**UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY**  **WA SHINGTON, D.C. 20460**  **OFFICE OF CHEMICAL SAFETY AND**  **POLLUTION PREVENTION MEMORANDUM**  **Date: 9**  **/ 7** **/20 1**  **2 SUBJECT:**  Fluazinam . Petition s for the Establishment of Tolerances and Registration of

New Uses on Soy

beans, the Melon Subgroup (9 - A), and the Pepper/Eggplant Subgroup ( 8 - 10 B) . Summary of Anal ytical Chemistry

and Residue Data **PC Code:** 129098 **DP Barcode s**  **:** D397721 , D3 98888 , D399475 **Decision No s**  **.:** 4 59107, 4 59565, 4 61245 **Registration No s**  **. :**  71512 - 1 **P etitions**  **:** 1 E7 959 , 8E7506, 2F7977 **Regulatory Action:** Section 3 Registration **Risk Assessment Type:** Single Chemical Aggregate **Case No.:** 7013 **T XR No.:**  NA **CAS No.:** 79622 - 59 - 6 **MRID No s**  **.:** 4 8704501 , 4 8704502 ,

48707301, 4 8712 601 **40 CFR:** § 180.574

**FROM:** Douglas Dotson, Ph.D., Chemist

Risk Assessment Branch II Health Effects Division (7509P) **THROUGH:** Dennis McNeill y , Chemist

Risk Assessment Branch II Health Effects Division (7509P) **TO:** Andrew Ertman/Barbara Madden, RM Team 5, RIMUERB

Dominic Schuler

/Tony Kish, PM Team 22 , Fungicide Branch Registration Division (7505P) **Executive Summary** Fluazinam ( 3 - chloro -N

- [3 - chloro - 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl ) - 2 - py ridinamine ) is a member of the phenyl - py ridinamine class of compounds. It is a non - sy stemic, preventive, contact fungicide with a multi - site mode of action. Wh en applied to plants, itFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 2 of 25 remains primaril y on the plant surface, it is not taken up to any extent by the plant, and it is not translocated within the pl ant. Fluazinam operates by disrupting the production of energy at several metabolic sites within the fungal cell. Tolerances have been established in 40 CFR §180.574(a)(1) for residues of fluazinam in/on plant commodities at levels ranging from 0.01 in or on Brassica leafy vegetable s ( Crop Group 5) to 7.0 ppm in or on the Bushberry subgroup (13 - 07B). A tolerance has been established in 40 CFR §180.574(a)(2) for residues of fluazinam and its metabolite AMGT on wine grapes at 3.0 ppm (40 CFR) . Finall y, a tolerance of 0.05 ppm has been established for fluazinam and its metabolites AMPA and DAPA and their sulfamate conjugates in or on the fat and meat by products of cattle, goats, horses, and sheep. The registrant s , ISK Biosciences and the Interregional Research Project No. 4 (IR - 4) submitted two petitions to e stablish tolerances for fluazinam in/on soy beans and the commodities of the melon and pepper/eggplant subgroups (9 - A and 8 - 10B, respectivel y). In addition, the registrant submitted residue data for the metabolite, AMGT (see Table 2 for chemical name and structure) , on lettuce in order to fulfill a condition of registration cited in a previous HED risk assessment. This document summarizes the available residue chemistry data in support of the tolerance petitions. The end - use product (EP) relevant to all petitions is OMEGA ® 500F ( EPA Reg. No. 71512 - 1 ), a flowable concentrate (FlC) formulation containing 40% fluazinam (equivalent to 4.17 lb ai/gal). In PP# 2F7977 , IS K Biosciences requested the regi stration of fluazinam for use on soy beans. In conjunction with this petition, the registrant proposed tolerances of 0.01 ppm for soy bean seed and 0.02 ppm for so ybean hulls. InPP# 1E7959 , IR- 4 requested the registration of fluazinam for use on the commo dities of the melon and pepper/eggplant subgroups. In conjunction with this petition, IR- 4 proposed tolerances of 0.08 ppm for melons and 1.5 ppm for peppers and eggplant. In a previous tolerance petition, PP# 8E7506, IR- 4 requested registration of fluazinam for use on both head and leaf lettuce . In conjunction with this use, a tolerance of 0.02 ppm was established for head lettuce and a tolerance of 2.0 ppm was established for leaf lettuce. HED cited the following data deficiency with respect to the lettuce field trials: “ Samples from the lettuce field trial need to be anal yz ed for residues of AMGT. The residue data should also be supported by data depicting the frozen storage stability of AMGT in the lettuce samples. HED recommends that these data be made a condition of registration ” (D360840, D. Dotson, 3/31/2010). IR - 4 submitted the requested data. The data are adequate. Residues of AMGT were below the LOQ of 0.01 ppm in all field trial samples. Use Directions The registrant submitted adequate use directions for the application of fluazinam to soy beans as well as the commodities of the melon and pepper/eggplant subgroups. The u se directions are sufficient to allow for evaluation of the submitted residue data relative to the proposed use patterns. The available field trial data support the proposed use directions for the crops addressed in this s ummary document .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 3 of 25 Nature of the Residue The nature of f

luazinam residues in plants is adequately understood based o n metabolism studies on potatoes, peanuts, and grapes . The Agency previously concluded that the residue of concern in peanuts and root and tuber vegetables is parent fluazinam for purposes of both dietary risk assessment and tolerance enforcement . For all other crops, the residues of concern include both fluazinam and its metabolite AMGT for purposes of dietary risk assessment. For setting tolerances, the residues of concern in plants include fluazinam and AMGT for wine grapes, but o nly fluazinam for all other plant commodities. The nature of the residue in rotational crops is adequately understood. Based on the absence of metabolites containing the intact fluazinam nucleus, HED has determined that the residue of concern in rotational crops is the parent compound, and that rotational crop tolerances are not required. The available confined field rotational crop study supports the 30 - day plant - back interval (PBI) that is currently listed on the label for crops without direct uses of fluazinam. The nature of the residue in livestock is also understood based on acceptable goat and hen metabolism studies. The fluazinam residues of concern in l ivestock commodities for tolerance enforcement and risk assessment were determined by HED to be parent plus the m etabolites AMPA and DAPA, and their sulfamate conjugates. Analy tical Methods Enforcement Method An adequate GC/ECD method (6148 - 94 - 0170 - MD - 001 ) is available for enforcing fluazinam tolerances on plant commodities. The method was adequately radiovalidated and underwent a successful ILV trial. The method was forwarded to BEAD’s Anal ytical Chemistry Branch (ACB) for a TMV trial, and was subsequentl y determined to be suitable as a tolerance enforcement method. The method LOQ is 0.01 ppm for fluazinam in p lant commodities. An adequate enforcement method for determination of AMGT is also available. The method is an HPL C/UV method entitled “Method Evaluation for the Anal ys is of AMGT in Grapes. ” The registrant submitted an adequate ILV for the method. The range of fortification levels and the percent recovery

values were acceptable. Data - Collection Methods Samples collected in the cantaloupe and pepper field trials, as well as in the soy bean field trials and storage stability

study , were anal yz ed for resi dues of fluazinam and AMGT using LC/MS/MS methods that were based on the GC/ECD plant enforcement method. The methods are adequate for data collection based on acceptable method recovery data included in the reviewed studies. The fortification levels use d in the method validation trials bracketed the expected field residues. The LOQ was 0.01 ppm in all tested commodities. The LOD was 0.0045 ppm in cantaloupes and peppers and 0.003 ppm in soy bean seed, forage, and hay . In all trials, the data - collection method was validated prior to and in conjunction with the anal ys is of the field trial samples .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 4 of 25 Multiresidue Methods Adequate FDA multiresidue method ( MRM) testing data are available for fluazinam and its metabolite AMGT. As fluazinam is partially recovered through Sections 302, 303, and 304 of PAM Volume I , the M RM s can serve as a confirmatory procedure for residues of fluazinam. The FDA MRM methods are not suitable for determining residues of AMGT. St orage Stability The registrant submitted storage stability data for soy

