Page 1 of 44 UNITED STA

TES ENVIRONMENTA L PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDE AND TOXIC SUBSTANCES MEMORANDUM Date : January 2 1, 2010 SUBJECT: Fomesafen Sodium . Petition for the Establishment of Tole rances and Registration

of New Uses on Potato and Tomato; and Response to Data Gaps for Conditional Registration on Cotton, Dry Bean, and Snap Bean. Summary of Analy tical Chemistry

and Residue Data . PC Code: 123802 DP Barcode s : D 365199 and D366116 Dec ision No.: 409397 and 415115 Registration No. : 100 - 993 Petition No s : 9F7563 (potato and tomato) , 1E6228 (dry bean) , 9F5068 (cotton) , and 6E4653 (snap bean) Regulatory Action: Amended Section 3 Risk Assessment Type: NA Case No.: NA T XR No.: NA C AS No.: 72178 - 02 - 0 MRID No.: See MRID Summary Table 40 CFR: § 180. 433 FROM: Christine L . Olinger, Chemist

Risk Assessment Branch VI I Health Effects Division (7509P) THROUGH: Toiya Goodlow , Chemist

Michael S. Metzger, Chi ef Risk Assessment Branch VI I Health Effects Division (7509P) TO: Dan Kenny /Michael Walsh , PM Team 23 Herbicide Branch Registration Division (7505P) MRID Sum ma ry Table MRID No. Study Type Com me nts 4 7473901 860.1300 Tom ato New DER; 47473901.der.doc 47473902 860.1500 Tom ato Crop Field Trials New DER; 47473902.de1.doc 860.1520 Tom ato Processing Study New DER; 47473902.de2.doc 47473903 860.1500 Potato Crop Field Trials New DER; 47473903.de1.doc 86 0.1520 Potato Processing Study New DER; 47473903.de2.doc 47761901 860.1360 Multiresidue Methods New DER; 47761901.der.doc 47761902 860.1380 Storage Stability New DER; 47761902.der.doc 47761903 - 04 860.1340 Residue Analytical Methods New DER 47761903.der .doc (Includes MRID 47761904)Page 2 of 44

MRID Sum ma ry Table MRID No. Study Type Com me nts 47761905 Response to Conditions of Registration No DER generated; registrant’s response s to deficiencies are incorporated i n this Summary Document. This document was originally prepared under contract by Dy namac Corporation ( 1901 Research Boulevard, Suite 220 ; Rockville, MD 20850). Dy namac QC Reviewer: Date: 10 / 14 /200 9

Tracey Cowen Dy namac Program Manager : Date: 10/14 /200 9

Danilo Martinez The document has been reviewed by the Health Effects Division (HED) and revised to reflect current Office of Pes ticide Programs (OPP) policies.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 3 of 44 Executive Summary Fomesafen sodium is a contact broadleaf herbicide in the diphenylether chemical class. The herbicide acts through inhibition of the enzy me protoporphy

rinogen oxidase (PPO) in plants. The active ingredient was originally registered on 09/11/ 1987 by Zeneca Ag Products and was transferred to Sy

ngenta Crop Protection, Inc. on 02/23/2001. Fomesafen is currently registered for use on the crops cotton, dry beans, snap beans, and soy beans. It is applied to treat various broadleaf weeds, annual grasses, perennial weeds and sedges. Sy ngenta has proposed, in PP#9F7563 , the establishment of permanent tolerances for residues of fomesafen in/on the following raw agricultural commodities: Potato ................................ ................................ ................................ ....... 0.025 ppm Tomato ................................ ................................ ................................ ..... 0.025 ppm Insupport of the proposed tolerances and new crop uses , Sy ngenta has submitted a tomato metabolism study

and magnitude of the residue studies on potatoes and tomatoes. In ad dition, the petitioner has submitted various residue chemistry studies in response to the data gaps identified by as a condition of registration for a request previously made by Sy ngenta and IR - 4 to amend the Reflex® Herbicide . This Summary Document addre sses the adequacy of the submitted residue chemistry data in support of the proposed new uses on potatoes and tomatoes as well as the adequacy

of Sy ngenta’s responses to the conditions of registration . Reflex® Herbicide is proposed for one broadcast preem ergence application on potatoes after planting but before potato emergence at a maximum rate of 0.25 lb ae/A and a 70 - day preharvest interval (PHI ). On tomatoes, Reflex® Herbicide is proposed for one broadcast preplant non incorporated preemergence applic ation up to 7 day s prior to transplanting tomato seedlings at a maximum rate of 0.375 lb ae/A and a 70 - day PHI . The metabolism of fomesafen in soy bean, cotton, and tomato has been investigated. The soy bean and cotton metabolism studies were reviewed in D P# 325801, and the tomato study was included as part of the current petition package. The cotton metabolism study has now been upgraded to acceptable status based on Sy ngenta’s submission of the requested information . The terminal residue of concern in c otton is fomesafen. The tomato metabolism study is acceptable and supports the proposed use on tomatoes. T he terminal residue of concern in tomatoes is fomesafen. HED generally

recommends that three metabolism studies on diverse crops when a pesticide is to be used on several different commodities. Although three metabolism studies have been submitted, tomatoes, soy

beans and cotton are not sufficiently diverse to define the nature of the residue in all crops. Since no data on a root crop have been pro vided that can be translated to the p roposed use on potatoes , a potato metabolism study , in which both the root and tops/foliage are analy zed, is requi red to support the proposed use on potatoes . HED cannot recommend for a tolerance in/on potatoes until an adequate metabolism study is submitted. There are no livestock feedstuffs associated with the proposed use on tomatoes. The nature of the residue in ruminants is adequately understood. At this time no tolerances have beenFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 4 of 44 established on any

livestock commodity

in association with the existing uses of fomesafen. Li vestock feeding studies are not required to support the proposed /registered uses of fomesafen. Sy ngenta should note that if additional uses are proposed in the future which result in an increase in the dietary

burden s , livestock feeding studies may be required. Adequate residue analy

tical methods are available for the purpose of tolerance enforcement. Sy ngenta s ubmitted a new high performance liquid chromatography method with tandem mass s pectrometry

detection ( LC /MS/MS ) method (GRM045.01A) as an enforcement method . The method uses extraction procedures similar to previous methods, SPE cleanup procedures, and the final determination step by L C/MS/MS technology

for analy sis of fomesafen res idues. The validated limit of quantitation (L OQ) of the method is 0.02 ppm. Method GRM045.01A was adequately

validated at fortification levels of 0.02 ppm and 0.2 ppm in snap beans, pinto beans (dry bean), corn oil, cotton, undelinted seed and gin by prod ucts, and soy

bean forage, hay , and aspirated grain fractions. Methods for the determination of fomesafen residues of concern in livestock commodities are not required at this time but may be required in the future. The requirements for multiresidue method testing data for fomesafen are fulfilled. FDA multiresidue methods are not suitable for determining residues of fomesafen ; the submitted data will be forwarded to U.S. FDA for further evaluation. Samples of raw and processed commodities of potatoes and tomatoes, which were collected from the magnitude of the residue studies, were analy zed for residues of fomesafen using a LC /MS/MS based on an liquid chromatography with ultraviolet detection ( HPL C/UV ) method (GAM - RM - 001/86). The method was adequatel y validated during concurrent analysis of samples. The lowest level of method of validation (LLM V) was 0.025 ppm for each matrix. Analy tical standards for fomesafen are currently available in the EPA National Pesticide Standards Repository . Adequate s torage stability data are available to support the storage conditions and durations of samples collected from the magnitude of the residue studies on tomatoes. Interim storage stability data were additionally

submitted for various crop commodities in resp onse to a data gap cited in DP# 325801 , and the registrant intends to submit a final report with analyses after 18 and 24 months of storage . Residues of fomesafen appear to be relatively stable in/on corn, wheat, soy bean , and cotton commodities through 13 months of storage. The submitted field trial data for fomesafen on tomatoes are acceptable and support the proposed uses. An adequate number of trials were conducted in the appropriate geographic regions at ~1x the maximum proposed rate using Reflex® He rbicide, and the appropriate samples were collected from each test around the proposed PHI . All treated samples bore residues below the LLM V (<0.025 ppm). Based on these data, HED recommends a tolerance of 0.025 ppm for residues of fomesafen in/on tomato es. Provided the requested met abolism study does not indicate that there are additional metabolites/degradates of concern, an adequate number of field trials were conducted to support the proposed new use on potatoes . Residues of fomesafen were below the LLM V of 0.025 ppm in all trials. HED reiterates that a root/tuber metabolism study is required to support this use. I fFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 5 of 44 the new study

identifies additional residues of concern, then additional field trials reflecting analy sis of the new residues will be required to support this use. The previously

submitted cotton field trial data have now been upgraded to acceptable status based on Sy

ngenta’s submission of the requested information pertaining to weather conditions, soil characteristics, and raw data of field notes, calibration of equipment, and sampling procedures that were employed in the conduct of the cotton trials. The Agency concludes that adequate residue data are available to support the established tolerance s of 0.025 ppm each for cotton gin by

p roducts and undelinted cottonseed. The results of submitted potato and tomato processing studies show that residues of fomesafen were each below the LLMV (<0.025 ppm) in/on the respective RACs following application of Reflex® Herbicide at 1x. Since the s tudies involved processing of RACs bearing nonquantifiable residues, no measurable processing factors can be calculated. Although, the Agency would have preferred the use of exaggerated rates in the conduct of the processing studies to yield RACs with quantifiable residues , HED will not require additional processing data at this time . The nature of the residue in rotational crops remains inadequately understood. Sy

ngenta has previously

been requested to conduct a new confined rotational crop study reflec ting separate application of CP - and NP - label fomesafen at the maximum seasonal application rate to rotatable crops. According to Sy

ngenta, a new confined rotational crop study is ongoing and will be completed by

12/31/2009. Satisfaction of the confined rotational crop data should be a condition of these registrations. At this time, data are not available to support rotation to other crops beyond those commodities that are currently

registered and proposed as primary crops; therefore , the registrant must revise the Reflex® Herbicide label to permit immediate replanting of soy beans, cotton, dry

beans, snap beans, potatoes, and tomatoes only with a restriction that other crops can only be planted 12 months after treatment or 18 months after treatment if bas ed on phy totoxicity concerns. No Codex, Canadian, or Mexican MRL s have been established for residues of fomesafen in/on potato or tomato. Canadian MRL s have been established for residues of fomesafen in/on dry beans, lima beans, snap beans, and soy beans at 0.05 ppm, and a Mexican MRL of 0.05 mg/kg has been established for residues of fomesafen in/on soy beans. The registrant has advised the Agency that they intend to petition the Canadian government for revised tolerances to address any potential harmoni zation issues raised by establishing the new tolerances requested in this action. Regulatory Recommendations HED has examined the residue chemistry database for fomesafen sodium. Pending resolution of the deficiency

pertaining to directions for use and provided the submission of a confined rotational crop study is made a condition of the registration , there are no residue chemistry issues that would preclude granting the petitioner’s request to amend the Reflex® Herbicide label for the purpose of add ing the requested use on tomatoes. HED recommends a conditionalFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 6 of 44 registration for this herbicide on the crops requested and/or the revision of 40 CFR §180.433 for the establishment of tolerances for residues of fomesafen as follows: Tom ato ................................ ................................ ................................ ..... 0.025 ppm The registrant’s most recent Reflex® Herbicide label reflects regional use of fomesafen on tomatoes . H owever, the residue chemistry data submitted in support of this action are of sufficient geographic representation to support full U.S. re gistration; therefore, HED recommends that these tolerances be listed in the general section of 40 CFR § 180.433. Tolerances for fomesafen residues are listed in 40 CFR §180.433. Currently , the single established tolerance is expressed in terms of “sodium salt of fomesafen, 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] -N - (methylsulfonyl) - 2 - nitrobenzamide.” HED has determined that the residue of concern for tolerance expression is fomesafen. Therefore, the established tolerance expression should be revised to b e expressed in terms of fomesafen, by removing the phrase “sodium salt of” from 40 CFR §180.433(a). Note to PM: According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner), the tolerance expression for fomesafen should be revised to state: “Tolerances are established for residues of fomesafen, including i t s 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 fomesafen [5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] - N - (methylsulfonyl) - 2 - nitrobenzamide].” A human health risk assessment is forthcoming. Residue Chemistry Deficiencies Deficiencies
- Tomato Petition ( 9F7563) The following deficiency must be resolved prior to granti ng of the registration on tomatoes. 860.1200 Directions for Use

