Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **1** of **78 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**  **WASHINGTON, DC 20460 OFFICE OF CHEMICAL S**  **AFETY AND POLLUTION PREVENTION**  **MEMORANDUM D**  **ATE :**  **7 July 2014 SUBJECT:**  **Metrafenone.** Petition to Establish Permanent Tolerances (with Section 3

Registration) for Residues Resulting from Use of the Fungicide on Apricot , Cherry S ubgroup 12 - 12A, Peach Subgroup 12 - 12B, F ruiting V egetables Group 8 - 1 0 , S mall Vine C limbing Fruit E xcept Fuzzy Kiwifruit S ubgroup 13 - 07F , Hops , Pome F ruit s Group 11 - 10 , and Cucurbit Vegetable s Group 9 ; Evaluation of Conditional Data . **Summary of Analytical Chemistry and Residue Data. PC Code:**  000325 **DP Barcodes:** D407432, D 411389, D414077, D 416465 , D417602 **Decision N umbers**  **:** 472590, 476552, 480739, 4 84338 **Registration N umber**  **:** 7969 - 284 **Petition Numbers**  **:** 3F8163 , 3F8187, 3E8211 **Regulatory Action:** Section 3 Registration **Risk Assessment Type:** NA **Case Number**  **:** 7052 **T XR N**  **umber :**  NA **CAS Number**  **:** 220899 - 03 - 6 **MRID Numbers:** 489813 03, - 04, - 07 & - 08; 49055901 & - 02 ; 49119101 to - 09 ; 49145401 to - 08 ; 49267201 to - 05 **40 CFR:** § 180.624 **FROM:** William T. Drew, Chemist

Dennis McNeill y, Chemist Risk Assessment Branch II (RAB2) Health Effects Division (HED) , 7509P **THRU:** Elizabeth Holman, Physical Scientist

Michael Doherty , PhD, Senior Scientist RAB2/HED, 7509P **TO:** Tony

Kish and Heather Garvie , RM Team 22 Fungicide Branch (FB) Registration Division ( RD), 7505P and Barbara Madden and Andrew Ertman, RM Team 5 Risk Integration Minor Use, and Emergency Response Branch (RIMUERB) RD, 7505PMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **2** of **78 Table of Contents**  1.0 Executive Summary ................................ ................................ ................................ .............. 4 2.0 Regulatory

Recommendations ................................ ................................ .............................. 7 2.1 Data Deficiencies/Data Needs ................................ ................................ .......................... 7 2.2 Tolerance Considerations ................................ ................................ ................................ .. 8 2.2.1 Enforcement Analy tical Method/Multiresidue Methods ................................ .......... 8 2.2.2 Recommended Tolerances ................................ ................................ ........................ 9 2.2.3 Revisions to Petitioned - For Tolerances ................................ ................................ .... 9 2.2.4 International Harmonization ................................ ................................ ..................... 9 2.3 L abel Recommendations ................................ ................................ ................................ 10 2.4 Submittal of Analy tical Reference Standards (860.1650) ................................ ............. 10 3.0 Chemical Identity ................................ ................................ ................................ ............... 10 3.1 Nomenclature ................................ ................................ ................................ ................. 11 3.2 Phy sic oc hemical Characteristics ................................ ................................ .................... 11 3.3 Pesticide Use Pattern/Directions for Use (860.1200) ................................ .................... 12 4.0 Metabolite/Degradate Residue Profile ................................ ................................ ............... 13 4.1 Nature of the Residue ................................ ................................ ................................ ..... 1 9 4.1.1 Summary

of Plant and

/ or Li vestock Metabolism (860.1300) ................................ . 24 4.1.2 Summary

of Confined Rotational Crops (860.l850) ................................ ............... 27 4.1.3 Summary

of Rat Metabolism ................................ ................................ ................ 27 9 4.1.4 Summary

of Environmental Degradation ................................ ............................... 29 5.0 Residue Profile ................................ ................................ ................................ ................... 30 5.1 Residue Anal ytical Methods (860.1340) ................................ ................................ ...... 30 5.1.1 Data Collection Methods ................................ ................................ ........................ 30 5.1.2 Multi - Residue Methods (860.1360) ................................ ................................ ........ 33 5.1.3 Tolerance Enforcement Methods ................................ ................................ ............ 34 5.2 Storage Stability

(860.1380) ................................ ................................ .......................... 38 5.3 Residue Data ................................ ................................ ................................ .................. 40 5.3.1 Crop Field Trials (860.1500) ................................ ................................ .................. 40 5.3.2 Field Rotational Crops (860.1900) ................................ ................................ ......... 55Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **3** of **78** 5.3.3 Processed Food and Feed (860.1520) ................................ ................................ ..... 55 5.3.4 Meat, Milk, Poultry and Eggs (860.1480) ................................ .............................. 60 5.3.5. Food Handling (860.1460) ................................ ................................ ...................... 61 5.3.6 Water, Fish and Irrigated Crops (860.1400) ................................ ........................... 61 5.4 Food Residue Profile ................................ ................................ ................................ ...... 61 6.0 Tolerance Derivation ................................ ................................ ................................ ......... 62 References ................................ ................................ ................................ ................................ ..... 6 3 Attachment 1: International Residue Limit Statu s ................................ ................................ ....... 6 5 Attachment 2: OECD MRL(Tolerance) Assessment Calculations ................................ .............. 6 6Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **4** of **78 1.0**  **Executive Summary** Metrafenone (with CAS name (3 - bromo - 6 - methoxy- 2 - methylphenyl)(2,3,4 - trimethox y- 6 - methylphenyl )methanone ) is a benzophenone fungicide that has preventative properties for control of powdery

mildew produced b y assorted pathogens in various fruit s and vegetables . In PP# 3F8163, BASF Corporation has proposed the establishment of permanent tolerances for residues of the fungicide metrafenone in/on the following raw agricultural commodities (RAC s ), at the level listed below. Fruits, pome group 11 - 10 ................................ ................................ . 1 .5 ppm In PP#3F 8187 , BASF Corporation has proposed the establishment of permanent tolerances for residues of the fungicide metrafenone in/on the following RAC s , at the level listed below. V egetables, Fruiting, group 8 - 10 ................................ ..................... 1.0 ppm In PP#3 E 8211 , Interregional Research Project Number 4 (IR- 4) has proposed the establishment of permanent tolerances for residues of the fungicide metrafenone in/on the following RACs, at the levels listed below. Apricot ................................ ................................ ............................. 0.7 ppm Cherry subgroup 12 - 12A ................................ ................................ .... 2 ppm Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F ................................ ................................ .............. 4.5 ppm Hop , dried cones ................................ ................................ .............. 70 ppm Peach subgroup 12 - 12B ................................ ................................ ... 0.7 ppm Vegetable, cucurbit, group 9 ................................ ............................ 0.5 ppm The nature of the residue in plants is adequatel y understood , based on acceptable grape and cucumber metabolism studies . HED has previously determined that , for tolerance enforcement purposes, the residue of concern ( ROC) in primary crops is parent metrafenone only . HED also concluded previously that certain unidentified and tentatively identified residues from the grape metabolism study

should be accounte d for in the dietary risk assessment. In conjunction with PP# 3F8163, BASF submitted a FIFRA Section 3 requesting registration of a suspension concentrate (SC) formulation (Vivando ; EPA Reg istration #7969 - 284) , containing 2.5 pounds of the active ingredi ent per gallon (lb ai/gal), for use on pome fruit s group 11 - 10 . The product is proposed for up to 3 foliar applications to pome fruit s at 0.2 - 0.3 lb ai per acre (lb ai/A) per application , with a maximum seasonal application rate of 0.9 lb ai/A, a minimum re treatment interval (RTI) of 7 day s, and a pre - harvest interval (PHI) of 7 day s.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **5** of **78** In conjunction with PP# 3F8187, BASF submitted a FIFRA Section 3 requesting registration of the SC formulation, Vivando , for use on fruiting vegetables group 8 - 10 . The product is proposed for up to 3 foliar applications to fruiting vegetables at 0.2 - 0.3 lb ai/A per application, with a maximum seasonal application rate of 0.9 lb ai/A, a minimum RTI of 7 day s, and a PHI of 0 day s. In conjunction with PP# 3F8211, IR - 4 submitted a FIFRA Section 3 requesting registration of the SC formulation, Vivando, for use on apricots, cherry subgroup 12 - 12A, peach subgroup 12 - 12B (up to 2 foliar applications at 0.2 - 0.3 lb ai/A per application, with a maximum seasonal application rate of 0.6 lb ai/A, a minimum RTIof 7 day s, and a PHI of 7 day s ), hops (same use pattern, except a PHI of 3 day s), cucurbit vegetables group 9 (up to 3 foliar applications at 0.2 - 0.3 lb ai/A per application, with a maximum seasonal application rate of 0.9 lb ai/A, a minimum RTIof 7 day s, and a PHI of 0 day s), and small vine - climbing fruit except fuzzy kiwifruit subgroup 13 - 07F (same use pattern, except a minimum RTIof 14 day s, and a PHI of 14 days ) . Crop Field Trials: The number and geographic distribution of the field trials are adequate, and the use patterns are consistent with the maximum proposed use pattern regarding application rate, PHI, and minimum RTI s. Adequate pome fruit field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 1 .5 ppm in pome fruit s (group 11 - 10) . Adequate fruiting vegetable field trial data were submitted in support of the proposed use. The submitted data support a recommended tolerance of 0.9 0 ppm , rather than the proposed tolerance of 1.0 ppm , in fruiting vegetables (group 8 - 10) . Adequate cucurbit vegetable field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 0.5 ppm in cucurbit vegetables (group 9); HED recommends that the tolerance be established at 0.50 ppm . Adequate cherry

field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 2 ppm in the cherry subgroup (12 - 12A) ; HED recommends that the tolerance be established at 2.0 ppm . Adequate peach field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance o f 0.7 ppm in the peach subgroup (12 - 12B); HED recommends that the tolerance be established at 0.70 ppm. Adequate hops field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 70 ppm in hops.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **6** of **78** The proposed tolerance of 4.5 ppm in small vine climbing fruits except fuzzy kiwifruit (subgroup 13 - 07F) is based upon existing data for grapes (the representative commodity for the subgroup). Upon establishment of the tolerance in subgroup 13 - 07F, the existing tolerance in grapes sh ould be removed. The proposed tolerance of 0.7 ppm in apricots is based upon the submitted data for peaches. HED recommends that the tolerance be established at 0.70 ppm. Processing Studies: The apple processing study data indicate d that residues of metrafenone do not concentrate appreciably in any apple processed commodities, with the exception of apple sauce, in which the processing factor was 4.5X . Processing factors range d from <1 X to 1.2 X (average of 2 trials for each commodity) for the other processed commodities. The t omato processing study data indicated that residues of metrafenone do not concentrate in tomato processed commodities , with the exception of peel and wet pomace, in which residues concentrate, on average, by factors of 6.3 X and 5.1 X , respectively . The mean transfer factor of tomato peel and wet pomace (> 1) indicates that the metrafenone residues are mainly located in the tomato peels. Residue Analytical Methods: There is an adequate enforcement method available for the quantitation of metrafenone in plant commodities (Method FAMS 105 - 01). Additionally , BASF has proposed the QuEChERS (Quick, Eas y, Cheap, Effective, Rugged, and Safe) method as a new enforcement method for metrafenone residues in plant commodities, and DFG Method S19 (extended revision) as the new enforcement method for metrafenone residues in livestock commodities . Storage Stability: Adequate storage stability data are available to support the stora ge durations and conditions of samples from the submitted field trial , metabolism and processing studies. Meat, Milk, Poultry and Eggs: The onl y livestock feed item associated with the proposed new uses is apple wet pomace , and it is fed only to dairy cattle . Based on the dietary burden to dairy cattle of metrafenone residues in apple wet pomace , and the results of the goat metabolism study , it is not expected that detectable residues would be found in cattle commodities. Therefore, tolerances in live stock commodities are not required. Conditional Data: Additional method validation data were requested for the anal ytical Method FAMS 105 - 01. In addition, radiovalidation data were required to demonstrate that Method FAMS 105 - 01 adequately recovers weathered residues of metrafenone from grapes. BASF submitted the information requested to satisfy the conditions of registration ( MRIDs #48981305, 48981306 and 48981307).Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **7** of **78** HED accept s the cucumber metabolism and other extraction efficiency data which show adequate extractability using the 4: 1 n - heptane/acetone solvent . This resolves HED concern s about the anal ytical Method FAMS 105 - 01 adequately recovering weathered residues of metrafenone from grapes , and the issue of accounting for aged residues in the grape metabolism study . It also resolves the issue of the extraction solvent used in the data collection method, BASF Method 535/0, being different than that used in the propos ed enforcement method. Therefore, all of HED ’s previously identified conditional data requirements have been sufficiently

addressed. MRL Harmonization: The proposed uses in IR - 4’s petition (PP#3E8211) are also being reviewed b y C anada’s Pest Managem ent Regulatory Agency (PMRA). EPA and PMRA have agreed to harmonize (wherever possible) the recommended tolerances and maximum residue limits (MRL s), based on use of the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedure. H armonization of EPA’s recommended tolerances with PMRA’s recommended MRL s ha s been agreed upon for all commodities requested in PP#3E8211 except apricot . PMRA has decided against translating the peach field trial data to apricot, and will there fore not be establishing an MRLin apricot. **2.0 Regulatory Recom**  **m endations**  HED has examined the residue chemistry database for metrafenone. Pending submission of a revised Section F (to propose tolerance levels in accordance with those recommended by HED, and to correct some of the commodity definitions), there are no residue ch emistry issues that would preclude establishing tolerances in the requested commodities. HED recommends in favor of establishing tolerances for residues of metrafenone as specified in Section 2.2.2 , below . **2.1 Data Deficiencies/Data Needs**  No additional data are required to support HED’s currentl y recommended tolerance s in pome fruit s , fruiting vegetables , cucurbit vegetables , the cherry subgroup (12 - 12A) , the peach subgroup (12 - 12B) , hops, small vine climbing fruits except fuzzy kiwifruit subgroup ( 13 - 07 F ) , and apricots . HED previousl y recommend ed that the following actions be required as a condition of registration ( D331685 ; D. McNeilly ; 18 February 2010 ) . The c onditional d ata ( MRIDs #48981305, 48981306 and 48981307) w ere submitted in response to the data deficiencies listed below.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **8** of **78** 1 . Additional method validation data should be submitted for Method FAMS 105 - 01 reflecting fortifications at 4.5 ppm for grapes, and at both 0.05 ppm , the limit of quantitation ( LOQ) , and 17 ppm for raisins. 2 . Radiovalidation data are required to demonstrate that Method FAMS 105 - 01 adequatel y recovers weathered residues of metrafenone from grapes. HED is willing to accept cucumber data currentl y being co llected , as proposed b y the registrant, provided such data show adequate extractability

by the 4:1 n - heptane/acetone solvent mixture . 3 . Because the extraction solvent used in the data collection method is different than that used in the proposed enforcement method, radiovalidati on data are required to support the data collection method, BASF Method 535/0. Samples from the cucumber metabolism study may also be used to generate these data. These conditional data submissions (D407462) have been reviewed , and have adequatel y resolved all of HED ’s previously identified issues. **2.2 Tolerance Con**  **sid erations**  **2.2.1 Enforcement Analytical Method/Multiresidue Methods**  There is an adequate enforcement method available for the quantitation of metrafenone in pla nt commodities (Method FAMS 105 - 01). Additionally , BASF has proposed the QuEChERS method as a new enforcement method for metrafenone that will cover fortifications at 4.5 ppm in grapes, and at both the LOQ (0.05 ppm) and 17 ppm in raisins. QuEChERS stands for “ Quick, E asy , Ch eap, E ffective, R ugged and S afe.” The method that was initially submitted for enforcement (Method FAMS 105 - 01) of metrafenone in grapes is an older gas chromatography (GC) method that was developed in 1998. Although Method FAMS 105 - 01 performs adequatel y for metrafenone in grapes and raisins, it was decided that a more modern methodology was needed which could take advantage of current advances in sample clean - up and liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) techniques. The QuEChERS method was validated on eight diverse matrices (MRID #48981303) according to the OECD guidance document on pesticide anal ytical methods (ENV/JM/MONO(2007)17). The method has also been subjected to an independent laboratory validation (ILV) by

Sprecht Laboratories (MRID #48981304) in accordance with the OECD guidance document . Acceptable multiresidue methods testing data have previousl y been submitted for metrafenone in grapes. The data indicate that multiresidue methods may be suitable for determining residues of metrafenone in grapes for tolerance enforcement.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **9** of **78 2.2.2**  **Recommended Tolerances TABLE**  **2.2.2 Tolerance Summary for M**  **etrafenone .**  **Comm odity as Proposed by**  **Registrant Proposed**  **Tolerance (ppm) Recommended** 

**Tolerance (ppm) Comments;**  **Correct Commodity Definition**  Apricot 0.7 0.70 Based on submitted peach data. Cherry subgroup 12 - 12A 2 2.0 Fruits, pome group 11 - 10 1.5 1.5 Fruit, pome, group 11 - 10 Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F 4.5 4.5 * Based on data supporting the existing tolerance in grape. Hop, dried cones 70 70 Peach subgroup 12 - 12B 0.7 0.70 Vegetable, cucurbit, group 9 0.5 0.50 Vegetables, Fruiting, group 8 - 10 1.0 0 .90 Vegetable, fruiting, group 8 - 10 *Upon establishment of the tolerance in subgroup 13 - 07F, the existing tolerance in grapes should be removed. **2.2.3 Revisions to Petitioned**  **- For Tolerances**  Instead of the proposed tolerance in cucurbit vegetables (0. 5 ppm), HED recommends establishing the tolerance at 0. 5 0 ppm, in order to avoid the situation where a field sample containing residues significantly above the tolerance (0. 5 4 ppm, for example) would be considered non - violative. For the same reason, HED recommends that the proposed tolerance s of 0. 7 ppm in the peach subgroup (12 - 12B) and apricots be revised to 0. 7 0 ppm. Similarly, HED recommends that the proposed tolerance of 2 ppm in the cherry subgroup (12 - 12 A) be revised to 2 .0 ppm. Because HED determined that 2 of the 9 pepper field trial s s hould be considered replicates , the OECD tolerance calculation procedure result for 8 trials was 0.9 ppm, instead of the 1 ppm result when 9 trial values were entered. Th e tolerance calculation result for tomatoes was 0.6 ppm, which is in accordance with the Agency ’s guidelines for setting a crop group tolerance (within 5X of the result for peppers) . Since a crop group tolerance is set based on the representative commodity

having the larger (or largest) tolerance calculation result , HED recommends that the tolerance in fruiting vegetables (group 8 - 10) be established at 0.90 ppm. **2.2.4 International Harmonization**  The proposed uses in IR - 4’s petition (PP#3E8211) are also being reviewed by Canada’s PMRA . EPA and PMRA have agreed to harmonize (wherever possible) the recommended tolerances and MRL s, based on use of the OECD tolerance calculation procedure. Harmonization of EPA’s recommended tolerances with PMRA’s recommended MRL s has been agreed upon for all commodities requested in PP#3E8211 except apri cot. PMRA has decided against translating the peach field trial data to apricot, and will therefore not be establishing an MRL in apricot.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **10** of **78 2.3**  **Label Recommendations** None. **2.4 Submittal of Analytical Reference Standards**  **( 860.1650**  **)** The anal ytical standard for metrafenone, with an expiration date of 1 August 2019, is currently available in the EPA’s National Pesticide Standards Repository (NPSR), per Email communication from Theresa Cole of the Biological and Economic Analy sis Divisio n’s (BEAD’s) Analy

tical Chemistry

Branch (ACB) on 7 January 201 4 . The metrafenone metabolite is also currentl y available, with an expiration date of 1 November 201 4 . The registrant is required to maintain reasonable amounts of the analy tical reference st andard for metrafenone in the NPSR . However, as th e metabolite is not included in the tolerance expression, it is not required to be stocked in the NPSR. When necessary , a new reference standard, or updated certificate of anal ys is (COA), should be sent t o the ACB, which is located at Fort Meade, MD. It should be sent to the attention of either Theresa Cole or Thuy Nguyen at the address listed below, along with a letter of transmittal. **Please note that the full 9 -**  **digit ZIP Code is required, or the mail w**  **ill be returned to the registrant.**

