Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 1 of 54 UNITED STA

TES ENVIRONMENTA L PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDE AND TOXIC SUBSTANCES MEMORANDUM Date: 3 /3 1 /20 1 0 SUBJECT: Fluazinam . Petition s for the Establishment of Tolerances and Registration of

New Uses on Apple s , Carrot s , Lettuce , and Bulb Onion Subgroup ( 3 - 07A ) , and a Request for a Reduced Tolerance on Bushberry S ubgroup ( 13 - 07B) . Summary of Analy tical Chemistry

and Residue Data. PC Code: 129098 DP Barcode s : D360840 and D366 506 Decision No s .: 404254 and 412727 Registration No. : 71512 - 1 P etitions : 8E7506 , 9E7570, and 9F7571 Regulatory Action: Section 3 Registration Risk Assessment Type: NA Case No.: NA T XR No.: NA CAS No.: 79622 - 59 - 6 MRID No s . : 47631001, 47631002, and

47756601 through 47756611 40 CFR: § 180.574

FROM: Douglas Dotson, Ph.D., Chemist

Risk Assessment Branch I I Health Effects Division (7509P) THROUGH: William Drew, Chemist

Richard L oranger, Ph.D., Senior Scientist Risk Assessment Branch I I Health Effects Division (7509P) TO: Laura Nollen/Barbara Madden, RM Team 5, RIMUERB

John Bazuin/ Tony

Kish, PM Team 22 , Fungicide Branch Registration Divi sion (7505P)Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 2 of 54 This document was originally prepared under contract by Dy namac Corporation ( 1901 Research Boulevard, Suite 220 ; Rockville, MD 20850 and 1910 Sedwick Rd., Building 100, Sui te B; Durham, NC 27713 ). The document has been reviewed by the Health Effects Division (HED) and revised to reflect current Office of Pes ticide Programs (OPP) policies. Executive Summary Fluazinam ( 3 - chloro -N

- [3 - chloro - 2,6 - dinitro - 4 - (trifluoromethyl)ph enyl] - 5 - (trifluoromethyl) - 2 - py ridinamine ) is a member of the phenyl - py ridinamine class of compounds. Fluazinam is a non sy stemic, preventive, contact fungicide with a multi - site mode of action. Itdisrupts the production of energy

at several metabolic si tes within the fungal cell. Fluazinam is a protectant fungicide . That is, when applied to plants, it remains primarily on the plant surface, it is not taken up to any

extent by the plant, and it is not translocated within the plant. The Agency

has recei ved three separate tolerance petitions to e stablish permanent tolerances for fluazinam residues of concern in/on various raw agricultural and animal commodities. This document summarizes the available residue chemistry data in support of these tolerance p etitions. 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# 8E7506, the Interregional Research Project No. 4 (IR - 4) , on behalf of the Agricultural Experiment Stations of Arizona, California, Colorado, Georgia, I daho, New York, Ohio, Tennessee , and Texa s has requested registration of fluazinam for use on lettuce (head and leaf) and O nion , bulb , subgroup 3 - 07A . T he proposed use of OMEGA ® 500F on lettuce is for a single broadcast or banded foliar application or soil drench application at crop thinning at up to 1 . 0 lb ai/A. The proposed use for the bulb onion subgroup is for a maximum of six broadcast foliar applic ations during vegetative development at up to 0.52 lb ai/A/application for a maximum seasonal rate of 3.1 lb ai/A. The minimum retreatment interval (RTI) is 7 day s for onions , and both uses only

allow for a

pplication s using ground equipment. The minimum preharvest intervals ( PHI s ) are 50 days for head lettuce, 30 days for leaf lettuce , and 7 days for onions. In conjunction with these uses, IR - 4 has proposed the establishment of permanent tolerances for residues of fluazinam in/on the following commoditie s:

Lettuce, head ................................ ................................ ..... 0.02 ppm Lettuce, leaf ................................ ................................ ............ 2 ppm Onion, bulb, subgroup 3 - 07A ................................ ........... 0.15 ppm Also included in PP# 8E7506 is a request by IR - 4 to rev ise the established 7.0 - ppm tolerance for fluazinam residues in/on the B ushberry subgroup ( 13B ) and other bushber ry ty pe crops (aronia berry , buffalo curr ant, Chilean guava, European barberry , highbush cranberry , edible honey suckle, jostaberry , juneberry , lingonberry , native currant, salal, and sea buckthorn) . These tolerances were originally established under PP# 6 E7137 ( Memo, D335640, W. Drew , 8/22/07 ). IR - 4 is requesting that a single tolerance be established for the updated B ushberry subgroupFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 3 of 54 ( 13 - 07B ) for residues of fluazinam at a level of 4.5 ppm. This proposed tolerance would then replace the multiple tolerances on the various bushberries . In PP# 9E7570, IR - 4, on behalf of the Agricultural Experiment Stations of California, Georgia, Texas , and Washington , has requested the registration of fluazinam for use on carrots. The proposed use includes a maximum of four directed band applications prior to or during disease development at up to 0.52 lb ai/A/application , with a 7 - day RTI , f or a maximum seasonal rate of 2. 1 lb ai/A. Applications may be made using ground equipment. A 7 - day PHIis proposed. Concurrentl y, IR - 4 has proposed the establishment of the following permanent tolerance for residues of fluazinam:

Carrot, root s ................................ ................................ ......... 0.8 ppm In PP# 9F7571, I SK Biosciences Corporation requested the registration of fluazinam for use on apples. The proposed use includes a maximum of ten broadcast foliar applications prior to or during disease development at up to 0. 45 lb ai/A/application , with a 7 - day RTI , for a maximum seasonal rate of 4.50 lb ai/A. Applications may be made using ground and aerial equipment. A 28 - day P HIis proposed. Inconjunction with this use, I SK Biosciences has proposed the establishment of permanent tolerances for residues of the fungicide fluazinam and its metabolite AMGT in or on the following commodities:

Apples ................................ ................................ .................. 1.7 ppm Apple, pomace, wet ................................ .............................. 5.0 ppm Inaddition, I SK Biosciences has proposed tolerances for residues of fluazinam and its metabolites DAPA and AMPA in the following livestock commodities:

Cattle, fat ................................ ................................ ............ 0.03 ppm Cattle, kidney ................................ ................................ ..... 0.03 ppm Cattle, liver ................................ ................................ ......... 0.03 ppm Cattle, meat ................................ ................................ ........ 0.03 ppm Cattl e, meat by

products ................................ ...................... 0.03 ppm Goat, fat ................................ ................................ .............. 0.03 ppm Goat, kidney ................................ ................................ ....... 0.03 ppm Goat, liver ................................ ................................ .......... 0.03 ppm Goat, meat ................................ ................................ .......... 0.03 ppm Goat, meat by

products ................................ ....................... 0.03 ppm Horse, fat ................................ ................................ ............ 0.03 ppm Horse, kidney ................................ ................................ ..... 0.03 ppm Horse, liver ................................ ................................ ......... 0.03 ppm Horse, meat ................................ ................................ ........ 0.03 ppm Horse, meat by

products ................................ ...................... 0.03 p pm Milk ................................ ................................ .................... 0.03 ppm Sheep, fat ................................ ................................ ............ 0.03 ppm Sheep, kidney ................................ ................................ ..... 0.03 ppmFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 4 of 54 Sheep, liver ................................ ................................ ........ 0.03 ppm Sheep, meat ................................ ................................ ........ 0.03 ppm Sheep, meat by

products ................................ ..................... 0.03 ppm P ermanent tolerances have been established for residues of fluazinam in/on plant commodities at levels ranging from 0.01 to 7.0 ppm [40 CFR §180.574(a)(1)], and a tolerance has also been established for residues of fluazinam and its metabolite AMGT on wine grapes at 3.0 ppm ( 40 CFR §180.574(a)(2) ) . N o tolerances have been established for livestock commodities. There are c urrently

no established Codex, Canadian, or Mexican maximum residue limits (MRL s) for fluazinam on apple s , carrot s , lettuce, onions , or berry crops. Therefore, there are no harmonization issues for the requested tolerances. The nature of f

luazinam residu es in plants is adequately understood based on metabolism studies on potatoes, peanuts, and grapes . The Agency previously concluded that the residue of concern in peanuts and root and tuber vegetables is fluazinam per se 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 AMG T for wine grapes, but o nly fluazinam for all other plant commodities. The nature of fluazinam residues 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 for fluazinam. The available confined field rotational crop study supports the 30 - day plant - back interval (PBI) that is currently listed o n 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 regulatory interest in animal commodities were determined by HED to be parent plus the metabolites AMPA and DAPA, and their sulfamate conjugates. An adequate gas chromatography with electron capture detection ( GC/ECD ) method (6148 - 9 4 - 0170 - MD - 001 ) is available for determination of fluazinam residues in crop matrices . The method was deemed to be suitable for tolerance enforcement after it successfully completed the routes required for an enforcement method including radiovalidation, independ ent laboratory validation (ILV) , and tolerance method validation ( T MV). Samp les collected from the magnitude of the residue and storage stability studies were analy

zed for residues of fluazinam using various GC/ECD methods based on, and revised slightly from , the plant enforcement method. The GC/ECD methods are adequate for data collection based on acceptable method recovery data. The lowest limit of method validation (LLM V) was 0.01 ppm in all tested commodities except in carrots where the LLM V was 0.02 ppm.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 5 of 54 An enforcement method for determination of AMGT, a residue of concern in wine grapes, is available. The registrant requested that the blueberry submission serve as the ILV for the method. The range of fortification levels and the percent recovery values are acceptable. As a result, HED considers the AMGT analy tical porti on of the blueberry field trial study

to be adequate , and that it can serve as the ILV for the analy tical method for AMGT residues in plant commodities. PTRLMethod 1676W was the data - collection method used for the analysis of samples collected from the d airy

cattle feeding study . The method is written for L C/MS/MS analy sis of fluazinam, AMPA , and DAPA in bovine milk and tissues, and for GC/MS analysis of DAPA in milk only . The limit of quantitation was 0.01 ppm for each analy te in milk, muscle, fat, liv er and kidney . Preliminary

method validation data showed that Method 1676W adequately recovered residues of fluazinam, AMPA, and DAPA in milk, muscle , and fat. However, poor and/or marginal recoveries were obtained for AMPA and DAPA residues in kidney and liver. Method 1676W was marginally

validated by

an independent laboratory during the third trial and following slight modifications to make the method more rugged. For the purpose of developing an animal enforcement method, radiovalidation data are re quired to determine whether the method can detect aged residues. HED forward ed Method 1676W to AC B /BEAD for a tolerance method validation (TMV) because the method encountered difficulties in the ILV (e.g., three attempts for successful validation and/or m arginal recoveries with wide variability and high coefficient of variation). The method was forwarded to ACB/BEAD for method validation. ACB/BEAD reported that the lab that performed the ILV made major modifications to the original method. As a result, HED requested that the registrant submit a revised method that incorporated the revisions made by

the ILV lab. I SK Biosciences revised the method and re - submitted it. ACB/BEAD performed a cursory review of the revised method. The registrant incorporated the modifications made by

the ILV lab. However, the revision eliminated the cleanup steps that were in the original method, and the only recovery data for the revised method were data provided by the ILV lab. ACB/BEAD was concerned that the elimination of the cleanup steps could lead to dirty samples which would, in turn, lead to analy tical problems, such as interference. ACB/BEAD performed no further validation of the method. As the revised method contains major revisions to the original method, and A CB/BEAD believes it is very likely that the revised method still is not adequate for sample analysis or tolerance enforcement, HED recommends that the registrant submit an ILV of the revised method. 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. Multiresidue method testing data are required for the regulated metabolites, AMPA and DAPA, in animals. Analy tical reference standards for fluazinam , AMPA , and DAPA are c urrently available in the EPA Nati onal Pesticide Standards Repository ; however an analy tical standard for the AMGT metabolite is not currently available.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 6 of 54 Adequate storage stability data are available to support the storage conditions and durations of samples collected from the magnitude o f the residue studies on apples, carrots, lettuce, and onions. As residues of fluazinam were found to be stable in tested crop matrices, storage stability corrections do not need t o be applied to the recommended tolerances for fluazinam residues in/on app les, carrots, lettuce, and onions. Storage stability data for the fluazinam metabolite AMGT in apple commodities were also submitted , and showed that residues in wet apple pomace were reasonably stable for 12 months, but declined to an average corrected r ecovery of 58 - 63% at the 19 - month interval, 61% at the 32 - month interval, and 33% at the 37 - month interval . The submitted storage stability data for bovine milk, meat, and meat by products showed mixed results. Based on the poor recoveries of metabolites AMPA and DAPA from liver and kidney and the mixed storage stability

results, the residue data from the cattle feeding study are not adequate to satisfy data requirements. The feeding study data (adjusted for residue decline) along with the calculated diet ary

burdens for beef cattle (0.04 ppm) and dairy cattle (1.27 ppm) indicate that tolerances are needed for the combined residues of fluazinam and its metabolites DAPA and AMPA in the fat and meat by products of cattle and other ruminants at 0.0 5 ppm to supp ort the proposed use s on apples and carrots and the established tolerances on potatoes and peanuts . However, no tolerances are required for milk and meat of ruminants , as the expected combined residues in these matrices are below the combined method limit of quantitation ( LOQ ) of 0.03 ppm for the regulated compounds . Based on the transfer coefficients for livestock tissues and the relatively low dietary

burden for swine of 0.003 ppm for fluazinam, tolerances for hog commoditie s are not needed. A poultry feeding study is not required at this time because of the low dietary

burden for poultry

(0.005 ppm ). With the exception of the use of adjuvants, the submitted field trial data for fluazinam on head lettuce, leaf lettuce, bulb onions, carrots, and apples 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 using a representative FlC formulation , and the appropriate samples were collected from each tes t at the proposed PHI . However, no residue data were provided on AMGT residues in lettuce. Although AMGT residue data on lettuce are still required for purposes of dietary

risk assessment, the available data would support tolerances of 0.0 2 ppm for head lettuce, 2.0 ppm for leaf lettuce, 0.20 ppm for the bulb onion (subgroup 3 - 07A), 1. 5 ppm for apple, and 0.7 ppm for carrot. The tolerance spreadsheet ( Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP) was used for determining approp riate tolerance levels. For dietary

risk assessment, HED will calculate AMGT residues in lettuce using a ratio of 0.35:1 for AMGT:fluazinam residues (ChemSAC Memo, meeting of 2/6/08) . The samples from the lettuce field trials still need to be analy zed fo r residues of AMGT. AMGT is not a residue of concern for risk assessment for carrots or onions; therefore, for these commodities it does not need to be included in the dietary exposure assessment. AMGT residues were measured in apples and the combined re sidues of parent and AMGT need to be included in the dietary exposure assessment.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 7 of 54 After re evaluatin g the available residue data for blueberries, HED conclude s that the residue data for fluazinam from the blueberry field trials are distributed lognormally . As a result, the recommended tolerance for the revised B ushberry subgroup 13 - 07B is 7 .0 ppm , which is equivalent to the current tolerance for Subgroup 13B . The apple processing study is not adequate to satisfy data requirements. Inapples, the metaboli te AMGT is a residue of concern for risk assessment. In the processing study there were no quantifiable residues of AMGT in raw apples. In several of the field trials that were performed, however, raw apples contained AMGT residues at, or above, the limi t of quantitation. In a few cases, residues of AMGT were comparable to those of the parent fluazinam. Canadian and U.S. residue chemistry

guidelines both stipulate that in the processing study , if residues in the raw agricultural commodity

