Py

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Page **1** of **18 UNITED STA** 

**TES ENVIRONMENTA L PROTECTION A** **GENCY WA** **SHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY**  **AND POLLUTION PREVENTION MEMORANDUM**  **Date :**  04/16/2013 **SUBJECT: Pyraclostrobin**  **:** Request for the Use on Sugarcane . Summary of Analy tical Chemistry

and Residue Data. **PC Code:** 099100 **DP Barcode s**  **:** 403449; ,403451; 403452; 403453; 403454; 403456 ; 403462; **Decision No.:** 465126 **Registration No s**  **. :**  7969 - 185; 7969 - 186; 7969 - 247; 7969 - 258; 7969 - 289; 7969 - 291 **Petition Nos.:** 2F8038 **Regulatory Action:** Sectio n 3 Registration **Risk Assessment Type:** Single Chemical/Aggregate **Case No.:** N/A **T XR No.:**  N/A **CAS No.:** 175013 - 18 - 0 **MRID No.:** 4 8 237401 **40 CFR:** 180.582 **FROM:** Stephen Funk , Senior Chemist

Risk Assessment Branch I II ( RAB I II) Health Effects Division (HED; 7509P) **THROUGH:** Christine Olinger, Branch Chief

Risk Assessment Branch III (RAB III) Health Effects Division ( HED; 7509P) **TO:** T . Kish/ d. Schuler , RM# 22

Fungicide Branch R egistration D ivision ( RD; 7 505P) And Barry O’Keefe , Senior Biologist Risk Assessment Branch I II (RAB III) Health Effects Division (HED; 7509P) **Executive Summary** Py raclostrobin , or methyl N - [2 - [[[1 - (4 - chlorophenyl) - 1 H - py razol - 3 - yl ]oxy]methyl]phenyl ] -Nmethoxycarbamate , belongs to the strobilurin class of fungicides. Strobilurins are sy ntheticPy

raclostrobin D 403449

Page **2** of **18** analogs of a natural antifungal substance which inhibits spore germination, mycelial growth, and sporulation of the fun gi causing diseases such as fruit rot i n strawberry , early leaf rot in peanuts, late blight in pi stachios, rust diseases in soy beans, and pre - and post - fruit rot of pome and stone fruits. The fungicide is currently registered to BASF Corporation (BASF) for use on a variety of field, vegetable, fruit, and nut crops. It is formulated as water - dispersible granules (WDG) or an emulsifiable concentrate (EC) and is ty pically applied as foliar applications using ground or aerial equipment at maximum seasonal rates of 0.3 - 3.0 lb ai/A. The 20% WDG for mulation is also registered for use as a seed treatment on some crops. BASF is proposing a new use for py raclostrobin on sugarcane. The proposed use is for up to four applications of an EC or SC formulation at 0.20 lb ai/acre with a seasonal maximum rate of 0.80 lb ai/acre and a 14 day preharvest interval ( PHI) . There is an existing Section 18 tolerance for sugarcane. B ASF has proposed the establishment of a tolerance for the combined resi dues of the fungicide py raclostrobin (carbamic acid, [2 - [[[1 - (4 - ch lorophenyl) - 1H - py razol - 3 - yl ]oxy]methyl]phenyl]methoxy- , methyl ester) and its desmethoxy metabolite methyl -N - [[[1 - (4 - chlorophenyl) py

razol - 3 - yl ]oxy]o - tolyl] carbamate, expressed as parent compound, in or on the following raw agricultural commodity : Sugar cane, cane........................................0.2 ppm T olerances have been established in 40 CFR §180.582 for residues of the fungicide py raclostrobin, including its metabolites and degradates. Compliance with the tolerance levels is to be determined by measuring on ly the sum of py raclostrobin (carbamic acid, [2 - [[[1 - (4 - chlorophenyl) - 1 H

- py razol - 3 - yl ]oxy]methyl]phenyl]methoxy- , methyl ester) and its desmethoxy metabolite (methyl N

- [[[1 - (4 - chlorophenyl) - 1 H - py razol - 3 - yl ]oxy]methyl]phenyl carbamate), calculated as the stoichiometric equivalent of py raclostrobin . The established tolerances for plant food commodities range from 0.02 ppm in/on wheat grain to 29 ppm in/on leafy vegetables, except Brassica . Tolerances for livestock commodities are listed in 40 CFR §180.582 (a)(2) and are expressed in terms of the combined residues of the fungicide py raclostrobin and its metabolites convertible to 1 - (4 - chlorophenyl) - 1 H - py razol - 3 - ol and 1 - (4 - chloro - 2 - hydroxy phenyl) - 1 H

- py razol - 3 - ol, expressed as parent compound. The established tolerances for livestock commodities range from 0.1 to 1.5 ppm; no tolerances are established for poultry commodities. HED ( D278044, Metabolism Assessment Review Committee (MARC ) , 10/09/01 ) has determined that for purposes of tolerance and dietary risk assessments, the residues of concern in plant and rotational crop commodities include py raclostrobin and desmethoxy metabolite (BF 500 - 3) . The residues of concern in livestock commodities include py raclostrobin and its metabolites convertibl e to 1 - (4 - chlorophenyl) - 1 H - py razol - 3 - ol (BF 500 - 5) and 1 - (4 - chloro - 2 - hydroxy phenyl) - 1 H

- py razol - 3 - ol (BF 500 - 8) . There are adequate residue analy tical methods for tolerance enforcement. The analy tical methods for plant commodities ar e liquid chromatography with tandem mass spectro metry (LC/MS/MS ) and high pressure liquid chromatography with ultraviolet detec tion ( HPL C/UV) ,Py

