- 716* 72155

- 74 72155

- 77 72155

- 78 0. 1 NS NS N/A No aerial, groundboom, or chemigation

Wheat

Groundboom

and Aerial applications 100

- 1429 264

- 666* 264

- 1073* 264

- 1075 0.08 3 1 0.083 70 No chemigation 24 hour REI

Proposed Grass grown for seed (Oregon, Washington, Utah) Groundboom

application 264

- 266 0.082 NS NS 60 No chemigation no aerial applicationsFenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 9 of 17 4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue

4.1.1 Summary of Plant Metabolism (860.1300)

HED has previously concluded that the metab olism of fenoxaprop

- ethyl is adequately under stood. P lant metabolism studies have been submitted for barley (PP#3F4182, D.Davis

, 08/17/1993 ), soybeans (P P#3G2940, R. Lorang er, 11/ 0 9/83), rice (PP # 4G3035, R. Loranger, 0 6/ 0 7 /84), cotton, peanuts and wheat (PP # 8F3599, M. Bradley, 0 5/20/88). It has been concluded that the metabolic pathway for fenox aprop

- ethyl is similar in these plants. The parent compound fenox aprop

- ethyl is cleaved to yield 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)o xy]phenoxy]propanoic acid which subsequently loses phenoxypropionic acid to yield 6

- chloro

- 2,3

-- dihydrobenzoxazol

2

- one. The residue of conc ern in plants consists of fenoxaprop

- ethyl, its free acid metaboli te {2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]pro panoic acid

, } and 6

- chloro

- 2,3

-- dihydrobenzoxazol

- 2

- one

. Additionally, a comparison of the metabolism of FE and FPE was submitted for soybeans, rice, and wheat (MRID 47113302). The results showed that th ere is no significant difference in the metabolism for FE and FPE. No racemisation occurs for FPE and all metabolites stay in the d configuration. The metabolism of FE and FPE follow the same path leading to the metabolic pathway being identical for the two compounds.

Conclusions

. The nature of the residue for is conside red to be adequately understood. Plant metabolism data on barley, soybeans, rice, cotton, peanuts, and wheat were submitted/ reviewed and found to be scientifically acceptable. Metabolism in these crops shared a common metabolic pathway.

4.1.2 Summary of Livestock Metabolism (860.1300)

Ruminant The metabolism of fenoxaprop

- ethyl in animals has been previously considered in lactating ruminants (PP#6F3316

, N. Dodd, 0 2 /0 4/1986 ). It was reported that 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one constituted 75% of the residue in milk and 50% of the residue in the tissues of liver and kidney. No information was available con cerning the relative amounts of parent and the two metabolites in ru minant tissues, since the analytical method used in the

rum inant study was the enforcement method resulting in a common analyte, 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one. In HED reviews of 0 2/ 0 2/90 and 12/14/90, (PP # 9F3714), it was concluded that the residue of concern in ruminants and swine are parent compound, its free acid, fenoxaprop

, and 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one.
Poultry A poultry metabolism stud y (MRID #43426201 , 01/22/1998 ) was submitted in response to deficiencies note d in the review of PP#3F4182 (D.Davis, 0 8 /17/93 ). T he submitted study resolved all outstanding deficiencies re garding poultry metabolism ( S. Knizner, 0 1/22/98). The nature of the residue in poultry has been adequately delineated. The p rincipal route of metabolism is de

- ester ification to the free acid , followed by cleavage o f the ether linkage to yield 6

- chloro

- 2,3

- dihydrobe nzoxazol

- 2

- one and phenoxypropionic acid . Further, based on the low l evels of TRR found in edible tiss ues of poultry following dosing at highly exaggerated rates,Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 10 of 17 the re is no reasonable expectation of finite residues (180.6(a)(3) ). Therefore, a poultry feeding study is not required, nor are tolerances for poultry/eggs required.

Conclusion s

. The nature of the residue in livestock for FPE based on the currently registered and proposed uses is considered to be adequately understood. Both ruminant and poultry metabolism studies were submitted/reviewed and found to be scientifically acceptable.