· At this time, data are not available to support rotation to other crops beyond those commodities that are currently registered and proposed as primary crops; therefore , the petitioner mus t revise the Reflex® Herbicide label to permit immediate replanting of soy beans, cotton, dry

beans, snap beans, potatoes, and tomatoes only

with a restriction that other crops can only be planted 12 months after treatment or 18 months after treatment if ba sed on phy totoxicity concerns. The deficienc y listed below must be fulfilled as a condition for the registration of Reflex® Herbicide label to add the requested use on tomatoes.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 7 of 44 860.1850 Confined Accumulation in Crops

· The ongoing confined rotational crop study , which is expected to be completed by 12/2009, should be submitted at the earliest possible convenience. Based on this future submission, HED will determine the terminal residues of concern in rotational crops and will re - evaluate the existing field rotational crop studies for determination of appropriate plantback restrictions. Deficiencies
- Potato Petition ( 9F7563) HED cannot recommend for the requested tolerance in/on potatoes due to the lack of an adequate root/tuber metabolism study . Th e following study must be submitted to support the proposed tolerance. 860.1300 Plant Metabolism

· A potato metabolism study in which both the roots and tops are analy zed is required to support the proposed use and tolerance on potatoes. Remaining De

ficiencies

– PP#s 1E6228 (Dry Bean), 9F5068 (Cotton), and 6E4653 (Snap Bean) All data gaps previously identified by HED (DP# 325801, 4/25/2006, D. Davis) as a condition of registration under the petitions cited above have now been adequately fulfilled ex cept for the requirements for confined rotational crop data noted above as well as the deficiency pertaining to storage stability listed below. 860.1380 Storage Stability

· The registrant intends to submit a final storage stability report, including ana ly ses at 18 and 24 months. When this study is submitted the registrant should ensure that the dates documented in the report should reflect the actual storage intervals, and not the proposed intervals, as there was some discrepancy in the interim report.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 8 of 44 Background The chemical name and structure of fomesafen sodium and fomesafen are listed below in Table 1. The phy sicochemical properties of fomesafen are listed in Table 2; data pertaining to the phy sicochemical properties of fomesafen sodium are not available. T able 1. Test Compound Nom enclature. Compound F 3 C

Cl O N O 2

O N S C H 3 O O Na+

Common name Fomesafen Sodium Company experimental name Not provided. IUPAC name 5 - (2 - chloro - α,α,α - trifluoro - p - tolyloxy) - N - methylsulfonyl - 2 - nitrobenzamide, sodium salt CAS name 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] - N - (methylsulfonyl) - 2 - nitro - benzamide, sodium salt CAS registry number 108731 - 70 - 0 Compound F 3 C

Cl O N O 2

O N H S C H 3 O O

Common name Fomesafen Company experimental name Not provided. IUPAC name 5 - (2 - chloro - α,α,α - trifluoro - p - tolyloxy) - N - methylsulfonyl - 2 - nitrobenzamide CAS name 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] - N - (methylsulfonyl) - 2 - nitrobenzamide CAS registry number 72178 - 02 - 0 End - use pro duct (EP) Reflex® Herbicide, 2 lb ae/gal SL ; EPA Reg . No . 100 - 993 T able 2. P hysicochemical Properties of Fom esafen. Parameter Value Reference Melting point/range 220 - 221  C HED Memo, 9/3/82, W. Anthony pH 8.2 (94% TGAI) CSF (EPA Reg. No. 100 - 1017; 1 0/13/00) Density 1.28 g/cm3 at 20  C HED Memo, 9/10/86, C. Trichilo Water solubility at 25 °C 600 g/L at pH 7 <10 ppm at pH 1 - 2 50 mg/L HED Memo, 9/3/82, W. Anthony HED Memo, 9/10/86, C. Trichilo Solvent solubility g/L Acetone 300 Cyclohexanone 150 Methanol 25 Hexane 0.5 Xylene 1.9 HED Memo, 9/10/86, C. Trichilo

Vapor pressure <7.5 x 10 - 7 mm Hg at 50  C The Pesticide Manual 1 Dissociation constant, pK a 2.7 at 20  CFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 9 of 44 T able 2. P hysicochemical Properties of Fom esafen. Parameter Value Reference Octanol/water partition coefficient, Log(KOW) Log KOW = 2.9 at pH 1 UV/visible absorption spectrum Not available 1 The Pesticide Manual, A World Compendium, The British Crop Protecti on Council ( toxnet.nlm.nih.gov). 860.1200 Directions for Use The end - use product relevant to the potato and tomato petition ( PP#9F7563 ) is Reflex® Herbicide (EPA Reg. No. 100 - 993), a soluble concentrate liquid (SL) formulation containing 22.8% sodium sal t of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of fomesafen). Reflex® is a selective herbicide which may be applied preplant surface, preemergence, and/or postemergence for control or partial control of broadleaf weeds, grasses, and se dges in registered crops cotton, dry

beans, snap beans, and soy beans. In support of the proposed uses on potatoes and tomatoes , the petitioner submitted a draft label for Reflex® Herbicide dated 4/27/2009. A s ummary of the proposed use directions for pot atoes and tomatoes is presented in Table 3 A . Table 3A . Summary of Proposed Use Directions of Reflex® Herbicide (EPA Reg. No. 100 - 993 ; 2 lb ae/gal)

on Potato es and Tom ato es . Applic. Timing, Type, and Equip. Applic. Rate (lb a e /A) Max. No.

Applic. per Se ason Max.

Seasonal Applic. Rate (lb a e /A) PHI

(days) Use Directions and Limitations Potato

Broadcast preemergence application after planting but before potato emergence Ground/Aerial/Center pivot irrigation 0.25 1 0.25 70 Refer to Syngenta’s Regional Us e Map for Reflex® 1 ( summarized in the ‘General Use Directions’ below) for determination of maximum use rate that may be applied in each geographic region . D o not apply to any field in Regions 2, 3, 4, or 5 more than once every two years. Do not apply to sweet potatoes or yams . Do not apply as a preplant incorporated application as crop injury may occur. Do not apply to emerged potato plants or severe crop injury will occur. Tom ato (Transplanted ) Broadcast pre plant non incorporated pre emergence applic ation up to 7 days prior to transplanting tomatoes Ground/Aerial/Center pivot irrigation 0.25 - 0.375 1 0.375 70 Refer to Syngenta’s Regional Use Map for Reflex® 1 ( summarized in the ‘General Use Directions’ below) for determination of maximum use rate that may be applied in each geographic region. Do not apply to any field in Regions 2, 3, 4, or 5 more than once every two years. 1 The draft label specifies five use regions with specific seasonal maximum application rates. The rates range with the label u seFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 10 of 44 Region 1 having the highest seasonal application rate reflects application at 0.375 lb ae/A each year and label use Region 5 with the lowest seasonal application rate reflects application of up to 0.1875 lb ae/A in alternate years . Details of the seaso nal maximums for all label use Regions are presented below under “General Use Directions”. General U se D irections Sy ngenta’s regional use map for Reflex® : The draft label specifies that product may only be use d in the eastern half of the U.S . Sy ngenta’ s r egional u se m ap for Reflex® is subdivided into the following five regions: Region 1: Reflex® may

be applied at a maximum of 0.375 lb ae/A per year in Region 1 per year which includes the following states or portion of states: AL , AR, FL, GA, LA, MS, MO (counties of Bollinger, Butler, Cape Girardeu, Dunklin, Madison, Mississippi, New Madri d , Pemiscot, Perry , Ripley , Scott , Stoddard, and Way ne), NC, OK (East of U.S. Highway 75 and East of Indian Nation Parkway ), SC, TN, and TX (includes area East of U.S . Highway 77 to State Road 239 including all of Calhoun County ). Region 2: Reflex® may

be applied at a maximum of 0.375 lb ae/A in alternate years in Region 2 which includes the following states or portion of states: DE, KY, MD, VA, WV, and South of Int erstate 70 in the following states: IL, I N, and OH and all areas South of the Interstate 80 to the intersection of U.S. Highway 15 and East of U.S. Highway 15 and U.S. Highway

522 in PA. Region 3: Reflex® may

be applied at a maximum of 0.313 lb ae/A in alternate years in Region 3 which includes the following states or portion of states: CT, IA, ME, MA, M O (all counties except those listed in Region 1), NH, NJ, NY, PA (all areas except those listed in Region 2), RI , VT, and WI(South of U.S. Highway 18 b etween Prairie Du Chien and Madison, and South of Interstate 94 between Madison and Milwaukee), and North of Interstate 70 in the following states: I N, IL, and OH. Region 4: Reflex® may

be applied at a maximum of 0.25 lb ae/A in alternate years in Regi on 4 which includes the following states or portion of states: KS ( all counties East of or intersected by U.S. Highway

281), MI(Southern Peninsula), MN (all areas South of Interstate 94), NE (all counties East of or intersected by U.S. Highway

281), and WI(all areas, except those in Region 3, South of Interstate 94 from MN state line to Eau Claire and South of U.S. Highway from Eau Claire to Green Bay

plus Barron, Chippewa, Clark, Door, Dunn, Eau Claire, Kewaunee, Marathon, Menominee, Oconto, Polk, Shawano, and St. Croix counties. The following counties are excluded: Adams, Marquette, Portage, Waupaca, Waushara, and Wood). ND (all areas East of Interstate 29 from Fargo South to the S D state line). SD (all areas East of Interstate 29 from the ND state line to Watertown, all areas East of Highway 81 from Watertown to Madison and all areas East and South of State Road 34 and U.S. Highway 281 to the NE state line. Region 5: Reflex® may

be applied at a maximum of 0.1875 lb ae/A in alternate years in Regio n 5 which includes the following states or portion of states: ND (all areas East of the U.S. Highway 281 except those areas in Region 4), SD (all areas East of the U.S. Highway 281 except those areas in Region 4), and MN (all areas South of the U.S. Highw ay 2 except those areas in Region 4).Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 11 of 44 Spray additives : The draft label specifies that spray additives cleared for use on growing crops under 40 CFR §180.1001 may be used in the spray

mixture. A nonionic surfactant (NI S), crop oil concentrates (COC), or other adjuvant s may be used for postemergence applications only . Since the proposed uses on potatoes and tomatoes are either preemergence or pretransplant, the use of surfactants is not needed when Reflex® is applied to these crops. Application equipment : Ground applications are to be made in a minimum of 10 gal/A, and aerial applications are to be made in a minimum of 5 gal/A. Applications are not to be made through any

ty pe of irrigation equipment except center pivot sy stems. Reflex® alone or in tank mixture with other herbicides on the label, which are registered for center pivot application, may be applied in irrigation water preemergence (after planting but before weeds or crop emerge) at label - recommended rates. Tank mixtures with other products registered for use on potatoes and tomatoes : The draft label provides mixing procedures for tank mixes but does not specify specific tank mix partners for potatoes and tomatoes. The use directions state that, for tank mix combinations, the recommendation s, restrictions, and limitations for all products must be followed and that the most restrictive labeling is to apply . For preemergence application in potatoes, Reflex® may be tank mixed with other pesticide products registered for use in this way and tim ing in potatoes. For preplant non - incorporated preemergence applications prior to transplanting tomatoes, Reflex® may

also be tank mixed with other pesticide products registered for use in this way and timing in tomatoes. Rotational crop plantback inte rvals : The draft label specifies that the rotational crops listed in Table 3B may

be planted after applying Reflex® at recommended rates. Table 3B. Rotational Crop Plantback Intervals Listed on the Reflex® Herbicide. Crop To Be Planted Minimum Rotation Interval (Months After Last Reflex® Application) Cotton, dry beans, potatoes, snap bean, soybeans, and transplanted tomatoes 0 Small grains such as wheat, barley, and rye 4 Corn 1 , peanuts, peas, rice, seed corn 10 To avoid crop injury, do not plant a lfalfa, sunflowers, sugar beet, sorghum 2 , or any crop within 18 1 Use a 12 month minimum rotation interval for popcorn in the states of OH, KY, IL, IN, IA, and Region 4 when applied at rates of 0.25 lb ae/A or more. Use 18 month minimum rotation for sweet corn in the states of CT, ME, MA, NH, NY, RI, VT, and Region 5. 2 Sorghum may be planted back after 10 months in Region 1. Additional consideration : HED previously re quested (DP# 325801, 4/25/2006, D. Davis) that the product label for Reflex® Herbic ide be revised to reflect a 45 - day PHI for dry

