                                       
                    UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                               WASHINGTON, D.C.  20460
                                       
                                                 	OFFICE OF CHEMICAL SAFETY AND
                                                                                                        	 POLLUTION PREVENTION


MEMORANDUM

Date:	17-November-2011

SUBJECT:	Quizalofop-P-ethyl.  Petition for Registration of New Use on Corn (PP#1F7822) and Sorghum Grain, and Rapeseed Subgroup 20A, Except Flaxseed (PP#0E7802).  Summary of Analytical Chemistry and Residue Data.


PC Codes:  128711 (quizalofop-ethyl) and 128709 (quizalofop-P-ethyl)
DP Barcode:  395630
Decision No.: 441518 and 443799
Registration No.:  352-541 and 352-542
Petition No.: 1F7822 and 0E7802
Regulatory Action: Tolerance Petition
Risk Assessment Type: N/A
Case No.: NA
TXR No.: N/A
CAS No.:  100646-51-3
MRID No.:  See MRID Summary Table
40 CFR:  §180.441


FROM:			     Ideliz Negrón-Encarnación, Ph.D., Chemist		
			     Risk Assessment Branch V (HED; 7509P)
			  	

THROUGH:	William Donovan, Ph.D., Chemist
		Michael Metzger, Branch Chief
		Risk Assessment Branch V (HED; 7509P)


TO:		Laura Nollen, Risk Manager
		Risk Management Division (RM 5; 7508 P)

			and

		Mindy Ondish, Risk Manager 
		Risk Management Division (RM 25; 7508P)




Note: This DER was originally prepared under contract by Versar, Inc. (6850 Versar Center, Springfield, VA 22151; submitted 8/05/11).  The DER has been reviewed by the Health Effects Division (HED) and revised to reflect current Office of Pesticide Programs (OPP) policies.

MRID Summary Table
MRID No.
Study Type
Comments
48310101
860.1300 (field corn metabolism study)
New DER; 48310101.der (860.1300)
48260704
860.1500 (corn field trials)
860.1520 (corn processing study)
New DER; 48260704.der1-quizalofop (860.1500)
New DER; 48260704.der2-quizalofop (860.1520)
48273601
860.1500 (sorghum field trials)
860.1520 (sorghum processing study)
New DER; 48273601.der1-quizalofop (860.1500)
New DER; 48273601.der2-quizalofop (860.1520)


Executive Summary

Quizalofop ethyl is a selective herbicide currently registered for the control of annual and perennial grasses on noncrop and on crop land areas.  The technical quizalofop ethyl is a mixture of R- and S-enantiomers.  The pesticide active isomer is the R-enantiomer (quizalofop-P-ethyl) which is the active ingredient (ai) in DuPont(TM) Assure[(R)] II herbicide (EPA Reg. No. 352-541).  The 0.88 lb ai/gal emulsifiable concentrate (EC) formulation of DuPont(TM) Assure II[(R)] herbicide is registered to E.I. du Pont de Nemours and Company for use on canola, crambe, cotton, crops grown for seed, eucalyptus, dry beans (including Chickpea), dry and succulent peas, flax, hybrid poplar plantings, lentils, mint (spearmint and peppermint), pineapple, ryegrass grown for seed, snap beans, soybeans, sugar beets, sunflowers, and noncrop areas.  This summary document covers two petitions, one for new uses in field corn (PP#1F7822) and the other for new uses in sorghum and the rapeseed subgroup 20A (PP#0E7802).  

E.I. du Pont de Nemours & Company (Dupont) is proposing to amend the label of Assure(R) II herbicide to include uses on herbicide-tolerant field corn containing the aryloxyalkanoate dioxygenase-1 gene (DAS-40278-9) and in propagation of corn seed containing DAS-40278-9.   The proposed uses are postemergence applications to field and seed corn containing the quizalofop-resistant trait at a maximum seasonal rate of 0.083 lb ai/A.  The proposed preharvest interval (PHI) is 30 days for forage; a PHI for corn grain or stover is not specified.  Applications must include either a crop oil concentrate or a non-ionic surfactant.  Dupont is applying for registration, but Dow Agrosciences LLC has provided the residue studies.

The Interregional Research Project No. 4 (IR-4) is proposing to amend the label of Assure(R) II herbicide to include uses on sorghum grain containing the DuPont(TM) INZEN(TM) AII Herbicide Tolerance Trait and on rapeseed subgroup 20A, except flaxseed [borage, crambe, gold of pleasure (Camelina), cuphea, echium, hare's ear mustard, lesquerella, lunaria, meadowfoam, milkweed, mustard seed, oil radish, poppy seed, rapeseed (canola), sesame, and sweet rocket].  The proposed uses are postemergence applications to sorghum at a maximum seasonal rate of 0.138 lb ai/A, and postemergence applications to rapeseed subgroup 20A at a maximum seasonal rate of 0.124 lb ai/A.  The proposed preharvest intervals (PHIs) are 30 days for sorghum forage, 45 days for sorghum grain and stover, and 60 days for rapeseed subgroup 20A.

Under PP#1F7822, Dupont is proposing the establishment of permanent tolerances for combined residues of the herbicide quizalofop-P-ethyl (ethyl-2-[4-(6-chloroquinoxalin-2-yl oxy)phenoxy]propanoate), including its metabolites and degradates in/on the following raw agricultural commodities:

            Corn, forage	0.01 ppm
            Corn, grain	0.01 ppm
            Corn, stover	0.03 ppm

Under PP#0E7802, IR-4 is proposing the establishment of permanent tolerances for combined residues of the herbicide quizalofop-P-ethyl ester [ethyl (R)-(2-[4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propanoate] and its acid metabolite, quizalofop-P [R-ethyl(ethyl-2-[4-(6-quinoxalin-2-yl)oxy)phenoxy)propanoic acid], and the S enantiomers of both the ester and the acid, all expressed as quizalofop-P-ethyl ester in/on the following raw agricultural commodities:

            Gold of Pleasure, seed	1.0 ppm
            Gold of Pleasure, meal	1.5 ppm
            Borage, seed	1.0 ppm
            Crambe, seed	1.0 ppm
            Crambe, meal	1.5 ppm
            Cuphea, seed	1.0 ppm
            Echium, seed	1.0 ppm
            Hare's ear mustard, seed	1.0 ppm
            Lesquerella, seed	1.0 ppm
            Lunaria, seed	1.0 ppm
            Meadowfoam, seed	1.0 ppm
            Milkweed, seed 	1.0 ppm
            Mustard, seed	1.0 ppm
            Oil Radish, seed	1.0 ppm
            Poppy, seed	1.0 ppm
            Rapeseed	1.0 ppm
            Sesame, seed	1.0 ppm
            Sweet Rocket, seed	1.0 ppm
            Sorghum, grain	0.2 ppm
            Sorghum, forage	0.2 ppm
            Sorghum, stover	0.35 ppm
            Sorghum, aspirated grain	1.0 ppm

Under PP# 0E7802, IR-4 is also proposing to amend quizalofop ethyl tolerance expressions under 40 CFR part 180.441. Currently, tolerances for the combined residues of quizalofop ethyl and quizalofop, expressed as quizalofop ethyl, are established under §180.441(a)(1) in/on commodities including dry and succulent beans and peas, cowpea forage and hay, field pea vines and hay, soybean commodities, and sugar beet roots and tops; tolerance levels range from 0.02 ppm for soybean hulls to 3.0 ppm for the forage/vines and hay of cowpea and field pea.  Under §180.441(a)(2), tolerances for combined residues of quizalofop ethyl, quizalofop, and quizalofop methyl, expressed as quizalofop ethyl, have been established in eggs, milk, milk fat, and the fat, meat, and meat byproducts of cattle, goat, hog, horse, poultry, and sheep, at 0.01-0.25 ppm.  Under §180.441(a)(3), tolerances for the combined residues of quizalofop-P-ethyl ester, acid metabolite quizalofop-P, and the S-enantiomers of the ester and the acid, expressed as quizalofop-P-ethyl ester, have been established in/on barley commodities, sugar beet molasses, canola meal and seed, cotton seed, flaxseed, lentil seed, peppermint and spearmint tops, sunflower seed, and wheat commodities at 0.05-2.0 ppm.  Time-limited tolerances which expired 6/14/99 were established under §180.441(a)(4) for combined residues of quizalofop-P-ethyl ester, acid metabolite quizalofop-P, and the S-enantiomers of the ester and the acid, expressed as quizalofop-P-ethyl ester, in/on sugar beet commodities, crop group 6, and crop subgroup 7A.  A tolerance with regional registration has been established for combined residues of quizalofop-P-ethyl ester, acid metabolite quizalofop-P, and the S-enantiomers of the ester and the acid, expressed as quizalofop-P-ethyl ester, in/on pineapple.  

The nature of residue in plants is adequately described in previously submitted plant metabolism studies with soybean, cotton, tomatoes, potatoes, and sugar beets. In addition, plant metabolism studies were submitted with this petition to describe the nature of residue in genetically modified corn containing the AAD-1 gene (Event 278).  In the corn metabolism study, the parent quizalofop ethyl ester was not identified in forage and was not conclusively identified in fodder; however, radioactivity did elute in the region of quizalofop ethyl ester in fodder.  Quizalofop acid accounted for 0.7% TRR in forage and 0.9-1.1% TRR in fodder.  No other metabolites were identified.  In forage and fodder, respectively, polar unknowns at 2.0-2.6 minutes were 9.8-12.1% TRR and 2.1-13.8% TRR, polar unknowns at 2.6-3.0 minutes were 2.2-4.5% TRR and 4.7-17.0% TRR, and unknowns eluting at 13.2-13.5 minutes were tracked <=4.6% TRR and <=6.1% TRR.  Characterization of nonextractable residues in fodder indicated that incorporation into pectin and lignin accounted for 1.3% and 5.8% TRR, respectively.  Following acid detergent fiber (ADF) isolation/hydrolysis, remaining residues in fodder were characterized as hemicellulose or as cellulose, accounting for 1.7-3.7% TRR.  Based on the results of the metabolism study with AAD-1 corn (Event 278), the petitioner proposed that the metabolism of quizalofop-P-ethyl ester proceeds from the ester to the acid, the active form.  Metabolism continues through incorporation of the radiolabeled carbon into natural plant constituents, such as lignin and cellulose.

HED has determined that the residues of concern (ROC) in plant commodities are quizalofop-P-ethyl, its acid metabolite quizalofop-P, and the S -enantiomers of both compounds, each expressed as quizalofop-P-ethyl.  Overall, the metabolism studies indicate that quizalofop ethyl does not accumulate but is rapidly hydrolyzed at the ethyl ester to form the quizalofop acid.  The acid then undergoes cleavage of the enol ether linkage between the phenyl and quinoxalinyl rings in the acid, and/or cleavage of the ether linkage between the isopropanoic group and the phenyl ring to form phenols.  The phenols conjugate with plant sugars; some hydroxylation or further cleavage of the phenols occurs.  Metabolism studies with soybeans demonstrated that the racemic mixture of quizalofop ethyl and the R-enantiomer, quizalofop-P-ethyl, have nearly identical pathways.

The qualitative nature of the residue in livestock is adequately understood based on metabolism studies with goats and poultry.  The studies indicated that quizalofop ethyl is metabolized in livestock via hydrolysis to quizalofop acid which then undergoes methylation to form quizalofop methyl ester.  No phenols were detected in either goat or hen commodities, indicating that cleavage of the ether linkages of quizalofop does not occur.  The ROC in livestock commodities are quizalofop ethyl, quizalofop-methyl, and quizalofop acid.

HED previously concluded that the existing high performance liquid chromatography/ultra violet (HPLC/UV) method used for tolerance enforcement of soybean commodities (Method AMR-153-83, Revision 3) or newer method LAN-1 would not be adequate for the enforcement of tolerances in/on barley, flax, sunflower, or wheat commodities.  The petitioner did not include any validation data reflecting analysis of barley, flax, sunflower, or wheat commodities using the current enforcement method, and the extraction procedures of the methods used for data collection in the studies submitted with the previous petition differ significantly from the extraction procedures of the existing enforcement method.  By translation the current enforcement method would not be adequate for the enforcement of tolerances in/on corn commodities.  However, the petitioner submitted an analytical method amendment report for the determination of residues in sunflower seed, meal and oil which is currently under review by HED and will be addressed in a separate residue chemistry chapter.

In conjunction with a previous petition (PP#0F6076; DP#266204, S. Oonnithan, 7/24/2006), HED concluded that sufficient data are available to support the use of the HPLC data-collection method, Morse Method Meth-147 (used for barley and wheat), for enforcement purposes, pending petition method validation (PMV).  The method involves hydrolysis of samples with methanolic potassium hydroxide (KOH) to convert quizalofop-P-ethyl and quizalofop-P residues to 2-methoxy-6-chloroquinoxaline (MeCHQ).  Residues of MeCHQ are partitioned into hexane, and the extract is cleaned up by gel permeation chromatography (GPC) prior to analysis by HPLC using fluorescence detection.  The validated limit of quantitation (LOQ) is 0.05 ppm for all matrices.  The method was forwarded to the BEAD's Analytical Chemistry Branch (ACB) for PMV (DP#330973, S. Oonnithan, 7/24/2006); however, the PMV results are not available.  Subsequently, Morse Method Meth-147 has been re-evaluated using "SOP for Reviewing Tolerance Methods", SOP Number:ACB-019, which is the current procedure for determining if a method is suitable for tolerance enforcement.  After reviewing Morse Method Meth-147 against the Tolerance Method Validation (TMV) Review Checklist, the analytical method data appear to satisfy the requirements, provided the solvent exchange modification made by the ILV laboratory is incorporated into the final method.  A TMV by ACB will not be necessary.

Adequate methods are available for the enforcement of tolerances in/on livestock commodities.  HPLC/UV Method AMR-627-86 is available for the determination of residues of quizalofop ethyl, quizalofop acid, and quizalofop-methyl in livestock tissues, and HPLC/UV Method AMR-515-86 (Revision A) is available for determination of residues of quizalofop ethyl, quizalofop acid, and quizalofop-methyl in milk.  Methods AMR-627-86 and AMR-515-86 have undergone PMV and have been forwarded to FDA for publication in the Pesticide Analytical Manual (PAM) Volume II.  In addition, HPLC/UV Methods AMR-846-87, AMR-845-87, and AMR-623-86 are available for the determination of residues of quizalofop ethyl, quizalofop acid, and quizalofop-methyl in livestock fat, cream, and eggs, respectively.  Methods AMR-846-87, AMR-845-87, and AMR-623-86 have been forwarded to the FDA for publication in PAM Volume II as letter methods.  

Multiresidue method data for quizalofop ethyl are available; quizalofop ethyl is completely recovered using Multiresidue Methods Section 302 (Luke Method; Protocol D).  No data are available pertaining to recovery of quizalofop acid or quizalofop-methyl using the multiresidue methods.

The storage duration of the samples of the submitted crop field trial studies with sorghum are supported by adequate storage stability data of the residues of concern.  However, storage stability data for quizalofop P-ethyl and quizalofop acid in/on field corn and processed commodities are not currently available.  The petitioner indicated that a storage stability study is in progress.  Storage stability data for quizalofop ethyl and quizalofop in/on various matrices, including cotton, soybean, and wheat commodities, have been submitted previously.  The available wheat storage stability data are tentatively considered adequate to support submitted crop field trial on corn.  Storage stability data were not provided for the corn processed commodities and are required to support the processing studies.  When the storage stability study on corn is submitted, the adequacy of the storage stability data will be re-evaluated.

Adequate ruminant and poultry feeding studies were submitted previously.  These studies indicate that tolerances are needed for livestock commodities to support the current and proposed uses of quizalofop-P-ethyl.  The maximum reasonable dietary burdens (MRDBs) of quizalofop-P-ethyl to livestock have been re-calculated using the registered and proposed uses.  Based on the calculated MRDBs, the established tolerances are adequate for all livestock commodities.

The submitted residue data for field corn commodities (forage, grain, and stover) are tentatively considered to be adequate, pending submission of storage stability data demonstrating the stability of quizalofop-P-ethyl and quizalofop acid in/on field corn forage, grain, and stover.  The number and locations of crop field trials are in accordance with OCSPP Guideline 860.1500.  The field trials reflect the proposed use pattern.  The maximum total quizalofop-P-ethyl residues [sum of quizalofop-P-ethyl and quizalofop acid residues (as parent equivalents)] were <0.02 ppm in/on forage and grain and <0.022 ppm in/on stover.  Using the OECD MRL calculator, the recommended tolerances are 0.02, 0.02, and 0.03 ppm in/on corn forage, grain, and stover, respectively.  The forage and grain recommendations are higher than the tolerance levels proposed by the petitioner and the stover recommendation is identical to the tolerance level proposed by the petitioner.

Adequate processing data for corn have been submitted, pending submission of storage stability data demonstrating the stability of quizalofop-P-ethyl and quizalofop acid in/on field corn processed commodities.  Tolerances for the processed commodities of corn are not needed for the purpose of this petition based on the results of processing trials which showed that residues of quizalofop-P-ethyl and quizalofop acid (as parent equivalents) were <LOQ in/on field corn grain RAC (treatment at ~2x the proposed maximum seasonal rate), and in field corn processed commodities (starch, refined oil (wet and dry milling), meal, grits, flour, and AGF).  The registrant explained that phytotoxicity concerns preclude corn processing studies at higher treatment rates.