beans . The data are adequate and indicate that residues of fluazinam and AMGT are relatively stable in/on soy

bean forage, hay , and seed sto red frozen for up to 153 day s (5.0 months) . Field Trials The submitted field trial data for fluazinam on soybeans , cantaloupes , and p eppers are acceptable and support the proposed uses. Adequate number s of trials were conducted in the appropriate geographic regions at ~1x the maximum proposed rate , and the appropriate samples were collected from each test at the proposed PHI. The data support the establishment of tolerances of 0.01 ppm on soy

bean seed, 0.07 ppm for melons, and 0.09 ppm for peppers and eggplant . The OECD MRLcalculation procedures were used for determining appropriate tolerance levels. The conditional AMGT residue data for lettuce and the supporting storage stability data are acceptable. Processing Studies The submitted soy

bean processing study

is adequate. Following application of fluazinam at a 1x application rate, residues of fluazinam and AMGT were each below the LOQ (<0.01 ppm) in/on all samples of soy

bean seed (RAC) and AGF; therefore, processing factors were not calculated for AGF. Following application of fluazinam at a 10x application rate, fluazinam residues concentrated in hulls (5.3x) and in refined oil (1.1x), but did not concentrate in meal (processing factor of <0.22x). Residues of AMGT were below the LOQ in/on seed, hulls, meal, and refined oil; therefore, processing factors were not calculated. The observed concentration factors were less than the theoretical concentration factors. Analy tical Reference S tandards Analy tical reference standards for fluazinam, AMPA, DAPA , and AMGT are currentl y available in the EPA National Pesticide Standards Repository . The analy tical standard s for AMPA and DAPA are due to expire in June and July of 201 7, respectivel y . The standard for AMGT is due to expire in December 2012 . By that date, the registrant will need to submit a new standard or an updated certificate of analysis for the current AMGT standard .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 5 of 25 MRLHarmonization There are currently

no Codex or Mexican maximum residue limits (MRL s) for fluazinam on melons, bell peppers, non - bell peppers, or so ybeans. There are no Canadian MRL s for melons or peppers . The petition for melons and peppers is being evaluated jointly

by the U.S. and Canada’s PMRA. Both countries are using the OECD MRLcalculation procedures to determine the recommended tolerances. For this reason, the MRL s for melons and peppers will be harmonized between the two countries. There is a Canadian MRLof 0.10 ppm for edible - podded soy bean. There is no need to harmonize th is MRLwith HED’s recommended tolerance of 0.01 ppm for soy bean seed because edible - podded soy bean and so ybean seed are different commodities. Edible - podded so yb ean is an immature seed that includes the pod . It is likel y to have a higher residue level than soybean seed , which is the dried seed alone . **Regulatory Recommendations and Residue Chemistry Deficiencies** HED has examined the residue chemistry database for f

luazinam . Pending submission of a revised Section F, there are no residue chemistry issues that would preclude granting full registration for the requested use of f luazinam on soy

beans, the melon subgroup, and the pepper/eggplant subgroup. The recommended tolerances are listed in Table 1. **Table 1**  **. Tolerance Summary for F**  **luazinam** Commodity as Proposed by Registrant Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition Melon subgroup 9A 0.08 0.07 Pepper/eggplant subgroup 8 - 10B 0.10 0.09 Soy bean, Seed 0.01 0.01 Soy bean, seed Soy bean, Hulls 0.02 0.05 Soy bean, hulls 860.1550 Proposed Tolerances

 The registrant needs to submit a revised Section F in which the tolerances and correct commodity

definitions recommended in Table 1 are proposed. **Background** Fluazinam is a contact, multi - site fungicide with activity against a number of plant pathogenic fungi. It disrupts the production of energy at several metabolic sites within the fungal cell. Fluazinam is a protectant fungicide that remains primarily on the plant surface . It is not taken up to any extent by the plant, and is not translocated within the plant. The nomenclature f o r f luazinam and its metabolites AMGT, AMPA, and DAPA is presented in Table 2 , and the physicochemical properties of f luazinam ar e summarized in Table 3 .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 6 of 25 **Table 2**  **. Fluazinam** **Nomenclature** Com pound

Common name Fluazinam Com pany experimental name IKF - 1216 IUPAC name 3 - chloro -N - (3 - chloro - 5 - trifluoromethyl - 2 -py ridyl) - α,α,α - trifluoro - 2,6 - dinitro - p toluidine CAS name 3 - chloro -N - [3 - chloro - 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl) - 2 -py ridinamine CAS registry number 79622 - 59 - 6 End - use product (EP) Omega ® 500F Fungicide ( EPA Reg. No. 71512 - 1) Com pound

Common name AM GT Chemical name 3 - [[4 - amino - 3 - [[3 - chloro - 5 - (trifloromethyl) - 2 -py ridinyl]amino] - 2 - nitro - 6 - (trifluoromethyl) phenyl] thio] - 2 - (beta - D - glucopyranosyloxy) propionic acid) Com pound

Common name AMP A Chemical name 2 - (6 - amino - 3 - chloro - α,α,α. - trifluoro -p - toluidino) - 3 - chloro - 5 - (trifluoromethyl) pyridine Cl N H

C F 3 N O 2 O 2 N N Cl F 3 C

O O H O H O H O H O N H

C F 3 O 2 N N Cl F 3 C

N H 2 S HO O C

Cl

N H

C F 3 O 2 N N Cl F 3 C N H 2Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 7 of 25 **Table 2**  **. Fluazinam** **Nomenclature** Com pound

Common name DAP A Chemical name 3 - chloro - 2 - (2,6 - diamino - 3 - chloro - α,α,α. - trifluoro -p - toluidino) - 5 - (trifluoromethyl)pyridine **Table 3**  **. Physicochemical Properties of the**  **Technical Grade Fluazinam** Parameter Value References Melting P oint/Range 115 - 117oC DP# 335640, 8/22/07, W. Drew pH 5.85 Density (25oC) 1.02 g/cm3 Water S olubility (25oC) 0.131 mg/L (pH buffered to 5) 0.157 mg/L (pH buffered to 7) 3.384 mg/L (pH buffered to 9) Solvent S olubility (g/L at 20oC) acetone: 853 dichloromethane: 675 ethyl acetate: 722 ethyl ether: 231 hexane: 8

methanol: 192 octanol: 41 toluene: 451 Vapor P ressure at 25oC 1 . 73 x 10 - 7 mm Hg 2.3 x 10 - 5 Pa Dissociation C onstant, pKa 7.22 in 50% ethanol/water (v/v, average) Octanol/W ater P artition C oefficient Log Kow = 4.03 (Kow = 10 , 8 00) UV/visible absorption spectrum (λmax , nm) 238 at pH 5 239, 342 at pH 7 260, 343, 482 at pH>10 **860.1200 Directions for Use** There is currentl y a single end - use product (EP) for fluazinam registered in the U.S. for use on several food and feed crops. This product is Omega ® 500F (EPA Reg. No. 71512 - 1), which is a 4.17 lb/gal FlC formulation . IR- 4 is proposing to add uses on soy beans , the melon subgroup (9A) and the pepper/eggplant subgroup (8 - 10B). Proposed supplemental labels were provided for these new use s . The proposed use directions are summarized in Table 4 . Cl N H

C F 3 N Cl F 3 C N H 2 N H 2Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 8 of 25 **Table 4**  **. Summary of Directions for Use of Fluazinam**  **Applic. Timing, Type, and Equip.**  **Form ulation**  **1 Applic.**  **Rate (lb ai/A)**  **† Max. No.** 