beans based on the submitted data and remove Frontier as a recommended tank mix partner for snap beans . An examination of the draft label for Reflex® Herbicide indicate s that a 45 - day PHIis now listed for dr y beans and Frontier is no longer listed as a tank mix partner for snap beans ; therefore, this data gap is fulfilled. Conclusions . The available draft label for Reflex® Herbicide is adequate to allow evaluation of residue data relative to the proposed us e on potatoes and tomatoes.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 12 of 44 At this time, data are not available to support rotation to other crops beyond those commodities that are currently

registered and proposed as primary crops; therefore the petitioner must revise the Reflex® Herbicide label to p ermit immediate replanting of soy beans, cotton, dry

beans, snap beans, potatoes, and tomatoes only with a restriction that other crops can only be planted 12 months after treatment or 18 months after treatment if based on phy totoxicity concerns. 860.1300 Nature of the Residue - Plants Tomato DER Reference List : 47473901.der.doc Sy ngenta Crop Protection has submitted a study investigating the metabolism of [trifluo ro methylphenyl - U 14 C]fomesafen (TMP label; specific activity 55.8 μCi/mg ) and [nitrophenyl - U 14 C]fomesafen (NP label; specific activity 56.2 μCi/mg ) in tomatoes. Each radiolabeled test substance was formulated as ReflexTM Herbicide in water and applied by spraying onto the bare ground soil of designated plots, four days before tomato seedlings were transplanted into the plots. The t arget application rate was 0.375 lb ai/A (1x the proposed rate) . Actual application rates were 0.369 lb ai/A for the TMP label and 0.385 lb ai/A for the NP label. Ripe tomatoes were harvested 98 days after treatme nt (DAT) . A second harvest, 104 DAT , provided additional red ripe fruit s and immature green fruit s (both not analy zed) and foliage for analy sis that might generate more information of the metabolism of the test substance. The field phase of the study

was conducted at an outdoor field site maintained by Excel Research Services (Fresno, C A ). The analy

tical phase of the study

was performed by

PTRLWest, Inc. (Hercules, CA). T otal radioactive residues (TRR) in tomato matrices were determined by both combust ion and the sum of ppm levels detected in extracts and the post - extraction solids (PES). The TRR in ripe tomatoes were very

low ( 0.005 and 0.002 ppm for the TMP and NP label s, respectively ). The TRR in tomato foliage ( 0.0 84 and 0.080 ppm for the TMP and NP label s, respectively ) were at l east 17x higher than fruits. Residues in harvested matrices were extracted with acetonitrile:water (1:1, v:v) twice , a procedure wh ich adequately released the majority

of radioactivity . Additional extraction with acetoni trile released no radioactivity , and the post - extractions solid (PES) was devoid of radioactivity

as demonstrated by

combustion. The combined acetonitrile:water extracts were analy zed by HPL C, which showed numerous products that generally partition ed into water rather than organic solvent (ethyl acetate). The combined acetonitrile:water extracts were acidified (pH ~1) and extracted with ethyl acetate to characterize/identify residues by

chromatographic techniques. From the TMP label study , the parent f omesafen was identified in fruits (3.7% TRR) and foliage (2.4% TRR). In addition, the metabolite 3 - chloro - 4 - hydroxy benzoic acid (R052850) was detected in fruits (5.5 - 6.9% TRR) but not in foliage. A major unknown (up to 78 .4 % TRR) was characterized as aci d labile, to volatile residues. A ll identified residues were below 0.01 ppm.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 13 of 44 From the NP label study , fomesafen was identified in fruits (3.6% TRR) and foliage (1.3% TRR). Approximately

39.6% of the TRR in the extract eluted at the solvent front and 31 .6% at retention time 12.8 minutes. When the concentrated extract was partitioned between ethyl acetate and water (pH ~4), all radiolabel was in the aqueous phase. The extract was reanaly zed by HPL C when two cy steine (Cy s) conjugates became available as reference standards. The peak at ~13 min co - eluted with the Cy s conjugate of sulfonamide (R290493) and was detected in fruits (31.1 - 31.6% TRR) and foliage (8.8% TRR). The following metabolites were additionally identified: (i ) 2 - NO 2 - 5 - OH benzoic acid (R 012156) in fruits (5.9% TRR); and (ii ) 2 - NH 2 - 5 - OH benzoic acid (R089135) in fruits (3.7% TRR). Tomato fruits and foliage were stored frozen for maximum durations of 70 and 36 days, respectively , prior to the completion of chromatographic analyses. No storage stability data were submitted and none are required since sample integrity was maintained by

appropriate freezer storage and final analy sis was completed within 70 day s of sample collection. Based on the results of the conducted study , the petitio ner provided a proposed metabolic pathway of fomesafen in tomato. A s also found in a concurrent confined accumulation study in rotational crops, the ether bridge is cleaved by a nucleophilic addition of glutathione with subsequent formation of cy steine co njugate(s) of the nitro - [ 14 C - U - phenyl] moiety and conjugation and/or oxidation of the trifluoromethyl - [ 14 C - U - phenyl] moiety as well as formation of polar weak acid metabolites of each ring moiety . 14 C - In corporation into very polar natural products is also likely . A ccording to the petitioner, these findings are also similar and consistent with previous metabolism work reported on fomesafen and acifluorfen (an analogous dipheny l ether herbicide) with soy

bean foliage and cotton. See Appendix I I for the chem ical names and structures of metabolites identified. Conclusions . The submitted tomato metabolism study is adequate. TRR in ripe tomatoes were very low (0.005 and 0.002 ppm for the TMP and NP labels, respectively ) following application of the test subst ances at a target rate of 0.375 lb ai/A. In ripe tomatoes , fomesafen ( 3.6 - 3.7 % TRR) was identified as were the metabolites 3 - chloro - 4 - hydroxy benzoic acid (R052850) ( 5.5 - 6.9 % TRR) , 2 - NO 2 - 5 - OH benzoic acid (R012156) ( 5.9 % TRR) , and 2 - NH 2 - 5 - OH benzoic acid ( R089135) (3.7% TRR) . The cy steine conjugate of sulfonamide (R290493) was a major product from the NP radiolabel (31 .1 - 3 1.6 % TRR). A major unknown from the TMP radiolabel (up to 78 .4 % TRR) was characterized by the registrant as acid labile, to volatile re sidues. Although the corresponding %TRR appears high for characterized/identified components, all residues were below 0.01 ppm. Residues in the rest of the tomato plant (foliage/stalks) was > 10 x higher than in fruit and generally

consist ed of fomesafen and the same metabolites.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 14 of 44 Sy ngenta’s Res ponse to Cotton Metabolism Study Data Gap s as a Condition of Registration Reference List : 47 761905 (No DER generated) HED previously

reviewed (DP# 325801 , 4/25/2006, D. Davis) a cotton metabolism study (MRID 44754 706) submitted by

Sy ngenta in support of a cotton tolerance petition (PP#9F5068) . Although the study

was deemed unacceptable to fulfill data requirements , HED concluded that the cotton study may

be upgraded p ending submission of additional information pertaining to the conduct and other experiment al details . In response, Sy ngenta has submitted MRID 47761905 which provides responses to the information requested. T he specific deficiencies are re - stated below followed by

the petitioner’s response and HED’s comments regarding the adequacy of response . Deficiency : “ The actual application rate for the higher treatment rate must be provided (Sy ngenta only

provided the target application rate for plants treated at 1.5 lb ai/A). The lighting and temperature con ditions used in the greenhouse should be provided. ” Sy ngenta’s r esponse : Sample calculations included in the cotton metabolism report indicated that 2.15 mCi and 2.47 mCi [2 - chloro - 4 - (trifluoromethyl)phenoxy- U 14 C] and 2 - [nitrobenzamide
- U 14 C ] fomesafen, respectively , at specific activities of 54.5 and 62.5 Ci/mol were required to achieve an application rate of 1.5 lb ai/A to the test pots. Dosing solutions for each label were confirmed by scintillation counting of aliquots. Application of [2 - chloro - 4 - (trifluoromethyl)phenoxy- U 14 C] fomesafen (CF 3 label) was made to three pots and determined to be equivalent to 1.51, 1.51 and 1.51 lb ai/A. Application of 2 - [nitrobenzamide
- U 14 C ] fomesafen (NO 2 label) was also applied to three pots at rates of 1.55, 1.55 an d 1.56 l b ai/A. Calculations of application rates are presented in Table 4 .Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 15 of 44 Table 4. Am ount of the Test Substance Applied to the Soil (3x Treatm ent).

(N ote : table was copied directly from MRID 47761905 . ) The exaggerated application rates (3 x ) were included in the study for the sole purpose of generating adequate residues for characterization and identification. Documentation supporting the higher application rate was included in the study notebooks and raw data. L ighting and temperature conditions in the greenhouse were adjusted periodically to minimize temperature shifts. Hygrothermograph records maintained in the laboratory notebook indicate that ty pical temperatures ranged 77 - 98 °C. Lamps were used to irradiat e the plants during early morning (7 am - 11 am) and mid - afternoon to evening (3 pm - 1 1 pm). As warmer weather arrived, lamp schedules were changed to 6 am - 9 am and 4 pm - 1 0 pm to reduce the heat in the greenhouse. Ty

pical plant heights were observed at harv est. All harvested crops were grown to maturity in good health and yield. HED’s comments /conclusions : The petitioner has provided the c alculations of the higher treatment rate used in the cotton metabolism study . The actual 3x applications rates were 1.51 and 1.55 - 1.56 lb ai/A for the CF 3 and NO 2 labels, respectively . The requested information pertaining to lighting and temperature conditions used in the greenhouse was provided and appeared optimum for the ty pe of study

conducted. This deficiency is resolved.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 16 of 44 Deficiency : “ Sy

ngenta must provide the dates of sample analysis for all samples and all analy ses. I f final analy ses of cotton gin by product samples were not completed within 6 months of sample collection, Sy

ngenta must provide evidence that th e metabolite profile in samples did not change during storage. We note that based on the study completion date, samples may have been stored >50 0 day s prior to final analy sis.” Sy ngenta’s r esponse : The RACs collected from cotton test plots treated with 14 C - fomesafen w ere extracted, chromatographically profiled , and quantified within 3.5 months of harvest. Additional analy sis of the samples was conducted beyond this point in order to isolate and characterize the radioactive residues. Comparison of chrom atography obtained towards the end of the analy

tical phase of the study

indicated a qualitatively similar chromatographic profile, thus providing evidence for storage stability . Cotton plants treated with CF 3 and NO 2 labeled fomesafen were grown to maturi ty , harvested and separated into seed/fiber and gin by products. TRR in seeds from treatment at 0.5 l b ai/A were below 0.01 ppm for both labels and were not extracted or profiled. The TRR in gin by products from cotton treated with either test compound s at both the 0.5 and 1.5 l b ai/A application rates were >0.01 ppm . The samples were extracted, profiled , and quantified in two chromatographic sy stems within 3.5 months of harvest (page 16 of MRID 47761905 ) . The cotton gin by

product extracts from the two 3 x treatment samples were further analy zed to characterize the radioactive residues. Inan effort to further characterize metabolites B, C, and D from the CF 3 labeled fomesafen treated gin by

products, the aqueous extract from the 3 x treatment was subjected to semi - prep HPL C in January