**USEPA National Pesticide Standards Repository**  **Analytical Chemistry Branch/BEAD/OPP 701 Mapes Road**  **Fort George G. Meade, MD 20755**  **- 5350**  The letter of transmittal should include the assay of the standard, name of the anal ytical method used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for safe handling. Replacement of standards may be required periodicall y if supplies are exhausted, if the standards expire, or if decomposition occurs during storage. Material Safety Data Sheets (MSDSs) must accompany all anal ytical standards as specified in 29CFR§1910.1200 by the Occupational Safety and Health Administration (OSHA). **3.0 Chemical Identit** **y** Metrafenone is a benzophenone fungicide with preventative properties. It is intended for the control of powdery

mildew produced b y Uncinula necator in grapes and Podosphaera in pome fruit . The chemical structure and nomenclature of metrafenone are presented in Table 3. 1 , below . The phys icochemical properties of the technical grade of metrafenone are presented in Table 3. 2 , below .Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **11** of **78 3.1**  **Nomenclature TABLE**  **3.1 Me** **trafenone Nom enclature**  Com pound

Common name Metrafenone Com pany experimental name s BAS 560 F; AC 375839; CL 375839 Molecular formula C 19 H 2 1 Br O 5 Molecular weight 409.27 IUPAC name 3 ′ -bromo - 2,3,4,6 ′ - tetramethoxy - 2 ′,6 - dimethylbenzophenone CAS name (3 -bromo - 6 - methoxy - 2 - methylphenyl)(2,3,4 - trimethoxy - 6 - methylphenyl)methanone CAS registry number 220899 - 03 - 6 End - use product (EP) Vivando Fungicide ( 2.5 lb ai/gal ; EPA Registration # 7969 - 284) **3.2 Physic**  **oc hemical Characteristics**  **TABLE 3.2**  **Physicochem ical Properties of Metrafenone.** 

**Param eter**  **Value Reference**  Melting point/range 99.2 - 100.8oC Petition administrative materials (MRID 49055900) pH 3.45 (1% aqueous suspension) Density 1.45 g/cm3 (20°C) Water solubility deionized pH >5 pH 7 pH 9 mg/L 0.474 0.552 0.492 0.457 Solvent solubility acetone acetonitrile dichloromethane ethyl acetate n - hexane methanol toluene g/L 403 165 1950 261 4.8 26.1 363 Vapor pressure 1.15 x 10 - 6 mm Hg (20oC) Dissociation constant, pKa No dissociation Octanol/water partition coefficient, Log [KOW ] 4.3 (25oC, pH 4) UV/visible absorption spectrum Not available O C H 3 CH 3

O CH 3 O O C H 3 C H 3 O C H 3 BrMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **12** of **78** Metrafenone is a solid under ambient conditions, and has low volatility . The compound has a relativel y low solubility

in water, and moderate to high solubility in organic solvents. Its octanol/water partition coefficient suggests that accumulation of met rafenone in fatty

tissues is possible. **3.3 Pesticide Use Pattern/Directions for Use (860.1200)**  BASF submitted an undated draft label for the BASF 2.5 lb ai/gal formulation (Vivando , EPA Reg istration #7969 - 284 ). A summary of the proposed use pattern s is presented in Table 3. 3 , below . **TABLE 3.3**  **Summary of Proposed**  **Directions for Use of M**  **etrafenone .**  **Application Ti**  **ming; Type; Equipment**  **1 Use**  **Rate (lb ai/A)**  **Max im**  **um**

**Uses Per Season**  **Max. Seasonal**

**Use Rate (lb ai/A)**  **PHI 2** 

**(Days) Use Directions,**  **Application**

**Timing, and Limitations**  **Pom e**  **F ruit**  **s Group**  **11 -**  **10** Prior to disease development; f

oliar; ground/aerial equipment . 0. 20 - 0.3 0 3 0 .90 7 Minimum RTI **3** of 7 days. Apply in a minimum

of 10 gallons of spray solutio n per acre (GPA) for aerial applications . **Fruiting V**  **egetable s**  **Group 8**  **- 10**  Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 3 0.90 0 Minimum RTI of 7 days. Apply in a minimum

of 10 GPA for aerial applications . **Peach S**  **ubgroup 12**  **- 12B**  Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 2 0 .6 0 7 Minimum RTI of 7 days. Apply in a minimum of 10 GPA for aerial applications. **Apricot** Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 2 0.60 7 Minimum RTI of 7 days. Apply in a minimum of 10 GPA for aerial applications. **Cherry S**  **ubgroup 12**  **- 12A**  Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 2 0.60 7 Minimum RTI of 7 days. Apply in a minimum of 10 GPA for aerial applications. **Hops** Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 2 0.60 3 Minimum RTI of 7 days. Apply in a minimum of 10 GPA for aerial applications. **Cucurbit Vegetables G roup 9**  Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 3 0.90 0 Minimum RTI of 7 days. Apply in a minimum of 10 GPA for aerial applications.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **13** of **78 TABLE**  **3.3 Summary of**  **Proposed Directions for Use of**  **M etrafenone**  **. Application**  **Ti ming;**  **Type; Equipment 1**  **Use Rate**  **(lb ai/A) Max** **im um** 

**Uses Per Season**  **Max. Seasonal**

**Use Rate (lb ai/A)**  **PHI 2** 

**(Days) Use Directions,**  **Application**

**Timing, and Limitations**  **Sm all**  **V ine**  **C lim** **bing Fruit**  **( E**  **xcept Fuzzy K** **iwifruit) S**  **ubgroup 13**  **- 07F**  Prior to disease development; foliar; ground/aerial equipment. 0.20 - 0.30 3 0.90 14 Minimum RTI of 14 days. Apply in a minimum of 10 GPA for aerial applications. 1 . The labels state that the product must be applied before visual symptoms of powdery mildew appear, as it has no curative properties, and will not control latent or established infections of powdery mildew. A erial applications may be made where the use of ground equipment is not possible. Not to be applied via chemigation. No mo re than 2 sequential applications may be made before alternating to a labeled fungicide with a different mode of action. 2 . PHI = Pre - Harvest Interval. 3. RT I = Re - Treatment Interval. A 12 - hour re - entry

interval (REI) is specified. Discrepancies in the stated minimum RTI(7 versus 14 day s) and minimum PHI ( 0 versus 7 day s) for pome fruit w ere noted in various proposed master and supplemental label s for Vivando. The registrant stated that the correct RTI and PHI are both 7 days for the use on pome fruit. RD should ensure that the final label lists the correct RTIand PHI . Conclusions : The proposed use directions are adequate to allow evaluation of the residue data relative to the request ed use s . The proposed maximum seasonal use rate s , minimum RTI s , and minimum PH I s are supported by the submitted crop field trial data. **4.0 Metabolite/Degradate Residue Profile**  Grape: Based on the results of the grape metab olism study, the petitioner concluded that metrafenone is rapidl y m etabolized in grapes and grape vines to compounds more polar than the parent. There was no evidence of cleavage of the methanone bridge between the two rings of the compound. One metaboli te that was tentativel y identified in grape juice suggested a two - fold oxidation of the methyl group of the bromophenyl ring. Two metabolites tentatively identified in the acetone surface wash of mature grape leaves appeared to have been formed by oxidati on of the methyl group of the bromophenyl or trimethoxy phenyl ring (with lactone formation), and a third metabolite suggested de - halogenation of the bromophenyl ring in addition to oxidation. The proposed metabolic profile in grapes is summarized in Figure 4.0.1 , below. HED notes that the grape metabolism is only marginally

adequate with respect to elucidation of all metabolites of concern, due to high percentages of unidentified residues. HED has not required a new grape metabolism study since the data were considered a cceptable for bothMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **14** of **78** tolerance enforcement and conducting an upper - boun d dietary exposure assessment ( D 312307; D. McNeill y ; 24 August 20 06 ) . Cucumber : In the cucumber metabolism study, m etrafenone accounted for 95.0% (6.076 ppm) of the t otal radioactive residues (TRR) in 0 day s after treatment 1 ( 0 - DAT1 ) foliage, 12.6% TRR (0.0021 ppm) in 14 - DAT1 whole fruit, 42.4% TRR (0.0216 ppm) in 3 day s after treatment 2 ( 3 - DAT2 ) whole fruit, 6.5% TRR (0.0009 ppm) in 3 - DAT2 pulp, 61.0% TRR (0.1607 ppm) in 3 - DAT2 peel , and 80.4% TRR (7.084 ppm) in 3 - DAT2 rest of the plant. No other components were identified in cucumber matrices. Remaining radioactivity consisted of multiple unknown components, characterized as polar, medium polar, or nonpolar. Polar unknowns (4 - 6/m atrix) accounted for 13.1 - 36.9% TRR (0.0041 - 0.0067 ppm) in whole fruit (both sampling intervals) and pulp , and for 0.82% TRR (0.0715 ppm) in the rest of the plant, with no single component accounting for >18.9% TRR or >0.0299 ppm. Medium polar unknowns (4 - 20/matrix) accounted for 3.8 - 46.8% TRR (0.0062 - 1.2278 ppm) in all cucumber matrices, with no single component accounting for >12.2% TRR or >0.2742 ppm. Based on the cucumber metabolism study, metrafenone is metabolized in cucumber and cucumber plant to m ore polar components. The unchanged parent was the major residue component in most matrices; in pulp, where metrafenone was a minor component, some polar components were detected at concentrations similar to those of metrafenone ; see the data evaluation record (DER) for MRID #48981307 .Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **15** of **78 FI**  **GURE 4**  **.0 .**  **1 Proposed Metabolic Profile of Metrafenone in Grapes** 

Wh eat: Based on the results of the wheat metabolism study, the petitioner proposed that metrafenone initially

undergoes Phase I biotransformations, beginning with a single oxidative de - methylation of the parent to form CL434223, CL376991 and CL 377160, followed by a second oxidative de - methylation to form CL 1500835 ( see Figure 4.0.2, below) . The lactones CL3000402 and CL 1500831 are formed by ox i datio n at each benzyl ic carbon followed b y cyc lization. Oxidation of the methyl groups on either of the two phenyl rings g ives rise to the aldehyde derivatives , CL 1500833, CL1500834 and CL15008 37 . Aromatic oxidation and O C H 3 C H 3

O C H 3 O O C H 3 C H 3 O CH 3 Br

O C H 3 O

O C H 3

O C H 3 O

O C H 3

Br C H 3 O O O

C H 3 C H 3 C H 3

C H O Br O CH 3 O C H 3

O O O

O Br C O O H

C H 3 C H 3 C H 3 O C H 3 C H 3 O O O

O

C H 3 C H 3 C H 3 O C H 3 C H 3 C H O Metr af en on e

Sur fa ce rins e metab ol ite2 Sur fa ce rins e metab ol ite 3

Juice metabol ite Sur fa ce rins e metab ol ite 1Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **16** of **78** oxidative de - methylations can produce CL1500832 . Additionally , CL1500836 is formed b y oxidation at the benzylic carbon of the bromophenyl - ring to an aldehyde followed by reductive de - bromination . The ox i dations are proposed to be either enz ym atic and/or chemical (photoly s i s) in nature. These P hase I processes are then followed b y P hase II transformation reacti ons, which are enzymatic glucoside conjugation reactions to yi eld the conjugates CL 1500838 and CL1500839 from their corresponding agl yc ones, CL 434223 and CL376991. These results show that the benzophenone backbone of metrafenone remains intact w ithout cleavage at the carbonylgroup. Rather, the metabolites are derived from metrafenone through various reactions occurring on the ring s ys tems ( see the DER for MRID #49 1 1 91 0 1 ) . **FI GURE 4.**  **0. 2**  **Proposed Metabolic Profile of Metrafenone in Wheat** 

Goat: Following oral dosing with [bromophenyl - 6 - 14 C] - metrafenone at 13 and 87 ppm in the diet for 5 consecutive days, TRR in the low and high dose groups, respectively , were <0.005 and 0.008 - 0.010 ppm in milk, 0.231 and 1.278 ppm in liver, 0.060 and 0.329 ppm in kidney , <0.005Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **17** of **78** and 0.008 ppm in muscle, and <0.005 and 0.015 ppm in fat. Following oral dosing with [trimethox yp henyl - U 14 C] - metrafenone at 8 and 60 ppm in the diet for 5 consecutive days, TRR in the low and high dose groups, respectively , were <0.005 and <0.005 - 0.006 ppm in milk, 0.208 and 0.718 ppm in liver, 0.047 and 0.157 ppm in kidney , <0.005 and 0.006 ppm in muscle, and <0.005 and 0.022 ppm in fat. Radioactivity in milk was generall y stable throughout the dosing period. Most of the administered dose was excreted (75.7 - 85.7%), with the majority (61.8 - 74.1%) excreted in the feces. Parent was the major residue in milk (24.12% TRR), and was the major and only identified residue component in fat, accounting for 60.00 - 85.32% TRR. Metrafenone was a minor residue in liver (2.74 - 3.49% TRR) and kidney (3.25 - 4.35% TRR). Region of interest 13 ( ROI - 13 ) was a major residue component in milk (10.67% TRR) and was the major residue component in liver and kidney , accounting for 14.77 - 21.05% TRR and 26.29 - 28.15 % TRR, respectively . ROI - 9 was also a major component in liver and kidney , accounting for 9.89 - 13.23% TRR and 9.51 - 13.57% TRR, respectively ; ROI - 9 was a minor component in milk (2.83% TRR). ROI - 16 was a minor residue component in milk (3.8% TRR), liver ( 6.41 - 7.12% TRR), and kidney (1.46 - 4.19% TRR). Remaining radioactivity was found to consist of up to 18 minor ROIs, together accounting for: 55.94% TRR in milk; 13.45 - 14.46% TRR in fat; 50.63 - 61.70% TRR in liver; and 48.81 - 55.08% TRR in kidney . The singl e largest ROIaccounted for 11.7% TRR in TMP label liver, with the majority (10.86% TRR) found in the pepsin hydrol ys ate. Based on the submitted goat metabolism study , the registrant has proposed the following metabolic pathway

for metrafenone in ruminants ( see Figure 4.0. 3 , below). Metabolism of metrafenone in lactating goat occurred at the methyl and methoxy groups on the rings. Hydroxylation of the methyl groups yielded hydroxy methyl derivatives, whereas O demethylation yielded hydrox yp henyl derivatives. These hydrox yl ated metabolites underwent Phase II glucuronidation to produce various mono - O - glucuronides. All of the prominent goat metabolites were identified as O - glucuronides (see the DER for MRID #49267201).Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **18** of **78 FI**  **GURE 4.0. 3**  **Proposed Metaboli c Profile of Metrafenone in**  **Go at**  **s**

Rat: In the rat metabolism and pharmacokinetics study, excretion was 91 - 100 % after 168 hours, most of which was excreted in the feces within the first 48 hours. The highest concentration of metrafenone was found in the liver. Bile was the major excretion pathway, based on the results in bile duct - cannulated rats. Six urinary and biliary

metabolites were identified. In urine, up toMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **19** of **78** 21 other minor unknowns were found. In bile, up to 24 minor unknowns were found. Th e parent compound was not detected in urine or bile. Most of the fecal radioactivity consisted of parent metrafenone, and an additional 12 fecal metabolites were 0.03 - 15% of administered dose. There were up to 45 other fecal minor unknowns. The absorbed material was metabolized by ortho - dealkyl ation, aliphatic oxidation, debromination, ring hydrox yl ation and conjugation reactions. Primary

excretion was as glucuronic acid conjugates in bile and urine. Residues in feces were primaril y as parent and aglyc ones of bile and urine conjugates ( D354166 ; D. McNeilly ; 1 March 2010 ) . **4.1 Nature of the Residue**  **Residue Chemistry Summary**  **D 312307;**  **D. McNeilly ; 24 August 20**  **06 Me** **tabolism DER for MRID #48981307**  **( Cucum** **ber )**  **Me tabolism**  **DER for MRID #49119101 (** **Wheat )**  **Me tabolism**  **DER for MRID # 49267201**  **( Goat** **)** Grape : The nature of the residue in grapes is adequately understood. Although the previously submitted metabolism study reflects treatment at roughl y 0.5 X the proposed maximum seasonal rate to grapes, sufficient radioactive residues were obtained in grapes to enable characterization/ identification of residues. The ROC in grapes for risk assessment and tolerance enforcement is metrafenone. For risk assessment purposes, HED’s Residues of Concern Knowledge - based S ubcommittee (ROCKS) conclude d that the residues described as “acetone unknowns” and “juice” in the metabolism study should be included (D370903 ; G. F. Kramer ; 18 Nov 2009). The metabolite profile was very similar for both radiolabels. Metrafenone was the onl y component of the residue that was conclusivel y identified in grapes and leaves. Metrafenone accounted for 41 - 53% TRR in grapes harvested immediately following the last of five foliar applications of radiolabeled metrafenone , and it accounted for 23 - 2 5% TRR in grapes harvested 35 day s after the final application. Based on the results of the study , metrafenone is rapidly metabolized in grapes and grape vines to more polar compounds. There was no evidence of cleavage of the methanone bridge between the two rings of the compound. One metabolite that was tentativel y identified in grape juice suggested a two - fold oxidation of the methyl group of the bromophenyl ring. Two metabolites tentatively

identified in the acetone surface wash of mature grape leaves appeared to have been formed b y oxidation of the methyl group of the bromophenyl or trimethox yphenyl ring (with lactone formation), and the third metabolite suggested de - halogenation of the bromophenylring in addition to oxidation. (See Tables C.2.2. 1, C.2.2.2, C.2.3.1, C.2. 3 .2 and C.2.3.3 in the DER for MRID #46415749.) Cucumber : BASF Corporation has submitted a study investigating the metabolism of uniformly ring - labeled [ trimethoxy

phenyl - U 14 C ]metrafenone ( specific activity 6 MBq/mg) in cucumber. The radiolabeled test substance was formulated as an S C , and applied to greenhouse - grown cucumber plants as two broadcast foliar applications at 0.18 lb ai/A/application (200 gMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **20** of **78** ai/ha/application), for a total application of 0.36 lb ai/A (400 g ai/ha). The applications were made at a 14 - day