Based on the submitted poultry metabolism

, the existing and proposed proposed uses can be classified as 40 CFR 180.6 (a) (3), no reasonable expectation of finite residues in poultry livestock commodities. However, this decision may be reconsidered if the use pattern changes and/or additional poultry fe edstuff s are proposed in the future.

4.1.3 Summary of Confined Rotational Crops (860.l850)

A confined rotational crop study was submitted and reviewed in support of an experimental use permit (EUP) on soybeans (8340

- EUP

- T, 0 1/ 0 4/1984). Rotational crop s were planted at 120 and 364 days after the first application of radiolabeled FE. Wheat, lettuce, carrots, radishes, soybeans, and corn were then allowed to grow to maturity. Samples of these representative rotational crops did not show significant upta ke of radiolabeled FE after 120 and 364 days. The parts of the plants that had measurable levels of radioactivity are not used for human consumption. Only total radioactive residue (TRR) was measured in the study.

Additionally, the European Food Safety Authority (EFSA) has published its conclusions regarding the peer review FPE (EFSA Scientific Report 2007

- 121, 11/29/2007). In this report, two separate confined rotational crop studies are discussed; one with FPE and one with FE. TRR in plants grown at 30 days, 120 days, and 365 days at labeled application rates (similar to rates in the US) were below the LOQ for all crops tested (leafy vegetables, root vegetables, and small grains). Based on that, EFSA concluded that field trials for rotational crops a re not required.

Conclusions. Confined rotational crop data were submitted, reviewed and found to be scientifically acceptable

. B a sed on the results of this study and the results of the studies from EFSA , no field accumulation studies are required.

4. 2 Comparison of Metabolic Pathways

The m etabolism of FPE in plants is similar. The parent compound is rapidly metabolized to yield 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)o xy]phenoxy]propanoic acid which subsequently loses phenoxypropionic acid to yield 6

- chloro

- 2 ,3

-- dihydrobenzoxazol

- 2

- one. Residues in pla nts tend to be surface residues with no translocation to newly formed leaves or plants parts. There is no difference between the metabolic profiles of FE and the enriched FPE.

Metab olism studies performed in r at, goat , and laying hen showed a common metabolic pathway in animals. FPE is metabolized in animals primarily by de

- ester ification to the free acid

, followed by cleavage o f the ether linkage to yield 6

- chloro

- 2,3

- dihydrobe nzoxazol

- 2

- one and phenoxypropion ic acid

.Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 11 of 17 4.3 Residues of Concern Summary

The residues of concern for FPE are summarized below in Table 4.3.

Table 4.3. Summary of Metabolites and Degradates Recommended for inclusion in the Risk Assessment and Tolerance Expression

Matrix Residues Included In Risk Assessment Residues Included In Tolerance Expression Plants fenoxaprop

- ethyl

, 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoic acid

, 6

- chloro

- 2,3 dihydrobenzoxazol

- 2

- one Same as those included in RA

Rotational crops NA NA Livestock (ruminants and poultry) fenoxaprop

- ethyl 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoic acid 6

- chloro

- 2,3 dihydrobenzoxazol

- 2

- one Same as those included in RA

Drinking Water fenoxaprop

- ethyl and all degradates containing the 6

- chloro

2

- benzoxazol moiety NA

NA

– Not applicable

.

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1 .1 Data Collection Method (Grass Hay)

Samples of grass hay were analyzed for fenoxaprop

- p

- ethyl (AE F046360), fenoxaprop

- p (AE F088406), and 6

- chlorobenzoxazolone (AE F054014) using Cornell Analytical Laboratory Method “Residue Analysis of Fenoxaprop

- P

- Ethyl (AE F046360) and its Metabolites on Grasses by GC/Mass Spectrum Detection. Version #1”. This working method was derived from Hoechst HRAV Analytical Method HRAV