**Applic. per Season**  **Max. Seasonal**

**Applic. Rate (lb ai/A)**  **PHI**

**(days) Use Directions and** 

**Limitations Melons (Crop Group 9A)**  Broadcast ; Ground, Chemigation (Sprinkler System). OMEGA® 500F

40% ai, Soluble Concentrate (4.17 lb ai/gal) 0.78 lb ai/A

(24 fl oz/A) 6 4.68 lb ai/A ( 144 fl oz/A) 30 Re - treatment Interval = 7 - 10 days . Apply when disease symptoms first appear. **Peppers (Crop Group 8 -**  **10B)** Broadcast; Ground, Chemigation (Sprinkler System), Soil Drench (at transplanting).. OMEGA® 500F 40% ai, Soluble Concentrate (4.17 lb ai/gal) 0.78 lb ai/A

(24 fl oz/A) 6 4.68 lb ai/A ( 144 fl oz/A) 30 Re - treatment Interval = 7 - 14 days . Apply as a soil drench at transplanting. Foliar applications should begin 7 days after transplanting. **Soybean** Apply at early bloom to full bloom stage of development. Broadcast; Aerial, Ground. OMEGA® 500F

40% ai, Soluble Concentrate (4.17 lb ai/gal) 0.52 lb ai/A

(16 fl oz/A) 2 1.04 lb ai/A (32 fl oz/A) Gro wth

Stage R3 3 Re - treatment Interval = 10 - 14 days (at early pod formation). For preventive treatment or low disease pressure use low rate. Do not feed hay from treated field to livestock or allow livestock to graze on treated areas. Do not apply after early pod formation. 1 EPA Reg. No. 71512 - 1 2 Maximum Single Application Rate (lb ai/A) = (1 pint/A)(16 fl oz/1 pint) (4.17 lb ai/gal)(1 gal/128 fl oz) = 0.52 lb ai/A. 3 Do not apply after growth stage R3, early pod formation. The proposed (and current) product label for the 4.17 lb/gal FlC formulation specifies that a pplications are allowed through the following types of irrigation s ys tems: center pivot, motorized lateral move, traveling gun, solid set or portable (wheel move, side roll, end tow, or hand move). The label contains the following rotational crop restriction s : all crops on the label may be replanted immediately after treatment . A ll other crops can be replanted 30 day s after the last application. Conclusions . The submitted use directions are sufficient to allow for evaluation of the submitted residue data relative to the proposed use patterns. The available field trial data support the proposed use directions for the crops addressed in this s ummary document . **860.1300 Nature of the Residue –**  **Plants** MARC Decision Memo, DP# 272624 , 4/23/01 , W. Cutchin Residue Chemistry Memo DP# 2 5 7115 , 5/21/01 , W. Cutchin Residue Chemistry Memo DP# 335640 , 8/22/07 , W. Drew The nature of the residue in plants is adequatel y understood , based on acceptable potato, peanut, and grape metabolism studies. The metabolism of fluazinam appears to be similar in testedFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 9 of 25 crops . Fluazinam undergoes reduction of one of the nitro groups to an amine, forming AMPA. AMPA can then be conjugated with glutathione, with subsequent degradation of the glutathione moiety to cy steine. The AMPA - cysteine conjugate then undergoes transamination, reduction, and conjugation with glucose to form AMGT. In addition, both rings of fluazinam appear to be la bile to ring cleavage, and they subsequently degrade into small fragments that c an then be incorporated into a variety of natural plant components. The residues of concern in primary crops for tolerance enforcement and risk assessment are listed in Table 5 . **Table 5**  **. Fluazinam Residues of Concern in Plants** 

Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression Primary crop: grapes Parent fluazinam and AMGT Parent fluazinam and AMGT Primary crop: peanuts , bulb vegetables, and root and tuber vegetables Parent fluazinam Parent fluazinam Primary crops: all others Parent fluazinam and AMGT Parent fluazinam The registrant submitted an apple metabolism study (MRID 46991301). HED has not performed a formal review of the study . The results of the study indicate that parent fluazinam would be the residue of concern in apples for both risk assessment and tolerance enforcement. As a result, all residues of concern in apples are included in the current determinations. **860.1300 Nature of the Residue -**  **Livestock** The nature of the residue in livestock is adequately understood, based on adequate goat and hen meta bolism studies . The metabolism of fluazinam in ruminants and poultry has been discussed previously

( D272624, W. Cutchin, 4/23/01 , D360840, D. Dotson, 3/31/2010 ). **860.1340 Residue Analytical Methods** Plant commodities Enforcement M ethods Fluazinam An adequate GC/ECD method (6148 - 9 4 - 0170 - MD - 001 ) entitled “Fluazinam: Method for the Analysis in Peanut Nutmeat” ( MRID 43521016 ) is available for enforcing fluazinam tolerances on plant commodities. The method was adequately radiovalidated and underwent a successful independent laboratory

validation ( ILV) trial. The method was forwarded to BEAD’s Anal ytical Chemistry

Branch (ACB) for a T MV trial, and was subsequently determined to be suitable as a tolerance - enforcement method (Memo, D266802, P. Golden, 6/22/2001). For this method, residues of fluazinam are extracted with methanol :acetic acid (100:2, v/v), filtered , diluted with 0.2 N HCl , and partitioned into hexane. Residues are then further partitioned into 0.5 N NaOH, the aqueous phase is acidified, and residues are partition ed back into hexane. The resulting hexane fraction is concentrated, and residues are purified using a Florisil column eluted withFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 10 of 25 hexane:ethyl ether (80:20, v/v). Residue s are concentrated to dry ness, redissolved in hexane , and anal yz ed b y GC/ECD using external standards for quantitation. The method LOQ is 0.01 ppm for fluazinam in plant commodities. AMGT An adequate enforcement method for determination of AMGT, a residue of concern in wine grapes, is available. The method is an HPL C/UV method entitled “ Method Evaluation for the Analysis of AMGT in Grapes . ” The registrant submitted an adequate ILV for the method. The range of fortification levels and the percent recovery values were acceptable. Data - collection M ethods Sampl es collected in the cantaloupe and pepper field trials , as well as in the soy bean field trials and storage stability

study , were anal yz ed for residues of fluazinam and AMGT using LC/MS/MS methods that were based on the GC/ECD plant enforcement method. The methods are adequate for data collection based on acceptable method recovery data included in the reviewed studies . The fortification levels used in the method validation trials bracketed the expected field residues. The L OQ was 0.01 ppm in all tested c ommodities . The LOD was 0.0045 ppm in cantaloupes and peppers and 0.003 in soy bean seed, forage, and hay . In all trials, the data - collection method was validated prior to and in conjunction with the anal ys is of the field trial samples . Soy beans Homo genized so ybean samples were blended with methanol:acetic acid (98:2, v:v) and shaken. The mixture was filtered, the filter cake was rinsed twice with methanol:acetic acid, and the resulting filtrates were combined and diluted to volume with methanol. Se ed extracts were diluted with acetonitrile (ACN):water (80:20, v:v) for anal ys is by L C/MS/MS. Forage and hay extracts were cleaned up using a Waters OASI S HLB extraction cartridge. Residues were eluted with ACN:water (80:20, v:v), and the eluate was anal yz ed b y LC/MS/MS. Cantaloupes and Peppers Residues of fluazinam and AMGT were extracted from cantaloupes using 25 mLof methanol/acetic acid (98/2, v/v). Samples were shaken at room temperature for 30 minutes, filtered, and then cleaned up using a conditioned Evolute SPE cartridge. Residues were eluted from the column with 6 mLof acetonitrile/water (80/20, v/v) and anal yz ed by L C /MS/MS (negative ionization mode for fluazinam; positive ionization mode for AMGT). Conclusions. A dequate m ethod s for fluazinam and AMGT are available for enforcement of tolerances in crop matrices. Adequate methods were used for collection of data in the soy bean, cantaloupe, and pepper field trials. Inall trials, the data - collection method was validated prior to and in conjunction with the anal ys is of the field trial samples .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 11 of 25 **860.1360 Multiresidue Methods** Parent Fluazinam Data depicting the recovery of fluazinam through FDA multiresidue methods (MRM) were submitted and forwarded to FDA for review. The MRM testing data indicate that fluazinam is partially recovered through Sections 302, 303, and 304 of PAM Volume I, with its recovery being dependent on which Florisil elution system is used. The MRMs can serve as a confirmatory