The submitted residue data for sorghum commodities (forage, grain, and stover) are adequate to satisfy data requirements.  The sorghum field trials reflected the maximum proposed application rates and the proposed PHIs.  The maximum total quizalofop-P-ethyl residues [sum of quizalofop-P-ethyl and quizalofop acid residues (as parent equivalents)] were <0.180 ppm in/on forage, <0.158 ppm in/on grain, and <0.266 ppm in/on stover.  Using the OECD MRL calculator, the recommended tolerances are 0.20, 0.20, and 0.30 ppm in/on sorghum forage, grain, and stover, respectively.  These recommendations are identical to the tolerance levels proposed by the petitioner for sorghum forage and grain.  The tolerance level recommendation for sorghum stover is slightly lower than the level (0.35 ppm) proposed by the petitioner.

No residue data were submitted to support the proposed use on mustard seed and other members of the rapeseed subgroup 20A, except flaxseed.  The available field trial data for canola seed, the representative crop of the rapeseed subgroup 20A, may be translated to support the proposed uses on mustard seed and other members of the rapeseed subgroup 20A, except flaxseed.  These data are adequate to fulfill data requirements and reflect ~0.8-1.5x the maximum proposed seasonal application rate for the EC formulation with 38- to 74-day PHI.  The data for 0.8x and 1.5x was analyzed to recommend a tolerance that may support use of the 0.88 lb ai/gal EC formulation.

Adequate processing data for sorghum have been submitted.  The processing data indicate that total quizalofop-P-ethyl residues concentrate in sorghum AGF.  Based on the processing factor, 3.4x, and the HAFT for sorghum grain, 0.149 ppm, expected residues in sorghum AGF following treatment at 1x would be 0.507 ppm.  Because this value is greater than the recommended 0.2-ppm tolerance for sorghum grain, a tolerance is needed for total quizalofop-P-ethyl residues in/on sorghum, grain, aspirated grain fractions.  A tolerance of 1.0 ppm would be appropriate.  

No new processing data were submitted in support of the label amendment request to expand the use of quizalofop on rapeseed meal that would cover the rapeseed subgroup 20A, except flaxseed).  Acceptable processing data were previously submitted and reviewed for canola seed, the representative crop of subgroup 20A, under PP# 5F4545/FAP# 6H5737 (DP#s 220476, 220478, and 220480, F. Griffith, 2/21/96).  Based on the available canola processing data, a tolerance for canola meal was established at 1.5 ppm; a tolerance was not required for refined oil.  The canola processing data was used to recommend a tolerance for the rapeseed, meal of 2.0 ppm by adjusting for the proposed application rate.  

The available confined/field rotational crop data indicate that a 120-day plant back interval (PBI) is required for all crops other than those with registered uses.

No Codex MRLs have been established for residues of quizalofop ethyl.  Canadian MRLs have been established for residues of quizalofop ethyl and quizalofop in/on flax, oriental mustard seeds (condiment type and oil seed type), and rapeseeds (canola), the only crops included in the subject petition, at 0.05 ppm.  No Mexican MRLs have been established for any of the requested crops.  


Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for quizalofop ethyl.  Pending submission of the items requested below, there are no residue chemistry issues that would preclude granting registration for the proposed uses on corn, sorghum and rapeseed, subgroup 20A (except flaxseed) and the establishment of tolerances for combined residues of quizalofop-P-ethyl, quizalofop-P, and the S-enantiomers of these compounds, all expressed as quizalofop ethyl, as follows: 

            Corn, forage	0.02 ppm
            Corn, grain	0.02 ppm
            Corn, stover	0.03 ppm
            Rapeseed, subgroup 20A, except flaxseed	1.5 ppm
            Rapeseed, subgroup 20A, meal, except flaxseed	2.0 ppm
            Sorghum, grain, grain	0.20 ppm
            Sorghum, forage	0.20 ppm
            Sorghum, stover	0.30 ppm
            Sorghum, grain, aspirated grain fractions	1.0 ppm

A human health risk assessment is forthcoming.


860.1200 Directions for Use

The following changes are recommended in the draft label of Assure[(R)] II herbicide: 

	::	The application rate on the supplemental label for field corn and sorghum is presented in terms of "oz product/A."  The label should be amended to read "fl. oz product/A".

	::	The proposed grazing restrictions are impractical for field corn and sorghum and should be removed from the product label.

       The supplemental label for field corn should specify the PHI for corn grain and stover, and the concentration of either crop oil concentrate or nonionic surfactant.  These parameters should reflect those used in the crop field trials.


860.1340 Residue Analytical Methods

	::	After reviewing Morse Method Meth-147 against the Tolerance Method Validation (TMV) Review Checklist, provided the solvent exchange modification made by the ILV laboratory is incorporated into the final method, the analytical method data satisfy the requirements.  A TMV by ACB will not be necessary.


860.1380 Storage Stability

	::	Storage stability data for quizalofop P-ethyl and quizalofop acid in/on field corn and processed commodities are not currently available; the petitioner indicated that a storage stability study is in progress.  The available wheat storage stability data are tentatively considered adequate to support submitted crop field trial on corn.  Storage stability data were not provided for the corn processed commodities and are required to support the processing studies.  When the storage stability study on corn is submitted, the adequacy of the storage stability data will be re-evaluated.


860.1550 Proposed Tolerances

      ::	The proposed tolerance level for corn forage and grain is 0.01 ppm.  However, by using the OECD calculator the appropriate tolerance level for corn forage and grain is 0.02 ppm.  A revised tolerance should be proposed.

	::	The petitioner proposed separate tolerances in/on the individual commodities of the rapeseed subgroup 20A, except flaxseed [borage seed, crambe seed, gold of pleasure seed, cuphea seed, echium seed, hare's ear mustard seed, lesquerella seed, lunaria seed, meadowfoam seed, milkweed seed, mustard seed, oil radish seed, poppy seed, rapeseed, sesame seed, and sweet rocket seed] at 1.0 ppm.  The recommended tolerance differs since the residues levels were scaled to reflect the proposed use pattern and a tolerance was estimated by using the OECD calculator.  Therefore, for the proposed use pattern a subgroup tolerance in/on rapeseed subgroup 20A, except flaxseed should be proposed at 1.5 ppm.  Also, a tolerance of 2.0 ppm is recommended for rapeseed, subgroup 20A, meal, except flaxseed.

	::	The proposed tolerance level for sorghum stover is 0.35 ppm.  However, by using the OECD calculator the appropriate tolerance level for sorghum stover is 0.3 ppm.  A revised tolerance should be proposed.  

	::	The proposed tolerances should be revised to reflect the correct commodity definitions as specified Table 12.









Background

Dupont has submitted a label amendment for Assure(R) II herbicide (EPA Reg. No. 352-541) to include uses on corn seed containing DAS-40278-9 and field corn containing DAS-40278-9.  The Interregional Research Project No. 4 (IR-4) is proposing to amend the label of Assure(R) II herbicide to include uses on the rapeseed subgroup 20A, except flaxseed, and sorghum grain containing the DuPont(TM) INZEN(TM) AII Herbicide Tolerance Trait (native trait).  Assure[(R)] herbicide contains quizalofop-P-ethyl as the sole ai, which is an R-enantiomer of quizalofop ethyl.  Chemically, quizalofop ethyl is a racemic mixture containing R- and S-enantiomers and the former is the pesticide active component.  Quizalofop ethyl is a selective preplant, pre- and postemergence herbicide registered for the control of annual and perennial grasses on noncrop and on crop land areas.

The chemical structure of quizalofop-P-ethyl and its major breakdown products are presented in Table 1 and its physicochemical properties are presented in Table 2.


Table 1.  Quizalofop-P-ethyl Nomenclature.
Chemical structure
                                       
Common name
Quizalofop-P-ethyl
IUPAC name
ethyl (R)-2-[4-((6-chloroquinoxalin-2-yl)oxy)phenoxy]propanoate
CAS name
(2R)-2-[4-[(6-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid, ethyl ester
CAS registry number
100646-51-3
End-use product (EP)
0.88 lb ai/gal EC formulation (EPA Reg. No. 352-541)
Chemical structure of the R-enantiomer of quizalofop-P acid
                                       
(2R)-2-[4-[(6-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid
Chemical structure of quizalofop-methyl
                                       
methyl 2-[4-(6-chloroquinoxalin-2-yl-oxy)phenoxy]propanoate
Chemical structure of the S-enantiomer of quizalofop ethyl
                                       
(2S)-2-[4-[(6-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid, ethyl ester
Chemical structure of the S-enantiomer of quizalofop-P acid
                                       
(2S)-2-[4-[(6-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid

Table 2.  Physicochemical Properties of the Technical Grade Test Compound - Quizalofop-P-ethyl.
Parameter
Value
Reference
Melting point
76.0-77.0 C (pure form)

CB Nos. 5852 & 5853, 3/29/90, W. Hazel
pH
6.6 (1% aqueous slurry)

Density
1.35 g/cm[3] at 20 C (pure form)

Water solubility
0.4 ppm (20 C)

Solvent solubility
Solvents
acetone
benzene
carbon disulfide
chloroform
cyclohexanone
dichloromethane
dimethyl sulfoxide
ethanol
n-hexane
methanol
tetrahydrofuran
toluene
xylene		
g/L at 20 ºC
650
680
660
1350
440
1970
200
22
5
22
1160
430
360

Vapor pressure
8.3 x 10[-10] mm Hg (20 C)

Dissociation constant, pKa
Not applicable

Octanol/water partition coefficient
log POW = 4.66

UV/visible absorption spectrum
Not available


860.1200 Directions for Use

The petitioner has submitted a draft specimen supplemental labeling for the 0.88 lb ai/gal EC formulation of quizalofop-P-ethyl (Assure(R) II Herbicide; EPA Reg. No. 352-541).  Dupont is proposing a label amendment for this product to add new uses on field corn containing DAS-40278-9 and propagation of corn seed containing DAS-40278-9.  The currently registered EPA label, dated 4/14/2010, was obtained from PPLS.  The currently registered uses include canola, crambe, cotton, crops grown for seed, eucalyptus, dry beans (including Chickpea), dry and succulent peas, flax, hybrid poplar plantings, lentils, mint (spearmint and peppermint), pineapple, ryegrass grown for seed, snap beans, soybeans, sugar beets, sunflowers, and noncrop areas.  The use patterns for the proposed new uses are presented in Table 3.


Table 3.  Summary of Directions for Use of Quizalofop-P-ethyl Formulation.[1]
Applic. Timing, Type, and Equip.
                                     Form.
                                [EPA Reg. No.]
                                 Applic. Rate 
                                   (lb ai/A)
                          Max. No. Applic. per Season
                          Max. Seasonal Applic. Rate
                                   (lb ai/A)
                                  RTI 
(days)
                                  PHI (days)
                        Use Directions and Limitations
                       Field Corn containing DAS-40278-9
Postemergence, Broadcast foliar application by ground
                               0.88 lb ai/gal EC
                                   [352-541]
                                  0.034-0.083
                                       2
                                     0.083
                                     NS[2]
                                30 (forage)[3]
For use in propagation of corn seed containing DAS-40278-9 and quizalofop-tolerant field corn containing DAS-40278-9.  Applications may be made to emerged corn that is at the V2 through V6 stage of development.  Applications must include either a crop oil concentrate or a non-ionic surfactant.  Aerial application is prohibited. The grazing of livestock on treated corn or harvesting forage within 30 days of application is prohibited.
Sorghum, grain containing the DuPont(TM) INZEN(TM) AII Herbicide Tolerance Trait
Postemergence, Broadcast application by ground or air
                               0.88 lb ai/gal EC
                                   [352-541]
                                  0.034-0.083
                                       2
                                     0.138
                                     NS[2]
                                30 (forage)[4]
                                       
                             45 (grain and stover)

Applications must include either a crop oil concentrate or a non-ionic surfactant.
                    Rapeseed Subgroup 20A, Except Flaxseed
[includes Borage, Crambe, Cuphea, Echium, Gold of Pleasure (Camelina), Hare's ear mustard, Lesquerella, Lunaria, Meadowfoam, Milkweed, Mustard seed, Oil Radish, Poppy seed, Rapeseed (Canola), Sesame, and Sweet Rocket]
Postemergence, Broadcast application by ground or air
                               0.88 lb ai/gal EC
                                   [352-541]
                                      NS
                                      NS
                                     0.124
                                       7
                                      60

Applications must include either a crop oil concentrate or a non-ionic surfactant.
[1] General use directions, restrictions, and precautions were obtained from the currently registered label for Assure(R) II Herbicide (EPA Reg. No. 352-541), dated April 14, 2010
[2]  NS = Not specified
[3] The supplemental labeling indicates that a 30-day PHI is proposed for forage; a PHI for corn grain or stover is not specified.  The currently registered label indicates that the grazing of livestock in treated areas or feeding of forage, hay, or straw from the treated crops to livestock is prohibited.  
[4] Under Section B, "The Amount, Frequency and Time of Application of Quizalofop-Ethyl Use in Sorghum Grain", the petitioner indicates that forage may be harvested 30 (+-2) days following one broadcast application; however, the supplemental labeling provided in Section B indicates that a 45-day PHI between grazing or feeding of treated grain, forage, fodder, straw, or hay to livestock must be maintained.
[5] The Section 3 label describes the crop rotation restrictions as required.

For field corn, applications are to be made using ground equipment, in a minimum of 10 gal/A in nonarid areas or 15 gal/A in arid areas.  Aerial application or application through any type of irrigation system is prohibited.  The grazing of livestock on treated corn or harvesting forage within 30 days of application is prohibited.  Tank-mix applications may be made with broadleaf herbicides, insecticides, and fungicides.  Tank mix products should be registered for use on the specific crop and the most restrictive label directions are to be followed.  The label specifies a PBI of 120 days for crops not registered for treatment with quizalofop ethyl.  The use of either crop oil concentrate or nonionic surfactant is recommended in the supplemental label but the concentration is not specified.

For sorghum, applications are to be made using ground equipment, in a minimum of 10 gal/A in nonarid areas or 15 gal/A in arid areas, or aerial equipment, in a minimum of 3 gal/A in nonarid areas or 5 gal/A in arid areas.  Application through any type of irrigation system is prohibited.  The grazing of livestock in treated areas or feeding of forage, hay, or straw from the treated crops to livestock within 45 days of application is prohibited.  Tank-mix applications may be made with broadleaf herbicides, insecticides, and fungicides.  Tank mix products should be registered for use on the specific crop and the most restrictive label directions are to be followed.  The label specifies a PBI of 120 days for crops not registered for treatment with quizalofop ethyl.  A crop oil concentrate (1% v/v) is the preferred adjuvant recommended in the label but the alternative use of a non ionic surfactant (0.25% v/v) is also permitted.


Conclusions.  The proposed use patterns for the 0.88 lb ai/gal EC formulation (Assure(R) II Herbicide; EPA Reg. No. 352-541) are adequate to allow evaluation of the residue data submitted in support of this petition.  The following label amendments are recommended for clarity and to conform to the field trial data submitted on the proposed crops.

1.	The application rate on the supplemental label for field corn and sorghum is presented in terms of "oz product/A."  The label should be amended to read "fl. oz product/A".  

2.	The proposed grazing restrictions are impractical for field corn and sorghum and should be removed from the product label.


860.1300 Nature of the Residue  -  Plants

DER References: 48310101.der (AAD-1 field corn metabolism)
Residue Chemistry Memo DP#s 196041, 196043, 205430, 205432, 206200, 206201 and 212620-212622, F. Griffith, 3/30/1995; PP#3F4268
Residue Chemistry Memo DP# 182751, J. Stokes, 7/15/1993
Residue Chemistry Memo DP#s 160972 and 166083, J. Stokes, 3/4/1992; PP#1F3951
Residue Chemistry Memo DP# none, CB. No. 1127, M. Firestone, 9/25/1985; PP#5F3252

The qualitative nature of the residue in plants is adequately understood based on a previously submitted plant metabolism studies with soybean, cotton, tomatoes, potatoes, and sugar beets.  The metabolism studies indicate that quizalofop ethyl does not accumulate but is rapidly hydrolyzed at the ethyl ester to form quizalofop acid.  The acid then undergoes cleavage of the enol ether linkage between the phenyl and quinoxalinyl rings and/or cleavage of the ether linkage between the isopropanoic group and the phenyl ring to form phenols.  Metabolism studies with soybeans demonstrated that the racemic mixture of quizalofop ethyl and the resolved R-enantiomer, quizalofop-P-ethyl have nearly identical pathways (DP# 182751, J. Stokes, 7/15/93).  The ROC in plant commodities are quizalofop-P-ethyl, quizalofop-P (acid metabolite), and S- enantiomers of both the parent and acid, each expressed in terms of quizalofop-P-ethyl.