( RAC ) are belo w the LOQ, but quantifiable residue s occurred in the RAC in field trials performed at the maximum requested label rate, that the processing study should be conducted at exaggerated rates in order to ensure that quantifiable residues will be present in the RAC . Quantifiable residues are needed in the RAC in order to determine a reliable concentration factor. As a result, the processing study needs to be repeated at a sufficiently high rate that residues of both parent and AMGT are quantifiable in the RAC. Inthe event that the potential for phy

totoxicity exists, the application rate does not need to be greater than the rate at which phy

to to xicity occurs. Regulatory Recommendations and Residue Chemistry Deficiencies No major deficien cies were noted in the current petition s that would preclude establishing permanent tolerance s for fluazinam residues of concern on head lettuce ; leaf lettuce ; Onion, bulb, subgroup 3 - 07 A ; and Bushberry , subgroup 13 - 07B. In addition, the deficiency listed below for lettuce field trials needs to be resolved as a condition of registration. A revised Section F is needed as detailed below (860.1550). Because of major data deficiencies, HED does not recommend in favor of the establishment of tolerances for ap ples or carrots. HED also does not recommend in favor of tolerances for animal commodities. The data deficiencies associated with the apple and carrot petitions are discussed below. For PP# 8E7506, pending submission of residue data for AMGT on lettuce as a condition of registration , the submitted data support the proposed use s of OMEGA ® 500F on lettuce and O nion, bulb, subgroup 3 - 07A along with the establishment of tolerances for residues of fluazinam in/on:

Lettuce, head ................................ ................................ ..... 0.02 ppm Lettuce, leaf ................................ ................................ ......... 2 .0 p pm Onion, bulb, subgroup 3 - 07A ................................ ........... 0. 20 ppm The petition also supports revising the existing Bushberry subgroup 13 - B tolerance to a Bushberry s ubgroup 13 - 07B tolerance at 7.0 ppm along with deletion of existing individual tolerances on various berries as det ailed in Table 13.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 8 of 54 Li st of Deficiencies 860.1200 Directions for Use

• The use directions for all the subject crops (lettuce, onions, bushberries, apples, and carrots) should include a prohibition against addition of adjuvants to the spray mixture. Th e following deficiency applies to both existing and proposed uses of fluazinam 860.1650 Submittal of Analy tical Reference Standards

• An analy

tical reference standard for the AMGT metabolite is not available. RD should request that the registrant submi t this standard to the EPA’s National Pesticide Repository

as soon as possible. Li st of Deficiencies by

Petition PP# 8E 75 06 (Lettuce, Onion, Bushberry Subgroup) 860.1500 Crop Field Trials

• Samples from the lettuce field trial need t o be analy zed f or 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. 860.1550 Proposed Tolerances

• The registrant should submit a r evised section F in which a tolerance of 0.2 ppm is proposed for Onion, bulb, s ubgroup 3 - 07A , and a tolerance of 7 .0 ppm is proposed for Bushberry , s ubgroup 13 - 07B. PP# s 9F757 0 (Carrots) and 9F7571 (Apples) 860.1340 Residue Analy

tic al Methods

• At the present time, an analy tical method is not available for enforcement of fluazinam tolerances in animal commodities. The registrant should submit an ILV of the revised method. This method needs to be adequate for analysis of parent flu azinam as well as the metabolites AMPA and DAPA in animal commodities for which tolerances will be established.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 9 of 54 • If the registrant resolves the data deficiencies associated with the apple and carrot petitions and re - submits the tolerance petitions, multi residue method testing data will be required for the regulated metabolites, AMPA and DAPA, in animals. 860.1480 Meat, Milk, Poultry , and Eggs

• The residue data from the cattle feeding study are not adequate to satisfy data requirements. To support tol erances for apples and carrots, the registrant needs to submit a new cattle feeding study in which a method with better recoveries of AMPA and DAPA from liver and kidney was used . When this study is repeated, the samples need to be analy zed as soon as pos sible after sacrifice in order to minimize degradation of residues. 860.1520 Processed Food and Feed (Applies Only to Apple Petition, 9F7571 )

• The apple processing study is not adequate to satisfy data requirements. T he processing study

needs to be repeated at a sufficiently high rate that residues of both parent and AMGT are quantifiable in the RAC. In the event that the potential for phy

totoxicity exists, the application rate does not need to be greater than the rate at which phy to to xicity occurs. Note to RD: HED recommends that 40CFR §180.574(a)(1) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of f luazinam ( 3 - chloro -N

- [3 - chloro 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl) - 2 - py ridinamine ), including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only

fluazinam.” HED further recommends that 40CFR §180.610(a)(2) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of fluazinam , including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels s pecified below is to be determine d by measuring only

fluazinam and its metabolite AMGT ( 3 - [[4 - amino - 3 - [[3 - chloro - 5 - (triflu oromethyl) - 2 - py ridinyl]amino] - 2 - nitro - 6 - (trifluoromethyl) phenyl]thio] - 2 - (beta - D - glucopy ranosyloxy

) propionic acid) .” Background Fluazinam is a contact, multi - site fungicide with activity against a number of plant pathogenic fungi. Itdisrupts 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 1, and the phy sicochemical properties of f luazinam are summarized in Table 2.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 10 of 54 Table 1. FluazinamNom enclature. Compound

Cl N H

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

Common name Fluazinam Company experimental name IKF - 1216 IUPAC name 3 - chloro -N - (3 - chloro - 5 - trifluoromethyl - 2 - pyridyl) - 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 - pyridinamine CAS registry number 79622 - 59 - 6 End - use product (EP) 4.17 lb/gal FlC ( Omega® 500F Fungicide; EPA Reg. No. 71512 - 1) Compound

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 H O O C

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

Cl N H

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

Common name AMPA Chemical name 2 - (6 - amino - 3 - chlor o - α,α,α. - trifluoro - p - toluidino) - 3 - chloro - 5 - (trifluoromethyl) pyridineFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 11 of 54 Table 1. FluazinamNom enclature. Compound

Cl N H

C F 3 N Cl F 3 C N H 2 N H 2 Common name DAPA Chemical name 3 - chloro - 2 - (2,6 - diamino - 3 - chloro - α,α,α. - trifluoro - p - toluidino) - 5 - (trifluoromethyl)pyridine Table 2. Physicochemical Properties of the T echnical Grade Fluazinam . Parameter Value References Melting point/range 115 - 117oC DP# 335640, 8/22/07, W. Drew pH 5.85 Density (25oC) 1.02 g/cm3 Water solubility (25oC) (pH buffered to 5) 0.131 mg/L (pH buffered to 7) 0.157 mg/L (pH buffered to 9 ) 3.384 mg/L Solvent solubility (g/L at 20oC) acetone: 853 dichloromethane: 675 ethyl acetate: 722 ethyl ether: 231 hexane: 8

methanol: 192 octanol: 41 toluene: 451 Vapor pressure (Pa) 2.3 x 10 - 5 at 25oC 1.3 x 10 - 4 at 35oC 6.7 x 10 - 5 at 45oC Dissociation constant, pKa 7.22 in 50% ethanol/water (v/v, average) Octanol/water partition coefficient, Log (KOW ) 1.08 x 10 4 (Log Kow = 4.03) UV/visible absorption spectrum (λ max , nm) 238 at pH 5

239, 342 at pH 7 260, 343, 482 at pH>10 860.1200 Directions for Use There is currently

a single end - use product (EP) for fluazinam registered to I SK Biosciences in the U.S. for use on food/feed crops. This EP is Omega ® 500F (EPA Reg. No. 71512 - 1), which is a 4.17 lb/gal FlC formulation . It is registered for use on ginseng, peanuts, potatoes, turnip greens, Crop Group 5 (

Brassica leafy

vegetables), Subgroup 6A (except pea), Subgroup 6B (except pea), Subgroup 6C (except pea), the B ushberr y S ubgroup ( 13B), and other bushberries .Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 12 of 54 IR - 4 is proposing to add uses on c arrot, lettuce, and members of the B ulb onion subgroup , 3 - 07A , to the label for the 4.17 lb/gal FlC formulation for control of fungal diseases. Proposed supplemental labels were provided for these new use s . The proposed use directions are summarized in T able 3. IS K Biosciences is propos ing to add use on apple to the product label for the 4.17 lb/gal FlC formulation . The proposed use directions are summarized in Table 3. Table 3. Summary of Directions for Use of Fluazinam . Applic. Timing ; Ty

pe ; and E quip ment Formulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations 1 Apple Broadcast foliar applications prior to or during disease development; Ground and aerial equipment 4.17 lb/gal FlC [71512 - 1] 0.33 -

0.45 10 4.50 28 Apply in a minimum of 5 gal/A (both ground and aerial equipment) . The minimum RTI is 7 days. Bulb Onion Subgroup 3 - 07A Broadcast foliar applications prior to or during disease development ; Ground equipment 4.17 lb/gal FlC [71512 - 1] 0.52 6 3.12 7 Apply in a minimum of 5 gal/A. The minimum RTI is 7 days. Carrot Directed band to the crop prior to or during disease development; Ground equipment 4.17 lb/gal FlC [71512 - 1] 0.52 4 2.0 8 (impli ed) 7 Apply in a minimum of 30 gal/A. The minimum RTI is 7 days. Lettuce (Head and Leaf) Broadcast or banded foliar application or soil drench application at thinning ; Ground equipment 4.17 lb/gal FlC [71512 - 1] 0.52 -

0.99 1 1 . 0 50 - head lettuce ; 30 - leaf lettuce Apply in a minimum

of 50 gal/A.

1 A 48 - hour restricted entry interval is specified. T he current (and proposed) product label for the 4.17 lb/gal FlC formulation specifies that a pplications are allowed through the following ty pes of irri gations systems: 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 : a ll crops on the label may be replanted immediately after treatment . A ll other crops can be replanted 30 days after the last application.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 13 of 54 Conclusions . The submitted use directions are sufficient to allow for evaluation of the submitted residue data relative to the proposed use patterns. The available f ield trial data support the proposed use directions for the crops addressed in this s ummary d ocument , with the exception of the use of adjuvants . As the crop field trials did not include adjuvants, the use directions for all proposed crops should include a prohibition against the addition of adjuvants to the spray mixture . 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 adequately understood , based on acceptable potato, peanut, and grape metabolism studies. The metabolism of fluazinam appears to be similar in tested 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 - cy steine conjugate then undergoes transamination, reduction, and conjugation with glucose t o form AMGT. In addition, both rings of fluazinam appear to be labile to ring cleavage, and they subsequent ly degrad e i nto small fragments that c an then be incorporated into a variety of natural plant components. The residues of regulatory interest in primary crops are listed in Table 4. Table 4. 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 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); however, HED has not reviewed it . In the event that the registrant resolves the data deficiencies associated with the apple petition and re - submits it, the apple metabolism study should be reviewed. 860.1300 Nature of the Residue - Livestock MARC Decision Memo, D272624 , W. Cutchin, 4/23/01 Residue Chemistry Memo D2 5 7115 , W. Cutchin, 5/21/01 The nature of the residue in livestock is adequately understood, based on adequate goat and hen metabolism studies . The metabolism of [ 14 C] - fluazinam in ruminants and poultry is similar, and invo lves reduction of one or both nitro groups on the phenyl ring to form AMPA, MAPA, or DAPA. Fluazinam also undergoes dehalogenation and hydroxylation of the chlorine on the phenyl ring to form HYPA. These compounds can then undergo conjugation with glutathione, and subsequent degradation of the glutathione moiety yi elds a variety of polar compounds. Although the ring structure of the parent molecule remains intact, fluazinam per se was only aFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 14 of 54 minor component ( ≤2.7% TRR) of the [ 14 C] - residues in poultry tissues and eggs, and was not detected in ruminant tissues or milk. The residues of concern in livestock are listed in Table 5. Table 5 . FluazinamResidues of Concern in Livestock Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression Ruminant Parent fluazinam, AMPA, and DAPA, and their sulfamate conjugates Parent fluazinam, AMPA, and DAPA, and their sulfamate conjugates Poultry Parent fluazinam, AMPA, and DAPA, and their sulfamate conjugates Parent fluazinam, AMPA, and DAPA, and their sulfamate conjugates 860.1340 Residue Analytical Methods Residue Chemistry Memo D33 5640 , W. Drew , 8/22/07 Residue Chemistry Memo D212612 , G. Herndon, 9 / 5 /9 5 T MV Results Memo, D 266802 , P. Golden, 6/22/01 Plant commodities Enforcement M ethods Fluazinam An adequate GC/ECD method (6148 - 9 4 - 0170 - MD - 001 ) entitled “Fluazinam: Method for the Analy sis in Peanut Nutmeat” ( MRID 43521016 ) is available for enforcing fluaz inam tolerances on plant commodities. The method was adequately radiovalidated and underwent a successful ILV trial. The method was forwarded to BEAD’s Analy tical 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 with hexane:ethyl ether (80:20, v/v). Residue s are concentrated to dry ness, redissolved in hexane , and analy zed by GC/ECD using external standards for quantitation. The method L OQ is 0.01 ppm for fluazinam in plant commodities. AMGT An enforcement method for determination of AMGT, a residue of con cern in wine grapes, is available. HED recommended in a previous memorandum ( Memo, D33 5640 , W. Drew, 8/22/07) that a previously

submitted HPL C/UV method based on Method Evaluation for the Analysis of AMGT in Grapes (MRID 45593101) undergo an ILV trial, an d potentially , a T MV trial by the ACB. This method was used to measure AMGT residues in the blueberry field trials that theFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 15 of 54 registrant performed. The method procedure and fortification recoveries were discussed in the DER for MRID 46986701. Concurrent recoveries were measured in samples fortified with AMGT at 0.020 ppm, 0.100 ppm, 0.200 ppm, and 1.00 ppm (1 x , 5 x , 10 x , and 50 x the LLM V). Individual recoveries of AMGT (n = 35) ranged from 58 to 125% (see TABLE 6 , below). At each fortification level, av erage recoveries were within the generally recognized acceptable range (70 - 120%) except for 2 samples spiked with 0.020 ppm AMGT (125 and 65% recovery ) and 3 samples spiked with 0.100 ppm AMGT (58, 68, and 68% recovery ). Overall, peaks were well - defined and sy mmetrical in all chromatograms. Three untreated control samples showed identifiable peaks at or near the retention time for AMGT (ranging from 0.0333 to 0.1307 ppm). Treated sample chromatograms showed analy te peaks within the area of analy tical int erest, and no carryover from controls. Calibration curves were not provided for AMGT. Treated and control blueberry samples were stored frozen (at - 21 ± 7°C) for durations of up to 229 days before AMGT analysis. A concurrent freezer storage stability study was conducted in/on blueberry samples fortified with AMGT at 0.15 ppm. Residues in the concurrent freezer storage stability samples remained stable for intervals of 251 days. Therefore, there are no concerns with the stability of residues over time i n this study . TABLE 6 . Summary of Method Validation and Concurrent Recoveries of AMGT fromBlueberries. Crop [Matrix] Recovery

