UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES,

AND TOXIC SUBSTANCES

MEMORANDUM

Date:		22-JUL-2009

Subject:	Saflufenacil in/on Legume Vegetables (group 06), the Foliage of Legume Vegetables (group 07), Citrus Fruits (group 10), Pome Fruits (group 11), Stone Fruits (group 12), Tree Nuts (group14), Pistachio, Cereal Grains (group 15), Forage, Fodder and Straw of Cereal Grains (group 16), Sorghum Stover, Undelinted Cotton Seed, Cotton Gin Byproducts, Grapes, Pistachio, Almond Hulls, Sunflower Seed, and Livestock Commodities.  Summary of Analytical Chemistry and Residue Data.

PC Code:  118203	DP Barcodes:  D349938, D350198, D354472

Decision No.:  389161	Registration Nos.:  7969-ETA, 7969-ETI, 7969-ETO, 7969-EIN

Petition No.:  8F7322	Regulatory Action:  Sec. 3 Registration

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  372137-35-4

MRID Nos.:  471280-01 thru -21, 471282-22 thru -33, 474459-02 thru -05, 47523801, 47796103, 47796104	40 CFR:  §180.xxx

From:		George F. Kramer, Ph.D., Senior Chemist

		Risk Assessment Branch 1 (RAB1)

		Health Effects Division (HED) (7509P)

Through:		Dana M. Vogel, Branch Chief

		RAB1/HED (7509P)

To:	       Kathryn Montague/Joanne Miller, PM Team 23

Registration Division (RD; 7505P)

Executive Summary

Saflufenacil (BAS 800 H) is a broad-spectrum herbicide developed by BASF.  It belongs to the herbicide mode-of-action Group 14 (cell membrane disruptors).  Saflufenacil acts through the inhibition of protoporphyrinogen oxidase (PPO), resulting in cell membrane damage and subsequent plant death.  There are currently no registrations for saflufenacil in the U.S.  Saflufenacil is being evaluated as part of a trilateral joint review with Canada and Australia.

BASF has submitted draft labels for the 2.85 lb ai/gal suspension-concentrate (SC) formulation (BAS 800 04H FiRoCrop Herbicide; EPA Reg. 7969-ETI), the 70% ai wettable-granule (WG) formulation (BAS 800 01H TNV Herbicide; EPA Reg. No. 7969-ETA), the 0.57 lb ai/gal emulsifiable-concentrate (EC) formulation (BAS 781 02H Herbicide; EPA Reg. 7969-ETO), and the 17.8% WG formulation (BAS 804 00H LegVeg Herbicide; EPA Reg. 7969-EIN) for use on legume vegetables, citrus fruit, pome fruit, stone fruit, tree nuts, cereal grains, cotton, sunflowers, and grapes.  This registration request represents the first food use for this herbicide.  The end-use products are proposed for a preplant/preemergence spray application at 0.011-0.134 lb ai/A/application (legume vegetables, cereal grains, cotton); for postemergence-directed spray applications at 0.022-0.044 lb ai/A/application to weeds in orchards/vineyards (citrus fruit, pome fruit, stone fruit, tree nuts, grapes); and for 2 foliar spray applications at 0.0225-0.045 lb ai/A/application as a harvest aid (sunflowers).  Applications may be made using ground or aerial equipment, and use of an adjuvant is required.  Preharvest intervals (PHIs) of 0-7 days are proposed.

Concurrently, BASF has submitted a petition for the establishment of permanent tolerances for “the combined residues of saflufenacil (N'-[2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dih ydro-1(2H)-pyrimidinyl)benzoyl]-N-isopropyl-N-methylsulfamide) plus metabolites M800H11 (N-[2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-pyrimidi nyl)-4-fluorobenzoyl]-N'-isopropylsulfamide) and M800H35 (N-[4-chloro-2-fluoro-5-({[(isopropylamino)sulfonyl]amino}carbonyl)pheny l]urea),” in/on the following raw agricultural commodities (RACs):

Vegetable, legume, group 06	0.03 ppm

Vegetable, foliage of legume, group 07	0.1 ppm

Fruit, citrus, group 10	0.03 ppm

Fruit, pome, group 11	0.03 ppm

Fruit, stone, group 12	0.03 ppm

Nut, tree, group 14	0.03 ppm

Almond, hulls	0.2 ppm

Grain, cereal, group 15	0.03 ppm

Grain, cereal, forage, fodder and straw group 16	0.1 ppm

Sorghum stover	0.1 ppm

Cotton, undelinted seed	0.03 ppm

Cotton, gin byproducts	0.03 ppm

Sunflower, seed	0.7 ppm

Grape	0.03 ppm

Animal - Kidney	0.02 ppm

Animal - Liver	0.8 ppm

The nature of the residue in plants (resulting from preplant/preemergence application), rotational crops, and livestock is adequately understood based on acceptable metabolism studies conducted on corn, soybean, tomato, rotational crops, lactating goats, and laying hens.  A waiver request for a sunflower (postemergence) metabolism study was approved.

In plants, the main reactions involved in the metabolic pathway of saflufenacil are N-demethylation at the uracil ring, stepwise degradation (N-dealkylation) of the N-methyl-N-isopropyl group, hydrolytic cleavage of the uracil ring generating a urea side chain, and hydroxylation of the phenyl ring.  M800H11 was found in all corn and soybean matrices from both 14C-labeled uracil and 14C-labeled phenyl saflufenacil.  M800H11 is formed when saflufenacil undergoes demethylation at both nitrogen atoms.  M800H35 was detected only after 14C-labeled phenyl saflufenacil treatment and was detected at higher levels in soybean matrices.  M800H35 is formed when parent saflufenacil undergoes demethylation at the sulfonylurea side chain and cleavage of the uracil ring.  The HED Residues of Concern Knowledgebase Subcommittee (ROCKS) determined that residues of concern for the tolerance expression and risk assessment consist of saflufenacil, M800H11, and M800H35 (Memo, B. Daiss, 1/6/09; D359645).  This conclusion applies only to preplant/preemergence and sunflower harvest-aid uses.

The metabolism of saflufenacil in rotational crops appears to be consistent with the pathway observed in the plant metabolism studies.  The residues of concern for rotational crops are saflufenacil, M800H11, and M800H35 (Memo, B. Daiss, 1/6/09; D359645).  Unless the petitioner requests plantback intervals (PBIs) shorter than 4 months, no additional data are required, and tolerances for inadvertent residues in/on rotational crops need not be established in conjunction with the currently proposed uses.

In livestock, saflufenacil was metabolized by several dealkylation steps occurring at two different sites in the molecule (N-isopropyl-N-methylsulfamide side chain and at the uracil ring) and via hydrolytic opening of the uracil ring (goat only).  In the ruminant metabolism study, saflufenacil was a major residue in all matrices.  M800H04, a ring opening product, was the only significant metabolite found (liver).  In the poultry metabolism study, saflufenacil was a major residue in all matrices and no significant metabolites were found.  The HED ROCKS determined that saflufenacil per se is the only residue of concern in livestock for the tolerance expression and risk assessment (Memo, B. Daiss, 1/6/09; D359645).

The petitioner has submitted two liquid chromatography/mass spectroscopy/mass spectroscopy (LC-MS/MS) analytical methods for the determination of residues of the parent and its metabolites in/on plant and livestock commodities.  BASF Method D0603/02 was developed for determination of residues of saflufenacil and its metabolites M800H11 and M800H35 in different plant matrices using LC-MS/MS.  The limit of quantitation (LOQ) was 0.01 ppm for each analyte in food matrices (human consumption) and 0.025 ppm for each analyte in feed matrices (livestock consumption).  BASF analytical Method No. L0073/01 was developed for determination of saflufenacil (BAS 800 H) in livestock matrices using LC-MS/MS.  The LOQ was 0.01 ppm in all matrices.  These methods were used as the data-collection methods in the analysis of samples for residues of concern from the various studies associated with the current petition.  Each method has been adequately validated by the petitioner as well as by independent laboratories.  Method No. L0073/01 was also adequately radiovalidated using weathered samples obtained from metabolism studies.

HED has determined that Methods D0603/02 and L0073/01 are suitable enforcement methods for plant and livestock commodities, respectively, as defined in Standard Operating Procedure (SOP) No. ACB-019 (9/15/08).

The submitted magnitude of the residue data for the raw and processed commodities of legume vegetables, citrus fruit, pome fruit, stone fruit, tree nuts, cereal grains, cotton, sunflowers, and grapes are adequate.  There are also adequate storage stability data to validate the storage conditions and intervals of samples collected from the field and processing trials.  As no concentration of the total saflufenacil residue was found in any processed commodity, separate tolerances for residues in/on processed commodities are not required.

An adequate dairy cow feeding study has been submitted; this study is acceptable for determining tolerance levels for ruminant commodities.  Based on the submitted data, HED has concluded that the tolerances, expressed as saflufenacil per se, are required for ruminant commodities.  Based on the results of the laying hen metabolism study and the proposed tolerances in poultry feed components, there is no reasonable expectation of finite residues of saflufenacil in the meat, meat byproducts, and eggs of poultry as a result of the proposed uses.

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

Pending submission of revised Sections B and F (see requirements under Directions for Use and Proposed Tolerances), and the submission of reference standards for the saflufenacil metabolites (see requirements under Submittal of Analytical Reference Standards); there are no residue chemistry issues that would preclude granting an unconditional registration for the use of saflufenacil on the requested crops.

The proposed uses and the submitted data support:  “Tolerances are established for residues of saflufenacil, 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 the sum of saflufenacil (2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-py rimidinyl]-4-fluoro-N-[[methyl(1-methylethyl)amino]sulfonyl]benzamide) and its metabolites N-[2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-pyrimidin yl)-4-fluorobenzoyl]-N'-isopropylsulfamide and N-[4-chloro-2-fluoro-5-({[(isopropylamino)sulfonyl]amino}carbonyl)phenyl ]urea, calculated as the stoichiometric equivalent of saflufenacil, in or on the commodities.”

Vegetable, legume, group 6	0.03 ppm

Vegetable, foliage of legume, group 7	0.10 ppm

Fruit, citrus, group 10	0.03 ppm

Fruit, pome, group 11	0.03 ppm

Fruit, stone, group 12	0.03 ppm

Nut, tree, group 14	0.03 ppm

Pistachio	0.03 ppm

Almond, hulls	0.10 ppm

Grain, cereal, group 15	0.03 ppm

Grain, cereal, forage, fodder and straw group 16	0.10 ppm

Cotton, undelinted seed	0.03 ppm

Cotton, gin byproducts	0.10 ppm

Sunflower, seed	1.0 ppm

Grape	0.03 ppm

The proposed uses and the submitted data also support:  “Tolerances are established for residues of saflufenacil, 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 saflufenacil, 2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyr imidinyl]-4-fluoro-N-[[methyl(1-methylethyl)amino]sulfonyl]benzamide, in or on the commodities.”

Milk	0.01 ppm

Cattle, meat	0.01 ppm

Cattle, fat	0.01 ppm

Cattle, liver	0.80 ppm

Cattle, meat byproducts, except liver	0.02 ppm

Goat, meat	0.01 ppm

Goat, fat	0.01 ppm

Goat, liver	0.80 ppm

Goat, meat byproducts, except liver	0.02 ppm

Hog, meat	0.01 ppm

Hog, fat	0.01 ppm

Hog, liver	0.80 ppm

Hog, meat byproducts, except liver	0.02 ppm

Sheep, meat	0.01 ppm

Sheep, fat	0.01 ppm

Sheep, liver	0.80 ppm

Sheep, meat byproducts, except liver	0.02 ppm

Horse, meat	0.01 ppm

Horse, fat	0.01 ppm

Horse, liver	0.80 ppm

Horse, meat byproducts, except liver	0.02 ppm

860.1200 Directions for Use

The BAS 800 04H FiRoCrop Herbicide contains directions for use on varieties of forage sorghum.  However, forage sorghum is a member of the grass crop group, for which no data were submitted or tolerances proposed.  The BAS 800 04H FiRoCrop Herbicide label should thus be amended to limit the sorghum use to sweet and grain varieties only.

All of the sunflower field trials were performed with a WG formulation; whereas, the proposed use is for the SC formulation.  These formulation types are not considered to be equivalent for mid- to late-season foliar applications.  The proposed sunflower use should thus be removed from the BAS 800 04H FiRoCrop Herbicide (SC) label and may be added to the BAS 800 01H TNV Herbicide (WG) label.  Alternatively, bridging trials could be performed to determine the effect of the formulation type on residue levels.

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

Analytical standards for of saflufenacil, M800H11, and M800H35 are currently available in the National Pesticide Standards Repository [Source:  personal communication with T. Cole of the Analytical Chemistry Laboratory/Biological and Economics Analysis Division (ACL/BEAD), 1/15/09].  However, since the standards for M800H11 and M800H35 expired on 10/1/08, the petitioner is requested to provide a new supply to the Repository.

860.1550 Proposed Tolerances

The petitioner is requested to submit a revised Section F specifying the following:

The tolerance expression for plant commodities should be revised to:  “Tolerances are established for residues of saflufenacil, 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 the sum of saflufenacil (2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-py rimidinyl]-4-fluoro-N-[[methyl(1-methylethyl)amino]sulfonyl]benzamide) and its metabolites N-[2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-pyrimidin yl)-4-fluorobenzoyl]-N'-isopropylsulfamide and N-[4-chloro-2-fluoro-5-({[(isopropylamino)sulfonyl]amino}carbonyl)phenyl ]urea, calculated as the stoichiometric equivalent of saflufenacil, in or on the commodities.”

The tolerance expression for livestock commodities should be revised to:  “Tolerances are established for residues of saflufenacil, 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 saflufenacil, 2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyr imidinyl]-4-fluoro-N-[[methyl(1-methylethyl)amino]sulfonyl]benzamide, in or on the commodities.”

Revised tolerance levels and commodity definitions are presented in Table 35 (summarized above).

A human-health risk assessment is forthcoming in a separate document.

Background

Saflufenacil is a broad-spectrum herbicide developed by BASF.  It belongs to the herbicide mode-of-action Group 14 (cell membrane disruptors).  Saflufenacil acts through the inhibition of PPO, resulting in cell membrane damage and subsequent plant death.  Susceptible weeds develop symptoms within hours of application under active growing conditions.  Plant death occurs within 3-5 days depending upon growing conditions.  The chemical structure and nomenclature of saflufenacil and its metabolites M800H11 and M800H35, and the physicochemical properties of the technical grade of saflufenacil, are presented in Tables 1 and 2.

TABLE 1.  Saflufenacil and Metabolite Nomenclature.

Chemical Structure

Common name	Saflufenacil

Company experimental name	BAS 800 H (synonyms:  AC 433 379, BASF Reg. No. 4054449)

IUPAC name N'-[2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihy dro-1(2H)-pyrimidinyl)benzoyl]-N-isopropyl-N-methylsulfamide

CAS name 2-Chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyr imidinyl]-4-fluoro-N-[[methyl(1-methylethyl)amino]sulfonyl]benzamide

CAS registry number	372137-35-4

End-use product (EP)	BAS 800 00H (70% WG formulation)

Chemical Structure

Common name	M800H11

Chemical name N-[2-Chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-pyrimidin yl)-4-fluorobenzoyl]-N'-isopropylsulfamide

Chemical Structure

Common name	M800H35

Chemical name N-[4-Chloro-2-fluoro-5-({[(isopropylamino)sulfonyl]amino}carbonyl)phenyl ]urea

TABLE 2.  Physicochemical Properties of Technical Grade Saflufenacil.

Parameter	Value

Melting point	Average = 189.9 °C, peak max = 193.4 °C

pH	4.43 of 1% solution at 25 °C

Bulk Density (ambient temp.)	0.661 kg/L (free fall), 0.736 kg/L (packed)

Water solubility (20°C)	in g/100-mL:

0.0025 in water (pH = 5); 0.0014 in pH 4 buffer; 0.21 in pH 7 buffer; not determined due to degradation in pH 9 buffer

Solvent solubility (20°C)	in g/100-mL:

19.4 acetonitrile; 24.4 dichloromethane; 55.4 N,N-dimethylformamide; 27.5 acetone; 6.55 ethyl acetate; 36.2 tetrahydrofuran; 35.0 butyrolactone; 2.98 methanol; 0.25 isopropyl alcohol;

0.23 toluene; <0.01 1-octanol; <0.005 n-heptane

Vapor pressure at 20/25°C	20° C = 4.5 x 10-15 Pa

wavelength maximum:  λmax = 271.6 nm

extinction coefficient:  ε = 9709 L/mol-cm

Reference:  BASF Registration Document Number (DocID) 2005/1026464.