1998 (page 17 of MRID 47761905 ). The HPL C method employed in semi prep analy sis of this extract was similar in nature to the HPL C method used to generate the initial profiles (RR 97 - 056B). Therefore, a comparison of the two r esulting chromatograms (page 20 of MRID 47761905 ) can be made for storage stability purposes. Such a comparison demonstrates the extracts are qualitatively similar and, as such, provides evidence, that the extract was stable under storage conditions. Sy n genta reported that a

pproximately

10 months after harvest , an additional analy sis was conducted with the aqueous extracts of gin by products treated with N O 2 labeled fomesafen at the 3 x rate in an attempt to characterize metabolite G. Metabolite G, isolate d from an aqueous extract, was subjected to hydroly sis and was characterized by HPL C as a complex mixture of products. No storage stability data w ere collected to support this work. Metabolite G, however, only represented 0.006 ppm (13.9% TRR) in gin by p roducts treated at the 1x rate ; thus , additional characterization of this minor radioactive residue was not necessary . Therefore, Sy ngenta believes that the lack of storage stability data for this sample does not impact any of the report conclusions. HED ’s comments /conclusions : The petitioner has provided the requested dates of sample analy sis for all samples and all analyses. Based on these dates , all samples were extracted, profiled , and quantified within 3.5 months of harvest. Efforts to further an aly ze the aqueous extracts of gin by

products treated at the 3 x rate did result in analy tical work being conducted more than 6 months after harvest. Inthe case of the extracts coming from treatment with the N O 2 labeled fomesafen, no viable results in the characterization of the residues were obtainedFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 17 of 44 due to low residue levels. HED concurs with Sy ngenta’s assessment that c omparison of the resulting chromatography from the aqueous extracts of gin by products resulting from CF 3 labeled fomesafen provided a qu alitative profile similar to the definitive profile obtained within 6 months of harvest and, therefore, provides evidence of storage stability . This deficiency is resolved . Deficiency : “ There was a large difference between the total extractable radioact ivity and the total of the identified and characterized radioactivity for each sample. For samples treated at the lower rate, Sy

ngenta referred to this “fraction” as “total % unknown.” The total unknown fraction ranged 11.0 - 49.5% TRR (0.009 - 0.112 ppm) in gin by product samples. No explanation was provided. Sy

ngenta also did not provide any quantitative chromatographic raw data. Sy ngenta must provide an explanation for this apparent loss in radioactivity . In addition, quantitative chromatographic data s hould be provided for all chromatograms included in the submission. ” Sy ngenta’s r esponse : The exaggerated application rate (3 x ) samples were generated for the sole purpose of ensuring adequate radioactive residues were available to aid in characterizatio n and identification. As such, the material balance was quantitated on the 1x treatment rate. Unknown constituents in the 1x and 3 x applications are an accumulation of unresolved peaks and background radioactivity . To illustrate this point, raw data w er e used to recreate the quantitation of the CF 3 label and N O 2 label ( 1x ) organic and aqueous profiles and were presented in Figures 2 and 3 MRID 47761905 , respectively . These profiles illustrated that unknown peaks constitute multiple minor components and background radioactivity . All residues, except fomesafen, were at or below trigger ( ≤0 .010 ppm) in the organic profiles. All residues, except metabolite C, were at or below trigger ( ≤ 0.010 ppm) in the aqueous profiles. Fomesafen, metabolite C, and metab olite D were isolated for characterization and identification by mass spectrometry . Quantitation of unknown peaks in the exaggerated application rates was not pursued as the study objective was to use these 3 x treated crop fractions for isolation, if nece ssary . Chromatographic quantitation of the CF 3 labeled fomesafen ( 1 x ) unknowns had 0.020 ppm residue which c onsisted of multiple minor components, none of which, except metabolite C, had individual residues o f >0.010 ppm. No unknown residues (>0.010 ppm) requiring further characterization were present in NO 2 labeled fomesafen ( 1x ) samples. HED’s comments /conclusions : The petitioner responded to the above deficiency by recreat ing the quantitation of organic and aqueous extracts of cotton gin by products from the 1x study of the CF 3 label and N O 2 label . The unknowns comprised 32% and 8.9% TRR of the CF 3 and N O 2 label s, respectively . Chromatographic quantitation of the CF 3 labeled fomesafen unknowns c onsisted of multiple minor components, none of which, except metabolite C, had individual residues o f >0.010 ppm. No unknown residues (>0.010 ppm) requiring further characterization were present in NO 2 labeled fomesafen ( 1x ) samples. Total accountability of residues in gin by products treated at 1x was re - ca lculated at 106% and 90% the CF 3 and N O 2 label s, respectively . This deficiency is resolved. Deficiency : “ Sy

ngenta should provide an interpretation of the L C/MS spectra that were included in the submission for Metabolites B - 3 and C - 1 and provide proposed structures for these metabolites, if possible. ”Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 18 of 44 Sy ngenta’s r esponse : Structures were suggested in the raw data files but were not included in the final report as the data to support structural confirmation w ere limited. A possible structure for Metaboli te B - 3 is shown in Figure 1 while that for Metabolite C - 1 is shown in Figure 2 . Sy ngenta offered s ome possible interpretation s below which are consistent with the proposed structures. Mass spectra for both peaks (B - 3 and C - 1 ) showed that they are chlorin ated (based on the isotope pattern of the base peak) ; they also suggest that they

are radiolab e led (based on the A+12 peak from the fully labeled phenyl ring). Therefore both rings are confirmed to be intact for both moieties. The spectrum for metabolite B - 3 (Figure 1 ) showed a m/z 459 peak in negative electro spray ionization ( ESI ) consistent with the deprotonated sodium salt formed by loss of the acidic proton of the sulfonylbenzamide functionality ; i.e., [M - 2H+Na ] - . An MS/MS experiment showed a cleava ge product ion at m/z 241 and a product ion at m/z 423 from loss of HC l that was consistent with the dibenzodioxin product structure in Figure 4. Sy ngenta opined that this ty pe of intramolecular cyclization with loss of HC l is a common process. The negat ive electrospray spectrum for metabolite C1 showed a deprotonated molecule at m/z 425, which was consistent with an aryl sulfate conjugate structure as shown in Figure 2 . MS/MS product ions were observed at m/z 329 (loss of

– SO 4 ) and m/z 393 (loss of 2 ox ygens); as well as, m/z 97 (HS O 4 - ) and m/z 80 (S O 3 - ). Because of the rare occurrence of sulfate conjugates observed from the metabolism of pesticides in plants, further evidence of structure C1 would be required before this structure could be assigned with confidence. Furthermore, ambiguities observed in the MS data; for example, missing chlorine isotopes and the apparent losses of multiple (3) units of 16, demonstrate that the experiments were being conducted near the performance limits of the instrument with respect to signal intensity and chemical noise. However, given the low residue levels in the samples and limited capabilities of available L C/MS instruments, compared to today ’ s standards, the MS data represent the best possible results at the time the study was c onducted , and no additional supporting data was obtainable. HED’s comments /conclusions : The petitioner responded to the above deficiency by assigning possible structure for Metabolite s B - 3 ( Figure 1 ) and C - 1 (Figure 2 ). This deficiency i s resolved . Deficiency : “Sy

ngenta should provide an explanation for not making any attempts to characterize the nonextractable radioactivity in gin by products treated with NP label [ 14 C]fomesafen at the higher rate. According to the requirements of OPPT S 860.1300, additional attempts to extract this radioactivity should have been made (nonextractable radioactivity was >10% TRR and >0.05 ppm).” Sy ngenta’s r esponse : The N O 2 label fomesafen samples (3 x ) were generated to ensure adequate residues for ident ification and characterization. No additional attempts were made to characterize the non - extractable radioactivity for gin by

products treated with N O 2 label fomesafen at the h igher rate because of the low residue (0.011 ppm) at the 1x rate. HED’s comment s /conclusions : HED concurs with Sy ngenta that no further characterization of nonextractable residues in gin by products treated with NP label [ 14 C]fomesafen at the higher rateFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 19 of 44 is required because of the low residues at the 1x rate. HED will consider the residue characterization of cotton RACs from the 1x treatment rate as adequate and the characterization of residues from the 3x treatment rate as supplemental data. Insummary , the cotton metabolism study has now been upgraded to acceptable status based o n Sy ngenta ’s submission of the requested information pertaining to actual application rate for the higher treatment rate, the lighting and temperature conditions used in the greenhouse, the dates of sample analy sis , quantitative data for the unknowns and n onextractable residues, and the designation of possible structure s for Metabolite s B - 3 and C - 1. The supplementary data indicate that following application of CF 3 - labeled fomesafen at 1x, approximately 61% TRR (0.040 ppm) resulted in extractable peaks (A - 1 , A - 2, A - 3, fomesafen, B, C, D) in cotton gin by products with the parent fomesafen comprising 11.6% TRR (0.008 ppm). Following application of NO 2 - labeled fomesafen at 1x, approximately 55% TRR (0.0 24 ppm) resulted in extractable peaks (fomesafen, E, F, G) in cotton gin by products with fomesafen comprising 27.0% TRR (0.012 ppm).Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 20 of 44 Figure 1 . Proposed Structure and MS/MS Product Ion Assignm ent s for Metabolite B - 3 in Cotton Gin

B yproducts.

(Note: figure was copied directly from MRID 47761905.)Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 21 of 44 Figure 2 . Proposed Structure and MS/MS Product Ion Assignm ent s for Metabolite C - 1 in Cotton Gin

B yproducts.

(Note: figure was copied directly from MRID 47761905.)Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 22 of 44 Potato When a pesticide will be used on several different crops the Agency requires plant metabolism studies on three diverse crops. Currently adequate tomato, soy

bean, and cotton metabolism studies are available for fomesafen. The HED Chemistry Science Advisory

Council (ChemSAC) specifically

considered the need for metabolism studies for fom esafen in a meeting on 7/25/2007. According to the 07/25/2007 minutes, the ChemSAC specifically recommended submission of a root/tuber metabolism study because cotton and soy

beans are considered similar within the Agency and internationally

(e.g., OECD). Given this fact, ChemSAC concluded that a potato metabolism study

would still be required. A potato metabolism study , in which both the root and tops/foliage are analy

zed, is required to support the proposed use on potatoes. HED cannot recommend for a t olerance in/on potatoes until an adequate potato metabolism study is submitted. 860.1300 Nature of the Residue - Livestock MRID 00110508 (PP#2G2745, 1/28/83, A. Rathman, and PP#4F2997, 9/25/94, A. Smith) MRID 00135635 (PP#4F2997, 9/25/84, A. Smith) Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis Sy ngenta submitted a goat metabolism study in conjunction with the temporary tolerance petition for soy beans (PP#2G2745). A single goat was dosed with [nitrophenyl 14 C]fomesafen at 0.1 ppm in the diet for 7 day s; the goat was sacrificed 16 hours after the final dose. The dosing level corresponds to ~2x and 5x the maximum theoretical dietary burden s to beef and dairy cattle , respectively . TRR reached a maximum in milk of 0.0008 ppm on Day 3. TRR were 0.00 3 ppm in liver, 0.004 ppm in kidney , <0.003 ppm in meat, and <0.005 ppm in fat. Approximately 70% of the dosed radioactivity was excreted. No residue characterization was conducted because of low radioactivity

levels. A goat metabolism study

was revie wed in conjunction with the soy bean permanent tolerance petition (PP#4F2997). A single goat was dosed with [nitrophenyl 14 C]fomesafen at 10.3 ppm in the diet for 3 consecutive days; the goat was sacrificed 4 hours after the final dose. The dosing level c orresponds to ~ 184 x and 468 x the maximum theoretical dietary burdens to beef and dairy cattle, respectively . TRR were 0.20 ppm in liver, 0.28 ppm in kidney , 0.009 ppm in meat, 0.006 ppm in fat, and 0.014 ppm in milk. Approximately 47% of the dosed radioa ctivity was excreted. Fomesafen was not found in any milk, tissue, or excreta sample. The identifi ed metabolites were 5 - (2 - chloro - α,α,α - trifluoro - p - tolyloxy ) - N - methylsulfonylanthranilamide (compound XV) and 5 - (2 - chloro - α,α,α - trifluoro - p - tolyloxy ) anthranilic acid (compound V). Compound XV was found at 10% TRR in liver and 20.9% TRR in kidney , and comp ound V was found at 34.5% TRR in liver and 33.9% TRR in kidney . Conclusions . The available livestock metabolism data are adequate to satisfy data requirements. The significant components of the animal residues are fomesafen and its metabolites 5 - (2 - chl oro α,α,α - trifluoro - p - tolyloxy ) anthranilic acid (compound V) and 5 - (2 - chloro - α,α,α - trifluoro - p tolyloxy ) - N - methylsulfonylanthranilamide (compound XV).Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 23 of 44 Based on the residue levels in goat matrices following dosing at to ~ 184 x and 468 x the maximum theore tical dietary burdens to beef and dairy cattle, respectively , HED concludes that the proposed/registered uses of fomesafen on cotton, dry and snap beans, soy

beans , potatoes, and tomatoes result in a 40 CFR §180.6(a)(3) situation for livestock commodities; i.e., there is no reasonable expectation of finite residues in livestock commodities. T here are no poultry and swine feedstuffs associated with the proposed uses. 860.1340 Residue Analytical Methods MRID 40007101 (Enforcement method for soybean ; PP#4F29 97, CB No. 2253, 8/18/87, W. Chin) MRIDs 44754703 and 44754704 (Enforcement method for cotton; DP# 325801, 4/25/06, D. Davis) MRIDs 45093602 and 45093603 (Revised enforcement method for soybean; DP# 325801, 4/25/06, D. Davis) Plant commodities Enforcement methods Three residue analy