Type 1 Spike Level

(ppm) Sample

Size (n) Recoveries (%) Mean ± Std. Dev. (%) AMGT Blueberry [Berry] MV 0.020 3 110, 95, 100 1 02 ± 8

MV 0.100 3 95, 81, 94 90 ± 8 MV 1.00 3 110, 110, 110 110 ± 0 CR 0.020 5 125 2 , 65, 70, 70, 110 88 ± 28 CR 0.100 27 93, 76, 81, 82, 71, 58, 84, 82, 78, 79, 74, 72, 100 3 , 73 3 , 70, 88, 68 3 , 68 3 , 110 3 , 70 3 , 80, 90,

89, 83, 84, 82, 88 80 ± 11 C R 1.00 1 77 77 CR 0.200 2 95, 80 88 ± 11 1. MV = Method Validation; CR = Concurrent Recovery. 2. High recovery might be due to a slight interference in the peak. 3. After interference found in the untreated sample is subtracted. The registrant request ed that the blueberry submission serve as the ILV for the method. The range of fortification levels and the percent recovery values are acceptable. As a result, HED considers the AMGT analy tical portion of the blueberry field trial study

to be adequate , and that it can serve as the ILV for the analy tical method for AMGT residues in plant commodities.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 16 of 54 Data - collection M ethods Fluazinam Samples collected from the magnitude of the residue and storage stability studies were analy

zed for residues of fluaz inam using GC/ECD methods revised from the plant enforcement method. The GC/ECD methods are adequate for data collection based on acceptable method recover y data included in the reviewed studies . The fortification levels used in the method validation tri als bracket ed the expected field residues. The LLM V was 0.01 ppm in all tested commodities , except in carrots , where the LLMV was 0.02 ppm. AMGT Samples of apple s and apple processed commodities were also analy zed for residues of AMGT using an HPL C/UV m ethod similar to th at reviewed in Memo, D33 5640 , W. Drew, 8/22/2007 . The HPL C/UV method is adequate for data collection based on acceptable method verification and concurrent method recoveries. The validated method LOQ was 0.01 ppm in all apple matrices. Animal commodities DER Reference: 47756602.der.doc (Includes method validation data from MRID 47756605) IS K Biosciences submitted PTRL Method 1676W (MRID 47756602 ) entitled “Fluazinam, AMPA and DAPA Method in Milk and Tissues as Described in ‘Magnitude of Fluazinam Residues in Bovine Tissues and Milk from a 28 - Day Feeding Study . ’ ” Method 1676W was the data - collection method used for the analysis of samples collected from a companion cattle feeding study

(MRID 47756605 ). As a result of a June 30, 2007 meeting between HED and I SK representatives to discuss concerns about the analy tical approach for the feeding study , the method has incorporated a mild acid hydroly sis step to convert the sulfamate conjugates to free AMPA and DAPA. The method is written f or LC/MS/MS analysis of fluazinam, AMPA , and DAPA in bovine milk and tissues, and for GC/MS analysis of DAPA in milk only . The reported method L OQ was 0.01 ppm for each analy te in milk, muscle, fat, liver , and kidney . The method is described briefly

belo w . For milk , a sample was mixed with HCl, and residues were extracted with methanol. The extract was concentrated, and residues were mixed with water and sodium chloride for partitioning with dichloromethane (DCM) or hexane for L C/MS/MS analy sis for fluazinam, AMPA , and DAPA residues, or for GC/MS analy sis of DAPA residues. For muscle , residues were extracted with acetonitrile (ACN)/water, with acetic acid for fluazinam and without acetic acid for AMPA and DAPA. After concentration and/or dilution, the extracts were cleaned up through a solid phase extraction (SPE) column prior to L C/MS/MS analy sis. For fat , residues were extracted with ACN/water with acetic acid, then again with ACN. The combined extract was diluted for partitioning with A CN - saturated cyclohexane. The ACN phase was evaporated and reconstituted for LC/MS/MS analy sis. For analysis of liver and kidney using the non - hydroly sis method ,Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 17 of 54 residues were extracted with ACN/water with acetic acid, then again with ACN/water. The combined extrac t was diluted, concentrated, and mixed in water with sodium chloride for partitioning with DCM prior to L C/MS/MS analy sis. For analy sis of liver and kidney using the hydroly sis method , residues were extracted with ACN/water . T he extract was diluted and c oncentrated prior to the addition of HCl (held for 1 hour at 37°C). Water and sodium chloride were added for partitioning with hexane (liver) or ethyl acetate (kidney ). The hexane phase was concentrated and reconstituted for LC/MS/MS analysis. The L C/MS /MS method cites two transition ions for each analy te in order to provide confirmation. Method validation data, generated by PTRLWest, Inc. (Hercules, CA), were included in the cattle feeding study . Milk was fortified with fluazinam, AMPA, and DAPA at 0 .010 and 0.10 ppm each. Muscle, liver, and kidney were fortified with the same analy tes at levels of 0.01 and 0.05 ppm each. Fat was fortified with fluazinam, AMPA, and DAPA at 0.01, 0.02, 0.1, and 0.5 ppm each. Overall, the results show ed that Method 1 676W adequately recovered residues of fluazinam, AMPA, and DAPA in milk, muscle , and fat. Method recoveries in these matrices were generally

within the acceptable recovery range of 70 - 120%. However, recoveries in liver and kidney

were low and declined wi th an increase in fortification level. For hydroly zed liver, overall mean recoveries of fluazinam, AMPA, and DAPA were 87%, 68%, and 38%, respectively , at a fortification level of 0.01 ppm . O verall mean recoveries of fluazinam, AMPA, and DAPA were 79%, 6 5%, and 34%, respectively , at a fortification level of 0.05 ppm. For hydroly zed kidney , overall mean recoveries of fluazinam, AMPA, and DAPA were 96%, 75%, and 31%, respectively , at a fortification level of 0.01 ppm . O verall mean recoveries of fluazinam, AMPA, and DAPA were 63%, 39%, and 9%, respectively , at a fortification level of 0.05 ppm. The petitioner reported that extensive method development work was performed on liver in an effort to obtain acceptable recoveries for DAPA residues. An ILV of Method 1676W was performed by ADPEN L aboratories, Inc. (Jacksonville, FL) using two fortification levels: at the L OQ (0.01 ppm) and 10x the L OQ. Although minor modification s of the method for some matrices were made to make it more rugged , the ILV was compl eted within three trials . The performing laboratory concluded that , based on a cceptable recoveries of fluazinam , AMPA , and DAPA in milk, beef fat , and beef liver down to a level of 0.01 ppm for each compound , Method 1676W , with minor modifications , is a s uitable method for use on bovine tissues and milk . Inthe first trial, the metho d was successfully validated for fluazinam and AMPA in milk, for AMPA in beef fat , an d for AMPA in the liver non - hydroly sis procedure. Inthe second trial, analysis of fluazi nam and DAPA in beef fat w as successfully completed after communication with the s ponsor and the method developers. Inthe third trial , f luazinam, AMPA , and DAPA in milk and non - hydroly zed liver were successfully completed after minor method modification. The method was forwarded to ACB/BEAD for method validation. ACB/BEAD reported that the lab that performed the ILV made major modifications to the original method. As a result, HED requested that the registrant submit a revised method that incorporated the revisions made by the ILV lab. ISK Biosciences revised the method and re - submitted it. ACB/BEAD performed a cursory review of the revised method. The registrant incorporated the modifications made by the ILV lab. However, the revision eliminated th e cleanup steps that were in the original method,Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 18 of 54 and the only

recovery data for the revised method were data provided by the ILV lab. ACB/BEAD was concerned that the elimination of the cleanup steps could lead to dirty samples which would, in turn, lead to analy tical problems, such as interference. ACB/BEAD performed no further validation of the method. As the revised method contains major revisions to the original method, and ACB/BEAD believes it is very likely that the revised method still is not adequate for sample analysis or tolerance enforcement, HED recommends that the registrant submit an ILV for the revised method. Conclusions . An adequate GC/ECD method (6148 - 91 - 0170 - MD - 001) is available for determination of fluazinam residues in crop matrices . The method has been deemed suitable for tolerance enforcement because it has successfully completed the routes required for an enforcement method , including radiovalidation, ILV trial, and TMV trial. An enforcement method for determination of AMGT in p lants is available. AMGT is a residue of concern for tolerance expression in wine grapes. The registrant requested that the blueberry submission serve as the ILV for the method. The range of fortification levels and the percent recovery values are accep table. As a result, HED considers the AMGT analy tical portion of the blueberry field trial study

to be adequate , and that it can serve as the ILV for the analy tical method for AMGT residues in plant commodities. At the present time, an analy tical metho d is not available for enforcement of fluazinam tolerances in animal commodities. The registrant should submit an ILV of the revised method. This method needs to be adequate for analysis of parent fluazinam as well as the metabolites AMPA and DAPA in ani mal commodities for which tolerances will be established. 860.1360 Multiresidue Methods Parent Fluazinam Reference: Residue Chemistry Memo , D2 5 7115, W. Cutchin, 5/21/01 Data depicting the recovery of fluazinam through FDA multiresidue methods (MRM) we re 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. Data depicting the recovery of AMGT through FDA MRM s were submitted in support of the apple petition. M etabolite AMGT DER Reference: 4775660 3 .der.doc IS K Biosciences submitted multiresidue m ethod testing data for the fluazinam metabolite AMGT following testing and analysis 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 determinin g the response patterns. Metabolite AMGT was tested through ProtocolsFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 19 of 54 A, B, C, D, E, and F . T esting under Protocol G is not required because AMGT is not a substituted urea. The study was conducted by

Colorado Analy

tical R&D Corporation (Colorado Springs , CO). AMGT does not have an N - methylcarbamate structure and was not found to be naturally fluorescent in testing under Protocol A. In Protocol B testing, the methyl ester of AMGT was not recovered from Florisil; therefore, no additional work was perfor med under Protocol B. Protocol C testing of the compound indicated that further testing using Protocols D, E, and F was required for all test substances. The Protocol C results indicated that AMGT was detected using GC with electron capture detect i o n (EC D) and nitrogen phosphorous detection (NPD). Metabolite AMGT was not recovered from grapes (non - fatty matrix) fortified at 0.05 and 0.25 ppm using Protocol D (DB - 1 column with NPD) because of matrix interference. AMGT was not recovered from any

of the F lorisil screens in Protocol E, and Protocol F testing was not performed. These data indicate that FDA multiresidue methods are not suitable for determining residues of the fluazinam metabolite AMGT. The submitted data will be forwarded to U.S. FDA for further evaluation. Conclusions : Adequate FDA MRM testing data are available for fluazinam and 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 confi rmatory procedure for residues of fluazinam. The FDA MRM methods are not suitable for determining residues of AMGT. Multiresidue method testing data are required for the regulated metabolites, AMPA and DAPA, in animals. 860.1380 Storage Stability Residue Chemistry Memo : D2 5 7115 , W. Cutchin, 5/21/01 Residue Chemistry Memo : D335640 , W. Drew , 8/22/07 Plant commodities The storage durations and conditions of crop samples from the submitted magnitude of the residue and processing studies are presented in Table 7 .Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 20 of 54 Table 7 . Sum ma ry of Storage Conditions and Durations of Samples fromCrop Field Trials. Matrix Storage

Tem perature (°C) Actual Storage

Duration (days) Interval of Demonstrated

Storage Stability (days) for Fluazinam Apple , RAC - 24.4 t o - 6.0 40 - 291 1,097 Apple, processed commodities - 20 to - 18 758 - 914 1,09 4 - 1,096 Carrot - 22 to - 4 4 5 0 470 1 Lettuce, head <0 64 - 229 419 1 Lettuce, leaf <0 42 - 214 419 1 Onion < - 6 70 - 418 429 1 1 Storage stability determined from concurrent field trial samples. The available storage stability data from previous fluazinam petitions ind icat e that the stability of fluazinam is variable under frozen conditions , depending on the crop matrix. Fluazinam has been found to be reasonably stable for up to 12 months in grapes and snap beans, 6.7 months in blueberries , and 7.6 months in broccoli. Fluazinam was also stable for up to 36 months in peanut nutmeats, hulls, hay , and oil, but declined by ~60% in meal after 36 months of storage. In potato commodities, flu azinam was stable in frozen chip s for up to 18 months, but declined by 35% in whole potatoes and ≥70% in granules within 18 months . Residues declined by 40% in wet peel within 5 months. Residue declines during storage have also been observed for the following crops: 70% decline in cab bage by 18.3 months, 55% decline in mustard greens by 19 months, 30% decline in ginseng by 11.4 months, 45% decline in dried beans by 10 months, and a 40% decline in lima beans by

15 months. To account for dissipation of residues during frozen storage, HE D incorporated correction factors into the recommended tolerances for fluazinam residues for certain crop commodities. To support the current lettuce , onion , and carrot field trial data, s torage stability studies were conducted in conjunction with the fie ld trials. For each crop , control samples of the respective matrices were fortified w ith f luazinam at 1.0 ppm and placed in storage under the same frozen c onditions as the treated samples. No zero - day analyses were conducted on the fortified samples plac ed 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 duration from the field trials. Average corrected recoveries of f luazinam following f

rozen storage were 73% f rom lettuce after 13.8 months , 86% from onion s after 14.1 months , and 73% from carrots after 15. 5 months . Although no 0 - day analysis was con ducted, the data indicate that f luazinam is stable under frozen storage conditions for up t o 14 months in lettuce and onion and 16 months in carrot. Storage Stability

Data for Apple Fruit, Juice, and Wet Pomace S torage stability

data for fluazinam and its metabolite AMGT in apple fruit, juice, and wet pomace were submitted in support of the ap ple petition. DER Reference: 4775660 4. der.doc IS K Biosciences submitted storage stability data for fluazinam and its metabolite AMGT in apple fruit, juice, and wet pomace. Homogenized untreated s amples of fruit, juice, and wet pomaceFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 21 of 54 were spiked with fluazinam or AMGT at 0.50 ppm, and stored frozen ( - 20 to - 18oC) for up to 37 months. Samples were analy zed initially

(after 0 or 1 day

) and following storage for 1, 2, 3, 6, 12, 18, 30, and 36 months. Samples of apple fruit, juice, and wet pomace were anal yz ed for residues of fluazinam and AMGT . The GC/ECD method used for fluazinam analysis is similar to the current enforcement method for fluazinam in crops. In addition, the HPL C/UV method used for AMGT is similar to the method described in “ Method Evaluation for the Analysis of AMGT in Grapes” (Memo, D335640, W. Drew, 8/22/2007). The methods were adequate for data collection based on acceptable concurrent method recoveries. The reported “limit of detection” (LOD) was 0.025 ppm for each analy

te in apple fruit and wet pomace, and 0.05 ppm for each analy te in apple juice. Residues of fluazinam appear to be relatively stable in/on apple fruit, juice, and wet pomace stored frozen for up to 36 months. Residues of AMGT were relatively st able in/on apple fruit and juice stored frozen for up to 36 - 37 months . R esidues of AMGT declined slightly in apple fruit to an average corrected recovery of 69% at the 36 - month interval. However, AMGT residues in/on apple wet pomace were relatively stabl e for only