AAD-1 Field Corn

Dow AgroSciences submitted a study investigating the metabolism of [U-[14]C-phenyl]-quizalofop ethyl ester (PH label; specific activity 25.5 mCi/mmol) and [[14]C]-quizalofop ethyl ester - quinoxaline (QU label; specific activity 32.8 mCi/mmol) in quizalofop-tolerant field corn.  The field corn seed used in the study was genetically modified AAD-1 corn (Event DAS-40278-9, also known as Event 278).  The modification makes the corn resistant to both 2,4-D and "fop" grass herbicides including quizalofop and haloxyfop.

The radiolabeled test substance was formulated as an emulsifiable concentrate (EC) and applied to field-grown quizalofop-tolerant corn as a single broadcast foliar application at the V6 growth stage at a rate of 0.09 lb ai/A (101-104 g ai/ha).  Samples of forage were harvested at a preharvest interval (PHI) of 48 days and samples of grain, cob, and fodder were harvested at a PHI of 72 days.  The in-life phase of the study was conducted by Research For Hire (Porterville, CA), and the analytical phase of the study was conducted by ABC Laboratories (Columbia, MO).

Total radioactive residues (TRR) determined by combustion/LSC in PH-labeled and QU-labeled samples, respectively, were 0.007 and 0.122 ppm in forage, 0.004 and 0.005 ppm in grain, 0.002 ppm in cobs (both labels), and 0.260 and 0.353 ppm in fodder.  Due to the low TRR levels, samples of cob, grain, and PH-labeled forage were not further analyzed.

Extraction with ACN/water (replicates 1 & 2) or methanol/water (replicates 3 & 4) released the majority of the radioactivity from all replicate samples of forage and fodder:  50-52% TRR from forage (QU label) and 43-52% TRR from fodder (both labels).  Subsequent extraction with methanol/10 N NaOH released an additional ~11-13% TRR from replicate 3 & 4 samples of forage (QU label) and fodder (both labels).  Subsequent extraction with ACN/1 N HCL (replicates 1 & 2) or 1 N HCl (replicates 3 & 4) released an additional 16-21% TRR from all replicate samples of forage (QU label) and 20-29% TRR from all replicate samples of fodder (both labels).  Nonextractable residues in all replicates following these extraction procedures were 14-33% TRR in QU-labeled forage (0.017-0.041 ppm), 24-29% TRR (0.063-0.101 ppm) in fodder (both labels, replicates 1 & 2), and 11-15% TRR (0.029-0.052 ppm) in fodder (both labels, replicates 3 & 4).  The nonextractable residues were not further analyzed, except for replicates 3 & 4 of QU-labeled fodder.  The distribution of the nonextractable residues of QU-labeled fodder (replicates 3 & 4) into natural components including pectin, lignin, hemicellulose, and cellulose was investigated by a series of extraction/hydrolysis procedures.  Nonextractable residues remaining following these procedures accounted for 0.8% TRR (0.003 ppm) in fodder (QU label).  These procedures adequately extracted the majority of the residues from field corn matrices.  Accountabilities were 93-102% for forage and fodder (replicates 1 & 2) and 89-102% for forage and fodder (replicates 3 & 4).

Residues were identified and quantitated in corn forage and fodder by high performance liquid chromatography (HPLC) following purification of extracts by solid phase extraction (SPE).  Initial HPLC analysis of extracts was completed within 2.0-2.1 months of harvest and final HPLC analysis of repeated extracts was completed within 6.1-6.9 months of harvest.  Because quantitation of residues and initial residue identifications were completed within ~4-6 months of harvest, no storage stability data are required to support the study.

The parent, quizalofop ethyl ester, was not identified in forage (QU label, all replicates) and was not conclusively identified in fodder; however, radioactivity did elute in the region of quizalofop ethyl ester in fodder (both labels, replicates 3 & 4) at 0.4-1.4% TRR (0.001-0.004 ppm).  Quizalofop acid accounted for 0.7% TRR (0.001 ppm) in forage (QU label, 1 & 2 replicates) and 0.9-1.1% TRR (0.003 ppm) in fodder (both labels, replicates 3 & 4).  No other metabolites were identified.  Polar unknowns at 2.0-2.6 minutes were 9.8-12.1% TRR (0.012-0.015 ppm) in forage (QU label, all replicates) and 2.1-13.8% TRR (0.006-0.048 ppm) in fodder (both labels, all replicates).  Polar unknowns at 2.6-3.0 minutes were 2.2-4.5% TRR (0.002-0.005 ppm) in forage (QU label, all replicates) and 4.7-17.0% TRR (0.017-0.043 ppm) in fodder (both labels, all replicates).  Unknowns eluting at 13.2-13.5 minutes were tracked and accounted for <=4.6% TRR in forage and <=6.1% TRR in fodder.

Characterization of nonextractable residues indicated that incorporation into pectin and lignin accounted for 1.3% and 5.8% TRR, respectively, in fodder (QU label, 3 & 4 replicates).  Following acid detergent fiber (ADF) isolation/hydrolysis, remaining residues in fodder were characterized as hemicellulose or as cellulose, accounting for 1.7-3.7% TRR.

The forage and fodder methanol/water extracts (replicates 3 & 4) were also subjected to acid hydrolysis procedures and analyzed by HPLC.  Quizalofop acid accounted for 1.4% TRR (0.002 ppm) in QU-labeled forage and 0.3% TRR (0.001 ppm) in PH-labeled fodder (replicates 3 & 4).  The acid hydrolyzed methanol/water extract of forage and fodder contained multiple, polar, low level metabolites.  Some of the nonpolar peaks in the methanol/water extract SPE eluents were not observed in the acid hydrolyzed samples; however, multiple peaks remained, including several polar components.  The petitioner reported that no common moieties were formed via acid hydrolysis, which indicated that the multiple, low level components in the original extract were not related and not easily cleaved sugar conjugates.

Based on the results of the metabolism study with AAD-1 corn (Event 278), the petitioner proposed that the metabolism of quizalofop-P-ethyl ester proceeds from the ester to the acid, the active form.  Metabolism continues through incorporation of the radiolabeled carbon into natural plant constituents, such as lignin and cellulose.



860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo DP# none, CB Nos. 2806, 2810, & 2811, G. Otakie, 12/18/1987; PP#5F3252

The nature of the residue in livestock is adequately understood based on metabolism studies with goats and poultry.  The studies indicate that quizalofop ethyl is metabolized in livestock via hydrolysis to quizalofop acid which then undergoes methylation to form quizalofop methyl ester.  No phenols were detected in either the goat or hen matrices, indicating that cleavage of the ether linkages of quizalofop does not occur.  In hens, quizalofop-P acid is utilized in fatty chain elongation to form quizalofop-pentanoic acid.  The ROC in livestock commodities are quizalofop-P-ethyl, quizalofop-methyl, and quizalofop-P, each expressed in terms of quizalofop-P-ethyl.


860.1340 Residue Analytical Methods  -  Plant Commodities

Residue Chemistry Memo DP# 266204, S. Oonnithan, 7/24/2006; PP# 0F6076
Residue Chemistry Memo DP# 330973, S. Oonnithan, 7/24/2006; PP# 0F6076 (PMV Request)
Residue Chemistry Memo DP# 219639, F. Griffith, 10/11/1995

Data Collection Method for Field Corn Commodities:

Samples from the submitted crop field trials and processing study on field corn were analyzed for residues of quizalofop-P-ethyl and quizalofop acid using an LC/MS/MS method detailed in the study.

Briefly, samples were extracted with methanol:water (90:10, v:v) and centrifuged.  An aliquot of the extract was mixed with water:formic acid (99.9:0.1, v:v), filtered, and analyzed by on-line solid-phase extraction (SPE) and LC/MS/MS.  The reported LOQ (determined as the lower limit of method validation) was 0.01 ppm, and the limit of detection (LOD) was 0.003 ppm for quizalofop-P-ethyl and quizalofop acid in all matrices.

The LC/MS/MS method used to analyze field corn samples from the submitted crop field trials and processing study for residues of quizalofop-P-ethyl and quizalofop acid is adequate for data collection based on acceptable concurrent method recovery data.  Concurrent method recoveries were generally within the acceptable range of 70-120% from field corn grain, forage and stover fortified with quizalofop-P-ethyl and quizalofop acid at 0.01-1.0 ppm, with the exception of quizalofop acid recoveries in corn stover at the 1.0 ppm fortification level which were above 120% in the majority of the samples (117-138%) and a mean recovery of 127%.  In processed commodities, concurrent method recoveries were also generally within the acceptable range of 70-120%, with the exception of quizalofop acid recoveries in refined oil at both the 0.01 and 1.0 ppm fortification levels which were above 120% in about half the samples (95-143%) and mean recoveries of 112% and 121%, respectively.  Fortification levels were adequate to bracket residues found in treated samples.

Data Collection Method for Sorghum Commodities:

Samples from the submitted crop field trials and processing study on sorghum were analyzed for residues of quizalofop-P-ethyl and quizalofop acid using an LC/MS/MS method ("Working Method for Quizalofop P-Ethyl and Quizalofop Acid [Forage]) modified from the method in Du Pont Study No. AMR-1854-90.

Briefly, samples were extracted twice with acetonitrile (ACN):1% acetic acid (3:1, v:v) and the combined extracts diluted to volume.  An aliquot of the extract was concentrated then the pH adjusted to 5 with ammonium acetate.  The extract was incubated with cellulase and β-glucoidase and the pH adjusted to 3 with glacial acetic acid.  Cleanup of the extract was done through a Strata-X solid-phase extraction (SPE) cartridge, followed by elution with methanol (quizalofop acid) and ACN (quizalofop-P-ethyl).  The fractions were combined and diluted for analysis by LC/MS/MS.

The LLMV for quizalofop-P-ethyl and quizalofop acid was 0.05 ppm for sorghum forage, grain, stover, and AGF.  The petitioner used the LLMV as the LOQ for reporting residue results. The LOD for quizalofop-P-ethyl was determined to be 0.0062, 0.0033, 0.0053, and 0.0068 ppm, respectively, in/on sorghum forage, grain, stover, and AGF, and the LOD for quizalofop acid was determined to be 0.0072, 0.0075, 0.0058, and 0.0058 ppm, respectively, in/on sorghum forage, grain, stover, and AGF.

The LC/MS/MS method used to analyze sorghum samples from the submitted crop field trials and processing study for residues of quizalofop-P-ethyl and quizalofop acid is adequate for data collection based on acceptable method validation and concurrent method recovery data.  Method verification and concurrent method recoveries were within the acceptable range of 70-120% in sorghum forage, grain, and stover fortified with quizalofop-P-ethyl and quizalofop acid at 0.05-0.5 ppm.  Method verification and concurrent method recoveries were within the acceptable range of 70-120% from sorghum aspirated grain fractions (AGF) fortified with quizalofop-P-ethyl at 0.5 and 1.0 ppm, and quizalofop acid at 0.05, 0.5 and 1.0 ppm.  However, they were outside the acceptable range of 70-120% for quizalofop-P-ethyl at 0.05 ppm with mean recoveries of 59% and 66%.  Fortification levels were adequate to bracket residues found in treated samples.


Enforcement methods:

DuPont Method AMR-153-83, Revision 3:  In conjunction with a previous petition (PP#0F6076; DP#266204, S. Oonnithan, 7/24/2006), the petitioner proposed the existing enforcement method, "Determination of Residues of DPX-Y6202, DPX-Y6202 Acid, and DPX-Y6202 Acid Conjugates in Soybeans and Soybeans Fractions" (DuPont Method AMR-153-83, Revision 3, January 1987; MRID 40322410; PP# 5F3252, 12/18/87, G. Otakie), for the enforcement of tolerances for quizalofop-P-ethyl residues in/on barley, flax, sunflower, and wheat commodities.  This method involves extraction of samples, other than oil, with acetone and water acidified with glacial acetic acid.  Oil samples are mixed with hexane, and residues are extracted into acetonitrile.  The extracts are adjusted to pH 5 using base or buffer and then a mixture of -glucosidase and cellulase enzymes are used to convert any quizalofop conjugates to quizalofop.  Residues of quizalofop ethyl and quizalofop are then extracted from the aqueous phase using chloroform.  Liquid chromatography is used to separate quizalofop from quizalofop ethyl, and quizalofop residues are methylated.  Residues of quizalofop ethyl and quizalofop-methyl are determined by HPLC/UV.  The LOQ is 0.05 ppm.

This method has been validated by ACB and submitted to FDA for publication in PAM Vol. II; however, the method was accepted for the soybean tolerance only.  ACB noted that the complexity of the method may require an analyst to perform several practice runs.  It was concluded that additional methodology development work would be necessary if tolerances were proposed for other crops (PP# 3F3252, 6/27/88, G. Otakie).  However, the petitioner submitted an analytical method amendment report (MRID 47910506) for the determination of residues in sunflower seed, meal and oil which is currently under review by HED and will be discussed in a separate residue chemistry chapter.

LAN-1:  E.I. du Pont de Nemours has since submitted a different, less complex method, referred to as LAN-1.  The method involves extraction of samples with acetonitrile/1% acetic acid, hydrolysis of extracts with a mixture of cellulase and -glucosidase, and further hydrolysis with esterase.  Residues are partitioned into acetonitrile/dichloromethane, concentrated, and transferred into acetonitrile and phosphate buffer.  After HPLC column cleanup, extracts are analyzed by HPLC/UV.  The LOQ is 0.05 ppm (PP# 3F4268, F. Griffith, 3/30/95).

The LAN-1 method was forwarded to ACB for PMV; ACB examined the method and identified several deficiencies which needed addressing before the PMV is finalized (D219639, 10/11/95, F. Griffith). 

No validation data for the current enforcement method (AMR-153-83), or the newer method (LAN-1), have been submitted for the crop commodities (barley, flax, sunflower, and wheat commodities) proposed in the previous petition.

Morse Method Meth-147:  In conjunction with a previous petition (PP#0F6076; DP#266204, S. Oonnithan, 7/24/2006), the petitioner also submitted sufficient data to support the use of an HPLC data-collection method, Morse Method Meth-147 (used for barley and wheat), for enforcement purposes, pending petition method validation (PMV).  The method involves hydrolysis of samples with methanolic potassium hydroxide (KOH) to convert quizalofop-P-ethyl and quizalofop-P residues to 2-methoxy-6-chloroquinoxaline (MeCHQ).  Residues of MeCHQ are partitioned into hexane, and the extract is cleaned up by gel permeation chromatography (GPC) prior to analysis by HPLC using fluorescence detection.  The validated LOQ is 0.05 ppm for all matrices.  The method was forwarded to the BEAD's Analytical Chemistry Branch (ACB) for PMV (DP# 330973, 7/24/2006, S. Oonnithan).

A successful independent laboratory validation (ILV) trial was conducted using samples of wheat straw fortified with quizalofop-P-ethyl and quizalofop-P at 0.05, 0.10, and 6.5 ppm each. The first and second ILV trials failed due to problems in the final evaporation step in the method.  The ILV laboratory contacted Morse Laboratories after the second trial to discuss the final evaporation step of the method.  The ILV laboratory tried a different solvent exchange procedure for this final step, and the third trial was successful.  The laboratory reported that, other than the solvent exchange modification, the method was followed as written with minor modifications in the type of equipment used and the volumes of solvents used to elute residues from the GPC and SPE columns.

No radiovalidation data were submitted for the method.  Because the extraction procedures of the method are relatively rigorous, no radiovalidation data will be required to support the method.

Conclusions.  HED previously concluded that the existing high performance liquid chromatography/ultra violet (HPLC/UV) method used for tolerance enforcement of soybean commodities (Method AMR-153-83, Revision 3) or newer method LAN-1 would not be adequate for the enforcement of tolerances in/on barley, flax, sunflower, or wheat commodities.  The petitioner did not include any validation data reflecting analysis of barley, flax, sunflower, or wheat commodities using the current enforcement method, and the extraction procedures of the methods used for data collection in the studies submitted with the previous petition differ significantly from the extraction procedures of the existing enforcement method.  By translation the current enforcement method would not be adequate for the enforcement of tolerances in/on field corn commodities.  However, the petitioner submitted an analytical method amendment report for the determination of residues in sunflower seed, meal and oil by using the Morse method Meth-147 which is currently under review by HED and will be discussed in a separate residue chemistry chapter.  

HED also previously concluded that sufficient data are available to support the use of the HPLC data-collection method, Morse Method Meth-147 (used for barley and wheat), for enforcement purposes, pending petition method validation (PMV).  The method was forwarded to the BEAD's Analytical Chemistry Branch (ACB) for PMV (DP#330973, S. Oonnithan, 7/24/2006); however, the PMV results are not available.  Subsequently, Morse Method Meth-147 has been re-evaluated using "SOP for Reviewing Tolerance Methods", SOP Number:ACB-019, the current procedure for determining if a method is suitable for tolerance enforcement.  After reviewing Morse Method Meth-147 against the Tolerance Method Validation (TMV) Review Checklist, provided the solvent exchange modification made by the ILV laboratory is incorporated into the final method, the analytical method data appear to satisfy the requirements.  A TMV by ACB will not be necessary.  