tical methods have been submitted to the Agency for the purpose of tolerance enforcement. All of these methods quantitate residues of fomesafen in/on crop commodities and are briefly described below. (i) The HPL C/UV method, GAM - RM - 001/86, was submitted in the initial soy bean petition (PP#4F2997). The method, entitled “The Determination of PP021 in Soy beans - A High Performance Liquid Chromatography Method”, involves the extraction of residues in crop samples with acetonitril e:concentrated HCl (98:2, v:v). The extract is diluted with water and partitioned with hexane. The aqueous phase is partitioned with dichloromethane ( DCM ) , and the DCM phase is cleaned up by ion - exchange chromatography on an amino column for HPL C analy si s using a C18 column and UV detection at 290 nm. The limit of quantitation ( LOQ ) reported in the method is 0.01 - 0.02 ppm . The method has successfully passed an Agency tolerance method validation . (ii) The G C/NPD method, TMR0836B, was submitted and revi ewed in DP# 325801 to replace the existing HPL C/UV method for soy bean commodities. The method is entitled “Determination of Fomesafen in Soy

beans by Gas Chromatography

with Nitrogen/Phosphorus Detection.” The new method differs from the existing enforcem ent method in the use of GC/NPD for analy sis of extracts . The extraction procedures of the method are similar to those of the existing H P LC /UV method; however, in the new method, fomesafen is converted to its methylated analog to allow GC determination. Briefly , residues in/on soy bean forage, hay , and seed samples are extracted with acidified ACN, and the extract is acidified and partitioned with hexanes. The resulting aqueous phase is partitioned with DCM, and the DCM phase is redissolved in methy l isob utyl ketone (MIBK). The MIBK solution is mixed with iodomethane and then heated to methy late fomesafen. The methylated residues are cleaned up on a silica gel column for GC/NPD analysis. Results are reported in terms of fomesafen. The validated L OQ rep orted in the method is 0.02 ppm for soy

bean forage, hay , and seed. A limit of detection (L OD) was not reported; Sy ngenta estimated the L OD to be less than 10 - 20% of the L OQ in these commodities. (iii) A GC/NPD method (TMR0800B ) was submitted in the cott on petition (PP#9F5068) and reviewed in DP# 325801 . The method is entitled “Determination of Fomesafen in CottonseedFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 24 of 44 and Gin Trash by

Gas Chromatography .” Using this method , residues in cotton matrices are extracted with acidified ACN, and the extract is partitioned with hexanes. The resulting aqueous phase is partitioned with DCM, and the DCM phase is redissolved in MIBK. The MIBK solution is mixed with iodomethane and then heated to methylate fomesafen. The methylated residues are cleaned up on a sil ica gel column for GC/NPD analy sis. Results are reported in terms of fomesafen per se . The validated L OQ reported in the method is 0.02 ppm for cotton seed and gin by products. An L OD was not reported; Sy ngenta estimated the LOD to be less than 10 - 20% of the L OQ in cotton seed and gin by products. HED’s review (DP# 325801, 4/25/06, D. Davis) of GC/NPD Methods TMR0836B (soy beans) and TMR0800B (cotton) required the submission of additional data before the methods can be deemed suitable for tolerance enforce ments. The Agency required confirmatory

raw data, the modification of the method to incorporate extraction and analysis of specific crop commodities, and the submission of confirmatory methods. Sy ngenta’s Res ponse to Analy tical Method Data Gaps as a Co ndition of Registration Reference List: 47761905 (No DER generated)

47761903.der.doc (Includes MRID 47761904) Sy ngenta has submitted MRID 47761905 which provides responses to the information and data requested by

the Agency . For purposes of clarity , the specific deficiencies pertaining to residue analy tical methods are re - stated below followed by the petitioner’s response as well as HED’s comments regarding the adequacy of response . Deficiency : “ Sy

ngenta must submit raw data to support the method val idation data reported in MRIDs 44754703, 45093602, 45093603, 45268502 and 45268503. ” Sy ngenta’s r esponse : Sy

ngenta has been unable to locate the method validation raw data as requested. Inthe absence of these raw data, Sy ngenta undertook additional wor k to confirm the validity of the method extraction procedure specified in the MRID numbers cited above. Specifically , soy

bean and cotton commodities, as well as dry beans, were analy

zed using an updated method , GRM045.01A. This method utilizes the same e xtraction procedure as the previous methods. This method did differ from the previous methods by the inclusion of a SPE clean - up step , and the analy sis was conducted using L C /MS /MS. These results are reported in MRIDs 47761903 and 47761904 . HED’s comm ents /conclusions : Sy ngenta Crop Protection has submitted descriptions and validation data for a new proposed enforcement method, Method GRM045.01A, which is entitled “Fomesafen Analy tical Method for the Determination of Residues of Fomesafen in Crop Commodities by L C - MS/MS.” This high performance liquid chromatography with tandem mass spectrometry detection (L C/MS/MS) method is based on previously submitted gas chromatography with nitrogen phosphorus detection (GC/NPD) methods (refer to DP# 325801, D. D avis, 4/25/06) developed by Zeneca AG. Method GRM045.01A uses extraction procedures modified from the previous GC/NPD methods. Inthe revised method, fomesafen residues are extracted with 1% hydrochloric acid inFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 25 of 44 acetonitrile . An aliquot is subjected to an SPE cleanup and analy zed using L C/MS/MS. A second ion transition may be monitored for confirmation. The L OQ is 0.02 ppm for fomesafen in each matrix. Representative spectra and linearity data were submitted demonstrating adequate sensitivity . No ind ependent laboratory validation (ILV) or radiovalidation data have been submitted for Method GRM045.01A. Because the method is an improvement on the previously established GC/NPD methods, these data will not be required. HED will also not request ACB/BEAD for a tolerance method validation, and will forward the method to FDA for inclusion in the Pesticide Analy tical Manual (PAM) Volume I I as an enforcement method. This deficiency is resolved. Deficiency : “ Sy

ngenta should modify

GC/NPD Method No. TMR0836B to include instructions for the extraction and analysis of dry bean, snap bean, and aspirated grain fractions. The modified method should then be forwarded to FDA for inclusion in the Pesticide Analy tical Manual (PAM) Volume I I. ” Sy ngenta’s r esponse : T he new analy tical m ethod GRM045.01A meets this requirement. HED’s comments /conclusions : LC /MS/MS method ( GRM045.01A ) is written to include analy sis of a wider variety of commodities ( including snap beans, dry beans, and soy

bean aspirated grain fractions ) for residues of fomesafen; special instructions are included in the analy tical procedures for separate extraction of residues in crop commodities except for oil and for oil samples. This deficiency is resolved. Deficiency : “ Sy

ngenta must propose alter native confirmatory

methods for the proposed new enforcement methods. The currently proposed confirmatory

methods involve substitution of columns with only

slight polarity

differences and likely

very similar elution times and are not considered sufficient for confirmation of an enforcement method. ” Sy ngenta’s response : The new analy tical method, (GRM045.01A), which i ncorporates the highly specific LC /MS /MS detection, satisfies this requirement. HED’s comments /conclusions : The new analy tical method, (G RM045.01A) includes a second transition for confirmatory analy sis. The ion transition monitored for fomesafen is m/z 437 →195; the ion transition m/z 437→222 is available as a confirmation. Insummary , Sy

ngenta has submitted a new LC /MS/MS method (GRM045.01A) for analy sis of fomesafen residues in crop commodities. This method is the updated version for previous Z eneca AG data - gathering methods (T MR08055B, TMR0879B, TMR0800B, and TMR0881B ) . Th e method uses extraction procedures as previously described in the above - mentioned method s, SPE cleanup procedures, and the final determination step by L C /MS/MS technology

fo r analy sis of fomesafen residues. The validated LOQ of the method is 0.02 ppm. Method GRM045.01A has been adequately

validated at fortification levels of 0.02 ppm and 0.2 ppm in snap beans, pinto beans (dry

bean), corn oil, cotton, undelinted seed and gi n by products, and soy

bean forage , hay , and aspirated grain fractions .Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 26 of 44 No radiovalidation data have been submitted for LC /MS/MS method (GRM045.01A) ; however, because the extraction procedures of the method are similar to those of the soy bean metabolism stu dy , radiovalidation data are not needed. Sinc e LC /MS/MS method (GRM045.01A) appears to be a superior method to the previously submitted methods for fomesafen due to its state of the art technology and its specificity , HED will not require independent labo ratory validation data. HED will also not request ACB/BEAD for a TMV and will forward the method to FDA for inclusion in the Pesticide Analy tical Manual (PAM) Volume I I as an enforcement method. Data - collection methods Samples of raw and processed commo dities of potatoes and tomatoes, which were collected from the magnitude of the residue studies, were analy zed for residues of fomesafen using a high performance liquid chromatography method with tandem mass spectrometry detection based on an HPL C/UV metho d (GAM - RM - 001/86). The method was adequately validated during concurrent analy sis of samples. The lowest level of method of validation (LLM V) was 0.025 ppm for each matrix. Livestock commodities Because there are no established or proposed tolerances f or livestock commodities, an enforcement method for livestock commodities is not required. 860.1360 Multiresidue Methods DER Reference List : 47761901.der.doc Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis HED ( DP# 325801 ) previously required the submission of multiresidue method testing data for fomesafen. In response, the petitioner submitted MRID 4776190 1 . The s ubmission has been reviewed by

HED , and the Executive Summary of the study

DER is reproduced below. Sy ngenta Crop Protection has sub mitted multiresidue testing data for fomesafen (free acid) following testing and analy sis according to FDA Multiresidue Test Guidelines in PAM Vol. I (1/94). The Decision Tree for MRM Testing found in the Multiresidue Protocols was followed in determining the response patterns. Fomesafen (free acid) was tested through Protocols A, B, and C. Protocols D, E, and F were not tested as no residues were detected using Protocol C. The compound was not tested under Protocol G because it is not a substituted ure a. Fomesafen does not have an N - methylcarbamate structure and did not produce a response on the fluorescence detector under Protocol A. In Protocol B testing, methylated fomesafen was not recovered from Florisil; therefore, no additional work was perfo rmed under Protocol B. Fomesafen (free acid) did not produce a response under Protocol C, using gas chromatography with either the nitrogen phosphorus or the electron capture detector (GC/NPD or GC/ECD). Therefore, it was not tested using Protocol D, E, or F. Conclusions : These data indicate that FDA multiresidue methods are not suitable for determining residues of fomesafen. The submitted data will be forwarded to U.S. FDA forFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 27 of 44 further evaluation. 860.1380 Storage Stability DER Reference : 47 761902 .d er.doc (c orn, soybean, cotton, and w heat matrices storage stability data) DER Reference : 4 7473903.de1.doc (potato tuber concurrent storage stability data) DER Reference : 4 7473903.de2.doc (potato processed commodities concurrent storage stability data) DE R Reference : 4 7473902.de1.doc (tomato fruit concurrent storage stability data) DER Reference : 4 7473902.de2.doc (tomato processed commodities concurrent storage stability data) Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis Sample storage duration and conditions The storage durations and conditions of potato and tomato samples from the submitted magnitude of the residue and processing studies are presented in Table 5 . Table 5 also includes the storage conditions and durations o f samples from the crop field trial , processing, and field rotational crop studies which were submitted to support previous petitions (PP#s 1E6228, 9F5068, and 6E4653). Table 5 . Summary of Storage Conditions and Durations of Sam ples fromCrop Field Trial, Processing, and

Field Rotational Crop Studies. Matrix Storage

Tem perature (°C) Actual Storage

Duration Interval of Demonstrated Storage Stability Samples from Previous Petitions (PP#s 1E6228, 9F5068, and 6E4653)

reviewed under DP# 325801, 4/25/06, D. Davis Cotton Fi eld Trials (MRID 44754701) Cotton gin byproducts ~ - 18 232 - 324 days (7.6 - 10.7 months) Storage stability data indicate that r esidues of

fomesafen appear to be erratic in/on cotton gin byproducts , but overall show general stability ; corrected stored recoveri es were 69% at 2.5 mo nths, 80% at 3.2 months, 142% at 8.8 mo nths, and 68% at 14.6 months. Soybean Processing Study (MRID 45093601) Soybean hulls - 20 294 days (9.7 months) Storage stability data indicate that r esidues of

fomesafen appear to be relatively stable in/on soybean hulls s tored frozen at - 31 to - 3 oC for up to ~15 months. Soybean refined oil 288 days (9.5 months) Storage stability data indicate that r esidues of

fomesafen appear to be relatively stable in/on soybean oil for up to ~9 months but i ncreased to a recovery of 149% by ~15 months. Field Rotational Crop Study (MRID 00158936) 1 Corn forage - 20 235 - 272 days (7.7 - 8.9 months) Storage stability data indicate that r esidues of

fomesafen appear to be relatively stable in/on corn K+CWHR, forage, and stover, and w heat forage and straw s tored frozen at - 31 to - 3 oC for up to ~15 months. Corn cob 178 - 223 days (5.8 - 7.3 months) Corn fodder 178 - 223 days (5.8 - 7.3 months) Wheat forage 361 - 388 days (11.9 - 12.7 months)Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 28 of 44 Table 5 . Summary of Storage Conditions and Durations of Sam ples fromCrop Field Trial, Processing, and