860.1200 Directions for Use

BASF has submitted draft labels dated 1/31/08 for the 2.85 lb ai/gal SC formulation (BAS 800 04H FiRoCrop Herbicide; EPA Reg. 7969-ETI), for the 70% ai WG formulation (BAS 800 01H TNV Herbicide; EPA Reg. No. 7969-ETA), the 0.57 lb ai/gal EC formulation (BAS 781 02H Herbicide; EPA Reg. 7969-ETO), and the 17.8% WG formulation (BAS 804 00H LegVeg Herbicide; EPA Reg. 7969-EIN).  Information pertaining to the proposed end-use product is listed in Table 3.  A summary of the proposed use patterns on legume vegetables, citrus fruit, pome fruit, stone fruit, tree nuts, cereal grains, cotton, sunflowers, and grapes is detailed in Table 4.

Table 3.  Summary of Proposed End-Use Products.

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

BAS 800 04H FiRoCrop Herbicide 	7969-ETI	29.74	SC	legume vegetables, cereal grains, cotton, sunflowers	Broadleaf weeds	Draft labels submitted 1/31/08

BAS 800 01H TNV	7969-ETA	70.0	WG	citrus fruit, pome fruit, stone fruit, tree nuts, grapes

BAS 781 02H Herbicide	7969-ETO	6.24 + 55.04% dimethenamid	EC	corn, grain sorghum

BAS 804 00H LegVeg Herbicide 	7969-EIN	17.8 + 50.2% imazethapyr	WG legume vegetables, corn

Table 4.  Summary of Directions for Use of Saflufenacil.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	App. ate

(lb ai/acre)	Max. No. App. per Season	Max. Seasonal App. Rate

(lb ai/acre)	PHI

(days)	Use Directions and Limitations

Corn, Sorghum, Small Grains

Preplant/

Preemergent

Broadcast,

Ground or aerial	BAS 800 04H FiRoCrop Herbicide

2.85 lb/gal SC

[7969-ETI]	0.0225-0.134	Not specified	0.134	80 (forage, silage) Applications are to be made in ≥3 gal/acre using ground or aerial equipment.

Legumes

Preplant/

Preemergent

Broadcast,

Ground or aerial	BAS 800 04H FiRoCrop Herbicide

2.85 lb/gal SC

[7969-ETI]	0.011-0.089	Not specified	0.089	Not specified	Applications are to be made in ≥3 gal/acre using ground or aerial equipment.

Cotton

Preplant/

Preemergent

Broadcast,

Ground or aerial	BAS 800 04H FiRoCrop Herbicide

2.85 lb/gal SC

[7969-ETI]	0.045	Not specified	0.045	Not specified	Applications are to be made in ≥3 gal/acre using ground or aerial equipment.

Citrus, Pome, & Stone Fruit; Tree Nuts

Post, Directed to Orchard Floor

	BAS 800 01H TNV Herbicide

30% WG

[7969-ETA]	0.022-0.044	3	0.131	7 (nuts)

0 (fruit)	Applications are to be made in ≥10 gal/acre using ground equipment.

Grapes

Post, Directed to Vineyard Floor

	BAS 800 01H TNV Herbicide

30% WG

[7969-ETA]	0.022	3	0.066	0	Applications are to be made in ≥10 gal/acre using ground equipment.

Sunflower

Preharvest

Dessication

Broadcast,

Ground or aerial	BAS 800 04H FiRoCrop Herbicide

2.85 lb/gal SC

[7969-ETI]	0.0225-0.045	2	0.090	7	Applications are to be made in ≥3 gal/acre using ground or aerial equipment.

Note:  Use of an adjuvant is required for burndown application to emerged weeds or sunflower.

Table 5.  Rotational Crop PBIs for Saflufenacil.

Crop	PBI (months)

	Application rate (lb ai/acre)

	0.0225	0.045	0.067	0.089	0.112	0.134

Corn	0	0	0	0	0	0

Sorghum	0	0	0	0	0	0

Small Grains	0	0	0	0	3	3

Chickpea

Field Pea	0	0	3	3	6	6

Lentil	0	2	3	3	6	9

Soybean	1	2	4	4	6	6

Cotton	1	3	4	6	6	9

Other Crops	4	4	6	6	6	9

Conclusions:  The submitted use directions for BAS 800 04H FiRoCrop Herbicide, BAS 800 01H TNV Herbicide, BAS 781 02H Herbicide, and BAS 804 00H LegVeg Herbicide are adequate to allow evaluation of the residue data relative to the proposed use.  The BAS 800 04H FiRoCrop Herbicide contains directions for use on varieties of forage sorghum.  However, forage sorghum is a member of the grass crop group, for which no data were submitted or tolerances proposed.  The BAS 800 04H FiRoCrop Herbicide label should thus be amended to limit the sorghum use to sweet and grain varieties only.  Additionally, all of the sunflower field trials were performed with a WG formulation; whereas, the proposed use is for the SC formulation.  These formulation types are not considered to be equivalent for mid- to late-season foliar applications.  The proposed sunflower use should thus be removed from the BAS 800 04H FiRoCrop Herbicide (SC) label and added to the BAS 800 01H TNV Herbicide (WG) label.  Alternatively, bridging trials could be performed to determine the effect of the formulation type on residue levels.

860.1300 Nature of the Residue - Plants

DER Reference List:	Soybean (47128002.der.doc)

			Corn (47128001.der.doc)

			Tomato (47128003.der.doc)

Soybean

The metabolism of saflufenacil was investigated in soybean following a single pre-emergent spray application to loamy sand soil of either [phenyl-U-14C]-saflufenacil or [uracil-4-14C]-saflufenacil formulated as BAS 800 UBH at a nominal target application rate of 0.134 lbs. ai/A (1.5X).  The actual application rates were 0.132 lbs. ai/A (1.5X) and 0.161 lbs. ai/A (1.8X) for the phenyl and uracil labels, respectively.  Samples of soybean forage were harvested 39-40 days after treatment (DAT), corresponding growth stage BBCH 70; and samples of soybean seed, pod (without seed), and straw were harvested 95 DAT (BBCH stage 96).  The soybean plants were cultivated in containers in climatic chambers (phytotrons) and under greenhouse conditions under simulated conditions for a typical U.S. soybean growing area.  The interval of frozen storage of samples for both labels was supported by the re-extraction and analysis of soybean pod (phenyl label) and forage (uracil label) RAC samples; and by the re-analysis of the methanol extracts at the end of the analytical phase.

14C-Residues in homogenates of soybean forage, pod, seed and straw were extracted sequentially three times with methanol (3X) and water (2X).  The seed extracts (methanol and water, for both labels) and the NH4OH solubilizates of seed and pod (uracil label) were subjected to protein precipitation with acetone at low temperatures.  The deproteinated methanol extracts of seed were additionally partitioned three times with cyclohexane, followed by mixing the aqueous phases with acetonitrile (ACN) and centrifugation to remove precipitates.  The freeze-dried protein precipitates from the water extracts of seed and from the NH4OH solubilizates of seed and pod (uracil label) were incubated with protease to release radioactive residues associated with proteins.  The unextractable residues after solvent extraction of soybean seed and pod for both labels and of soybean straw (phenyl label) were subjected to solubilization procedures with 1% aqueous ammonia (two times) followed by incubation with macerozyme (seed, pod, straw; all phenyl label only) or macerozyme/cellulase (pod, uracil label), amylase/amyloglucosidase (seed, pod and straw; all phenyl label only) and tyrosinase/laccase (seed; phenyl label only).

The identity of residues in the purified methanol extracts of soybean forage (phenyl label) and straw (phenyl label) as well as the purified fractions from the methanol extract of straw (phenyl label) and from the methanol extract of forage (uracil label) were confirmed by LC-MS and LC-MS/MS analyses.  Additional metabolites were identified/characterized by co-chromatography and comparison of retention times with the respective radiolabeled reference standards; and by comparison of the metabolite profiles.  The reference standards included isolated high-performance liquid chromatography (HPLC) fractions from the rat metabolism study containing the metabolites M800H01, M800H02 and M800H06, M800H03, M800H05, M800H10, and M800H37; the purified fractions isolated from the methanol extract of soybean straw (phenyl label) containing the metabolites M800H10, M800H36, M800H11, and M800H35; and M800H11 from corn straw (phenyl label).

The total radioactive residues (TRR) within soybean matrices were highest in the pod and straw and were generally lower in forage and seed.  The TRR, determined indirectly by the summation of the extractable and unextractable residues, were 0.431 ppm (straw), 0.179 ppm (pod), 0.081 ppm (forage), and 0.038 ppm (seed) for the phenyl label; and 2.031 ppm (pod), 1.183 ppm (straw), 0.383 ppm (forage), and 0.221 ppm (seed) for the uracil label.  With respect to label differences, the TRR were the highest in all soybean matrices for the uracil label.

The major residues (>10% TRR or >0.1 ppm) identified in soybean forage 39-40 DAT were saflufenacil (23.5% of the TRR; 0.019 ppm) and M800H02 (18.2% of the TRR; 0.014 ppm) for the phenyl label only.  The only major residue identified with the uracil label was trifluoroacetic acid (TFA) (85.2% of the TRR; 0.074 ppm).  In soybean seed 95 DAT, the major residues identified were M800H10 and/or M800H36 (14.5% of the TRR; 0.006 ppm) for the phenyl label only and TFA (65.4% of the TRR; 0.033 ppm) for the uracil label only.  The major residues identified in soybean pod 95 DAT were M800H10 and/or M800H36 (12.2% of the TRR; 0.022 ppm) and M800H35 (12.8% of the TRR; 0.023 ppm) for the phenyl label only.  The only major residue identified for the uracil label was TFA (92.4% of the TRR; 0.429 ppm).  In soybean straw 95 DAT, the major residues identified were M800H10 and/or M800H36 (11.4% of the TRR; 0.050 ppm), M800H11 (24.9% of the TRR; 0.107 ppm), and M800H35 (15.6% of the TRR; 0.067 ppm) for the phenyl label only.  The only major residue identified with the uracil label was TFA (69.2% of the TRR; 0.187 ppm).

The main metabolic reactions involved in the proposed metabolic pathway of radiolabeled saflufenacil are:

N-demethylation at the uracil ring.

stepwise degradation (N-dealkylation) of the N-methyl-N-isopropyl group to NH2 forming a sulfonamide group.

hydrolytic cleavage of the uracil ring generating a urea side chain.

hydroxylation of the phenyl ring.

TABLE 6.  Summary of Characterization and Identification of Radioactive Residues in Soybean Forage, Seed, Pod and Straw Following Pre-Emergent Application of [Phenyl-U-14C]-Saflufenacil at 0.132 lbs. ai/ (1.5X).

Compound	Forage 	Seed	Pod	Straw

	TRR = 0.081 ppm	TRR = 0.038 ppm	TRR = 0.179 ppm	TRR = 0.431 ppm

	% TRR	ppm	% TRR	ppm	% TRR	ppm	% TRR	ppm

Saflufenacil	23.5	0.019	2.3	0.001	1.5	0.003	2.5	0.011

M800H01	6.0	0.005	2.1	0.001	1.0	0.002	3.0	0.013

M800H02	18.2	0.0142	6.2	0.002	5.6	0.010	8.3	0.036

M800H03	1.2	0.001	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.

M800H05	n.d.	n.d.	3.2	0.001	n.d.	n.d.	2.3	0.010

M800H10 and / or M800H36	6.6	0.005	14.5	0.006	12.2	0.022	11.4	0.050

M800H11	6.0	0.005	1.8	0.001	9.0	0.016	24.9	0.107

M800H35	5.3	0.004	3.8	0.001	12.8	0.023	15.6	0.067

M800H37	6.5	0.005	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.

Total identified 	73.3	0.0582	33.9	0.013	42.1	0.076	68.0	0.294

Total characterized 	14.8	0.012	37.6	0.014	20.1	0.035	14.1	0.060

Total identified and/or characterized 	88.1	0.0702	71.5	0.027	62.2	0.111 82.1	0.354

Unextractable 	8.2	0.007	40.3	0.015	38.0	0.068	14.6	0.063

Total characterized after solubilization of unextractable residues 	n.a. n.a.	26.9	0.011	27.3	0.049	7.5	0.032

Total identified and/or characterized	n.a.	n.a.	98.4	0.038	89.5	0.160 89.6	0.386

Post-extraction solids1	n.a.	n.a.	10.8	0.004	9.8	0.017	6.3	0.027

Accountability2	95%	111%	99%	96%

1  Residues remaining after exhaustive extractions.

2  Accountability = (Total extractable + Total unextractable)/(calculated TRR) x 100.

Note:  M800H10 and M800H36 were not separated in HPLC systems B and C.  However, both M800H10 and M800H36 were identified by LC-MS/MS analysis of the purified fraction from the methanol extract of soybean straw.

TABLE 7.  Summary of Characterization and Identification of Radioactive Residues in Soybean Matrices Following Application of Radiolabeled BAS 800 H (Uracil Label) at 0.161 lbs. ai/A (1.8X).

Compound	Forage (40 DAT)	Seed (95 DAT)	Pod (95 DAT)	Straw (95 DAT)

	TRR = 0.383 ppm	TRR = 0.221 ppm	TRR = 2.031 ppm	TRR = 1.183 ppm

	% TRR	ppm	% TRR	ppm	% TRR	ppm	% TRR	ppm

Saflufenacil	4.0	0.015	0.8	0.002	n.d.	n.d.	2.9	0.034

M800H01	2.3	0.009	1.1	0.002	n.d.	n.d.	2.0	0.023

M800H02	5.0	0.019	1.4	0.003	1.0	0.021	5.3	0.062

M800H11	2.5	0.010	n.d.	n.d.	1.3	0.026	14.5	0.173

TFA1	85.2	0.074 (0.326)	65.4	0.033 (0.145)	75.9	0.352 (1.54)	69.2	0.187 (0.819)

Total identified 	99.0	0.128 (0.379)	68.7	0.040 (0.152)	78.2	0.399 (1.59)	93.9	0.479 (1.11)

Total characterized 	3.1	0.012	9.8	0.021	n.d.	n.d.	6.6	0.080

Total identified and/or characterized 	102.1	0.139 (0.391)	78.5	0.061 (0.173)	78.2	0.399 (1.59)	100.5	0.559 (1.19)

Unextractable 	1.8	0.007	18.8	0.042	21.0	0.426	3.9	0.046

Total identified after solubilization of unextractable residues (TFA1) n.a.	n.a.	n.a.	n.a.	16.5	0.077 (0.336)	n.a.	n.a.

Total characterized after solubilization of unextractable residues	n.a. n.a.	13.72	0.0302 	2.3	0.048	n.a.	n.a.

Total identified and/or characterized 	n.a.	n.a.	13.7	0.030	18.8	0.125 (0.384)	n.a.	n.a.

Total identified	n.a.	n.a.	68.7	0.040 (0.152)	94.7	0.476 (1.93)	n.a. n.a.

Total identified and/or characterized	n.a.	n.a.	92.2	0.091 (0.203)	97.1 0.524 (1.98)	n.a.	n.a.

Post-extraction solids3	n.a.	n.a.	6.0	0.013	1.0	0.020	n.a.	n.a.

Accountability4	104%	98%	98%	104%

1  Absolute amount (ppm) was calculated using the conversion factor of 0.228 [(molecular mass of TFA 114 g/mol) ÷ (molecular mass of Saflufenacil 500 g/mol)].  The number in parentheses is the absolute amount expressed as parent equivalents).

2  Sum of fractions characterized from the unextractable residues after protein precipitation from the NH4OH solubilitzate and protease treatment of the precipitate.

3  Residues remaining after exhaustive extractions.

4  Accountability = (Total extractable + Total unextractable)/(calculated TRR) x 100.

Corn

The metabolism of saflufenacil was investigated in corn following a single pre-emergent spray application immediately after sowing to sandy loam soil of either [phenyl-U-14C]-saflufenacil or [uracil-4-14C]-saflufenacil formulated as BAS 800 UBH (EC) at a nominal target application rate of 0.179 lbs. ai/A (1.3X).  The actual application rates were 0.169 lbs. ai/A (1.3X) and 0.196 lbs. ai/A (1.5X) for the phenyl and uracil labels, respectively.  Samples of corn forage were harvested 42 and 101-102 DAT, corresponding to growth stages BBCH 18 and 85, respectively.  Samples of corn husks, cob, grain, and stover were harvested 133 DAT (BBCH 89).  The corn plants were cultivated in containers in climatic chambers (phytotrons), simulating the climate of a typical U.S. corn-growing areas.  The interval of frozen storage of samples for both labels was supported by the re-extraction and analysis of corn forage and grain samples and the re-analysis of the methanol extracts at the end of the analytical phase.