12 months of frozen storage. Residues of AMGT declined in wet pomace to an average corrected recovery of 58 - 63% at the 19 - month interval, 61% at the 32 - month interval, and 33% at the 37 - month interval. Storage Stability

Data for Cattle Milk, M eat, and Meat By products Samples collected from the dairy cow feeding study

(MRID 47756605) were held under frozen storage conditions prior to residue analysis. The maximum storage durations of samples, from collection to analysis, were 146 days for milk , 185 days for cream, 179 days for skim milk, 157 day s for muscle, 203 day s for fat, and 255 days for liver and kidney . A storage stability study was conducted to validate sample storage conditions and duration s. The results showed mixed results. Inmil k, cream, and skim milk, residues of fluazinam, AMPA, and DAPA were found to be stable for 183 days. In muscle: (i) fluazinam was stable for 1 day , but declined after 164 days to an average corrected recovery of 55%; (ii) AMPA was stable for 2 days, but declined after 161 day s to an average corrected recovery of 41%; and (iii) DAPA was stable for 2 days, but declined after 161 days to an average corrected recovery of 10%. Infat: (i) f

luazinam and AMPA were stable for 205 days; and (ii) DAPA showed relative instability with average corrected recoveries of 64% after 205 days. Inliver and kidney : (i) fluazinam was un stable , average recoveries in liver were 26 - 34% after 210 days , and 41 - 44% in kidney after 218 days; (ii) AMPA was stable in liver for 80/8 9 day s , but not in kidney wh ere average corrected recoveries were 53 - 58% after 218 day s; and (iii) DAPA is not stable with average corrected recoveries of 43 - 52% in liver after 209 day s and 17 - 25% in kidney after 218 days. Conclusions . Adequate storage s tability data are available to support the storage conditions and durations of samples collected from the magnitude of the residue studies on apples, carrots, lettuce , and onions . As residues of fluazinam w ere found to be stable in tested crop matrices , s torage stability

corrections do not need to be applied to the recommended tolerances for fluazinam residues in/on apples, carrots, lettuce, and onions. Storage stability data for the fluazinam metabolite AMGT in apple commodities we re also submitted and s howed thatFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 22 of 54 residues in apple wet pomace were reasonably stable for 12 months in apple wet pomace , but declined to an average corrected recovery of 33% at the 37 - month interval . The submitted storage data for bovine milk, meat, and meat by products showed m ixed results. Because of major data deficiencies, HED is not recommending in favor of tolerances on apple and carrot commodities. It is very

possible that the registrant will resolve the deficiencies and re - submit the tolerance petitions. As a result, H ED has determined the maximum reasonable dietary burdens for livestock based on the assumption that tolerances will be established for apples and carrots. 860.1400 Water, Fish, and Irrigated Crops There are no proposed uses that are relevant to this guid eline topic. 860.1460 Food Handling There are no proposed uses that are relevant to this guideline topic. 860.1480 Meat, Milk, Poultry, and Eggs Li vestock D ietary B urdens The livestock feedstuffs associated with the proposed uses discussed in this summary document are wet apple pomace and carrot culls. The livestock feedstuffs associated with registered crops include peanut meal and processed potato waste. F luazinam is registered for use on Subgroup 6A, the Edible - podded legume vegetables subgroup. However, the approved label excludes the use o n peas; therefore, feedstuffs derived from peas were not considered for dietary burden calculations. The maximum reasonable dietary burdens of fluazinam t o livestock are presented in Table 8 . The calculated d ietary burdens of fluazinam are 0.04 p p m for beef cattle, 1. 2 7 ppm for dairy cattle, 0.005 ppm for poultry , and 0.003 ppm for swine. Table 8 . Calculation of Dietary Burdens of Fluazinam Residues to Livestock. Feedstuff

1 Ty pe 1 % Dry Matter2 % Diet2 Tol erance (ppm) Dietary Contribution (ppm) 3 Beef Cattle R not registered R -- 15 -- -- Potato, processed waste CC 15 30 0.02 0.04 CC not registered CC -- 50 -- -- PC not registered PC -- 5 -- -- TOTAL BURDEN -- -- 100 -- 0.04 Dairy Cattle R not regist ered R -- 45 -- -- Apple, wet pomace CC 40 10 5 .0 1 . 2 5 Potato, processed waste CC 15 10 0.02 0.013 CC not registered CC -- 25 -- -- Peanut, meal PC 85 10 0.02 0.002Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 23 of 54 Table 8 . Calculation of Dietary Burdens of Fluazinam Residues to Livestock. Feedstuff

1 Ty pe 1 % Dry Matter2 % Diet2 Tol erance (ppm) Dietary Contribution (ppm) 3 TOTAL BURDEN -- -- 100 -- 1.27 Poultry CC not registered CC -- 75 -- -- Peanut meal PC 85 25 0.02 0.005 TOTAL BURDEN -- -- 100 -- 0.005 Swine CC not registered CC -- 85 -- -- Peanut meal PC 85 15 0.02 0.003 TOTAL BURDEN -- -- 100 -- 0.003 1 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate. 2 OPPTS 860.1000 Table 1 Feedstuffs ( June 2008 ). 3 Contribution = ( ( tolerance )  ( % DM )) x ( % of diet) for beef and dairy cattle C ontribution = ( ( tolerance ) x ( % of diet) ) for poultry and swine. Dairy C attle F eeding S tudy DER Reference: 47756605.der.doc Fourteen lactating Holstein cows were divided into four treatment groups. Three groups w ere dosed orally

with gelatin capsules containing fluazinam at target levels of 2.5 ppm (three cows), 7.5 ppm (three cows), and 25 ppm (six cows) in the feed (dry weight basis ) for 28 consecutive day s . T he fourth group , consisting of two cows , served as a control. Based on feed consumption data, the actual dosing levels were 2.91, 8.72, and 28.84 ppm. Fluazinam was weighed directly into gelatin capsules , and the c apsules wer e administered using a balling gun, once per day after the morning feeding. One control cow and three cows dosed at 25 ppm were reserved to investigate the depuration of residues in cow’s milk and tissues. Milk was collected twice daily on Day s 0, 1, 3, 4, 5, 6, 7, 10, 13, 16, 19, 22, 25, and 28. In addition, extra milk samples from one control animal and three cows from the 2.91 - and 28.84 - ppm dose groups were collected on Study Day s 13 and 28 to produce data on skim milk and cre am. Cows from the three treatment groups were sacrificed ≤ 24 hours after the final dose administration. One cow from the depuration group was sacrificed on Study Day s 30, 32, and 36. At sacrifice, samples of liver, kidney , fat (s ubcutaneous , abdominal, and perir enal ), and muscle (leg and loin) were collected from each anima l . Samples of milk plus cream , skim milk, muscle, liver, kidney , and fat were analy zed using PTRL Method 1676W entitled “Fluazinam, AMPA and DAPA Method in Milk and Tissues as Descri bed in Magnitude of Fluazinam Residues in Bovine Tissues and Milk from a 28 - Day Feeding Study , ” which was included in Appendix B of the feeding study . This method has not been reviewed by

the PMRA or the USEPA. The method is written for L C/MS/MS analy sis of fluazinam, AMPA , and DAPA in bovine milk and tissues, and for GC/MS analysis of DAPA inFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 24 of 54 milk only . The method has a mild acid hydroly sis step for analysis of some matrices (milk, liver, and kidney

) to convert the sulfamate conjugates to free AMPA and DAPA . The method limit of quantitation ( LOQ ) was 0.01 ppm for each analy te in milk and tissues . The initial validation of Method 1676W showed that it adequately recovered residues of fluazinam, AMPA, an d DAPA in milk and fat. In muscle, recoveries in mo st were acceptable. Mean recoveries of fluazinam, AMPA, and DAPA at the 0.01 ppm spiking level were 82%, 9 6 % and 9 0% , respectively . Mean recoveries of fluazinam, AMPA, and DAPA at the 0.05 ppm spiking level were 66% , 9 5% , and 95%, respectively . R ecoveri es of AMPA and DAPA in liver and kidney were low. Recoveries of fluazinam from non - hydroly zed kidney

samples were also low. The results of concurrent method validation also show ed similar low recoveries of the metabolites in liver and kidney . Mean recov eries of AMPA ranged from 48 to 93% in hydroly zed liver and from 36 to 7 5 % in hydroly zed kidney . Mean recoveries of DAPA ranged from 35 to 51% in hydroly zed liver and from 9 to 33% in hydroly zed kidney . Because of low recoveries, the petitioner corrected residues in cow liver and kidney

for concurrent method recoveries <70%. According to the petitioner, correspondence with I SK’s Central Institute in Japan indicates that, based on their experience with a variety

of matrices, DAPA is easily oxidized and e asily

absorbed to protein and organic matter. This information is consistent with the observed instability and the difficulty

experienced with recovering DAPA from some matrices. Samples were held under frozen storage conditions prior to residue analys is. Refer to the s torage s tability section of this memorandum for information pertaining to sample storage duration as well as supporting storage stability data. As Method 1676W gave very poor recovery

for AMPA and DAPA in liver and kidney , the method ne eds to be revi s ed and the feeding study needs to be repeated. When the feeding study is repeated, the samples need to be analy zed as soon as possible after sacrifice in order to minimize degradation of residues. In muscle, fluazinam declined by

45%, AMPA by

59%, and DAPA by

90% after 161 - 164 day s. In fat , f luazinam and AMPA were stable while DAPA declined by 36% after 205 days. In liver, fluazinam declined by as much as 74% after 210 days, AMPA was stable , and DAPA declined by 57% after 209 days. In ki dney , fluazinam declined by 59% after 218 days , AMPA declined by 47% , and DAPA declined by

83% after 218 days. The m aximum residues of concern in cow milk and tissues at the dose level closest to the maximum reasonabl y balanced diet ( M RB D) , uncorrected an d corrected for storage stability recoveries, are summarized in Table 9 . Residues in milk increased until about Day 5 and were essentially

stable beyond that time.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 25 of 54 Table 9 . Results of a Dairy Cattle Feeding Study with Fluazinam . Matrix Feeding Level 1 Maximum Uncorrected Residues for

Storage Decline Maximum Corrected Residues for Storage Decline 2 Parent AMPA DAPA Total Parent AMPA DAPA Total Milk (Days 0 - 28) 8.72 <0.01 <0.01 <0.01 <0.03 -- -- -- -- Cream 28.84 <0.01 0.0582 0.1200 <0.19 -- -- -- -- Skim milk 28.84 <0.01 <0.01 <0.01 <0.03 -- -- -- -- Muscle (loin) 28.84 <0.01 0.0101 0.0179 <0.0 4 <0.0 18 <0.0 25 <0. 179 <0. 222 Muscle (round) 28.84 <0.01 <0.01 <0.01 <0.03 <0.018 <0.024 <0.100 <0.142 Liver (hydrolysis method) 2.91 <0.01 <0.01 <0.01 < 0.03 <0.0 38 <0.01 <0.0 23 <0.0 71 Liver (non - hydrolysis method) 2.91 <0.01 <0.01 <0.01 <0.03 <0.038 <0.01 <0.023 <0.071 Kidney (hydrolysis method) 2.91 <0.01 <0.01 <0.01 <0.03 <0.024 <0.019 <0.059 <0.102 Kidney (non hydrolysis method) 2.91 <0.01 <0.01 <0. 01 <0.03 <0.0 24 <0.0 19 <0.0 59 <0. 102 Fat, perirenal 2.91 <0.01 <0.01 <0.01 <0.04 <0.01 <0.01 <0.0 16 <0.0 36 Fat, abdominal 2.91 <0.01 0.0169 0.0219 <0.05 <0.01 0.0169 <0.0 34 <0.0 61 Fat, subcutaneous 2.91 <0.01 <0.01 0.0107 <0.03 <0.01 <0.01 0.0167 <0.0 37 1 Dose level closest to the M RB D or only dose level represented. 2 Individual residues were corrected for decline w hile in storage. Correcting residues for decline was made by dividing uncorrected residues by ( 100% - % decline ) . For milk, cream, and skim milk, no correction of individual residues was made. For muscle: fluazinam declined by 45%, AMPA by 59%, and DAPA by 90% after 161 days. For fat: fluazinam and AMPA were stable while DAPA declined by 36% after 205 days. F or liver: fluazinam dec lined by as much as 74% after 210 days, AMPA was stable, and DAPA declined by 57% after 209 days. For kidney: fluazinam declined by 59% after 210 days, AMPA declined by 47% , and DAPA declined by 83% after 218 days. For the depuration study , total resid ues were not observed at levels higher than the combined LOQ (0.03 ppm) by

Day 29, one day

after dosing was discontinued. Total residues in tissues, except fat, of the animals sacrifice d on Day s 29, 31, and 35 after the last dose administration were all b elow the combined L OQ (0.03 ppm). In fat of animals sacrificed on Day 35, total residues were <0.031 ppm in perirenal fat, <0.053 ppm in abdominal fat, and <0.051 ppm in subcutaneous fat. Expected S econdary R esidues in M ilk, M eat, and M eat B yp roducts To determine the need for tolerances for the combined residues of flu azinam, AMPA, DAPA, and their sulfate conjugates in milk and tissues, the anticipated secondary residues in cattle matrices were estimated using transfer coefficient factors calculated from the maximum combined residues of flu azinam observed at the dose level closest to the reasonabl y balanced dietary burden in the dairy

cattle feeding study . The transfer coefficients (calculated as residue level to feed level ratios) are presented in Table 10 . The transfer coefficient for each matrix was then used to calculate the expected secondary residues by

multiplying the transfer coefficient by the calculated dietary

burden. The expected combined residues and the recommended tolerances based on expe cted residues are presented in Table 1 1 .Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 26 of 54 Table 10 . Residue - Level - to - Feed Ratios (Transfer Coefficients) in Dairy Cattle Milk and Tissues . Matrix Total Residues (Fluazinam + AMPA + DAPA, and Their Sulfamate Conjugates) in ppm Feeding Level (ppm) Tr ansfer

Coefficient 2 Uncorrected Corrected for Storage

Decline 1 Milk (Day 0 to Day 28) <0.03 <0.03 8.72 <0.0034 Cream <0.19 <0.19 28.84 <0.0066 Skim milk <0.03 <0.03 28.84 <0.0010 Muscle (loin) <0.04 <0.22 28.84 <0.007 7 Muscle (round) <0.03 <0.14 28.84 <0.00 49 Liver (hydrolysis method) <0.03 <0.07 2.91 <0.0 244 Liver (non - hydrolysis method) <0.03 <0.07 2.91 <0.0 244 Kidney (hydrolysis method) <0.03 <0.10 2.91 <0.0 351 Kidney (non - hydrolysis method) <0.03 <0.10 2.91 <0.0351 Fat, perirenal <0.04 < 0.04 2.91 <0.012 4 Fat, abdominal <0.05 <0.06 2.91 <0.0 210 Fat, subcutaneous <0.03 <0.04 2.91 <0.01 26 1 Individual residues were corrected for decline while in storage. For milk, cream, and skim milk, no correction was necessary . 2 Calculated from th e maximum corrected residues at the dose level closest to the M RB D divided by the dose level. Table 1 1 . Expected Total FluazinamResidues of Concern in Meat and Milk. Matrix Dietary Burden (ppm) Total Residues 1