Field Rotational Crop Studies. Matrix Storage

Tem perature (°C) Actual Storage

Duration Interval of Demonstrated Storage Stability Wheat straw 289 - 339 days (9. 5 - 11.1 months) Field Rotational Crop Study (MRID 45268501) Field corn, forage < - 10 280 - 316 days (9.2 - 10.4 months) Storage stability data indicate that r esidues of

fomesafen appear to be relatively stable in/on corn forage and stover, and w heat forage an d straw s tored frozen at - 31 to - 3 oC for up to ~15 months. Field corn, stover 239 - 279 days (7.9 - 9.2 months) Sorghum, forage 232 - 289 days (7.6 - 9.5 months) Sorghum, stover 182 - 273 days (6.0 - 9.0 months) Samples from Current Petition (PP#9F7563) Po tato Field Trials and Processing Study (MRID 47473903) Potato tuber - 40 to - 6 316 - 399 days (10.4 - 13.1 months) Concurrent storage stability data indicate that

r esidues of fomesafen appear to be relatively stable for u

p to 420 days in/on frozen potato tuber , 311 days in potato flakes , 308 days in potato chips , and 307 days in wet potato peel. Potato, tuber (RAC) - 40 to - 6 308 days (10.1 months) Potato, flakes 299 days (9.8 months) Potato, chips 298 days (9.8 months) Potato, w et peel 293 days (9.6 mo nths) Tom ato Field Trials and Processing Study (MRID 47473902) Tom ato fruit - 40 to - 5 211 - 302 days (6.9 - 9.9 months) Concurrent storage stability data indicate that

r esidues of fomesafen appear to be relatively stable for up to 319 days in/on tomato fr uit and 236 days in tomato paste and puree. Tom ato, fruit (RAC) - 40 to - 5 241 days (7.9 months) Tom ato, paste 229 days (7.5 months) Tom ato, puree 229 days (7.5 months) 1 For the field rotational crop study reported in MRID 00158936, the dates of sample analysis were not provided. The maximum storage interval for each sample, based on the study completion date, was calculated by the study reviewer. Storage stability

data S torage stability data were concurrently generated with the potato /tomato f ield and processing studies. For each crop, control samples of the respective matrices were fortified with fomesafen at ~0.25 ppm and placed in storage under the same frozen c onditions as the treated samples. No zero - day analy ses were conducted on the fo rtified samples placed into storage. Rather, triplicate stored samples were analy zed along with a control sample and freshly fortified samples at an interval reflecting the maximum storage intervals from the field and processing studies . Average correcte d recovery

ranges of f

omesafen were: 7 8 - 9 0 % in potato tubers after 420 day s, 7 9 - 99 % inFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 29 of 44 potato flakes after 311 day s, 72 - 7 7% in potato chips after 308 day s, 71 - 8 1 % in potato wet peel after 307 day s, 8 1 - 9 2 % in tomato fruits after 319 day s, 8 9 - 10 8 % in tomato paste after 236 day s, and 87 - 1 09 % in tomato puree after 236 days. Although no 0 - day analy sis was conducted, the data indicate that f

omesafen is stable under frozen storage conditions at the maximum intervals tested . These data indicate that no correctio ns of residues need to be applied to the study results . Sy ngenta’s Response to Storage Stability Data Gap s as a Condition of Registration HED previously requested additional storage stability data to support the storage conditions and intervals of sample s collected from various field and rotational crop studies (DP# 325801, 4/25/2006, D. Davis) . The specific deficienc y is re - stated below followed by the petitioner’s response and HED’s comments regarding the adequacy of response . Deficiency : Data are re quired depicting the stability of residues of fomesafen in/on the following commodities: cotton gin by products stored frozen for up to 11 months; soy bean hulls and oil stored frozen for up to 10 months; corn cob stored frozen for up to 7 months; wheat for age and straw during frozen storage for up to 13 months; and field corn or sorghum forage and stover during frozen storage for up to 10 months. Sy ngenta’s response : The r equested storage stability data have been developed and are reported in MRID 4776190 2 . This interim report included stability data through 13 months as required but the study

will continue with planned analy sis at both 18 and 24 months. Upon completion of the analy sis of the 24 month samples, the final report will be submitted. HED has reviewed the study submission; the Executive Summary of the completed study

DER is presented below. HED’s comments /conclusions : Sy ngenta Crop Protection has submitted interim storage stability data for fomesafen in corn kernel plus cob with husks remo ved (K+CWHR), forage, and stover; cotton gin by

products; soy

bean hulls and oil; and wheat forage and straw. These data were submitted in response to data gaps for fomesafen storage stability data to support use of the sodium salt on these crops (DP# 32580 1, D. Davis, 4/25/06). Samples of eight commodities (corn K+CWHR, forage, and stover; cotton gin by products; soy bean hulls and oil; and wheat forage and straw) were spiked with fomesafen at 1.00 ppm. Fortified and unfortified samples were stored at - 31 t o - 3 °C. The petitioner reports that samples of each commodity

were analy

zed after 0, 1, 3, 6, and 13 months of storage, with planned additional intervals of 18 and 24 months; however, inspection of the fortification and analysis dates provided in MRID 47 761902 yield different intervals. The study was conducted by ADPEN L aboratories, Inc. (Jacksonville, FL). Crop samples were analy zed using Sy

ngenta method GRM045.01B. The extraction and analysis procedures for this method are similar to those of method GRM045.01A. The validated LOQ is 0.02 ppm for fomesafen in each crop matrix. Residues of fomesafen appear to be relatively stable in/on corn K+CWHR, forage, and stover, soy bean oil and hulls, and wheat forage and straw s tored frozen at - 31 to - 3 oC for u p to ~15 months. Residues of fomesafen appear to be erratic in/on cotton gin by products, but overall show general stability . An adequately validated method was used for the quantitation ofFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 30 of 44 fomesafen in the crop matrices tested in the storage stability study . The interim storage stability data adequately

support the storage conditions and intervals of crop commodity samples discussed in DP# 325801 . In the interim report, the petitioner report ed that samples of each commodity were analy

zed after 0, 1, 3, 6, and 13 months of storage, with planned additional intervals of 18 and 24 months. When actual storage intervals were recalculated using dates from the raw data, samples were extracted after 0, 1.1 - 2.5, 3.2 - 4.0, 8.2 - 9.2, and 14.6 - 15.0 months. It appears from the raw data that samples from the 0 - , 1 - , and 3 - month storage intervals were fortified at later dates than samples from the 6 - and 13 - month storage intervals. The petitioner must explain in the final report why the fortification times are different and why

the actual storage intervals differ so greatly from the nominal storage intervals. 860.1400 Water, Fish, and Irrigated Crops There are no proposed uses that are relevant to this guideline topic . 860.1460 Food Handling There are no proposed use s that are relevant to this guideline topic. 860.1480 Meat, Milk, Poultry, and Eggs The re are no livestock feedstuffs associated with the proposed use on tomatoes. Although, there are ruminant livestock feedstuffs associated with the petition on potatoe s, they are not addressed in this review, due to the lack of a root/tuber metabolism study . A ruminant feeding study was not submitted and is not needed for the purpose of this petition. HED concludes that the registered uses of fomesafen on cotton, dry and snap beans, and soy bean and the proposed use of fomesafen on potato result in a 40 CFR §180.6(a)(3) situation for livestock commodities; there is no reasonable expectation of finite residues in livestock. Therefore, no livestock feeding studies are re quired to support the proposed/registered uses of fomesafen sodium. Sy ngenta should note that if additional uses are proposed in the future which result in an increase in the dietary burden, livestock feeding studies may be required.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 31 of 44 860.1500 Crop Field Trials DER Reference List 47473903.de1 (Potato) 47473902.de1 (Tom ato) A summary

of the reviewed crop field trial data for potato and tomato is presented in Table 6 . T able 6 . S ummary of Residue Data fromCrop Field Trials with Fom esafen . Commodity Total Applic.

Rate (lb a e /A) PHI

(days) Residue Levels (ppm)

n Min. Max. HAFT 1 Median (STMdR) Mean

(STMR) Std. Dev. Potato (Proposed use = One preemergence application after planting but before crop emergence at 0.25 lb ae/A; 70 - day PHI) Potato tubers 0.237 - 0.263 70 - 141 26 <0.025 <0.025 <0.025 0.025 0.025 --- Tom ato (Proposed use = One preplant non - incorporated preemergence application up to 7 days prior to transplanting of tomatoes at 0.375 lb ae/A; 70 day PHI ) Tomato fruit 0.373 - 0.399 71 - 104 2 4 <0.025 <0.025 <0.025 0.025 0.025 -- 1 HAFT = Highest Average Field Trial. Potato Sy ngenta Crop Protection has submitted field trial data for fomesafen on potatoes. Thirteen trials were conducted in the United States in Zones 1 (NY; 1 trial), 2 (MD, NC and NJ; 3 trials), 3 (FL ; 1 trial), 5 (MI

and WI ; 2 trials), 8 (CO; 2 trials), and 11 (ID and WA; 4 trials) during the 2006 growing season . At each test location, a single preemergence application of Reflex® Herbicide (EPA Reg. N o. 100 - 993) was made to potatoes at 0.237 to 0.263 lb a e (acid equivalents) /A. Reflex® Herbicide is a soluble concentrate liquid formulation containing 22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of fomesafen). Appl ications were made using ground equipment in spray

volumes of 16 - 36 gal/A without an adjuvant. Samples of mature potatoes were collected at a PHI

of 70 - 141 day s. Additional samples were collected from one trial to conduct a processed food and feed study ; refer to the 860.1520 DER for MRID 47473903 for the study details and results. Samples of potatoes were analy zed for residues of fomesafen using a LC/MS/MS method based on an HPL C/UV method (GAM - RM - 001/86), entitled “The Determination of PP021 in Soy bean s

– A High Performance Liquid Chromatographic Method,” which is an enforcement method for fomesafen. The method was adequate for data collection based on adequate concurrent recovery data. The LLMV was 0.025 ppm for potato. The maximum storage duration of potatoes from harvest to analysis was 399 day s (13.1 months) for analy sis of fomesafen. Sample storage conditions and durations are supported by concurrent storage stability

data. However, zero - day data were not provided with the storage stability stu dy . The petitioner is reminded that storage stability studies should alway s include a zero - day sampling interval to ensure that the samples were fortified properly [see OPPTS 860.1380(d)(6)(i)].Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 32 of 44 Residues of fomesafen were less than the LLM V (<0.025 ppm) in/on potatoes harvested 70 - 141 day s following a single pre - emergence application of the 2 lb ae/gal SL formulation of fomesafen at a total rate of 0.237 - 0.263 lb ae/A. Tomato Sy ngenta Crop Protection has submitted field trial data for fomesafen on tomatoes. Twelve trials were conducted in the United States in Zones 1 (NY; 1 trial), 2 (NC; 1 trial), 3 (FL ; 2 trials); 10 (CA and NM; 8 trials) during the 2006 growing season. At each test location, a single pre - transplant applicatio n of Reflex® Herbicide (EPA Reg. No. 100 - 993) was made to tomatoes at 0.373 to 0.399 lb a e /A. Reflex® Herbicide is a SL formulation containing 22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of fomesafen). Applications were made using ground equipment in spray volumes of 21 - 35 gal/A without an adjuvant. Samples of mature tomatoes were collected at a PHI of 71 - 104 day s. Additional samples were collected from one trial to conduct a processed food and feed study ; refer to the 860.1520 DER for MRID 47473902 for the study details and results. Samples of tomatoes were analy zed for residues of fomesafen using a high performance liquid chromatography

method with tandem mass spectrometry detection (L C/MS/MS) based on an HPL C/UV method (GAM - RM - 001/86), entitled “The Determination of PP021 in Soy beans