- 4B “Gas Chromatographic Determination of Fenoxaprop

ethyl [Ethyl

- 2

- (4

- (6

- Chloro

- 2

- Benzoxazolyloxy) Phenoxy)Propanoate] and its Metabolites, 2

- (4

- (6

- Chloro

- 2

- Benzoxazolyloxy) Phenoxy)Propanoic acid and 6

- Chloro

- 2,3

- Dihydrobenzoxazol

2

- one, as Residues in Wheat and Barley Grain, Straw, and Milled Products”. Modifications were made to improve the performance of the method

. Briefly, samples were refluxed with a solution of acetonitrile, concentrated HCl, and water for 6 hours and filte red through filer paper. An aliquot was transferred onto an Extrelut column and equilibrated with the column matrix. The hydrolysis product 6

- chlorobenzoxazolone was eluted with hexane:diethyl ether and evaporated to dryness. The residue was dissolved w ith ethyl acetate and the ethyl acetate evaporated to dryness. The residue was then derivatized in a mixture of toluene, acetic anhydride, and pyridine for 2 hours at 130° C. The residue with reaction product acyl 6

- chlorobenzoxazolone (AE F083312) was d ried, dissolved in toluene followed by hexane, and transferred onto a silica gel SPE cartridge. The acyl 6

- chlorobenzoxazolone was eluted with toluene, collected, dried, brought to volume with toluene, and analyzed by GC/MS.

The LLMV in this study was 0.05 ppm for the three fenoxaprop

- ethyl

- derived analytes. Based on recoveries of samples fortified at the LLMV, the limit of detection (LOD) and limit of quantitation (LOQ) were calculated as 0.0066 ppm and 0.020 ppm, respectively, for fenoxaprop

p

- ethyl; as 0.017 ppm and 0.052 ppm, respectively, for fenoxaprop

- p; as 0.0031 ppm and 0.0094 ppm, respecti vely, for 6

- chlorobenzoxazolone.Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 12 of 17 5.1.2 Tolerance Enforcement Method

An adequate analytical method is available to enforce tolerances for FE in plant and an imal commodities. A gas chromatography with electron capture detection (GD

- ECD) method, based

on Hoechst HRAV Analytical Method HRAV

- 4B , was previously reviewed by the Agency and was incorporated into the Food and Drug Administration (FDA) Pesticide Analy tical Manual, Volume II (PAM II). The method has a limit of quantitation (LOQ) of 0.0 5 ppm for residues of FE in all matrix types.

The method is described as follows. Briefly, samples are refluxed with a solution of acetonitrile, concentrated HCl, and water for 6 hours and filtered through filer paper. An aliquot is transferred onto an Extrelut column and equilibrated with the column matrix. The hydrolysis product 6

- chlorobenzoxazolone is eluted with hexane:diethyl ether and evaporated to dryness. T he residue is dissolved with ethyl acetate and the ethyl acetate evaporated to dryness. The residue is then derivatized in a mixture of toluene, acetic anhydride, and pyridine for 2 hours at 130° C. The residue with reaction product acyl 6

- chlorobenzoxaz olone (AE F083312) is dried, and cleaned up on a silica gel SPE cartridge. FE and its metabolites are then determined as 6

- chlorobenzoxazolone (AE F083312) by GC

- ECD. Total residue is then expressed as FE equivalents.

5.1. 3 Multi

- Residue Methods (860.1360)

FE has also been subjected to analysis by the Food and Drug Administration (FDA) multi

residue method (MRM) protocols. Multi

- residue methods are available for residues of FE and the metabolites of concern under Protocols 1 through 4.

5.1. 4 Su bmittal of Analytical Reference Standards (860. 1650)

The analytical standard for FE , with an expiration date of 07/04/2018 , is currently available in the EPA National Pesticide Standards Repository [personal communication from T. Cole of BEAD/ACB to D. Wi lbur, 11/18 /2013]

. R eference standard supplies need to be replenished as requested by the Repository. The reference standards should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of Theresa Cole at the followin g address:

USEPA National Pesticide Standards Repository/Analytical Chemistry Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755

- 5350

The full 9 digit zip code is mandatory or the mail will be returned.