RTI. Samples of foliage were harvested immediatel y after the first application (0 - DAT1), and samples of whole fruit were harvested 14 day s after the first application (14 - DAT1), immediatel y before the second application. Samples of mature whole fruit, pulp, peel, and rest of plant were harvested 3 day s after th e second application (3 - DAT2). The TRR , determined b y summing extractable and nonextractable radioactivity, were 6.397 and 0.016 ppm in 0 - DAT1 foliag e , and 14 - DAT1 in whole fruit harvested f ollowing the first application at 0.18 lb ai/A ; TRR were 0.051, 0.013, 0 .263 and 8.807 ppm, respectivel y, in 3 - DAT2 whole fruit, pulp, peel, and rest of plant harvested following two applications at 0.36 lb ai/A. Extraction with methanol released the majority of the radioactivity from cucumber matrices: ~99% TRR for 0 - DAT1 foliage, ~88% for 14 - DAT1 whole fruit, ~93% for 3 - DAT2 whole fruit, ~91% for 3 - DAT2 pulp and peel, and ~93% for 3 - DAT2 rest of plant. Extracti on with water released an additional 0.3 - 3.2% TRR from all matrices. Remaining nonextractable residues were, respectively , 0.9% TRR (0.058 ppm), 11.0% TRR (0.0018 ppm), 5.7% TRR (0.0029 ppm), 7.8% TRR (0.0010 ppm), 7.8% TRR (0.0205 ppm), and 4.2% TRR (0.3 74 ppm). The extraction procedures adequatel y extracted the majority of residues from cucumber matrices. Results were normalized ; therefore, accountabilities were 100%. Residues were identified and quantitated in cucumber matrices by high performance li quid chromatography with UV detection ( HPLC /UV). Id entification of metrafenone was achieved by HPL C co - chromatography with an unlabeled reference standard in 0 - DAT1 cucumber foliage , and 14 - DAT1 whole fruit . No other reference standards were included in the study . Id entification of metrafenone in the other samples was achieved by comparison of the retention times and the HPL C elution profiles with those of the extracts investigated by co chromatography. Confirmatory HPLC/UV anal ys is was condu cted on all samples . Samples were stored frozen ( approximately - 18°C) after collection , and were processed, extracted and subjected to initial analy sis by HPL C for quantitation purposes within 67 - 86 day s (2.2 - 2.8 months) of harvest. Final analy ses were completed wi thin 80 - 203 day s ( 2.6 - 6.7 months ) of harvest. Because samples were anal yz ed within roughl y 4 - 6 months of harvest, no storage stability data are required to support the study . M etrafenone account ed for 95 .0 % TRR (6.076 ppm) in 0 - DAT1 foliage, 12.6% TRR (0 .0021 ppm) in 14 - DAT1 whole fruit, 42.4% TRR (0.0216 ppm) in 3 - DAT2 whole fruit, 6.5% TRR (0.0009 ppm) in 3 - DAT2 pulp, 61.0% TRR (0.1607 ppm) in 3 - DAT2 peel, and 80.4% TRR (7.084 ppm) in 3 - DAT2 rest of plant . No other components were i dentified in cucumber matrices. Remaining radioactivity consisted of multiple unknown components, characterized as polar, medium polar, or nonpolar. Polar unknowns (4 - 6/matrix) accounted for 13.1 - 36.9% TRR (0.0041 - 0.0067 ppm) in whole fruit (both samplin g intervals) and pulp , and for 0.82% TRR (0.0715 ppm) in the rest of the plant, with no single component accounting for >18.9% TRR orMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **21** of **78** >0.0299 ppm. M edium polar unknowns (4 - 20/matrix) accounted for 3.8 - 46.8% TRR (0.006 - 1.228 ppm) in all cucumber matrices, with no single component accounting for >12.2% TRR or >0.2742 ppm. A single nonpolar component was detected in 3 - DAT2 rest of plant at 0.02% TRR ( 0.0016 ppm). (See Tables C.2.1, C.2.2. 1 , C.2.2.2, C.2.3.1 and C.2.3. 2 in the DER for MRID #48981307.) Wh eat: BASF Corporation has submitted a study investigating the metabolism of [bromophenyl 6 - 14 C]metrafenone (BP label; specific activity 20.30 μCi/mg) and uniformly ring - labeled [trimethox yp henyl - U 14 C]metrafenone (TP label; specific activity 18.16 μCi/mg) in wheat. The radiolabeled test substance s w ere formulated as emulsifiable concentrate s ( EC s ) , and applied to field - grown wheat plants as three broadcast foliar applications, the first two at nominal application rates of 0.268 lb ai/A (300 g ai/ha), and the third at 0.179 lb ai/A (200 g ai/ha). The actual total application rates were 0.674 lb ai/A (756.0 g ai/ha) for the BP label, and 0.642 lb ai/A (719.3 g ai/ha) for the TP label. Applications were made at 13 - to 14 - day RTIs. Samples of immature whole plants were collected within roughly 3 hours of each application; forage (whole plant) was collected 3 days after the first application; hay was collected 14 day s after the second application; and mature straw, chaff and grain were collected at maturity , 35 day s after the third application. The in - life phase of the study was conducted b y Excel Research Services (Fresno, CA) and Qualls Agricultural Laboratory (Ephrata, WA), while the anal ytical phase of the study was conducted by BASF ( Princeton, NJ ) . F ollowing three broadcast foliar applications of [bromophenyl - 6 - 14 C]metrafenone or [trimethox yp henyl - U 14 C]metrafenone at total application rates of 0.674 lb ai/A (756 g ai/ha) for the BP label, and 0.642 lb ai/A (719.3 g ai/ha) for the TP label, TRR in imm ature wheat plants sampled immediately

following applications 1, 2 and 3, respectivel y, were 7.275, 5.959 and 6.997 ppm in BP - label samples, and 9.890, 8.416 and 5.382 ppm in TP - label samples. Although immature plants were subjected to further extraction and anal ys is procedures, results were not included in the submission, and these matrices are not discussed further herein. TRR in remaining BP - and TP - label samples, respectivel y, were 8.167 and 5.265 ppm in forage, 7.784 and 8.498 ppm in hay , 8.914 and 8 .248 ppm in straw, and 0.209 and 0.399 ppm in grain. The higher TRR in hay

and straw were attributed by the petitioner to dehydration of the samples. Results were similar for both labels, although residues of parent were consistently higher in BP label s amples. Metrafenone was the major identified residue in wheat forage, hay and straw, accounting for 58.9 - 64.4% TRR in forage, 12.7 - 26.0% TRR in hay , and 7.7 - 13.6% TRR in straw. Metrafenone was the only identified residue in wheat grain, accounting for 3 .1 - 7.7% TRR. All remaining metabolites were identified in all samples of forage, hay and straw. Metabolites CL3000402 , which was ROI 4, CL 1500838 (ROI 5), and CL 434223 (ROI 8) each accounted for 0.8 - 6.6% TRR. Combined residues of the following metabo lite pairs or groups each accounted for 1.5 - 6.5% TRR: CL1500837 + CL1500836 (ROI 3), CL 1500839 + CL 1500832 (ROI 6), and CL 1500833 + CL1500834 + CL1500835 + CL377160 + Unknown ROIMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **22** of **78** 7C (ROI7). Two remaining metabolites, CL 376991 (ROI 9) and CL 150 0831 (ROI 10), each accounted for ≤1.8% TRR. No other components were identified in wheat matrices. Polar unknowns ROI1 and ROI 2, comprised of multiple minor components, each accounted for 3.1 - 4.3% TRR in forage, 11.5 - 17.4% TRR in hay , and 8.3 - 10.6% TRR in straw ; one additional multicomponent unknown, ROI 11, accounted for ≤1.7% TRR in forage, hay and straw. Polar unknown ROI 1 accounted for 21.3 - 26.2% TRR in grain, while remaining unknowns together accounted for <2.0% TRR. Although quantitative res ults were not reported for α - amyl ase hydroly sis of grain, ROI 1 comprised ~59% and 74%, respectively , of the recovered radioactivity following hydrol ys is. (See Tables C.2.1, C.2.2.1, C.2.2.2, C.2.2. 3 , C.2.3.1 , C.2. 3 .2 and C.2.3. 3 in the DER for MRID # 4911 9101 .) Goat: BASF Corporation has submitted a study investigating the metabolism of [bromophenyl 6 - 14 C] - metrafenone (BP label; specific activity 8.03 μCi/mg) or uniformly ring - labeled [trimethox yp henyl - U 14 C] - metrafenone (TMP label; specific activity 8.02 μCi/mg) in the lactating goat. The test substances were administered orall y via gelatin capsule to two lactating goats per label , once daily for 5 consecutive day s , at 13 and 87 ppm in the feed for the BP lab el , and at 8 and 60 ppm in the feed for the TMP label. A control goat received capsules containing carrier onl y. Milk was collected twice dail y, in the morning and afternoon, prior to dosing. Goats were sacrificed approximately 21 - 23 hours after adminis tration of the final dose, and the following tissues were collected: Liver (entire), kidney (both), muscle (composite of loin and leg), and fat (omental). The in - life phase of the study was conducted b y Fort Dodge Animal Health, Division of American Home Products Corporation, Agricultural Research Center (Princeton, NJ), and the analy tical phase of the study

was conducted by

BASF Agro Research (Princeton, NJ). TRR in BP - label milk and tissues from the low and high dose goats, respectively , were <0.005 and 0.008 - 0.010 ppm in milk, 0.231 and 1.278 ppm in liver, 0.060 and 0.329 ppm in kidney , <0.005 and 0.008 ppm in muscle, and <0.005 and 0.015 ppm in fat. TRR in TMP - label samples from low and high dose goats, respectivel y, were <0.005 and <0.005 - 0.006 pp m in milk, 0.208 and 0.718 ppm in liver, 0.047 and 0.157 ppm in kidney , <0.005 and 0.006 ppm in muscle, and <0.005 and 0.022 ppm in fat. In general TRR were higher in BP - label samples than in TMP label samples. Radioactivity in milk was generally

stable throughout the dosing period. Most of the administered dose was excreted (75.7 - 85.7%), with the majority (61.8 - 74.1%) excreted in the feces. The following samples from high dose goats were subjected to further extraction and anal ys is: Day 5 BP - label m ilk, and BP - and TMP - label liver, kidney , and fat; samples of TMP - label Day 5 milk and muscle (both labels) were not were not analyzed further because TRR were <0.01 ppm. The majority

of the radioactivity

in milk (98.9% TRR) was extracted with acetone. S equential extraction with acetonitrile (ACN), ACN/water, methanol/acetone/water/triethylamine (TEA),Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **23** of **78** and methanol/water/trifluoroacetic acid (TFA) released the majority of the radioactivity in liver (59.2 - 68.9% TRR) and kidney (87.1 - 93.1% TRR). The majori ty of the radioactivity

in fat (~100% TRR) was extracted with methanol. The nonextractable residues of liver and kidney were subjected to hydrolysis with pepsin , followed by extraction with acidic methanol, which together released an additional 25.9 - 37.6% TRR in liver , and 7.5 - 10.6% TRR in kidney . Remaining nonextractable residues following extraction and hydrol ys is procedures were 14.3% TRR (0.001 ppm) in milk, 5.3 - 7.5% TRR (0.054 - 0.068 ppm) in liver, 4.6 - 7.7% TRR (0.012 - 0.015 ppm) in kidney , and 6.0% TRR (0.0013 ppm) in TMP - label fat (nonextractable residues in BP - label fat were not reported). The extraction procedures adequatel y extracted the majority of residues from goat milk and tissues. Accountabilities were roughl y 100 - 122%. Residues were quantitated in milk and tissues by HPL C/UV. Metrafenone was identified in milk, liver and fat b y co - chromatography. Three ROI s, ROI - 9, - 13 and - 16, were major residue components in milk, liver and/or kidney . Individual components of these ROI s were identified primarily in liver b y LC/MS , in conjunction with hydrol ys is via beta - glucuronidase. The three ROI s were found to include O - glucuronide conjugates of metabolites . ROI - 9 was comprised of metabolites CL1023361, CL1023362 and CL 150070 2; ROI - 13 was comprised of metabolites CL1500698, CL 1023363 and a minor unknown; and ROI - 16 was comprised of met abolites CL 1500701, CL1500699 and a minor unknown. The metabolite profiles were similar for both labels, and the metabolite profiles in liv er and kidney were similar. Parent was the major residue in milk (24.12% TRR, 0.0024 ppm), and was the major and onl y identified residue component in fat, accounting for 60.00 - 85.32% TRR (0.0090 - 0.0188 ppm). Metrafenone was a minor residue in liver (2. 74 - 3.49% TRR; 0.025 - 0.035 ppm) and kidney (3.25 - 4.35% TRR; 0.005 - 0.014 ppm). ROI - 13 was a major residue component in milk (10.67% TRR, 0.001 ppm) , and was the major residue component in liver and kidney , accounting for 14.77 - 21.05% TRR (0.106 - 0.269 ppm) and 26.29 - 28.15% TRR (0.044 - 0.086 ppm), respectivel y. ROI 9 was also a major component in liver and kidney, accounting for 9.89 - 13.23% TRR (0.071 - 0.169 ppm) and 9.51 - 13.57% TRR (0.021 - 0.031 ppm), respectivel y; ROI - 9 was a minor component in milk (2.83% TRR). ROI - 16 was a minor residue component in milk (3.8% TRR), liver (6.41 - 7.12% TRR), and kidney (1.46 - 4.19% TRR). Remaining radioactivity was found to consist of up to 18 minor ROI s, together accounting for 55.94% TRR (0.0056 ppm) in milk, 13.45 - 14.46% TRR (0.0022 - 0.0030 ppm) in fat , 50.63 - 61.70% TRR (0.443 - 0.647 ppm) in liver, and 48.81 - 55.08% TRR (0.077 - 0.181 ppm) in kidney . The single largest ROI accounted for 11.7% TRR (0.084 ppm) in TMP - label liver, with the majority (10.86% TRR) found in the pepsin hydrol ys ate. Based on the submitted goat metabolism study , the registrant has proposed the following metabolic pathway

for metrafenone in ruminants. Metabolism of metrafenone in lactating goat occurred at the methyland methoxy groups on the rings. Hydroxylation of the methyl groups yi elded hydrox ym ethylderivatives, whereas O - demethylation yielded hydrox yp henyl derivatives. These hydroxylated metabolites underwent Phase II glucuronidation to produceMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **24** of **78** various mono - O - glucuronides. All of the prominent g oat metabolites were identified as O glucuronides. (See Tables 8a , 8b , 8c , 8d , 8e, 8f and 8g in the DER for MRID #49267201.) Conclusions : Based on the wheat, cucumber and grape metabolism studies , metrafenone is metabolized in plant s to more polar components. The unchanged parent was the major residue component in most matrices; in cucumber pulp, where metrafenone was a minor component, some polar components were detected at low concentrations similar to those of metrafenone. All of the prominent goat metabolites were identified as O - glucuronides. **4.1.1 Summary of Plant and/or Livestock Metabolism (860.1300)**  **ROCKS Mem o D370903; G.F. Kram**  **er; 18 Nov 2009 Residue Chemistry**  **Summary D312307; D. McNeilly; 24 August 2006**  **Me tabolism** **DER for MRID #48981307 (Cucum** **ber) Me** **tabolism DER for MRID #49119101 (Wheat)**  Data have been submitted and reviewed depicting the metabolism/degradation of m e trafenone in numerous crops and the environment. HED has determined the plant and livestock ROCs for purposes of tolerance enforcement and risk assessment ( see Table 4.1.1 .1 , below) . **TABLE 4.1.1.1**  **Summary of Metrafenone Metabolites and Degradates to be included in the Risk**

**Assessment and Tolerance Expression. Matrix**  **Residues Included in Risk Assessment**  **Residues Included in Tolerance Expression**  Plants Primary crops Metrafenone + acetone unknowns + juice (correction factor derived from grape metabolism study) Metrafenone Rotational crops Not Applicable Not applicable Livestock Ruminants Not Applicable Not applicable

Poultry Not Applicable Not applicable Drinking water Metrafenone + total extractable residues Not applicable For primary

crops, metrafenone parent serves as an adequate measure of misuse based on its percentage of the TRR in the metabolism studies, and the significant residues seen in crop field trials. For dietary

risk assessment purposes, HED concludes that some of the significant amounts of tentatively

identified and unidentified material in the grape metabolism study nee d to be included. The tentativel y identified metabolites in the “acetone unknowns” and “juice” fractions retain the dual ring structure of the parent compound. Such residues may be of comparable toxicity to the parent , metrafenone. At this time, the res idues described as “acetone unknowns” and “juice” should be included along with the parent for assessing dietary risk. This approach would account for 93% and 77% of the TRR in grapes harvested after the fifth application of the BP - labeled metrafenone ( [b romophenyl - 6 - 14 C]metrafenone ) and TMP labeled metrafenone ( [trimethox yp henyl - U 14 C]metrafenone ), respectively . Data from the metrafenone grape and cucumber metabolism studies w ere used to derive a dietary exposure adjustment factor by dividing residues ( a s a percent of the TRR) of the parent plus theMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **25** of **78** “acetone unknowns” and “juice” fractions by the residue of parent only in the grape metabolism study . Conducting this evaluation for both radiolabels , and both harvesting intervals resulted in a maximum ratio of 2.1 , and an average ratio of 1.9. HED decided to use a dietary exposure ratio factor of 2.0. This adjustment factor was then used to convert tolerance levels f or the parent to residues of parent plus the “acetone unknowns” and “juice” fractions (see ROCKS Memo, D370903 ; G. Kramer ; 19 November 2009). The wheat metabolism study was classified as marginall y scientifically acceptable . Insufficient attempts were made to characterize/identify radioactivity

in the nonextractable residues of wheat hay and straw, which accounted for 20.8 - 23.0% TRR (1.615 - 1.95 2 ppm) in hay and at least 27.7 - 38.1 % TRR (2.465 - 3.139 ppm) in straw. In addition, insufficient quantitative data were provided concerning the characterization of radioactivity in the nonextractable residues of grain for HED to ascertain whether these residues were sufficientl y characterized. In addition, the study

was missing much of the data supporting the limited characterization attempts that were des cribed. However, the finding that metrafenone is the major residue of concern in wheat is consistent with the previous plant metabolism studies, and the European Food Safety Authority (EFSA) has accepted the results of this study in conjunction with the o ther metabolism studies in establishing MRL s. Also, the progression of residue distribution from forage to hay

and straw in terms of the relative amounts of extractable and nonextractable residues, and the consistency of the metabolite profile across the se matrices are mitigating factors. It is likel y that the nonextractable residues of hay and straw ar e comprised of further breakdown products incorporated into natural components (conjugates), which are not considered toxic . Furthermore, previous metabo lism studies ( in grape, cucumber and rat) have demonstrated that metrafenone tends to be broken down into a multitude of metabolites, many of which were ultimately

unidentified. Because there are no current or proposed uses on cereal grains at this time , data from the wheat metabolism study were not included in calculation of the dietary exposure adjustment factor . Should the registrant submit any future petition requesting the use of metrafenone on cereal grain (s) , the derivation and calculation of this adjustment factor will need to be revis ited. Id eall y, a new metabolism study in a cereal grain would be conducted, with a more thorough attempt to identify

many of the resulting metabolites. Otherwise, an adjustment factor of 6 ( as calculated in Tab le 4.1.1 .2 , below) would need to be included for cereal grain commodities in the column for adjustment factor 2 in the dietary exposure assessment . **TABLE 4.1.**  **1. 2**  **Me trafenone Metabolism** **Adjustment Factor .**  **BP Label TM**  **P Label Maximum** **/Average Ratio**  **1 G**  **rape Residue**  **%TRR 2** 