14C-Residues in homogenates of corn forage, husks, cob, grain, and stover were extracted by homogenization sequentially with methanol (three times) and water (two times).  Unextractable residues were characterized by sequential treatment with 1% aqueous ammonia, macerozyme, tyrosinase/laccase, and amylase/amyloglucosidase.

Residues were characterized/identified by reversed-phase HPLC co-chromatography or comparison of retention times to reference standards.  The identity of metabolites isolated from corn stover (phenyl label) and corn husks (uracil label) was confirmed by LC-MS and LC-MS/MS.

The TRR levels within corn matrices were highest in the husks and stover (referred to as straw in the trial report) and were generally relatively lower in forage, cob and grain.  The TRR were 0.215 ppm (husks), 0.096 ppm (stover), 0.029 ppm (forage 101 DAT), 0.020 ppm (grain), 0.018 ppm (forage 42 DAT), and 0.016 ppm (cob) for the phenyl label; and were 0.553 ppm (stover), 0.226 ppm (husks), 0.149 ppm (forage 102 DAT), 0.065 ppm (cob), 0.049 ppm (grain), and 0.039 ppm (forage 42 DAT) for the uracil label.

The major residues (>10% TRR or >0.1 ppm) identified in corn forage 42 DAT were M800H01 (14.6% of the TRR; 0.003 ppm), M800H03 (13.5% of the TRR; 0.002 ppm), M800H05 (11.1% of the TRR; 0.002 ppm), M800H09 (20.0% of the TRR; 0.004 ppm), and M800H10 (16.0% of the TRR; 0.003 ppm) for the phenyl label only.  The only major residue identified for the uracil label was TFA (63.7% of the TRR; 0.006 ppm).  The major residues identified in corn forage 101-102 DAT included M800H09 (21.4% of the TRR; 0.006 ppm), H800H10 (20.4% of the TRR; 0.006 ppm), and M800H34 (21.0% of the TRR; 0.006 ppm) for the phenyl label only.  The only major residue identified for the uracil label was TFA (75.7% of the TRR; 0.026 ppm).  In corn husks, the only major residue identified was TFA (87.7% of the TRR; 0.045 ppm), for the uracil label only.  The major residues identified in corn cob were M800H34 (16.7% of the TRR; 0.003 ppm) for the phenyl label only and TFA (66.0% of the TRR; 0.010 ppm) for the uracil label only.  The only major residue identified in corn grain was TFA (30.5% of the TRR; 0.004 ppm), for the uracil label only.  Identified residues in corn grain from the phenyl label were all <10% TRR.  In corn stover, the major residues identified were M800H09 (12.6% of the TRR; 0.012 ppm), M800H10 (12.8% of the TRR; 0.012 ppm), and M800H34 (12.2% of the TRR; 0.012 ppm) for the phenyl label only; and TFA (77.4% of the TRR; 0.098 ppm) for the uracil label only.

The main metabolic reactions involved in the proposed metabolic pathway of radiolabeled saflufenacil are:

N-demethylation at the uracil ring.

stepwise degradation (N-dealkylation) of the N-methyl-N-isopropyl group to NH2 forming a sulfonamide group.

hydrolytic cleavage of the uracil ring generating a urea side chain.

TABLE 8.  Summary of Characterization and Identification of Radioactive Residues in Corn Forage Following Pre-Emergent Application of [Phenyl-U-14C]-Saflufenacil at 0.169 lbs. ai/A (1.3X).

Metabolite Fraction	Corn Forage (42 DAT)	Corn Forage (101 DAT)

	TRR = 0.018 ppm	TRR = 0.029 ppm

	% TRR	ppm	% TRR	ppm

Saflufenacil	2.1	<0.0005	n.d.	n.d.

M800H01	14.6	0.003	1.6	<0.0005

M800H02	3.8	0.001	n.d.	n.d.

M800H03	13.5	0.002	1.1	<0.0005

M800H05	11.1	0.002	n.d.	n.d.

M800H09	20.0	0.004	21.4	0.006

M800H10	16.0	0.003	20.4	0.006

M800H11	8.9	0.002	7.3	0.002

M800H34	1.2	<0.0005	21.0	0.006

Total identified 	91.2	0.017	72.8	0.020

Total characterized 	19.2	0.003	28.5	0.008

Total extractable	110.4	0.020	101.3	0.028

Post-extraction solids	13.8	0.002	22.8	0.007

Accountability1	122%	121%

1  Accountability = (Total extractable + Total unextractable)/(calculated TRR) x 100.

TABLE 9.  Summary of Characterization and Identification of TRR in Corn Husks, Cob, Grain and Stover Following Pre-Emergent Application of [Phenyl-U-14C]-Saflufenacil at 0.169 lbs. ai/A (1.3X).

Metabolite Fraction	Corn Husks	Corn Cob	Corn Grain	Corn Stover

	TRR = 0.215 ppm	TRR = 0.016 ppm	TRR = 0.020 ppm	TRR = 0.096 ppm

	% TRR	ppm	% TRR	ppm	% TRR	ppm	% TRR	ppm

Saflufenacil	0.7	0.001	n.d.	n.d.	n.d.	n.d.	0.3	<0.0005

M800H03	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.	0.3	<0.0005

M800H05	1.2	0.002	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.

M800H09	1.4	0.003	7.0	0.001	0.3	<0.0005	12.6	0.012

M800H10	4.1	0.009	3.1	<0.0005	0.5	<0.0005	12.8	0.012

M800H11	1.6	0.003	1.9	<0.0005	0.6	<0.0005	4.6	0.004

M800H34	6.0	0.013	16.7	0.003	2.0	<0.0005	12.2	0.012

Total identified 	15.0	0.031	28.7	0.005	3.4	0.001	42.8	0.041

Total characterized 	56.0	0.121	26.4	0.005	7.6	0.001	23.1	0.022

Total identified and/or characterized 	71.0	0.152	55.1	0.010	11.0	0.002 65.9	0.063

Unextractable 	23.8	0.051	80.8	0.013	81.6	0.017	16.8	0.016

Total characterized after solublization of unextractable residues	9.8 0.021	16.0	0.002	49.7	0.010	5.5	0.005

Total identified and/or characterized	80.8	0.173	71.1	0.012	60.7	0.012 71.4	0.068

Post-extraction solids1	not determined	not determined	20.6	0.004	8.7 0.008

Accountability2	94% 	144%	80%	79%

1  Residues remaining after exhaustive extractions.

2  Accountability = (Total extractable + Total unextractable)/(calculated TRR) x 100.

TABLE 10.  Summary of Characterization and Identification of Radioactive Residues in Corn Forage Following Pre-Emergent Application of [Uracil-4-14C]-Saflufenacil at 0.196 lbs. ai/A (1.5X).

Metabolite Fraction	Corn Forage (42 DAT)	Corn Forage (102 DAT)

	TRR = 0.039 ppm	TRR = 0.149 ppm

	% TRR	ppm	% TRR	ppm

Saflufenacil 	1.1	<0.0005	n.d.	n.d.

M800H01	4.4	0.002	n.d.	n.d.

M800H02	1.0	<0.0005	n.d.	n.d.

M800H03	3.4	0.001	n.d.	n.d.

M800H05	1.8	0.001	n.d.	n.d.

M800H09	3.1	0.001	2.2	0.003

M800H10	3.1	0.001	2.9	0.004

M800H11	2.0	0.001	1.9	0.003

TFA1	63.7	0.006 (0.025)	75.7	0.026 (0.113)

Total identified 	83.6	0.013 (0.032)	82.7	0.036 (0.123)

Total characterized 	4.8	0.001	5.6	0.008

Total identified and/or characterized 	88.4	0.014 (0.033)	88.3	0.044 (0.131)

Post-extraction solids	4.0	0.002	5.2	0.008

Accountability2	90%	93%

1  Absolute amount (ppm) was calculated using the conversion factor of 0.228 [(molecular mass of TFA 114 g/mol) ÷ (molecular mass of saflufenacil 500 g/mol)].  The number in parentheses is the absolute amount expressed as parent equivalents.

2  Accountability = (Total extractable + Total unextractable)/(calculated TRR) x 100.

TABLE 11.  Summary of Characterization and Identification of TRR in Corn Husks, Cob, Grain and Stover Following Pre-Emergent Application of [Uracil-4-14C]-Saflufenacil at 0.196 lbs. ai/A (1.5X).

Metabolite Fraction	Corn Husks	Corn Cob	Corn Grain	Corn Stover

	TRR = 0.226 ppm	TRR = 0.065 ppm	TRR = 0.049 ppm	TRR = 0.553 ppm

	% TRR	ppm	% TRR	ppm	% TRR	ppm	% TRR	ppm

Saflufenacil 	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.

M800H09	0.3	0.001	0.3	<0.0005	n.d.	n.d.	1.8	0.010

M800H10	0.6	0.001	n.d.	n.d.	n.d.	n.d.	2.7	0.015

M800H11	0.5	0.001	n.d.	n.d.	n.d.	n.d.	0.8	0.004

TFA1	87.7	0.045 (0.198)	66.0	0.010 (0.043)	30.5	0.004  (0.015)	77.4 0.098  (0.428)

Total identified 	89.1	0.048 (0.201)	66.3	0.010 (0.043)	30.5	0.004 (0.015)	82.7	0.127 (0.457)

Total characterized 	4.8	0.011	9.4	0.006	12.0	0.006	6.1	0.034

Total identified and/or characterized 	93.9	0.059 (0.212)	75.7	0.016 (0.049)	42.5	0.010 (0.021)	88.8	0.161 (0.491)

Unextractable 	5.7	0.013	22.6	0.015	39.9	0.019	3.6	0.020

Total characterized after solubilization of unextractable residues	1.3 0.002	4.4	0.003	18.8	0.009	1.8	0.010

Total identified and/or characterized	95.2	0.061 (0.214)	80.1	0.019 (0.052)	61.3	0.019 (0.030)	90.6	0.171 (0.501)

Post-extraction solids2	4.0	0.009	17.6	0.011	18.2	0.009	1.5	0.008

Accountability3	99%	97%	80%	92%

1  Absolute amount (ppm) was calculated using the conversion factor of 0.228 [(molecular mass of TFA 114 g/mol) ÷ (molecular mass of Saflufenacil 500 g/mol)]. The number in parentheses is the absolute amount expressed as parent equivalents.

2  Residues remaining after exhaustive extractions.

3  Accountability = (Total extractable + Total unextractable)/(calculated TRR) x 100.

Tomato

The metabolism of saflufenacil was investigated in tomato after one single spray application of the test substance in the EC formulation BAS 800 UB H at a nominal application rate of 100 g ai/ha (0.089 lbs. ai/A).  The active substance was applied to soil directly before planting of tomato plants (pre-plant treatment).  Treatment was performed with either [phenyl-U-14C]-saflufenacil or [uracil-4-14C]-saflufenacil.  Tomato plants at BBCH growth stage 16/17 were planted into the sprayed soil after drying and were grown in climatic chambers (phytotrons) and later on in the greenhouse.  Immature tomato plants (BBCH growth stage 62/63) were sampled 68 DAT.  The mature tomato plants were harvested 113 DAT and separated into plant and fruit samples.  Frozen samples were homogenized and extracted with methanol and water.  The extractable radioactive residues were measured by liquid-scintillation counting (LSC), and the residual radioactive residues after solvent extraction were determined by combustion analysis.  The residual radioactive residue of immature tomato plant (BBCH 62/63; phenyl label) and of mature tomato plant at harvest (phenyl label and uracil label) were further characterized by means of sequential solubilization procedures using base and acid hydrolysis and microwave treatment.  The nature of the residues in the methanol extracts was investigated using two methods of HPLC radiodetection.  Metabolite identification was based on HPLC co-chromatography experiments performed with reference items obtained from other metabolism studies with saflufenacil in corn, rotational crops, and rats.

The TRR were determined by combustion/LSC of homogenized sample material.  The TRR in immature tomato plant (BBCH 62/63; 68 DAT) accounted for 0.089 ppm (phenyl label) and 0.131 ppm (uracil label).  In tomato plants at harvest (113 DAT), the TRR were 0.113 ppm for the phenyl label and 0.138 ppm for the uracil label.  In tomato fruits (113 DAT), the TRR levels were significantly lower, accounting for 0.015 ppm (phenyl label) and 0.037 ppm (uracil label).  Extractability of radioactive residues with methanol and water was good and ranged from 102.5-103.9% in immature tomato plant, 80.9-90.5% in tomato plant at harvest, and 68.4-84.0% in tomato fruit.

The common major metabolite identified in tomato plant matrices following the soil application of [phenyl-U-14C]-saflufenacil was the parent compound, saflufenacil, accounting for 28.6% of the TRR (0.026 ppm) in immature tomato plants and 10.9% of the TRR (0.012 ppm) in the tomato plant at harvest.  Two other major metabolites, M800H07 and M800H11, were also identified in immature tomato plant, accounting for 14.1% of the TRR (0.013 ppm) and 12.6% of the TRR (0.011 ppm), respectively.  In tomato fruit, the only major residue was a sugar compound (probably fructose), accounting for 52.9% of the TRR (0.008 ppm).

The common major metabolite identified in all tomato matrices following the soil application of [uracil-4-14C]-saflufenacil was TFA, accounting for 82.2% of the TRR (0.025 ppm) in immature tomato plant, 51.7% of the TRR (0.016 ppm) in tomato plant at harvest, and 48.6% of the TRR (0.004 ppm) in tomato fruit.  The concentration of TFA was calculated using the molecular mass of the compound.  In tomato fruit, a sugar compound (probably fructose) was also identified as a major compound and accounted for 33.7% of the TRR (0.012 ppm).

Saflufenacil was metabolized in tomato by N-dealkylation at two sites in the molecule and via hydrolysis of the uracil ring.  The metabolites M800H01, M800H02, M800H09, M800H10, and M800H11 were produced by dealkylation at either the sulfonamide nitrogen or the uracil nitrogen of saflufenacil.  The metabolites M800H07, M800H35, and TFA were produced when the uracil ring was hydrolyzed.  In addition, a sugar metabolite (probably fructose) found in tomato fruit resulted from the uptake of the small carbon fragments generated by further degradation of the other identified metabolites.  All these metabolites were found at very low level (<0.02 ppm), although the % TRR levels varied among matrices.

Table 12.  Summary of Characterization and Identification of Radioactive Residues in Tomato Matrices Following Application of [Phenyl-U-14C]-Saflufenacil at 0.089 lbs. ai/A.

Metabolite Fraction	Tomato Plant(BBCH 62/63)	Tomato Plant(Harvest) Tomato Fruit(Harvest)

	TRR = 0.089 ppm	TRR = 0.113 ppm	TRR = 0.015 ppm

	% TRR	ppm	% TRR	ppm	% TRR	ppm

Saflufenacil 	28.6	0.026	10.9	0.012	0.7	<0.0005

M800H01	1.9	0.002	1.5	0.002	n.d.	n.d.

M800H02	5.9	0.005	2.3	0.003	n.d.	n.d.

M800H07	14.1	0.013	5.8	0.007	n.d.	n.d.

M800H09	-2	-2	5.0	0.006	n.d.	n.d.

M800H11	12.6	0.011	5.9	0.007	n.d.	n.d.

M800H35	5.22	0.0052	5.8	0.007	n.d.	n.d.

M800H10 and Unknown1	9.4	0.008	10.2	0.012	n.d.	n.d.

Sugar (most probably fructose)	n.d.	n.d.	n.d.	n.d.	52.9	0.008

Total identified	68.2	0.061	37..3	0.042	53.6	0.008

Total characterized	35.7	0.032	43.6	0.05	14.9	0.002

Total extractable	103.9	0.093	80.9	0.092	68.4	0.01

Post-extraction solids3	3.9	0.003	7.1	0.008	32.2	0.005

Accountability4	108%	88%	100%

1   “M800H10 and unknown” were counted as characterized.

2   M800H09 and M800H035 co-eluted in the methanol extract of immature tomato plants and were quantified together.

3   Residues remaining after exhaustive extractions.

4   Accountability = (Total extractable + Total unextractable)/(TRR from combustion analysis) * 100.

n.d. = not detected.