– A High Performance Liquid Chromatographic Method,” which is an enforcement method for fomesafen. The method was adequate for data collection based on adequate concurrent recovery data. The lowest level of method of validation (LLM V) was 0.025 ppm for tomato. The maximum storage duration of tomatoes from harvest to analysis was 302 day s ( 9.9 months) for analy sis of fomesafen . Sample storage conditions and durations are supported by concurrent storage stability

data. However, zero - day data were not provided with the storage stability study . The petitioner is reminded that storage stability studies should alway s include a zero - day sampling interval to ensure that the samples were fortified properly [see OPPTS 860.1380(d)(6)(i)]. Residues of fomesafen were less than the LLM V (<0.025 ppm) in/on tomatoes harvested 71 - 104 day s following a single pre - transplant application of the 2 lb ae/gal SL formulation of fomesafen at a total rate of 0.373 - 0.399 lb ae/A. Conclusions . The submitted field trial data for fomesafen on tomatoes are acceptable and support the proposed uses. An adequate number of trials were conducted in the appropriate geographic regions at ~1x the maximum propos ed rate using Reflex® Herbicide , and the appropriate samples were collected from each test around the proposed PHI . All treated samples bore residues below the LLM V (<0.025 ppm). Based on these data, HED recommends a tolerance of 0.025 ppm for residues of fom esafen in/on tomatoes. The submitted field trial s for potatoes may be adequate, pending outcome of the required metabolism study . An adequate number of trials were conducted in the appropriate geographic regions at ~1x the maximum proposed rate using Ref lex® Herbicide, and the appropriateFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 33 of 44 samples were collected from each test around the proposed PHI . A potato metabolism study is outstanding, as described in section 860.1300 above. I f the new study does not identify

any additional residues of concern, th en the field trial data are adequate. However, if additional residues of concern are found, then a full set of field trials reflecting analysis of the additional residues will be required. Sy ngenta’s Res ponse to Cotton Field Trial Data Gaps as a Conditio n of Registration Reference List : 47 761905 (No DER generated) HED previously

reviewed (DP# 325801, 4/25/2006, D. Davis) a magnitude of the residue study on cotton (MRID 4475470 1 ) submitted by Sy ngenta in support of a cotton tolerance petition (PP#9F5068 ). Although the study was deemed unacceptable to fulfill data requirements , HED concluded that the cotton study may be upgraded p ending submission of additional information pertaining to the conduct and other experiment al details. Inresponse, Sy ngenta h as submitted MRID 47761905 which provides responses to the information requested. T he specific deficiencies are re - stated below followed by the petitioner’s response and HED’s comments regarding the adequacy

of response . Deficienc ies : “ The available cro p field trial data are adequate to support the proposed use on cotton provided the following data are provided:

· A summary

of weather conditions at the individual sites, indication as to whether irrigation was used, and average historical data for temper ature and rainfall for the duration of the field intervals of the trials.

· Soil characteristics data (percent organic matter, pH, and cation exchange capacity ) for the individual sites.

· Raw data including at least: (i) field notes and/or reports on application (including which spray

adjuvant was used), plot maintenance, and sample harvest; (ii) calibration of application equipment (for confirmation of application rate); and (iii) a specific description (which may be in the field notes) as to how and where (within the plot) the sample was taken and what was done to ensure that samples were representative of the test plot.” Sy ngenta’s response : Raw data from the previously reviewed cotton field trials were attached in Appendix 2 of MRID 47761905 . The raw data provided specific details on the application, plot maintenance , and sample harvest. The raw data confirm the conditions reported in the initial report. The c alibration of application equipment (for confirmation of application rate) and weather conditions (NOAA Climatological Data) were also provided in these reports. At each trial location, information pertaining to the soil ty pe, percent organic matter, pH and cation exchange capacity

were provided from the Soil Survey Geographic (SSURGO) Data base. HED’s comments /conclusions to deficienc ies : T he available c otton field trial data have now been upgraded to acceptable status based on Sy ngenta’s submission of the requested information pertaining to field weather conditions, soil characteristics , raw data of field notes, calibration of equipment, and sampling procedures that were employed in the conduct of the cotton trials. TheFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 34 of 44 Agency concludes that adequate residue data are available to support the established tolerance s of 0.025 ppm each for cotton gin by products and undelinted cottonseed. This deficiency is resolved. 860.1520 Processed Food and Feed DER Reference List 47473903.de2 (Potato) 47473902.de2 (Tom ato) T he observed processing factors reported for potatoes and tomatoes, resulti ng from treatment at 1x, are presented in Table 7 . Table 7 . Summary of Observed Processing Factors for Fom esafen in Potatoes and Tom atoes Following

Treatm ent at 1x . RAC Processed Commodity Processing Factor Potato , tuber Flakes N C 1 Chips NC Wet peel NC Tom ato , fruit Paste NC Puree NC 1 NC = Not calculated. The processing factor could not be calculated bec ause residues were below the LLMV (<0.025 ppm) in both the RAC and the processed fraction s. Potato Sy ngenta Crop P rotection submitted magnitude of the residue data f or fomesafen on the processed commodities of potatoes. Samples used for processing were generated from one potato field trial conducted in ID ( Zone 1 1) during the 2006 growing season . The test formulatio n used in the trial was Reflex® Herbicide (EPA Reg. No. 100 - 993), a SL formulation containing 22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of fomesafen). Potatoes were harvested 130 day s following a single preemergenc e application of a 2 lb ae/gal SL formulation of fomesafen at 0.256 lb a e /A (~1x field application rate) . Application was made using ground equipment in a spray volume of 20 gal/A without an adjuvant. The potatoes were processed into potato flakes, chips and wet peel. Samples of potatoes and potato processed commodities were analy zed for residues of fomesafen using a high performance liquid chromatography method with tandem mass spectrometry detection (L C/MS/MS) based on an HPL C/UV method (GAM - RM - 001/86) , entitled “The Determination of PP021 in Soy beans

– A High Performance Liquid Chromatographic Method,” which is an enforcement method for fomesafen. The method was adequate for data collection based on adequate concurrent recovery data. The lowest level of method of validation (LLM V) was 0.025 ppm for potato tuber and processed commodities flakes, chips, and wet peel. The maximum storage duration of the processing study samples were 308 day s ( 10.1 months) from harvest to analy sis for potatoes (RAC) and 299 day s (9.8 months), 298 day s (9.8 months), and 293 day s (9.6 months) from processing to analy sis for potato flakes, chips and wet peel, respectively . Sample storage conditions and durations are supported by concurrent storage stability data. However, zero - day data were not provided with the storage stability study . TheFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 35 of 44 petitioner is reminded that storage stability studies should alway s include a zero - day sampling interval to establish the residue levels present at the time samples are placed into storage [see OPPTS 860.1380(d)(6)(i)]. Residues of fomesafen were less than the LLM V (<0.025 ppm) in/on the potato tuber (RAC) and potato processed commodities. Therefore, concentration factors could not be calculated. The petitioner is reminded that sample s used in processing studies should contain field - treated quantifiable residues so that concentration factors can be determined. Field treatment of the processing samples should have been done at exaggerated application rates to ensure that the samples we re fortified properly [see OPPTS 860.1 520 ( c )( 2 ) ] . According to Tables 2 and 3 of OPPTS 860.1520, the theoretical concentration factors for potato processed fractions are 4.0x for processed waste (wet peel) and 4.7x for flakes/granules. Tomato Sy ngenta C rop Protection submitted magnitude of the residue data f or fomesafen on the processed commodities of tomatoes. Samples used for processing were generated from one tomato field trial conducted in CA ( Zone 10 ) during the 2006 growing season . The test formu lation used in the trial was Reflex® Herbicide (EPA Reg. No. 100 - 993), a soluble concentrate liquid (SL) formulation containing 22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of fomesafen). Tomatoes were harvested 104 d ay s following a single pre - transplant application of a 2 lb ae/gal SL formulation of fomesafen at 0.380 lb a e /A (~1x field application rate) . Application was made using ground equipment in a spray volume of 25 gal/A without an adjuvant. The tomatoes were processed into tomato paste and puree using standard commercial practices . Samples of tomatoes and tomato processed commodities were analy zed for residues of fomesafen using a high performance liquid chromatography method with tandem mass spectrometry

de tection (L C/MS/MS) based on an HPL C/UV method (GAM - RM - 001/86), entitled “The Determination of PP021 in Soy beans

– A High Performance Liquid Chromatographic Method,” which is an enforcement method for fomesafen. The method was adequate for data collection based on adequate concurrent recovery data. The lowest level of method of validation (LLM V) was 0.025 ppm for tomato fruit, paste, and puree. The maximum storage duration of the processing study samples were 241 day s ( 7.9 months) from harvest to analy sis for tomatoes (RAC) and 229 day s (7.5 months) from processing to analy sis for tomato paste and puree. Sample storage conditions and durations are supported by concurrent storage stability data. However, zero - day data were not provided with the storage st ability study . The petitioner is reminded that storage stability studies should alway s include a zero - day sampling interval to ensure the samples were fortified properly [see OPPTS 860.1380(d)(6)(i)]. Residues of fomesafen were less than the LLM V (<0.025 ppm) in/on the tomato fruit (RAC) and tomato processed commodities. Therefore, concentration factors could not be calculated. The petitioner is reminded that samples used in processing studies should contain field - treated quantifiable residues so that c oncentration factors can be determined. Field treatment of theFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 36 of 44 processing samples should have been done at exaggerated application rates to obtain sufficient residue levels for this processing study [see OPPTS 860.1 520 ( c )( 2 ) ] . According to Table 2 of OPP TS 860.1520, the theoretical concentration factors are 5.5x for tomato paste and 1.4x for tomato puree. Conclusions . The results of submitted potato and tomato processing studies show that residues of fomesafen were each below the LLMV (<0.025 ppm) in/on the respective RACs following application of Reflex® Herbicide at ~ 1x . Following processing of RACs bearing nonquantifiable residues , no measurable processing factors can be calculated because the processed commodities of potatoes and tomatoes also bore residues below the LLM V (<0.025 ppm). The Agency

would have preferred the use of exaggerated rates in the conduct of the processing studies to yield RACs with quantifiable residues ; the registrant provided no justification for conducting the study at only a 1x rate . Since the proposed use is for preemergence /pre - transplant application and all RAC samples from the current potato and tomato field trials show residues below the LLM V and the residue data cover all significant growing regions for the crop requ ested as delineated in OPPTS 860.1500, for the purpose of this petition only , HED recommends a waiver f or the conduct of new tomato processing studies at exaggerated rates . The submitted processing study for potatoes may

be adequate, pending outcome of th e required metabolism study . A potato metabolism study is outstanding, as described in section 860.1300 above. I f the new study

does not identify

any additional residues of concern, then the processing study is adequate. However, if additional residues of concern are found, then a new processing study at exaggerated rates reflecting analysis of the additional residues will be required. 860.1650 Submittal of Analytical Reference Standards Analy tical standards for fomesafen are cur rently available in the EPA National Pesticide Standards Repository (personal communication with Dallas Wright, ACB, 9 /22 /0 9 ). The Repository

has received from Sy

ngenta new standards for fomesafen on 9/3/2009 ; the standard has an expiration date of 8/1/2 012 . Analy tical reference standards of fomesafen must be supplied and supplies replenished as requested by

the Repository . The reference standards should be sent to the Analy tical Chemistry Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy Nguyen at the following address: USEPA National Pesticide Standards Repository /Analy tical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 (Note that the mail will be returned if the extended zip code is n ot used.)Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 37 of 44 860.1850 Confined Accumulation in Rotational Crops Reference List: 47761905 (No DER generated) Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis HED previously concluded (DP# 325801, 4/25/2006, D. Davis) that the nature of the residue in r otational crops remains inadequately understood and requested a new study . Inresponse, Sy ngenta has submitted MRID 47761905 which provides a narrative response to the data gap . T he specific deficienc y is re - stated below followed by the petitioner’s resp onse and HED’s comments regarding the adequacy of response . Deficienc y : “I f the registrant wishes to support a plant back interval <12 months, they must conduct a new confined rotational crop study . The study should reflect separate application of CP - and NP - label fomesafen at the maximum seasonal application rate to rotatable crops. The study should include the plantback intervals (PBI s) that Sy ngenta wishes to include on product labels, up to 12 months. For complete guidance on the conduct of the stu dy , OPPTS GL N 860.1850 should be conducted.” Sy ngenta’s response : A confined rotational crop study is ongoing and will be completed by 12/31/2009 . HED’s comments /conclusions : The nature of the residue in rotational crops remains inadequately

understood . Sy

ngenta has previously

been requested to conduct a new confined rotational crop study

reflecting separate application of CP - and NP - label fomesafen at the maximum seasonal application rate to rotatable crops. According to Sy ngenta, a new confined rotational crop study

is ongoing and will be completed by 12/31/2009 . 860.1900 Field Accumulation in Rotational Crops Reference List: 47761905 (No DER generated) Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis HED previously summarized (DP# 325801, 4/25/2006, D. Davis) the available field accumulation data for fomesafen. The available data consisted of: (i) MRID 00110509 which was reviewed by