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Page **3** of **18** which both measure py

raclostrobin and its desmethoxy metabolite. The analy

tical methods for livestock commoditie s , gas chromatography with mass spectro metry (GC/MS ) and LC/MS/MS, convert py

raclostrobin and related metabolites to chlorophenylpy razolol (BF 500 - 5) and hydroxylated chlorophenylpy razolol (BF 500 - 8) in goats and chlorophenylpy razolol (BF 500 - 5) and a hydroxylated chlorophenylpy razolol isomer of BF 500 - 8 (BF 500 - 9) in poultry . Samples were analy

zed for py

raclostrobin using BASF Analy tical Method Number D9908 (Version 2) , "Method for Determining BAS 500 F, BF 500 - 3 and BAS 510 F Residues in Plant Matrices using LC/MS/MS." The final chromatographic analysis of residues was determined by LC /MS/MS . The lower limit of method validation (LLM V) in this study was 0.02 ppm for both py raclostrobin and BF 500 - 3. The L C/MS/MS method used to determine residues of p yr aclostrobin and BF 500 - 3 were adequately validated in conjunction with the field sample analyses. The average recovery of all py raclostrobin and BF 500 - 3 fortifications was adequate. The method is adequate for data collection. The requirements for mul tiresidue methods testing data are fulfilled. Py raclostrobin was successfully

evaluated through several of the FDA protocols (complete recovery through protocols D and E), while recovery of metabolite BF 500 - 3 was unsuccessful in all protocols. Samples o f sugarcane from field trials were stored frozen for up to 24.9 months prior to analysis. Samples of sugarcane RAC, blackstrap molasses, and refined sugar from the processing study were stored frozen for up to 17.0 months from collection to extraction Sub mitted freezer storage stability data indicate that residues of py raclostrobin and BF 500 - 3 are stable in diverse representative crop matrices for up to 25 months. These data are adequate to support the storage conditions and durations of samples from the sugarcane field trials and processing stud ies. Sugarcane molasses is a livestock feed item of regulatory interest, comprising up to 10% of the diet of dairy

and beef cattle. Low concentration of py raclostrobin in the processed commodity from the propos ed use will have no effect on the calculated livestock diet. BASF has submitted field trial data for eight trials for py raclostrobin sugarcane in the USA. At each trial location, the treate d plots received four foliar directed or foliar broadcast applicat ions of a 2.09 lb ai/gal emulsifiable concentrate (EC) formulation of py raclostrobin ( Headline ® ) during the vegetative or bloom stages of development at rates of 0.189 - 0.206 lb ai/A/application (0.21 - 0.23 kg ai/ha/application), for total seasonal rates of 0.78 - 0.81 lb ai/A (0.88 - 0.91 kg ai/ha). Retreatment intervals (RTI s) were 13 - 14 days. Applications were made using ground equipment in spray volumes of 15.54 - 27.15 gal/A of water (145 - 254 L/ha). A nonionic surfactant (NI S) was added to the spray

mixture at each trial in the LA and TX trials ; however, no adjuvant was used in the FLtrials. Samples of sugarcane were harvested from trials at preharvest intervals (PHI s) of 13 - 14 and 27 - 28 days. Residues (and per trial averages) of py raclostrobin, of BF 50 0 - 3, and of combined py raclostrobin and BF 500 - 3 in/on sugarcane harvested at a 13 - to 14 - day PHIwere <0.02 - 0.1049 (<0.02 - 0.099), <0.02 - 0.02 67 (<0.02 - 0.02 7 ), and <0.04 - <0.1249 (<0.040 - <0.119) ppm, respectively . Following the same treatment at a 27 - to 28 - day PHI , residues of BF 500 - 3 in/on all sugarcane samples were <0.02 ppm, and r esidues (and per trial averages) of py raclostrobin and of combinedPy

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Page **4** of **18** py raclostrobin and BF 500 - 3 were <0.02 - 0.0866 (<0.020 - 0.068) and <0.04 - <0.1066 (<0.040 - <0.088) ppm, respectiv ely . A processing study

was also conducted for sugarcane. At two trial locations (Trial IDs 08 - FL32 and 08 - TX24), an additional plot received four foliar directed or foliar broadcast applications of the Headline ® formulation of py raclostrobin during th e vegetative or bloom stages of development at rates of 0.977 - 1.04 lb ai/A/application (1.09 - 1.13 kg ai/ha/application), for total seasonal rates of 3.94 - 3.99 lb ai /A (4.42 - 4.47 kg ai /ha , 5x rate). Sugarcane was processed within 21 - 27 days of harvest into blackstrap molasses and refined sugar using simulated commercial procedures. Concentration of py raclostrobin and BF 500 - 3 did not occur. Analy tical reference standards for py raclostrobin and its regulated metabolites are available at the EPA National Pe sticide Standards Repository . Adequate confined, limited and extensive field rotational crop studies are available supporting the existing tolerances for indirect residues of py raclostrobin in rotational crops. These data support the 14 - day

plant - back i nterval currently specified for crops without py raclostrobin uses. No additional rotational crop data are required for purposes of this petition. **Regulatory Recommendations and Residue Chemistry Deficiencies** HED has examined the residue chemistry datab ase for py

raclostrobin and concludes that pending submission of a revised label there are no residue chemistry deficiencies that would preclude granting Section 3 registration for the requested crop commodity use of py raclostrobin, or establishment of a to lerance for residues of py raclostrobin. It is recommended that a tolerance be established for residues of the fungicide py raclostrobin, including its metabolites and degradates, in or on sugarcane, cane at 0.2 ppm. Compliance with the tolerance levels is to be determined by measuring only

the sum of py

raclostrobin (carbamic acid, [2 - [[[1 - (4 - chlorophenyl) - 1 H - py razol 3 - yl ]oxy]methyl]phenyl]methoxy- , methyl ester) and its desmethoxy metabolite (methyl N