procedure for residues of fluazinam . M etabolite AMGT Data depicting the recovery of AMGT through FDA MRMs were submitted in support of the apple petition. IS K Biosciences submitted multiresidue method testing data for the fluazinam metabolite AMGT following testing and anal ys is according to FDA Multiresidue Method 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. Metabolite AMGT was tested through Protocols A, B, C, D, E , and F. T esting under Protocol G is not required because AMGT is not a substituted urea. The multiresidue methods were not found to be suitable for determining residues of AMGT because of poor recovery . **860.1380 Storage Stability** Soy beans: MRID 4871 2601 ISK Biosciences submitted the results of a storage stability study with fluazinam and AMGT in soy bean matrices . Untreated samples of so ybean forage, hay , and seed were fortified with each anal yt e separatel y at a fortification level of 0.10 ppm. Samples were placed in frozen storage at < - 1 0 oC and analyzed at storage intervals of 0, 37 , 62, 125, and 153 day s. In the study , residues of fluazinam and AMGT were stable in/on soy bean forage, hay , and seed stored frozen for up to 153 days ( 5.0 months ) . L ower recoveries of fluazinam and AMGT were obtained in stored samples at the 37 - and 62 - day intervals than at the 125 - and 153 - day intervals. The petitioner assumed that this was an anal ytical variation bec ause it occurred in all three matrices. The results of the storage stability studies are presented in Table 6 .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 12 of 25 **TABLE 6**  **. Stability**  **of Residues of Fluazinam and AGMT in**  **Soybean Following Storage at**  **< -**  **1 0**   **C** Commodity Actual

Spike Level (ppm) Storage

Interval (days) Recovered Residues

(ppm) Mean Recovered

Residues (ppm) Mean

Recovery (%) Corrected

Recovery (%) 1 **Fluazinam** Soybean Forage 0.10 0 0.0965, 0.1025, 0.0960 0.0983 98.3 96.4 37 0.0785, 0.0860, 0.0715 0.0787 78.7 83.0 62 0.0755, 0.0760, 0.0670 0.0728 72.8 79.4 125 0.0835, 0.0860, 0.1040 0.0912 91.2 84.4 153 0.0820, 0.0870, 0.1020 0.0903 90.3 86.9 Soybean Hay 0.10 0 0.1200, 0.1185, 0.1070 0.1152 115.2 98.0 37 0.0720, 0.0855, 0.0700 0.0758 75.8 85.9 62 0.0730, 0.0680, 0.077 0.0727 72.7 65.8 125 0.0690, 0.0790, 0.0820 0.0767 76.7 76.1 153 0.0775, 0.0805, 0.0800 0.0793 79.3 77.8 Soybean Seed 0.10 0 0.0845, 0.0865, 0.0860 0.0857 85.7 102.9 37 0.0780, 0.0730, 0.0865 0.0792 79.2 70.8 62 0.0760, 0.0650, 0.0650 0.0687 68.7 70.1 125 0.0820, 0.0810, 0.0800 0.0810 81.0 81.2 153 0.0740, 0.0730, 0.0725 0.0732 73.2 75.6

**AGMT** Soybean Forage 0.10 0 0.1075, 0.1195, 0.1180 0.1150 115.0 114.1 37 0.0865, 0.0870, 0.0790 0.0842 84.2 74.3 62 0.0930, 0.0860, 0.0820 0.0870 87.0 80.9 125 0.0835, 0.0805, 0.0920 0.0853 85.3 78.5 153 0.0855, 0.0875, 0.0945 0.0892 89.2 80.0 Soybean Hay 0.10 0 0.1175, 0.1160, 0.118 0.1172 117.2 126.7 37 0.0775, 0.0770, 0.0740 0.0762 76.2 69.2 62 0.0770, 0.0705, 0.0760 0.0745 74.5 71.3 125 0.0855, 0.0855, 0.0850 0.0853 85.3 85.8 153 0.0795, 0.0910, 0.0820 0.0842 84.2 79.8 Soybean Seed 0.10 0 0.1185, 0.1175, 0.1185 0.1182 118.2 124.1 37 0.0705, 0.0755, 0.0710 0.0723 72.3 66.4 62 0.0535, 0.0565, 0.0585 0.0562 56.2 53.9 125 0.0725, 0.0750, 0.0720 0.0732 73.2 69.4 153 0.0750, 0.0700, 0.0720 0.0723 72.3 77.4 1 C orrected for mean concurrent recovery Conclusion: The storage stability data are adequate and indicate that residues of fluazinam and AMGT are relativel y stable in/on soy bean forage, hay , and seed stored frozen for up to 153 day s (5.0 months) . **860.1400 Water, Fish, and Irrigated Crops** There are no proposed uses that are relevant to this guideline topic.Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 13 of 25 **860.1460 Food Handling** There are no proposed uses that are relevant to this guideline topic. **860.1480 Meat, Milk, Poultry, and Eggs** Livestock D ietary B urdens The livestock feedstuffs associated with the proposed uses discussed in this summary document are soy bean seed and hulls . The livestock feedstuffs associated with registered crops include peanut meal , processed potato waste , wet apple pomace, and carrot culls . F luazinam is registered for use on Subgroup 6A, the Edible - podded legume vegetables s ubgroup. However, the approved label excludes the use o n peas; therefore, feedstuffs derived from peas were not included in dietary

burden calculations. The proposed soy bean label includes restrictions that prohibit the feeding of soybean forage and h ay to livestock. The maximum reasonable dietary burdens of fluazinam t o livestock were calculated for the previous risk assessment. A tolerance of 0.05 ppm was established for the fat and meat by products of cattle, goat, horse, and sheep. As a result of the establishment of tolerances for soy bean seed and hulls, the dietary burden for beef cattle increases from 0.04 to 0.049 ppm, and the dietary

burden for dairy

cattle increases from 1.27 to 1.28 ppm. These small increases do not result in a n eed to incr ease the tolerances that are established for ruminant commodities. The dietary burdens for poultry

and swine are the same as those calculated for the previous risk assessment. As a result, no tolerances are needed for poultry and swine commodities. Conc lusions. The current tolerances for livestock commodities are adequate . **860.1500 Crop Field Trials** DER Reference s : 4 8712601 . DER .doc ( Soybeans )