**0 DALT 3**  **35 DALT**  **0 DALT 35**  **DALT** Metrafenone 53.3% 24.7% 40.7% 22.8%Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **26** of **78 TABLE**  **4.1. 1.**  **2 Me** **trafenone Metabolism Adjustment Factor**  **. BP Label**  **TM P Label**  **Maximum /Average**  **Ratio 1**  “Acetone Unknown” 32.6% -- 23.5% -- “T RR in Juice fraction” 7.1% 18% 12.5% 25.3% Ratio 1.74 1.73 1.88 2.11 2.1 /1.9 **C ucumber**  **(Whole fruit) Residue**  **%TRR (** **Note: Only one ring was labeled in the cucumber**  **metabolism study. )**  **14 DAT1**  **5 3**  **DAT2** Metrafenone 12.6% 42.4% P olar unknowns 24.0% 13.1% M edium polar unknowns 41.3% 23.4% Ratio 6.0 **4** 2.0 2.0 **W heat**  **(Grain) , 3**  **5 DAT**  **3 Residue**  **%TRR ppm**  **%TRR ppm**  Metrafenone 7.7% 0.016 3.1% 0.013 Unknown ROI 15.1% 0.032 20.2% 0.081 Unknowns ROI 2 - 11 <2% <0.004 <2% <0.004 Ratio 3.22 8.16 8.16/5.69 **W heat**  **(Forage) , 3**  **DAT1 Residue**  **%TRR ppm**  **%TRR ppm**  Metrafenone 64.4% 5.261 58.9% 3.101 All metabolites and unknowns in extract 27.3% 2.228 27.6% 1.444 Ratio 1.42 1.47 1.47/1.45 **Wheat (Hay)**  **, 14**  **DAT 2**  **Residue %TRR**  **ppm %TRR**  **ppm** Metrafenone 26.0% 2.021 12.7% 1.078 All metabolites and unknowns in extract 50.0% 3.905 59.8% 5.095 Ratio 2.92 5.71 5.71/4.32 **Wheat (Straw)**  **, 3 5**  **DAT 3**  **Residue %TRR**  **ppm %TRR**  **ppm** Metrafenone 13.6% 1.215 7.7% 0.635 All metabolites and unknowns in extract 39.1% 3.511 44.9% 3.702 Ratio 3.88 6.83 6.83/5.36 1 . Ratio = [parent + other ROC]/parent. 2 . TRR= Total Radioactive Residues 3. DALT = Days After Last Treatment. 4. While the percentages of these fractions are high, the actual TRR is less than 0.005 ppm and therefore, were not used in the calculation of the correction factor. 5. (#) DAT(#) = (numbe r of) Days After Treatment (treatment number).Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **27** of **78** To obtain dietary

exposure residue values for all commodities, a factor of 2.0 w as entered into the column for adjustment factor 2 in the dietary exposure assessment ( D371367 ; D. McNeilly ; 18 Feb ruary 2010 ) . Conclusion s : The nature of the residue in plants and animals has been adequately delineated. **4.1.2 Summary of Confined Rotational Crops (860.l850)**  **Confined Accumulation in Rotational Crops DER for MRID #49119105**  BASF Corporation has submitted a confined rotational crop study with [bromophenyl - 6 - 14 C]metrafenone (BP label; specific activity 10.15 μCi/mg) and [ trimethoxy phenyl - U 14 C] metrafeneone ( TP label; specific activity 8.97 μCi/mg). The radiolabeled test substance s w ere formul ated as EC s , and applied to bare sandy loam soil in outdoor plots at a rate equivalent to 0.558 lb ai/A ( 625 g ai/ha). Rotation al crops (lettuce, radish and canola) were planted at plant back interval s (PBI s ) of 30, 60 , 90 and 365 day s after soil treatment. Immature and mature lettuce, mature radish roots and tops, and canola straw, seed and whole plant were harvested. The in - life phase of the study was conducted b y Excel Research Services at the Qualls Agricultural Laboratory ( Ephrata, WA) , and the analy tical phase of the study

was conducted by BASF Corporation ( Princeton, NJ ). Following a single foliar broadcast application of [bromophenyl - 6 - 14 C]metrafenone or [trimethox yp henyl - U 14 C]metrafenone at 0.558 lb ai/A, TRR, determined by combustion/L SC, accumulated at ≥0.01 ppm in immature lettuce at the 90 - day PBI (both labels), radish tops at the 30 - , 60 - (TP label onl y) and 90 - day PBIs, radish root at the 30 - , 60 - and 90 - day PBIs (BP label only), canol a seed at the 90 - day PBI (BP label only), and canola straw at the 30 - , 60 - , 90 - and 365 - day PBIs (both labels). The petitioner also analyzed samples where TRR were <0.01 ppm , but greater than the reported L OQ (0.004 ppm) , which included mature lettuce at the 30 - day PBI (both labels), radish tops at the 60 - day PBI (BP label only), radish roots at the 90 - day PBI (TP label only), and canola (whole plant) at the 60 - day PBI(both labels). TRR were below the LOQ in mature lettuce at the 60 - and 365 - day PBI (both labels). TRR in 365 - day samples were ≤0.008 ppm in all matrices , and were not further analyzed with the exception of 365 - day canola straw (0.023 - 0.029 ppm). TRR were generall y highest in 30 - day PBI matrices, ranging from 0.005 ppm in mature lettuce to 0.048 ppm in canola straw. For lettuce, higher residues of 0.030 - 0.034 ppm were detected at the 90 - day PBI ; however, the petitioner attributed the increase in residues to harvesting the crop at an immature stage due to late planting. TRR generally decrea sed at the 60 - day

PBI, ranging from <0.004 ppm in mature lettuce to 0.027 ppm in canola straw, but residues increased slightly at the 60 - day PBI in radish top s (0.018 ppm). TRR increased at the 90 - day

PBI in radish top s , and canola straw and seed, ranging from 0.010 ppm in canola seed to 0.033 ppm in canola straw , and decreased slightly in 90 - day

radish root (0.009 - 0.010 ppm).Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **28** of **78** Extraction with MeOH/water released the majority of the radioactivity , 62.1 - 85.2% TRR, in 30 - and 90 - day

lettuce, 30 - , 60 - and 90 - day radish tops and roots, 30 - , 60 - , 90 - and 365 - day canola straw, and 60 - day

canola whole plant (BP label only). Extraction with hexane released the majority of radioactivity, 51.6 - 86.2% TRR, in 30 - and 90 - day canola seed (BP label only) and 60 - day canol a seed (TP label only); extraction with hexane released 41.9% TRR in 60 - day canola seed samples (BP label) , and 45.6 - 47.9% TRR in 30 - and 90 - day canola seed samples (TP label). Samples of 90 - day immature lettuce, 30 - day radish tops, 60 - day

radish roots, and 30 - , 60 - , 90 - and 365 - day

canola straw were subjected to additional extraction procedures to release bound residues. Extraction with MeOH/2% HCl released 5.9 - 19.9 % TRR from immature lettuce, radish tops and roots, and canola straw . Remaining nonextractable residues in the matrices that were subjected to additional extraction procedures to release bound residues were 18.7 - 19.6% TRR (0.006 ppm) in immature lettuce, 17.6 - 20.8 % TRR (0.003 - 0.005 ppm) in radish tops , 25.0 - 31.8 % TRR (0.005 ppm) in radish roots , and 11.8 - 29.4 % TRR (0.004 - 0.008 ppm) in canola straw . For the remaining matrices , nonextractable residues were 17.7 % TRR (0. 001 ppm) in 30 - day mature lettuce , 14.8 - 36.0 % TRR (0.0 02 - 0.0 0 6 ppm) in 60 - and 90 - day radish tops, 19.8 - 31.2 % TRR (0.0 0 3 - 0.0 05 ppm) in 30 - and 90 - day

radish roots, 13.8 - 58.1 % TRR (0.0 01 - 0. 005 ppm) in 30 - , 60 - and 90 - day canola seed, and 23.9 - 100 % TRR (0.0 01 - 0. 006 ppm) in 60 - day canola whole plant. Initial extraction results were normalized; therefore, accountabilities were approximately 100%. Select s ample extracts were anal yz ed b y HPL C/UV. All samples of rotational crop commodities were anal yz ed within 205 - 740 day s (6.7 - 24.3 months) of harvest . No storage stability data were submitted. However, a 2012 storage stabili ty study (MRID #48981308) reviewed in conjunction with the recent pome fruit petition ( PP#3F8163 ) support s the sample storage conditions and durations of samples in this rotational crop study . Metrafenone was identified by HPL C co - chromatography with reference standards . Additional ROI s were characterized on the bas is of HPL C fractionation profile s . HPLC analy sis of the MeOH/water extracts showed multiple unknown peaks in each sample . Metrafenone was identified at 6.2 - 11.1% TRR (<0.001 - 0.004 ppm) in 30 - day and 90 - day

(BP label only) lettuce samples, and 3.9 - 27.7% TRR (<0.001 - 0.004 ppm) in 30 - , 60 - and 90 - day radish roots. The most abundant residue in the majority of samples was the polar ROI 1 , which accounted for 8.1 - 17.3 % TRR ( 0.001 - 0.003 ppm) in 30 - and 90 - day lettuce , 15.3 - 43.7% TRR (0.001 - 0.01 ppm) in 60 - and 90 - radish tops (BP label), 10.3 - 17.9% TRR (0.002 - 0.003 ppm) in 30 - , 60 - an d 90 - day radish tops (TP label), 16.6 - 26.5% TRR (0.002 - 0.004 ppm) in 30 - , 60 - and 90 - day radish roots, and 25.1 - 42 .4% TRR (0.007 - 0.015 ppm) in canola straw, all PBIs . A se cond ROI, ROI 2, was present at 11.9% TRR (0.004 ppm) in 90 - day i mmature lettuce (TP label only), 8.8 - 20.0% TRR (<0.001 - 0.005 ppm) in 60 - and 90 - day radish tops (BP label onl y), 12.8% TRR (0.002 ppm) in 60 - d ay radish roots (TP label only), 9.6 - 12.4% TRR (0.003 - 0.005 ppm) in 30 - and 90 - day (BP label only) canola straw. These peaks were not further investigated in any matrix.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **29** of **78** Because onl y parent was identified in the submitted confined rotational crop study , a metabolic profile was not provided. Conclusions: The results from the confined rotational crop study indicat ed that there is no expected accumulation of metrafenone or its degradation products in the parts of plants used for human food or animal feed consumption. The levels of individual metabolites were below 0.01 ppm. Owing to the low concentrations of metrafenone and related residues in subsequent rotated crops, no field rotational crop trials are required. Plant - back restrictions are not necessary for metrafenone . **4.1.3 Summary of Rat Metabolism**  **Risk Assessment D354166; D. McNeilly; 1 March 2010**  In a rat metabolism and pharmacokinetics study, excretion was 91 - 100% after 168 hours. Most radioactivity was excreted wi thin the first 48 hours ( 84 - 99% in feces, 0.5 - 4.8% in urine). The highest concentration was in the liver. Bile was the major excretion pathway . In bile duct cannulated rats, total recovery was 97 - 100% at 72 hours. At the low dose, bile recovery was 85 - 90%; at the high dose, feces had 80 - 82% , with bile having 15 - 17% (indicating absorption was saturated). Six urinary

and biliary

metabolites were found. In urine, up to 21 other minor unknowns were found. In bile, up to 24 minor unknowns w ere found (21 - 24% for the low dose , and 3 - 4% for the high dose). The parent compound was not detected in urine or bile. Twelve fecal metabolites along with the parent were found. Most of the fecal radioactivity was contained in parent metrafenone. Fecal metabolites were 0.03 - 15% of the administered dose. There were up to 45 other fecal minor unknowns. In feces of bile duct - c annulated animals, metabolites plus parent were identified. The parent accounted for most of the activity ; however, there were u

p to 17 minor unknowns. The absorbed material was metabolized by ortho dealkyl ation, aliphatic oxidation, debromination, ring hydrox yl ation , and conjugation. Primary excretion was as glucuronic acid conjugates in bile and urine. Residues in feces were p rimaril y as parent and agl ycones of bile and urine conjugates. **4.1.4 Summary of Environmental Degradation**  **EFED Drinking Water Memo D411540,**  **D 414403,**  **D 416312**  **; J .**  **A. Hetrick; 25**  **Novem ber 2013**  The only positivel y identified major degradate of metrafenone in the environmental fate studies was CL377160 ( 3 - bromo - 6 - methoxy- 2 - methylphenyl)(3 - hydrox y- 2,4 - dimethoxy- 6 - methylphenyl ) - methanone ) . CL377160 was formed through soil photoly sis at up to 18.9% of the applied radioactivity

(AR) , and through anaerobic aqu atic metabolism at up to 10.8% AR in the total sy stem. It was also formed as a minor degradate through aquatic photoly sis , and aerobic aquatic metabolism. In one anaerobic aquatic metabolism study, another six degradates were formed at >9%, but these w ere either unidentified or only tentatively

identified. These included TN (tentativel yMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **30** of **78** identified as a lactone compound at maximum s of 3.3%, 26.9% and 28.0% in the water layer, sediment and total sy stem, respectivel y), MB (tentatively identified as a hydroxylation product of TN at maximum s of 1.1%, 11.6% and 11.7% in the water layer, sediment and total sy stem, respectivel y), and four unidentified degradates formed in the total system at 9.3% to 13% AR. Carbon dioxide was also a major degradate, formed through aquatic photolysis at up to 25% AR , and through all other measured processes as a minor degradate. Most processes also resulted in formation of a substantial amount of minor degradates, some individually

measured and identified, but most not. Al though all of these degradates were present at less than 10%, and some at very low levels, they

still may be of exposure concern because of the large overall amounts. In some cases , minor degradates, mostly unidentified, mad e up more than 50% of the AR in a single sampling event. In addition, based on the structure of the parent compound , and the proposed degradation pathway s, many of the minor degradates may

have a high degree of structural similarity to each other and/or the parent, and so may have toxi c properties similar to those of the parent. **5.0 Residue Profile**  **5.1 Residue Analytical Methods (860.1340)**  **5.1.1 Data Collection Methods**  QuEChERS: The hops (NAFTA trials ) , pome fruit , fruiting vegetable , cucurbit, cherry and peach RAC samples , and apple processed commodities were anal yz ed for residues of metrafenone using an LC/MS/MS method which is described in Metrafenone (BAS 560 F): Validation of the Multi-Residue Enforcement Method QuEChERS for the Determination of Residues in Plant Matrices us ing LC/MS/MS (BASF Study # 398340). A QuEChERS method uses dispersive s olid p hase e xtraction (dSPE) to prepare the sample for analy sis. The method detects parent metrafenone , which has been determined to be the ROC for tolerance enforcement purposes in primary

crop s , based on plant metabolism studies. A summary of the methodology used to anal yz e the samples follows. Briefl y, metrafenone residues in RAC samples are extracted by shaking with a buffered solution of water and ACN in the presence of salts ( Supelco 55227 - u mixture, containing sodium chloride, magnesium sulfate, and citrate buffering agents) and centrifuged. An aliquot of the supernatant is further purified on a dSPE clean - up tube (Restek 26215, containing magnesium sulfate to remove residual water , and primary secondary

amine sorbent to remove sugars and fatty acids) and centrifuged. An aliquot of the extract is diluted with an acidified solution of ACN and water (0.1% formic acid in 1 : 1 ACN/water) prior to anal ys is by LC/MS/MS. Metrafeno ne is quantitated via MS/MS detection using the positive ionization mode monitoringMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **31** of **78** ion transitions from m/z 409 →209 for quantitation , and m/z 409 →227 for confirmation . Quantitation was obtained using an external calibration curve of metrafenone standards . The method was validated before the anal ys is of any treated pome fruit samples by fortifying untreated control apple fruit samples at 0.01 0 and 0.1 0 ppm. Concurrently with the anal ys is of field trial samples, the method was also validated using samples of untreated pome fruits fortified with metrafenone at 0.01, 0.1 0 and 1 .0 ppm. Additionally, the method was validated, before the anal ys is of any treated apple processed commodities, by fortifying untre ated control dried apple samples at 0.01 and 0.1 0 ppm. Concurrentl y with the anal ys is of processed commodities, the method was also validated using samples of untreated apple RAC and processed commodities fortified with metrafenone at 0.01 to 1 0 ppm. The method was validated before the anal ys is of any treated tomato samples by fortifying untreated control tomato fruit samples at 0.01, 0.1 0 and 1 .0 ppm. Concurrently with the anal ys is of field trial samples, the method was also validated using samples of untreated tomato es fortified with metrafenone at 0.01 and 0.1 0 ppm. The method was validated before the anal ys is of any treated pepper samples by fortifying untreated control pepper fruit samples at 0.01 , 0.1 0 , and 3 .0 ppm. Concurrently with the anal ys is of field trial samples, the method was also validated using samples of untreated pepper s fortified with metrafenone at 0.01 and 0. 1 0 ppm. The method was validated before the anal ys is of any treated cucurbit samples by fortifying untreated control samples of cantaloupe and summer squash at 0.01, 0.10 and 1.0 ppm , and untreated cucumber samples 0.01 and 0.10 ppm. Concurrentl y with the analysis of field trial samples, the method was also validated using samples of untreated cantaloupe s , cucumber s and summer squash fortified with metrafenone at 0.01 and 1.0 ppm. The method was validated before the anal ys is of any treated cherry samples by fortifying untreated control cherry

fruit samples at 0.01, 0.1 0 and 1 .0 ppm. Concurrently with the anal ys is of field trial samples, the method was also validated using samples of untreated cherries fortified with metrafenone at 0.01, 0.1 0 and 1.0 ppm. The method was validated before the anal ys is of any treated peach samples by f ortifying untreated control peach fruit samples at 0.01, 0.10, 1.0 and 2.0 ppm. Concurrentl y with the anal ys is of field trial samples, the method was also validated using samples of untreated peach es fortified with metrafenone at 0.01, 0.10 and 1.0 ppm. The method was validated before the anal ys is of any treated hops cone samples (reported in MRID #49145403 ) by

fortifying untreated control samples of dried and fresh hops cones at 0.01 - 200 and 0.01 - 1.00 ppm, respectivel y. Concurrently with the anal ys is of field trial samples, theMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **32** of **78** method was also validated using samples of untreated dried and fresh hops cones fortified with metrafenone at 0.01 - 200 and 0.01 - 50 ppm, respectively . QuEChERS Conclusions: The metrafenone residues in hops (NAFTA trials ), pome fruit, fruiting vegetable, cucurbit, cherry and peach RAC samples, and apple processed commodities were quantitated using an LC /MS/MS multi - residue QuEChERS method (BASF Study #398340). The method was successfully

validated for all these commodities in conjunction with the studies prior to analy sis of the field trial samples. Acceptable concurrent method recovery data in all matrices were also obtained for metrafenone. The validated L OQ for residues of metrafenone in pome fruits RAC and processed co mmodity samples was 0.01 ppm ; the method limit of detection (LOD) was 0.003 ppm. The validated LOQ for residues of metrafenone in fruiting vegetable samples was 0.01 ppm ; the estimated method LOD was reported as 0.001 ppm, or approximately 10% of the LOQ. The validated L OQ was 0.01 ppm for metrafenone in dried and fresh hops cones ; the calculated LODs were 0.0034 and 0.0035 ppm in dried and fresh hops cones, respectivel y. The validated LOQ was 0.01 ppm for metrafenone in all cucurbit matrices ; the report ed LOD in cucumber was 0.001 ppm (10% LOQ). The LOQ was 0.01 ppm for metrafenone in cherries. The LOQ was 0.01 ppm for metrafenone in peaches ; the calculated LOD was 0.0041 ppm. No additional data are required in support of this data collection method. BASF M ethods #535/1 and #535/3: The hops ( German trials ) RAC samples were anal yz ed for residues of metrafenone using BASF M ethods #535/1 (L 0076/01) and #535/3 (L 0076/03) . The tomato processed commodities were anal yz ed for residues of metrafenone using BASF M ethod #535/1 (L 0076/01). The two methods are essentially identical . Briefly , samples were extracted with methanol/water