- [[[1 - (4 - chlorophenyl) - 1 H

- py razol - 3 - yl ]oxy]methyl]phenyl carbamate), calculated as the stoichiometric equivalent of py raclostrobin . A human health risk assessment is forthcoming. 860.1200 Direction for Use A revised label is required for EPA Reg.No. 7969 - 247 (12.0% EC , Multiva® ). The proposed label has a maximum seasonal rate of 0.52 lb ai/acre. However, the directions state that no more than 80 ozs of MultivaTM should be applied per season, which is equivalent to 0.68 lb ai. The 80 ozs is incorrect and must be changed to 62 ounces of product. **Backgroun d**  Py raclostrobin belongs to the strobilurin class of fungicides. Strobilurins are sy nthetic analogs of a natural antifungal substance which inhibits spore germination and mycelial growth and sporulation of the fungus on the leaf surface. T he chemical structure and nomenclature ofPy

raclostrobin D 403449

Page **5** of **18** py racl ostrobin are presented in Tabl e 1. The phy sicochemical properties of the technical grade of py raclostrobin are presented in Table 2 . **TABLE 1. Test Com** **pound Nom enclature.**  Compound

N N Cl O N O C H 3 O OCH 3 Common name Py raclostrobin Company e xperimental name BAS 500 F IUPAC name methyl 2 - [1 - (4 - chlorophenyl)pyrazol - 3 - yloxymethyl] -N - methoxycarbanilate CAS name methyl N - [ 2 - [[[1 - (4 - chlorophenyl) - 1 H - pyrazol - 3 - yl]oxy]methyl]phenyl] -Nmethoxycarbamate CAS registry number 175013 - 18 - 0 End - use produ ct (EP) Headline® EC Fungicide , EPA Reg. No. 7969 - 186. **TABLE 2**  **. Physicochem** **ical Properties of Technical Grade Pyraclostrobin.** Parameter Value References 1 (MRID) Melting point/range 63.7 - 65.2oC 45118213 pH Not applicable Density 1.367 g/cm3 45118 21 4 Water solubility at 20 oC 1.9 ± 0.17 mg/L (deionized water, pH 5.8) 451182 3 3 Solvent solubility n - heptane (0.37 g/100mL); 2 - propanol (3.0 g/100mL); 1 - octanol (2.42 g/100mL); olive oil (2.80 g/100m/L); methanol (10.08 g/100mL); >50 g/100mL in ac etone, ethyl acetate , acetonitrile, dichloromethane and toluene. 451182 28 Vapor pressure 2.6 x 10 - 10 hPa at 20 oC 4511821 4 Dissociation constant, pKa None (no dissociable moieties) Octanol/water partition coefficient, Log(KOW) at room temperature 3.9 90 mean log Pow; Pow is 9772 4511821 5 UV/visible absorption spectrum The structural identity of BAS 500 F was confirmed by NMR and MS spectra. UV molecular extinction (e [1 mol - 1 cm- 1 ]): 2.5x10 4 at 205 nm; 2.4x10 4 at 275 nm. 1996/10955 2

1 Product Chemi stry data were reviewed by the Registration Division (D P# 269848 and D P# 274191, 5/3/01, 5/15/01, and 6/7/01, S. Malak) . 2 BASF Document Number. **860.1200 Directions for Use**  Proposed supplemental labels were provided for end use products7969 - 186, 7969 - 247, 7969 - 289, and 7969 - 291. Supplemental labels were also supplied for the technical products 7969 - 185 (98.0%) and 7969 - 258 (90.2%).Py

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Page **6** of **18 TABLE**  **3 . Sum**  **ma ryof Proposed**  **Use Patterns of Pyraclostrobin .**  Applic. Timing, Ty pe, and Equip. 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 **Sugarcane** Foliar with ground equipment, aerial equipment , or sprinkler irrigation 1 23/6%

2.09 lb ai/gal Headline TM EC 7969 - 186 0.146 - 0.196 N/S 0.78 14 Apply at 14

– 28 day intervals with no more than 2 sequential applications before alternating to a labeled non Group 11 fungicide. Foliar with groun d equipment, aerial equipment, or sprinkler irrigation 1 12.0%

+ 7.4 % metconazole 1.083 lb ai/gal [0.67 lb metconazole /gal] MultivaTM EC 7969 - 247 0.10 - 0.13 4 0. 52 14 Apply at 14

– 28 day intervals with no more than 2 sequential applications before alternating to a labeled non Group 11 or non Group 3 fungicide. Do not apply more than 80 oz of Multiva per acre per season [0. 68 lb ai/acre].. Foliar with ground equipment, aerial equipment, , or sprinkler irrigation 1 23.3%

2.08 lb ai/gal Headline TM SC 7969 - 289 0.195 N/S 0.78 14 Apply at 14

– 28 day intervals with no more than 2 se quential applications before alternating to a labeled non Group 11 fungicide. Foliar with ground equipment, aerial equipment, or sprinkler irrigation 1 13.64%

+5.14% metconazole 1.22 lb ai/gal [0.46 lb metconazole /gal] BAS 556 SC 7969 - 291 0.14 - 0.19 4 0.7 6 14 Apply at 14

– 28 day intervals with no more than 2 sequential applications before alternating to a labeled non Group 11 or non Group 3 fungicide. Do not apply more than 80 oz of Multiva per acre per season [0.76 lb ai/acre].. 1 From approved existing master label. Not included in proposed supplemental label. The label for 7969 - 247 (12.0% EC) has a maximum seasonal rate of 0.52 lb ai/acre. However, the directions state that no more than 80 oz of MultivaTM should be applied per season, which is equiv a lent to 0.68 lb ai. The 80 oz is incorrect and must be changed to 62 oz of product. Conclusion s: The submitted use directions are sufficient to allow for evaluation of the submitted residue data relative to the proposed use pattern. **860.1300 Nature of the Residue**  **- Plants** Py