4 8704501 . DER .doc ( Cantaloupe ) 4 8704502 . DER .doc (Peppers ) IR- 4 and ISK Biociences Corporation submitted magnitude of the residue studies in which fluazinam and AMGT were measured in soy bean s, c antaloupes , and both bell and non - bell peppers. In addition, I SK Biociences submitted magnitude of the residue studies in which AMGT was measured in both he ad and leaf lettuce. The results from these field trials are discussed below , and the residue data are summarized in Table 7 . Soy bean s (MRID 4 8712601 ) ISK Biosciences Corporation submitted field trial data for fluazinam on soybean s . Sixteen field trials were conducted in the United States and Canada during the 2010 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 2 (NC and VA; 2 trials), 4 (LA and AR; 2 trials), and 5 (IA, IL, IN, MN, MO, ND, OH, SD, WI , and ON; 12 trials).Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 14 of 25 Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated plot received two foliar broadcast applications of a 4.17 lb ai/gal suspension concentrate (SC ) formulation of fluazinam (Omega ® 500F for the U.S. trials and AllegroTM 500F for the Canadian trial ) at 0.49 - 0.64 lb ai/A/application, for a total seasonal rate of 0.99 - 1.17 lb ai/A. Applications were made at 9 - to 11 - day retreatment intervals, except for the SD trial, where the retreatment interval was 16 day s. Applications were made using ground equipment in spray volumes of 19.2 - 30.6 gal/A. No adjuvants were added to the spray mixtures. Samples were harvested from all trials at 29 - to 35 - day

preharvest intervals (PHIs) for f orage and hay

and 56 - to 94 - day

PHIs for seed. Hay

samples were allowed to dry in the field for 1 - 15 day s prior to collection, except at one Minnesota trial (06) where samples were allowed to dry in the field for 42 days prior to collection (no explanatio n provided). Additional forage and hay samples were harvested at PHIs of 10, 20, and 40 day s (NC and OH trials), and additional seed samples were harvested at PHIs of 66, 76, and 95 day s (NC; target PHI 87 day s) and 36, 46, and 66 days (OH; target PHI 56 days) to assess residue decline. Samples were anal yz ed for residues of fluazinam and its metabolite AMGT using a high performance liquid chromatography method with tandem mass spectrometric detection (L C/MS/MS) adapted from Ricerca, Inc. analy tical method s. The limit of quantitation ( LO Q ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analy te. The method was adequate for data collection based on acceptable method validation and concurrent recovery

data. The fortificatio n levels used in concurrent method recovery were adequate to bracket expected residue levels . C oncurrent recoveries and residues in treated samples were not corrected for apparent residues in controls. Samples were stored frozen (< - 10°C) from collection to analysis for 57 - 150 day s (1.9 - 4.9 months) for forage and hay , and 38 - 108 days (1.3 - 3.6 months) for seed. Samples were anal yz ed within 0 - 32 days of extraction . Adequate storage stability data are available to support the storage conditions and durations of samples from the submitted field trials. Following two foliar broadcast applications of the 4.17 lb ai/gal SC formulation of fluazinam at 0.99 - 1.17 lb ai/A, residues of fluazinam in/on soy bean forage, hay , and seed, respectivel y, harvested at a 29 - to 35 - day PHI(forage and hay) or a 56 - to 94 - day PHI (seed) were: 0.021 - 3.725, <0.017 - 5.207 , and <0.01 ppm. Residues of AMGT were below the LOQ (<0.01 ppm) in/on all samples of soy

bean forage, hay , and seed. In the residue decline trials, averag e residues of fluazinam generall y declined with increasing PHIin forage and hay . Residues of fluazinam in/on seed and residues of AMGT in/on forage, hay , and seed were below the LOQ (<0.01 ppm) in/on all samples; therefore, residue decline could not be a ssessed. Melons (MRID 48704501) IR- 4 submitted field trial data for fluazinam on cantaloupes. A total of 11 cantaloupe field trials were conducted in the United States and Canada during the 2007 growing season encompassing Zones 2 (1 trial each in GA an d MD), 5 (2 trials in ON), 5B (1 trial in QC), 6 (2 trials in TX), 9 (1 trial in NM), and 10 (2 trials in AZ, 1 trial in CA). At each test location, fluazinamFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 15 of 25 (formulated as Omega 500F or Allegro 500F, a suspension), was applied to cantaloupes as 6 foliar broadcast or directed applications at rates of 832

– 958 g a.i./ha/application ( 0.769

– 0.855 lbs a.i./ha/application) , with retreatment intervals of 6

– 9 day s, for a total application rate of 5.18

– 5.35 kg a.i./ha/season (4.62

– 4.77 lb a.i./ha/season) . Commerciall y mature cantaloupes were harvested 28 - 32 day s after the last applications. At Trial NM06 (Las Cruces, NM), cantaloupes were harvested at additional preharvest intervals (PHI s) of 6, 12, 19, and 34 day s to assess residue decline behavior. No adjuvants were used in any of the spray

mixtures. Cantaloupe samples were anal yz ed for residues of fluazinam and AMGT using a working method based on anal ytical method I SK/FLU/08002 (PMRA# 2140647) with a few modifications. Method ISK/FLU/08002 has been reviewed and deemed adequate for data gathering purposes in potatoes and grapes (PMRA# 2179742). The validated LOQ for each anal yt e is 0.01 ppm. The L OD was reported to be 0.0045 ppm. The working method was validated prior to sample anal ys is. Method v alidation recoveries from cantaloupe samples spiked with 0.01

– 1.0 ppm of fluazinam or AMGT ranged from 77

– 92% and 83

– 97%, respectively . Method suitability

was also verified concurrently during sample anal ys is. Concurrent recoveries from pepper samp les spiked with 0.01

– 1.0 ppm of fluazinam or AMGT ranged from 84

– 101% and 79

– 102%, respectively . All recoveries for each anal yt e fell within the acceptable range of 70

– 120%, indicating that the working method is adequate for the determination of residues of fluazinam and AMGT in/on cantaloupe samples from this study . Treated cantaloupe samples were stored frozen ( - 20 o C) for up to 1180 day s prior to extraction. All samples were anal yz ed within 6 day s of extraction. The freezer storage stability of fluazinam and AMGT residues in/on cantaloupes was assessed concurrentl y in this study, with control cantaloupe samples spiked with 1.03 ppm of fluazinam or 0.1 ppm of AMGT. The mean corrected residue recovery (corrected for concurrent recoveries from fre shly spiked samples) ± SD of fluazinam in samples stored frozen for 1184 days was 113 % ± 3% (n=3). The mean corrected residue recoveries (corrected for concurrent recoveries from freshly spiked samples) ± SD of AMGT in samples stored frozen for 1035 day s and 1055 day s were 99 % ± 3% (n=3) and 97 % ± 6%, respectivel y. Although cantaloupe samples were stored frozen for 125 day s longer than the demonstrated interval of storage stability for residues of AMGT, given that very good recoveries were observed after a storage period of 1105 days it is not likely that significant residue losses would be observed over the additional storage period. Furthermore, residues of AMGT were all below the LOQ of 0.01 ppm in all samples whose storage durations ranged from 1111 to 1180 days. As such, there are no concerns with the stability of residues of fluazinam and AMGT during the frozen storage time period for the cantaloupe samples in this study . T otal residues of fluazinam and AMGT in/on cantaloupes treated with a suspension formulation, as 6 foliar broadcast or directed applications at total rates of 4.62

– 4.77 lb a.i./ha/season and harvested at PHI s of 27 - 32 day s, ranged from <0.020 - <0.087 ppm . The residue decline data indicate that total residues of fluazinam and AMGT in/on cantaloupes decline with increasing PHI s. Peppers (MRID 48704502 ) ISK Biosciences submitted field trial data for fluazinam on field peppers (bell peppers and non -Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 16 of 25 bell peppers). Thirteen field trials were conducted in the United States and Canada during the 2007 growing season. Nine of the trials were conducted using bell peppers and encompassed Zones 2 (1 trial each in NJ and NC), 3 (1 trial in FL), 5 (2 trials in ON), 5B (1 trial in QC), 6 (1 trial in TX), and 10 (2 trials in CA). The remaining 4 trials were conducted using non - bell peppers and encompassed Zones 3 (1 trial in FL), 5A (1 trial in WI), 6 (1 trial in TX), and 9 (1 trial in NM). At each test locatio n, fluazinam (formulated as Omega 500F or Allegro 500F, a suspension), was applied to field peppers as 6 applications (2 soil directed applications around the base of the plant + 4 foliar applications) at rates of 0.412