(ppm) T olerance (ppm) Dairy Cattle M ilk (Day 0 to Day 28) 1.27 < 0.00 43 Not required Cream 1.27 < 0.00 84 Not required Skim milk 1.27 < 0.00 13 Not required Muscle (loin) 1.27 < 0.00 98 Not required Muscle (round) 1.27 < 0.00 62 Not required Liver (hydrolysis method) 1.27 <0.0 310 A tolerance of 0.0 5 ppm is considered to be a reasonable upper - bound estimate for meat byproducts based on expected residues i n kidney 2

. This tolerance level is also considered to be a reasonable upper - bound estimate for fat. Liver (non - hydrolysis method) 1.27 <0.0 310 Kidney (hydrolysis method) 1.27 <0.0 446 Kidney (non - hydrolysis method) 1.27 <0.0 446 Fat, perirenal 1.27 <0.0 157 Fat, abdominal 1.27 <0.0 267 Fat, subcutaneous 1.27 <0.0 160 Swine Liver 0.003 0.0000 7 Not required Kidney 0.003 0.00011 Not require d Muscle 0.003 0.0000 2 Not required Fat 0.003 0.0000 6 Not required 1 Calculated from dietary burden x transfer coefficient from Table 9 . 2 According to the July 18, 2007 Minutes of the Chemistry Science Advisory Council Meeting, t he ChemSAC recomme nded that the guidance document be revised to include language detailing the use of the highest residue data for any tissue (liver, kidney, fat, skin , or muscle) to determine the tolerance for meat byproducts. A single tolerance on “meat byproducts” will be recommended based on that highest residue , and individual tolerances will no longer be set on liver, kidney, or meat byproducts (except liver and kidney).Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 27 of 54 Conclusions . Based on the poor recoveries of metabolites AMPA and DAPA from liver and kidney and the mixed storage stability results, the residue data from the cattle feeding study are not adequate to satisfy

data requirements. The feeding study data (adjusted for residue decline) along with the calculated dietary burdens for beef cattle (0.04 ppm) and dairy cattle ( 1.27 ppm) indicate that tolerances might be needed for the combined residues of fluazinam and its metabolites DAPA and AMPA in the fat and meat by products of cattle and other ruminants at 0.0 5 ppm to support the proposed use on apples. T he feeding study also indicates that tolerances probably will not be needed for milk and meat of ruminants , as the expected combined residues in these matrices are below the combined method L OQ of 0.03 ppm for the regulated compounds . Based on the transfe r coefficients for livestock tissues and the relatively low dietary burden for swine of 0.003 ppm for fluazinam, tolerances for hogs are not needed. A poultry feeding study

is not required at this time because of low dietary burden for poultry

(0.005 ppm) . To support tolerances for apples and carrots, the registrant needs to submit a new cattle feeding study in which a method with better recoveries of AMPA and DAPA from liver and kidney was used . When this study

is repeated, the samples need to be analy z ed as soon as possible after sacrifice in order to minimize degradation of residues . 860.1500 Crop Field Trials DER Reference s : 47631001.der .doc ( Bulb Onion)

4763100 2 .der .doc ( Leaf and Head Lettuce) 47755601.der.doc (Carrot) 47756609.der.doc ( Appl es : 2006 Trials) 47756606.de 1 .doc (Apples: 1992 - 1994 Trials , Include s MRIDs 47756607, 47756608, 47756610, and 47756611) IR - 4 and I SK Biociences Corporation have submitted magnitude of the residue studies on apples, carrots, lettuce, and onions. The results from these field trials are discussed below , and the residue data are summarized in Table 1 2 . Table 11 . Summary of Residue Data fromCrop Field Trials with Fluazinam . Crop M atrix Total Applic.

Rate ( lb ai/A) [kg ai/ha] PHI

(days) Residue s of Fluazinam (ppm) 1

n Min. Max. HAFT 2 Median Mean Std. Dev. Head Lettuce (proposed use = 1 . 0 lb ai/A total application rate, 50 - day PHI) Lettuce, h ead 0.952 - 1.02 46 - 52 14 < 0.01 0.021 0.016 0.010 0.011 0.010

Leaf Lettuce (proposed use = 1. 0 lb ai/A total application rate, 30 - day PHI) Lettuce, leaf 0.974 - 1.05 20 - 32 14 < 0.01 1.690 1.570 0.021 0.260 0.010Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 28 of 54 Table 11 . Summary of Residue Data fromCrop Field Trials with Fluazinam . Crop M atrix Total Applic.

Rate ( lb ai/A) [kg ai/ha] PHI

(days) Residue s of Fluazinam (ppm) 1

n Min. Max. HAFT 2 Median Mean Std. Dev. Onion s (proposed use = 3.1 lb ai/A total application rate, 7 - day PHI) Onion , dry bulb 3.11 - 3.17 6 - 8 18 < 0.01 0.101 0.098 0.014 0.027 0.028

Carrot s (proposed use = 2. 1 lb ai/A total application rate, 7 - day PHI) Carrot root 2.04 - 3.03

[2.29 - 3.40] 6 - 8 52 <0.02 0.56 0.51 0.10 0.14 0.13 Apples (proposed use = 4.5 lb ai/A total application rate, 28 - day PHI) Apples 3 4.44 - 4.77

[4.98 - 5.34] 28 - 29 24 0.02 1.75 1.75 0.15 0.38 0.58 Apples 4 3.97 - 5.40

[4.45 - 6.05] 28 - 32 16 <0.01 0.06 0.06 0.03 0.03 0.02 1 AMGT was measured in apples and the maximum residue value for this metabolite was 0.03 ppm. 2 HAFT = highest average field trial result. 3 Results of trials conducted during the 2006 growing season (MRID 47756609). 4 Results of trials conducted during the 1992 - 1994 growing season s (MRIDs 47756606, 47756607, 47756608, 47756610, and 47756611). Head and Leaf Lettuce. In fourteen field trial s conducted in the United States in EPA Growing Zones 2, 3 , and 10 during 2005 - 2006, 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 harvest ed at commercial maturity , 46 - 52 day s after application (DAT) for head lettuce and 20 - 32 DAT for leaf lettuce. Head and leaf lettuce samples were stored at ≤0°C for up to 7.6 months prior to extraction for analysis. The storage conditions and duration are supported by the available storage s tability data . Residues of fluazinam in/on lettuce were determined using an adequate GC/ECD method (6148 - 91 - 0170 - MD - 001, modified), which has a calculated L OQ of 0.007 ppm, and a L OD of 0.002 ppm. The LLMV in/on le ttuce was 0.01 ppm. Following a single foliar application of fluazinam (FlC) to lettuce at a rate of 0.952 - 1.05 lb ai/A (1x), residues of fluazinam were <0.01 - 0.021 ppm in/on 14 head lettuce samples harvested at 46 - 52 DAT, with only

one sample (0.021 ppm) having residues above the LLMV. For leaf lettuce, residues were <0.01 - 1.69 ppm in/on 14 samples harvested at 20 - 32 DAT, with only 2 samples having residues <LLMV. For head lettuce, average residues were 0.011 ppm and the highest average field trial (HAF T) residues were 0.016 ppm. For leaf lettuce, average residues were 0.26 ppm and the HAFT residue w as 1.57 ppm. No residue decline study was conducted . In addition, samples were not analy

zed for residues of AMGT, as required for dietary risk assessment.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 29 of 54 Bulb Onion Subgroup (3 - 07A) . Innine field trials conducted in the United States in EPA Growing Zones 1, 5, 6, 8, 10, 11 , and 12 during 2005 - 2006, fluazinam (4.17 lb/gal FlC) was applied to bulb onions as six broadcast foliar applications during vegetative development and bulb formation at rates of 0.495 - 0.563 lb ai/A/application and RTI s of 5 - 8 day s, for a total of 3 . 11 - 3 . 17 lb ai/A (1x the proposed maximum seasonal rate). Applications were made using ground equipment in volumes of 19 - 60 gal/A, and no adjuvants were used. Single control and duplicate treated samples of onion bulbs were harvested at commercial maturity, 6 - 8 DAT. Onion bulb samples were stored at ≤ - 6°C for up to 13.9 months prior to extraction for analysis . The storage conditions and duration are supported by the available storage stability data . Residues of fluazinam in/on bulb onions were determined using an adequate GC/ECD method (6148 - 9 4 - 0170 - MD - 001, modified), which has a calculated L OQ of 0.011 ppm, and a L OD of 0.004 ppm. The LLM V in/on onion was 0.01 ppm. Following six broadcast foliar applications of fluazinam (FlC) to onions at rates totaling 3.11 - 3.17 lb ai/A (1x), residues of fluazinam were <0.01 - 0.101 ppm in/on 18 onion bulb samples harvested at 6 - 8 DAT, with 7 samples having residues <0.01 ppm. Average residues were 0.027 ppm and the HAFT residues were 0.098 ppm. In the residue decline trial, average fluazinam residues declined steadily from 0.085 ppm at 0 DAT to <0.01 ppm by 14 DAT. Carrot s : Thirteen carrot field trials were conducted in the United States and Canada in NAFTA Growing Zones 1A, 3, 5, 5B, 6, 10, and 11 during the 2005 and 2006 growing seasons. At each test location, Omega 500F (U.S. trials) or Allegro 500F (Canadi an trials), a 4.17 lb/gal flowable sus pension concentrate ( FlC ) formulation of fluazinam was applied to carrot plants as four broadcast or directed foliar applications (five applications were made in one trial ) during vegetative development at rates of 0.492 - 0.786 lb ai/A/application (0.551 - 0. 881 kg ai/ha/application) and RTI s of 6 to 9 days, for a total rate of 2.04 - 3.03 lb ai/A (2.30 - 3.40 kg ai/ha; 1.0 - 1. 4 x the proposed maximum seasonal rate). Applications were made using ground equipment in volumes of 24 - 60 gal/A (220 - 560 L/ha), and no adjuvants were used. One untreated p l ot and two treated plots were used at each site. Each treated plot received treatments in similar rates and volumes; however, one treated plot was irrigated within two hours of each application, and the other treated plot received no irrigation for at least 24 hours after each application. Duplicate treated and untreated samples of carrot root were harvested at commercial maturity at a 6 - to 8 - day

PHI . Additional samples were harvested at 1, 13, and 20 - day PHI s at the Re verside, CA trial site to assess residue decline behavior. Samples of carrot root were stored frozen for up to 450 days (14.8 months) between harvest and analysis. Concurrent storage stability data were provided demonstrating the relative stability of fluazinam in/on carrot root for up to 470 days (15.5 months) of frozen storage. However, zero day data were not provided . S torage stability studies should always include a zero - day sampling interval to establish the residue levels present at the time sampl es are placed into storage ( see OPPTS 860.1380(d)(6)(i) ) . Residues of fluazinam in carrot root samples were determined using the gas chromatography / electron capture detect i o n (GC/ECD) Method YARL - 0605A (Method No. 94 - 017 in PMRAFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 30 of 54 #1407042). The modified method was adequate for data collection based on acceptable method validation and concurrent recoveries. The validated limit of quantitation (L OQ; or the LLM V) was 0.02 ppm. The calculated L OQ was 0.024 ppm . The calculated limit of detection (L OD) was 0 .0081 ppm. Following four foliar applications of the 4.17 lb/gal FlC formulation of fluazinam to carrots at total rates of 2.04 - 2.94 lb ai/A (2.29 - 3.29 kg ai/ha ; 1 .0 - 1.4 x application rates ) with irrigation within 2 hours of the last application, residues of fluazinam ranged <0.02 - 0.56 ppm in/on 26 carrot root samples harvested at a 6 - to 8 - day PHI . Residues of fluazinam ranged from <0.02 - 0.45 ppm following applications at 2.04 - 3.03 lb ai/A (2.29 - 3.40 kg ai/ha ; 1.0 - 1.4x ) with irrigation withheld for at lea st 24 hours following the last application. Fluazinam residues from each treatment pattern were comparable: the average residues for carrot samples receiving irrigation within 2 hours or after 24 hours of the final application were 0.15 and 0.12 ppm, res pectively , and the HAFT residues were 0.51 and 0.43 ppm, respectively . In the residue decline trial, average residues of fluazinam in/on carrot roots declined from the 1 - to the 8 - day PHI(from 0.67 to 0.15 ppm), increased at the 13 - day PHI(0.36 ppm) and declined slightly at the 20 - day PHI (0.34 ppm) for the early- irrigation treatment pattern. F or the late - irrigation treatment pattern, average residues declined from the 1 - to the 8 - day PHI(from 0.53 to 0.21 ppm), increased at the 13 - day

PHI(0.45 ppm), then declined again at the 20 - day PHI(0.33 ppm). Apples (MRID 47756609 ): Twelve apple field trials were conducted in the United States and Canada in NAFTA Growing Zones 1, 5 A, 5B , 9, 10, and 11 during the 2006 growing season. At each test location, cons isting of one untreated and one treated plot, a 4.17 lb/gal FlC formulation of fluazinam was applied to apple trees (ages 5 - 38 years) as ten airblast foliar applications during fruit development at rates of 0.435 - 0.713 lb ai/A/application (0.488 - 0.799 kg a i/ha/application) and RTI s of 6 to 8 days, for a total rate of 4.44 - 4.77 lb ai/A (4.98 - 5.34 kg ai/ha). The identical product was used in both the U.S. and Canadian trials. In the U.S., the name of this product is Omega 500F , and in Canada, the name of th is product is Allegro 500 F. Applications were made using ground equipment (tractor or backpack sprayer) in volumes of 51 - 152 gal/A (480 - 1420 L/ha), and no adjuvants were used. Duplicate treated and untreated samples of apple fruit were harvested at comm ercial maturity at a 28 - or 29 - day

PHI . At two trials, additional samples were harvested at 0 - , 7 - , 14 - , and 21 - day PHI s to evaluate residue decline. Samples of apple fruit were stored frozen for up to 144 days (4.7 months) between harvest and analysis. A dequate storage stability data are available (refer to the DER for MRID 4 7756604 ) for fluazinam and AMGT to support the storage conditions and durations of apple samples discussed in this summary

document . These data indicate that residues of fluazinam and AMGT appear to be relatively

stable under frozen storage in apple fruit for up to 36 months. The GC/ECD method used for fluazinam analysis is similar to the current enforcement method for fluazinam in crops. In addition, the HPL C/UV method used for AMGT is similar to the method described in “ Method Evaluation for the Analysis of AMGT in Grapes” (Memo, D335640, W. Drew, 8/22/2007). The methods used for fluazinam and AMGT were adequate for data collection based on acceptable method validation and con current recovery data. The validated L OQ was 0.01 ppm for each analy te in apple fruit; the calculated L OQs were 0.011 andFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 31 of 54 0.017 ppm, respectively , for fluazinam and AMGT. The calculated L ODs were 0.0031 and 0.0055 ppm for fluazinam and AMGT, respectively , in apple fruit. Following ten foliar airblast applications of the 4.17 lb/gal FlC formulation of fluazinam to apples at total rates of 4.44 - 4.77 lb ai/A (4.98 - 5.34 kg ai/ha; 1.0 - 1. 1 x), maximum residues of fluazinam were 1.75 ppm and maximum residues of AMGT were 0.03 ppm. In the residue decline trials, residues of fluazinam in/on apple fruit declined from the 0 - and 7 - day PHI s to the 28 - or 29 - day