Table 13.  Summary of Characterization and Identification of Radioactive Residues in Tomato Matrices Following Application of [Uracil-4-14C]-Saflufenacil at 0.089 lbs. ai/A.

Metabolite Fraction	Tomato Plant

(BBCH 62/63)	Tomato Plant

(Harvest)	Tomato Fruit

(Harvest)

	TRR = 0.131 ppm	TRR = 0.138 ppm	TRR = 0.037 ppm

	% TRR	ppm	% TRR	ppm	% TRR	ppm

Saflufenacil 	4.8	0.006	8.5	0.012	n.d.	n.d.

M800H10	2.4	0.003	2.9	0.004	n.d.	n.d.

M800H11	3.9	0.005	3.6	0.005	n.d.	n.d.

TFA	82.2	0.108

(0.025*)	51.7	0.071

(0.016*)	48.6	0.018

(0.004*)

Sugar (most probably fructose)	n.d.	n.d.	n.d.	n.d.	33.7	0.012

Total identified	93.2	0.122	66.8	0.092	82.3	0.03

Total characterized	9.3	0.012	23.7	0.033	1.8	0.001

Total extractable	102.5	0.134	90.5	0.125	84.0	0.031

Post-extraction solids1	6.4	0.008	6.4	0.009	11.8	0.004

Accountability2	108%	97%	95%

*   ppm calculated using the molecular mass of TFA.

1   Residues remaining after exhaustive extractions.

2   Accountability = (Total extractable + Total unextractable)/(TRR from combustion analysis) * 100.

n.d. = not detected.

Sunflower

On 8/30/06, the HED Chemistry Science Advisory Council (ChemSAC) reviewed a waiver request for a sunflower metabolism study:

“BAS 800-H Sunflower Metabolism Waiver Request – BASF has requested a waiver for a crop metabolism study to support use of BAS 800-H as a foliar agent on sunflower.  ChemSAC agreed that the proposed sunflower use is acceptable without a sunflower metabolism study - so long as the results of existing non-GLP studies of velvet leaf metabolism and of cell culture metabolism are submitted.  A major concern, however, was addressed not to the use on sunflower, but to possible future attempts to extend use to other crops.  It was felt that acceptance of the currently requested waiver should not serve as a precedent for also waiving studies on those other crops.

In sum, ChemSAC concluded that submission of the cell culture and velvet leaf studies would be adequate to support the sunflower use without need for additional metabolism data. But ChemSAC also concluded that if it is desired to expand this treatment to any major crop in the future ChemSAC will require proper GLP metabolism studies on any such crops.”

The summaries of the non-GLP studies (included in MRID# 47128004) confirm that there were no additional metabolites seen in these studies.  No additional metabolism data are required to support the sunflower desiccation use.

Conclusions:  The submitted metabolism data for corn, soybean, and tomato are adequate to elucidate the nature of the residue in plants resulting from preplant/preemergence application.  The main reactions involved in the metabolic pathway of saflufenacil are N-demethylation at the uracil ring, stepwise degradation (N-dealkylation) of the N-methyl-N-isopropyl group, hydrolytic cleavage of the uracil ring generating a urea side chain, and hydroxylation of the phenyl ring.  Three metabolites of saflufenacil were present either in all plant matrices or were relatively prominent in some plant matrices; i.e., exceeded 10% of the TRR and, 0.05 ppm.  M800H11 was found in all corn and soybean matrices from both 14C-labeled uracil and 14C-labeled phenyl saflufenacil.  M800H11 is formed when saflufenacil undergoes demethylation at both nitrogen atoms.  Metabolite M800H11 thus has a very similar chemical structure compared to the parent compound.  M800H35 was detected only after 14C-labeled phenyl saflufenacil treatment and was detected at higher levels in soybean matrices.  M800H35 is formed when parent saflufenacil undergoes demethylation at the sulfonylurea side chain and cleavage of the uracil ring.  The third prominent metabolite, designated as M800H29 and commonly known as TFA, was detected only after treatment with 14C-labeled uracil saflufenacil and was detected at relatively high levels in all matrices.  However, TFA is a polar, low-molecular-weight organic acid with no chemical structural resemblance to the parent molecule.  The HED ROCKS determined that residues of concern for the tolerance expression and risk assessment consist of saflufenacil, M800H11, and M800H35 (Memo, B. Daiss, 1/6/09; D359645).  This conclusion applies only to preplant/preemergence and sunflower harvest-aid uses.

FIGURE 1.  Proposed Metabolic Profile of Saflufenacil in Corn.

FIGURE 2.  Proposed Metabolic Profile of Saflufenacil in Soybean.

860.1300 Nature of the Residue - Livestock

DER Reference List	Lactating Goat (47128005.der.doc)

			Hen (47128007.der.doc)

Goat

[Phenyl-U-14C]-saflufenacil or [uracil-4-14C]-saflufenacil were administered to two lactating goats (one goat per label) at an average dose of 13.9 ppm feed (corresponding to 18.4 mg/animal/day) for the phenyl label and an average dose of 13.4 ppm feed (corresponding to 17.8 mg/animal/day) for the uracil label (~57X).  The radiolabeled compound was administered orally by gavage once a day in the morning for eight consecutive days.  Milk was collected twice a day (in the morning before the administration of the test substance and in the afternoon) and excreta samples were collected once a day throughout the study period.  The animals were sacrificed 23 hours after the last administration and the following tissues were collected for analysis: liver, kidney, blood, fat, muscle, gastrointestinal tract and contents, and bile.

The majority of the administered dose (AD) was eliminated via urine (62.0% AD and 45.6% AD for phenyl and uracil label, respectively) and feces (28.5% AD and 41.9% AD for phenyl and uracil label, respectively).  An additional 0.8% AD (phenyl label) and 0.5% AD (uracil label) was recovered from the stomach and gut contents.  Throughout the study period (8 days), only 0.04% AD (phenyl label) and 0.10% AD (uracil label) was transferred into milk and less than 0.4% AD (phenyl label) and 1.6% AD (uracil label) was transferred to edible tissues (muscle, fat, kidney, and liver).  The highest concentration of residues were detected in liver and kidney (0.962 ppm and 0.130 ppm, respectively, for the phenyl label and 3.832 ppm and 0.171 ppm, respectively, for the uracil label).

Extractability of residues from feces, urine, milk, and tissues was high, with 82.0% to 105.7% (phenyl label) and 80.9% to 107.7% (uracil label) of 14C-residues released after treatment of homogenized matrices with ACN (all matrices, except urine) and water (kidney) or isohexane (muscle and fat).  Characterization and identification of metabolites by HPLC was conducted on tissues, feces, and milk following organic extraction of samples.  TRR identified in tissues and milk ranged from 58.8% to 103.0% for the phenyl label and from 80.2 % to 106.3% for the uracil label, while TRR identified in excreta ranged from 89.2% to 100.0% (phenyl label) and 92.9% to 98.7% (uracil label).  Metabolite identification and peak assignment was confirmed by HPLC, LC-MS/MS analysis of selected concentrated extracts, co-chromatography, and by comparison of the retention time with those of the respective reference items.

For the phenyl label, the predominant metabolite identified in all matrices was the parent compound, saflufenacil, constituting 44.2 % of the TRR (0.004 ppm) in muscle, 44.1% of the TRR (0.004 ppm) in fat, 73.8% of the TRR (0.096 ppm) in kidney, 80.2% of the TRR (0.772 ppm) in liver, 47.0% of the TRR (0.003 ppm) in milk, 91.8% of the TRR (8.119 ppm) in urine, and 41.5% of the TRR (0.432 ppm) in feces.  Other major metabolites identified in milk and tissues were M800H04 accounting for 12.9% of the TRR (0.017 ppm) in kidney and 13.2% of the TRR (0.127 ppm) in liver, and M800H10, accounting for 37.5% of the TRR (0.003 ppm) in muscle, 14.7% of the TRR (0.001 ppm) in fat, and 39.1% of the TRR (0.002 ppm) in milk.  Major metabolites identified in excreta were M800H01, accounting for 5.2% of the TRR (0.463 ppm) in urine and 30.3% of the TRR (0.316 ppm) in feces, and M800H03 accounting for 3.0% of the TRR (0.262 ppm) in urine.  Minor metabolites (<10% of the TRR and/or <0.1 ppm) identified in some of the goat matrices were M800H01, M800H03, M800H07, M800H10, and M800H11.

For the uracil label, the predominant metabolite (except in milk and feces) identified in all matrices was the parent compound, saflufenacil, constituting 56.7% of the TRR (0.006 ppm) in muscle, 65.1% of the TRR (0.011 ppm) in fat, 71.3% of the TRR (0.122 ppm) in kidney, 75.7% of the TRR (2.900 ppm) in liver, 25.4% of the TRR (0.003 ppm) in milk, 69.4% of the TRR (7.010 ppm) in urine, and 33.8% of the TRR (0.460 ppm) in feces.  Other major metabolites identified in milk and tissues were M800H04, accounting for 10.0% of the TRR (0.017 ppm) in kidney and 14.2% of the TRR (0.543 ppm) in liver, and M800H10, accounting for 49.6% of the TRR (0.005 ppm) in muscle, 15.1% of the TRR (0.003 ppm) in fat, and 39.9% of the TRR (0.005 ppm) in milk.  Major metabolites identified in excreta were M800H01, accounting for 8.8 % of the TRR (0.893 ppm) in urine and 39.5% of the TRR (0.538 ppm) in feces, M800H03, accounting for 10.2% of the TRR (1.027 ppm) in urine and 11.0% of the TRR (0.150 ppm) in feces, M800H05, accounting for 1.8% of the TRR (0.184 ppm) in urine, and M800H11, accounting for 2.7% of the TRR (0.268 ppm) in urine and 9.3% of the TRR (0.127 ppm) in feces. Minor metabolites identified in some of the goat matrices were M800H01, M800H02, M800H03, and M800H10.

Saflufenacil was metabolized in lactating goat by several dealkylation steps (phase-I reaction) occurring at two different sites in the molecule (N-isopropyl-N-methylsulfamide side chain and at the uracil ring) and via hydrolytic opening of the uracil ring.

TABLE 14.  Summary of Characterization and Identification of Radioactive Residues in Goat Matrices Following Application of [Phenyl-U-14C]-Saflufenacil at a Mean of 13.87 ppm/day (~57X).

Metabolite Fraction	Muscle	Fat	Kidney	Liver	Milk1

	TRR = 0.008 ppm	TRR = 0.010 ppm	TRR = 0.130 ppm	TRR = 0.962 ppm	TRR = 0.006

ppm2

	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm

Saflufenacil	44.2	0.004	44.1	0.004	73.8	0.096	80.2	0.772	47.0	0.003

M800H01

	2.2	0.003	1.2	0.011	9.1	0.001

M800H03

	7.8	<0.0005

M800H04

	12.9	0.017	13.2	0.127

M800H10	37.5	0.003	14.7	0.001	1.7	0.002

	39.1	0.002

Total identified	81.7	0.007	58.8	0.006	90.6	0.118	94.7	0.911	103.0	0.006

Total characterized	0.3	<0.0005	23.6	0.002	5.8	0.008	1.5	0.015	2.7 <0.0005

Total extractable	82.0	0.007	82.4	0.008	96.4	0.126	96.2	0.925	105.7 0.006

Unextractable3	16.5	0.001	12.0	0.001	3.7	0.005	2.7	0.026	4.0	<0.0005

Accountability4	100%	90%	101%	99%	100%

Shaded areas = not detected.

1   Calculated for Day 1-8 in the case of the pooled milk samples.

2   Milk TRR values were calculated assuming a density of 1.0 g/mL.

3   Residues remaining after exhaustive extractions.

4   Accountability = (Total extractable + Total unextractable)/(TRR from combustion analysis) * 100.

TABLE 15.  Summary of Characterization and Identification of Radioactive Residues in Goat Matrices Following Application of [Uracil-4-14C]-Saflufenacil at a Mean of 13.37 ppm/day (~57X).

Metabolite Fraction	Muscle	Fat	Kidney	Liver	Milk1

	TRR = 0.011 ppm	TRR = 0.017 ppm	TRR = 0.171 ppm	TRR = 3.832 ppm	TRR = 0.012 ppm2

	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm

Saflufenacil	56.7	0.006	65.1	0.011	71.3	0.122	75.7	2.900	25.4	0.003

M800H01

	5.2	0.009	1.4	0.054	6.7	0.001

M800H03

	3.7	0.006

	8.8	0.001

M800H04

	10.0	0.017	14.2	0.543

M800H10	49.6	0.005	15.1	0.003	2.5	0.004

	39.9	0.005

Total identified	106.3	0.012	80.2	0.014	92.8	0.159	91.3	3.497	80.9	0.009

Total characterized	1.4	<0.0005	26.8	0.005	4.5	0.008	1.9	0.073	---	---

Total extractable	107.7	0.012	107.0	0.018	97.3	0.167	93.2	3.570	80.9 0.009

Unextractable3	1.0	<0.0005	9.2	0.002	3.5	0.006	2.4	0.094	14.1	0.002

Accountability4	109%	118%	101%	96%	92%

Shaded areas = not detected.

1   Calculated for Day 1-8 in the case of the pooled milk samples.

2   Milk TRR values were calculated assuming a density of 1.0 g/mL.

3   Residues remaining after exhaustive extractions.

4   Accountability = (Total extractable + Total unextractable)/(TRR from combustion analysis) * 100.

Hen

The nature of the residue in egg and tissues was investigated in laying hens (n = 8 animals per treatment group) dosed orally once daily by gavage with either [phenyl-U-14C]-saflufenacil or [uracil-U-14C]-saflufenacil at a rate of 0.83-0.84 mg ai/kg bw/day (12.6-12.7 ppm in the feed) for 10 consecutive days (~47X).  Samples of eggs and excreta were collected daily.  The treated hens were sacrificed ~23 hours after the final dosage.  Samples of blood, liver, muscle (leg and chest), fat, and gastrointestinal (GI) tract (plus contents) were collected.  The maximum storage interval of samples from collection to analysis was 4.4 months.

The majority of the AD was detected in the excreta, accounting for 78-85% of the AD.  Only 0.04-0.05% of the AD and 0.029-0.046% of the AD were detected in the edible tissues and eggs, respectively.  In edible tissues, the TRR were highest in liver (0.060-0.062 ppm) and were relatively lower in muscle (0.011 ppm) and fat (0.011 ppm).  The TRR in Day-10 egg samples were 0.010-0.016 ppm.  Peak egg residues were observed on Day-6 (0.012 ppm for the phenyl label and 0.018 ppm for the uracil label).

The majority of the TRR in excreta (pooled samples Day 1-Day 10), muscle, fat, liver, and eggs (pooled sample Day 2-Day 10) were each extracted with ACN (78.5-98.9% of the TRR; 0.008-4.690 ppm).  Residues in liver and fat were further extracted with water (11.3-13.1% of the TRR; 0.007-0.008 ppm) and isohexane (4.3-12.7% of the TRR; 0.0004-0.001 ppm), respectively.  The isohexane extract of fat was not further characterized.  Unextractable residues in excreta, muscle, fat, liver, and eggs each accounted for 1.1-18.1% of the TRR (0.0004-0.052 ppm).  Pronase treatment of the unextractable residues in liver released a further 2.7-4.6% of the TRR (0.002-0.003 ppm).  Sample extracts were analyzed by reversed-phase HPLC with UV-VIS and radioactivity detection.  Identification of metabolites was confirmed by LC-MS and LC-MS/MS.

The parent compound saflufenacil was identified as a major residue in excreta (50.4-53.2% of the TRR; 2.027-2.525 ppm), muscle (38.2-54.7% of the TRR; 0.005-0.006 ppm), fat (24.0-26.1% of the TRR; 0.002 ppm), liver (47.0-47.4% of the TRR; 0.028-0.029 ppm), and eggs (20.8% of the TRR; 0.002 ppm for the phenyl label only).  Additional major residues identified included M800H01 in excreta (20.6-22.1% of the TRR; 0.888-0.979 ppm) and liver (21.0-24.0% of the TRR; 0.012-0.014 ppm); M800H02 in excreta (6.7-7.6% of the TRR; 0.305-0.0316 ppm); M800H03 in excreta (3.8-3.9% of the TRR; 0.153-0.186 ppm), M800H05 in excreta (7.2-7.6% of the TRR; 0.289-0.362 ppm); M800H10 in muscle (22.0-23.1% of the TRR; 0.002-0.003 ppm), fat (12.7-15.8% of the TRR; 0.001 ppm) and eggs (51.6-67.6% of the TRR; 0.008-0.009 ppm) and M800H11 in excreta (3.9-4.4% of the TRR; 0.177-0.185 ppm).