– 0.859 lbs a.i./ha/application, with retreatment intervals (RTI s) of 6

– 53 day s, for a total application rate of 3.99

– 4.86 lb a.i./ha/season. Commerciall y mature peppers were harvested 28

– 31 day s after the last applications. At Trial 07 -NJ16 (Bridgeton, NJ), bell peppers were harvested at additional preharvest intervals (PHI s) of 7, 13, 20, and 35 day s to assess residue decline behavior. No adjuvants were used in any of the spray mixtures. Pepper samples were analy zed for residues of fluazinam and AMGT using a working method based on anal ytical method I SK/FLU/08002 (PMRA# 2140647) with a few modifications. Method I SK/FLU/08002 has been reviewed and deemed adequate for data gathering purposes in potatoes and grapes (PMRA# 2179742). The validated LOQ for each analy te is 0.01 ppm. The LO D was reported to be 0.0045 ppm. The working method was validated prior to sample anal ys is by

spiking control samples with 0.01

– 1.0 ppm of fluazinam or AMGT. Method suitability was also verified concurrentl y during sample anal ys is at the same spiking levels for each anal yt e. All recoveries for each anal yt e fell within the acceptable range of 70

– 120%, indicating that the working method is adequate for the determination of residues of fluazinam and AMGT in/on pepper samples from this study . Treat ed pepper samples were stored frozen ( - 20 o C) for up to 1249 day s prior to extraction. All samples were anal yz ed the same day of extraction. The freezer storage stability of fluazinam and AMGT residues in/on peppers was assessed concurrentl y in this study , with bell pepper samples being spiked with 1.03 ppm of fluazinam or 0.1 ppm of AMGT. The mean corrected residue recovery (corrected for concurrent recoveries from freshly spiked samples) ± SD of fluazinam in samples stored frozen for 1241 day s was 93 ± 8% (n=3). The mean corrected residue recovery (corrected for concurrent recoveries from freshl y s piked samples) ± SD of AMGT in samples stored frozen for 1106 days was 80 ± 3% (n=3). Although pepper samples were stored frozen for 143 days longer than the demonstrated interval of storage stability for residues of AMGT , given that good recoveries were observed after a storage period of 1106 day s it is not likely that significant residue losses would be observed over the additional storage period. Furthermo re, residues of AMGT were all below the LOQ of 0.01 ppm in all samples whose storage durations ranged from 1165 to 1249 day s. As such, there are no concerns with the stability of residues of fluazinam and AMGT during the frozen storage time period for the pepper samples in this study . T otal residues of fluazinam and AMGT in/on bell peppers and non - bell peppers treated with a suspension formulation, as two soil directed applications plus 4 foliar applications at a total rates of 3.99

– 4.86 lb a.i ./ha/season and harvested at PHI s of 28

– 31 day s, ranged from <0.020 - <0.048 ppm for bell peppers and from <0.020

– 0.064 for non - bell peppers. The residue declineFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 17 of 25 data indicate that total residues of fluazinam and AMGT decline in/on peppers with increa sing PHI s. Lettuce: Head and Leaf (MRID 48707301) ISK Biosciences previously submitted the results of 14 field trials on head and leaf lettuce (D360840, D. Dotson, 3/31/2010). These samples were anal yz ed for parent fluazinam, but not for the metabolite AMGT (a residue of concern for risk assessment) . HED made the following statement in its original review of the lettuce field trial data: “Samples from the lettuce field trial need to be anal yz ed for residues of AMGT. The residue data should also be supported b y data depicting the frozen storage stability of AMGT in the lettuce samples.” This stipulation was necessary because the field trial samples would have been stored for a significant period of time between sampling and analy sis. IR - 4 anal yz ed th e stored samples for AMGT and performed a storage stability

study . Seven of the lettuce trials were performed on head lettuce and 7 were performed on leaf lettuce. The trials were conducted in the U.S. during the 200 5 growing season. One of the head lettuce trials was conducted in EPA Growing Zone 2 (MD), one was conducted in Zone 3 (FL), and 5 were conducted in Zone 10 (4 in CA and 1 in NM). One of the head lettuce trials was conducted in EPA Growing Zone 2 ( GA), one was conducted in Zone 3 (FL), and 5 were conducted in Zone 10 (4 in CA and 1 in NM). For these trials, fluazinam (4.17 lb/gal FlC) was applied to head and leaf lettuce as a single broadcast foliar application during vegetative development at a rate of 0.952 - 1.05 lb ai/A (1x the proposed maximum seasonal rate). Applications were made using ground equipment in volumes of 32 - 77 gal/A, and no adjuvants were used. Single control and duplicate treated samples of lettuce leaves or heads, with wrapper leaves attached, were harvested at commercial maturity , 46 - 52 day s after application for head lettuce and 20 - 32 day s after application for leaf lettuce. The lettuce samples were anal yz ed for AMGT residues using the method “Method Evaluation for the Anal ys is of AMGT in Grapes,” Document Number 6268 - 94 - 1231 - MD - 001. Minor modifications to the analytical procedure were made to improve method performance. Homogenized samples were blended with acetonitrile/water (4:1, v/v). After filtration, the sample together with the filter paper was extracted for a second time by shaking with acetonitrile/water (1:1, v/v). The combined filtrate was rotary evaporated to remove all acetonitrile. The final extract was adjusted with acetonitrile/water (35.2:67.5, v/v) for LC/MS/MS analy sis. The method was validated at 3 fortification levels (0.02, 0.1, and 1 .0 ppm) prior to sample anal ys is. Both fortified and unfortified control samples were anal yz ed concurrently

with each sample set to demonstrate the absence of significant interferences and adequate recoveries. The lowest level of method validation was 0.02 ppm . In all 28 samples anal yz ed for AMGT, the residue level was below the LLMV of 0.02 ppm. For the storage stability

study , the performing laboratory anal yz ed samples that had been stored for 1 088 to 1110 days ( 3.0 to 3.04 ye ars). This storage interval was equivalent to 50 - 63% of the actual sample storage duration (4.8 to 5.9 years) . IR - 4 reported that additional data will be collected and anal yz ed under a separate protocol . Samples were fortified at 0.1 ppm and storedFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 18 of 25 in the same freezer as the field trial samples. AMGT storage stability ranged from 71 - 78% (n=7) for samples analyzed at 1088 to 1110 days. Concurrent recoveries for spikes analyzed along with the storage stability

samples were in the range of 82 - 87%. HED considers the submitted storage stability

data to be adequate to demonstrate that residues of AMGT are sufficientl y stable in lettuce to resolve the data deficiency cited in the lettuce tolerance petition. Conclusions . The submitted field trial data for fluazinam on soy beans, cantaloupes , and peppers are acceptable and support the proposed uses. Adequate numbers of trials were conducted in the appropriate geographic regions at approximately 1x the maximum proposed rate, and the appropriate samples were collected from each test at, or close to, the proposed PHI. The conditional AMGT residue data for lettuce and the supporting storage stability data are also acceptable. **TABLE 7**  **. Summary of Fluazinam** **F ield Trial**  **Residue Data** Co mmodity Analyte Total Rate (lb ai/A) PHI

(days) Residue Levels (ppm) n Sample Min. Sample Max. LAFT 1 HAFT 2 Median Mean Std . Dev. Soybeans Soybean Forage Fluazinam 0.99 - 1.17 29 - 35 16 0.021 3.7 3 0.034 3.0 6 0.427 0.63 0.7 4

AM GT <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA Soybean Hay Fluazinam 29 - 35 16 <0.017 5.2 1 0.028 5.2 1 0.868 1.4 1 1.4 8