PHI . Inone trial, the 0 - day samples were not analy

zed. Apples (MRIDs 47756606, 47756607, 47756608, 47756 610, and 47756611): Eight apple field trials were conducted in the United States and Canada in NAFTA growing Zones 1, 1A, 2, 5, and 5 A during the 1992, 1993, and 1994 growing seasons. Three additional trials were conducted in Zones 10 (CA; 1 trial) and 1 1 (WA; 2 trials); however, these trials were conducted at lower total application rates (2.17 - 3.15 lb ai/A) and a longer PHI(90 days). At each test location , consisting of one untreated plot and one treated plot , a 4.17 lb/gal FlC formulation of fluazinam was applied to apple trees (age s 6 - 30 years) as 9 to 12 (5 to 7 for the WA and CA trials) airblast foliar applications during fruit development at rates of 0.43 - 0.48 lb ai/A/application (0.48 - 0.54 kg ai/ha/application) and RTI s of 7 to 23 days . The tota l application rates ranged from 3.97 - 5.40 lb ai/A (4.45 - 6.05 kg ai/ha ; 0.9 - 1.2x the proposed maximum seasonal rate ). At the other three trials, 5 to 7 airblast foliar applications were made at rates of 0.43 - 0.45 lb ai/A/application (0.48 - 0.50 kg ai/ha/app lication) and RTI s of 4 to 15 days, for a total rate of 2.17 - 3.15 lb ai/A (2.43 - 3.53 kg ai/ha). Applications were made using ground equipment (tractor - mounted sprayer) in volumes of 72 - 184 gal/A (673 - 1721 L/ha), and no adjuvants were used. Two additional plots were established at the PA site, one treated at a low spray volume (~20 - 21 gal/A ( 191 - 197 L/ha) ) and the other at twice the nominal rate (0.9 lb ai/A ( 1.0 kg ai/ha) ) and a dilute spray volume (195 - 198 gal/A ( 1824 - 1852 L/ha) ). Duplicate treated and untreated samples of apple fruit were harvested at commercial maturity at a 28 - to 32 - day

PHI . Samples were stored frozen for up to 291 days (9.6 months) prior to determination of residues of fluazinam. For AMGT analysis, four samples from the 1992 trial s were stored frozen for up to 1189 days (39.1 months) and twenty- two samples from the 1993 - 1994 trials were stored frozen up to 797 days (26.2 months) . The submitted storage stability data for fluazinam and AMGT are adequate to support the storage durati ons and conditions of samples from the apple field trials (refer to the DER for MRID 47756604) . Although apple samples from the 1992 trials were stored longer than 36 months prior to AMGT analysis, the submitted storage stability data are adequate to supp ort the storage durations and conditions of samples from the apple field trials a s the majority

of samples were stored less than 36 months , and residues in these samples are comparable. The GC/ECD method used for fluazinam analysis is similar to the curre nt enforcement method for fluazinam in crops. In addition, the HPL C/UV method used for AMGT is similar to the method described in “ Method Evaluation for the Analysis of AMGT in Grapes” (Memo, D335640, W. Drew, 8/22/2007). The methods used for fluazinam and AMGT were adequate for data collection based on acceptable method validation and concurrent recovery data. The validated L OQ was 0.01 ppm for each analy te in apple fruit.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 32 of 54 Following 9 to 12 foliar airblast applications of the 4.17 lb/gal FlC formulation of fluazinam to apples at total rates of 3.97 - 5.40 lb ai/A (4.45 - 6.05 kg ai/ha), maximum residues of fluazinam were 0.0 8 ppm and maximum residues of AMGT were 0.02 ppm. Residue decline data were not generated for these trials, but are available in the 20 06 apple field trial data (refer to the DER for MRID 47756609). Inthe PA trial performed at a total application rate of 9.0 lb ai/A (10.1 kg ai/ha), the fluazinam residue levels were 0.08 and 0.10 ppm and the AMGT residue levels were 0.01 and <0.01 ppm. Bushberry subgroup 13 - 07B . IR - 4 submitted a request to rev ise the established 7.0 - ppm tolerances for fluazinam residues in/on the B ushberry subgroup 13B and other bushberry ty pe crops (aronia berry , buffalo curr ant, Chilean guava, European barberry , highbush cranberry , edible honeysuckle, jostaberry , Juneberry , lingonberry , native currant, salal, sea buckthorn) . These tolerances were originally established under PP# 6E7137 ( Memo, D335640, W. Drew, 8/22/07). IR - 4 is requesting that a single tolerance be established for the B ushberry subgroup 13 - 07B for residues of fluazinam at a level of 4.5 ppm. No new residue data were submitted in support of the tolerance amendment request. The original blueberry residue data for fluazinam per se were entered into the tolerance spreadsheet. HED conclude s that the residue data for fluazinam from the blueberry field trials are distributed lognormally . Therefore, the recommended tolerance for the bushberry subgroup is 7.0 ppm, which is equivalent to the current tolerance for blueberries. Therefore, the recommended tolerance for the revised B ushberry subgroup 13 - 07B is also 7 .0 ppm. Conclusions . With the exception of the use of adjuvants (see 860.1200), the submitted field trial data for fluazinam on head lettuce, l eaf lettuce, bulb onions , carrots, and apples are a cceptable and support the proposed uses. Adequate number s of tests were conducted in the appropriate geographic regions at ~1x the maximum proposed rate , and the appropriate samples were collected from ea ch test at, or close to, the proposed PHI . Samples from all the field trials were analy zed for fluazinam residues using an adequate GC/EC D method, and the storage stability data support the sample storage duration s for these crops. However, no residue data were provided on AMGT residues in lettuce. Although, AMGT residue data on lettuce are still required for purposes of dietary risk assessment, the available data support tolerances of 0.0 2 ppm for head lettuce, 2.0 ppm for leaf lettuce, 0.20 ppm for the bulb onion ( S ubgroup 3 - 07A), 1.7 ppm for apple, and 0.7 ppm for carrot. For dietary risk assessment, HED will calculate AMGT residues in lettuce using a ratio of 0.35:1 for AMGT:fluazinam residues (ChemSAC Memo, meeting of 2/6/08) . However, the samples from the lettuce field trials still need to be analy zed for residues of AMGT. After reevaluating the available residue data for blueberries, HED conclude s that the residue data for fluazinam from the blueberry field trials are distributed lognormally . Th erefore, the recommended tolerance for the B ushberry subgroup 1 3 - 07B is 7 .0 ppm.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 33 of 54 860.1520 Processed Food and Feed DER Reference: 47756606.de 2 .doc (Include s MRIDs 47756610 and 47756611) Apples : Ina single crop field trial conducted in NY during the 19 93 growing season, a 4.17 lb/gal FlC formulation of fluazinam was applied to mature apple trees as ten foliar airblast applications at a rate of 0.45 lb ai/A/application (0.50 kg ai/ha/application), with 7 - to 14 - day RTI s, for a total rate of 4.50 lb ai/A (5.04 kg ai/ha; 1x the proposed maximum seasonal rate). The first application was made when fruit development was at the green tip growth stage, with subsequent applications being made up to 6.3 - 6.6 cm diameter fruit, and all applications were made using ground equipment in 99 - 104 gal/A (926 - 973 L/ha) volumes without an adjuvant. Mature apple s w ere collected at a 29 - day PHIand processed into wet and dry apple pomace, raw apple juice, and apple cider. Samples of whole apple s and processed commodities wer e analy zed for residues of fluazinam and AMGT . The GC/ECD method used for fluazinam analysis is similar to the current enforcement method for fluazinam in crops. In addition, the HPL C/UV method used for AMGT is similar to the method described in “ Method Evaluation for the Analysis of AMGT in Grapes . ” These methods were reviewed under DP# 335640, W. Drew, 8/22/07. The s e method s are adequate for data collection based on acceptable method verification and concurrent method recoveries. The fortification l evels used in method verification and concurrent method validation were adequate to bracket expected residue levels in/on apple fruits , the raw agricultural commodity (RAC), wet and dry pomace, juice, and cider . The validated method L OQ was 0.01 ppm for e ach analy

te in all matrices. Samples of apple fruits were stored frozen for up to 191 days (6.3 months) prior to determination of residues of fluazinam and 805 days (26.4 months) prior to determination of residues of AMGT . S amples of processed commoditie s were stored frozen for 194 - 236 day s (6.4 - 7.8 months) prior to fluazinam analysis and for 758 - 914 day s (24.9 - 30.0 months) prior to AMGT analysis. T he submitted storage stability data (refer to the DER for MRID 47756604) for fluazinam and AMGT are adequat e to support the storage durations and conditions of sample s from the apple processing study . The results of the apple processing study are summarized in Table 1 3 . Average residues of fluazinam and AMGT were 0.025 ppm and below the L OQ (<0.01 ppm), respe ctively , in/on apple fruit (RAC) harvested 29 days following foliar airblast treatments with the 4.17 lb/gal FlC formulation at a 1x application rate . Respective average residues of fluazinam and AMGT were 0.07 and <0.01 ppm in wet pomace; 0.09 and 0.01 p pm in dry pomace; and <0.01 ppm each in both raw juice and cider. In the processing study , residues of fluazinam concentrate d in wet pomace (2.8x) and dry

pomace (3.6x), but d id not concentrate in juice or cider (<0.4x in each matrix). Residues of AMGT d id not concentrate in dry pomace (1x) . P rocessing factors were not calculated for AMGT in wet pomace, juice, or cider as the observed residues were <LOQ in both the RAC and the processed commodity . The observed processing factors are less than the theore tical concentration factor of 14x for wet apple pomace (OPPTS 860.1520, Table 4).Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 34 of 54 T able 1 3 . Residue Data fromApple Processing Study with Fluazinam . Location (Ci ty, State; Year) Total Rate (lb ai/A) [ kg ai/ha] PHI

(days) Commodity Fluazinam residues (ppm) [Avg.] Fluazinam

Processing Factor AMGT

residues (ppm) [Avg.] AMGT

Processing Factor 1 Williamson, NY; 1993 4.50 [5.04] 29 Fruit (RAC) 0.03, 0.02 [0.025] -- <0.01, <0.01 [<0.01] -- Wet pomace 0.07, 0.07

[0.07] 2.8x <0.01, <0.01 [<0.01] NC Dry pomace 0.10, 0.08

[0.09] 3.6x 0.01 2 , 0.01 2 [0.01] 1x Raw juice <0.01, <0.01

[<0.01] <0.4x <0.01, <0.01 [<0.01] NC Cider <0.01, <0.01,

<0.01 [<0.01] <0.4x <0.01, <0.01, <0.01 [<0.01] NC

1 NC = Not calculated; residues were below the LOQ (<0.01 pp m) in both the RAC and the processed fraction. Conclusions : The apple processing study is not a dequate to satisfy data requirements. Inapples, the metabolite AMGT is a residue of concern for risk assessment. In the processing study there were no quant ifiable residues of AMGT in raw apples. In several of the field trials that were performed, however, raw apples contained AMGT residues at, or above, the limit of quantitation. Ina few cases, residues of AMGT were comparable to those of the parent fluaz inam. Canadian and U.S. residue chemistry guidelines both stipulate that in the processing study , if residues in the raw agricultural commodity ( RAC ) are below the LOQ, but quantifiable residue s occurred in the RAC in field trials performed at the maximum requested label rate, that the processing study should be conducted at exaggerated rates in order to ensure that quantifiable residues will be present in the RAC . Quantifiable residues are needed in the RAC in order to determine a reliable concentration factor. As a result, the processing study needs to be repeated at a sufficiently high rate that residues of both parent and AMGT are quantifiable in the RAC. In the event that the potential for phy

totoxicity exists, the application rate does not need to be greater than the rate at which phy

to to xicity occurs. 860.1650 Submittal of Analytical Reference Standards Analy tical reference standards for fluazinam (expiration date 4/12/2012) A M PA (expiration date 5/31/2011) , and DAPA (expiration date 4/2012) are c urrently available in the EPA National Pesticide Standards Repository ( electronic communication D. Wright, ACB, to D. Dotson, HED, 11 /1 8 /20 09) . An analy

tical standard for the AMGT metabolite is not currently available in the EPA Nat ional Pesticide Standards Repository . The standard 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 /Analy tical Chem istry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 T he mail will be returned if the extended zip code is not used.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 35 of 54 860.1850/1900 Confined and Field Accumulation in Rotational Crops Residue Chemistry Memo DP# s 212612 , 216941, and 217 467 ; 9 / 5 /9 5; G. Herndon Residue Chemistry Memo DP# 342005 , 2/1/08 , W. Drew An adequate confined rotational crop study is available in which barley , carrots, and lettuce were grown in soil treated with [phenyl - U 14 C]fluazinam or [py ridyl - 2,6 - 14 C]fluazinam at 2.0 lb ai/A . All three crops were planted at PBI s of 30, 120, and 365 days , and no crops were grown in the soil during the aging period. B e cause of crop failure, the 30 - day PBI barley

in the plot treated with [phenyl - U 14 C]fluazinam was replanted at a 68 - day PBI . Although total radioactive residues (TRR) were greater than 0.01 ppm in/on all rotational crop RACs (except 365 - day

PBIpy ridine - labeled carrot roots), no fluazinam or any other metabolite resembling the intact fluazinam molecule was detect ed in any rotational crop RAC, from even the shortest rotation interval (30 - 68 day s). The majority of the radioactivity

was found in the aqueous soluble fractions of plant extracts, although some of the barley samples exhibited a high percentage of bound radioactivity . The organic fraction of each crop matrix contained <10% or <0.01 ppm of the TRR. Radioactivity in aqueous fractions accounted for up to 75 - 95% of the TRR (0.06 - 0.27 ppm) in phenyl - labeled crops, and up to 27 - 60% (0.02 - 0.046 ppm) in py ridyl labeled crops. Analysis of the phenyl - labeled aqueous fractions indicated that the majority of the radioactivity

eluted early

(4 - 5 minutes) in a single band which was identified as TFA. The py ridine - labeled aqueous fractions exhibited late - eluting radio activity (15 - 20 minutes), indicating different metabolism pathways between the two labels. No metabolites from the py ridine - labeled aqueous fractions were identified. Based on the absence of metabolites containing the intact fluazinam nucleus, HED conclu ded that the residue of concern in rotational crops is the parent compound , and that rotational crop tolerances are not required for fluazinam . HED originally recommended that labels specify rotational crop restrictions of 70 days for cereal grain and 30 day s for all other crops. However, in a recent reexamination of the data ( Memo, D342005, W. Drew, 2/01/08 ) , HED concluded that a 30 - day PBIis sufficient for all rotated crops not on the label. No additional rotational crop data are required for the prop osed uses on carrots, lettuce , and onions. 860.1550 Proposed Tolerances For purposes of tolerance expression, HED previously determined that the resi due of concern is f luazinam per se for all plant commodities, except for wine grapes where the parent compound and the metabolite AMGT are the re sidues of concern . For poultry and ruminants, the fluazinam residues of regulatory

interest include the parent plus the metabolites AMPA and DAPA, and their sulfamate conjugates. Tolerances for residues of fluazinam are listed under 40 CFR §180.574. Permanent tolerances have been established for residues of fluazinam in/on plant commodities at levels ranging from 0.01 ppm on turnip greens and Brassica leafy vegetables to 7.0 ppm in/on the Bushberry subgroup and oth er bushberries ( 40 CFR §180.574(a)(1) ) . A tolerance without a U.S.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 36 of 54 registration has also been established for residues of fluazinam and its metabolite AMGT in/ on wine grapes at 3.0 ppm ( 40 CFR §180.574(a)(2) ) . The tolerance expression proposed by IR - 4 i n PP# 8E7506 and PP#9E7570 for head lettuce , leaf lettuce , carrots, and the B ulb onion S ubgroup ( 3 - 07A ) , is in terms of fluazinam. The tolerance expression proposed by