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Page **7** of **18** HED M ARC , DP# 278044 , L. Cheng , 10/9/01 PP#0F6139, DP# 269668 , L. Cheng , 11/28/01 Adequate metabolism studies with py raclostrobin on grapes, potatoes, and wheat have been reviewed (D269668, 11/28/01, L . Cheng) in conjunction with PP#0F06139. The results of these studies indicate that the metabolism of py raclostrobin is similar in the three crops investigated. The HED Metabolism Assessment Review Committee (MARC) discussed the results of these studies on 9/20/01, and concluded that the nature of the residue in plants is understood. For the purpose of tolerance and risk assessment, the terminal residues of concern in plants consist of py raclostrobin and its desmethoxy metabolite (BF 500 - 3). **860.1300 Nature of the Residue –**  **Livesto ck**  HED M ARC , DP# 278044, L. Cheng, 10/9/01 PP#0F6139, DP# 269668, L. Cheng, 11/28/01 The nature of the residue in livestock is adequately understood based on acceptable ruminant and poultry metabolism studies. In goat , the major residues are py raclostro bin and BF 500 - 3 in muscle and fat; py

raclostrobin, BF 500 - 3, and BF 500 - 5 and its sulfate conjugate in milk; py raclostrobin, BF 500 - 3, and BF 500 - 5 and its sulfate conjugate, and hydroxylated desmethoxy metabolite (500M67) in kidney ; and metabolites hydro ly zed to BF 500 - 5 and its hydroxylated compound (BF 500 - 8) in liver. In poultry , the major residues are py raclostrobin and BF 500 - 3 in eggs; py raclostrobin, BF 500 - 3, and hydroxylated BF 500 - 3 (500M64) in fat; and the glucuronic acid conjugate of hydroxyl ated BF 500 - 3 (500M32) in liver. Radioactive residues were below detection in muscle. The main degradation reactions in livestock consist of demethoxy lation, hydroxylation, and conjugation, and breaking of the ether bond. HED has determined that for the tolerance and risk assessment, the residues of concern in livestock commodities consist of py raclostrobin and its metabolites convertible to 1 - (4 - chlorophenyl) - 1 H

- py razol - 3 - ol (BF 500 - 5) and 1 - (4 - chloro - 2 - hydroxy phenyl) - 1 H

- py razol - 3 - ol (BF 500 - 8). **860.13 40 Residue Analytical Methods**  PP#0F6139 , DP# 269668 , L. Cheng , 11/28/01 PP#0F6139, DP# 269850 , L. Cheng , 11/8/00 MRID: 48049201, W. Cutchin, in process Enforcement : Two adequate methods are available for enforc ement purposes for residues of py raclostrobi n and the metabolite BF 500 - 3 in/on plant commodi ties: an LC/MS/MS method (BASF Method D9 9 08) and an HPL C/UV method (Method D9904). The validated method L OQ for both py

raclostrobin and BF 500 - 3 is 0.02 ppm in all tested plant matrices, for a combined LOQ of 0.04 ppm. Adequate independent method validation and radiovalidation data were submitted for both methods and forwarded to Analy tical Chemistry

Branch/Biological and Economic Analysis Division ( ACB/BEAD ) for a petition method validation. Data Collecti on: Samples from field trial and processing studies were analy zed for py raclostrobin and its metabolite BF 500 - 3 using BASF Analy tical Method Number D9908, "Method for Determining BAS 500 F, BF 500 - 3 and BAS 510 F Residues in Plant Matrices using LC/MS/MS . ” Briefly , residues were extracted from sugarcane with methanol:water:2 NPy

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Page **8** of **18** HCl (70:25:5, v : v : v) by P oly tron homogenization. After centrifugation, an aliquot of the supernatant was removed and cleaned up by liquid/liquid partitioning using cyclohexane and 1N HCl saturated with NaCl. An aliquot of the cyclohexane phase was taken, evaporated to dry ness, and re - dissolved in a buffered methanol:water (80:20, v :v, each containing 0.1% formic acid and 4 mM ammonium formate) for analysis by L C/MS/MS. MS/MS detec tion using the positive ionization mode monitored ion transitions from m/z 388 →194 for py raclostrobin and m/z 358 →164 for BF 500 - 3. The LLMV in this study

was 0.02 ppm for each of py raclostrobin and BF 500 - 3. Concurrent recoveries from fortifications of sugarcane at 0.02 and 20 ppm ranged from 76% to 110%. Concurrent recoveries from blackstrap molasses at the same fortifications ranged from 85

– 112%, and for refined sugar, 85

– 101% The re were acceptable concurrent method recovery data. Conclusion s: There are adequate residue analy tical methods for tolerance enforcement an d data collection. **860.1360 Multiresidue Methods** PP#0F6139 , DP# 269668 , L. Cheng , 11/28/01 Py raclostrobin was successfully evaluated through several of the FDA protocols, while recovery of BF 500 - 3 was unsuccessful in all protocols. Py raclostrobin was completely recovered through Protocol D (in grape) and E (in grape), and partially recovered through Protocol F (in peanut). Metabolite BF 500 - 3 had poor peak shape and inadequate sensitivity with Protocol C columns, and therefore was not further analy zed under Protocol D, E, and F. The results of the multiresidue testing for py raclostrobin were forwarded to FDA on 1/4/02 for the purpose of updating the Pesticide Analytical Manual , Volume I ( PAM I) . **860.1380 Storage Stability** PP#0F6139 , DP# 269668 , L. Ch eng , 11/28/01 Samples of sugar cane from the field trials were stored frozen (< - 17 °C) for up to 757 days (about 25 months) . Samples of processed commodities were stored frozen ( ≤ - 12 °C) for up to 518 days (17 months). Residues of py raclostrobin and i ts metabolite BF 500 - 3 are stable under frozen storage conditions in/on representative crop commodities of grape juice, sugar beet tops and roots, tomatoes, and wheat grain and straw for up to 25 months, and peanut nutmeat and processed oil for up to 19 mo nths . Conclusion s: T hese data are adequate to support the storage conditions and durations of samples from the sugarcane field trials and processing study . **860.1400 Water, Fish, and Irrigated Crops** This guideline requirement is not relevant to the current petition s as there are no aquatic uses being proposed for py