AM GT <0.01 < 0.01 <0.01 <0.01 0.01 0.01 NA Soybean Seed Fluazinam 56 - 94 16 <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA

AM GT <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA Cantaloupes Cantaloupe Fluazinam 5.18 - 5.35 27 - 32 22 <0.0 1 0.0 7 7 <0.0 1 0.0 4 8 0.0 1 0.0 1 7 0.015

AM GT < 0.01 <0.01 <0.01 <0.01 0.01 0.01 NA Peppers (Bell and Non - Bell) Bell Pepper Fluazinam 4.47 - 5.45 28 - 31 18 <0.01 0.038 <0.01 0.030 0.01 0.014 0.007

AM GT <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA Non - Bell Pepper Fluazinam 5.10 - 5.29 28 - 31 8 <0.01 0.053 < 0.01 0.045 0.01 0.02 0.016

AM GT <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA Lettuce Head Lettuce AM GT 0.95 - 1.02 46 - 52 14 <0.02 <0.02 <0.02 <0.02 0.02 0.02 NA Leaf Lettuce AM GT 0.97 - 1.05 20 - 32 14 <0.02 <0.02 <0.02 <0.02 0.02 0.02 NA 1 LAF T = lowest average field trial 2 HAFT = highest average field trial result. NA = not applicable **860.1520 Processed Food and Feed** Soy beans (MRID 48712601) ISK Biosciences Corporation submitted a processing study for fluazinam on soybean. In one crop field trial conducted in Louisiana, so ybeans grown in separate plots received two foliar broadcast applications of a 4.17 lb ai/gal suspension concentrate (SC) formulation of fluazinamFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 19 of 25 (Omega ® 500F) . Applications were made at a rate of 0.52 - 0.53 lb ai/A/application for a total seasonal rate of 1.05 lb ai/A to produce seed for generation of aspirated grain fractions (AGF), and at an exaggerated rate (10x field rate) of 5.30 - 5.34 lb ai/A/application f or a total seasonal rate of 10.64 lb ai/A to produce seed for generation of processed fractions. Applications were made at an 11 - day

retreatment interval (RTI) using ground equipment in spray volumes of 19.2 - 23.6 gal/A. Adjuvants were not used at either plot. Soy bean seed was harvested from the plots at a 90 - day

preharvest interval (PHI) and processed into AGF, hulls, meal, and refined oil using simulated commercial procedures . Processing was conducted by GLP Technologies (Navasota, TX) . The registrant provided adequate descriptions of the processing procedures, including material balance summaries . Samples were anal yz ed for residues of fluazinam and its metabolite AMGT using a high performance liquid chromatography method with tandem mass spectrometri c detection (L C/MS/MS) adapted from Ricerca, Inc. analy tical methods. The limit of quantitation ( LO Q ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analy te . The method was adequate for data collection based on acceptable method validation and concurrent recovery

data. The fortification levels used in method validation and concurrent method recovery

were adequate to bracket expected residue levels (within an order of magnitude for hulls) . C oncurrent recoveries and residues in treated samples were not corrected for residues in controls. Samples were stored under ambient conditions (field sites) and frozen (≤12°C at the processing facility and < - 10°C at the anal ytical laboratory) from harvest/processing to anal ys is . Processing took place within 71 days of harvest. Sample analyses were completed within 77 - 117 days (2.5 - 3.8 months) for seed (RAC) and 46 days (1.5 months) for the processed commodities. All samples were anal yz ed within 1 - 9 days of extraction. Adequate storage stability data are available to support the storage conditions and durations of samples from the submitted processing study . Following application of fluazinam at 1.05 lb ai/A, residues o f fluazinam and AMGT were each below the LOQ (<0.01 ppm) in/on all samples of soy bean seed (RAC) and AGF; therefore, processing factors were not calculated for AGF. Following application of fluazinam at 10.64 lb ai/A, average residues of fluazinam were 0. 044 ppm in/on seed, 0.231 ppm in hulls, 0.046 ppm in refined oil, and below the L OQ (<0.01 ppm) in meal. Residues of fluazinam concentrate d in hulls (5.3x) and refined oil (1.1x), but did not concentrate in meal (processing factor of <0.22x). Residues of AMGT were below the LOQ in/on seed, hulls, meal, and refined oil; therefore, processing factors were not calculated . The processing factors calculated in this study were less than the maximum theoretical concentration factor s for soy bean of 11.3 x for hulls, 2.2x for meal, and 12.0x for oil (based on separation into components ; OPPTS 860.1520, Table 3 ).Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 20 of 25 **TABLE 8**  **. Residue Data from Soybean Processing Study with Fluazinam**  **.** RAC Processed

Commodity Total

Rate (lb ai/A) PHI Residues (ppm) 1 [Average] Processing Factor2 Fluazinam AM GT Fluazinam AM GT Soybean Seed (RAC) 3 1.05 90 ND, ND [<0.01] ND, ND [<0.01] -- --

AGF <0.01, <0.01 [<0.01] ND, ND [<0.01] NC 4 NC Seed (RAC) 3 10.64 90 0.043, 0.044 [0.044] ND, ND [<0.01] -- -- Hulls 0.242, 0.220 [0.231] ND, ND [<0.01] 5.3x NC Meal <0.01, <0.01 [<0.01] ND, ND [<0.01] <0.22x NC Refined oil 0.047, 0.044 [0.046] ND, ND [<0.01] 1.1x NC 1 The LOQ was 0.01 ppm for all analytes in all matrices. Per trial average residues were calculated by the study reviewer using the LOQ for all residues reported as <LOQ. 2 Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the seed RAC]. 3 Values for bulk seed samples shipped to the processor. 4 NC = Not calculated; residues were below the LOQ in both the RAC and the processed fraction. Conclusions: The submitted soy bean processing study

is acceptable. Following application of fluazinam at 1.05 lb ai/A, residues of fluazinam and AMGT were each below the LOQ (<0.01 ppm) in/on all samples of soy bean seed (RAC) and AGF; therefore, processi ng factors were not calculated for AGF. Following application of fluazinam at 10.64 lb ai/A, average residues of fluazinam were 0.044 ppm in/on seed, 0.231 ppm in hulls, 0.046 ppm in refined oil, and below the L OQ (<0.01 ppm) in meal. The processing data indicate that residues of fluazinam may concentrate in hulls (5.3x) and may concentrate slightl y in refined oil (1.1x), but do not concentrate in meal (processing factor of <0.22x). The observed concentration factors were less than the theoretical concentration factors. Residues of AMGT were below the L OQ in/on seed, hulls, meal, and refined oil; therefore, processing factors were not calculated. An acceptable method was used for residue quantitation, and the study is supported by

adequate storage sta

bility data. **860.1650 Submittal of Analytical Reference Standards** Analy tical reference standards for fluazinam, AMPA, DAPA , and AMGT are currentl y available in the EPA National Pesticide Standards Repository (electronic communicatio n, T. Cole to D. Dotson, 7/18/2012 ). The anal ytical standard s for AMPA and DAPA are due to expire in June and July of 2017, respectively . The standard for AMGT is due to expire in December 2012. The registrant will need to submit new standards or update d certificates of analy sis for the current standards b y their respective e xpiration dates . The standard s should be sent to the Analy tical Chemistry