/2N HCl ( 14 :5: 1 , v/v/v) , and centrifuged. The supernatant was partitioned with cyclohexane/ 0. 2N NaOH (5:1, v/v), and the organic phase was evaporated to dry ness, then reconstituted in methanol/water ( 1 : 1, v/v) for L C/MS/MS analysis. The method monitors two ion transitions for determination of metraf enone , m/z 411 →209 for quantitation , and m/z 411 →229 for confirmation. BASF Methods #535/1 and #535/3 w ere validated before the anal ys is of any treated hops cone samples (reported in MRID s #4914540 7 and 4914540 8 ) by fortifying untreated control samples of dried and fresh hops cones at 0.01 - 200 and 0.01 - 1.00 ppm, respectively . Concurrentl y with the anal ys is of field trial samples, the method s w ere also validated using samples of untreated dried and fresh hops cones fortified with metrafenone at 0.01 - 200 and 0.01 - 50 ppm, respectively . Concurrentl y with the analysis of tomato RAC and processed commodity samples, BASF Method #535/1 was validated using samples of untreated control tomato RAC and processed commodity

samples (washed fruit, vegetable stock, p aste, wet pomace , and peel) fortified with metrafenone at 0.01 , 0.10, 1.0 and 5 .0 ppm .Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **33** of **78** BASF Methods #535/1 and #535/3 Conclusions: The hops ( German trials ) RAC samples were anal yz ed for residues of metrafenone using BASF Methods #535/1 and #535/3. The tomato processed commodities were anal yz ed for residues of metrafenone using BASF Method #535/1. The method s w ere successfully validated for these commoditi es in conjunction with th e studies prior to anal ys is of the field trial samples. Acceptable concurrent method recovery data in all matrices were also obtained for metrafenone. The validated LOQ was 0.01 ppm for metrafenone in tomato RAC and processed commodity samples ; the method L OD was not specified. The validated LOQ was 0.01 ppm for metrafenone in fresh hops cones, dried hops cones, and the hops processed commodities ; the method L OD was not specified. No additional data are required in support o f th ese data collection method s . **5.1.2 Multi**  **- Residue Methods (860.1360)**  **Multi -**  **Residue Method s**  **DER for MRID #46857701** BASF Corporation previously submitted multiresidue method testing data for metrafenone with PP#4E6884. Multiresidue method testing data were submitted for metrafenone and its metabolites CL376991, CL434223, and CL 3000402. Metabolite CL3000402 corresponds to a metabolite identified in the grape metabolism study as surface rinse metabolite 2 ; the other two metabolites appear to have been identified in cereal grains (data not submitted to EPA). The test substances were anal yz ed according to the Food and Drug Administration (FDA) Multiresidue Method Test guidelines in PAM Vol. I . Metrafenone and its metabolites were tested through Protocols A, B, C, D, E and F; the compounds were not tested under Protocol G because they are not substituted ureas. The study was conducted by

Maxim Technologies (Middleport, NY). The test substances do not have N - methylcarbamate structures and were not found to be naturall y fluorescent in testing under Protocol A. In Protocol B testing, metrafenone, CL376991, and CL 434223 were completel y recovered from grapes fortified at 0.05 and 0.50 ppm, and metrafenone an d CL376991 were partially recovered from peanuts fortified at 0.05 and 0.50 ppm; low recoveries were obtained for CL434223. CL 3000402 was not recovered in Protocol B testing due to matrix interferences in both grapes and peanuts. Protocol C testing of the compounds indicated that further testing using Protocols D, E and F was required for all test substances. The Protocol C results indicated that all analytes were detected using an electron capture detector (ECD). Metrafenone was recovered from grapes fortified at 0.05 and 0.50 ppm using Protocols D and E (mixed ether and methyl ene chloride elution sy stems), and from peanuts fortified at 0.05 and 0.50 ppm using Protocol F. CL376991, CL 434223, and CL3000402 were also recovered using Protocol D (without Florisil cleanup). CL 376991, CL434223, and CL 3000402 were not recovered from the Florisil column in Protocol E and F testing.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **34** of **78** These data indicate that FDA multiresidue methods Protocols D, E and F may be suitable for determining residues o f metrafenone in grapes and peanuts. Conclusions : The submitted multiresidue methods test data are adequate. The data indicate that multiresidue methods are probably suitable for determining residues of metrafenone in grapes for tolerance enforcement. These results were previously submitted to FDA. **5.1.3 Tolerance Enforcement Methods**  **Residue Analytical Method DER for**  **MRIDs #48981303 and 48981304 Residue Analytical Method DER for**  **MRIDs # 49267202**  **and 49267203** QuEChERS: BASF has submitt ed the QuEChERS method as the new enforcement method for metrafenone residues in plant commodities . The data previousl y requested regarding fortification at tolerance levels for the previous tolerance enforcement method (FAMS 105 - 01 for grape , and FAMS 106 - 01 for wine) are no longer relevant. This conditional data issue is considered resolved, and the new enforcement method and supporting ILV are discussed and reviewed below , and in the supporting DER for MRIDs # 48981303 and 48981304 . Briefl y, homogenized samples are extracted with ACN. A mixture of magnesium sulfate, sodium chloride, and citrate salts is added to buffer the solution to pH 5 - 5.5, and after shaking, the mixture is centrifuged to separate the phases. An aliquot of the A CN phase is cleaned - up by d SPE on primary

secondary

amine sorbent for analy sis using LC /MS/MS . Two parent - daughter ion transitions are monitored, one for quantitation (m/z 409 →209 ) , and the other for confirmation (m/z 411 →209 for dried hop cones , m/z 409 → 227 for all other matrices ) . Based on the lowest level of method validation (LLMV) , the v alidated LOQ is 0.01 ppm for metrafenone. The method was adequately validated using samples of dry bean seed, cucumber, dried hops cones, lemon, ra

peseed, and wheat forage, grain and straw. Samples were fortified with metrafenone at the LOQ (0.01 ppm) and 10 X the LOQ (0.1 ppm) for dry bean seed and rapeseed; at 0.01, 0.1 0 and 0.5 0 ppm for wheat grain; at 0.01, 0.1 0 , and 5 .0 ppm for cucumber, lemon, wheat forage, and wheat straw; and at 0.01, 0.1 0 , and 20 ppm for dried hop cones . For samples fortified at the LOQ, recoveries ranged from 79 - 91% (average of 86% and standard deviation of 4.9%) for dry

bean seed; 102 - 105% (average of 104% and standard deviation of 1.2%) for cucumber; 97 - 101% (average of 99% and standard deviation of 1.8%) for dried hop cones; 96 - 10 8 % (average of 104% and standard deviation of 4.6%) for lemon; 94 - 99% (average of 97% and standard deviation of 2.0%) for rapeseed; 96 - 102% (average of 100% and standard deviation of 2.5%) for wheat forage; 102 - 105% (average of 104% and standard deviation of 1.1%) for wheat grain; and 96 - 105% (average of 100% and standard deviation of 3.4%) for wheat straw. Individual recoveries at each fortification level were within the acceptable range of 70 - 120% and coefficients of variance ranged from 0.9 - 6.6% .Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **35** of **78** The QuEChERS method is proposed as an enforcement method for metrafenone residues in plant commodities. Because the method includes monitoring of two parent - daughter ion transitions, a separate confirmatory

method is not required. An adequate ILV study was submitted for the method (with dry

bean seed, cucumber, dried hop cones, lemon, rapeseed, and wheat forage, grain and straw) at fortification levels including the LOQ and 10 X the LOQ. No radiovalidation data were submitted . H owever, the cucumber metabolism study conducted with metrafenone include d data demonstrating the ability of ACN to extract incurred residues from treated crop matrice s . Ergo, no radiovalidation data are requir ed. Because the QuEChERS method is a German multi - residue method, Agency method validation is not required. DFG Method S19 : BASF has submitt ed DFG Method S19 (extended revision) as the new enforcement method for metrafenone residues in livestock commodities. The new enforcement method and supporting ILV are discussed and reviewed below , and in the supporting DER for MRIDs # 49267202 and 49267203 . Briefl y, the samples are extracted with acetone/water (2:1, v:v), and the extracts are partitioned with ethyl acetate/cyclohexane (1:1, v:v). An aliquot of the organic phase is evaporated to near dry ness, and the residue is re - dissolved in ethyl acetate. A salt m ixture and cyclohexane are added to the residue and mixed. The samples are cleaned up through gel permeation chromatography (GPC), and residues are eluted with ethyl acetate/cyclohexane (1:1, v:v). The eluate is concentrated, and dissolved in ethyl acetate for analy sis. The LOQ is 0.01 ppm in milk, and 0.05 ppm in meat and eggs. The LOD is 0.002 ppm in milk, and 0.01 ppm in meat and eggs. The method was adequately validated using samples of milk fortified with metrafenone at 0.01 0 and 0.1 0 ppm , and s amples of meat and eggs fortified with metrafenone at 0.05 and 0.50 ppm . Overall mean recoveries were 69 - 97%, with relative standard deviations of less than 20% , from each matrix tested. An ILV study

was also conducted using samples of milk fortified w ith metrafenone at 0.01 0 and 0.1 ppm , and samples of meat and eggs fortified with metrafenone at 0.05 and 0.50 ppm . Acceptable mean recoveries ranging from 76 % to 10 1 % , with relative standard deviations of less than 20% , were found fr om each matrix tested . No confirmatory

procedures, or radiovalidation data were included in the submission. Because this method monitors multiple ion s for the determination of metrafenone , no confirmatory procedures are needed. No radiovalidation data are required for the method because the solvent sy stems utilized in method DF G S 19 should efficiently extract metrafenone residues in meat, milk and eggs based on similar polarity of the solvents used in the goat metabolism study with metrafenone (refer to the DER for MRID # 49267201) .Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **36** of **78** Conditional Data - M

ethod V alidation/R adiovalidation : Additional method validation data were requested in the previous HED Risk assessment (D354166 ; D. McNeill y ; 1 March 2010 ) for the anal ytical Method FAMS 105 - 01 , reflecting fortifications at 4.5 ppm for grapes, and at both the LOQ (0.05 ppm) and 17 ppm for raisins. In addition, radiovalidation data were also required to demonstrate that Method FAMS 105 - 01 adequately recovers weathered residues of metrafenone from grapes. Since a new enfo rcement anal ytical method has been submitted these two issues related to the previous enforcement method are no longer relevant. It should be noted that the registrant did provide data showing adequate extractability using the 4:1 n - heptane/acetone extraction approach. HED notes that the cucumber data demonstrate adequate extractability using 4:1 n - heptane/acetone. Conditional Data - D ata C ollection M

ethod Radiovalidation: The extraction solvent used in the data collection method for grapes was different from that used in the proposed enforcement method, and radiovalidation data were required to support the data collection method, BASF Method 535/0. Samples from the grape field trial and processing studies submitted with PP#8F7371 were anal yz ed for residues of metrafenone using an L C/MS/MS method, BASF method 535 /0 . Briefl y, samples of grape commodities were extracted with methanol/water /2N HCl ( 14 :5: 1 , v/v/v) , and centrifuged. The supernatant was partitioned against cyclohexane under alkaline conditions, evaporated to dry ness, and reconstituted in methanol/water ( 1:1 , v/v) for LC/MS/MS determination of residues of metrafenone. This conditional data issue is considered resolved by the data extraction efficiency data discussed below , and summarized in T able s 5.1.3.1 and 5.1.3.2 , below . These data compare the extraction efficiency for the Method 535 /0 together with the extraction efficiency for the extraction sy stem used in the cucumber and grape metabolism studies. The data demonstrate a high extraction efficiency for the methanol/water /HCl sy stem. All the cucumber fruit samples had extraction efficiencies equal to or greater than 88%. Conditional Data

– E

xtraction E

fficiencies U

sing D ifferent S

olvent S ystems : C ucumber plants were treated with two applications of radio - labeled metrafenone (labeled in the trimethoxy phenyl ring) at a rate of 200 g ai/ha (total seasonal application rate of 400 g ai/ha). There was a 14 - day interval between treatments. L eaf samples were collected directl y after the first application , and three day s after the second application. Whole fruit samples were harvested 14 day s after the first application , and three day s after the second application. The whole fruit was divided into pulp and peel samples. The samples were homogenized and then extracted with the solvent sy stems listed in the table below. Radioactivity was determined by liquid scintillation counting.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **37** of **78 TABLE**  **5.1.3.1 Extractability of**  **14C -**  **Metrafenone in Cucumber Matrices (%TRR 1**  **) .**  **Sample Matrix (Timing 2**  **) Me** **tabolism Extraction**  **Me thod 535**  **Me thod 105**  **- 01**  **S19 Method 3**  **X M**  **ethanol Followed by** 

**2 X**  **W ater**  **Me thanol/Water/** 

**HCl (70/25/5) n**  **- Heptane/** 

**A cetone (80/20)**  **Acetone/**

**Water (2/1)** Cucumber Fruit (14 - DAT1 ) 87.5 1.6 87.6 71.0 86.2 Cucumber Fruit (3 - DAT2) 92.9 1.4 95.3 85.4 93.4 Cucumber Pulp (2 - DAT2 ) 91.1 1.1 93.5 **56.2** 91.0 Cucumber Fruit ( 3 - DAT2 ) 91.2 1.1 94.0 84.0 93.6 Cucumber Fruit (0 - DAT1 ) 98.8 0.3 94.2 95.8 96.8 Cucumber Fruit ( 3 - DAT2 ) 92.6 3.2 91.9 85.3 90.3 1. DAT = Days After first Treatment. 2. T RR = Total Radioactive Residues. The recoveries for metrafenone using the extraction profile in the cucumber metabolism study are similar to the other three extraction profiles test ed , except for one cucumber pulp sample which did have low r ecovery . The extractability of radioactive residues from cucumber peel in the metabolism study

was very high, 92.2% of the TRR from pulp , and 99.1% of the TRR from cucumber leaves. Most of the radioactive residue was extracted with methanol. The additional extraction with water released very low amounts of the TRR (1.1%). The extractability

with solvents was tested for all cucumber matrices (leaf, fruit, pulp, peel and the rest of the plant). Three one - step extraction methods were investigated: methanol/water/2N HCl ( 14: 5 :1 , v/v/v/) , n - heptane/acetone (4:1 , v/v), and acetone/water (2 : 1, v/v). The results of the extractability

tests are summarized in the table below. **TABLE 5.1.3.2**  **Extractability of Cucumber Whole Fruit Samples with Different Solvent System s**  **. Sample**  **Matrix DAT**  **1 Solvent**  **ERR 2**  **Mg/Kg %TRR RRR** **3 Mg/Kg %TRR**  Whole Fruit 14 3 X Methanol, 2 X water ( metabolism e xtraction) 0.015 89.0 0.002 11.0 **Me thanol/Water/2N HCl**  **(M ethod 535/1)**  **0.011 87.6**  **0.002 12.4**  n - Heptane/Acetone (Method 105 - 01) 0.004 71.0 0.002 29.0 Acetone/Water (S - 19 Method) 0.012 86.2 0.002 13.8 Whole Fruit 17 3 X Methanol, 2 X water 0.048 94.3 0.003 5.7