the Environmental Fate and Effects Division (EFED) and was found to contain numerous deficiencies; (ii) MRID 00158936 , a field rotational crop study on field corn and winter wheat; and (iii) MRID 45268501 , a field rotational crop study on field corn and safened sorghum. HED concluded that the adequacy of these data cannot be determined until the nature of fomesa fen residues in rotational crops has been delineated. The cited HED review identified deficiencies from the submitted studies. Inresponse, Sy ngenta has submitted MRID 47761905 which provides response s to the data gap . T he specific deficienc y is re - stat ed below followed by the petitioner’s response and HED’s comments regarding the adequacy of response . Deficienc y : “ At such time as the registrant has resolved any issues and the nature of the residue in rotational crops is understood, if the registrant w ishes to pursue a plant back interval <12 months for wheat and corn the following method validation data must be provided to support submitted wheat and corn rotational crop data. Data demonstrating that recoveries of the internal standard are linear relative to recoveries of fomesafen are required and information on the timingFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 38 of 44 of sample fortification is required. Additionally , data to support the reported method limit of quantitation of 0.01 ppm are required, as is information on the identity of the matrices fortified in the method validation.” Sy ngenta’s response : Crop samples collected from the field rotational crop study were analy z ed for residues of fomesafen following I CIPlant P rotection Division Residue Analy tical Method ( P PRAM) No. 66 . Briefly , the prepared r otational crop samples were extracted by homogeni z ation with acetonitrile and then acidified with concentrated HCl . After filtration and the addition of water and hexane, fomesafen was partitioned into dichloromethane and the residue taken up into chloroform. C o - extracted m aterials were removed by Fractosil adsorption chromatography . Final quantification was by 19 F - nuclear magnetic resonance spectroscopy (NMR) with internal standardi z ation. For example in study PP021B046, in Experimental Data Sheet Reference NCA/80/2, Internal Standard (R152748) at a concentration of 0.05 ppm was added to all the samples by the addition of 2.5 mLof a 1.0 μ g/mL standards reference 554/7 . External Standard (fomesafen reference standard) at concentrations of 0.05 ppm was added to the fortified recovery

samples by

the addition of 2.5 mLof a 1.0 μ g/mL standard reference 507/3. Raw data indicate that fortification of external recoveries, spiked with the internal standard R152748 plus f

omesafen reference stan dard took place prior to extraction. To support the reported LOQ of 0.01 ppm, the petitioner provided calculation of results and limit of determination/detection. Residues were calculated using simple proportion calculation: Response of sample (fomesa fen) x Concentration of Internal Standard Response of Internal Standard Response ratio of fomesafen to Internal Standard The Response Ratio (RR) was calculated by running standards of equal concentration of fomesafen and Internal Standard an d calculating the mean response. During each analy tical run of the study

samples, an assessment of the limit of determination (limit of detection) was calculated from the baseline noise over the entire scan. Where no peaks of fomesafen were detected, res idues were quoted in the report as less than this calculated value. Sy ngenta believes that an assessment of a theoretical LOQ may be made from the study

data. The lowest fortification level in this study was 0.05 ppm. For example in EDS NCA/86/2, an untreated control sample was spiked with 0.05 ppm Internal Standard (R152748) + 0.05 ppm fomesafen reference standard. The m ean measured baseline noise for the analy tical run at the retention time of fomesafen was 8 mm (l0, 7.5, 7 mm). The m easured peak hei ght of fomesafen was 159.5 mm . The m easured peak height of Internal Standard was 138 mm . C alculation of unknown sample with example peak height of 32 mm (x4 baseline noise) : [ 32 ÷ 138 ] x [ 0.05 ÷ 1.16] = 0.009995 ppm. Therefore , the L OQ when the anal ys is was performed using this method has been calculated at 0.01 ppm . Data were also included to demonstrate that the recoveries of the internal standard are linear to the recoveries of fomesafen. An assessment was carried out as part of the validation o f PPRAM 112. Samples were fortified with varying levels of fomesafen (0.1 - 5 . 0 ppm) keeping the Internal Standard fortification at a constant 0.5 ppm. A calibration graph giving fomesafen f ortification versus fomesafen Internal Standard peak heights was p lotted. A straight line passing through the origin was produced demonstrating that the instrument response to fomesafen was linear relative to the response to the internal standard.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 39 of 44 Finally , in response to HED’s request to provide identity of the matrice s fortified in the method validation, Sy

ngenta provided a table detailing the procedural recoveries of the matrices tested. The recoveries presented in Table 8 were compiled by Sy ngenta from r esidue trials performed between 1980 and 1985 where residues of fomesafen were determined in crops following I CI Plant Protection Division Residue Analy tical Method ( P PRAM No. 66). Procedural recoveries were carried out over expected residue levels for each matrix. Table 8 . Recoveries of Fom esafen Using PPRAM 066 Arising fromSupervised Residue Trials .

(Note

– table was copied directly from MRID 4 77 6 1 905). HED’s comments /conclusions : Sy ngenta has adequately

responded to HED’s concerns and comments regarding the analy tical method (P PRAM No. 66 ) used for the analy sis of fomesafen from a previously

submitted field rotational crop study (MRID 00158936). Sy

ngenta has provided detailed information/data concerning: (i) when the fortification of external recoveries were performed; (ii) data to support the reported LOQ of 0.01 ppm; (iii) data demonstrating thatFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 40 of 44 recoveries of the internal standard are linear relative to recoveries of fomesafen; and (iv) information on the identity of matrices fortified to validate the method. This deficiency is resolved. Deficienc y : “ Should HED determine that 2 - chloro - 4 - trifluoromethyl phenol is a residue of concern in rotated crops, the following method validation data are required to support the submitted wheat and corn rotational crop data. Data to support the reported method li mit of quantitation are required, as are data demonstrating that the method can extract weathered residues of 2 - chloro - 4 - trifluoromethyl phenol from field samples.” Sy ngenta’s response : To date, Sy ngenta is unaware of such a determination being made by the Agency . HED’s comments /conclusions : The Agency will make a determination as to what are the residues of concern in rotational crops when the results of an ongoing confined rotational crop study are submitted. At this time, data are not available to support rotation to other crops beyond those commodities that are currently

registered and proposed as primary crops; therefore the registrant must revise the Reflex® Herbicide label to permit immediate replanting of soy beans, cotton, dry

beans, snap beans , potatoes, and tomatoes only with a restriction that other crops can only be planted 12 months after treatment or 18 months after treatment if based on phy totoxicity concerns. 860.1550 Proposed Tolerances/Tolerance Reassessments for Fomesafen Tolerance s for fomesafen residues are listed in 40 CFR §180.433. The tolerance expression is in terms of “sodium salt of fomesafen, 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] -N - (methylsulfonyl) - 2 - nitrobenzamide.” HED has determined that the residue of concern for to lerance expression is fomesafen. Therefore, the established tolerance expression should be revised to be expressed in terms of fomesafen, by removing the phrase “sodium sal t of” from 40 CFR §180.433(a). Inaccordance with the HED Interim Guidance on Tole rance Expressions (5/27/09, S. Knizner), the tolerance expression for fomesafen should be revised to state: “Tolerances are established for residues of fomesafen, including its metabolites and degradates, in or on the commodities in the table below. Compl iance with the tolerance levels specified below is to be determined by measuring only

fomesafen [5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] - N - (methylsulfonyl) - 2 - nitrobenzamide].” HED cannot recommend for the requested tolerance in/on potatoes due to the lack of an adequate root/tuber metabolism study . The available crop field trial data and revised analy tical method will support the prop osed tolerance of 0.025 ppm for tomato. As all residues were below the LLM V (<0.025 ppm) in/on RAC samples treated at 1x, the Agency ’s tolerance spreadsheet was not used for determining the recommended tolerances. The petitioner’s draft label for Reflex® Herbicide reflects regional use of fomesafen on tomatoes. However, the residue chemistry data submitted in support of thi sFomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 41 of 44 action are of sufficient geographic representation to support full U.S. registration; therefore, HED recommends that th i s tolerances be listed in the general section of 40 CFR §180.433. T he previously

submitted cotton field trial data have now been upgr aded to acceptable status based on Sy

ngenta’s submission of the requested field trial information . The Agency concludes that adequate residue data are available to support the established tolerance s of 0.025 ppm each for undelinted cottonseed and cotton g in by products. No tolerances are required for meat, milk, poultry , and eggs for the purpose of this petition. Sy ngenta should note that if additional uses are proposed in the future which result in an increase i n the dietary

burden, livestock feeding stu dies and animal tolerances may be required. No Codex, Canadian, or Mexican MRL s have been established for residues of fomesafen in/on potato or tomato. Canadian MRL s have been established for residues of fomesafen in/on dry beans, lima beans, snap beans, and soy beans at 0.05 ppm, and a Mexican MRL of 0.05 mg/kg has been established for residues of fomesafen in/on soy beans. The registrant has advised the Agency that they intend to petition the Canadian government for revised tolerances to address any pot ential harmonization issues raised by establishing the new tolerances requested in this action. A summary

of the tolerance reassessment for fomesafen sodium is presented in Table 9 . Table 9 . Tolerance Sum ma ry for Fom esafen Sodium Commodity Establish ed/Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments ; C orrect Commodity D efinition Proposed Tolerance Under PP#9F7563 Tom ato 0.025 0.025 Tolerance Registered Under PP#9F5068 Cotton, gin byproducts 0.025 0.025 Cotton, undelinted seed 0.02 5 0.025Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 42 of 44 References DP#: 325801 Subject: Fomesafen Sodium. Residue Chemistry Summary

for the HED Human Health Risk Assessment, a Proposal To Amend Use on Soy beans, and Proposals to Add Uses on Cotton, Dry

Bean, and Snap Bean. PP#1E6228, PP#9F5068, an d PP#6E4653. From: D. Davis To: J. Stone/J. Miller Dated: 4/25/06 MRIDs: 00158936, 00158937, 40346603, 44754701 - 44754704, 44754706, 44727901,

45093601 - 45093604, 45237101, 45259801, 45268501 - 45268503, 45313001, & 45342601 CB#: 2253 Subject: PP#4F2997. Ame ndment of I CI ’s Enforcement Analy tical Method GAM - RM 001/86. From: W. Chin To: R. Mountfort and Toxicology Branch Dated: 8/18/87 MRIDs: 40007101 Attachments: Appendix I International Residue L imit Status S heet Appendix I I Chemical Names and Structures of Metabolites I dentified in Tomato Metabolism

Study (MRID 47473901 ) Template Version September 2005Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 43 of 44 Appendix I International Residue Limit Status Sheet 

## INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] - N - (methylsulfonyl) - 2 - nitrobenzamide Common Name: Fomesafen X Proposed tolerance □ Reevaluated tolerance □ Other Date: 9/21/09

Codex Status (Maximum Residue Limits) U. S. Tolerances X No Codex proposal step 6 or above □ No Codex proposal step 6 or above for the crops requested Petition Number: PP# 9F7563 DP#: 365199 Other Identifier : Residue definition (step 8/CXL): N/A Reviewer/Branch: M. Metzger/RAB7 Residue definition: fomesafen per se Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm) Potato 0.025 Tom ato 0.025

Limits for Canada Limits for Mexico □ No Limits X No Limits for the crops requested □ No Limits X No Limits for the crops requested Residue definition: 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] -N - (methylsulfonyl) - 2 - nitrobenzamide Residue definition: fomesafen Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg)

Notes/Special Instructions: S.Funk, 10/05/2009.Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 36519 9 and 366116

Page 44 of 44 Appendix II Chemical Names of Metabolites Identified in Tomato Metabolism Study (MRID 47473901) Identification of Compounds from Tom ato MetabolismStudy . Common name/code Figure C.3.1 ID No. Chemical name Chemical structure Fomesafen 5 - [2 - chloro - 4 - (trifluoromethyl)phenoxy] - N - (methylsulfonyl) - 2 - nitrobenzamide F 3 C

Cl O N O 2

O N H S C H 3 O O

R052850 3 - chloro - 4 - hydroxybenzoic acid O H Cl C O O H

Cys conjugate of sulfonamide (R290493) 2 - amino - 3 - (3

–methanesulfonylamino carbonyl - 4 - nitro - phenylsulfany1) - propionic acid N O 2

O N H S C H 3 O O S N H 2 O H O R012156 2 - NO 2 - 5 - OH benzoic acid O H C O O H

N O 2

R089135 2 - NH 2 - 5 - OH benzoic acid O H C O O H

N H 2