raclostrobin. **860.1460 Food Handling**Py

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Page **9** of **18** This guideline requirement is not relevant to the current petition s as there are no food - handling uses being proposed for py raclostrobin. **860.1480 Meat, Milk, Poultry, and Eggs**  Sugarcane blackstrap molasses is a carbohydrate concentrate (CC) feed item for dairy cattle and beef cattle and may

comprise up to 10% of the diet of each. The processing factor for conversion of sugarcane to blackstrap molasses is 0.3X (S. Funk, 48237401.der2). Applying that factor to the HAFT for sugarcane (0.12 ppm, Table 4 ) yields a residue of 0.04 ppm on blackstrap molasses. The contribution to the diet is 0.12 X 10% / 75% DM = 0.02 ppm. The dietary exposure of cattle wa s most recently determined to be 6.1 ppm for beef cattle and 12.9 ppm for dairy cattle (D 367409 , 12/29/09 , W. Cutchin ). Carbohydrate concentrates (CC) contributed 2.56 ppm to the dairy

diet and 1.0 ppm to the beef cattle diet. These represent the maximum percentages allowed (80% CC for beef cattle and 45% for dairy cattle). Sugarcane blackstrap molasses was included in the calculation at a concentration of 0.4 ppm, based on the temporary emergency

tolerance. It contributed minimally (0.03 ppm) to the burd en, and its contribution would now be less. Therefore, no significant changes to the dietary burden result from the present considerations. No changes to the existing livestock tolerances are indicated. Sugarcane blackstrap molasses is not a poultry or swine feed item. **860.1500 Crop Field Trials** MRID: 48237401 BASF Corp. has submitted field trial data for py raclostrobin on sugarcane. A total of 8 crop field trials on sugarcane were conducted in the United States during the 2008 growing season in North American Free Trade Agreement (NAFTA ) Growing Zones 3 (FL, 3 trials), 4 (LA, 4 trials), and 6 (TX). Examination of the field trial records indicates that one director supervised all three field trials in FL

(all in the same city

), and another director s upervised all field trials in both LA (four in the same city

) and the one trial approximately 600 miles distant in TX. Every crop field trial differed as to crop variety , and the four trials in LA involved three different soil ty pes. Also, the geographic area in which sugarcane is cultivated in the continental USA is relatively small. The trials are considered independent (n = 8) for purposes of OSCPP 860.1500 data requirements. Each trial consisted of one untreated (control) plot and one treated plot . At each trial location, the treated plots received four foliar directed or foliar broadcast applications of a 2.09 lb ai/gal EC formulation of py

raclostrobin ( Headline ® ) during the vegetative or bloom stages of development at rates of 0.189 - 0.206 lb ai/A/application (0.21 - 0.23 kg ai/ha/application), for total seasonal rates of 0.78 - 0.81 lb ai/A (0.88 - 0.91 kg ai/ha). RTI s were 13 - 14 days. Applications were made using ground equipment in spray volumes of 15.54 - 27.15 gal/A of water (145 - 254 L/ha), contain ing 0.125 - 0.126% (v/v) of the NI S Silwet as an adjuvant in all trials except for those in FL , which used no adjuvant. At two trial locations (Trial IDs 08 - FL32 and 08 - TX24) designed to produce samples for processing , an additional plot received four foliar directed or foliar broadcast applications of the Headline ® formulation of py raclostrobin ( Headline ® ) at rates of 0.977 - 1.04 lb ai/A/application (1.09 - 1.13 kg ai/ha/application ; 5x ) beginning 56 days prior to harvest during the vegetative or bloom stages, with RTI s of 13 or 14 days. The total seasonalPy

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Page **10** of **18** (5x) rates were 3.94 - 3.99 lb ai /A (4.42 - 4.47 kg ai /ha). Applications were made using ground equipment, and the spray

volumes were 21.65 - 22.32 gal/A of water (202 - 209 L/ha), containing 0.125 - 0.128% (v/v) of the NI S Silwet as an adjuvant in the TX trial; no adjuvant was used in the FL trial. Samples of sugarcane were harvested from all trials at PHI s of 13 - 14 and 27 - 28 days. Samples of sugarcane were fortified with py raclostrobin and BF 500 - 3 at 0.02 and 20 ppm. The method was adequate for data collection based on acceptable concurrent recovery data. Recoveries were all within the acceptable range of 70 - 120%. The fortification levels used in concurrent method recovery were adequate to bracket expected re sidue levels. No residues of py raclostrobin or its metabolite BF 500 - 3 equal to or above the LLM V were detected in any control samples . Results are summarized in Table 4. **TABLE.4. Summary of Residue Data from** **Crop Field Trials with Pyraclostrobin.** C ommodity Total

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

(days) Analyte Residue Levels 1 (ppm) n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev.