We note that the method descriptions did not address the issue of determination of the S- enantiomers of quizalofop ethyl and quizalofop.  Because the KOH hydrolysis step would convert both the R- and S-enantiomers of quizalofop ethyl and quizalofop acid to the intermediate MeCHQ, all reported results for total quizalofop-P-ethyl residues would include residues of both the R- and S-enantiomers of quizalofop ethyl and quizalofop acid.  This was specified in the analytical method amendment report for sunflowers which is under review by HED.

HED notes that the Morse Method Meth-147 is appropriate for tolerance enforcement since is considered adequate for barley and wheat, a preliminary review of the validation data for sunflowers suggests that it is also adequate for oily seeds, and it is considered less complex than method AMR-153-86.  Therefore, the proposed tolerance expression for plants, which is based on measurement of MeCHQ, is considered adequate.





860.1340 Residue Analytical Methods  -  Livestock Commodities

Residue Chemistry Memo DP# None, G. Otakie, 6/27/1988; PP#3F3252

Adequate methods are available for the enforcement of tolerances in livestock commodities (PP# 3F3252, 6/27/88, G. Otakie).  A HPLC/UV Method (AMR-627-86, MRID 40322403) is available for the determination of residues of quizalofop ethyl, quizalofop, and quizalofop-methyl in livestock tissues.  Another HPLC/UV Method (AMR-515-86, Revision A; MRID 40322408) is available for determination of residues of quizalofop ethyl, quizalofop, and quizalofop-methyl in milk.  Methods AMR-627-86 and AMR-515-86 have undergone PMV and have been forwarded to FDA for publication in PAM Volume II.  In addition, HPLC/UV Methods AMR-846-87 (MRID 40322405), AMR-845-87 (MRID 40322409), and AMR-623-86 (MRID 40322404) are available for the determination of residues of quizalofop ethyl, quizalofop, and quizalofop-methyl in livestock fat, cream, and eggs, respectively.  Methods AMR-846-87, AMR-845-87, and AMR-623-86 have been forwarded to FDA for publication in PAM Volume II as letter methods.  The methods involve extraction of samples with acetonitrile, methanol, acidified acetone, or acidified acetone/hexane (depending on the matrix), treatment of the extract with enzymes (lipase and esterase) to disassociate the fat and to convert residues of quizalofop ethyl and quizalofop-methyl to quizalofop.  Quizalofop residues are then partitioned into chloroform for analysis by HPLC/UV.  Residue results are reported in terms of residues of quizalofop.  The reported LOQs are 0.02 ppm for muscle and 0.05 ppm for liver, kidney, cream, and fat; based on validation data, the LOQ for egg and milk is 0.01 ppm.

860.1360 Multiresidue Methods

No multiresidue method data were submitted with the current petition; however, multiresidue method data for quizalofop ethyl have been submitted previously.  According to the Pesticide Analytical Manual (PAM) Volume 1, Appendix II (FDA PESTDATA database dated 10/99), quizalofop ethyl is completely recovered using Multiresidue Methods Section 302 (Luke Method; Protocol D).  The database did not contain any information pertaining to the recovery of quizalofop acid or quizalofop-methyl using the multiresidue methods.

It's important to emphasize that multiresidue methods used for enforcement need to be validated considering the residues of concern, in this case quizalofop ethyl and the metabolites quizalofop acid and quizalofop-methyl.  The latter being considered for livestock commodities only.

860.1380 Storage Stability

Residue Chemistry Memo DP# None, G. Otakie, 12/18/1987; PP#5F3252
Residue Chemistry Memo DP#s 220215-17, F. Griffith, 2/13/1996; PP#s 3F42681/5H5720
Residue Chemistry Memo DP# 266204, S. Oonnithan, 7/24/2006; PP# 0F6076

The storage durations and conditions of samples from the field corn and sorghum crop field trials and processing studies submitted to support this petition are presented in Table 4.

Table 4.   Summary of Storage Conditions and Durations of Samples from Crop Field Trial and Processing Studies.  
Matrix 
                           Storage Temperature (°C)
                          Actual Storage Duration[1]
                  Interval of Demonstrated Storage Stability
Corn, field, early forage
                             Frozen at field sites
                                       
                      Approximately -20 at analytical lab
                                 335-376 days
                              (11.0-12.4 months)
Storage stability data for quizalofop P-ethyl and quizalofop acid in/on field corn and processed commodities are not currently available; the petitioner indicated that a storage stability study is in progress.

Quizalofop P-ethyl and quizalofop acid in/on wheat forage and grain for 12.7 months, wheat hay for 11.3 months, and wheat straw for 11.2 months. 2
Corn, field, forage
                                       
                                 314-375 days
                              (10.3-12.3 months)
                                       
Corn, field, grain
                                       
                                 253-320 days
                               (8.3-10.5 months)
                                       
Corn, field, stover
                                       
                                 272-335 days
                               (8.9-11.0 months)
                                       
Corn, field, grain (RAC)
(prior to processing)
                             Frozen at field sites
                                       
                                   < -12
                             at processing facility
                                       
                                       
                              Approximately -20 
                               at analytical lab
                                 184-199 days
                               (6.1-6.5 months)
                                       
Flour
                                       
                                 185-199 days
                               (6.1-6.5 months)
                                       
Grits
                                       
                                       
                                       
Meal
                                       
                                       
                                       
Refined oil, wet
                                       
                                 171-186 days
                               (5.8-6.1 months)
                                       
Refined oil, dry
                                       
                                 171-191 days
                               (5.6-6.3 months)
                                       
Starch
                                       
                                 180-194 days
                               (5.9-6.4 months)
                                       
Corn, aspirated grain fractions
                                       
                                 175-182 days
                               (5.8-6.0 months)
                                       
Sorghum, forage
                                      -20
                                 142-227 days
                               (4.7-7.5 months)
                                   206 days
Sorghum, stover
                                       
                                 109-191 days
                               (3.6-6.3 months)
                                   188 days
Sorghum, grain
                                       
                                 144-224 days
                               (4.7-7.4 months)
                                   201 days
Sorghum, grain (RAC)
(prior to processing)
                                      -20
                                   116 days
                                 (3.8 months)
                                   201 days
Sorghum, aspirated grain fractions
                                       
                             110 days (3.6 months)
                                   101 days
[1]  For the processing study duration is from harvest/collection after processing to extraction; interval between extraction and analysis was not provided.  Samples were processed within 87-136 days of harvest.
[2]  PP# 0F6076, DP# 266204, 7/24/2006, S. Oonnithan


A concurrent storage stability study was conducted to support the storage durations and conditions of samples from the submitted sorghum field trials and processing study.  These data demonstrate that residues of quizalofop-P-ethyl and quizalofop acid are stable when stored frozen for up to 206 days (6.7 months) in/on fortified sorghum forage, 201 days (6.6 months) in/on fortified sorghum grain, 188 days (6.1 months) in/on fortified sorghum stover, and 101 days (3.3 months) in/on fortified AGF.

Storage stability data for quizalofop P-ethyl and quizalofop acid in/on field corn and processed commodities are not currently available; the petitioner indicated that a storage stability study is in progress.  Storage stability data for quizalofop ethyl and quizalofop in/on various matrices, including cotton, soybean, and wheat commodities, have been submitted previously.  Adequate storage stability data are available for soybean seed indicating that residues of quizalofop ethyl and quizalofop are stable under frozen storage for up to 48 and 36 months, respectively (PP# 5F3252, 12/18/87, G. Otakie).  In addition, data are available indicating that residues of quizalofop are relatively stable in/on cotton seed, meal, and oil stored frozen for up to 28 months (PP# 3F42681/5H5720; DP#s 220215-17, F. Griffith, 2/13/96).  Since the parent ethyl ester hydrolyzes rapidly to quizalofop after application, HED concludes that separate storage stability data for quizalofop ethyl/quizalofop-P-ethyl in cotton commodities are not necessary.  Adequate storage stability data are available for wheat commodities indicating that residues of quizalofop-P-ethyl and quizalofop-P are stable during frozen storage for up to 12.7 months in/on wheat forage and grain, 11.3 months in/on wheat hay, and 11.2 months in/on wheat straw (PP# 0F6076, DP# 266204, 7/24/2006, S. Oonnithan).

Conclusions. The available wheat storage stability data are tentatively considered adequate to support submitted crop field trial on corn.  Storage stability data were not provided for the corn processed commodities and are required to support the processing studies.  When the storage stability study on corn is submitted, the adequacy of the storage stability data will be re-evaluated.  The submitted concurrent storage stability data for sorghum forage, stover, grain, and aspirated grain fractions are adequate to support the sorghum crop field trials.  The data indicate that there are no storage stability issues and no corrections for decline during storage are needed.


860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

Residue Chemistry Memo DP# 266204, S. Oonnithan, 7/24/2006; PP# 0F6076
Residue Chemistry Memo DP#s 160972 and 166083, J. Stokes, 3/4/1992; PP#1F3951
Residue Chemistry Memo DP# None, G. Otakie, 12/18/1987; PP#5F3252

The livestock feedstuffs included in the current petitions are field corn (forage/silage, stover, grain, aspirated grain fractions, and milled byproducts) and sorghum (forage/silage, stover, grain, and aspirated grain fractions).  The potential dietary exposure of livestock to quizalofop-P-ethyl residues, considering both proposed and registered uses of quizalofop-P-ethyl, was calculated using recent Agency guidance on calculating dietary exposure from "reasonably balanced" livestock diets (ChemSAC draft memo, 6/2008).  The dietary burden is reproduced below in Table 5.

The maximum reasonable dietary burdens are estimated to be:  0.382 ppm for beef cattle, 2.455 ppm for dairy cattle, 0.625 ppm for poultry, and 0.463 ppm for swine.

Table 5.   Calculation of Dietary Burdens of Quizalofop-P-ethyl Residues to Livestock.
Feedstuff
                                    Type[1]
                                % Dry Matter[1]
                                   % Diet[1]
                          Recommended Tolerance (ppm)
                         Dietary Contribution (ppm)[2]
Beef Cattle
Sorghum, forage/silage
                                       R
                                      35
                                      15
                                     0.20
                                     0.086
Sorghum, grain
                                      CC
                                      86
                                      40
                                     0.20
                                     0.093
Aspirated grain fractions
                                      CC
                                      85
                                       5
                                      1.0
                                     0.059
Sugar beet, molasses
                                      CC
                                      75
                                      10
                                     0.20
                                     0.027
Barley, grain
                                      CC
                                      88
                                      25
                                     0.05
                                     0.014
Sunflower, meal
                                      PC 
                                      92
                                       5
                                      1.9
                                     0.103
TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     0.382
Dairy Cattle
Cowpea, forage
                                       R
                                      30
                                      20
                                      3.0
                                      2.0
Sorghum, forage/silage
                                       R
                                      35
                                      25
                                     0.20
                                     0.143
Sorghum, grain
                                      CC
                                      86
                                      45
                                     0.20
                                     0.105
Sunflower, meal
                                      PC 
                                      92
                                      10
                                      1.9
                                     0.207
TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     2.455
Poultry
Sorghum, grain
                                      CC
                                      86
                                      75
                                     0.20
                                     0.150
Sunflower, meal
                                      PC 
                                      92
                                      25
                                      1.9
                                     0.475
TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     0.625
Swine
Sorghum, grain
                                      CC
                                      86
                                      80
                                     0.20
                                     0.160
Barley, grain
                                      CC
                                      88
                                       5
                                     0.05
                                     0.003
Canola, meal
                                      PC 
                                      88
                                      15
                                      2.0
                                     0.300
TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     0.463
1  Table 1 (OCSPP Guideline 860.1000), ChemSAC memo dated June 30, 2008.  
2  Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle; contribution = ([tolerance] X % diet) for poultry and swine.

Ruminants

Dietary burdens of 2.70 and 2.72 ppm were previously calculated for beef and dairy cattle, respectively, in support of proposed uses on barley grain, hay, and straw; flax meal; sunflower meal; and wheat forage, grain, hay, straw, aspirated grain fractions, and milled byproducts (DP# 266204, S. Oonnithan, 7/24/2006).  A dairy cattle feeding study was submitted previously (PP# F3951, 12/18/87, G. Otakie, and PP# F3951, 3/4/92, J. Stokes).  In the study, three groups of three lactating dairy cows (plus a control group) were fed quizalofop ethyl ester at 0.1, 0.5, and 5.0 ppm in the diet for 28 consecutive days.  These levels corresponded to 0.04x, 0.19x, and 1.9x the calculated maximum theoretical dietary burden to beef and dairy cattle.  After re-calculating a "reasonably balanced" dietary burden, these levels correspond to 0.3x, 1.3x, and 13x the maximum reasonable dietary burden (MRDB) to beef cattle, 0.04x, 0.20x, and 2.0x the MRDB to dairy cattle, 0.2x, 1.1x and 10x the MRDB to swine.  Milk was collected daily, and a sub-sample was divided into skim milk and cream.  Two cows from each group were sacrificed after 28 days, and samples of fat, skeletal muscle, liver, and kidney were collected and analyzed.  The remaining cow in each test group was used to measure depuration, and was sacrificed 7 days after dosing finished.  The methods used for analysis converted residues of quizalofop ethyl and quizalofop-methyl to quizalofop; therefore, all reported residue results were expressed in terms of quizalofop.  Quizalofop residues in whole milk, skim milk, and cream from the control, and the 0.1- and 0.5-ppm dose groups were <0.01 ppm (<0.05 ppm in cream).  In samples from the 5-ppm dose group, quizalofop residues ranged 0.01-0.02 ppm in whole milk, reaching a plateau on the fourth day of dosing.  Quizalofop residues were found to partition into the cream samples from this group, with residues reaching plateaus of 0.26, 0.28, and 0.31 ppm after 2, 3, and 4 weeks of dosing, respectively.  Quizalofop residues were <0.02 ppm in skeletal muscle, and <0.05 ppm in liver, kidney, and fat samples from all three dose groups, with the exception of one kidney sample from the 5-ppm dose group which had quizalofop residues of 0.05 ppm.

Conclusions.  The available feeding study data indicate that the established tolerances for combined residues of quizalofop ethyl and its metabolites quizalofop and quizalofop-methyl in the fat, meat, and meat byproducts of cattle, goat, hog, horse, and sheep at 0.05 ppm for fat and meat byproducts and 0.02 ppm for meat are adequate and do not need to be revised based on the requested uses of quizalofop-P-ethyl.  Based on whole milk residues being 0.02 ppm at 2x feeding level, the established tolerance of 0.01 ppm for milk is still adequate.  Based on the maximum residues in milk of 0.02 ppm at a 2x dosing rate and an assumed 25x concentration factor for milk fat, expected residues at a 1x dosing rate would be 0.25 ppm; the established tolerance of 0.25 ppm for milk fat remains adequate.

Poultry

A poultry feeding study has been submitted and reviewed (PP#F3951, 12/18/87, G. Otakie).  Three groups of 20 hens per group (plus one control group) were dosed with quizalofop ethyl at 0.1, 0.5, and 5 ppm in the diet for 28 consecutive days; each dose group was subdivided into four subsets of five birds each.  These levels correspond to 0.20x, 1x, and 10x previously calculated maximum theoretical dietary burden.  After re-calculation, these levels correspond to 0.16x, 0.8x, and 8x the maximum reasonable dietary burden to poultry.  Eggs were collected daily.  After 28 days, 15 of the hens in each test group were sacrificed, and samples of fat, liver, kidney, breast and thigh muscles were collected and analyzed; tissues from each test group subset were pooled prior to analysis.  The remaining five hens in each test group were used to measure depuration, and were sacrificed 7 days after dosing finished.  The methods used for analysis converted residues of quizalofop ethyl and quizalofop-methyl to quizalofop; therefore, all reported residue results were expressed in terms of quizalofop.  Quizalofop residues were <0.05 ppm in liver samples and <0.02 ppm in breast and thigh muscle samples from all dose groups, and were <0.05 ppm in kidney and fat samples from the 0.1- and 0.5-ppm dose groups.  In samples from the 5-ppm dose group, quizalofop residues were 0.09 ppm in one pooled kidney sample, 0.05 and 0.06 ppm in two fat samples, and were <0.05 ppm in the other kidney and fat samples.  In eggs, residues were <0.02 ppm in all samples from all dose groups with the exception of one sample from the 5-ppm dose group which had quantifiable residues at 0.02 ppm. 

Conclusions.  The available feeding study data indicate that the established tolerances for combined residues of quizalofop ethyl and its metabolites quizalofop and quizalofop-methyl in egg at 0.02 ppm and the fat, meat, and meat byproducts of poultry at 0.05 ppm for fat and meat byproducts and 0.02 ppm for meat are adequate and do not need to be revised based on the requested uses of quizalofop-P-ethyl.