The metabolism of saflufenacil in laying hens proceeds via different dealkylation steps, which occur at either the sulfamide side chain or the uracil ring.  These reactions produce metabolites that are rapidly excreted, along with parent, and do not readily accumulate in tissues or eggs.

TABLE 16.  Summary of Characterization and Identification of Radioactive Residues in Hen Matrices Following Application of [Phenyl-U-14C] Saflufenacil (~47X).

Compound	Excreta(Pooled Sample Day 1-10)	Muscle	Fat	Liver	Eggs(Pooled Sample Day 2-10)

	TRR = 4.586 ppm	TRR = 0.011 ppm	TRR = 0.011 ppm	TRR = 0.062 ppm	TRR = 0.011 ppm

	%TRR	ppm	% TRR	ppm	% TRR	ppm	% TRR	ppm	%TRR	ppm

Saflufenacil	53.2	2.525	54.7	0.006	26.1	0.002	47.4	0.029	20.8	0.002

M800H01	20.6	0.979	3.2	<0.0005	1.7	<0.0005	24.0	0.014	-	-

M800H021	6.7	0.316	1.0	<0.0005	-	-	3.2	0.002	-	-

M800H03	3.9	0.186	1.2	<0.0005	-	-	2.0	0.001	-	-

M800H05	7.6	0.362	1.0	<0.0005	2.3	<0.0005	2.2	0.001	-	-

M800H10	1.6	0.074	23.1	0.002	15.8	0.001	7.6	0.005	67.6	0.008

M800H11 	3.9	0.185	1.0	<0.0005	-	-	2.6	0.002	–	–

Total identified	97.5	4.627	85.2	0.009	45.9	0.004	89.0	0.054	88.4	0.010

Total characterized	1.4	0.064	3.3	<0.0005	48.1	0.0044	6.5	0.004	9.2 0.001

Total extractable	98.9	4.690	93.4	0.010	94.7	0.0084	95.2	0.058	94.8 0.011

Unextractable2	1.1	0.051	6.6	0.001	5.3	0.0004	5.0	0.003	5.2	0.001

Accountability3	103%	100%	80%	98%	109%

1  The excreta extract contained the metabolite M800H02 (identified by LC-MS/MS) and potentially in addition the metabolite M800H06 (not separated by HPLC).

2  Residues remaining after exhaustive extractions.

3  Accountability = (Total extractable + Total unextractable)/(TRR from combustion analysis) × 100.

TABLE 17.  Summary of Characterization and Identification of Radioactive Residues in Hen Matrices Following Application of [Uracil-4-14C] Saflufenacil (~47X).

Compound	Excreta(Pooled Sample Day 1-10)	Muscle	Fat	Liver	Eggs(Pooled Sample Day 2-10)

	TRR = 3.825 ppm	TRR = 0.011 ppm	TRR = 0.011 ppm	TRR = 0.060 ppm	TRR = 0.016 ppm

	%TRR	ppm	% TRR	ppm	% TRR	ppm	% TRR	ppm	%TRR	ppm

Saflufenacil	50.4	2.027	38.2	0.005	24.0	0.002	47.0	0.028	9.9	0.002

M800H01	22.1	0.888	2.4	<0.0005	1.8	<0.0005	21.0	0.012	0.8	<0.0005

M800H021	7.6	0.305	0.3	<0.0005	2.4	<0.0005	1.9	0.001	–	–

M800H03	3.8	0.153	1.3	<0.0005	–	–	2.4	0.001	–	–

M800H05	7.2	0.289	–	–	0.7	<0.0005	1.2	0.001	1.3	<0.0005

M800H10	0.9	0.037	22.0	0.003	12.7	0.001	7.3	0.004	51.6	0.009

M800H11 	4.4	0.177	–	–	1.9	<0.0005	1.4	0.001	2.2	<0.0005

Total identified	96.4	3.876	64.2	0.009	43.5	0.004	82.2	0.048	65.8	0.012

Total characterized	2.4	0.093	18.4	0.003	49.3	0.005	8.3	0.006	17.6	0.003

Total extractable	98.7	3.970	81.9	0.011	93.7	0.009	91.6	0.056	87.7	0.015

Unextractable2	1.3	0.052	18.1	0.003	6.3	0.001	8.2	0.005	12.3	0.002

Accountability3	105%	127%	91%	102%	106%

1  The excreta extract contained the metabolite M800H02 and potentially in addition the metabolite M800H06 (not separated by HPLC).

2  Residues remaining after exhaustive extractions.

3  Accountability = (Total extractable + Total unextractable)/(TRR from combustion analysis) × 100.

Conclusions:  The submitted goat and poultry metabolism data are adequate to satisfy data requirements.  Saflufenacil was metabolized by several dealkylation steps occurring at two different sites in the molecule (N-isopropyl-N-methylsulfamide side chain and at the uracil ring) and via hydrolytic opening of the uracil ring (goat only).  In the ruminant metabolism study, saflufenacil was a major residue in all matrices.  Only M800H04, a ring opening product, exceeded 10% of the TRR and 0.05 ppm (liver; 14.2% of the TRR, 0.543 ppm).  In the poultry metabolism study, saflufenacil was a major residue in all matrices and no metabolites exceeded 10% of the TRR and 0.05 ppm.  The HED ROCKS determined that saflufenacil per se is the only for the tolerance expression and risk assessment (Memo, B. Daiss, 1/6/09; D359645).  This conclusion and the decision to exclude the plant metabolites M800H11 and M800H35 as residues of concern in livestock were based on the low potential for exposure associated with the currently proposed uses.  These conclusions will be reevaluated if future proposed uses result in a significant increase in the livestock dietary burden.

FIGURE 3.  Proposed Metabolic Profile of Saflufenacil in Lactating Goat.

860.1340 Residue Analytical Methods

Plant methods

DER Reference List	47128008.der.doc

BASF Method D0603/02 was developed for determination of residues of saflufenacil and its metabolites M800H11 and M800H35 in different plant matrices using LC-MS/MS.  Residues of saflufenacil and its metabolites M800H11 and M800H35 were extracted from non-oily crop matrices (wheat grain and hay, garbanzo bean, and peach fruit) with methanol:water (70:30; v:v). The methanol extract, or in some matrices the concentrated methanol extract, was partitioned with a mixture of ethyl acetate-cyclohexane (70:30; v:v) and 0.1% TFA.  An aliquot of the organic phase was evaporated and reconstituted in methanol:water (50:50; v:v) for LC-MS/MS analysis.  Oily crops (orange fruit and soybean seed) were extracted with methanol:water (70:30; v:v) and pre-partitioned with isooctane.  An aliquot of the aqueous methanol phase or the concentrated methanol phase was partitioned with a mixture of ethyl acetate-cyclohexane (70:30; v:v) and 0.1% TFA.  An aliquot of the organic phase was evaporated and reconstituted in methanol:water (50:50; v:v) for LC-MS/MS quantitation.  For the residues in oil matrices (corn oil), samples were extracted with acetonitrile.  Following partitioning of the acetonitrile extract with isooctane (3 times), an aliquot of the acetonitrile layer was diluted with methanol-water (50:50; v:v) for LC-MS/MS determination.  Two transitions per analyte were monitored for the quantitation and confirmation of saflufenacil, M800H11 and M800H35. The residues of each analyte were expressed as parent equivalents using a molecular weight conversion factor (1.0 for saflufenacil, 1.06 for M800H11, and 1.42 for M800H35).  The LOQ was 0.01 ppm for each analyte in food matrices (human consumption) and 0.025 ppm for each analyte in feed matrices (livestock consumption).  The limit of detection (LOD) was not tested, but set at 20% of LOQ.

.  The method detector response was determined to be linear in the range of 0.05 ng/mL to 0.5 ng/mL (r ≥0.98).

The method D0603/02 was successfully validated by an independent laboratory, ADPEN Laboratories, INC.

Residues of saflufenacil and its metabolites M800H11 and M800H35 in soybean matrices (phenyl label) from the metabolism study were extracted sequentially in methanol and water.  The extractability and accountability experiments indicate that the recoveries of bioincurred residues from soybean matrices (forage and straw, except for soybean pod) with methanol:water (70:30,v/v) were very similar to the metabolism study.

Conclusions:  Based on validation data provided by the petitioner and the successful ILV, HED has determined that BASF Method D0603/02 is suitable as an enforcement method for plant commodities as defined in SOP No. ACB-019 (9/15/08).  Note that the petitioner submitted a revised version of the method (MRID# 47796103) in which the calculations section was revised by removing the directions to correct the results for apparent residues in the control samples.

Livestock methods

DER Reference List	47128010.der.doc

BASF analytical Method No. L0073/01 was developed for determination of saflufenacil (BAS 800 H) in livestock matrices using LC-MS/MS.  Livestock tissue samples including bovine liver, kidney, fat, muscle, whole milk, skimmed milk, cream, and hen’s egg were extracted with acetonitrile.  The acetonitrile extract was cleaned-up by liquid/liquid partition using dichloromethane and water.  The dichloromethane phase was evaporated and reconstituted in methanol:water (50:50; v:v) for LC-MS/MS analysis.  Two transition ions were monitored (m/z of 501 to 459 and 501 to 349) for saflufenacil and either of the transitions can be used for quantitation purposes.

The LOQ and LOD of the method are 0.01 ppm and 0.000084 ppm, respectively.  Concurrent recovery samples were prepared at LOQ and 10X LOQ in each matrix and were found generally to be within the acceptable range of 70% to 120%.  Good linearity between detector response and concentration of the analyte was observed in the range of 0.01 to 0.25 ng/mL.  The extraction efficiency study was not performed since Method L0073/01 uses the same extraction solvent as that used in the livestock metabolism study.  Method L0073/01 was successfully validated by an independent laboratory.

Conclusions:  Based on validation data provided by the petitioner and the successful ILV, HED has determined that BASF Method L0073/01 is suitable as an enforcement method for livestock commodities as defined in SOP No. ACB-019 (9/15/08).  Note that the petitioner submitted a revised version of the method (MRID# 47796104) in which the calculations section was revised by removing the directions to correct the results for apparent residues in the control samples.

860.1360 Multiresidue Methods (MRM)

DER Reference List	47128010.der.doc

Saflufenacil and its metabolites M800H11 and M800H35 were screened through the MRM described in the United States Food and Drug Administration (FDA) Pesticide Analytical Manual, Vol. I (PAM I).  Saflufenacil and the metabolites were tested using procedures outlined in Protocols B, C, D, E, and F of the MRM.  All Protocols B, C, D, E, and F were found to be unsuitable for determination of residues of saflufenacil and its metabolites M800H11 and M800H35.  Since the analytes are not N-methyl-carbamates, naturally fluorescent or substituted urea derivatives, the tests using Protocol A and G were not performed.

Conclusions:  The MRMs are not suitable for the analysis of saflufenacil or its metabolites.  The multiresidue methods testing data will be forwarded to FDA for further evaluation and inclusion of results in PAM Vol. I.

860.1380 Storage Stability

Plant commodities

DER Reference List	47523801.der.doc

Samples of corn (forage, grain, and stover), garbanzo bean (chickpea), orange (fruit, juice, oil, and pulp), radish roots, grape (raisin), and soybean (forage, hay, and seed) were fortified separately with saflufenacil, M800H11, and M800H35 at a level of 1.0 ppm each and were stored at <-5 ºC for a duration of 0, 44, 130, 214, 410-422, and 548-553 days (approximately 0, 1.5, 4.3, and 7.1, 13.7-14.1, and 18.3-18.4 months).  The samples were analysed for residues of saflufenacil and the metabolites M800H11 and M800H35 by LC-MS/MS using BASF Analytical Method Number D0603/02.  The freezer storage stability results were corrected for mean concurrent recovery values obtained from freshly fortified samples.

Under these conditions, residues of saflufenacil and its metabolites M800H11 and M800H35 are stable in/on corn (grain, forage, stover); soybean (seed, forage, hay); orange (fruit, pulp, juice, oil); radish (root); grape (raisin); and garbanzo bean (seed) commodities during frozen storage for up to 548 days.

Sample storage conditions and intervals

The storage intervals and conditions of samples from the residue field trials, rotational crop field trials, and processing studies which were submitted to support this petition are presented in Table 18.

Table 18.  Summary of Storage Conditions and Intervals of Samples from Crop Field Trial, Processing, and Field Rotational Crop Studies.

Matrix 	Storage Temperature (°C)	Actual Storage Duration for Most Samples	Interval of Demonstrated Storage Stability

Legume Vegetables (MRID 47128218)

Pea, succulent seed with pod	<-5 	83-405 days	548 days

Pea, succulent seed without pod

83-399 days

	Pea, dry seed

317-372 days

	Garbanzo, dry seed

14-353 days

	Soybean, succulent seed with pod

250-342 days

	Soybean, succulent seed without pod

251-289 days

	Soybean, dry seed

193-236 days

	Soybean, forage

225-263 days

	Soybean, hay

228-266 days

	Citrus (MRIDs 47128219 & 47128228)

Orange	<-5	44-417 days	548 days

Grapefruit

57-451 days

	Lemon

43-257 days

	Citrus oil

430 days

	Sunflower (MRID 47128226)

Sunflower, seed	<-5	10-97 days	548 days

Cotton (MRID 47128224 & 47445902)

Cotton, undelinted seed	<-5	7-53 days	548 days

Cotton, gin byproducts	<-5	7-55 days

	Cotton Processed Commodities	<-5	129 days

	Grapes (MRID 47128225 & 47128232)

Grapes 	-5 to -28	389-450 days

	Cereal Grains (MRID 47128223 & 47128231)

Wheat, Forage	<-5	29-392 days	548 days

Wheat, Hay

33-493 days

	Wheat, Grain

10-367 days

	Wheat, Straw

15-387 days

	Corn, K+CWHR

281-462 days

	Corn, Forage

56-391 days

	Corn, Grain

70-429 days

	Corn, Stover

70-371 days

	Grain sorghum, Forage

253-363 days

	Grain sorghum, Grain

337-448 days

	Grain sorghum, Stover

250-401 days

	Rice, Grain

155-381 days

	Rice, Straw

329 days

	Barley, Grain

48-239 days

	Sweet sorghum

353 days

	Pome Fruit (MRIDs 47128220 & 47128229)

Apple Fruit	<-5	304-436 days	548 days

Pear Fruit

411-474 days

	Stone Fruit (MRID 47128221 & 47128230)

Cherry	<-5	32-448 days	548 days

Peach

303-428 days

	Plum

315-432 days

	Tree Nuts (MRID 47128222)

Almond Nutmeat	<-5	330-427 days	548 days

Almond Hulls

417-462 days

	Pecan Nutmeat

265-307 days

	Rotational Crop Study:  Wheat, Lettuce, and Radish as the Rotational Crops (MRID 47128018)

Wheat, Forage	<-5	109-144 days	548 days

Wheat, Hay

111-133 days

	Wheat, Grain

43-82 days

	Wheat, Straw

50-89 days

	Radish, Tops/Roots

105-267 days

	Lettuce, Leaves

88-273 days

Livestock commodities

DER Reference List	47128015.der.doc

Storage stability was demonstrated concurrently with the analytical phase of the ruminant feeding study (Table 19).

TABLE 19.  Summary of Storage Conditions and Intervals of Samples from the Ruminant Feeding Study.

Matrix	Storage Temperature (oC)	Actual Storage Duration1 (days)	Interval of Demonstrated Storage Stability (days)

Whole Milk	(-18	4-63	51	Demonstrated concurrently with the analytical phase by storing fortified and untreated control samples (5 g) of whole milk, muscle, liver, kidney and fat at <-18oC.  After the specified storage interval, one control sample, two freshly fortified samples and two stored fortified samples were analyzed.

Skim Milk

29	Not conducted

	Cream

29	Not conducted

	Muscle

23-30	31

	Liver

24-31	32

	Kidney

24-31	32

	Fat

27-34	35

	1  From sample collection to analysis.

Conclusions:  Adequate storage stability data have been submitted.  Residues of saflufenacil, M800H11, and M800H35 were stable (<30% degradation) in all plant matrices during freezer storage for up to 548 days; and residues of saflufenacil were stable in all ruminant matrices during freezer storage for up to 35 days.  These data support the storage conditions and intervals of samples collected from the various crop field trials, the rotational crop studies, and the ruminant feeding study.  There are no unresolved storage stability issues, and no corrections need to be applied to the various magnitude of the residue studies.