Sugarcane 0.78 - 0.81

(0.88 - 0.91) 13 - 14 Py raclostro bin 8 <0.02 0.1049 <0.02 0.099 0.058 <0.060 0.026 BF 500 - 3 8 <0.02 0.0267 <0.02 0.027 <0.02 <0.021 0.002 Combined 8 <0.04 <0.125 <0.040 <0.119 <0.076 <0.076 0.029 27 - 28 Py

raclostro bin 8 <0.02 0.0866 <0.020 0.068 0.043 <0.044 0.016 BF 500 - 3 8 <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 N/A Comb ined 8 <0.04 <0.1066 <0.04 0 <0.088 <0.062 <0.061 0.017 Sugarcane (for processing) 3.94 - 3.99

[4.42 - 4.47] 14 Py raclostro bin 2 0.0238 0.2935 0.028 0.255 0.141 0.141 N/A BF 500 - 3 2 <0.02 0.0253 <0.02 0.025 <0.022 <0.022 N/A Combined 2 <0.044 0.319 <0 .048 0.280 <0.164 <0.164 N/A 28 Py raclostro bin 2 0.0203 0.3811 3 0.026 0.268 0.147 0.147 N/A BF 500 - 3 2 <0.02 0.0405 <0.02 <0.030 <0.025 <0.025 N/A Combined 2 <0.040 0.422 <0.046 <0.299 <0.172 <0.172 N/A Conclusions: The number and geogr aphic distribution of the trials are adequate. The analy tical method was demonstrated to be acceptable via concurrent recoveries of fortified control samples. The intervals of frozen storage of samples are covered by previous storage stability studies, and no corrections for loss of residue are needed. The trials were conducted according to the proposed label for the EC formulation (single and seasonal application rates, PHI). The results of the field trials are acceptable for estimation of a sugarcane tolerance and for dietary risk assessment purposes.Py

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Page **11** of **18 860.1520 Processed Food and Feed**  PP#0F6139, DP# 269668, L. Cheng, 11/28/01 MRID 48237401 A processing study

was submitted for sugarcane. Ina single sugarcane field trial conducted in North American Fr ee Trade Agreement (NAFTA) Growing Zone 6 (TX) during the 2008 growing season, a 2.09 lb ai/g al e mulsifiable c oncentrate (EC) formulation of py

raclostrobin (Headline ® ) was applied to sugarcane as four broadcast foliar applications at rates of 0.977 - 0.993 lb ai/A/application (1.09 - 1.11 kg ai/ha/application; reported 5x rate) beginning 53 days prior to harvest during the vegetative stage, with a retreatment interval (RTI) of 13 days. The total seasonal rate was 3.9 4 lb ai/A (4.42 kg ai/ha; 5x). Bulk samp les of sugarcane were harvested 14 days after the last application. Sugarcane was processed within 21 - 27 days of harvest into blackstrap molasses and refined sugar using simulated commercial procedures. Samples of sugarcane cane and processed sugarcan e commodities were analy zed for residues of py raclostrobin and its metabolite BF 500 - 3 using a liquid chromatography method with tandem mass spectrometry detection ( LC /MS/MS), Method D9908 (Version I I). Samples of sugarcane RAC, blackstrap molasses, and r efined sugar were fortified with py raclostrobin and BF 500 - 3 at 0.02 and 20 ppm. The method was adequate for data collection based on acceptable concurrent recovery data. Recoveries were all within the acceptable range of 70 - 120%. Results are summariz ed in Table 5. **Table 5**  **Residue Data from Sugarcane**  **Processing Study with Pyraclostrobin**  **.** Sugarcane Commodity Total Rate (lb ai /A) [kg ai/A] PHI

(days) Residues (ppm) 1 Processing Factor Py raclostrobin BF 500 - 3 2 Combined 2 Sugarcane RAC 3.94 [4.42] 14 0.232 0.033 0.265 -- Blackstrap molasses 0.057 <0.02 <0.077 <0.29 x Refined sugar <0.02 <0.02 <0.04 < 0. 15 x 1 The petitioner used the lowest level of method validation (LLMV) of 0.0 2 ppm as the limit for reporting residues for both pyraclostrobin and its metabolite BF 500 - 3 . For determining the combined residues, the LLMV was used for values reported as <LLMV. 2 Residues of metabolite BF 300 - 3 were reported in parent equivalents. Conclusions: The submitted sugarcane processing study is adequate. An acceptable method was used for quantitation of py

raclostrobin and BF 500 - 3 residues in sugarcane RAC and sugarcane processed commodities. Samples were stored frozen for intervals covered by the storage stability

study . Residues of py

raclostrobin and BF 500 - 3 did not concentrate in blackstrap molasses or refined sugar, relative to the concentration in the raw agricultural commodity (sugarcane). Therefore, tolerances are not necessary for these processed commodities. **860.1650 Submittal of Analytical Ref erence Standards** Py

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Page **12** of **18** Analy tical reference standards for py raclostrobin and regulated metabolites (BF 500 - 3 ; BF 500 - 5; BF 500 - 8 ) are currently

available in the EPA Nationa l Pesticide Standards Repository (e - mail correspondence with T. Cole , 01/14/2013 ) . **860 .1850 Confined Accumulation in Rotational Crops**  MARC , DP# 278044 , L. Cheng , 10/9/01 PP#0F6139, DP# 269668, L. Cheng , 11/28/01 An adequate confined rotational crop study was reviewed in PP#0F6139. The study showed that the metabolism of py

raclostrobin in rotated crops is similar but more extensive than that in primary crops. Py

raclostrobin undergoes demethoxylation to yield BF 500 - 3, followed by further degradation to medium polar and polar metabolites, and subsequent conjugation reactions and incorporati on into natural products. The HED MARC has determined that the residues of concern in rotational crops consist of py raclostrobin and metabolite BF 500 - 3. **860.1900 Field Accumulation in Rotational Crops** PP#0F6139 , DP# 269668, L. Cheng , 11/28/01 A limited field rotational crop study was reviewed in PP#0F6139. The results indicate that r esidues of py