860.1500 Crop Field Trials

Residue Chemistry Memo DP# 266204, S. Oonnithan, 7/24/2006; PP# 0F6076 (flax)
Residue Chemistry Memo DP#s 220476, 220478, 220480, F. Griffith, 2/21/1996; PP#5F4545/FAP#6H5737 (canola)


Field Corn
DER References:  48260704.de1-quizalofop (AAD-1 field corn)

To support the use of quizalofop-P-ethyl (0.88 lb ai/gal EC formulation) on AAD-1 field corn containing DAS-40278-9, Dow Agrosciences has submitted field trial data for these commodities.  The results from these field trials are discussed below and summarized in Table 6.  We note that all crop field trials were conducted using a DuPont quizalofop-P-ethyl product (Assure II; 0.88 lb ai/gal EC; EPA Reg. No. 352-541).

Table 6.  Summary of Per Trial Average Residue Data from Crop Field Trials with Quizalofop-P-ethyl.
                       Field Corn containing DAS-40278-9
(Proposed Use:  0.083 lb ai/A total application rate, 30-day PHI for forage; plus adjuvant)
Crop matrix
                              Total Applic. Rate
                                   (lb ai/A)
                                  PHI (days)
               Total Quizalofop-P-ethyl Residue Levels (ppm)[1]



                                       n
                                  Sample Min.
                                  Sample Max.
                                   HAFT [2]
                                    Median
                                     Mean
                                   Std. Dev.
Corn, field, early forage
                                  0.078-0.088
                                     32-47
                                      24
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      ---
Corn, field, forage
                                       
                                     44-83
                                      24
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      ---
Corn, field, grain
                                       
                                    79-144
                                      25
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      ---
Corn, field, stover
                                       
                                    79-144
                                      25
                                   <0.02
                                   <0.022
                                   <0.022
                                     0.02
                                     0.02
                                      ---
1  Except for sample min/max, values reflect per trial averages; n = no. of field trials.  For calculation of median, mean, and standard deviation, the LOQ (0.01 ppm) was used for any results reported as ND (0.003 ppm) or between the LOD and LOQ in Table C.3.
[2]  HAFT = highest-average-field-trial.


Dow AgroSciences LLC has submitted field trial data for quizalofop-P-ethyl on field corn.  Twenty five field trials were conducted in the United States and Canada during the 2009 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (NJ and PA; 2 trials), 2 (GA; 2 trials), 5 (IA, IL, IN, KS, MI, MN, MO, NE, OH, and ON; 19 trials), and 6 (OK and TX; 2 trials). 

Each trial consisted of one untreated and two treated plots.  The treated plots were planted with hybrid field corn containing the Aryloxyalkanoate Dioxygenase-1 (AAD-1) gene.  Expression of the AAD-1 protein, which is encoded by the AAD-1 gene, provides tolerance to quizalofop-P-ethyl.  At each site, one treatment plot was planted with seed line Event DAS-40278-9 and the other treatment plot was planted with seed line Event DAS-40474-7.  Due to limited availability of the seed from the treated plots, the untreated plots were planted with field corn variety Mycogen 2M746 which is a hybrid field corn with a genetic background similar to the seed used at the treated plots.  The study indicated that the Sponsor discontinued development of AAD-1 Event DAS-40474-7 seed line; therefore, samples were collected from these plots but were not analyzed.  

The Event DAS-40278-9 treated plots received one broadcast foliar application of a 0.88 lb/gal emulsifiable concentrate (EC) formulation of quizalofop-P-ethyl (Assure II) at a target rate of 0.082 lb ai/A.  Applications were made using ground equipment in spray volumes of 20-33 gal/A.  A crop oil concentrate (COC) was added to the spray mixture for all applications; except for one site (MO-08) in which a non-ionic surfactant (NIS) was used.  HED prefers to have at least three side-by-side trials with the adjuvants recommended in the label; however, since residues with the NIS were below the LLMV, which was also the case for most trials with the COC, the three side-by-side trials will not be required.  The label should be modified to include the concentration of the adjuvant.  Three applications of 2,4-D dimethylamine salt (2,4-D DMA; Weedar[(R)] 64 Herbicide) were also made to the field corn with a non-ionic surfactant (NIS).  Two of the 2,4-D DMA applications were made before the quizalofop-P-ethyl application, including one as a pre-emergence application and one approximately 12 days before corn reached the V8 growth stage or 48 inch height.  One  2,4-D DMA application was made ~5 days after the quizalofop-P-ethyl application at approximately the V8 growth stage or 48 inch height.  Data pertaining to 2,4-D DMA are addressed under DP# 384441 (MRDI #48260704).  Field corn forage was harvested at two preharvest intervals (PHIs), reflecting early harvest before the typical growth stage to support a reduced PHI (targeted 40-day PHI) and typical harvest at the late-dough to early-dent stage (targeted 60-day PHI); grain and stover were harvested at maturity.  Based on the application of quizalofop-P-ethyl, PHIs were 32-47 days and 44-83 days for forage and 79-144 days for grain and stover.  Additional samples of forage, grain, and stover were collected from one trial each conducted in GA, MI, and OK at PHIs targeted at ~7 and 14 days before and after the desired PHI; for forage, the decline PHIs bracketed the second (60-day) PHI.

Samples were analyzed for residues of quizalofop-P-ethyl and quizalofop acid using a High Pressure Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) method detailed in the study.  The reported limit of quantitation (LOQ; determined as the lowest limit of method validation, LLMV) was 0.01 ppm for quizalofop-P-ethyl and quizalofop acid in all matrices.  The methods are adequate based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.

Samples were stored frozen (approximately -20 °C) from collection to extraction for analysis of quizalofop-P-ethyl and quizalofop acid for up to 376 days (12.4 months) for forage, 320 days (10.5 months) for grain, and 335 days (11.0 months) for stover.  Storage stability data for quizalofop-P-ethyl and quizalofop acid in/on field corn are not currently available; the petitioner indicated that a storage stability study with quizalofop-P-ethyl and quizalofop acid P in corn commodities was initiated in 2010 and will be submitted separately.

Following one foliar broadcast application of quizalofop-P-ethyl with an adjuvant at a total seasonal rate of 0.078-0.088 lb ai/A, residues of quizalofop-P-ethyl, quizalofop acid (parent equivalents) and total quizalofop-P-ethyl residues (sum of quizalofop-P-ethyl and quizalofop acid residues as parent equivalents) were below the LOQ (<0.01 ppm for individual analytes and <0.02 ppm for total analytes) in/on early forage (32-to 47-day PHI), forage (44- to 83-day PHI), and grain (79- to 144-day PHI).  In/on stover (79- to 144-day PHI), residues of quizalofop-P-ethyl were <0.01 ppm and residues of quizalofop acid were <0.01 to 0.012 ppm (per trial average residues were also <0.01 to 0.012 ppm).  Quizalofop acid was only detected above the LOQ in/on stover at one field trial.  Total quizalofop-P-ethyl residues in/on stover were <0.02 to 0.022 ppm.  

Residue decline on the three submitted studies (GA-04, MI-11, and OK-22) could not be assessed because the residues of quizalofop-P-ethyl and quizalofop acid were <LOQ in/on forage and grain samples and <LOQ or near the LOQ in/on the majority of the stover samples.
The results of the field corn crop field trials are presented in Table 6.

Conclusions. The submitted residue data for field corn commodities (forage, grain, and stover) 
are tentatively considered to be adequate, pending submission of storage stability data demonstrating the stability of quizalofop-P-ethyl and quizalofop acid in/on field corn forage, grain, and stover.  The number and locations of crop field trials are in accordance with OCSPP Guideline 860.1500. The field trials reflect the proposed use pattern.  However, the label should be modified to specify the concentration of the adjuvant used in the crop field trials, 1.25% (v/v).  The residue data were entered into the OECD MRL calculator (March 2011 version) to determine the appropriate tolerance levels; see Appendix I.  The OECD MRL calculator recommends tolerances of 0.02 ppm for corn forage and grain and 0.03 ppm for corn stover for total quizalofop-P-ethyl residues [sum of quizalofop-P-ethyl and quizalofop acid residues (as parent equivalents)].  The corn forage and grain recommendations are higher than the tolerance levels (0.01 ppm) proposed by the petitioner.  The corn stover recommendation is identical to the tolerance level proposed by the petitioner.

The submitted residue data for field corn are adequate to fulfill data requirements. 


Sorghum 
DER References:  48273601.der1 (sorghum)

To support the use of quizalofop-P-ethyl (0.88 lb ai/gal EC formulation) on sorghum, IR-4 has submitted field trial data for these commodities.  The results from these field trials are discussed below and summarized in Table 7.  We note that all crop field trials were conducted using a DuPont quizalofop-P-ethyl product (Assure II; 0.88 lb ai/gal EC; EPA Reg. No. 352-541).

Table 7.  Summary of Residue Data from Crop Field Trials with Quizalofop-P-ethyl.
 Sorghum grain containing the DuPont(TM) INZEN(TM) AII Herbicide Tolerance Trait
(Proposed Use:  0.138 lb ai/A total application rate, 30-day PHI for forage and 45-day PHI for grain and stover;
                                plus adjuvant)
Crop matrix
                              Total Applic. Rate
                                   (lb ai/A)
                                  PHI (days)
                 Total Quizalofop-P-ethyl Residue Levels (ppm)



                                       n
                                     Min.
                                    Max. 1
                                   HAFT [2]
                                    Median
                                     Mean
                                   Std. Dev.
Sorghum, forage
                                  0.136-0.145
                                     25-32
                                      13
                                   <0.104
                                   <0.180
                                   <0.169
                                     0.104
                                     0.112
                                     0.019
Sorghum, grain
                                       
                                     29-49
                                      12
                                   <0.104
                                   <0.158
                                   <0.149
                                     0.104
                                     0.111
                                     0.014
Sorghum, stover
                                       
                                     42-56
                                      13
                                   <0.104
                                   <0.266
                                   <0.212
                                     0.104
                                     0.129
                                     0.040
[1] The max value was determined from the individual samples 
[2] HAFT = Highest average field trial result.
n = number of field trials

IR-4 has submitted field trial data for quizalofop-P-ethyl on ACCase resistant grain sorghum.  Thirteen field trials were conducted in the United States during the 2009 growing season in Zones 2 (MD and NC; 2 trials), 4 (AR; 1 trial), 5 (KS and NE; 3 trials), 6 (TX; 2 trials), 7 (NE; 1 trial) and 8 (KS, NM, and TX; 4 trials). 

Each trial consisted of one untreated and one treated plot.  Each treated plot received a single broadcast or directed foliar application of a 0.88 lb ai/gal emulsifiable concentrate (EC) formulation of quizalofop-P-ethyl (Assure II; EPA Reg. No. 352-541) at a target rate of 0.138 lb ai/A.  Applications were made using ground equipment in spray volumes of 14.9-36.0 gal/A; an adjuvant (crop oil concentrate or non-ionic surfactant) was added to the spray mixtures at all trial sites.  Applications in all trials except one were performed with a crop oil concentrate (1% v/v) which is the preferred adjuvant recommended in the label.  A non ionic surfactant (0.25% v/v) was applied in the remaining trial.  HED prefers to have at least three side-by-side trials with the adjuvants recommended in the label; however, since the label specifies that the crop oil concentrate is the preferred adjuvant and residues with the non ionic surfactant were lower than those of with the crops oil concentrate the three side-by-side trials will not be required.  Samples of forage were harvested at a preharvest interval (PHI) of 25-32 days.  Grain and stover were harvested at 29- to 49-day and 42- to 56-day PHIs, respectively.  Additional forage samples were collected from trial TX08 at PHIs of 8, 14, 29 and 37 days to generate residue decline data.  

Additional samples were also collected from one trial (KS02) to conduct a processed food and feed study; refer to the 860.1520 DER for MRID 48273601 for the study details and results.

Samples of sorghum forage, grain, and stover were analyzed for residues of quizalofop-P-ethyl and quizalofop acid using an LC/MS/MS method modified from the method in Du Pont Study No. AMR-1854-90.  The lowest level of method validation (LLMV) for quizalofop-P-ethyl and quizalofop acid was 0.05 ppm for sorghum forage, grain, and stover.  The petitioner used the LLMV as the limit of quantitation (LOQ) for reporting residue results.  The method is adequate based on acceptable method validation and concurrent recovery data.  

Samples were stored frozen (approximately -20 °C) from harvest to analysis for quizalofop-P-ethyl and quizalofop acid for up to 227 days (7.5 months) for forage, 224 days (7.4 months) for grain, and 191 days (6.3 months) for stover; extracts were stored for up to 3 days prior to analysis for all samples.  Sample storage conditions and durations are supported by concurrent storage stability data.  However, zero-day data were not provided with the storage stability study.  IR-4 is reminded that storage stability studies should always include a zero-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].

The results of the sorghum crop field trials are presented in Table 6.  Following one foliar broadcast or direct application of quizalofop-P-ethyl at a total application rate of 0.136-0.145 lb ai/A, residues of quizalofop-P-ethyl were <LLMV (0.05 ppm) in/on forage (25- to 32-day PHI), grain (29- to 49-day PHI), and stover (42- to 56-day PHI).  Residues of quizalofop acid (as parent equivalents) were <0.054-0.130 ppm in/on forage, <0.054-0.108 ppm in/on grain and <0.054-0.216 ppm in/on stover.  Total quizalofop-P-ethyl residues (sum of quizalofop-P-ethyl and quizalofop acid residues (as parent equivalents)) were <0.104-<0.180, <0.104-<0.158 and <0.104-<0.266 ppm in/on forage, grain, and stover, respectively.

The submitted residue decline data indicate that residues of quizalofop acid (as parent equivalents) decreased in/on forage with increasing PHI.  Residues of quizalofop-P-ethyl in/on forage were <LLMV; therefore, residue decline could not be assessed.

Conclusions. The submitted residue data for sorghum commodities (forage, grain, and stover) are adequate to satisfy data requirements.  Trials were conducted according to the proposed use pattern, samples were analyzed for residues of residues of quizalofop-P-ethyl and quizalofop acid using an acceptable method, and adequate storage stability data were submitted to support the study.  The number and location of crop field trials are not in strict accordance with OCSPP 860.1500.  However, geographic representation of data is adequate considering the total number of field trials submitted (13 trials were submitted and 12 trials are required for sorghum).

The residue data for sorghum forage, grain, and stover were entered into the OECD MRL calculator (March 2011 version) to determine appropriate tolerance levels; see Appendix I.  The OECD MRL calculator recommends tolerances of 0.20, 0.20, and 0.30 ppm for total quizalofop-P-ethyl residues [sum of quizalofop-P-ethyl and quizalofop acid residues (as parent equivalents)] in/on sorghum forage, grain, and stover, respectively.  These recommendations are identical to the tolerance levels proposed by the petitioner for sorghum forage and grain.  The tolerance level recommendation for sorghum stover is slightly lower than the level (0.35 ppm) proposed by the petitioner.

Rapeseed Subgroup 20A, Except Flaxseed

IR-4 is proposing use of the 0.88 lb ai/gal EC formulation on mustard seed and other members of the rapeseed subgroup 20A, except flaxseed, as postemergence applications at a total seasonal application rate of 0.124 lb ai/A.  A 60-day PHI is proposed.

No new residue data were submitted in support of the label amendment request.  The petitioner has submitted a request to use acceptable field trial data for canola seed, the representative crop of subgroup 20A, that were previously reviewed under PP# 5F4545/FAP# 6H5737 (DP#s 220476, 220478, and 220480, F. Griffith, 2/21/96) in support of the proposed use on members of the rapeseed subgroup 20A, except flaxseed.  Currently tolerances are established for canola, seed at 1.0 ppm and flaxseed at 0.05 ppm. Acceptable field trial data for flaxseed for a different use pattern were previously reviewed in conjunction with a previous petition (DP# 266204, S. Oonnithan, 7/24/2006).

Table 8.  Summary of Residue Data from Crop Field Trials with Quizalofop-P-ethyl.
                    Rapeseed Subgroup 20A, Except Flaxseed
[includes Borage, Crambe, Cuphea, Echium, Gold of Pleasure (Camelina), Hare's ear mustard, Lesquerella, Lunaria, Meadowfoam, Milkweed, Mustard seed, Oil Radish, Poppy seed, Rapeseed (Canola), Sesame, and Sweet Rocket]
(Proposed Use:  0.124 lb ai/A total application rate, 60-day PHI; plus adjuvant)
Canola data available from a previous petition (PP#5F4545/FAP#6H5737; DP#s 220476, 220478, 220480, F. Griffith, 2/21/96)
Crop matrix
                              Total Applic. Rate
                                   (lb ai/A)
                                  PHI (days)
                 Total Quizalofop-P-ethyl Residue Levels (ppm)



                                       n
                                     Min.
                                     Max.
                                   HAFT [1]
                                    Median
                                     Mean
                                   Std. Dev.
Canola, seed
                                     0.094
                                     38-74
                                       9
                                   <0.05
                                      0.7
                                     0.65
                                     0.12
                                     0.19
                                     0.21
Canola, seed
                                     0.188
                                     38-74
                                       9
                                   <0.05
                                      1.5
                                      1.5
                                     0.25
                                     0.39
                                     0.46
n = number of field trials

A summary of residue data from the canola seed field trials is presented in Table 8.  The available data reflect nine field trials conducted in 1989.  Each trial had a one control plot and two test plots.  One canola test plot received a single broadcast ground spray at 1.5 oz ai/A (0.094 lb ai/A; ~0.8x proposed seasonal application rate) along with the surfactant.  The applica - tion was postemer - gence, when the canola was flowering, or at least 4 inches high.  The other canola plot received a single broadcast ground spray at a rate of 3 oz ai/A (0.188 lb ai/A; ~1.5x proposed seasonal application rate) with the surfactant.  Both the 0.8x and 1.5x applications were done at the same time.  One of the MN trials did not produce seed after the Assure(R) II application due to a lack of rain and an early frost.  The test sites in TN received the racemic Assure(R) application and the test site in the other four states received Assure(R) II containing the D+ isomer.  Neither of these situations affect the validity of the data presented.