860.1480 Meat, Milk, Poultry, and Eggs

Livestock dietary burdens

The potential for secondary transfer of saflufenacil residues of concern in meat, milk, and eggs exists because there are livestock feedstuffs associated with the proposed uses on apples, citrus, cereal grains, legumes, sunflowers, and almonds.  The livestock dietary burdens of saflufenacil and its metabolites are presented in Table 20 and reflect the most recent guidance from HED (June, 2008) concerning revisions of feedstuff percentages in Table 1 and constructing reasonably balanced dietary burdens (RBDBs).  The calculated total dietary burdens of saflufenacil and its metabolites (based on tolerance-level residues) are 0.12 ppm for beef cattle, 0.24 ppm for dairy cattle, 0.27 ppm for poultry, and 0.18 ppm for swine.

Table 20a.  Beef Cattle Dietary Burden Contribution for Saflufenacil.

Feedstuff	Type1	Tolerance

(ppm)	% Dry Matter	% Diet2	Dietary Contribution (ppm)3

Target % Diet Roughage	15

	Corn, field, forage	R	0.10	40	15	0.038

Target % Diet Carbohydrate Concentrate	80

	Corn, field, grain	CC	0.03	88	80	0.027

Target % Diet Protein Concentrate	5

	Sunflower meal	PC	1.0	92	5	0.054

TOTALS	100	0.12

Table 20b.  Dairy Cattle Dietary Burden Contribution for Saflufenacil.

Feedstuff	Type1	Tolerance

(ppm)	% Dry Matter	% Diet2	Dietary Contribution (ppm)3

Target % Diet Roughage	45

	Corn, field, forage	R	0.10	40	45	0.11

Target % Diet Carbohydrate Concentrate	45

	Corn, field, grain	CC	0.03	88	45	0.015

Target % Diet Protein Concentrate	10

	Sunflower meal	PC	1.0	92	10	0.11

TOTALS	100	0.24

Table 20c.  Poultry Dietary Burden Contribution for Saflufenacil.

Feedstuff	Type1	Tolerance

(ppm)	% Dry Matter	% Diet2	Dietary Contribution (ppm)3

Target % Diet Carbohydrate Concentrate	75

	Corn, field, grain	CC	0.03	--	75	0.022

Target % Diet Protein Concentrate	25

	Sunflower meal	PC	1.0	--	25	0.25

TOTALS	100	0.27

Table 20d.  Swine Dietary Burden Contribution for Saflufenacil.

Feedstuff	Type1	Tolerance

(ppm)	% Dry Matter	% Diet2	Dietary Contribution (ppm)3

Target % Diet Carbohydrate Concentrate	85

	Corn, field, grain	CC	0.03	--	85	0.026

Target % Diet Protein Concentrate	15

	Sunflower meal	PC	1.0	--	15	0.15

TOTALS	100	0.18

1  R:  Roughage; CC:  Carbohydrate concentrate; PC:  Protein concentrate.

2  OPPTS 860.1000 Table 1 Feedstuffs (June 2008).

3  Dietary contribution = tolerance ÷% dry matter x % diet (for poultry and swine % dry matter is not considered).

Livestock feeding studies

DER Reference List	47128015.der.doc (Dairy cattle feeding study)

			Poultry feeding waiver request

Dairy cattle feeding study

Saflufenacil was administered orally in treated feed to 14 Friesian dairy cows for 28-29 consecutive days.  The target doses were 0.1 (0.4X), 0.3 (1.2X), and 1.0 ppm (4.0X) (corresponding to target doses per unit body weight of 0.0036, 0.011, and 0.036 mg/kg bw/day).  The actual residue intakes (mean) in the diets were 0.118, 0.363, and 1.386 ppm.  Three animals were allocated each to the 0.1-ppm and 0.3-ppm dose groups, while five cattle were placed in the 1.0-ppm group, with the additional two animals being used for the depuration study.  Three animals were allocated to the untreated control group.  Samples of whole milk were collected twice daily during the dosing period.  Whole milk samples from each dose group were analyzed for saflufenacil residues on study days -3, -1, 1, 3, 6, 9, 12, 15, 18, 21, 24, 28 or 29, 30, and 35.  Samples of day-22 milk were separated into skim milk and cream, and each was analyzed.  On study day 28 or day 29, animals were sacrificed and samples of liver, kidney, composite muscle, and composite fat were collected for analysis.  Depuration studies were conducted for the 1.0-ppm dosing group where selected animals were sacrificed 2 days (day 30) and 7 days (day 35) after withdrawal of the dose.  Sample stability over the storage interval used during the study was demonstrated concurrently by storing fortified samples of untreated milk and tissues.  Residues of saflufenacil were determined using LC-MS/MS, BASF Analytical Method No. L0073/01.

In whole milk samples, residues of saflufenacil were <0.01 ppm (<LOQ) over the entire 28- to 29-day dosing period.  Residues of saflufenacil did not concentrate in samples of skim milk (<0.01 ppm) or cream (<0.01 ppm).  In tissues, residues of saflufenacil were not quantifiable in fat (<0.01 ppm) or muscle (<0.01 ppm).  There was a linear relationship between the feeding level and residues of saflufenacil in kidney and liver.  Residues of saflufenacil in kidney were <0.01 ppm at the 0.1-ppm dose level, 0.02 ppm at the 0.3-ppm dose level and ranged from 0.03 ppm to 0.04 ppm at the 1.0-ppm dose level.  In liver, residues of saflufenacil ranged from 0.17 ppm to 0.26 ppm at the 0.1-ppm dose level, 0.67 ppm to 0.88 ppm at the 0.3-ppm dose level, and from 2.09 ppm to 3.49 ppm at the 1.0-ppm dose level.

Following withdrawal of the dose, residues of saflufenacil were <0.01 ppm (<LOQ) in samples of whole milk, muscle, and fat on day 30 and day 35 of the study.  In kidney, residues of saflufenacil decreased from 0.03 ppm at day 30 to <0.01 ppm at day 35.  In liver, residues of saflufenacil decreased from 1.66 ppm at day 30 to 0.34 ppm at day 35.  Half lives of 2.5 and 4.0 days were calculated for saflufenacil residues in liver and kidney, respectively.

TABLE 21.  Summary of Residue Data from Ruminant Feeding Study with Saflufenacil.1

Matrix	Target Feeding Level (ppm)	Residue Levels (ppm)

n	Min.	Max.	Median	Mean	Std. Dev.

Whole milk/day 1-28/29	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	<0.01	<0.01	<0.01	<0.01	0

	0.3 (1.2X)	3	<0.01	<0.01	<0.01	<0.01	0

	1.0 (4.0X)	5	<0.01	<0.01	<0.01	<0.01	0

Skim milk/day 22	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	<0.01	<0.01	<0.01	<0.01	0

	0.3 (1.2X)	3	<0.01	<0.01	<0.01	<0.01	0

	1.0 (4.0X)	5	<0.01	<0.01	<0.01	<0.01	0

Cream/day 22	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	<0.01	<0.01	<0.01	<0.01	0

	0.3 (1.2X)	3	<0.01	<0.01	<0.01	<0.01	0

	1.0 (4.0X)	5	<0.01	<0.01	<0.01	<0.01	0

Fat	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	<0.01	<0.01	<0.01	<0.01	0

	0.3 (1.2X)	3	<0.01	<0.01	<0.01	<0.01	0

	1.0 (4.0X)	3	<0.01	<0.01	<0.01	<0.01	0

Muscle	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	<0.01	<0.01	<0.01	<0.01	0

	0.3 (1.2X)	3	<0.01	<0.01	<0.01	<0.01	0

	1.0 (4.0X)	3	<0.01	<0.01	<0.01	<0.01	0

Liver	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	0.17	0.26	0.19	0.21	0.047

	0.3 (1.2X)	3	0.67	0.88	0.76	0.77	0.105

	1.0 (4.0X)	3	2.09	3.49	2.25	2.61	0.77

Kidney	0	3	<0.01	<0.01	<0.01	<0.01	0

	0.1 (0.4X)	3	<0.01	<0.01	<0.01	<0.01	0

	0.3 (1.2X)	3	0.02	0.02	0.02	0.02	0

	1.0 (4.0X)	3	0.03	0.04	0.04	0.037	0.006

1  The LOQ for saflufenacil in all matrices analyzed was reported as 0.01 ppm.

Expected secondary residues in meat and milk

To determine the need for tolerances for saflufenacil residues in milk and tissues, the anticipated secondary residues in cattle matrices were estimated using transfer coefficient factors calculated from the maximum residues of saflufenacil observed in the ruminant feeding study.  The transfer coefficients (calculated as residue-level-to-feed ratios) are presented in Table 22.  The transfer coefficient for each matrix was then used to calculate the expected secondary residues by multiplying the transfer coefficient by the calculated dietary burden (Table 21).

Table 22.  Residue-Level-to-Feed Ratios (Transfer Coefficients) in Dairy Cattle Milk and Tissues.1

Matrix	Maximum Residue (ppm)	Feeding Level, ppm	Transfer Coefficient

Milk/Cream	<0.01	1.0	<0.01

Fat	<0.01

<0.01

Muscle 	<0.01

<0.01

Kidney	0.02	0.3	0.067

	0.04	1.0	0.04

Liver	0.26	0.1	2.6

	0.88	0.3	2.9

	3.49	1.0	3.49

1  Calculated from the maximum residues divided by the dose level.

Table 23.  Expected Secondary Residues in Meat and Milk.

Matrix	Dietary burden (ppm)	Secondary Residues (ppm)1	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)2

Milk 	0.24	<0.0024	-	0.01

Fat

<0.0024	-	0.01

Kidney

0.013	0.02	0.023

Muscle

<0.0024	-	0.01

Liver

0.72	0.80	0.80

1  Calculated from dietary burden x average transfer coefficient from Table 22.

2  HED is recommending for LOQ-level tolerances as a 10X feeding level was not included in the feeding study.

3  Meat byproducts, except liver.

Conclusions:  The residue data from the cattle feeding study is adequate to satisfy data requirements.  The feeding study data indicate that tolerances are needed for residues of saflufenacil at 0.80 ppm in liver and at 0.02 ppm in the meat byproducts, except liver of cattle, goats, horses, hogs, and sheep.  HED is recommending for LOQ-level tolerances (0.01 ppm) for fat, meat, and milk as a 10X feeding level was not included in the feeding study.

Poultry feeding study waiver request

BASF submitted a rationale to waive the data requirement for a poultry feeding study (MRID No. 47128019).  The petitioner argues that, based on the results of the laying hen metabolism study (conducted for 10 days, residues in eggs plateaued by day 6) and the proposed tolerances in poultry feed components, the potential for secondary residues in poultry products would be negligible.  The anticipated total residues (maximum TRR in each matrix from the hen metabolism study ÷ 47X) were 0.0013 ppm in liver and 0.0002-0.0003 ppm each in egg, muscle and fat.  Taking into account that the parent saflufenacil accounted for 47% of the TRR in liver from the hen metabolism study; the absolute amount of saflufenacil in liver would be 0.00061 ppm (47% x 0.0013 ppm TRR in liver) at the 1X feeding level and 0.0061 ppm at the 10X feeding level.  The LOQ of the proposed enforcement method is 0.01 ppm for saflufenacil in eggs and bovine matrices.  Therefore, assuming the maximum dietary burden, the anticipated levels of saflufenacil would <LOQ in all matrices.  The basis of the rationale to waive the data requirement for a poultry feeding study is deemed acceptable.  The results of the hen metabolism study indicate that there is no reasonable expectation of finite residues of saflufenacil in the meat, meat byproducts, and eggs of poultry as a result of the proposed uses.

860.1500 Crop Field Trials

Legume Vegetables, Crop Groups 6 and 7

DER Reference List	47128218.der.doc

BASF Agro Research has submitted field trial data for saflufenacil on pea, garbanzo beans (chickpeas), and soybean as representative crops of crop groups 6, legume vegetables; and 7, foliage of legume vegetables.  Thirty-nine trials were conducted on legume vegetables in the U.S. and Canada during the 2006 and 2007 growing seasons.  These included 13 trials on peas in NAFTA Zones 1 (NY and PA; 1 trial each), 5 (IL, IA, MB, and MN; 1 trial each), 10 (CA; 1 trial), 11 (ID; 1 trial), 12 (OR; 1 trial), and 14 (AB; 2 trials, MB; 1 trial, and SK; 1 trial); 11 trials on garbanzo beans (chickpeas) in NAFTA Zones 5 (MB and MN; 2 trials each), 6 (OK; 1 trial), 7 (SK; 1 trial), 7A (AB; 1 trial), 8 (TX; 1 trial), 9 (UT; 1 trial), 10 (CA; 1 trial), and 11 (ID; 1 trial); and 15 trials on soybeans in NAFTA Zones 2 (GA and VA; 1 trial each), 4 (AR and LA; 1 trial each), and 5 (IL; 1 trial, IA; 1 trial, KS; 2 trials, MB; 2 trials, MN; 2 trials, NE; 1 trial, ND; 1 trial, and ON; 1 trial).

Each trial location consisted of one control plot and one or two treated plots.  For sites with two treatment plots, one plot was designated to produce succulent peas/beans (representing edible-podded seed and succulent shelled seed) and the second plot was designated to produce dried pea and bean seeds.  At each treated plot, a single pre-plant incorporated or pre-emergence soil broadcast application of the 70% WG formulation of saflufenacil (BAS 800 00 H) was made at a rate of 0.083-0.093 lb ai/A (0.93-1.1X).  The applications were made using ground equipment in spray volumes of 16-31 gal/A.  An adjuvant was included in the spray mixture.

Samples of pea and soybean immature pod with seed were harvested by hand 62-119 days after treatment, targeting growth stage BBCH 73-77, to yield succulent seed with pod.  A portion was shelled to generate samples of succulent seed without pod.  Soybean forage and hay samples were harvested at the same time the succulent pods were collected; hay samples were air-dried under ambient conditions.  Samples of mature pea, garbanzo bean, and soybean dry seed were harvested 82-117 days after treatment, 93-148 days after treatment, and 82-162 days after treatment, respectively.  At four sites, additional samples of succulent pea, succulent soybean seed, soybean forage, and soybean hay were collected at 2-3 additional sampling intervals to evaluate residue decline.

Samples of legume vegetable RACs were analyzed for residues of saflufenacil and its metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.025 ppm for each analyte (0.075 ppm combined) in soybean forage and hay and 0.01 ppm for each analyte (0.03 ppm combined) in all other commodities.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all collected samples of the following RACs:  succulent pea seed with pod; succulent pea seed without pod; dried pea seed; dried garbanzo bean seed; succulent soybean seed with pod; succulent soybean seed without pod; mature soybean seed; soybean forage; and soybean hay.  Because residues were <LOQ in/on all samples from the four decline trials, residue decline could not be evaluated.

Conclusions:  The submitted residue data for legume vegetables, crop groups 6 and 7 are adequate to fulfill data requirements.  The number and locations of the crop field trials are in accordance with OPPTS Guideline 860.1500 (Table 24).  This residue program was previously approved by HED (Memorandum of Understanding, BASF with EPA and PMRA, 1/25/06; MRID No. 47128215).  The available data will support the proposed use pattern.

TABLE 24.  Trial Numbers and Geographical Locations for Legume Vegetables, Crop Groups 6 and 7.

NAFTA Growing Zones	Pea, Dry	Pea, Succulent	Garbanzo (Bean, Dried) Soybean

	Submitted	Requested1	Submitted	Requested1	Submitted	Requested1 Submitted	Requested1

Canada	U.S.2

Canada	U.S.2

Canada	U.S.3

Canada	U.S.4

1

	1	15

1A	2

	2	1

	2

15

2

2

4

2

2

5

2

	3	4	4	4	4	11	11	11

5B	4

	4	2

1

	6

	1

	7

	1

1

	7A

	1	1

8

	1

1

	9

	1

1

	10

	1

1

	11	1

	1

2	1

1

	12	1

	1	1	1

14	4	6

4

Total	13	8	5	13	8	8	11	5	9	15	12	15

1  As required under OPPTS 860.1500 Tables 1, 2, and 5 and PMRA Directive 98-02 Section 9 Table 2.

2  As required under OPPTS 860.1500 Tables 1 and 5 for succulent and dried pea; no regions specified for dried peas.

3  As required under OPPTS 860.1500 Table 5 for dried bean as a representative crop of crop group 6.

4  As required under OPPTS 860.1500 Table 5 for soybean as representative crop of crop groups 6 and 7.

5  One trial should be conducted in either Zone 1 or Zone 2.

The residue data for legume vegetables, crop groups 6 and 7 were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.025 ppm for each analyte (0.075 ppm combined) in soybean forage and hay and 0.01 ppm for each analyte (0.03 ppm combined) in all other commodities)).  The recommended tolerances for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, are 0.03 ppm for legume vegetables (group 6) and 0.10 ppm for the foliage of legume vegetables (group 7).