5.2 Storage Stability (860.1380)

Storage stability data have been previously submitted for residues of fenoxaprop

- ethyl on soybeans for intervals up to 2 years ( PP # 6F3316 , N. Dodd, 02/04/86)

, in peanuts for intervals for
up to 6 months (PP #8F3599, M. Bradley, 0 5/20/88) , and in barley grain and st raw for a period of 1 year ( MRID #425 63002, D. Davis, 08/17/93) . Crop field trial samples in the grass hay magnitude of the residue study were analyzed within one year and data from barley straw can be translated to grass hay

. Therefore, n o additional stor age stability data are required to support aFenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 13 of 17 permanent tolerance on grass hay

.

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)

Existing Uses (Barley, Cotton, Peanut, Rice, Soybean, Wheat) Field trial data have been previously submitted depicting residues of FPE in/on barley (PP#3F4182, D. Davis, 08/17/1993); rice and soybeans (PP#6F3316, N. Dodd, 02/04/1986); and cotton, peanuts and wheat (PP#8F3599, M. Bradley, 05/20/1988). All of these data are considered adequate for tolerance setting and support the existing tolerances and registrations.

Proposed Use (Grass Hay) The Interregional Research Project No. 4 (IR

- 4) has submitted field trial data for fenoxaprop

- p

ethyl (FPE) on grasses (grown for seed). Four field tri als were conducted in the United States during the 2008 growing season the North American Free Trade Agreement (NAFTA) Growing Zones 11 (Washington

- one trial) and 12 (Oregon

– three trials). These data were submitted in support of a regional registration (Oregon, Washington, and Utah) for the use FPE on grasses grown for seed.

In each trial, Puma 0.75EC was applied in one broadcast application of approximately 0.0825 lb ai/A

. Grass for hay was cut 56 to 62 days (8 to 9 weeks) after the application, and hay samples were collected 3 to 14 days after drying to a moisture content of approximately 10 to 20%. Based on ChemSAC’s review of a proposal submitted by IR

- 4 to EPA and their recommendations, magnitude of residue data were collected only for grass hay.

Sample analysis for residues of fenoxaprop

- p

- ethyl was conducted by Cornell Analytical Laboratories in Geneva, NY. FPE derived residues were determined using a laboratory working method based on Hoechst HRAV Ana lytical Method HRAV

- 4B “Gas Chromatographic Determination of Fenoxaprop

- ethyl [Ethyl

- 2

- (4

- (6

- Chloro

- 2

- Benzoxazolyloxy) Phenoxy)Propanoate] and its Metabolites, 2

- (4

- (6

- Chloro

- 2

- Benzoxazolyloxy) Phenoxy)Propanoic acid and 6

- Chloro

- 2,3

- Dihydrobenzoxazol

- 2

- on e, as Residues in Wheat and Barley Grain, Straw, and Milled Products.”

Fenoxaprop

- ethyl derived residues consist of three analytes: fenoxaprop

- p

- ethyl (AE F046360), fenoxaprop

- p (AE F088406), and 6

- chlorobenzoxazolone (AE F054014). The lowest level of

me thod validation (LLMV) was 0.05 ppm for the fenoxaprop

- ethyl derived analytes. The maximum storage interval for field

- treated samples in this study was 363 days. No supporting storage stability data were submitted with the petition , as data previously submitted on barley straw is adequate to cover the period of frozen storage.

The results from the trials show that no fenoxaprop

- ethyl derived residues above the respe ctive LLMVs were observed in dried hay collected 8 to 9 weeks after one application of Puma 0.75EC at approximately 0.0825 lb ai/A.