Mature canola seeds were harvested at 38 to 74 days PHI.  Samples were promptly frozen and remained frozen until preparation and analysis.  Samples were analyzed by the residue analytical methods which have adequate validation and concurrent recovery data for quizalofop ethyl ester and the phenol metabolites.  Residues of quizalofop and phenols 2 and 4 were not detected to the LOQ of 0.05 ppm in any of the control canola seeds.  From the 0.8x application, detect - able quizalofop residues ranged from < 0.05 ppm (3 trials) to 0.7 ppm, averaging 0.22 +- 0.22 ppm (n = 12).  The highest average field trial (HAFT) for the 0.8x application is 0.65 ppm.  From the 1.5x applica - tion, quizalofop residues ranged < 0.05 ppm (2 trials) to 1.5 ppm, averaging 0.45 +- 0.44 ppm.  No phenol 2 or phenol 4 residues were detected in any of the canola seed samples from the 0.8x and 1.5x appli - cations at any of PHIs.  

Based on the available data, a tolerance for canola seed was established at 1.0 ppm.  However, since proportionality is observed between the application rate, 0.10 lb ai/A and 0.20 lb ai/A, and the average residues, 0.22 ppm and 0.45 ppm, respectively, we adjusted the field trial residue data to reflect the residues that may be expected after application of the proposed rate (0.124 lb ai/A).  The residues originally reported as quizalofop acid equivalents were converted to quizalofop-P-ethyl equivalents, adjusted for the application rate, and included in the OECD calculator to estimate a tolerance of 1.5 ppm.  

Conclusions.  Previously separate tolerances for individual members of a subgroup were required in the appropriate section of the CFR entry until the new crop group regulation for the Rapeseed Subgroup 20A is published in the Federal Register.  Recently, the final rule (75 FR 76284-76292, December 8, 2010) for the pesticide tolerance crop grouping regulations which allow establishment of tolerances for multiple related crops, based on data from a representative set of crops, created a new crop group for Oilseed and also established a Rapeseed Subgroup 20A.

The available field trial data for canola seed, the representative crop of the rapeseed subgroup 20A, may be translated to support the proposed uses on mustard seed and other members of the rapeseed subgroup 20A, except flaxseed.  These data are adequate to fulfill data requirements and reflect ~0.8-1.6x the maximum proposed seasonal application rate for the EC formulation with 38- to 74-day PHI.  A new tolerance of 1.5 ppm will support use of the 0.88 lb/gal EC formulation.

HED, therefore, recommends a tolerance of 1.5 ppm for residues of quizalofop and its metabolites, all expressed as quizalofop-P-ethyl in/on rapeseed subgroup 20A, except flaxseed based on residue data from canola seed.  Individual tolerances for each member of the subgroup are no longer required because the Rapeseed Subgroup 20A may be published in the Federal Register.  The petitioner is required to submit a revised Section F to reflect this determination.


860.1520 Processed Food and Feed


Field Corn
DER References:  48260704.de2-quizalofop (AAD-1 field corn)

Dow AgroSciences LLC has submitted a processing study for quizalofop-P-ethyl on hybrid field corn containing the inserted aryloxyalkanoate dioxygenase-1 (AAD-1) gene (seed line Event DAS-40278-9).  Expression of the AAD-1 protein, which is encoded by the AAD-1 gene, provides tolerance to quizalofop-P-ethyl.  In two trials conducted in GA and NE during the 2009 growing season, one broadcast foliar application of a 0.88 lb/gal emulsifiable concentrate (EC) formulation of quizalofop-P-ethyl (Assure II) was made to field corn at a target rate of 0.164 lb ai/A (~2x the proposed maximum seasonal rate).  Applications were made using ground equipment in spray volumes of 22-31 gal/A with an adjuvant (crop oil concentrate; COC) at both trial sites.  Three applications of 2,4-D dimethylamine salt (2,4-D DMA; Weedar[(R)] 64 Herbicide) were also made to the field corn with a non-ionic surfactant (NIS).  Two of the 2,4-D DMA applications were made before the quizalofop-P-ethyl application, including one as a pre-emergence application and one approximately 12 days before corn reached the V8 growth stage or 48 inch height.  One  2,4-D DMA application was made ~5 days after the quizalofop-P-ethyl application at approximately the V8 growth stage or 48 inch height.  Data pertaining to 2,4-D DMA are addressed under DP# 384441 (MRID #48260704). Field corn grain was harvested at maturity, 79 days following the quizalofop-P-ethyl application at the GA site and 140 days after the quizalofop-P-ethyl application at the NE site.  Field corn grain raw agricultural commodity (RAC) samples were processed into field corn starch, refined oil (wet milling), refined oil (dry milling), meal, grits, flour, and aspirated grain fractions (AGF) using procedures simulating commercial processing.

The maximum theoretical concentration factor for corn is 25x based on separation into components in corn oil (OCSPP 860.1520 Tables 1 and 3).  An exaggerated rate of at least 5x is recommended in the guideline.  However, the petitioner noted that the application rate used in the study was only 2x that used in the corresponding crop field trials (refer to the 860.1500 DER for MRID 42860704) due to concerns over the potential for crop injury.  

Samples of field corn grain RAC and processed commodities were analyzed for residues of quizalofop-P-ethyl and quizalofop acid using a High Pressure Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) method detailed in the study.  The reported limit of quantitation (LOQ; determined as the lowest limit of method validation, LLMV) was 0.01 ppm for quizalofop-P-ethyl and quizalofop acid in all matrices.  The methods are adequate based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.

Samples were stored frozen (~-20 °C) from harvest/collection to extraction for analysis of quizalofop-P-ethyl and quizalofop acid for up to 199 days (6.5 months) in field corn grain, meal, grits, and flour; 194 days (6.4 months) in starch, 191 days (6.3 months) in refined oil (dry milling); 186 days (6.1 months) in refined oil (wet milling); and 182 days (6.0 months) in AGF.  Storage stability data for quizalofop-P-ethyl and quizalofop acid in/on field corn and processed commodities are not currently available; the petitioner indicated that a storage stability study with quizalofop-P-ethyl and quizalofop acid P in corn commodities was initiated in 2010 and will be submitted separately.

A summary of residue data from the field corn processing study is presented in Table 9.  Residues of quizalofop-P-ethyl and quizalofop acid (as parent equivalents) in/on field corn grain RAC were <LOQ (<0.01 ppm) at each trial following one application of quizalofop-P-ethyl at a target rate of 0.164 lb ai/A.  Processing factors for quizalofop-P-ethyl, quizalofop acid, and total quizalofop-P-ethyl in field corn processed commodities (starch, refined oil (wet and dry milling), meal, grits, flour, and AGF) could not be calculated because residues were also <LOQ in these matrices.









Table 9.	Residue Data from Field Corn Processing Study with Quizalofop-P-ethyl.
RAC
                              Processed Commodity
                                  Total Rate
                                   (lb ai/A)
                                     PHI 
                                    (days)
                                Residues (ppm)
                             Processing Factor[3]

                                       
                                       
                                       
                              Quizalofop. P-ethyl
                              Quizalofop acid[1]
                         Total Quizalofop. P-ethyl[2]
                                  Quizalofop
                                    P-ethyl
                              Quizalofop acid[1]
                         Total Quizalofop. P-ethyl[2]
                                  Trial GA-03
Field Corn
                                  Grain (RAC)
                                     0.164
                                      79
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                    (0.003)
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      --
                                      --
                                      --

Grain (from the processor prior to AGF generation)
                                       
                                       
                                      ND
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      --
                                      --
                                      --

Grain
(from the processor after AGF generation)
                                       
                                       
                                      ND
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      --
                                      --
                                      --

Starch
                                       
                                       
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                     NC[4]
                                      NC
                                      NC

Refined oil (wet milling)
                                       
                                       
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Refined oil (dry milling)
                                       
                                       
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Meal
                                       
                                       
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Grits
                                       
                                       
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Flour
                                       
                                       
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

AGF
                                       
                                       
                                      ND
                                      ND
                                   <0.02
                                      NC
                                      NC
                                      NC
                                  Trial NE-14
Field Corn
                                  Grain (RAC)
                                     0.163
140
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      ---
                                      ---
                                      ---

Grain (from the processor prior to AGF generation)


                                      ND 
                                    (0.004)
                                      ND
                                  [<0.01]
                                  ND, (0.005)
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      ---
                                      ---
                                      ---

Grain
(from the processor after AGF generation)


                                      ND
                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      ---
                                      ---
                                      ---

Starch


                                      ND
                                    (0.005)
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Refined oil (wet milling)


                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Refined oil (dry milling)


                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Meal


                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Grits


                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

Flour


                                      ND
                                      ND
                                  [<0.01]
                                      ND
                                      ND
                                  [<0.01]
                                   <0.02
                                   <0.02
                                  [<0.02]
                                      NC
                                      NC
                                      NC

AGF


                                      ND
                                      ND
                                   <0.02
                                      NC
                                      NC
                                      NC
[1]  ND = <LOD (<0.003 ppm).  The LOQ was 0.01 ppm for each analyte.  Residues between the LOD and LOQ are reported in parentheses and averages are reported in brackets.  When calculating averages, the LOQ was used for values reported as ND or between the LOD and LOQ.
2  Quizalofop acid reported as parent equivalent (quizalofop acid result x 1.0814)
[3] Total quizalofop-P-ethyl residues = residues of quizalofop-P-ethyl + quizalofop acid (in parent equivalents).
[4]  NC = Not calculated.  The processing factor could not be calculated because residues were below the LOQ in the RAC and the processed fraction.

Conclusions.  The submitted processing data for field corn are tentatively considered to be adequate, pending submission of storage stability data demonstrating the stability of quizalofop-P-ethyl and quizalofop acid in/on field corn grain starch, refined oil, meal, grits, flour, and AGF stored frozen for up to 6.0-6.5 months.  The results of submitted field corn processing study show that residues of quizalofop-P-ethyl and quizalofop acid (as parent equivalents) in/on field corn grain RAC at each trial were <LOQ (<0.01 ppm) following one application at a target rate of 0.164 lb ai/A (~2x the proposed maximum seasonal rate).  Processing factors for quizalofop-P-ethyl, quizalofop acid, and total quizalofop-P-ethyl in field corn processed commodities (starch, refined oil (wet and dry milling), meal, grits, flour, and AGF) could not be calculated because residues were also <LOQ in these matrices.  The Agency would have preferred the use of exaggerated rates in the conduct of the processing study to yield a RAC with quantifiable residues; however, the petitioner noted that the application rate used in the study was only 2x due to concerns over the potential for crop injury.


Sorghum, Aspirated Grain Fractions
DER References:  48273601.der2 (sorghum)

IR-4 has submitted a processing study for quizalofop-P-ethyl on ACCase resistant grain sorghum.  In one crop field trial conducted in 2009 in KS, sorghum samples were harvested 48 days after a single broadcast foliar application of a 0.88 lb/gal emulsifiable concentrate (EC) formulation of quizalofop-P-ethyl (Assure II; EPA Reg. No. 352-541) at a  rate of 0.139 lb ai/A (1x field application rate).  The sorghum grain samples were processed into aspirated grain fractions (AGF) by GPL Technologies (Navasota, TX).  Adequate descriptions were provided of the processing procedures, including material balance summaries.

The sorghum grain and AGF samples were analyzed for residues of quizalofop-P-ethyl and quizalofop acid using an LC/MS/MS method modified from the method in Du Pont Study No. AMR-1854-90.  The lowest level of method validation (LLMV) for quizalofop-P-ethyl and quizalofop acid was 0.05 ppm for sorghum grain and AGF.  The petitioner used the LLMV as the limit of quantitation (LOQ) for reporting residue results.  The method is adequate based on acceptable method validation and concurrent recovery data.  

Samples were stored frozen (approximately -20 °C) prior to processing and analysis.  The maximum storage duration for the sorghum grain raw agricultural commodity (RAC) was 116 days (3.8 months) from harvest to analysis and the maximum storage duration for AGF was 110 days (3.6 months) from processing to analysis.  Sample storage conditions and durations are supported by concurrent storage stability data.  However, zero-day data were not provided with the storage stability study.  IR-4 is reminded that storage stability studies should always include a zero-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].

Residues of quizalofop-P-ethyl, quizalofop acid (as parent equivalents), and total quizalofop-P-ethyl [sum of quizalofop-P-ethyl and quizalofop acid (as parent equivalents)] were <0.05, 0.108, and <0.158 ppm, respectively, in/on sorghum grain RAC.  The processing data indicate that residues of quizalofop acid and total quizalofop-P-ethyl may concentrate (processing factors of 4.5x and 3.4x, respectively) in AGF.  The processing factors for quizalofop-P-ethyl could not be calculated because the results in/on the RAC and the processed commodity were less than the LLMV.

Table 10.	Residue Data from Sorghum Processing Study with Quizalofop-P-ethyl.
RAC
                              Processed Commodity
                                  Total Rate
                                   (lb ai/A)
                                     PHI 
                                    (days)
                                Residues (ppm)
                             Processing Factor[3]

                                       
                                       
                                       
                              Quizalofop. P-ethyl
                              Quizalofop acid[1]
                         Total Quizalofop. P-ethyl[2]
                                  Quizalofop
                                    P-ethyl
                              Quizalofop acid[1]
                         Total Quizalofop. P-ethyl[2]
Sorghum
Grain (RAC)
                                     0.139
                                      48
                                   <0.05
                                     0.108
                                   <0.158
                                      ---
                                      ---
                                      ---

AGF
                                       
                                       
                                   <0.05
                                     0.49
                                   <0.54
                                     NC[4]
                                     4.5x
                                     3.4x
1   Quizalofop acid reported as parent equivalent (quizalofop acid result x 1.0814)
2   Total quizalofop-P-ethyl residues = residues of quizalofop-P-ethyl + quizalofop acid (in parent equivalents). 
3   Processing factors were calculated using the equation: Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the RAC prior to processing].  
[4]  NC = Not calculated.  The processing factor could not be calculated because residues were below the LLMV in the RAC and the processed fraction.

Conclusions.  The submitted sorghum processing study is adequate to satisfy data requirements.  The processing data indicate that total quizalofop-P-ethyl residues concentrate in AGF.  Based on the processing factor, 3.4x, and the HAFT for sorghum grain, 0.149 ppm, expected residues in sorghum AGF following treatment at 1x would be 0.507 ppm.  Because this value is greater than the recommended 0.2-ppm tolerance for sorghum grain, a tolerance is needed for total quizalofop-P-ethyl residues in/on sorghum, grain, aspirated grain fractions.  A tolerance of 1.0 ppm would be appropriate.  This recommendation is identical to the tolerance level proposed by the petitioner.

Crambe, Meal and Gold of Pleasure, Meal
Residue Chemistry Memo DP#s 220476, 220478, 220480, F. Griffith, 2/21/1996; PP#5F4545/FAP#6H5737 (canola)

No new processing data were submitted in support of the label amendment request to expand the use of quizalofop on members of the rapeseed subgroup 20A, except flaxseed, that may be processed (crambe and gold of pleasure).  Acceptable processing data were previously submitted and reviewed for canola seed, the representative crop of subgroup 20A, under PP# 5F4545/FAP# 6H5737 (DP#s 220476, 220478, and 220480, F. Griffith, 2/21/96).  Based on the available canola processing data, processing factor for canola meal was established as 2.3x; a processing factor was not required for refined oil. By using the HAFT (0.65 ppm) and adjusting for the application rate (0.806x), a tolerance of 2 ppm is calculated.

Conclusion:  HED concludes that the available canola processing data and the established processing factor for canola meal may be translated to rapeseed meal.  Separate tolerances for crambe meal and gold of pleasure meal need are covered by the tolerance recommended (2 ppm) for rapeseed meal.


860.1650 Submittal of Analytical Reference Standards

Analytical standards from DuPont for quizalofop-P-ethyl (expiration date 8/18/2014), quizalofop acid (expiration date 12/8/2019), and quizalofop-P-methyl (expiration date 3/28/2018) are currently available in the National Pesticide Standards Repository (personal communication with Theresa Cole, ACB, 8/2/11).