Citrus Fruit, Crop Group 10

DER Reference List	47128219.der.doc

BASF Corporation has submitted field trial data for saflufenacil on orange, grapefruit, and lemon as representative crops of crop group 10, citrus fruit.  A total of 23 citrus fruit field trials were conducted in the U.S. during the 2006 and 2007 growing seasons.  Twelve orange trials were conducted in NAFTA Zones 3 (FL; 8 trials), 6 (TX, 1 trial), and 10 (CA; 3 trials).  Six grapefruit trials were conducted in NAFTA Zones 3 (FL; 3 trials), 6 (TX; 1 trial), and 10 (AZ and CA; 1 trial each).  Five lemon trials were conducted in NAFTA Zones 3 (FL; 1 trial) and 10 (AZ and CA, 2 trials each).

Each trial location consisted of one untreated and one treated plot.  At each treatment plot, three broadcast applications of the 70% WG formulation of saflufenacil (BAS 800 00 H) were made to the orchard floor at 0.043-0.049 lb ai/A/application with a 20- to 22-day retreatment interval (RTI), for a total seasonal rate of 0.134-0.141 lb ai/A (1.0-1.1X).  Applications were made using ground equipment, in 20-36 gal/A spray volumes.  An adjuvant was included in the spray mixture.  Samples of mature citrus fruit were harvested on the day of the last application.  Additional samples of treated orange fruit were harvested at 7-, 14-, and 21-day PHIs from two FL sites.

Samples of citrus fruit RACs were analyzed for residues of saflufenacil and its metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  Residues were reported in ppm saflufenacil equivalents.  The LOQ was 0.01 ppm for each analyte in each matrix.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of orange, grapefruit, and lemon harvested the day of the last of three soil broadcast applications at a total rate of 0.134-0.141 lb ai/A.  Residues of saflufenacil, M800H11, and M800H35 were each <LOQ in/on samples of citrus fruit harvested 7, 14, and 21 days after the last application.

Conclusions:  The submitted field trial data for citrus are adequate to fulfill data requirements.  The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 25).  The available data will support the proposed use pattern.

TABLE 25.  Trial Numbers and Geographical Locations for Citrus.

NAFTA Growing Zones	Orange	Grapefruit	Lemon

	Submitted	Requested1	Submitted	Requested1	Submitted	Requested1

Canada	U.S.

Canada	U.S.

Canada	U.S.

3	8

8	3

3	1

1

6	1

1	1

1

	10	3

3	2

2	4

4

Total	12

12	6

6	5

5

1  As required under U.S. EPA OPPTS 860.1500 Tables 2 and 5 for orange, grapefruit, and lemon as representative crops of crop group 10, citrus fruit.

The residue data for citrus were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.01 ppm for each analyte (0.03 ppm combined)).  The recommended tolerances for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, are 0.03 ppm for fruit, citrus, group 10.

Pome Fruit, Crop Group 11

DER Reference List	47128220.der.doc

BASF Corporation has submitted field trial data for saflufenacil on apple and pear as representative crops of crop group 11, pome fruit.  A total of 25 pome fruit field trials were conducted in the U.S. and Canada during the 2006 growing season.  Fifteen trials were conducted on apples in NAFTA Zones 1 (NY; 3 trials), 2 (VA, 1 trial), 5 (MI; 2 trials, IL; 1 trial, and ON; 1 trial), 5B (QC; 1 trial), 9 (UT; 1 trial), 10 (CA; 1 trial), and 11 (ID and WA; 2 trials each).  Ten trials were conducted on pears in NAFTA Zones 1 (NY; 2 trials), 5 (MI; 2 trials and ON; 1 trial), 10 (CA; 2 trials), and 11 (ID; 1 trial and WA; 2 trials).

Each trial location consisted of one untreated and two treated plots.  At each treatment plot, three broadcast applications of the 70% WG formulation of saflufenacil (BAS 800 00 H) were made to the orchard floor at 0.042-0.047 lb ai/A/application for a total rate of 0.129-0.140 lb ai/A (1.0-1.1X).  The initial application was made at dormancy, 121-210 days before harvest [except at one apple site where the application was made during fruiting at 64 days prior to harvest].  The two subsequent applications were made, at 19-22 days before harvest (28 days before harvest at one apple site) and on the day of harvest.  The applications were made using ground equipment in 20-38 gal/A spray volumes.  An adjuvant was included in the spray mixture.

Samples of mature pome fruit were collected from each plot at each site on the day of the last application.  At one apple and one pear site, additional samples were collected 7, 14, and 21 days after the last application to evaluate residue decline.

Samples of apple and pear RACs were analyzed for residues of saflufenacil and the metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte in apple and pear.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of apple and pear harvested the day of the last of three soil broadcast applications at a total rate of 0.129-0.140 lb ai/A (1.0-1.1X).  Because residues were <LOQ in/on all samples from the decline trials, residue decline could not be evaluated.

Conclusions:  The submitted field trial data for pome fruit are adequate to fulfill data requirements.  The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 26).  The available data will support the proposed use pattern.

TABLE 26.  Trial Numbers and Geographical Locations for Pome Fruit.

NAFTA Growing Zones	Apple	Pear

	Submitted	Requested1`	Submitted	Requested1

Canada	U.S.

Canada	U.S.

1	3	1	3	2

1

1A

1

	1

	2	1

1

	5	4	4	2	3	3

	5A

5B	1	3

9	1

1

	10	1

1	2

2

11	4	3	4	3	1	3

Total	15	12	12	10	5	6

1  As required under OPPTS 860.1500 Tables 2 and 5 for apple and pear as representative crops of the pome fruit crop group (crop group 11), and PMRA Directive 98-02 Section 9 Table 2.

The residue data for pome fruit were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.01 ppm for each analyte (0.03 ppm combined)).  The recommended tolerances for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, are 0.03 ppm for fruit, pome, group 11.

Stone Fruit, Crop Group 12

DER Reference List	47128221.der.doc

BASF Corporation has submitted field trial data for saflufenacil on cherry, peach, and plum as representative crops of crop group 12, stone fruit.  A total of 29 stone fruit field trials were conducted in the U.S. and Canada during the 2006 and 2007 growing seasons.  Six trials were conducted on cherry (three each on sweet and tart cherry) in NAFTA Zones 5 (MI; 2 trials and ON; 1 trial), 10 (CA; 1 trial), and 11 (ID and WA, 1 trial each).  Thirteen trials were conducted on peach in NAFTA Zones 1 (NY; 1 trial), 2 (GA; 3 trials), 5 (IL and MI; 1 trial each and ON; 2 trials), 6 (OK; 1 trial), 10 (CA; 3 trials), and 11 (ID; 1 trial).  Ten trials were conducted on plum in NAFTA Zones 1 (NY; 1 trial), 5 (MI; 2 trials and ON; 1 trial), 10 (CA; 4 trials), 11 (WA; 1 trial), and 12 (OR; 1 trial).

Each trial location consisted of one untreated and two treated plots.  In each treated plot, three broadcast applications of the 70% WG formulation of saflufenacil (BAS 800 00 H) were made to the orchard floor at 0.041-0.047 lb ai/A/application with a 20- to 174-day RTI, for a total seasonal rate of 0.131-0.140 lb ai/A (1.0-1.1X).  Applications were made using ground equipment in 20-36 gal/A spray volumes.  An adjuvant was included in the spray mixture.

Samples of mature stone fruit were harvested on the day of the last application.  Additional samples of treated fruit were harvested at approximately 7-, 14-, and 21-day PHIs.

Samples of stone fruit RACs were analyzed for residues of saflufenacil and metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte in each matrix.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ (0.01 ppm each analyte) in/on all samples of cherry, peach, and plum fruit harvested the day of the last of three soil broadcast applications at a total rate of 0.131-0.140 lb ai/A (1.0-1.1X).  Residues of saflufenacil, M800H11, and M800H35 were also <LOQ in/on all fruit samples harvested 6-8, 13-14, and 20-21 days after the last application.

Conclusions:  The submitted field trial data for stone fruit are adequate to fulfill data requirements.  The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 27).  This residue program was previously approved by HED (Memorandum of Understanding, BASF with EPA and PMRA, 1/25/06; MRID No. 47128215).  The available data will support the proposed use pattern.

TABLE 27.  Trial Numbers and Geographical Locations for Stone Fruit.

NAFTA Growing Zones	Cherry	Peach	Plum

	Submitted	Requested1	Submitted	Requested1	Submitted	Requested1

Canada	U.S.2

Canada	U.S.2

Canada	U.S.2

1

	1 (tart)	1

1	1

1A

1

	2

3

3

	5	3 (tart)	3	2 (sweet); 4 (tart)	4	4	1	3	3	1

6

1

1

	9

	1 (tart)

10	1 (sweet)

2 (sweet)	3

3	4

4

11	2 (sweet)	2	2 (sweet)	1	1

1	1

	12

	1

1

Total	6	5	6	13	5	9	10	5	6

1  As required under OPPTS 860.1500, Tables 2 and 5 for cherry, peach, and plum as representative crops of Crop Group 12, Stone Fruit, and PMRA Directive 98-02 Section 9 Table 2.

2  To support a Crop Group 12 tolerance, OPPTS 860.1500, Table 2 requires six cherry field trials with sweet or tart cherry.

The residue data for stone fruit were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.01 ppm for each analyte (0.03 ppm combined)).  The recommended tolerance for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, is 0.03 ppm for fruit, stone, group 12.

Tree Nuts, Crop Group 14

DER Reference List	47128222.der.doc

BASF Corporation has submitted field trial data for saflufenacil on almond and pecan, the representative crops of crop group 14, tree nuts.  Ten tree nut field trials were conducted in the U.S. during the 2006 growing season.  Five trials were conducted on almond in NAFTA Zone 10 (CA; 5 trials) and five trials were conducted on pecan in NAFTA Zones 2 (GA; 2 trials), 4 (LA; 1 trial), 6 (TX; 1 trial), and 8 (TX; 1 trial).

Each trial location consisted of one untreated and two treated plots.  At each treatment plot, three broadcast applications of the 70% WG formulation of saflufenacil (BAS 800 00 H) were made to the orchard floor at 0.044-0.046 lb ai/A/application for a total seasonal rate of 0.133-0.137 lb ai/A (1.0X).  The first application was made at dormancy (169-243 days before harvest), the second 20-24 days before harvest, and the third at maturity, mostly at 7-14 DAT.  Applications were made using ground equipment, in 19-31 gal/A spray volumes.  An adjuvant was included in the spray mixture.

Samples of mature almond nutmeat, pecan nutmeat, and almond hulls were harvested approximately 7 and 14 days after the last application.  Additional samples of treated almond nutmeat and hulls were collected 0-, 21-, and 28-day PHIs at one CA site to evaluate residue decline.

Samples of tree nut RACs were analyzed for residues of saflufenacil and metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.025 ppm for each analyte in almond hulls and 0.01 ppm for each analyte in nutmeats.

Residues of saflufenacil, and the metabolites M800H11, and M800H35 were each below the LOQ in/on all samples of almond nutmeat, almond hulls, and pecan nutmeat harvested 7 or 14 days after the last of three soil broadcast applications at a total rate of 0.133-0.137 lb ai/A (1.0X).

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of almond nutmeat from the decline trial; therefore, residue decline in almond nutmeat could not be evaluated.  In almond hulls, residues of saflufenacil were 0.089-0.131 ppm at the 0-day PHI (only 4 samples were harvested at this interval) and below the LOQ in/on all samples harvested at later PHIs; residues of the metabolites M800H11 and M800H35 were each below the LOQ in/on all samples from the decline trials.

Conclusions:  The submitted field trial data for tree nuts are adequate to fulfill data requirements. The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 28).  The available data will support the proposed use pattern.

TABLE 28.  Trial Numbers and Geographical Locations for Tree Nuts.

NAFTA Growing Zones	Almond	Pecan

	Submitted	Requested	Submitted	Requested

Canada	U.S.1

Canada	U.S.1

2

2

2

4

1

1

6

1

1

8

1

1

10	5

5

	Total	5

5	5

5

1  As required under OPPTS 860.1500 Tables 2 and 5 for almond and pecan as representative crops of the tree nut crop group (crop group 14).

The residue data for tree nuts were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.025 ppm for each analyte in almond hulls and 0.01 ppm for each analyte in nutmeats) at the proposed PHI (7 days).  The recommended tolerances for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, are 0.03 ppm for tree nuts, group 14 and 0.10 ppm for almond hulls.  HED notes that pistachio residue data have not been submitted and concludes that the tree nut crop group tolerance may be translated to pistachio (see Reviewer's Guide and Summary of HED ChemSAC Approvals for Amending Commodity Definitions (40 CFR 180.1(h)) and Crop Group/Subgroups (40 CFR 180.41)).

Grapes

DER Reference List	47128225.der.doc

BASF Corporation has submitted crop field trial data for saflufenacil on grape.  Twelve grape field trials were conducted in the U.S. and Canada in Zones 1 (NY; 2 trials), 5 (MI, WI, ON; 1 trial each), 10 (CA; 6 trials), and 11 (WA; 1 trial) during the 2006 growing season.

Each trial location consisted of one untreated and two treated plots.  Each treated plot received three broadcast applications of the 70% WG formulation of saflufenacil (BAS 800 00 H) to the vineyard floor at 0.022-0.024 lb ai/A/application for a total seasonal rate of 0.066-0.070 lb ai/A (1.0-1.1X).  The first application was made at dormancy (115-159 days before harvest), the second 20-21 days before harvest, and the third at maturity.  Applications were made using ground equipment, in 20-36 gal/A spray volumes.  An adjuvant was included in the spray mixture.

Samples of mature grape fruit RAC were harvested 0 and 13-15 days after the last application.  The 0-day PHI samples from all sites were analyzed; the 14-day PHI samples from one CA site were analyzed.

Samples of grapes were analyzed for residues of saflufenacil and metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte.  Apparent residues of saflufenacil, M800H11, and M800H35 were each <LOQ in/on all samples of untreated grape.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of grape harvested on the day of the last of three soil broadcast applications at a total rate of 0.066-0.070 lb ai/A (1.0-1.1X).  Residue of saflufenacil, M800H11, and M800H35 were each <LOQ in/on two samples of grape samples harvested 14 days after the last application.

Conclusions:  The submitted field trial data for grapes are adequate to fulfill data requirements. The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 29).  This residue program was previously approved by HED (Memorandum of Understanding, BASF with EPA and PMRA, 1/25/06; MRID No. 47128215).  The available data will support the proposed use pattern.

TABLE 29.  Trial Numbers and Geographical Locations for Grapes.

NAFTA Growing Zones	Grape

	Submitted	Requested1

Canada	U.S.

1	2

2 [2]

5	3	4

	10	6

8 [5]

11	1	1	2 [2]

Total	12	5	12 [9]

1  As required under U.S. EPA OPPTS 860.1500 Tables 1 and 5 for grape, and PMRA Directive 98-02 Section 9 Table 2.  Numbers in brackets represent the required number of trials for a use resulting in no quantifiable residues.

The residue data for grapes were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.01 ppm for each analyte (0.03 ppm combined)).  The recommended tolerance for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, is 0.03 ppm for grape.

Cereal Grains, Crop Groups 15 and 16

DER Reference List	47128223.der.doc

BASF Corporation has submitted field trial data for saflufenacil on barley, corn (field and sweet), rice, grain sorghum, and wheat in support of registration of saflufenacil on crop group 15, cereal grains, and crop group 16, forage, fodder, and straw of cereal grains.  During the 2006-2007 growing seasons, 66 field trials were conducted on cereal grains in the U.S. and Canada.