5.3.2 Field Rotational Crops (860.1900 )

Based on the results and findings in the conf ined field rotational crop studies , no limited field rotational crop data are required.Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 14 of 17 5.3.3 Processed Food and Feed (860.1520)

Processing data have been previously submitted depicting residues of FPE in/on soybeans (PP#6F3316, N. Dodd, 02/04/1986); barley (PP#1G3827, R. Cook, 04/03/1991 ); rice (PP#14G3035, R. Loranger, 06/07/1984); and cotton, peanuts and wheat (PP#8F3599, M. Bradley, 05/20/1988). All of these data are considered adequate and support the existing tolerances and registrations. The results of all of these processing stud ies indicate that residues of FPE do not concentrate in processed commodities.

5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

The potential dietary exposure of ruminant livestock to FPE residues was previously calculated (PP#9G3714, S. Knizner, 11/03/1099 7) using conservative tolerance level residues. These high

end values were then extrapolated using the submitted ruminant feeding study (PP#8F3599, M. Bradley, 05/20/1988) to set tolerances on meat and milk . It is important to note that no detectable res idues were present on the commodities used to calculate this high

- end dietary burden. HED is confident that this previously calculated dietary burden is protective for the existing uses of FPE as well as the proposed new use on grass hay. This is due to the fact that the method used was much more conservative that the current method of using a maximum reasonably ba lanced diet (MRBD). Additionally, residues on grass hay were all below the LOQ of the method, which adds further support for this conclusion.

HED has previously concluded (PP#3F4182, D. Davis, 01/22/1998) that based on the low l evels of TRR found in edib le tiss ues of poultry following dosing at highly exaggerated rates, the re is no reasonable expectation of finite residues (180.6(a)(3) ) in poultry commodities . Therefore, tolerances for poultry/eggs are not required. The new use on grass hay does not chan ge this conclusion since it is not a poultry feed item.

5.3. 5

. Food Handling (860.1460)

There are no food handling establishment uses for FPE ; therefore a discussion of this guideline is not required.

5.3. 6 Water, Fish, and Irrigated Crops (860.1400)

There are no FPE uses involving the direct application to water; therefore a discussion of this guideline is not required.

5.4 Food Residue Profile

The results from plant metabolism for FPE indicate that the residues of concern are fenoxaprop

ethyl, its free acid metabolite {2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]pro panoic acid,} and 6

- chloro

- 2,3

-- dihydrobenzoxazol

- 2

- one

. These data also show that FPE undergoes limited translocation with plants. S upplemental metabolism studies on FE and FPE demonst rated that there is no significant difference in metabolism and no racemisation occurs. The metabolism of FE and FPE follows the same path leading to the metabolic pathway being identical for the two compounds.

Adequate residue chemistry data are availab le for FPE

. Field trials showed levels of FPEFenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 15 of 17 residues to be less than the LOQ (<0.05 ppm) for all crops with the exception of some animal feedstuffs (barley and wheat straw) where very few detects were seen slightly above the LOQ

. The data were generated using a validated data collection method and are adequately supported by frozen storage stability data

. Sufficient processing studies are available to elucidate the fate of FPE in processed commodities , with no concentration seen in any crop matrix

. Tol erances have been set on ruminant livestock commodities based on the previously calculated high

- end dietary burden . HED believes that these tolerances are protective for all uses of FPE since the method used was much more conservative that the current method of using a maximum reasonably balanced diet (MRBD). HED has determined that the uses of FPE are classified as 180.6 (a) (3), no reasonable expectation of finite residues with respect to residues in poultry commodities. Metabolism in rotational crops was seen to be limited; with radioactive residues less than the LOQ found at 30

- days, 120

- days, or 365

- days in leaf y vegetables, root vegetables, and small grains.

6.0 Tolerance Derivation

T olerances for residues of FE in/on grass, hay were not derived using the Organization for Economic Cooperation and Development Maximum Residue Level (O ECD MRL) Calculation Procedu res since all of the residue values were less than the limit of quantification (<LOQ).