860.1850/860.1900 Confined/Field Accumulation in Rotational Crops

Residue Chemistry Memo DP#s 219672 and 222000, F. Griffith, 1/26/1996; PP#5E4590

Adequate confined rotational crop studies were submitted previously.  In the studies, rotational crops of red beets, lettuce, wheat, peanuts, and cotton were planted 30 and 62 days following treatment of the soil with [phenyl-[14]C]quizalofop ethyl and [quinoxaline-[14]C]quizalofop ethyl.  Over 50% of the residues in rotational crops were characterized and identified; the studies indicate that the metabolic pathway in rotational crops is the same as for primary crops.  Total quizalofop residues were 0.032-0.104 ppm in rotational crop commodities from the 30-day PBI and 0.045-0.071 ppm in rotational crop commodities from the 62-day PBI.  HED concluded that a 120-day PBI is needed for quizalofop-P-ethyl (DP#s 219672 and D222000, 1/26/96, F. Griffith).

860.1900 Field Accumulation in Rotational Crops

Because the proposed label includes a 120-day PBI, no field rotational crop studies are needed.

860.1550 Proposed Tolerances

The Agency has previously determined that the ROC in plant commodities are quizalofop-P-ethyl, its acid metabolite quizalofop-P, and the S-enantiomers of both compounds, each expressed as quizalofop-P-ethyl.  The ROC in livestock commodities are quizalofop ethyl, quizalofop-methyl, and quizalofop, expressed as quizalofop.

No Codex MRLs have been established for residues of quizalofop ethyl.  Canadian MRLs have been established for residues of quizalofop ethyl and quizalofop in/on flax, oriental mustard seeds (condiment type and oil seed type), and rapeseeds (canola), the only crops included in the subject petition, at 0.05 ppm.  No Mexican MRLs have been established for any of the requested crops.  An International Residue Limit status sheet is attached.


Field Corn

An adequate number of field trials at ~1x the proposed use rate are available for corn forage, grain, and stover.  The OECD MRL calculator (March 2011 version) was utilized for determining appropriate tolerance levels for RACs that were treated according to the proposed use patterns; see Appendix I for tolerance calculations.

Adequate processing data for corn have been submitted.  Tolerances for the processed commodities of corn are not needed for the purpose of this petition based on the results of processing trials which showed that residues of quizalofop-P-ethyl and quizalofop acid (as parent equivalents) were <LOQ in/on field corn grain RAC (treatment at ~2x the proposed maximum seasonal rate), and in field corn processed commodities [starch, refined oil (wet and dry milling), meal, grits, flour, and AGF].  The petitioner mentions that concerns of phytotoxicity preclude corn processing studies at higher rates.  

A summary of the recommended tolerances from the current petition is presented in Table 8.  The petitioner should submit a revised section F reflecting the recommended tolerances and commodity definitions presented in Table 11.  These new tolerances should be included in the revised 40 CFR § 180.441 (a)(1).

Table 11. 	Tolerance Summary for Quizalofop-P-ethyl.
Commodity
                                Tolerance (ppm)
Comments; Correct Commodity Definition

                                   Proposed
                                  Recommended

Corn, forage
                                     0.01
                                     0.02
Corn, field, forage
Corn, grain
                                     0.01
                                     0.02
Corn, field, grain
Corn, stover
                                     0.03
                                     0.03
Corn, field, stover


Sorghum and Rapeseed Subgroup 20A (except flaxseed)

An adequate number of field trials at ~1x the proposed use rate are available for sorghum forage, grain, and stover.  The OECD MRL calculator (March 2011 version) was utilized for determining appropriate tolerance levels for RACs which showed quantifiable residues in/on samples that were treated according to the proposed use patterns; see Appendix I for tolerance calculations.

Adequate processing data for sorghum have been submitted.  The processing data indicate that total quizalofop-P-ethyl residues concentrate in sorghum AGF.  Based on the processing factor, 3.4x, and the HAFT for sorghum grain, 0.149 ppm, expected residues in sorghum AGF following treatment at 1x would be 0.507 ppm.  Because this value is greater than the recommended 0.2-ppm tolerance for sorghum grain, a tolerance is needed for total quizalofop-P-ethyl residues in/on sorghum, grain, aspirated grain fractions.  A tolerance of 1.0 ppm would be appropriate.  

Recently the final rule (75 FR 76284-76292, December 8, 2010) was published for the pesticide tolerance crop grouping regulations which allow establishment of tolerances for multiple related crops, based on data from a representative set of crops, created a new crop group for Oilseed and also established a Rapeseed Subgroup 20A.  HED, therefore, tentatively recommends a tolerance of 1.5 ppm for residues of quizalofop and its metabolites, all expressed as quizalofop-P-ethyl in/on rapeseed subgroup 20A, except flaxseed based on available residue data from canola seed.  Individual tolerances for each member of the subgroup are no longer required.  Canola seed is a member of crop subgroup 20A.  Pending revision of 40 CFR §180.441(a)(3), a separate tolerance for canola seed may be removed.

The available canola processing data and the established processing factor for canola meal were used to calculate a tolerance of 2 ppm for rapeseed meal.  Separate tolerances for crambe meal and gold of pleasure meal need not be established.

HED recommends the amendment of the tolerances in 40 CFR part 180.441 by combining the tables for sections (a)(1) and (a)(3) into one table under section (a)(1), and by removing section  (a)(3).   Also, the tolerance expressions under section (a)(1), (a)(2) and (c) can be modified as follows:  

Section (a)(1): "Tolerances are established for residues of the herbicide quizalofop ethyl, including its 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 those quizalofop ethyl residues convertible to 2-methoxy-6-chloroquinoxaline, expressed as the stoichiometric equivalent of quizalofop ethyl, in or on the commodity."  

Section (a)(2): "Tolerances are established for residues of the herbicide quizalofop ethyl, including its 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 those quizalofop ethyl residues convertible to quizalofop (2-[4-(6-chloroquinoxalin-2-yl-oxy)phenoxy]propanoic acid), expressed as quizalofop, in or on the commodity."

Section (c): "Tolerances with regional registrations. Tolerances with regional registration are established for residues of the herbicide quizalofop ethyl, including its 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 those quizalofop ethyl residues convertible to 2-methoxy-6-chloroquinoxaline, expressed as the stoichiometric equivalent of quizalofop ethyl, in or on the commodity."

A summary of the recommended tolerances from the current petition is presented in Table 8.  The petitioner should submit a revised section F reflecting the recommended tolerances and commodity definitions presented in Table 12.  These new tolerances should be included in the revised 40 CFR § 180.441 (a)(1).

Table 12. 	Tolerance Summary for Quizalofop-P-ethyl.
Commodity
                                Tolerance (ppm)
Comments; Correct Commodity Definition

                                Established[1]
                                   Proposed
                                  Recommended

Canola, seed
                                      1.0
                                      --
                                    Removed
HED recommends a tolerance of 1.5 ppm for residues of quizalofop and its metabolites, all expressed as quizalofop-P-ethyl in/on rapeseed subgroup 20A, except flaxseed, based on available residue data from canola seed.  Individual tolerances for each member of the subgroup are no longer required because the Rapeseed Subgroup 20A has been published in the Federal Register (75 FR 76284-76292, December 8, 2010).
Gold of Pleasure, seed
                                      --
                                      1.0
                                  Not needed

Borage, seed
                                      --
                                      1.0
                                  Not needed

Crambe, seed
                                      --
                                      1.0
                                  Not needed

Cuphea, seed
                                      --
                                      1.0
                                  Not needed

Echiuim, seed
                                      --
                                      1.0
                                  Not needed

Hare's ear mustard, seed
                                      --
                                      1.0
                                  Not needed

Lesquerella, seed
                                      --
                                      1.0
                                  Not needed

Lunaria, seed
                                      --
                                      1.0
                                  Not needed

Meadowfoam, seed
                                      --
                                      1.0
                                  Not needed

Milkweed, seed
                                      --
                                      1.0
                                  Not needed

Mustard, seed
                                      --
                                      1.0
                                  Not needed

Oil Radish, seed
                                      --
                                      1.0
                                  Not needed

Poppy, seed
                                      --
                                      1.0
                                  Not needed

Rapeseed
                                      --
                                      1.0
                                  Not needed

Sesame, seed
                                      --
                                      1.0
                                  Not needed

Sweet Rocket, seed
                                      --
                                      1.0
                                  Not needed

Canola, meal
                                      1.5
                                      --
                                    Remove
The available canola processing data was translated to the rapeseed subgroup 20A to calculate and propose a tolerance for the meal.
Rapeseed, subgroup 20A, meal, except flaxseed
Rapeseed, subgroup 20A, except flax, meal
                                       
                                       
                                      2.0

Gold of Pleasure, meal
                                      --
                                      1.5
                                  Not needed

Crambe, meal
                                      --
                                      1.5
                                  Not needed

Sorghum, grain
                                      --
                                      0.2
                                     0.20
Sorghum, grain, grain
Sorghum, forage
                                      --
                                      0.2
                                     0.20
Sorghum, grain, forage
Sorghum, stover
                                      --
                                     0.35
                                     0.30
Sorghum, grain, stover
Sorghum, aspirated grain
                                      --
                                      1.0
                                      1.0
Sorghum, grain, aspirated grain fractions
                      Tolerance that need to be proposed
Rapeseed, subgroup 20A, except flaxseed
                                      --
                                      --
                                      1.5
Canola seed is a member of crop subgroup 20A.  Pending revision of 40 CFR §180.441(a)(3), a separate tolerance for canola seed may be removed.
Rapeseed, subgroup 20A, except flaxseed
[1] Under 40 CFR §180.441(a)(3).



Milk, Meat, Egg and Poultry

Based on the results of the available ruminant feeding study and a re-calculated 1x maximum reasonable dietary burdens of 2.455 ppm for dairy cattle, the established tolerances for combined residues of quizalofop ethyl and its metabolites quizalofop and quizalofop-methyl in the fat, meat, and meat byproducts of cattle, goat, hog, horse, and sheep at 0.05 ppm for fat and meat byproducts and 0.02 ppm for meat are adequate and do not need to be revised based on the requested uses of quizalofop-P-ethyl.  Based on whole milk residues being 0.02 ppm at 2x feeding level, the established tolerance of 0.01 ppm for milk is still adequate.  Based on the maximum residues in milk of 0.02 ppm at a 2x dosing rate and an assumed 25x concentration factor for milk fat, expected residues at a 1x dosing rate would be 0.25 ppm; the established tolerance of 0.25 ppm for milk fat remains adequate.

The available poultry feeding study data indicate that the established tolerances for combined residues of quizalofop ethyl and its metabolites quizalofop and quizalofop-methyl in egg at 0.02 ppm and the fat, meat, and meat byproducts of poultry at 0.05 ppm for fat and meat byproducts and 0.02 ppm for meat are adequate and do not need to be revised based on the requested uses of quizalofop-P-ethyl.


Tolerance Expressions

On 27/May/2009 HED established interim guidance on writing tolerance expressions for enforcement purposes.  In order to add clarity to the language used to establish the coverage of the tolerance expression and measurement of the level of the residue in the RACs the text in the 40 CFR § 180.441 (a)(1) should read:  "Tolerances are established for the combined residues of the herbicide quizalofop ethyl, including its 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 quizalofop (2-[4-(6-chloroquinoxalin-2-yl oxy)phenoxy]propanoic acid) and quizalofop ethyl (ethyl-2-[4-(6-chloroquinoxalin-2-yl oxy)phenoxy]propanoate), all expressed as quizalofop ethyl."

For tolerances on meat, milk and poultry, the text in the 40 CFR § 180.441 (a) (2) should read:  "Tolerances are established for the combined residues of the herbicide quizalofop-P-ethyl, including its 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 quizalofop (2-[4-(6-chloroquinoxalin-2-yl-oxy)phenoxy]propanoic acid), quizalofop ethyl (ethyl-2-[4-(6-chloroquinoxalin-2-yl-oxy)phenoxy]propanoate), and quizalofop-methyl (methyl 2-[4-(6-chloroquinoxalin-2-yloxy)phenoxy]propanoate), all expressed as quizalofop ethyl"

In addition, the text in the 40 CFR § 180.441 (a)(3) should read:  "Tolerances are established for the combined residues of the herbicide quizalofop-P-ethyl, including its 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 quizalofop-P-ethyl ester [ethyl (R)-(2-[4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propanoate] and its acid metabolite, quizalofop-P [R-ethyl(ethyl-2-[4-(6-quinoxalin-2-yl)oxy)phenoxy)propanoic acid], and the S enantiomers of both the ester and the acid, all expressed as quizalofop-P-ethyl ester."

References

CB No.:	1127
Subject:	PP# 5F3252 [RCB # 1127].  DPX-Y6202 (Assure(R)) Herbicide on Cotton and Soybeans.  Evaluation of Analytical Methodology and Residue Data (Accession Nos. 073529 and 073547).
From:		M. Firestone
To:		R. Taylor and Toxicology Branch
Date:		9/25/1985
MRIDs:	[Accession Nos. 073529 and 073547]


CB Nos.:	2806, 2806, 2810, and 2811
Subject:	PP# 5F3252/FOP # 6H5479 Quizalofop ethyl (Assure(R)) on Soybeans. Amendment Dated August 31, 1987
From:		G. Otakie
To:		R. Taylor and Toxicology Branch
Date:		12/18/1987
MRIDs:	40322401-40322413, 40336201, and 40337101


CB No.:	None
Subject:	PP# 3F3252/FAP # 6H5479 Ethyl 2-[4-(6-chloroquinoxalin-2-yl oxy)phenoxy] Propanoate (Quizalofop ethyl) on Soybeans, Liver, and Milk - Results from EPA Method Validation Dated May 25, 1988
From:		G. Otakie
To:		R. Taylor
Date:		6/27/1988
MRIDs:	None


CB Nos.:	5852 & 5853
Subject:	Quizalofop-P-ethyl [D+ isomer]/Assure(R) II:  DuPont registration proposal (I.D.Nos. 352-LUE and 352-LUR; Record Nos. 250157 and 250158)
From:		W. Hazel
To:		R. Taylor	
Date:		3/29/1990
MRIDs:	41224001 & 41206101-41206103


DP#s:		160972 & 166083
Subject:	PP# 1F3951.  Quizalofop ethyl ester in/on cottonseed.  Evaluation of Analytical Method and Residue Data.  CBTS #'s 7640, 7641, 8229.
From:		J. Stokes
To:		R. Taylor and Toxicology Branch
Date:		3/4/1992
MRIDs:	41735401-41735403 & 41919801


DP#:		182751
Subject:	Quizalofop-P-ethyl ester.  Comparison of the Metabolism of DPX-79376, the R Enantiomer, Optically Active Ingredient, and DPX-Y6202, the Racemic Mixture, in Soybeans.  CB# 10606.
From:		J. Stokes
To:		R. Taylor
Date:		7/15/1993
MRID:		42643201


DP#s:		196041, 196043, 205430, 205432, 206201, 206200, & 212620-212622
Subject:	PP # 3F4268 - Quizalofop-P-ethyl Ester (Assure(R) II) On The Legume Vegetables (Succulent Or Dried) And Foliage Of Legume Vegetables Crop Groups, Sugar beet Tops, Roots, Molasses, and Cottonseed.  Review of Magnitude of the Residue Data and Residue Analytical Method and the February 22, 1995, Amendment.  [CBTS #s 12699, 12700, 14060, 14061, 14148, 14149, and 15196-98]
From:		F. Griffith
To:		R. Taylor and J. Smith
Date:		3/30/1995
MRIDs:	42827501-42827509, 43314001, & 42439101


DP#:		219639
Subject:	PP # 3F4268 - Quizalofop-P-ethyl ester (Assure(R) II) on Legume Vegetables (Succulent or Dried) and Foliage of Legume Vegetables Crop Group, Sugar beet Tops, Roots, and Molasses, and Cottonseed.  Evaluation of the Analytical Chemistry Laboratory Prereview of the Tolerance Method Validations for Quizalofop-P-ethyl Ester. [CBTS # 16260]
From:		F. Griffith
To:		R. Taylor and D. Marlow
Dated:		10/11/1995
MRIDs:	43314001 and 42927509


DP#s:		219672 and 222000
Subject:	PP # 5E4590 - Quizalofop-P-ethyl ester (Assure(R) II) on Pineapples.  Review of Magnitude of the Residue Data and Residue Analytical Method. [CBTS # 16279 and 16681].
From:		F. Griffith
To:		H. Jamerson and K. Whitby
Dated:		1/26/1996
MRIDs:	43782501


DP#s:		220215, 220216, and 220217
Subject:	PP # 3F4268/5H5720 - Quizalofop-P-ethyl ester (Assure(R) II) on the Legume Vegetables (Succulent or Dried) and Foliage of Legume Vegetables Crop Groups, Sugar beet Tops, Roots, Molasses, and Cottonseed.  Review of the July 27, Sept., 22 and 26, 1995, Amendments.  [CBTS #s 16400, 16401, and 16402].
From:		F. Griffith
To:		R. Taylor and K. Whitby
Dated:		2/13/96
MRID:		43804101


DP#s:		220476, 220478, and 220480
Subject:	PP # 5F4545/FAP # 6H5737 - Quizalofop-P-ethyl Ester (Assure(R) II) on the Foliage Of Legume Vegetables (Except Soybeans) Crop Group, Canola And Canola Processed Commodities.  Review of Magnitude of the Residue Data and Residue Analytical Method.  [CBTS #s 16392, 16393, and 16394]
From:		F. Griffith
To:		R. Taylor and K. Whitby
Date:		2/21/1996
MRIDs:	43695701 and 43695702