raclostrobin and its metabolite BF 500 - 3 were each less than the method L OQ (<0.02 ppm) in/on rotational crop matrices (radish, roots and tops; cabbage, with and without wrapper leaves; and wheat forage, hay , and grain) planted 14 days following the last of six sequential foliar applications to the primary crop, cucumbers, of the 2 lb/gal EC formulation at 0.19 - 0.20 lb ai/A/application. Residues of py raclostrobin in/on one sample of wheat straw from the CA test site were at the L OQ (0.02 ppm), but residues of py raclostrobin in/on a replicate sample from the same plot were below the L OQ (0.012 ppm) for an average residue of <0.02 ppm. Res idues of metabolite BF 500 - 3 were nondetectable (<0.02 ppm) in/on all samples of wheat straw. The registered py

raclostrobin end - use product labels presently specify a 14 - day plantback interval restriction for all crops that are not registered. **860.1550 Proposed Tolerances**  For the use of py

raclostrobin on sugarcane a tolerance is required. A time - limited Section 18 tolerance of 0.02 ppm exists (40 CFR §180.582(b). Based on evaluation of the sugarcane field trial data with the Organization for Economi c Cooperation and Development (OECD) tolerance calculation procedure, a tolerance of 0.2 ppm is appropriate for sugarcane , cane (see Appendix I). Codex and Canada have not established MRL s for py raclostrobin on sugarcane. Therefore, there is no issue of harmonization. Py raclostrobin residues did not concentrate in sugarcane molasses and sugarcane refined sugar. Therefore these commodities are covered by the tolerance for the raw agricultural commodity, sugarcane, cane. The recommended tolerances for su garcane commodities is presented in Table 6.Py

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Page **13** of **18 Table**  **6 .**  **Tolerance Sum ma**  **ry for Pyraclostrobin**  **.** Commodity Proposed/Existing Tolerance (ppm) Recommended/ Harmonized Tolerance (ppm) Comments; Correct Commodity

Definition 40 CFR §180.582(a) It is recommend ed that a tolerance be established for residues of the fungicide pyraclostrobin, including its metabolites and degradates, as indicated below . Compliance with the tolerance levels is to be determined by measuring only the sum of pyraclostrobin (carbamic a cid, [2 - [[[1 - (4 - chlorophenyl) - 1 H - pyrazol - 3 - yl]oxy]methyl]phenyl]methoxy- , methyl ester) and its desmethoxy metabolite (methyl N - [[[1 - (4 - chlorophenyl) - 1 Hpyrazol - 3 - yl]oxy]methyl]phenyl carbamate), calculated as the stoichiometric equivalent of pyraclostro bin Sugarcane, cane 0.2 0.2 0 - 40 CFR § 180.582(b ) Section 18 emergency exemptions Sugarcane, cane 0.02 Revoke Replaced with new tolerance in (a) Sugarcane, molasses 0.4 0 Revoke Replaced with new tolerance in (a) for sugarcane, cane **References** DP# s: 367409 Subject: Py

raclostrobin. Petition for New Uses and Tolerances on Alfalfa. Summary of Analy tical Chemistry

and Residue Data. From: W. Cutchin To: T. Kish/J. Bazuin Dated: 10/19/09 MRIDs: 47584401 DP#s: 281042, 286732, 287729, 288459, 290342, 29 0343, 290369, 292440, 293088,

293684, 295893, 298178 Subject: Py

raclostrobin. PP#3F06581, 2F06431, 2E6473, 3E6548, 3E6553, 3E6774, and 2F06139. Petitions for the establishment of permanent tolerances to allow uses on corn (field, sweet, and pop), hops, m int, pome fruits, edible - podded legume vegetables, succulent peas, sunflower, Brassica leafy greens, soy

beans, succulent beans, broccoli, cabbage, lettuce (head and leaf), spinach, celery , turnip greens, and the import commodities mango and papaya. Applic ation for amended Section 3 registration for citrus (reduced PHI). Petitioner’s response to data deficiencies identified in PP#0F06139 regarding storage stability data, dried shelled peas and beans (reduced PHI), and uses on dry and succulent peas. Summary of Analy tical Chemistry

and Residue Data. From: L. Cheng To: C. Giles - Parker/J. Bazuin Dated: 7/26/04 MRIDs: 45596211, 45623406, 45623407, 45623408, 45623410, 45645801, 45645802,

45645803, 45645804, 45702901, 45765401, 45832001, 45858801, 45858802, 4590 3601, 45903602, 46033901 - 04, 46084401 - 04, 46109101, 46109102Py

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Page **14** of **18** DP#s: 269668, 272771, 272789, 274095, 274192, 274471, 274957, 275843, and 278429 Subject: PP#0F06139. Py raclostrobin on Various Crops: Bananas (import), Barley, Berries, Bulb Vegetables, Citr us Fruits, Cucurbit Vegetables, Dried Shelled Pea & Bean (except Soy

bean), Fruiting Vegetables, Grapes, Grass, Peanut, Pistachio, Root Vegetables (except Sugar Beet), Rye, Snap Beans, Stone Fruits, Strawberry , Sugar Beet, Tree Nuts, Tuberous and Corm Veget ables, and Wheat. Review of Analy tical Methods and Residue Data. From: L. Cheng To: C. Giles - Parker/J. Bazuin Dated: 11/28/01 MRIDs: 45118428 - 451184 - 37, 45118501 - 45118512, 45118514 - 45118537, 45118601 -