Twenty-five field trials were conducted on wheat.  Eight trials were conducted on winter wheat in NAFTA Zones 2 (GA; 1 trial), 4 (AR; 1 trial), 5 (MI; 1 trial), 6 (OK and TX; 1 trial each), and 8 (KS; 2 trials and OK; 1 trial).  Seventeen trials were conducted on spring wheat in NAFTA Zones 5 (ND and WI; 1 trial each), 7 (NE and SK; 2 trials each and ND; 1 trial), 7A (AB; 1 trial), 11 (ID; 1 trial), and 14 (AB and SK; 3 trials each and MB; 2 trials).

Twenty field trials were conducted on corn.  Fifteen trials were conducted on field corn in NAFTA Zones 1 (NY; 1 trial), 2 (GA; 1 trial), 5 (ND and WI; 3 trials each, MI and MN; 2 trials each, MB and QC; 1 trial each), and 6 (TX; 1 trial).  Five trials were conducted on sweet corn varieties in NAFTA Zones 3 (FL; 1 trial), 7A (AB; 1 trial), 10 (CA; 1 trial), 11 (ID; 1 trial), and 12 (OR; 1 trial).

Nine trials were conducted on grain sorghum in NAFTA Zones 4 (AR; 1 trial), 5 (MI and ND; 1 trial each), 6 (OK; 1 trial and TX; 2 trials), 7 (ND; 1 trial), and 8 (KS; 2 trials).

Six trials were conducted on rice in Zones 4 (AR; 2 trials and LA; 1 trial), 5 (MO; 1 trial), 6 (TX; 1 trial), and 10 (CA; 1 trial).

Six trials were conducted on barley in NAFTA Zones 5 (MB; 3 trials) and 7 (AB; 1 trial and SK; 2 trials).

At each trial location, one untreated control and one or two treated plots were established.  The treated plots received a single broadcast pre-plant incorporated or pre-emergence application of the 70% WG formulation of saflufenacil (BAS 800 00 H) to the soil surface at 0.124-0.141 lb ai/A (0.93-1.1X).  The applications were made using ground equipment in 10-37 gal/A spray volumes.  An adjuvant was included in the spray mixture.

Samples of wheat forage were collected targeting the 6- to 8-inch stage to stem elongation (jointing) stage (Treatment 2; around BBCH stage 30) or early flowering (Treatment 3; around BBCH stage 61).  Wheat hay was harvested targeting early flower (boot; around BBCH 61) to soft dough stage (BBCH stage 85) and allowed to field dry to a moisture content targeting 10-20% (between 2 and 20 days of dry time).  Wheat grain and straw were harvested at normal maturity.  Wheat samples were collected from two sites (NE and MB) at additional sampling intervals to evaluate residue decline.

Corn kernel plus cob with husk removed (K+CWHR) samples were harvested at commercial maturity at the sweet corn trial sites.  At four of the field corn trials (Zone 5), field corn was sampled early (at the milk stage; around BBCH stage 73) to provide residue data translatable to sweet corn K+CWHR.  Corn forage samples (entire aerial portion of the plant) were harvested targeting the late dough/early dent stage (Treatment 2; around BBCH stage 85) or the milk stage (Treatment 3; around BBCH stage 73).  The milk stage samples were collected to provide residue data translatable to sweet corn forage.  Field corn grain and stover RAC samples were harvested at maturity.

Grain sorghum forage samples were harvested targeting the soft dough to hard dough stage (BBCH stage 85-87), and grain sorghum grain and stover samples were harvested at maturity.  Rice and barley grain plus hull samples were harvested at maturity.  Rice straw samples were collected from one site only, and no samples of barley hay or straw were collected.

Samples of cereal grain RACs were analyzed for residues of saflufenacil and metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.025 ppm for each analyte in forage, hay, straw, and stover, and 0.01 ppm for each analyte in grain and K+CWHR.

Following a single broadcast pre-plant incorporated or pre-emergence application of saflufenacil (70% WG) at 0.124-0.141 lb ai/A (0.93-1.1X), residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of treated wheat grain, corn grain, corn K+CWHR, sorghum grain, rice grain, and barley grain.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of treated wheat forage, hay, and straw; treated corn forage and stover; and grain sorghum forage.  Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all but four treated samples of sorghum stover.  Four grain sorghum stover samples, collected from the same trial in TX, bore quantifiable residues of M800H35 at 0.03-0.04 ppm; residues of saflufenacil and M800H11 were each below the LOQ in/on these samples.  Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on the two collected samples of treated rice straw.

Residue decline could not be evaluated because residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of wheat forage, hay, grain, and straw from the decline trials.

No samples of aspirated grains fractions were collected from the field corn, sorghum, or wheat trials.  Because application of the test substance was made pre-plant or pre-emergence and residues in grain were <LOQ for all samples, no residue data for aspirated grain fractions are required.

Conclusions:  The submitted field trial data for cereal grains are adequate to fulfill data requirements.  The number and locations of the trials are generally in accordance with OPPTS Guideline 860.1500 (Table 30).  This residue program was previously approved by HED (Memorandum of Understanding, BASF with EPA and PMRA, 1/25/06, MRID No. 47128215; and Minutes of the 1/18/06 ChemSAC).  The available data will support the proposed use pattern.

TABLE 30a.  Trial Numbers and Geographical Locations (Sorghum, Barley, and Rice Trials).

NAFTA Growing Zones	Grain Sorghum1	Rice1	Barley2

	Submitted	Requested	Submitted	Requested	Submitted	Requested

Canada	U.S.

Canada	U.S.

Canada	U.S.

1

	13

2

	13

4	1

1	3

7

	5	2

3	1

1	3	1	2

5B

1

	6	3

2	1

2

	7	1

1

3	2	3

8	2

2

9

	1

10

1

2

	1

11

	1

14

12

	Total	9

9	6

12	6	16	9

1  As required under OPPTS 860.1500 Tables 2 and 5 for grain sorghum and rice as representative crops of cereal grains (Crop Group 15) and forage, fodder, and straw of cereal grains (Crop Group 16).  For Canadian requirements, refer to PMRA Directive 98-02 Section 9, Table 2.

2  As required under OPPTS 860.1500 Tables 1 and 5 for barley, and PMRA Directive 98-02 Section 9 Table 2.  OPPTS 860.1500 does not require field trials on barley to support a U.S. crop group tolerance for Crop Groups 15 and 16.  The requested number of trials for U.S. reflect a 25% reduction due to the crop being a representative commodity used to obtain a crop group tolerance or due to pesticidal use resulting in no quantifiable residues.

3  For barley, either Zone 1 or Zone 2 is acceptable.

TABLE 30b.  Trial Numbers and Geographical Locations (Wheat and Corn Trials).

NAFTA Growing Zones	Wheat1	Field Corn1	Sweet Corn1

	Submitted	Requested	Submitted	Requested	Submitted	Requested

Canada	U.S.

Canada	U.S.

Canada	U.S.

1

1

1

	1

2	1

1	1

1

	1

3

	1

1

4	1

1

5	3	2	3	12	8	12	[4]2	4	3

5A

	5B

	4

	2

	6	2

1	1

1

	7	5	7	4

7A	1	1

	1	1

	8	3

4

10

	1

1

11	1

1

1

1

12

	1	1	1

14	8	10

	Total	25	20	15	15	12	15	9	8	9

1  As required under OPPTS 860.1500 Tables 2 and 5 for wheat, field corn, and sweet corn as representative crops of cereal grains (Crop Group 15) and forage, fodder, and straw of cereal grains (Crop Group 16), and PMRA Directive 98-02 Section 9 Table 2.

2  The number in brackets represents four trials on field corn in which samples were also collected at the milk stage to provide additional samples of K+CWHR and forage for sweet corn.

The residue data for cereal grains were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.025 ppm for each analyte in almond hulls and 0.01 ppm for each analyte in nutmeats) in/on all but four treated samples of sorghum stover (maximum residue of <0.09 ppm).  The recommended tolerances for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, are 0.03 ppm for crop group 15, cereal grains and 0.10 ppm for crop group 16, forage, fodder, and straw of cereal grains.

Cotton

DER Reference List	47128224.der.doc

BASF Corporation has submitted field trial data for saflufenacil on cotton.  Twelve cotton field trials were conducted in the U.S. in Zones 2 (GA, 1 trial), 4 (AR and MS, 1 trial each), 6 (TX; 1 trial), 8 (OK; 1 trial, TX; 3 trials), and 10 (AZ; 1 trial and CA; 3 trials) during the 2007 growing season.

At each trial location, two treated plots were established.  Each treated plot received a single, at-planting preemergence broadcast spray of the 70% WG formulation of saflufenacil (BAS 800 00 H) to the soil surface at 0.022-0.032 lb ai/A (0.49-0.71X; Treatment 2) or 0.044-0.064 lb ai/A (1.0-1.4X; Treatment 3).  The applications were made using ground equipment in 20-28 gal/A spray volumes.  An adjuvant was included in the spray mixture.  Samples of mature cotton were harvested by spindle-picker or stripper-picker, or by hand, at a 141- to 186-day PHI and ginned into undelinted cotton seed and cotton gin byproducts.  At one site, the cotton used to generate the undelinted seed RAC samples was harvested 130 days after treatment, to obtain samples for analysis earlier than the anticipated harvest for that location; samples used to generate the gin byproducts samples from this site were harvested at the expected time, 175 days after treatment.

Samples of cotton RACs were analyzed for residues of saflufenacil and metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603/02.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.025 ppm for each analyte in gin byproducts and 0.01 ppm for each analyte in cotton seed.  Apparent residues of saflufenacil, M800H11, and M800H35 were <LOQ in/on all samples of untreated cotton undelinted seed and gin byproducts.

Residues of saflufenacil, M800H11, and M800H35 were each below the LOQ in/on all samples of cotton undelinted seed and gin byproducts harvested 130-186 days after one preemergence soil broadcast application of the 70% WG formulation (BAS 800 00 H) at a rate of 0.022-0.032 lb ai/A (0.49-0.71X) or 0.044-0.064 lb ai/A (1.0-1.4X).

Because the submitted data reflect preemergence application, no residue decline studies are required.

Conclusions:  The submitted field trial data for cotton are adequate to fulfill data requirements.  The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 31).  The available data will support the proposed use pattern.

TABLE 31.  Trial Numbers and Geographical Locations for Cotton.

NAFTA Growing Zones	Cotton

	Submitted	Requested

Canada	U.S.1

2	1

1 [1]

4	2

3 [2]

6	1

1 [1]

8	4

4 [3]

10	4

3 [2]

Total	12

12 [9]

1  As per OPPTS 860.1500, Tables 1 and 5 for cotton seed.  Numbers in brackets represent the required number of trials for a use resulting in no quantifiable residues.  OPPTS 860.1000, Table 1, specifies that six field trials must be conducted for cotton gin byproducts, three

The residue data for cotton were not entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP as all residues were <LOQ (0.025 ppm for each analyte in gin byproducts and 0.01 ppm for each analyte in cotton seed).  The recommended tolerances for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, are 0.03 ppm for cotton seed and 0.10 ppm for cotton gin byproducts.

Sunflower

DER Reference List	47128226.der.doc

BASF Corporation has submitted field trial data for saflufenacil on sunflower.  Eight sunflower field trials were conducted in the U.S. and Canada in Zones 5 (KS, MI, WI; 1 trial each), 7 (ND; 3 trials), 8 (KS; 1 trial), and 14 (SK; 1 trial) during the 2007 growing season.

Each trial location consisted of one untreated and one treated plot.  Each treated plot received two late-season, over-the-top broadcast applications of the 70% WG formulation of saflufenacil (BAS 800 00 H) at 0.043-0.046 lb ai/A/application, with a retreatment interval of 7 days, for a total seasonal rate of 0.088-0.091 lb ai/A (1X).  The applications were made using ground equipment in 19-21 gal/A spray volumes.  An adjuvant was included in the spray mixture.

Samples of mature sunflower seed RAC were harvested at 6- to 8-day and 13- to 15-day PHIs.  Additional samples were taken from the KS site at 3-, 10-, and 20-day PHIs to evaluate residue decline.

Samples of sunflower seed were analyzed for residues of saflufenacil and metabolites M800H11 and M800H35 using an LC-MS/MS method, BASF Analytical Method Number D0603.  This method is adequate for data collection based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte.  Apparent residues of saflufenacil, M800H11, and M800H35 were <LOQ in/on all samples of untreated sunflower seed.

Maximum residues of saflufenacil, M800H11, and M800H35 were 0.50, 0.16, and 0.04 ppm, respectively, in/on sunflower seed harvested 6-8 days after the last of two over-the-top broadcast applications of saflufenacil at a total rate of 0.088-0.091 lb ai/A (1X).  Maximum combined residues at the 6- to 8-day PHI were 0.58 ppm.  Maximum residues of saflufenacil, M800H11, and M800H35 were 0.46, 0.33, and 0.06 ppm, respectively, in/on sunflower seed harvested 13-15 days posttreatment.  Maximum combined residues at the 13- to 15-day PHI were 0.56 ppm.

Average combined residues of saflufenacil, M800H11, and M800H35 appeared to decrease overall with increasing sampling intervals, from 0.12 ppm at the 3-day PHI to 0.06 ppm at the 20-day PHI.

TABLE 32.  Summary of Residue Data from Sunflower Field Trials with Saflufenacil.

Commodity	Total Applic. Rate (lb ai/A)	PHI (days)	Analyte	Residue Levels (ppm)1

n	Min.	Max.	HAFT2	Median	Mean	Std. Dev.

Sunflower, seed	0.088-0.091	6-8	Saflufenacil	16	0.03	0.50	0.44	0.11	0.15 0.13

	M800H11	16	<0.01	0.16	0.15	0.01	0.04	0.05

	M800H35	16	<0.01	0.04	0.04	0.01	0.01	0.01

	Combined	16	<0.05	<0.58	<0.50	0.17	0.20	0.14

13-15	Saflufenacil	16	0.02	0.46	0.39	0.07	0.12	0.12

	M800H11	16	<0.01	0.33	0.33	0.02	0.06	0.11

	M800H35	16	<0.01	0.06	0.05	0.01	0.02	0.02

	Combined	16	<0.04	<0.56	<0.48	0.12	0.20	0.17

1  Residues are reported in ppm saflufenacil equivalents.  For calculation of the HAFT, median, and mean, the LOQ (0.01 ppm for each analyte) was used for values reported as <LOQ.

2  HAFT = highest-average field trial.

Conclusions:  The submitted field trial data for sunflower seed are adequate to fulfill data requirements.  The number and locations of the trials are in accordance with OPPTS Guideline 860.1500 (Table 33).  However, all of the field trials were performed with a WG formulation; whereas, the proposed use is for the SC formulation.  These formulation types are not considered to be equivalent for mid- to late-season foliar applications.  The proposed sunflower use should thus be removed from the BAS 800 04H FiRoCrop Herbicide (SC) label and added to the BAS 800 01H TNV Herbicide (WG) label.  Alternatively, bridging trials could be performed to determine the effect of the formulation type on residue levels.

TABLE 33.  Trial Numbers and Geographical Locations for Sunflower Field Trials.

NAFTA Growing Zones	Sunflower

	Submitted	Requested1

Canada	U.S.

5	3	2	3

7	3	1	4

8	1

1

14	1	2

	Total	8	5	8

1  As required under U.S. EPA OPPTS 860.1500 Tables 2 and 5 for sunflower, and PMRA Directive 98-2 Section 9 Table 2.

The residue data for sunflower seed were entered into the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP to determine appropriate tolerance levels; see Appendix II.  In three of the trials, residues were higher at PHIs (10-14 days) that are greater than the proposed PHI (7 days).  In these cases, the higher values were entered into the spreadsheet.  The recommended tolerance for the combined residues of saflufenacil and its metabolites M800H11 and M800H35, expressed as parent equivalents, is 1.0 ppm for sunflower seed.

860.1520 Processed Food and Feed

Apple

DER Reference List	47128229.der.doc

A processing study was carried out to determine the magnitude of saflufenacil residues in apples and processed apple commodities (juice and pomace).  BAS 800 00 H (saflufenacil, 70% ai, WG) was applied to apples as three broadcast orchard floor applications of 0.22 lb ai/A for a total seasonal application rate of 0.67 lb ai/A (5X).  The applications were made at dormancy (179 days prior to harvest), 21 days prior to harvest and on the day of harvest with 25 gal/A of water using ground equipment.  An adjuvant was included in the spray mixture.

Mature apples were harvested on the day of the last application (0-day PHI) from one untreated control plot and one treated plot.  Bulk samples of apples were delivered to the processing facility on the same day and were placed in cool storage at 3-8ºC prior to processing into juice and wet pomace.  Processing was completed within one day of harvest and was carried out using protocols simulating commercial processing procedures.