**Me thanol/Water/** **2N HCl**  **0.042 95.3**  **0.002 4.7**  n - Heptane/Acetone 0.038 85.4 0.007 14.6 Acetone/Water 0.045 93.4 0.003 6.6 1 . DAT = Days A fter first T reatment. 2 . ERR = Extracted Radioactiv e Residue s . 3 . RRR = Remaining or bound Radioactiv e Residue s .Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **38** of **78** Conclusion s : Radiovalidation data are no longer required to demonstrate that Method FAMS 105 - 01 and BASF Method 535 adequatel y recover weathered residues of metrafenone from grapes. HED agrees that the cucumber data, and other extraction efficiency data conducted as a part of the cucumber metabolism study, adequately demonstrate the extractability of metrafenone residues using 4:1 n - h eptane/acetone solvent and methanol/water/2N HCl (70:25:5, v/v/v) solvent sy stem s . No additional data are required to satisfy the conditional data requirements that were previousl y identified by HED . Method validation and ILV data submitt ed for the QuEChERS method (MRIDs # 48981303 and 48981304) demonstrate that it is adequate as the new tolerance enforcement method for metrafenone. Method validation and ILV data submitted for the QuEChERS method (MRIDs #48981303 and 48981304) demonstrate that it is adequate as the new tolerance enforcement method for metrafenone. **5.2 Storage St**  **ability (860.1380) Residue Chemistry**  **Summary D312307; D. McNeilly; 24 August 2006**  **Storage Stability DER for**  **MRID #48981308** BASF submitted the results of a storage stability study with metrafenone in wheat (whole plant, grain, and straw), grape, tomato, dried pea, and soybean seed ( MRID #48981308 ) . These crops meet the OECD requirement for stability in five diverse crops , including high - water, high - oil, high - protein, high - starch and high - acid. Untreated samples were fortified with metrafenone at 0.1 0 pp m , and stored frozen at roughl y - 20°C , followed by anal ys is at intervals of 0, 28 - 31, 55, 84, 85, 174 - 178, 358 - 360, 455, and/or 726 - 739 day s. Samples were anal yz ed for residues of metrafenone using an LC /MS/MS method , BASF Method #535/1 (L 0076/01) . Thi s method was adequate for data collection , based on acceptable concurrent recovery

data . The LOQ , determined as the LLMV , was 0.01 ppm in each sample matrix. It was not reported whether c oncurrent recoveries and recoveries in stored samples were corrected fo r apparent residues in controls. The study results indicate that residues of metrafenone are stable in wheat (whole plant, grain, and straw), grape, tomato, dried pea, and so ybean seed stored frozen (roughly - 20 °C) for intervals of up to 726 - 739 day s ( approximately 2 years).Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **39** of **78 TABLE 5.2**  **Storage Stability of Metrafenone in Wheat, Grape, Tomato, Dried Pea, and Soybean.**  **Comm odity**  **Spike**

**Level (ppm)**  **Storage**

**I nterval**  **( D**  **ays) Recovered** 

**Residues (ppm** **) Me**  **an Recovered**

**Residues 1**  **(ppm )**  **Me an** 

**Recovery (%)**  **Corrected**

**R ecovery**  **(%) 2**  Wheat, Whole Plant 0.1 0 0 0.085, 0.087 0.086 86 -- 31 0.074, 0.072 0.073 73 94 178 0.083, 0.083 0.083 83 96 360 0.081, 0.079 0.080 80 100 732 0.081, 0.089 0.085 85 86 Wheat, Grain 0.1 0 0 0.105, 0.109 0.107 107 -- 31 0.079, 0.078 0.079 79 87 178 0.083, 0.083 0.083 83 85 360 0.085, 0.084 0.085 85 83 726 0.077, 0.077 0.077 77 86 Wheat, Straw 0.1 0 0 0.091, 0.091 0.091 91 -- 29 0.090, 0.091 0.091 91 100 176 0.083, 0.086 0.085 85 95 358 0.089, 0.093 0.091 91 96 732 0.077, 0.079 0.078 78 100 Grape 0.1 0 0 0.088, 0.090 0.089 89 -- 30 0.075, 0.079 0.077 77 95 176 0.095, 0.099 0.097 97 98 358 0.107, 0.105 0.106 106 110 730 0.078, 0.088 0.083 83 99 Tomato 0.1 0 0 0.088, 0.089 0.089 89 -- 29 0.088, 0.087 0.088 88 97 174 0.101, 0.101 0.101 101 100 358 0.074, 0.076 0.075 75 77 455 0.076, 0.076 0.076 76 98 726 0.092, 0.100 0.096 96 106 Dried Pea 0.1 0 0 0.104, 0.104 0.104 104 -- 29 0.087, 0.093 0.090 90 94 176 0.095, 0.097 0.096 96 92 358 0.089, 0.091 0.090 90 90 730 0.077, 0.090 0.084 84 87Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **40** of **78 TABLE 5.2**  **Storage Stability of Metrafenone in Wheat, Grape, Tomato, Dried Pea, and Soybean.**  **Comm odity**  **Spike**

**Level (ppm)**  **Storage**

**I nterval**  **( D**  **ays) Recovered** 

**Residues (ppm** **) Me**  **an Recovered**

**Residues 1**  **(ppm )**  **Me an** 

**Recovery (%)**  **Corrected**

**R ecovery**  **(%) 2**  Soy bean, Seed 0.1 0 0 0.098, 0.098 0.098 98 -- 28 0.071, 0.072 0.072 72 75 55 0.078, 0.079 0.079 79 84 84 0.089, 0.090 0.090 90 84 85 0.085, 0.079 0.082 82 81 176 0.057, 0.062 0.060 60 60 358 0.070, 0.073 0.072 72 72 739 0.096, 0.100 0.098 98 95 1. Mean recovered residues were determined by the study reviewer. 2. Corrected for mean concurrent recovery. Storage stability

data for grapes and wine were previously submitted and reviewed with PP#4E6884. Th ose data indicate that residues of metrafenone are stable under frozen storage conditions for intervals of up to 18 months in grapes and wine ( D312307; D. McNeill y; 24 August 2006 ) . Conclusions : The storage stability data are adequate and demonstrate that residues of metrafenone are stable in wheat (whole plant, grain, and straw), grape, tomato, dried pea, and soy bean seed stored frozen ( at approximately - 20 °C) for up to 726 - 739 day s ( roughly 2 years) . The submitted and available storage stability data are adequate to support the storage conditions and durations of samples from the submitted crop field trial and processing studies. **5.3 Residue Data**  **5 .3.1**  **Crop Field Trials (860.1500)** Pome Fruit (MRID #49055901 ) : BASF has submitted field trial data for metrafenone on representative crops (apple and pear) of the pome fruits crop group 11 - 10 . A total of 18 field trials were conducted on pome fruits during the 2010 growing season in North American Free Trade Agreement (NAFTA) Growing Zones: twelve trials on apple in Zones 1 (NY, two trials; PA, one trial), 2 (VA, one trial), 5 (MI, WI, one trial each), 9 (UT, one trial), 10 (CA, one trial), and 11 (ID, WA, two trials each), and six trials on pear in Zones 1 (NY, one trial), 10 (CA, two trials), and 11 (ID, two trials; WA, one trial). At 14 of the test sites (nine apple/ five pear), one untreated control and one treated plot (Treatment 2) were establis hed, with the treated plot receiving applications consisting of either concentrate d or dilute spray volumes of 50 - 100 or 100 - 400 gallons per acre ( GPA) , respectivel y . At the four remaining test sites (three apple and one pear), which were located in z ones whereMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **41** of **78** only one trial per crop was to be conducted, one untreated control and side - by- side treated plots were established, with the treated plots receiving either the concentrate (Treatment 2) or dilute (Treatment 3) spray

volume regime, described above. At each site, the treated plots received three foliar airblast applications of metrafenone (2.5 lb ai/gal SC, BASF formulation code BAS 560 03 F) targeting roughl y 0.3 lb ai/A/application (0.336 kg ai/ha/application), with a nominal 7 - day RTI , resulting in a total rate of roughl y 0.9 lb ai/A (1.0 kg ai/ha/season). The actual application rate ranged from 0.29 - 0.31 lb ai/A/application, with 5 - to 9 - day

RTIs, for a tot al rate of 0.8 9 - 0.9 2 lb ai/A (1.00 - 1.03 kg ai/ha/season). The applications were made in approximately 59 - 86 GPA of water (552 - 804 L/ha) for concentrate spray volumes and approximately 101 - 257 GPA of water (945 - 2404 L/ha) for dilute spray volumes using gro und (airblast) equipment. An adjuvant (non - ionic surfactant) was included in the spray mixture for each application. Single control and duplicate treated apple and pear RAC samples (fruit) were harvested at normal crop maturity 6 - to 7 - and 13 - to 16 - day PHIs at all test sites. At one pear and two apple test sites, additional treated samples were collected at PHIs of 0, 3 - 4, and 21 day s to examine residue decline. **TABLE 5.3.1.1**  **Summary of Residue Data from Pome Fruit Field Trials with Metrafenone.**  **Matrix Total Use** 

**Rate ± 5% kg ai/ha (lb**  **ai/A) Spray** 

**Volume (GPA)**  **PHI**

**(Days) Residue Levels (ppm)**  **1 n**  **Min. Max.**  **LAFT 2**  **HAFT** 2 **Median Me**  **an Std.**  **Dev.** Apple (Fruit) 1.0

(0.9) (50 - 100) **3** 6 - 7 7 0.07 0.85 0.08 0.76 0.23 0.31 0.23

13 - 16 7 0.04 0.57 0.05 0.54 0.20 0.22 0.16 1.0 (0.9) (100 -

400) **4** 6 - 7 8 0.13 0.60 0.14 0.54 0.29 0.31 0.15

13 - 15 8 0.09 0.49 0.10 0.45 0.25 0.27 0.13 1.0 (0.9) Both

(50 - 400) 6 - 7 15 0.07 0.85 0.08 0.76 0.23 0.31 0.19

13 - 16 15 0.04 0.57 0.05 0.54 0.20 0.25 0.14 Pear (Fruit) 1.0

(0.9) (50 - 100) **3** 6 - 7 4 0.13 0.43 0.16 0.41 0.29 0.29 0.13

13 - 14 4 0.08 0.36 0.10 0.33 0.22 0.22 0.12 1.0 (0.9) (100 -

400) **4** 7 3 0.12 0.52 0.14 0.48 0.41 0.34 0.18

14 3 0.09 0.43 0.09 0.37 0.28 0.25 0.14 1.0 (0.9) Both

(50 - 400) 6 - 7 7 0.12 0.52 0.14 0.48 0.39 0.31 0.14

13 - 14 7 0.08 0.43 0.09 0.37 0.28 0.23 0.12 All Pome Fruits 1.0

(0.9) Both

(50 - 400) **6 -**  **7 22**  **0.07 0.85**  **0.08 0.76**  **0.27 0.31**  **0.17**

**13 -**  **16 22**  **0.04 0.57**  **0.05 0.54**  **0.21 0.24**  **0.13** 1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 2. LAFT = Lowest Average Field Trial value; HAFT = Highest Average Field Trial value. 3. Concentrate spray. 4. Dilute spray. The residues of parent metraf enone in apple and pear RAC samples were quantitated using an LC/MS/MS multi - residue QuEChERS method (BASF Study # 398340) . The method was successfull y validated on apples in conjunction with this study prior to analy sis of the fieldMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **42** of **78** samples. Acceptable c oncurrent method recovery data for pome fruit RAC samples were also obtained for metrafenone. The validated LOQ for residues of metrafenone in pome fruits RAC samples was 0.01 ppm. The LOD was 0.003 ppm. The pome fruits RAC samples were stored frozen for a maximum of 734 day s (24 months) from collection to extraction for anal ys is. The interval between extraction and analy sis was 0 - 1 day . Adequate storage stability data for metrafenone are available to support the storage conditions and intervals incurred by

the pome fruit residue samples in this study . The results from these trials are summarized in Table 5.3.1.1 , above , and show that following the last of three foliar airblast applications of metrafenone at roughl y 0.3 lb ai/A/application, with 5 - t o 9 - day RTI s, residues of metrafenone (and per trial averages) were 0.07 - 0.85 (0.08 - 0.76) ppm (concentrate spray) and 0.13 - 0.60 (0.14 - 0.54) ppm (dilute spray) in 30 treated apple samples harvested at a 6 - or 7 - day PHI . At the same treatment rate and RTI s, metrafenone residues (and per trial averages) were 0.04 - 0.57 (0.05 - 0.54) ppm (concentrate spray) and 0.09 - 0.49 (0.10 - 0.45) ppm (dilute spray) in 30 treated apple samples collected at a 13 - to 16 - day PHI . After three foliar airblast applications of metraf enone at roughl y 0.3 lb ai/A/application, with 7 - to 8 - day RTI s, residues of metrafenone (and per trial averages) were 0.13 - 0.43 (0.16 - 0.41) ppm (concentrate spray) and 0.12 - 0.52 (0.14 - 0.48) ppm (dilute spray) in 14 treated pear samples harvested at a 6 - o r 7 - day PHI . At the same treatment rate and RTI s, metrafenone residues (and per trial averages) were 0.08 - 0.36 (0.10 - 0.33) ppm (concentrate spray) and 0.09 - 0.43 (0.09 - 0.37) ppm (dilute spray) in 14 treated pear samples collected at a 13 - or 14 - day PHI . No substantial differences in metrafenone residues were observed between the concentrate and dilute spray

applications. Data from the residue decline sites indicate that metrafenone residues in pome fruits declined with increasing PHIs (results not shown here ; see the DER for MRID #49055901 for further details) . Pome Fruit Conclusion s : The results have shown that the maximum residues of metrafenone in pome fruits (apple and pear fruit RAC samples) following three foliar airblast applications of the 2.5 lb ai/gal SC formulation using dilute or concentrate spray volumes and totaling roughl y 0.9 lb ai/A/season were 0.85 ppm at a 6 - to 7 - day PHI and 0.57 ppm at a 13 - to 16 - day PHI. There were no substantial differences in the residues of metrafenone between the application spray volume treatments. Data from the residue decline tests indicated that metrafenone residues in pome fruits declined with increasing PHI s. The maximum metrafenone residues in pome fruits are within a factor of 5 of each other (0.85 and 0.52 ppm for apple and pear, respectivel y, at the targeted 7±1 day

PHI ) ; therefore, the residues are within the EPA guidelines for the establishment of a group tolerance in c rop group 11 - 10 (pome fruits). An acceptable method w as used for residue quantitation, and adequate storage stability data are available to support the sample storage conditions and durations.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **43** of **78** Fruiting Vegetables, Tomato (MRID #49 11 9 1 0 8 ) : BASF has submitted field trial data for metrafenone (BAS 560 F) on t omato from a total of 1 8 trials conducted during the 2010 - 2011 growing season s in NAFTA Growing Zones 1 (NY, one trial), 2 (GA, NC, one trial each), 3 (FL, two trials), 5 (OH, MI, one trial each), and 10 (NM and AZ, one trial each; CA, nine trials). HED h as determined that one trial pair ( - CA123 and

–CA127 ) should be considered replicates; the above field trial distribution incorporates this conclusion. Each test location included one treated and one untreated plot. At each site, the treated plot recei ved three broadcast or directed foliar applications ( except as noted bel ow for the trial located in AZ) of metrafenone (2.5 lb ai/gal SC, BASF formulation code BAS 560 03 F) targeting 0.30 lb ai/A/application (0.336 kg ai/ha/application), with a nominal 7 - day RTI , resulting in a total rate of 0.90 lb ai/A (1.0 kg ai/ha/season). The actual application rate was 0.29 - 0.33 lb ai/A/application, with a 6 - to 8 - day RTI , for a total rate of 0.89 - 0.95 lb ai/A (0.999 - 1.066 kg ai/ha/season). At the trial in AZ, in o rder to allow the fruit to develop further and provide adequate samples for residue anal ys is, four foliar spray s of metrafenone at 0.30 - 0.32 lb ai/A/application were made , with a 7 - or 8 - day RTI , totalling 1.23 lb ai/A ( 1.38 kg ai/ha/ season). All applications were made in approximately 31 - 90 GPA of water (286 - 841 L/ha) using ground equipment. An adjuvant was included in the spray mixture for each application. At all test sites tomato RAC samples (fruit) were harvested at normal crop maturity, at a 0 day PHI , after the spray had dried on the fruit, and again at a 6 - 8 day PHI . At two test sites (Trial CA124 and FL38 ), additional treated samples were collected 1, 3, 9 - 10 and 12 - 14 day PHI to examine residue decline. The residues of parent metrafenone in tomato RAC samples were quantitated using an LC/MS/MS multi - residue QuEChERS method (BASF Study # 398340) . Sample anal ys is was conducted b y Py

xant Labs (Colorado Springs, CO) . The method was successfully validated on tomato in conjun ction with this study prior to analy sis of the field samples. Acceptable concurrent method recovery data for tomato RAC samples were also obtained for metrafenone. The validated LOQ for residues of metrafenone in tomato RAC samples was 0. 01 ppm. The estimated method LOD was reported as 0.001 ppm, or approximately 10% of the LOQ. The calculated LOD and LOQ for metrafenone in tomato fruit w ere 0.001 and 0.004 ppm, respectivel y. The tomato RAC samples were stored frozen for 303 - 730 day s (approximately 10 - 24 months) from collection to extraction for anal ys is. Adequate storage stability data for metrafenone are available to support the storage conditions and duration s incurred b y the tomato residue samples in this study . As summarized in Table 5.3.1.2, bel ow , the results from these trials show that following the last of three or four foliar applications of metrafenone at roughl y 0.3 lb ai/A/application, with 6 - to 8 - day RTI s, residues of metrafenone (and per trial averages) were 0.04 1 - 0.452 (0.069 - 0.427) ppmMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **44** of **78** in 38 treated tomato samples harvested at a 0 - day PHIand <0.01 - 0.188 (<0.011 - 0.163) ppm in 38 treated tomato samples harvested at a 6 - 8 day PHI . Data from the residue decline sites indicate that metrafenone residues in tomato generally declined with increasing PHI s. **TABLE 5**  **. 3.1.2**  **Summary of Residue Data from Tom**  **ato Field Trials with Metrafenone**  **Comm odity**  **Total Use**  **Rate**

**lb ai/A (g ai/ha) PHI** 

**( D**  **ays) 2**  **Residue Levels (ppm) 1** 

**n 3**  **Min. Max.**  **LAFT 4**  **HAFT** 4 **Median Me**  **an Std.**  **Dev.** Tomato (Fruit) 0.891 - 1.234

(999 - 1383) 0 18 0.0409 0.452 0.0694 0.427 0.110 0.164 0.094 0.910 - 0.922 (1020 - 1033) 5 1 2 0.0427 0.0865 0.0541 0.0721 0.0631 0.0631 NA 6

3 2 0.0512 0.0830 0.0572 0.0748 0.0660 0.0660 NA 0.891 - 1.234 (999 - 1383) 6 - 8 18 <0.01 0.188 <0.0107 0.163 0.0860 0.0770 0.0446 0.910 - 0.922 (1020 - 1033) 5 9, 10 2 0.0149 0.0719 0.0187 0.0536 0.0362 0.0362 NA

12, 14 2 0.0138 0.0327 0.0166 0.0247 0.0207 0.0207 NA 1 . Except for sample min/max, values reflect per trial averages. 2 . The first harvest wa s on the day of the last application (0 - day PHI) at all trials. The second harvest was 6 to 8 days after the last application (6 - to 8 - day PHI) at all trials, except field trials

– CA124 and

–FL38. At field trial

– CA124, a decline study was conducted with the last applic ation 0, 1, 3, 6, 10 and 12 days before harvest (0 - to 12 - day