45118625, 45160501, 45272801, 45274901, 45321101, 453 67501, 45399401, and 45429901 DP#: 278044 Subject: PP# 0F06139. PC Code 099100. Py raclostrobin. Outcome of the HED Metabolism Assessment Review Committee (MARC) Meeting Held on September 20, 2001. From: L. Cheng To: Y. Donovan Dated: 10/09/01 MRIDs: No ne DP#: 269850 Subject: PP# 0F06139. Py raclostrobin (BAS 500F) in or on Various Crops. Request for Tolerance Method Validation (TMV) Trial. From: L. Cheng To: F. D. Griffith, Jr. Dated: 11/8/00 MRIDs: 45118505, 45118504, 45118509, 45118510, 45118501, 451 18503, 45118507,

45118514Py

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Page **15** of **18** DP#: 281042, 286732, 287729, 288459, 290342, 290343, 290369, 292440, 293088,

293684, 295893, 298178 Subject: Py

raclostrobin. PP#3F06581, 2F06431, 2E6473, 3E6548, 3E6553, 3E6774, and 2F06139. Petitions for the establishment of p ermanent tolerances to allow uses on corn (field, sweet, and pop), hops, mint, pome fruits, edible - podded legume vegetables, succulent peas, sunflower, Brassica leafy greens, soy

beans, succulent beans, broccoli, cabbage, lettuce (head and leaf), spinach, c elery , turnip greens, and the import commodities mango and papaya. Application for amended Section 3 registration for citrus (reduced PHI). Petitioner’s response to data deficiencies identified in PP#0F06139 regarding storage stability data, dried shelle d peas and beans (reduced PHI), and uses on dry and succulent peas. Summary of Analy tical Chemistry

and Residue Data. From: L. Cheng To: Cy

nthia Giles - Parker Dated: 7/26 /0 4 MRIDs: 45596211, 45623406, 45623407, 45623408, 45623410, 45645801, 45645802, 45645 803,

45645804, 45702901, 45765401, 45832001, 45858801, 45858802, 45903601, 45903602, 46033901 - 04, 46084401 - 04, 46109101, 46109102Py

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Page **16** of **18** 

### I nternational Residue Limits Pyraclostrobin ( 099100; 01/31/2013 ) Summary of US and International Tolerances and Maximum Res idue Limits Residue Definition : US Canada Mexico 2 Codex 3 40 CFR §180.582. Plants: Tolerances are established for residues of the fungicide pyraclostrobin, including its metabolites and degradates. Compliance with the tolerance levels is to be determined by measuring on the sum of pyraclostrobin (carbamic acid, [2 - [[[1 - (4 - chlorophenyl) - 1 H

- pyrazol - 3 - yl]oxy]methyl]phenyl]methoxy- , methyl ester) and its desmethoxy metabolite (methyl N - [[[1 - (4 - chlorophenyl) - 1 H

- pyrazol - 3 - yl]oxy]methyl]phenyl carbamate), c alculated as the stoichiometric equivalent of pyraclostrobin methyl [2 - [[[1 - (4 - chlorophen yl) - 1 Hpyrazol - 3 - yl]oxy]met hyl]phenyl] methoxycar bamate, including the metabolite [2 - [[[1 - (4 - chlorophen yl) - 1 Hpyrazol - 3 - yl]oxy]met hyl]phenyl] carbamate - Py raclostrobi n. Residue is NOT fat soluble.

Commodity 1 Tolerance (ppm) /Maximum Residue Limit ( ppm ) US Canada Mexico 2 Codex 3 Sugarcane, cane 0.2 None None 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendatio ns and not those proposed by the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest tr eated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.Py

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Page **17** of **18** 

### Appendix I: Determination of Tolerance for Pyraclostrobi n in/on Sugarcane and Its Processed Fractions The Organization of Economic Cooperation and Development statistical procedure was used to calculate a tolerance estimate for sugarcane. The estimate agreed with the proposal of BASF. **Pyraclostrobin Sugarcane**  **USA 0.80 lb ai/A,**  

### PHI **14 day**  **Total number of data (n)** 8 **Percentage of censored data** 25% **Number of non -**  **censored data** 6 **Lowest residue** 0.040 **Highest residue** 0.119 **Median residue** 0.076 **Mean** 0.076 **Standard deviation (SD)** 0.029 **Correct ion factor for censoring (CF)**  0.833 **Proposed MRL estimate**

**- Highest residue**  0.119

**- Mean + 4 SD**  0.191

**- CF x 3 Mean**  0.190 **Unrounded MRL** 0.191 **Rounded MRL 0.2**  **Residues (mg/kg) n**  < 0.04 2 0.068 1 0.073 1 0.078 1 0.07 9 1 0.112 1 0.119 1 **Pyraclostrobin Sugarcane**  **USA 0.80 lb ai/A,**  

### 28 dayPy

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Page **18** of **18 Total number of data (n)**  8 **Percentage of censored data** 25% **Number of non -**  **censored data** 6 **Lowest residue** 0.040 **Highest residue** 0.088 **Median residue** 0.062 **Mean** 0.061 **S tandard deviation (SD)**  0.017 **Correction factor for censoring (CF)** 0.833 **Proposed MRL estimate**

**- Highest residue**  0.088

**- Mean + 4 SD**  0.131

**- CF x 3 Mean**  0.153 **Unrounded MRL** 0.153 **Rounded MRL 0.15**  **Residues (mg/kg) n**  < 0. 04 2 0.05 1 0.06 1 0.063 1 0.074 1 0.076 1 0.088 1 Processed Commodities Py raclostrobin and BF 500 - 3 declined in concentration from the raw agricultural commodity (RAC) to refined sugar and blackstrap molasses processed products. Therefore, the tolerance for sugarcane wil l cover the processed commodities. No separate tolerances are needed.