I SK Biosciences in PP#9F7571 for apples and apple wet pomace is in terms of the combined residues of fluazinam and its metabolite AMGT. However, only the parent needs to be regulated for these commodities. Parent and AMGT are the residues of concern for risk assessment, but not for tolerance expression. As a result, if and when I SK Bioscien ces resubmits the tolerance petition for apples, the tolerance expression for apples and apple wet pomace should be defined as fluazinam only . The tolerance expression proposed by IS K Biosciences in PP# 9F7571 for milk, meat, and meat by products is approp riate and adequately

reflects the combined residues of fluazinam and its metabolites DAPA and AMPA. HED recommends that 40CFR §180.574(a)(1) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of f luazinam ( 3 - chloro -N

- [3 - chloro 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl) - 2 - py ridinamine ), including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to b e determined by measuring only

fluazinam.” HED further recommends that 40CFR §180.610(a)(2) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of fluazinam, including its metabolites and degradat es, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only

fluazinam and its metabolite AMGT ( 3 - [[4 - amino - 3 - [[3 - chloro - 5 - (trifloromethyl) - 2 - py ridinyl]amino] - 2 - nitro - 6 - (triflu oromethyl) phenyl]thio] - 2 - (beta - D - glucopy ranosyloxy

) propionic acid) .” Adequate number s of field trials at ~1x the proposed use rate are available for head lettuce, leaf lettuce, bulb onions, carrots, and apples to support permanent tolerances on these crops. With the exception of head lettuce, the Agency ’s SOP “ Guidelines for Setting Pesticide Tolerances Based on Field Trial Data” were utilized for determining the appropriate tolerance level for each commodity

(Appendix I I). The recommended tolerances f or these crop commodities are listed in Table 1 4 . For head lettuce, the tolerance spreadsheet could not be used to calculate a possible tolerance because of the large number of residue values <LOQ (13 of 14 samples). Therefore, the maximum residue value (0.021 ppm) was used to determine the appropriate tolerance for head lettuce of 0.02 ppm. IR - 4 has requested that the Agency reconsider the established 7 - ppm tolerances for members of the B ushberry

subgroup 13B , as the established tolerances are 3.5 times as high as the maximum residue value. IR - 4 has also requested deletion of the separate tolerances for bushberry crops that are now covered by

the updated B ushberry

subgroup 13 - 07B. The existing blueberry residue data for fluazinam were reevaluated according to the Agency ’s SOP “ Guidelines for Setting Pesticide Tolerances Based on Field Trial Data . ” After reviewing the probability plot for the fluazinam residue data on blueberries, HED has determined that the residue data are lognormally distributed , and that the recommended tolerance for the B ushberry subgroup 13 - 07B should beFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 37 of 54 7 .0 ppm. In addition, the separate tolerances for the various bushberry crops can now be deleted, as all of the listed bushberrie s are now covered by the revised B ushberry

subgrou p 13 - 07B. The a pple processing study i s not acceptable . Inapples, the metabolite AMGT is a residue of concern for risk assessment. In the processing study there were no quantifiable residues of AMGT in raw apples. In several of the field trials that w ere performed, however, raw apples contained AMGT residues at, or above, the limit of quantitation. In a few cases, residues of AMGT were comparable to those of the parent fluazinam. Canadian and U.S. residue chemistry guidelines both stipulate that in the processing study , if residues in the raw agricultural commodity

( RAC ) are below the LOQ, but quantifiable residue s occurred in the RAC in field trials performed at the maximum requested label rate, that the processing study should be conducted at exagge rated rates in order to ensure that quantifiable residues will be present in the RAC . Quantifiable residues are needed in the RAC in order to determine a reliable concentration factor. As a result, the processing study needs to be repeated at a sufficiently high rate that residues of both parent and AMGT are quantifiable in the RAC. In the event that the potential for phy totoxicity exists, the application rate does not need to be greater than the rate at which phy to toxicity occurs. The residue data (adj usted for residue decline) from the cattle feeding study , along with the calculated dietary

burdens for beef and dairy cattle , indicate that tolerances might be needed for the combined residues of fluazinam and its metabolites DAPA and AMPA in fat and meat by products of cattle and other ruminants at 0.0 5 ppm. The feeding study also indicates that tolerances probably

will not be needed for milk and meat of cattle and ruminants , as the expected combined residues in these matrices are below the combined metho d L OQ of 0.03 ppm for the regulated compounds. According to the July 18, 2007 Minutes of the Chemistry Science Advisory Council Meeting, the ChemSAC recommended that the guidance document be revised to include language detailing the use of the highest res idue data for any tissue (liver, kidney , fat, skin or muscle) to determine the tolerance for meat by products. A single tolerance on “meat by products” w ou l d be recommended based on th e highest residue value, and individual tolerances will no longer be set on liver, kidney , or meat by products (except liver and kidney ). Based on the transfer coefficients for livestock tissues and the relatively low dietary

burden for swine of 0.003 ppm for fluazinam, tolerances for hogs are not needed. Tolerances are also n ot needed for poultry

eggs and tissues at this time because of the low dietar y burden for poultry . Tolerances for rotational crops are not required based on the review of a confined rotational crop study which showed the absence of metabolites containing the intact fluazinam nucleus. The existing 30 - day PBI for all rotated crops not on the label is appropriate , and preclude s the need for additional rotational crop data.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 38 of 54 There are currently

no established Codex, Canadian, or Mexican max imum residue limi ts (MRL s) for f

luazinam on the apple, carrot, lettuce, onions or berry crops . Therefore, there are no harmonization issues for the requested tolerances. An International Residue L imit Status Sheet is attached in Appendix I . Table 1 4 . Tolerance Sum ma ry for Fluazinam . Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity Definition PP#8E7506 Bushberry, subgroup 13 - 07B 4.5 7.0 Adequate blueberry residue data are available. The recommended tolerance for Subgroup 1 3 - 07B is the same as that for Subgroup 13B (i.e., 7.0 ppm) The established individual tolerances for aronia berry, b uffalo curr ant, Chilean guava, European barberry, highbush cranberry, edible honeysuckle , edible jostaberry, Juneberry, lingonberry, native currant, salal, and sea buckthorn should be deleted because they are included under the revised B ushberry subgroup, 13 - 07B. Onion, bulb, subgroup 3 - 07A 0.15 0.20 Adequate bulb onion residue data are available. Lettuce, head 0.02 0.02 Adequate head lettu ce residue data are available. Lettuce, leaf 2.0 2.0 Adequate leaf lettuce residue data are available. PP#9E7570 Carrot , roots 0.8 None Adequate carrot residue data are available. HED’s tolerance generator directs that the tolerance for this data set s hould be 0.70 ppm. PP#9F7571 Apple s 1.7 None Adequate apple residue data are available. HED’s tolerance generator directs that the tolerance for this data set should be 1. 5 0 ppm. The USEPA and Canada’s PMRA agreed to establish the tolerance at 2.0 pp m at such time as the data deficiencies are resolved. Apple, pomace, wet 5.0 None A dequate apple processing data are not available. Cattle, fat 0.03 None An adequate cattle feeding study is not available. Based on the results of the inadequate study, th e maximum expected residues in meat byproducts and fat is 0.0 5 ppm . This value can be used as a very conservative residue value for the dietary exposure assessment. Based on the results of the inadequate feeding study, tolerances will probably not be nee ded f or milk and meat of cattle , goat, horse, and sheep . Cattle, kidney 0.03 Not required Cattle, liver 0.03 Not required Cattle, meat 0.03 Not required Cattle, meat byproducts 0.03 None Goat, fat 0.03 None Goat, kidney 0.03 Not required Goat, liver 0.03 Not required Goat, meat 0.03 Not required Goat, meat byproducts 0.03 None Horse, fat 0.03 NoneFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 39 of 54 Table 1 4 . Tolerance Sum ma ry for Fluazinam . Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity Definition Horse, kidney 0.03 Not required Horse, liver 0.03 Not required Horse, meat 0.03 Not required Horse, meat byproducts 0.03 None Milk 0. 03 Not required Sheep, fat 0.03 None Sheep, kidney 0.03 Not required Sheep, liver 0.03 Not required Sheep, meat 0.03 Not required Sheep, meat byproducts 0.03 None References D 212612 , 216941, and 217467 , PP# 2G04099. Temporary Tolerance Petit ion and Experimental Use Permit for Use of Fluazinam on Peanuts; 050534 - EUP - E. Submission Dated 1/23/95 in Response to the Memo of G.J. Herndon Dated 6/19/92 , G. Herndon , 9/5 /9 5 D 272624 , Fluazinam. Decision by Metabolism Ass essment Review Committee (MARC ), W. Cutchin , 4/23/01 D 257115 , PP# 9F5079. Request for the Use of Fluazinam on Peanuts, Potatoes, and Wine Grapes. Evaluation of Analy tical Chemistry

and Residue Data , W. Cutchin , 5/21/01 D 335640 , Fluazinam. Tolerance Petitions Requesting the Establi shment of Permanent Tolerances (Associated with Section 3 Registration) for Food Use of the Fungicide on Edible Podded Beans (Subgroup 6 - A, Except Peas), Shelled Succulent Beans (Subgroup 6 - B, Except Peas), Shelled Dried Beans (Subgroup 6 - C, Except Peas), Brassica (Cole) Vegetables (Group 5), Bushberries (Subgroup 1 3 - B), and Ginseng. Summary of Analy tical Chemistry

and Residue Data , W. Drew , 8/22/07 D 342005 , Fluazinam. Request for L abel Amendments Adding Aerial Application of the Fungicide on Potatoes, and Reducing the Plant - Back Interval (PBI) for All Non - Label Crops from 70 to 30 Days Following Use of the Fungicide , W. Drew , 2/1/08 Attachments: Appendix I - International Residue L imit Status sheet Appendix I I - Tolerance Asses sment CalculationsFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 40 of 54 Appendix I 

## INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 3 - chloro N - [3 - chloro - 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl) - 2 - pyridinamine Common Name: Fluazinam X Proposed tolerances ⁯ Reevaluated tolerance ⁯ Oth er Date: 8 / 31 /09 Codex Status (Maximum Residue Limits) U. S. Tolerances √ No Codex proposal step 6 or above ⁯No Codex proposal step 6 or above for the crops requested Petition Numbers: PP#s 8E7506, 9E7570, and 9F7571 DP #s: 360840 and 366506 Other Ident ifier: Residue definition (step 8/CXL): N/A Reviewer/Branch: C. Swartz, RAB2 Established residue definition: parent fluazinam for all plant commodities, except wine grapes ; parent fluazinam and AMGT for grapes Proposed residue definition in PP#s 8E 7506 and 9E7570 for plant commodities: fluazinam Proposed residue definition in PP#9F7571 for apple commodities: fluazinam and its metabolite AMGT and for livestock commodities: fluazinam and its metabolites DAPA and AMPA Crop (s) MRL (mg/kg) Crop(s) Proposed Tolerance (ppm) PP#8E7506; fluazinam Bushberry, subgroup 13 - 07B 4.5 Onion, bulb, subgroup 3 - 07A 0.15 Lettuce, head 0.02 Lettuce, leaf 2.0

PP#9E7570; fluazinam Carrot , roots 0.8 PP#9F7571; fluazinamand AMGT Apple 1.7 Apple, pomace, wet 5.0 PP#9F7571; fluazinamand its m etabolites DAPA

and AMPA Cattle, fat 0.03 Cattle, kidney 0.03 Cattle, liver 0.03 Cattle, meat 0.03 Cattle, meat byproducts 0.03Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 41 of 54 Goat, fat 0.03 Goat, kidney 0.03 Goat, liver 0. 03 Goat, meat 0.03 Goat, meat byproducts 0.03 Horse, fat 0.03 Horse, kidney 0.03 Horse, liver 0.03 Horse, meat 0.03 Horse, meat byproducts 0.03 Milk 0.03 Sheep, fat 0.03 Sheep, kidney 0.03 Sheep, liver 0.03 Sheep, meat 0 .03 Sheep, meat byproducts 0.03 Limits for Canada Limits for Mexico ⁯No Limits √ No Limits for the crops requested ⁯ No Limits √ No Limits for the crops requested Residue definition: 3 - chloro -N - [3 - chloro - 2,6 - dinitro - 4 - (trifluoromethyl)phenyl] - 5 - (trifluoromethyl) - 2 - pyridinamine Residue definition: Fluazinam Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg) Potatoes 0.02 Beans 0.1 Potato 0.05 Notes/Special Instructions: S. Funk, 09/02/2009Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 42 of 54 Appendix II Tolerance Assessment Calculations For each of the crops listed below, the Guidance for Setting Pesticide Tolerances Based on Field Trial Data (SOP), along with the tolerance spreadsheet (January 2008 version) , was used for calculating recommended tolerances. As specified in the SOP, the minimum of the 95% upper confidence limit (UCL) on the 95 th percentile and the point est imate of the 99 th percentile was selected as the tolerance value in cases when the dataset was large (greater than 15 samples) and reasonably

lognormal. For datasets that were small ( ≤15 samples) and reasonably lognormal, the upper bound estimate of the 9 5th percentile based on the median residue value was compared to the minimum of the 95% UCL on the 95th percentile and the point estimate of the 99th percentile, and the minimum value was selected as the tolerance value. For datasets that were not lognorm al, the upper bound on the 89 th percentile was selected as the tolerance value (distribution - free method). The rounding procedures specified in the SOP were also used. Apple The dataset used to establish a tolerance for fluazinam on apple consisted of f ield trial data representing application rates of 3.97 - 5.40 lb ai/A ( 9 - 12 applications at 0. 43 - 0.71 lb ai/A/application) with PHI s of 28 - 32 day s. As specified in the SOP, the trial application rates and PHI s are within 25% of the maximum label application rate and minimum label PHI , respectively . The residue values used to calculate the tolerance for apple are provided in Table II - 1. All but 4 of the 4 2 field trial sample results for fluazinam in/on apple were above the LLM V (LLMV = 0.0 1 ppm ). The apple dataset was large (4 2 samples). The result from the approximate Shapiro - Francia test statistic (Figure II - 2 ) indicated that the assumption of lognormality

should be rejected. Visual inspection of the lognormal probability plot (Figure I I - 1 ) provided in the spreadsheet confirmed that the dataset is not lognormal. Using the tolerance spreadsheet, the recommended tolerance is 1. 5 ppm for apple.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 43 of 54 Table II - 1. FluazinamResidues in/on Apples Following Nine to Twelve Foliar Applications of