PHI). At field trial

–FL38, a decline study was conducted with the last application 0, 1, 3, 7, 9 and 14 days before harvest (0 - to 14 - day PHI). 3 . n = number of field trials. 4 . LAFT = Lowest Average Field Trial value; HAFT = Highest Average Field Trial value. 5 . Data from the two residue decline trials. 6. NA = Not Applicable. Fruiting Vegetables, Pepper (MRID #4911910 7 ) : BASF has submitted field trial data for metrafenone (BAS 560 F) on pepper from a total of eight trials conducted during the 2010 growing season: f

ive on bell pepper varieties in NAFTA Growing Zones 2 (GA, one trial), 3 (FL, one trial), 5 (IL, one trial), 6 (OK, one trial) and 10 (CA, one trial) and three on non - bell pepper varieties in NAFTA Growing Zones 2 (GA, one trial), 8 (KS, one trial) and 10 (CA, one trial). H ED has determined that one trial pair (R100014 and R100019) should be considered replicates; the above field trial distribution incorporates this conclusion. Each test location included one treated and one untreated plot. At each site, the treated plot received three broadcast foliar applications of metrafenone as an SC formulation , targeting 0.30 lb ai/A/application (0.336 kg ai/ha/application), with a nominal 7 - day RTI , resulting in a total rate of 0.90 lb ai/A (1.0 kg ai/ha/season). The actual application rate was 0.29 - 0.31 lb ai/A/application, with a 7 - day RTI, for a total rate of 0.88 - 0.91 lb ai/A (0.991 - 1.017 kg ai/ha/season). The applications were made in approximately 21 - 31 GP A of water (200 - 286 L/ha) using ground equipment. A nonionic surfactant (NI S) adjuvant was included in the spray mixture for each application.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **45** of **78** Pepp er RAC samples (fruit) were harvested at normal crop maturity, at a 0 - day PHI at all test sites, after the spray

had dried on the fruit, and again at a 7 day PHI. At one test site (Trial R100014, CA), additional treated samples were collected at 3, 10 and 14 day PHI s to examine residue decline. The residues of parent metrafenone in pepper RAC samples were quantitated using an LC/MS/MS multi - residue QuEChERS method (BASF Study #398340, reported as Method #R00033) . Sample anal ysis was conducted b y P yxant Labs (Colorado Springs, CO). The method was successfully

validated on pepper in conjunction with this study prior to anal ys is of the field samples. Acceptable concurrent method recovery data for pepper RAC samples were also obtained for metrafenone. Th e validated LOQ for residues of metrafenone in pepper RAC samples was 0.01 ppm. The method LOD was reported as 0.001 ppm, or 10% of the LOQ. The pepper RAC samples were stored frozen for 671 - 764 day s (approximately 22 - 25 months) from collection to extraction for anal ys is, and were anal yz ed within 16 days of extraction. Adequate storage stability data for metrafenone are available to support the storage conditions and durations incurred by the pepper residue samples in this study . As summarized in Tabl e 5.3 .1.3 , below, the results from these trials show that following the last of three foliar applications of metrafenone at roughly 0.3 lb ai/A/application, with 7 - day RTIs, residues of metrafenone (and per trial averages) were 0.067 - 0.667 (0.081 - 0.498) pp m in 18 treated pepper samples harvested at a 0 - day PHIand were 0.062 - 0.296 (0.065 - 0.295) ppm in 18 treated pepper samples harvested at a 7 - day PHI . The maximum residues were observed in the non - bell pepper cultivars, but were at relativel y similar lev els to those observed in the bell - pepper cultivars: Maximum metrafenone residues (and maximum per trial averages) for bell pepper varieties were 0.508 (0.417) ppm at the 0 - day PHIand 0.271 (0.221) ppm at the 7 - day PHI, and for non - bell pepper varieties, 0.667 (0.498) ppm at the 0 - day

PHI and 0.296 (0.295) ppm at the 7 - day PHI. Data from the residue decline site indicate that metrafenone residues in pepper declined with increasing pre - harvest intervals (results not shown here; see the DER for MRID #491191 07 for further details) . **TABLE 5**  **. 3.1.3**  **Summary of Residue Data from Pepper**  **Field Trials with Metrafenone Comm**  **odity Total Appl. Rate** 

**lb ai/A (g ai/ha) PHI** 

**(days) Residue Levels (ppm)**  **1 n**  **Min. Max.**  **LAFT 2**  **HAFT** 2 **Median Me**  **an Std. Dev.**  Bell Pepper (Fruit) 0.884 - 0.907

(991 - 1017) 0 5 0.112 0.508 0.148 0.417 0.270 0.297 0.113

7 5 0.0828 0.271 0.0991 0.221 0.163 0.158 0.0506 Non -bell Pepper (Fruit) 0 3 0.0665 0.667 0.0813 0.498 0.353 0.311 0.212 7 3 0.0622 0.296 0.0649 0.295 0.144 0.168 0.117 Com bined Pepper (Fruit) 0 8 0.0665 0.667 0.0813 0.498 0.312 0.302 0.142 7 8 0.0622 0.296 0.0649 0.295 0.154 0.162 0.0734 1 . Except for sample min/max, values reflect per trial averages; n = number of field trials 2 . LAFT = Lowest Average Field Trial Value; HAFT = Highest Average Field Trial value.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **46** of **78** Fruiting Vegetables Conclusions: The results have shown that the maximum residues of metrafenone in fruiting vegetables (tomato and pepper RAC samples) following three foliar b roadc ast applications of the 2.5 lb ai/gal SC formulation totaling roughly 0.9 lb ai/A/season were 0. 667 ppm at a 0 - day PHI . Data from the residue decline tests indicated that metrafenone residues in fruiting vegetable s declined with increasing PHI s. The maximum metrafenone residues in fruiting vegetables are within a factor of 5 of each other ( 0.452 and 0.667 ppm for tomato and pepper, respectively , at the targeted 0 - day PHI ) ; therefore, the residues are within the EPA guidelines for the establishment of a group tolerance in crop group 8 - 10 ( fruiting vegetables ). An acceptable method was used for residue quantitation, and adequate storage stability data are available to support the sample storage conditions and durations. Cherr y (MRID #491 454 02

) : IR - 4 submitted field trial residue data for metrafenone on cherry . Fourteen cherry

field trials (9 sweet cherry trials, and 5 tart cherry

trials) were conducted in the United States and Canada during the 2010 growing season in NAFTA Growing Zones 1 (NY; 1 trial), 5A (MI; 2 trials), 5 (ON; 3 trials), 9 (CO; 1 trial), 10 (CA; 2 trials) and 11 (ID, WA, and BC; 5 trials) . HED has conclud ed that three trials conducted in Zone 5 should be considered replicates for purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data requirements . The above field trial distribution incorporates this conclusion. Each trial consisted of one untreated and one treated plot. At each trial location, the treated plot received two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone ( BAS560 03 F SC) at 0. 286 - 0. 314 lb ai/A/application ( 321 - 352 g ai/ha/application) for a total seasonal rate of 0. 575 - 0. 626 lb ai/A ( 645 - 702 g ai/ha). Applications were made at 6 - to 9 - day RTI s using ground equipment (airblast sprayer) in spray volumes of 105 - 189 GPA ( 984 - 176 7 L/ha) , except at the NY trial, where higher than normal temperatures accelerated maturation, and required that applications be initiated earlier than anticipated; the first application at this trial was made in a spray

volume of 60.7 GPA (568 L/ha). An NI S, methylated seed oil (MSO), c rop oil concentrate (COC), or o rgano - silicone surfactant ( OSS ) was added to the spray mixtures for all applications. Samples of cherries were harvested from all trial sites at PHIs of 6 - 8 an d 13 - 15 day s. Additional cherry samples were collected from two tri al s at PHI s of 0 , 3, 17 and 21 day s to generate residue decline data. Samples of cherries were anal yz ed for residues of metrafenone using an LC /MS/MS method derived from Q uEChERS Method # R00033. The L OQ , determined as the LLMV , was 0.0 1 ppm. The method was adequate for data collection , based on acceptable method validation and concurrent recovery

data. The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels. Concurrent recoveries were corrected for apparent residues in controls ; residues in treated samples were not corrected for residues in controls.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **47** of **78** Samples of cherries were transferred to a sample preparation facility for homogenization prior to shipment to the analy

tical laboratory . Samples were stored frozen ( - 31 to - 3°C at the field sites, ≤ - 5°C at the sample preparation facility , and temperature unspecified at the anal ytical laboratory) from collection to anal ys i s for 676 - 784 day s (22.2 - 25.8 months ). Samples were anal yz ed within 2 - 9 day s of extraction. Adequate storage stability data are available to support the sample storage conditions and durations. The results from these trials are summarized in Table 5.3.1 .4 , below. Following two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone at a total rate of 0.575 - 0. 626 lb ai/A (645 - 702 g ai/ha) , residues (and per trial averages) of metrafenone in cherries harvested at PHI s of 6 - 8 day s and 13 - 15 day s, respectivel y, were 0.280 - 1.17 ( 0.317 - 1.16) and 0.117 - 0.704 (0.144 - 0.608) ppm. Itwas noted that the highest residues in cherries harvested at the 6 - to 8 - day

PHI were observed in samples from the NY trial, where the first application was made in a lower than targeted spray volume, and the highest residues in cherries harvested at the 13 - to 15 - day

PHI were observed in samples from one of the replicate MI trials, where adjuvant rates were lower than expected. At the residue decline trials, residues of metrafenone generall y declined with increasing PHI in cherries (results not shown here; see the DER for MRID #49145402 for further details) . **TABLE 5.3.1**  **. 4**  **Summary of Residue Data from C**  **herry Field Trials with Metrafenone.**  **Comm odity**  **Total Rate**

**lb ai/A (g ai** **/ha) PHI** 

**(days) Residue Levels (ppm** **) 1**  **n Min.**  **Max. LAFT**  **2 HAFT**  **2 Median**  **Me an**  **Std. Dev.**  Cherry 0.575 - 0.626

(645 - 702) 6 - 8 1 4 0.280 1.17 0.317 1.16 0.493 0.5 47 0 .221

13 - 15 14 0.117 0.704 0.144 0.608 0.34 0 0.370 0.146 1. Except for sample min/max, values reflect per trial averages; n = number of distinct field trials. 2. LAFT = Lo we st Average Field Trial; HAFT = Highest Average Field Trial. Cherry Conclusions: The submitted cherry field trial data are scientifically acceptable . Following two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone at a tot al rate of 0.575 - 0.626 lb ai/A (645 - 702 g ai/ha), residues (and per trial averages) of metrafenone in cherries harvested at PHI s of 6 - 8 day s and 13 - 15 day s, respectivel y, were 0.280 - 1.17 (0.317 - 1.16) and 0.117 - 0.704 (0.144 - 0.608) ppm. At the residue decline trials, residues of metrafenone generall y decreased with increasing PHI s in cherries. An acceptable method w as used for residue quantitation, and adequate storage stability data are available to support the sample storage conditions and durations. Hops (MRID #49145403): IR - 4 submitted field trial data for metrafenone on hops . Five hops field trials were conducted in the United States and Canada during the 2010 growing season in NAFTA Growing Zone s 5 (ON 1 trial), 5B (QC; 1 trial), 11 (ID and WA; 2 trials) and 12 (OR; 1 trial). Examination of the field trial records indicates that there were sufficient differencesMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **48** of **78** between the trials that each trial constitutes a separate trial for purposes of OCSPP Residue Chemistry

Test Guideline 860.1500 data re quirements. Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated plot received two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone (BAS560 03 F SC) at 0. 304 - 0. 319 lb ai/A/application ( 341 - 358 g ai/ha/application) for a total seasonal rate of 0. 609 - 0. 635 lb ai/A ( 683 - 712 g ai/ha). Applications were made at 6 - to 8 - day RTI s , except at the ON trial, where the second application was delayed due to a hurricane (10 - day RTI). Applications were made using ground equipment in spray volumes of 84.6 - 173.8 GPA ( 791 - 1626 L/ha). An NI S, MSO , COC or OSS was added to the spray mixtures for all applications. Samples of fresh hops cones were harvested b y hand at maturity from all trials at a PHIof 1 - 4 day s . Samples designated for dried hops cones were dried per normal cultural practices at or near the field sites. To assess residue dec line in dried hops cones, additional samples were collected at PHI s of 0, 4 , 7 and 14 day s from the WA trial. Additional samples were also collected at the ON trial at 0 - and 1 - day PHI s for a residue decline study that was terminated due to low yi elds. Samples were anal yz ed for residues of metrafenone using an LC /MS/MS method derived from QuEChERS Method # R00033. The L OQ , determined as the LLMV , was 0.0 1 ppm in dried and fresh hops cones. The analy tical method was adequate for data collection , based o n acceptable m ethod validation and concurrent recovery data. The fortification levels used in method validation and concurrent method recovery were adequate to bracket expected residue levels. Concurrent recoveries were corrected for apparent residues in controls; residues in treated samples were not corrected for residues in controls. Samples were transferred to a sample preparation facility for homogenization prior to shipment to the anal ytical laboratory . Samples were stored frozen ( - 42 to 4.2°F at the field sites, ≤ 5°C at the preparation facility , and - 29 to - 1 7°C at the analy tical laboratory) from harvest to anal ys is for 754 - 819 day s ( 24 .8 - 2 6. 9 months) for dried hops cones, and 752 - 778 day s (2 4 . 7 - 25 . 6 months) for fresh hops cones. Samples were anal yz ed within 1 - 7 days of extraction. Adequate s torage stability data are available to support the sample storage conditions and durations for residues of metrafenone. The results from these trials are summarized in Table 5.3.1. 5 , below. Following two foliar directed applications of the 2.5 lb ai/gal SC formulation of metrafenone at 0.609 - 0.635 lb ai/A (683 - 712 g ai/ha), residues (and per trial averages) of metrafenone in dried hops cones and fresh hops cones , respectivel y, harvested at 1 - to 4 - day PHI s were 15.72 - 158.8 (16.87 - 131.9) and 5.51 - 31.36 ppm . It was noted that the highest residues in dried hops cones were observed in samples from the ON trial where the second application was delayed due to a hurricane and where, according to the petitioner, h alf of the crop was destroyed b y insects between applications. Excluding results for the ON trial (because the hops cones were not of commercial quality) , the highest average residues observed were 23.52 ppm. At the WA residue decline trial, residues ofMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **49** of **78** metrafenone in dried hops cones decreased with increasing PHI . At the ON decline trial , residues decreased from the 0 - to 1 - day PHI, but the highest residues were observed in samples from the 2 - day

PHI (results not shown here; see the DER for MRID #491454 0 3 for further details) . It was noted that the highest residues in dried hops cones were observed in samples from the ON trial, where the second application was delayed due to a hurricane and where, according to the petitioner, half of the crop was destro yed b y insects between applications. There were several communications with the petitioner ( IR - 4 ) regarding the ON trial, and an outlier anal ys is (Grubbs test) was submitted by IR - 4 . The outlier anal ys is was evaluated by HED (D421923; Bayazid Sarkar; 2 1 August 2014). HED used a different approach for anal yzing the data (the Grubbs test was conducted on transformed data because there was sufficient evidence to reject the assumption of normality) , and ultimatel y concurred that the residue value obtained from the ON field trial constituted an outlier. The results of the HED anal ys is were shared with the PMRA reviewers, who then agreed to exclude that residue value from the dataset input to the OECD tolerance calculation procedure. Excluding results for the ON trial (the outlier), the highest average residue observed was 23.52 ppm. On a final note regarding hops, HED’s recommended tolerance includes the results from European field trials, even though the North American field trial data were adequate. Using the combined data sets results in a greater likelihood that any

future European and Canadian MRL s, and US tolerances will all be harmonized. **TABLE 5.3.1.5 Summary of Residue Data from** **Hops Field Trials with Metrafenone (M**  **RID #49145403) .**  **Comm odity**  **Total Rate**

**lb ai/A (g ai/ha) PHI** 

**(days) Me** **trafenone Residue Levels (ppm )**  **1 n**  **Min. Max.**  **LAFT 2**  **HAFT 2**  **Median Me**  **an Std. Dev.**  Hops cones, dried 0.609 - 0.635

(683 - 712) 1 - 2 5 1 5 . 72 158.8 1 6 . 8 7 131.9 21. 50 43.07 48.59 Hops cones, fresh 0.609 - 0.635

(683 - 712) 2 - 4 5 5.51 **3** 31.36 **3** 5.51 **3** 31.36 **3** 6.17 **3** 11.76 **3** 11.08 **3** 1. Except for sample min/max, values re flect per trial averages; n = number of field trials. 2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial. 3. Only one sample per trial was analyzed; therefore sample min = LAFT, and sample max = HAFT. Statistical data are therefore reflective of individual sample residues rather than per trial mean residue values. Hops (MRID #49145403) Conclusions : The submitted hops field trial data are scientificall y acceptable. Following two foliar directed applications of the 2.5 lb ai/gal SC formulation of metrafenone at 0.609 - 0.635 lb ai/A (683 - 712 g ai/ha), residues (and per trial averages) of metrafenone in dried hops cones and fresh hops cones, respectively , harvested at 1 - to 4 - day PHI s were 15.72 - 158.8 (16.87 - 131.9) and 5.51 - 31.36 ppm . Itwas noted that the highest residues in dried hops cones were observed in samples from the ON trial , where the second a pplication was delayed due to a hurricane and where, according to the petitioner, half of the crop was destroyed by

insects between applications. Excluding results for the ON trial (because the hops cones were not of commercial quality , and the average re sidue from the trial was deemed anMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **50** of **78** outlier via the Grubbs test) , the highest average residues observed were 23.52 ppm. At the WA residue decline trial, residues of metrafenone in dried hops cones decreased with increasing PHI. At the ON decline trial, residues decreased from the 0 - to 1 - day PHI, but the highest residues were observed in samples from the 2 - day PHI. An acceptable method w as used for residue quantitation , and the study is supported by

adequate storage stability

data. Hops (MRIDs #49145 40 7 & - 08 ): IR - 4 submitted crop field trial and processing study data for metrafenone on hops . Six field trials were conducted in Germany during the 2009 (four trials; MRID #49145407) and 2010 (two trials; MRID #49145408) growing seasons. Both studies reflected collection of fresh (green) and dried hops cones. In the 2009 study dried hops cones from three trials were processed to yield the following processed commodities: beer, brewer’s ye ast, extracted hops, and hops draff. Because the processed comm odities of hops are not considered significant food/feed commodities in the US, the results of the processing study are presented herein but are not discussed in detail. Each trial consisted of one untreated plot and one treated plot. At each trial loc ation, the treated plot received two foliar directed applications of a 4 lb ai/gal ( 500 g ai/L) SC formulation of metrafenone ( BAS 560 02 F ) at 0. 279 - 0. 321 lb ai/A/application ( 313 - 360 g ai/ha/application) for a total seasonal rate of 0. 580 - 0. 633 lb ai/A ( 650 - 710 g ai/ha). Applications were made at 6 - to 8 - day RTIs using ground equipment in spray volumes of 335 - 388 GPA ( 3133 - 3625 L/ha) without an adjuvant. S amples of fresh (green) hops cones were harvested at PHIs of 0, 1, 2 - 4, and 7 - 8 day s . A dditional s amples of green hops cones designated for dried hops cones were collected from the 2 - to 4 - day