L ab, which is located at Fort Meade, to the attention of Theresa Cole at the following address: USEPA National Pesticide Standards Repository /Anal ytical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 The mail will be returned if the extended zip code is not used.Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 21 of 25 **860.1850/1900 Confined and Field Accumulation in Rotational Crops** HED previousl y reviewed an adequate confined rotational crop study (D360840, D. Dotson, 3/31/2010). Based on the absence of metabolites containing the intact fluazinam nucleus, HED concluded that the residue of concern in rotational crops is the parent co mpound , and that rotational crop tolerances are not required for fluazinam . The 30 - day PBI on the label is sufficient for all rotated crops not on the label. No additional rotational crop data are required for the proposed uses on soy beans, melons, or peppers . **860.1550 Proposed Tolerances** The resi due of concern for tolerance enforcement is parent f luazinam for all plant commodities, except for wine grapes , for which the parent compound and the metabolite AMGT are the re sidues of concern . For poultry and ruminants, the residues of concern for tolerance enforcement are the parent compound plus the metabolites AMPA and DAPA, and their sulfamate conjugates. Adequate number s of field trials at ~1x the proposed use rate are available for cantal oupe, bell peppers, non - bell peppers, and soy beans to support the establishment of tolerances on these crops. Tolerances do not need to be recommended for so ybean forage and hay because the label contains a restriction that prohibits the feeding of forage and hay to livestock. The OECD MRLcalculation procedures were used to determine the recommended tolerances, which are listed in Table 9 . OECD MRLcalculation procedures were not used for so ybean seed be cause all of the residue values were below the LOQ of 0.01 ppm. HED is recommending in favor of a tolerance of 0.01 ppm for soy bean seed. There are currently

no Codex or Mexican maximum residue limits (MRL s) for fluazinam on melons, bell peppers, non - bell peppers, or so ybeans. There are no Canadian MRL s for melons or peppers. The petition for melons and peppers is being evaluated jointly

by the U.S. and Canada’s PMRA. Both countries are using the OECD MRLcalculation procedures to determine the recommended tolerances. For this reason, the MRL s for mel ons and peppers will be harmonized between the two countries. There is a Canadian MRLof 0.10 ppm for edible - podded soy bean. There is no need to harmonize this MRLwith HED’s recommended tolerance of 0.01 ppm for soy bean seed because edible - podded soy bean and so ybean seed are different commodities. Edible - podded so yb ean is an immature seed that includes the pod. It is likel y to have a higher residue level than soybean seed, which is the dried seed alone. An International Residue Limit Status Sheet can be found in Attachment 1 .Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 22 of 25 **References** D 272624 , Fluazinam. Decision by Metabolism Ass essment Review Committee (MARC), W. Cutchin , 4/23/01 D360840, Fluazinam. Petitions for the Establishment of Tolerances and Registration of New Uses on Apples, Carrots, Lettuce, and Bulb Onion Subgroup (3 - 07A), and a Request for a Reduced Tolerance on Bushberry Subgroup (13 - 07B). Summary of Anal yt ical Chemistry

and Residue Data , D. Dotson, 3/31/2010 D387187, Fluazinam. Human Health Risk Assessment for the Section 3 Registration Action on Turfgrass , D. Dotson, et al., 2/7/2012

Attachments: Attachment 1: International Residue Limit Status sheet Att achment 2: Tolerance Assessment CalculationsFluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 23 of 25 **Attachment 1: International Residue Limits**  

### Fluazinam ( 129098 ; 7 - 10 - 2012 ) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3 40 CFR 180. 574 : Plant s : Fluazinam, 3 - chloro -N - [3 - chloro 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl) - 2 -pyridinamine Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex 3 Soybean, Seed 0.01 0.10 ppm: Edible podded soybean Soybean, Hulls 0.0 2 Melon subgroup 9A 0.0 7 Pepper/Eggplant Subgroup 8 - 10B 0. 09 Completed: M. Negussie; 07/16/2012 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 24 of 25 **Attachment 2: Tolerance Assessment Calculations** Soy beans HED’s current policy

is to use OECD MRLcalculation procedures to determine recommended tolerances. In the case of soy beans, all of the residue values were below the L OQ of 0.01 ppm. When all residue values are below the LOQ, HED recommends in favor of establishing the tolerance at the LOQ. Therefore, HED recommends in favor of a tolerance of 0.01 ppm for soy bean seed. The average processing factor for so yb ean hulls is 5. 25 x. Multiplying this value by the soy bean seed LOQ of 0.0 1 ppm yields a value of 0. 05 25 ppm. HED recommends in favor of a tolerance of 0.0 5 ppm for so ybean hulls. Melon Subgroup (9A) For melons , the OECD MRLCalculator was used for calculating recommended tolerances. Average cantaloupe field trial values were entered into the calculator. The dataset u sed to establish tolerances on the melon subgroup consisted of field trial data representing applications at rates of 4. 6 - 4.8 lb ai/A ( six applications at approximately 0. 78 lb ai/A/application) with a 27 - 32 day PHI . Using the MRLcalculator , the recommended tolerance is 0.07 ppm . Pepper /Eggplant Subgroup (8 - 10B) For peppers , the OECD MRLCalculator was used for calcul ating recommended tolerances. Average field trial values were entered into the calculator. Field trial data for bell and non - bell peppers were entered separatel y and the higher of the two recommended tolerances (i.e., that for the non - bell peppers) is th e one that HED is recommending as the tolerance for the entire subgroup. The dataset u sed to establish tolerances on the pepper/eggplant subgroup consisted of field trial data representing applications at rates of 4.6 - 4.7 lb ai/A ( six applications at approximately 0. 78 lb ai/A/application) with a 28 - 31 day PHI . Using the MRLcalculator , the recommended tolerance is 0.09 ppm . The MRLcalculator recommends a tolerance of 0.05 ppm for the bell peppers. As stated above, the recommended tolerance for the non - bell peppers is being recommended as the tolerance for the entire subgroup because it is the higher of the two values.Fluazinam Summary of Analytical Chemistry and Residue Data DP No. 397721

Page 25 of 25 **Fluazinam: OECD MRL Calculator Results**  **OECD MRL Calculator Results for the Melon Subgroup (9A) and the Pepper/Eggplant Sub group (8**  **- 10B)**  **Compound Fluazinam**  **Fluazinam Fluazinam**  **Crop Bell Peppers**  **Non -**  **Bell Peppers Cantaloupes**  **Region / Country US & Canada**  **US & Canada US & Canada**  **GAP 4.47**  **- 5.45 kg a.i./ha**  **(3.99 -**  **4.86 lb a.i./A) PHI = 28**  **- 31 days**  **5.10 -**  **5.29 kg a.i./ha (4.55**  **- 4.72 lb a.i./A** **) PHI = 28**  **- 31 days)**  **5.18 -**  **5.35 kg a.i./ha (4.62**  **- 4.77 lb a.i./A)**  **PHI = 27 -**  **32 days Total number of**  **data points**  **(n)** 9 4 11 **Percentage of censored data**  33% 50% 45% **Number of non**   ** censored data** 6 2 6 **Lowest residue** 0.010 0.010 0.010 **Highest residue** 0.030 0.045 0.048 **Median residue** 0.011 0.013 0.011 **Me an**  0.014 0.020 0.017 **Standard deviation (SD)**  0.007 0.017 0.012 **Correction factor for censoring (CF)**  0.778 0.667 0.697

**- Highest residue**  0.030 0.045 0.048

**- Mean + 4 SD**  0.041 0.087 0.063

**- CF x 3 Mean**  0.034 0.041 0.036 **Unrounded MRL** 0.041 0.087 0.063 **Rounded MRL 0.05**  **0.09 0.07**  High uncertainty of MRL estimate due to small dataset. **Residues (mg/kg) Residues (mg/kg)**  **Residues (mg/kg)** 0.010 * 0.016 0.020 0.019 0.010 * 0.010 * 0.010 * 0.045 0.011 0.010 * 0.010 * 0.010 * 0.015 0.010 * 0.015 0.048 0.030 0.010 * 0.011 0.024 0.010 0.014 0.021 0.010 *