Fluazinam(FlC) at Rates Totaling ~4.5 lb ai/A/season. Regulator: EPA EPA Chemical: Fluazinam Fluazinam Crop: Apple Apple PHI: 28 - 32 Days 28 - 29 Days Total App. Rate: 3.97 - 5.40 lb ai/A 4.44 - 4.77 lb ai/A Submitter: ISK Biosciences Corporation ISK Biosciences Corporation MRID Citation: MRIDs 47756607, 47756608, 47756610,

and 47756611 MRID 47756609 Residues of Fluazinam(ppm) 1 0.050 0.160 0.030 0.160 0.050 0.160 0.03 0.160 0.05 0.030 0.060 0.020 0.030 0.090 0.040 0.150 0.010 0.150 0.010 0.120 0.010 0. 150 0.010 0.120 0.020 1.680 0.040 1.390 0.020 0.050 0.040 0.020 0.080 0.170 0.080 0.090 0.020 1.310 0.030 1.490 0.150 0.130 0.050 0.300 0.120 0.170 1 Residue values <LLMV (0.01 ppm) are listed in bold .Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 44 of 54 Figure II - 1 . Lognorm al probability plot of fluazinamfield trial data for apple. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 2.0000 1.0000 0.5000 0.2500 0.1250 0.0625 0.0313 0.0156 0.0078 y = 1.3151x - 2.6003 R 2 = 0.932

PercentilesConcentrations EPA Fluazinam Apples 28 Days

Figure II - 2 . Tolerance spreadsheet sum ma ry of fluazinamfield trial data for apple. Reg ulat or: EP A Ch emic al: Fl uazi nam Cr op: Ap ples P H I: 28 Day s App . Ra te: Sub mitt er:

n: 42 m i n: 0.0 1 m a x: 1.6 8 medi an: 0.0 7 a v era ge: 0.2 1 95th Per centi le 9 9 th P erce ntile 99.9 th Pe rcen tile 1. 0 1.2 1. 6 (1. 1) ( 1 .5) (--) 0 . 70 1.7 5. 0 (1. 3) ( 4 .0) (--) 0.3 0 1.5 0.3 5 0.93 20 0.05 >= p-val ue > 0.0 1 : R ejec t log norm ality ass umpt ion Appr oxima te Sh apir o-Fra ncia Norm alit y Tes t EU M ethod I Norm al

U C LMe dian9 5th 95 /99 Rule EU Meth od II Dis trib ution -Fre e M e an+ 3SDFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 45 of 54 Bulb O nion s (Subgroup 3 - 07A) The dataset used to establish a tolerance for fluazinam on th e b ulb o nion subgroup consisted of field trial data for bulb onion s representing application rates of 3.11 - 3.17 lb ai/A (6 applications at ~0.52 lb ai/A/application) with PHI s of 6 - 8 day s. As specified by the SOP, the trial application rates and PHI s are within 25% of the maximum label application rate and minimum label PHI , respectively . The residue values used to calculate the tolerance for bulb onion are provided in Table I I - 2 . As 7 of the 18 field trial sample results for bulb onion were <L OQ, maximum likelihood estimation (MLE) procedures were used to impute the censored values for onions. The censored dataset for onions, which consisted of 18 samples, was then entered into the tolerance spreadsheet. Visual inspection of the lognormal probability p lot ( Figure I I - 3 ) and the results from the approximate Shapiro - Francia test statistic ( Figure I I - 4 ) indicate that the dataset is reasonably

lognormal. The recommended tolerance is 0.20 ppm fo r bulb onion, which is the representative crop for the bulb on ion subgroup 3 - 07A. Table II - 2. FluazinamResidues in/on Onions Following Six Foliar Applications of Fluazinam(FlC) at

Rates Totaling ~3.12 lb ai/A/season. Regulator: EPA Chemical: Fluazinam Crop: Bulb Onion (MLE) PHI: 6 - 8 days App. Rate: 3.11 - 3. 17 lb ai/A Submitter: IR - 4 MRID Citation: MRID 47631001 Residues (ppm) 1 0.002 0.015 0.003 0.016 0.004 0.021 0.005 0.031 0.006 0.033 0.007 0.035 0.009 0.045 0.013 0.095 0.013 0.101 1 Residue values <LLMV (0.01 ppm) are listed in bold .Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 46 of 54 Figure II - 3 . Lognorm al probability plot of fluazinamfield trial data for bulb onion . Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000 0.5000 0.2500 0.1250 0.0625 0.0313 0.0156 0.0078 0.0039 0.0020 y = 1.1368x - 4.2304 R 2 = 0.9858

PercentilesConcentrations EPA Fluazinam Bulb Onion (MLE) 6-8 days 3.11-3.17 lb ai/A IR-4

Figure II - 4 . Tolerance spreadsheet sum ma ry of fluazinamfield trial data for bulb onion . Regulator: EPA Chemical: Fluazinam Crop: Bulb Onion (MLE) PHI: 6-8 days App. Rate: 3.11-3.17 lb ai/A Submitter: IR-4

n: 18 min: 0.00 max: 0.10 median: 0.01 average: 0.03 95th Percentile 99th Percentile 99.9th Percentile 0.08 0.10 0.15 (0.10) (0.15) (--) 0.09 0.20 0.45 (0.25) (0.60) (--) 0.07 0.15 0.08 0.9858 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SDFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 47 of 54 Bushberry

subgroup ( 13 - 07B) Based on prev iously

reviewed blueberry data (PP# 6E7137 ; D335640, W. Drew, 8/22/07), a 7 .0 ppm tolerance was established on the B ushberry subgroup 13B and several related bushberry crops. To assess IR - 4’s request to lower the bushberry tolerance, HED has reexamined the original blueberry

residue data supporting the tolerance (Table II - 3). Only the fluazinam residue data were included, as fluazinam per se is the residue of concern for tolerance assessment. The data were entered into the tolerance spreadsheet. The results from the approximate Shapiro Francia test statistic ( Figure I I - 6 ) indicated that the assumption of lognormality should not be rejected . Therefore, the recommended tolerance for the B ushberry subgroup 13 - 07B is 7 .0 ppm. Table II - 3. FluazinamResidues in/on Blueberries Followi ng Six Foliar Applications of Fluazinam(FlC)

at Rates Totaling ~3.12 lb ai/A/season. Regulator: EPA Chemical: Fluazinam Crop: Blueberry PHI: 23 - 32 Days App. Rate: 3.8 - 4.1 lb ai/A Submitter: IR - 4 MRID Citation: MRID 46986701 Residues (ppm) 1 0.06 4 0.64 0.07 0 0.68 0.07 4 0.70 0.12 1.0 0.13 1.2 0.16 1.2 0.17 1.5 0.42 1.6 0.45 1.6 0.49 1.7 0.50 2.0 0.55Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 48 of 54 Figure II - 5 . Lognorm al probability plot of fluazinamfield trial data for blueberry . Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 2.0000 1.0000 0.5000 0.2500 0.1250 0.0625 y = 1.1139x - 0.7696 R 2 = 0.9251

PercentilesConcentrations EPA Fluazinam Blueberry 23-32 Days 3.8-4.1 lb ai/A IR-4Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 49 of 54 Figure II - 6 . Tolerance spreadsheet summary of fluazinam field trial data for blueberry. Regulator: EPA Chemical: Fluazinam Crop: Blueberry PHI: 23-32 Days App. Rate: 3.8-4.1 lb ai/A Submitter: IR-4

n: 23 min: 0.06 max: 2.00 median: 0.55 average: 0.74 95th Percentile 99th Percentile 99.9th Percentile 1.8 2.5 3.0 (2.5) (3.0) (--) 3.0 7.0 15 (7.0) (17) (--) 2.5 3.0 3.0 0.9251 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SD

Carrot The dataset used to establish a tolerance for fluazinam on carrot consisted of field trial data representing application rates of 2.04 - 3.03 lb ai/A ( 4 - 5 applications at 0. 49 2 - 0.786 lb ai/A/ap plication) with PHI s of 6 - 8 day s. Each field trial consisted of two treatment plots (Treatments 2 and 3). Both plots received treatments in similar rates and volumes; however, Treatment 2 was irrigated within 2 hours of each application, and Treatment 3 received irrigation after 24 hours of each application. As specified by the SOP, the trial application rates and PHI s are within 25% of the maximum label application rate and minimum label PHI , respectively . The residue values used to calculate the tolerance for carrot are provided in Table I I - 4 . All but 4 of the 52 field trial sample results for fluazinam in/on carrot were above the LLM V (LLMV = 0.02 ppm ). The carrot dataset was large (52 samples). Visual inspection of the lognormal probability

plot ( Figure I I - 7 ) and the results from the approximate Shapiro - Francia test statistic ( Figure I I - 8 ) indicate d that the carrot dataset was reasonably lognormal. Using the tolerance spreadsheet, the recommended tolerance is 0.7 ppm for carrot.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 50 of 54 Table II - 4. Fluaz inamResidues in/on Carrots Following Four to Five Foliar Applications of

Fluazinam(FlC) at Rates Totaling ~2.09 lb ai/A/season. Regulator: EPA EPA Chemical: Fluazinam Fluazinam Crop: Carrot (Treatment 2; irrigated w /in 2 hours of each application) Carrot (Treatment 3; irrigated after 24 hours of each application) PHI: 6 - 8 Days 6 - 8 Days Total App. Rate: 2.04 - 2.94 lb ai/A 2.04 - 3.03 lb ai/A Submitter: IR - 4 IR - 4 MRID Citation: MRID 47756601 MRID 47756601 Residues of Fluazinam(ppm) 1 0.040 0.050 0.060 0.060 0.340 0.240 0.390 0.280 0.020 0.020 0.020 0.020 0.120 0.030 0.120 0.040 0.120 0.100 0.140 0.110 0.050 0.170 0.060 0.190 0.110 0.410 0.120 0.450 0.070 0.050 0.190 0.070 0.460 0.160 0.560 0.250 0.100 0.090 0 .100 0.090 0.090 0.080 0.110 0.090 0.220 0.020 0.230 0.020 0.080 0.040 0.090 0.050 1 Residue values <LLMV (0.02 ppm) are listed in bold .Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 51 of 54 Figure II - 7 . Lognorm al probability plot of fluazinamfield trial data for carrot. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156 y = 0.9014x - 2.3559 R 2 = 0.9756

PercentilesConcentrations EPA Fluazinam Carrot (combined irrigation data) 6-8 Days 2.04-3.03 lb ai/A IR-4

Figure II - 8 . Toler ance spreadsheet sum ma ry of fluazinamfield trial data for carrot. Regulator: EPA Chemical: Fluazinam Crop: Carrot (combined irrigation data) PHI: 6-8 Days App. Rate: 2.04-3.03 lb ai/A Submitter: IR-4

n: 52 min: 0.02 max: 0.56 median: 0.10 average: 0.14 95th Percentile 99th Percentile 99.9th Percentile 0.35 0.45 0.60 (0.45) (0.60) (--) 0.45 0.80 1.6 (0.70) (1.3) (--) 0.40 0.60 0.50 0.9756 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SDFluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 52 of 54 Head Lettuce The dataset used to assess a tolerance for fluazinam residues on head lettuce consisted of field trial data representing application rates of 0.952 - 1.02 lb ai/A with PHI s o f 46 - 52 day s. As specified by

the SOP, the field trial application rates and PHI s are within 25% of the maximum label application rate and minimum label PHI , respectively . Because all but one of the residue values for head lettuce were <LOQ (<0.01 ppm), the tolerance spreadsheet could not be used to calculate a possible tolerance ( Table I I - 5 ). Therefore, the maximum residue value (0.021 ppm) was used to determine the tolerance. Table II - 5. FluazinamResidues in/on Head Lettuce Following a Broadcast Fo liar Application of

Fluazinam(FlC) at a Rate of ~0.99 lb ai/A/season. Regulator: EPA Chemical: Fluazinam Crop: Head Lettuce PHI: 46 - 52 days App. Rate: 0.952 - 1.02 lb ai/A Submitter: IR - 4 MRID Citation: MRID 47631002 Residues (ppm) 1 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.021 1 Residue values <LLMV (0.01 ppm) are listed in bold . Leaf Lettuce The dataset used to assess a tolerance for fluazinam residues on leaf lettuce consisted of field trial data repre senting application rates of 0.974 - 1.05 lb ai/A with PHI s of 20 - 32 day s. As specified in the SOP, the field trial application rates and PHI s are within 25% of the maximum label application rate and minimum label PHI , respectively . The residue values used to calculate the tolerance are provided in Table I I - 6 . The leaf lettuce dataset, which is relatively small (14 samples), was entered into the tolerance spreadsheet. Field trial sample results were above the LLM V (0.01 ppm) for 12 of 14 samples. V isua l inspection of the lognormal probability plot ( Figure I I - 9 ) and the result from the approximate Shapiro - Francia test statistic ( Figure I I - 10 ) indicated that the assumption of lognormality

should be rejected. Using the tolerance spreadsheet, the recomme nded value is 2.0 ppm for leaf lettuce.Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 53 of 54 Table II - 6. FluazinamResidues in/on Leaf Lettuce Following a Broadcast Foliar Application of

Fluazinam(FlC) at a Rate of ~0.99 lb ai/A/season. Regulator: EPA Chemical: Fluazinam Crop: Leaf Lettuce PHI: 20 - 32 days App. Rate: 0.974 - 1.05 lb ai/A Submitter: IR - 4 MRID Citation: MRID 47631002 Residues (ppm) 1 0.01 0.021 0.01 0.022 0.011 0.038 0.017 0.150 0.019 0.159 0.020 1.45 0.020 1.69 1 Residue values <LLMV (0.01 ppm) are listed in bold .

Fig ure II - 9 . Lognorm al probability plot of fluazinamfield trial data for leaf lettuce. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 2.0000 1.0000 0.5000 0.2500 0.1250 0.0625 0.0313 0.0156 0.0078 y = 1.6054x - 3.098 R 2 = 0.7821

PercentilesConcentrations EPA Fluazinam Leaf Lettuce 20-32 days 0.974-1.05 lb ai/A IR-4Fluazinam Summary of Analytical Chemistry and Residue Data DP#: 360840

Page 54 of 54 Figure II - 10 . Tolerance spreadsheet sum ma ry of fluazinamfield trial data for leaf lettuce. Regulator: EPA Chemical: Fluazinam Crop: Leaf Lettuce PHI: 20-32 days App. Rate: 0.974-1.05 lb ai/A Submitter: IR-4

n: 14 min: 0.01 max: 1.69 median: 0.02 average: 0.26 95th Percentile 99th Percentile 99.9th Percentile 1.2 1.6 2.0 (1.8) (2.5) (--) 0.80 3.0 10 (4.5) (25) (--) 0.35 2.0 0.15 0.7821 p-value <= 0.01: Reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SD