However, the method used for data

- collection (as well as tolerance enforcement) converts the residues of concern for FE, namely parent fenoxaprop

- ethyl, (±)

- ethyl 2

- [ 4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoate

, 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoic acid and 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one to acyl 6

- chlorobenzoxazolone for detection. It is necessary to then convert this residue value to paren t equivalents using molecular weight ratios. Since the residues found on grass, hay were <LOQ of 0.05 ppm for acyl 6

- chlorobenzoxazolone , HED multiplied this LOQ value by the ratio of the molecular weight s (1.71) to arrive at a recommended tolerance of 0. 09 ppm.

7.0 ChemSAC Reference

The FPE registration for grass, hay was discussed by the Chemistry Science Advisory Council (ChemSAC) on 02/13/2008. The ChemSAC determined that there was not sufficient information available to support translation of wheat straw data to grass hay. Instea d, the Council agreed that IR

- 4 should conduct the four trials (in OR and WA), ensuring that the hay samples are analyzed for all residues of concern. The Chem SAC concurred with IR

- 4 that it would not be appropriate to try to analyze grass forage samples in this case since the forage stage of grass would be long past by following the 60

- day PHI restriction.Fenoxaprop

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 16 of 17 Appendix A . International Residue Limits Table



### Fenoxaprop

- p

- ethyl (129092)

, Fenoxaprop

- ethyl (128701; 09/09/2013) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 Codex 40 CFR 180.430: Plant and Livestock: Compliance with the tolerance levels specified is to be determined by measuring only the sum of fenoxaprop

- ethyl, (±)

- ethyl 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoate, and its metabolites, 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoic acid and 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one, calculated as the stoichiometric equivalent of fenox aprop

- ethyl ( RS )

- ethyl

- 2

- [4

- (6

- chloro

- 1,3

- benzoxazol

- 2

- yloxy) phenoxy]propanoate, including the metabolites 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)

- oxy]phenoxy]propionic acid and 6

- chloro

- 2,3

- dihydrobenzoxalazol

- 2

- one None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 1 Codex Barley, grain 0.05 0.05 Barley, straw 0.1 Cattle, fat 0.05 Cattle, meat byproducts 0.05 Cattle, meat 0.05 Cotton, undelinted seed 0.05 Goat, fat 0.05 Goat, meat byproducts 0.05 Goat, meat 0.05 Hog, fat 0.05 Hog, meat byproducts 0.05 Hog, meat 0.05 Horse, fat 0.05 Horse, meat byproducts 0.05 Horse, meat 0.05 Milk 0.02 0.02 Peanut 0.05 Peanut, hulls 0.05 Rice, grain 0.05 0.05 Sheep, fat 0.05 Sheep, meat byproducts 0.05 Sheep, meet 0.05 Soybean 0.05 0.05 dry soybeans Wheat, grain 0.05 0.05 Wheat, straw 0.50 Proposed Tolerances Grass, hay** 0.15 Completed: M. Negussie; 9/11/13

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

- p

- ethyl Summary of Analytical Chemistry and Residue Data Barcode D 415998, D416001

Page 17 of 17 ** Grass hay is a new use. Grass, hay also has a time

- limited tolerance of 0.05 ppm expiring 12/31/2013. *** Time limited tolerance expiring 12/31/2013.

(b) Section 18 emergency exemptions. Time

- limited tolerances are established for residues of the herbicide fenoxaprop

- ethyl, including its metabolites and degradates, in or on the commodities in the table in this paragraph in connection with use of fenoxaprop

- ethyl under section 18 emergency exemptions granted by EPA. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only the sum of fenoxaprop

- ethyl, (±)

- ethyl 2

- [4

- [(6

- chloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoate, and its metabolites, 2

- [4

- [(6

- c hloro

- 2

- benzoxazolyl)oxy]phenoxy]propanoic acid and 6

- chloro

- 2,3

- dihydrobenzoxazol

- 2

- one, calculated as the stoichiometric equivalent of fenoxaprop

- ethyl, in or on the commodity. The tolerances expire and are revoked on the dates specified in the table in this paragraph.

Commodity Parts per million Expiration/ revocation date
Grass, forage 0.05 12/31/13
Grass, hay 0.05 12/31/13