DP#:				266204
Subject:		Quizalofop-P-ethyl:  New Uses on Barley, Wheat, Sunflower, and Flax.  Summary of Analytical Chemistry and Residue Data.
From:			S. Oonnithan
To:				J. Tompkins
Dated:			7/24/2006
MRID(s):		44967701-05, 45089201-03, and 45885801-04


DP#:				330973
Subject:		PP# 0F6076.  New Food Uses on Quizalofop-Ethyl on Barley, Flax, Sunflower, and Wheat.  Request of Petition Method Validation (PMV) of the proposed tolerance enforcement methods.
From:			S. Oonnithan
To:				F. Siegelman
Dated:			7/24/2006
MRID(s):		44967703, 44967704, 45885803, and 45885804

International Residue Limits 

                Quizalofop-P-ethyl (PC Code 128709; 08/05/2011)
                       Quizalofop-ethyl (PC Code 128711)
Summary of US and International Tolerances and Maximum Residue Limits 
Residue Definition:
US
Canada
Mexico[2]
Codex[3]
40 CFR 180.441:
Plants (commodities in this action):  combined residues of the herbicide quizalofop-P-ethyl ester [ethyl ( R )-(2-[4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propanoate], and its acid metabolite quizalofop-p [ R -(2-(4-((6-quinoxalin-2-yl)oxy)phenoxy)propanoic acid], and the S enantiomers of both the ester and the acid, all expressed as quizalofop-P-ethyl ester

Livestock:  combined residues of the herbicide quizalofop (2-[4-(6-chloroquinoxalin-2-yl oxy)phenoxy]propanoic acid), quizalop-ethyl (ethyl-2-[4-(6-chloroquinoxalin-2-yl oxy)phenoxy]propanoate), and quizalofop-methyl (methyl 2-[4-(6-chloroquinoxalin-2-yl-oxy)phenoxy]propanoate, all expressed as quizalofop ethyl 
ethyl (RS) 2-[4-(6-chloroquinoxalin-2-yloxy) phenoxy] propionate, including the acid metabolites of (RS)2-[4-(6-chloroquinoxalin-2-yloxy) phenoxy]propanoic acid, all expressed as quizalofop ethyl


None
Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

                                      US
Canada
Mexico[2]
Codex[3]
Rapeseed, subgroup 20A, except flaxseed
1.5
0.05 flax, oriental mustard seeds (condiment type and oilseed type), rapeseeds (canola)


Sorghum, grain
0.20



Corn, field, forage
0.02



Corn, field, grain
0.02



Corn, field, stover
0.03








Completed:  M. Negussie; 08/09/2011 and 08/05/2011 (for corn in a separate table)
[1] Includes only commodities of interest for this action.  Tolerance values should be the HED recommendations and not those proposed by the applicant.
2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains.  PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.


Appendix I.  Tolerance Assessment Calculations.

For each of the corn commodities listed below, the OECD MRL calculator (March 2011 version), was used for calculating recommended tolerances.  The statistical goal of the OECD MRL calculator is to produce an MRL proposal in the region of the 95[th] percentile of the underlying residues distribution.  The average residue values used to calculate the tolerances are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.

Table I-1.	Residue data used to calculate tolerance for quizalofop-P-ethyl in/on corn commodities.
Regulator:
EPA
Chemical:
Quizalofop-P-ethyl
Crop:
Corn forage 
Corn grain
Corn stover
PHI:
32-47 Days (early harvest)
79-144 Days
79-144 Days
App. Rate:
0.078-0.088 lb ai/A
0.078-0.088 lb ai/A
0.078-0.088 lb ai/A
Submitter:
Dow AgroSciences
Dow AgroSciences
Dow AgroSciences
MRID Citation:
MRID 48260704
MRID 48260704
MRID 48260704

                       Total Quizalofop-P-ethyl Residues
      [quizalofop-P-ethyl + quizalofop acid (in parent equivalents); ppm]

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.02

                                   <0.02
                                   <0.02
                                   <0.022

                                   <0.02
                                   <0.02
                                   <0.02

                                       
                                   <0.02
                                   <0.02

Corn forage

The dataset used to establish a tolerance for quizalofop-P-ethyl on corn forage consisted of field trial data representing application rates of 0.078-0.088 lb ai/A with a 32- to 47-day PHI (early forage).  The field trial application rates are within 25% of the proposed maximum label application rate; however, the majority of the field trials (22 of 24) were conducted at a PHI up to 57% greater than the proposed minimum label PHI.  The average residues values used to calculate the tolerance are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.  For corn forage, all residues of quizalofop-P-ethyl and quizalofop acid, converted to parent equivalents, were below the LLMV.  Because >50% of the corn forage dataset is censored, there is high uncertainty of MRL estimate.

The quizalofop-P-ethyl-corn forage dataset was entered into the OECD MRL calculator; the recommended tolerance is 0.02 ppm for corn forage.

 
 
 
 
 
                           Total Quizalofop-P-ethyl
                                       
 
                                  Corn Forage
                                       
 
                                U.S. and Canada
                                       
 
                            1 app at 0.083 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                      24
                                       
 
Percentage of censored data
                                     100%
                                       
 
Number of non-censored data
                                       0
                                       
 
Lowest residue
                                     0.020
                                       
 
Highest residue
                                     0.020
                                       
 
Median residue
                                     0.020
                                       
 
Mean
                                     0.020
                                       
 
Standard deviation (SD)
                                     0.000
                                       
 
Correction factor for censoring (CF)
                                     0.333
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.020
 
 
- Mean + 4 SD
                                     0.020
 
 
- CF x 3 Mean
                                     0.020
 
 
Unrounded MRL
                                     0.020
                                       
 
 
                                       
 
 
Rounded MRL
                                     0.02
                                       
 
 
                                       
                                       
 
 High uncertainty of MRL estimate.
                                       
 
[High level of censoring]
 
 
 
 
 


Corn grain

The dataset used to establish a tolerance for quizalofop-P-ethyl on corn grain consisted of field trial data representing application rates of 0.078-0.088 lb ai/A with a 79- to 144-day PHI.  The field trial application rates are within 25% of the proposed maximum label application rate.  The average residues values used to calculate the tolerance are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.  For corn grain, all residues of quizalofop-P-ethyl and quizalofop acid, converted to parent equivalents, were below the LLMV Because >50% of the corn grain dataset is censored, there is high uncertainty of MRL estimate.

The quizalofop-P-ethyl-corn grain dataset was entered into the OECD MRL calculator; the recommended tolerance is 0.02 ppm for corn grain.

 
 
 
 
 
                           Total Quizalofop-P-ethyl
                                       
 
                                  Corn Grain
                                       
 
                                U.S. and Canada
                                       
 
                            1 app at 0.083 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                      25
                                       
 
Percentage of censored data
                                     100%
                                       
 
Number of non-censored data
                                       0
                                       
 
Lowest residue
                                     0.020
                                       
 
Highest residue
                                     0.020
                                       
 
Median residue
                                     0.020
                                       
 
Mean
                                     0.020
                                       
 
Standard deviation (SD)
                                     0.000
                                       
 
Correction factor for censoring (CF)
                                     0.333
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.020
 
 
- Mean + 4 SD
                                     0.020
 
 
- CF x 3 Mean
                                     0.020
 
 
Unrounded MRL
                                     0.020
                                       
 
 
                                       
 
 
Rounded MRL
                                     0.02
                                       
 
 
                                       
                                       
 
 High uncertainty of MRL estimate.
                                       
 
[High level of censoring]
 
 
 
 
 



Corn stover

The dataset used to establish a tolerance for quizalofop-P-ethyl on corn stover consisted of field trial data representing application rates of 0.078-0.088 lb ai/A with a 79- to 144-day PHI.  The field trial application rates are within 25% of the proposed maximum label application rate.  The average residues values used to calculate the tolerance are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.  For corn stover, all residues of quizalofop-P-ethyl were below the LLMV and all quizalofop acid residues, converted to parent equivalents were below the LLMV except for one sample.  Because >50% of the corn stover dataset is censored, there is high uncertainty of MRL estimate.

The quizalofop-P-ethyl-corn stover dataset was entered into the OECD MRL calculator; the recommended tolerance is 0.03 ppm for corn stover.


 
 
 
 
 
                           Total Quizalofop-P-ethyl
                                       
 
                                  Corn Fodder
                                       
 
                                U.S. and Canada
                                       
 
                            1 app at 0.083 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                      25
                                       
 
Percentage of censored data
                                      96%
                                       
 
Number of non-censored data
                                       1
                                       
 
Lowest residue
                                     0.020
                                       
 
Highest residue
                                     0.022
                                       
 
Median residue
                                     0.020
                                       
 
Mean
                                     0.020
                                       
 
Standard deviation (SD)
                                     0.000
                                       
 
Correction factor for censoring (CF)
                                     0.360
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.022
 
 
- Mean + 4 SD
                                     0.022
 
 
- CF x 3 Mean
                                     0.022
 
 
Unrounded MRL
                                     0.022
                                       
 
 
                                       
 
 
Rounded MRL
                                     0.03
                                       
 
 
                                       
                                       
 
 High uncertainty of MRL estimate.
                                       
 
[High level of censoring]
 
 
 
 
 



Sorghum

For each of the sorghum commodities listed below, the OECD MRL calculator (March 2011 version), was used for calculating recommended tolerances.  The statistical goal of the OECD MRL calculator is to produce an MRL proposal in the region of the 95[th] percentile of the underlying residues distribution.  The average residues values used to calculate the tolerances are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.

Table I-1.	Residue data used to calculate tolerance for quizalofop-P-ethyl in/on sorghum commodities.
Regulator:
EPA
Chemical:
Quizalofop-P-ethyl
Crop:
Sorghum forage
Sorghum grain
Sorghum stover
PHI:
25-32 Days
29-49 Days
42-56 Days
App. Rate:
0.136-0.145 lb ai/A
0.136-0.145 lb ai/A
0.136-0.145 lb ai/A
Submitter:
IR-4
IR-4
IR-4
MRID Citation:
MRID 48273601
MRID 48273601
MRID 48273601

                       Total Quizalofop-P-ethyl Residues
      [quizalofop-P-ethyl + quizalofop acid (in parent equivalents); ppm]

                                   <0.104
                                   <0.115
                                   <0.119

                                   <0.104
                                   <0.104
                                   <0.104

                                   <0.110
                                   <0.104
                                   <0.171

                                   <0.104
                                   <0.112
                                   <0.104

                                   <0.129
                                   <0.104
                                   <0.132

                                   <0.106
                                   <0.104
                                   <0.104

                                   <0.104
                                   <0.104
                                   <0.104

                                   <0.104
                                   <0.104
                                   <0.204

                                   <0.104
                                   <0.149
                                   <0.108

                                   <0.104
                                   <0.127
                                   <0.104

                                   <0.169
                                   <0.104
                                   <0.212

                                   <0.104
                                   <0.104
                                   <0.104

                                   <0.104
                                       
                                   <0.104













Sorghum forage

The dataset used to establish a tolerance for quizalofop-P-ethyl on sorghum forage consisted of field trial data representing application rates of 0.136-0.145 lb ai/A with a 25- to 32-day PHI.  The field trial application rates and PHIs are within 25% of the maximum label application rate and minimum label PHI, respectively.  The average residues values used to calculate the tolerance are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.  For sorghum forage, all residues of quizalofop-P-ethyl were below the LLMV and average residues of quizalofop acid, converted to parent equivalents, were above the LLMV in 4 of 13 trials.  Because >50% of the sorghum forage dataset is censored, there is high uncertainty of MRL estimate.

The quizalofop-P-ethyl-sorghum forage dataset was entered into the OECD MRL calculator; the recommended tolerance is 0.20 ppm for sorghum forage.






Sorghum grain

The dataset used to establish a tolerance for quizalofop-P-ethyl on sorghum grain consisted of field trial data representing application rates of 0.136-0.145 lb ai/A with a 29- to 49-day PHI.  The field trial application rates are within 25% of the maximum label application rate.  The PHIs are within 25% of the minimum label PHI, with the exception of one trial (29-day PHI) that was harvested early due to damage caused by birds.  This trial was included in the data set because residues were not significantly different from the other field trials.  The average residues values used to calculate the tolerance are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.  For sorghum grain, all residues of quizalofop-P-ethyl were below the LLMV and average residues of quizalofop acid, converted to parent equivalents, were above the LLMV in 4 of 12 trials.  Because >50% of the sorghum grain dataset is censored, there is high uncertainty of MRL estimate.

The quizalofop-P-ethyl-sorghum grain dataset was entered into the OECD MRL calculator; the recommended tolerance is 0.20 ppm for sorghum grain.



Sorghum stover

The dataset used to establish a tolerance for quizalofop-P-ethyl on sorghum stover consisted of field trial data representing application rates of 0.136-0.145 lb ai/A with a 42- to 56-day PHI.  The field trial application rates and PHIs are within 25% of the maximum label application rate and minimum label PHI, respectively.  The average residues values used to calculate the tolerance are provided in Table I-1.  Residue values represent total residues of quizalofop-P-ethyl and quizalofop acid, converted to quizalofop-P-ethyl equivalents.  For sorghum stover, all residues of quizalofop-P-ethyl were below the LLMV and average residues of quizalofop acid, converted to parent equivalents, were above the LLMV in 6 of 13 trials.  Because >50% of the sorghum stover dataset is censored, there is high uncertainty of MRL estimate.

The quizalofop-P-ethyl-sorghum stover dataset was entered into the OECD MRL calculator; the recommended tolerance is 0.30 ppm for sorghum stover.







Rapeseed, subgroup 20A, except flaxseed

The available data for canola reflect nine field trials conducted in 1989 (for residue values refer to MRID# 43695701).  Each trial had a one control plot and two test plots.  The canola test plots received either a single broadcast ground spray at 1.5 oz ai/A (0.094 lb ai/A; ~0.8x proposed seasonal application rate) or 3 oz ai/A (0.188 lb ai/A; ~1.6x proposed seasonal application rate) along with the surfactant.  Both the 0.8x and 1.5x applications were done at the same time.  Mature canola seeds were harvested at 38 to 74 days PHI.  

Based on the available data, a tolerance for canola seed was established at 1.0 ppm.  However, since proportionality is observed between the application rate, 0.10 lb ai/A and 0.20 lb ai/A, and the average residues, 0.22 ppm and 0.45 ppm, respectively, we adjusted the data to reflect the residues that may be expected after application at the proposed rate (0.124 lb ai/A).  The residues originally reported as quizalofop acid equivalents were converted to quizalofop-P-ethyl equivalents, adjusted for the application rate by using a scaling factor, and included in the OECD calculator to estimate a tolerance of 1.5 ppm.  HED understand that this new tolerance is more consistent with the proposed use pattern. 

                           Residues for 0.10 lb ai/A
                                Scaling Factor
                              Scaled Residues[1]

                           Residues for 0.20 lb ai/A
                                Scaling Factor
                              Scaled Residues[1]







                                                                          0.120
                                                                          0.806
                                                                          0.161

                                                                          0.180
                                                                           1.61
                                                                          0.121
                                                                          0.081
                                                                          0.806
                                                                          0.109

                                                                          0.250
                                                                           1.61
                                                                          0.168
                                                                          0.050
                                                                          0.806
                                                                          0.067

                                                                          0.050
                                                                           1.61
                                                                          0.034
                                                                          0.125
                                                                          0.806
                                                                          0.167

                                                                          0.510
                                                                           1.61
                                                                          0.342
                                                                          0.050
                                                                          0.806
                                                                          0.067

                                                                          0.084
                                                                           1.61
                                                                          0.056
                                                                          0.050
                                                                          0.806
                                                                          0.067

                                                                          0.050
                                                                           1.61
                                                                          0.034
                                                                          0.310
                                                                          0.806
                                                                          0.415

                                                                          0.600
                                                                           1.61
                                                                          0.402
                                                                          0.210
                                                                          0.806
                                                                          0.281

                                                                          0.280
                                                                           1.61
                                                                          0.188
                                                                          0.700
                                                                          0.806
                                                                          0.938

                                                                          1.500
                                                                           1.61
                                                                          1.006

[1] Converted to quizalofop-P-ethyl equivalents by multiplying for a conversion factor of 1.08.















 
 
 
 
 
                              Quizalofop-P-ethyl
                                       
 
                                  Canola seed
                                       
 
                                      USA
                                       
 
                              0.10 - 0.20 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                      18
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                      18
                                       
 
Lowest residue
                                     0.034
                                       
 
Highest residue
                                     1.006
                                       
 
Median residue
                                     0.164
                                       
 
Mean
                                     0.257
                                       
 
Standard deviation (SD)
                                     0.287
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     1.006
 
 
- Mean + 4 SD
                                     1.404
 
 
- CF x 3 Mean
                                     0.771
 
 
Unrounded MRL
                                     1.404
                                       
 
 
                                       
 
 
Rounded MRL
                                      1.5
                                       
 
 
                                       
                                       
 
 
 
 