PHIs at each site and were dried in hops kilns. Samples were anal yz ed for residues of metrafenone using LC/MS/MS via BASF method s # 535/1 (L 0076/01) and # 535/3 (L0076/03). The methods are essentially identical. The LOQ , determined as the LLMV , was 0.0 1 ppm in all sample matrices . The anal ytical methods were adequate for data collection , based on acceptable m ethod validation and concurrent recovery data. The f

ortification levels used in method validation and concurrent method recovery were adequate to bracket expected residue levels. Recoveries were corrected for apparent residues in controls; residues in treated samples were not corrected for residues in controls. Samples were stored frozen (≤ - 18°C at the field sites, preparation facility , and anal ytical laboratories ) from harvest to analy sis for 147 - 242 day s (4.8 - 8.0 months) for green hops cones and 151 - 236 day s (5.0 - 7.8 months) for dried hops cones. Samples were analyzed within 1 - 2 day s of extraction. Adequate s torage stability data are available to support the sample storage durations and conditions for residues of metrafenone. The results from these trials are summarized in Table 5.3.1. 6 , below. Following two foliar directed applications of the 4 lb ai/gal ( 500 g ai/L ) SC formulation of metrafenone at 0.5 80 - 0.633Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **51** of **78** lb ai/A (6 50 - 710 g ai/ha) , residues (and per trial averages) of metrafenone in green hops cones and dried hops cones , respectivel y, harvested at a 2 - to 4 - day PHI were 1.78 - 8.50 (1.78 - 8.50) and 13.3 - 34.4 (13.3 - 34.4) ppm. At the residue decline trials, residues of metrafenone in green hops cones generall y declined with increasing PHI in four of the six trial s , but remained relativel y sta ble in two trials from the 0 - day PHI to 7 - day

PHI (results not shown here; see the DER for MRID s #4914540 7 and - 08 for further details) . **TABLE 5.3.1.6 Summary of Residue Data from** **Hops Field Trials with Metrafenone (M**  **RID s**  **#4914540 7 &** 

**49145408 )**  **. Comm**  **odity Total Rate** 

**lb ai/A (g ai/ha)**  **PHI**

**(days) Me** **trafenone Residue Levels (ppm )**  **1 n**  **Min. Max.**  **LAFT 2**  **HAFT 2**  **Median Me**  **an Std.**  **Dev.** Hops cones, green 0.580 -

0.633 (650 - 710) 2 - 4 6 1.78 8.50 1.78 8.50 3.57 4.16 2.31 Hops cones, dried 2 - 4 6 13.3 34.4 13.3 34.4 22.8 24.7 8.98 1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 2. LAFT = L owest Average F ield Trial; HAFT = H ighest Average F ield T rial. Hops (MRID #4914540 7 & - 08 ) Conclusions: Following two foliar directed applications of the 4 lb ai/gal (500 g ai/L) SC formulation of metrafenone at 0.580 - 0.633 lb ai/A (650 - 710 g ai/ha), residues (and per trial averages) of metrafenone in green hops cones and dried hops cones, respectivel y, harvested at a 2 - to 4 - day PHI were 1.78 - 8.50 (1.78 - 8.50) and 13.3 - 34.4 (13.3 - 34.4) ppm. In the residue decline trials, residues of metrafenone in green hops cones generally declined with increasing PHIin four of the six trials, but remained relatively stable in two trial s from the 0 - day

PHI to 7 - day

PHI . Acceptable methods were used for quantitation of residues, and the study i s supported by adequate storage stability data. Peach (MRID #4914540 1 ) : IR - 4 submitted field trial residue data for metrafenone on peach. F ourteen peach field trials were conducted in the United States and Canada during the 2011 growing season in NAFTA Growing Zones 1 (NY; 1 trial), 2 (NJ and NC; 4 trials), 4 (AR; 1 trial), 5A (MI; 1 trial), 5 (ON; 2 trials) , 6 (TX; 1 trial), 10 (CA; 3 trials) and 11 (BC; 1 trial). HED has determined that two Zone 10 and two Zone 5 peach trials should be considered replicates for purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data requirements . The above field trial distribution incorporates this c onclusion. Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated plot received two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone (BAS560 03 F SC) at 0.291 - 0.307 lb ai/A/application (326.2 - 344.2 g ai/ha/application) for a total seasonal rate of 0.583 - 0.610 lb ai/A (653.6 - 683.9 g ai/ha). Applications were made at 6 - to 8 - day RTIs using ground equipment in spray volumes of 10 4 - 18 2 GPA (973 - 1701 L/ha). An NIS,Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **52** of **78** COC or OSS was added to the spray mixtures for all applications. Samples of peaches were harvested at PHI s of 6 - 8 day s and 13 - 15 day s at all trial sites. Additional samples of peaches were collected from two trials at PHI s of 0, 3, 15/17 and 17/21 day s to generate residue decline data. Samples of peaches were anal yz ed for residues of metrafenone using an LC /MS/MS method derived from a QuEChERS Method #R00033. The LOQ , determined as the LLM V , was 0.01 ppm. The method was adequate for data collecti on , based on acceptable method validation and concurrent recovery

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

were adequate to b racket expected residue levels. Concurrent recoveries and residues in the treated samples were not corrected for residues in controls. S amples were transferred to a sample preparation facility for homogenization prior to shipment to the anal ytical laboratory . Samples were stored froz en (frozen at the field sites, ≤ - 5°C at the sample preparation facility , and temperature unspecified at the anal ytical laboratory) from collection to anal ys is for 297 - 397 day s ( 9.8 - 13.1 months). Samples were anal yz ed within 0 - 15 day s of extraction . Adequ ate storage stability data are available to support the sample storage conditions and durations. The results from these trials are summarized in Table 5.3.1. 7 , below. Following two foliar directed applications of the 2.5 lb ai/gal SC formulation of metrafenone at 0.583 - 0.610 lb ai/A (653.6 - 683.9 g ai/ha), residues (and per trial averages) of metrafenone in peaches harvested at PHI s of 6 - 8 day s and 13 - 15 day s , respectively , were 0.041 - 0.520 (0.051 - 0.48 9 ) and 0.029 - 0.39 4 (0.035 - 0.355) ppm. At the residue d ecline trials, residues of metrafenone in peaches declined with increasing PHI in peaches (results not shown here; see the DER for MRID #4914540 1 for further details) . **TABLE 5.3.1.7**  **Summary of Residue Data from Peach Field Trials with Metrafenone.**  **Comm odity**  **Total Rate** 

**lb ai/A (g ai/ha)**  **PHI**

**(days) Residue Levels (ppm)**  **1 n**  **Min. Max.**  **LAFT 2**  **HAFT 2**  **Median Me**  **an Std. Dev.**  Peach 0.583 - 0.610

(653.6 - 683.9) 6 - 8 1 4 0.041 0.520 0.051 0.489 0.208 0.21 1 0 .098

13 - 15 14 0.029 0.394 0.035 0.355 0.1 42 0.143 0.075 1. Except for sample min/max, values reflect per trial averages; n = number of distinct field trials. 2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial. Peach Conclusions : Following two foliar directed applications of the 2.5 lb ai/gal SC formulation of metrafenone at 0.583 - 0.610 lb ai/A (653.6 - 683.9 g ai/ha), residues (and per trial averages) of metrafenone in peaches harvested at PHI s of 6 - 8 day s and 13 - 15 day s, respective ly , were 0.041 - 0.520 (0.051 - 0.489) and 0.029 - 0.394 (0.035 - 0.355) ppm. At the residue decline trials, residues of metrafenone in peaches declined with increasing PHI in peaches. An acceptable method was used for residue quantitation, and adequate storage stability data are available to support the sample storage conditions and durations.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **53** of **78** Cucurbits (MRIDs #4914540 4, - 05 & - 0 6 ) : IR - 4 has submitted field trial residue data for metrafenone on cantaloupe, cucumber and summer squash, the representative commo dities of the cucurbit vegetable group 9 , from 32 crop field trials conducted in the United States and Canada during the 2010 growing season. Twelve cantaloupe trials were conducted in NAFTA Growing Zones 2 (GA and MD; 2 trials), 5 (OH and ON; 2 trials); 5B (QC; 1 trial), 6 (TX; 2 trials) and 10 (AZ , CA , and NM ; 5 trials); six cucumber trials were conducted in Zones 2 (GA; 2 trials), 3 (FL, 1 trial), 5 (IA and MN; 2 trials) and 6 (OK; 1 trial); and fourteen squash trials were conducted in Zones 1 (NY; 1 trial), 2 (MD, NC, and SC; 3 trials), 3 (FL; 1 trial), 5 (ON; 2 trials), 5B (QC; 1 trial), 6 (TX; 2 trials), 10 (AZ and CA; 2 trials), 11 (WA; 1 trial) and 12 (BC; 1 trial). Examination of the field trial records indicates that there were sufficient differences between the trials that each trial constitutes a separate trial for purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data requirements. Each trial consisted of one untreated and one treated plot . At each trial location, the treated plot received three foliar broadcast or directed applications of a 2.5 lb ai/gal SC formulation of metrafenone (BAS560 03 F SC) at 0. 286 - 0. 316 lb ai/A/application ( 0.321 - 0.354 kg ai/ha/application) for a total seasonal rate of 0.8 8 4 - 0.936 lb ai/A ( 0.993 - 1.049 kg ai/ha). Applications were made at 6 - to 9 - day RTIs using ground equipment in spray volumes of 29.2 - 74.2 GPA (273 - 693 L/ha). At one ON squash trial, the first application was made in error at half the target appli cation rate (0.124 lb ai/A; 0.139 kg ai/ha); therefore, the test substance was re applied 3 day s later at 0.312 lb ai/A (0.350 kg ai/ha), and the remaining two applications were made according to the study protocol. This trial received a total of four app lications for a total rate of 1.042 lb ai/A (1.168 kg ai/ha). An NIS, MSO, COC or OSS was added to the spray mixtures for all applications. Samples of cantaloupe, cucumber and summer squash were harvested at a PHI of 0 day s. Additional samples were coll ected from two trials for cantaloupe at PHI s of 1, 3, 7, 10/11 and 13/15 day s, one trial for cucumber at PHIs of 1, 3, 7 and 10 day s, and one trial for summer squash at PHIs of 1, 4, 6, 9 and 13 day s to generate residue decline data. Samples were anal yz ed for residues of metrafenone using an LC /MS/MS method derived from QuEChERS Method # R00033. The LOQ , determined as the LLMV , was 0.01 ppm for metrafenone in all crop matrices. The method w as adequate for data collection , based on acceptable method validation and concurrent recovery data. The fortification levels used in method validation and concurrent method recovery were adequate to bracket expected residue levels. Concurrent r ecoveries were corrected for apparent residues in controls for cantaloupe and summer squash , but recoveries were not corrected for apparent residues in controls for cucumber. Residues in treated samples were not corrected for residues in controls . Samples of cucurbit vegetables were transferred to a sample preparation facility for homogenization prior to shipment to the analy tical laboratory . Samples of cucurbit vegetables were stored frozen (frozen at the field sites, < - 10 or - 5°C at the sample preparation facility , and - 29 to - 10°C at the anal ytical laboratories) from collection to anal ys is for 450 - 842 day s (14.8 - 27.7Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **54** of **78** months). Samples were anal yz ed within 0 - 2 day s of extraction. Adequate storage stability data are available to support the sample storage conditions and durati ons. The results from these trials are summarized in Table 5.3.1. 8 , below. Following three (or four) foliar broadcast or directed applications of a 2.5 lb ai/gal SC formulation of metrafenone (BAS560 03 F SC) at a total seasonal rate of 0.884 - 1.042 lb ai/A (0.993 - 1.168 kg ai/ha), residues (and per trial averages) of metrafenone in cantaloupe, cucumber and summer squash harvested at a 0 - day PHI, were 0.038 - 0.332 (0.038 - 0.282), 0.046 - 0.168 (0.053 - 0.157), and 0.067 - 0.357 (0.072 - 0.305) ppm , respectively . It was noted that at the one summer squash trial in which four applications were made for a total seasonal rate of 1.042 lb ai/A, residues were consistent with those observed at other trials, and are included in the values reported above. At the residue decl ine studies, residues of metrafenone generally declined with increasing PHI in cantaloupe, cucumbers and summer squash (results not shown here; see the DER for MRID s #4914540, - 05 and - 06 for further details) . **TABLE 5.3.1.8 Summary of Residue Data from**  **Cuburbit Field Trials with Metrafenone. Comm**  **odity Total Rate,** 

**lb ai/A (kg ai/ha)**  **PHI**

**(days) Residues (ppm** **) 1**  **n Min.**  **Max. LAFT**  **2 HAFT**  **2 Median**  **Me an**  **Std. Dev.**  Cantaloupe 0.886 - 0.936

(0.993 - 1.049) 0 12 0.038 0.332 0.038 0.282 0.143 0.152 0.068 Cucumber 0.894 - 0.920

(1.002 - 1.035) 6 0.046 0.168 0.053 0.157 0.099 0.105 0.038 Summer squash 0.884 - 1.042

(0.993 - 1.168) 14 0.067 0.357 0.072 0.305 0.127 0.162 0.079 1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial. Cucurbits Conclusions: The submitted cucurbit vegetable field trial data are scientificall y acceptable. Following three (or four) foliar broadcast or directed applications of a 2.5 lb ai/gal SC formulation of metrafenone (BAS560 03 F SC) at a total seasonal rate of 0.884 - 1.042 lb ai/A (0.993 - 1.168 kg ai/ha), residues (and per trial averages) of metrafenone in cantaloupe, cucumber and summer squash harvested at a 0 - day PHI, were 0.038 - 0.332 (0.038 - 0.282), 0.046 - 0.168 (0.053 - 0.157), and 0.067 - 0.357 (0.072 - 0.305) ppm , respectivel y . It was noted that residues at the one summer squash trial in which four applications were made for a total seasonal rate of 1.042 lb ai/A, residues were consistent with those observed at other trials, and are included in the values reported above. In the residue decline studies, residues of metrafenone generally declined with increasing PHI in cantaloupe, cucumbers and summer squash. An acceptable method was used for residue quantitation, and the study is supported by

adequate storage stability

data.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **55** of **78 5.3.2**  **Field Rotational Crops (860.1900)** A study investigating f

ield accumulation in rotational c rops has not been conducted with metrafenone , and i s not required . **5.3.3 Processed Food and Feed (860.1520)**  Apple (MRID #49055902 ) : An apple processing study was conducted to determine the potential for concentration of residues of metrafenone in apple processed fractions. Two trials were conducted to generate samples for processing in NAFTA Growing Zones 1 (NY, one trial) and 11 (ID, one trial) during the 2010 growing season. At each test location, one untreated control and one treated plot were established. The treated plots received three foliar airblast applications of metrafenone (2.5 lb ai/gal SC ) applying at roughl y 1.68 kg ai/ha/application (1.5 lb ai/A/application), with a nominal 7 - day RTI, resulting in a total exaggerated rate of roughl y 5.0 kg ai/ha (4.5 lb ai/A/season). The actual application rates were 1.67 - 1.71 kg ai/ha/application (1.49 - 1.53 lb ai/A/application), with 6 - or 7 - day RTIs, f or a total rate of 5.1 kg ai/ha/season (4.52 - 4.53 lb ai/A/season). The applications were made in 80 - 102 GPA of water (748 - 954 L/ha) using ground equipment (airblast sprayers). An NI S adjuvant was added to the spray mixture for all applications. At eac h site, one untreated control and one treated bulk apple RAC sample were harvested at normal crop maturity, at a 6 - or 7 - day PHI. The samples were shipped to the processing facility , ACDS Research (North Rose, NY) , where they were processed , according to simulated commercial procedures , into processed apple commoditi es (juice, wet pomace, apple sauce, canned apples, and dried apples). Adequate descriptions of the processing procedures were provided, including material balance summaries. The residues of parent metrafenone in apple RAC and processed commodity samples were quantitated using an LC /MS/MS multi - residue QuEChERS method (BASF Study # 398340). The method was successfully

validated on dried apples in conjunction with this study pri or to anal ys is of the field samples. Acceptable concurrent method recovery data for each apple matrix were also obtained for metrafenon e. The validated L OQ for metrafenone residues in apple RAC and processed commodity samples was 0.01 ppm. The method LO D was 0.003 ppm. The processing residue results are summarized in Table 5.3.3.1 , below. A fter three exaggerated rate applications of metrafenone (2.5 lb ai/gal SC) to apples at a rate of 1.68 kg ai/ha/application (roughly 5.0 kg ai/ha/season), metrafenon e residues were 1.46 ppm (New York) and 2.17 ppm (Idaho) in two treated apple RAC samples (whole fruit) harvested at a 6 - or 7 - day PHI. The apple RAC samples were separately processed , using simulated commercial processing procedures , into the currently E PA - regulated commodities of apple, wet pomace and juice. Apple sauce, canned apples, and dried apples were also generated and collected for anal ys is.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **56** of **78** Metrafenone residues were 0.28 ppm in juice, 1.88 ppm in wet pomace, 7.01 ppm in apple sauce, 0.20 ppm in canned apples, and 1.05 ppm in dried apples collected from New York. Metrafenone residues were 0.49 ppm in juice, 2.37 ppm in wet pomace, 8.94 ppm in apple sauce, 0.23 ppm in canned apples, and 0.85 ppm in dried apples collected from Idaho. A comparis on of the residues in the RAC samples with those in each processed fraction indicated that metrafenone residues do not concentrate (processing factors <1 X to 1.2 X , average of two trials) in any

apple processed commodities, with the exception of apple sauce , in which the processing factor was 4.5 X on average, with individual results of 4.8X and 4.1 X calculated from the samples collected at the sites in New York and I daho, respectivel y. The processing factors calculated in this study were less than the max imum theoretical concentration factor of >14 X for apple s (based on the maximum theoretical/ experimental concentration factor; OCSPP 860.1520, Table 1) , and 14 X for apple pomace (based on the maximum observed experimental concentration factor; OCSPP 860.152 0, Table 4). The apple RAC and processed commodity samples were stored frozen for a maximum of 683 day s (roughl y 22 months) from collection to extraction for anal ys is. Samples were anal yz ed on the day

of extraction. Processing was compl eted within 4 days of harvest. **Table 5. 3**  **. 3.**  **1 Me** **trafenone Residues in Apple Processed Fractions .**  **Trial ID**  **(City, State/Year)**  **Total Use** 

**Rate lb ai/A**  **(kg ai/ha) PHI** 

**(days) Processed** 

**Comm odity**  **Me trafenone** 

**Residues (ppm** **) Processing** 

**Factor 1**  **Average**

**Processing Factor**  R080753 (Alton, NY/2010) 4.52

(5.06) 7 Whole Fresh Fruit **1.46** NA2

Juice (raw) 0.276 0.189 <1 (0.2) Wet Pomace 1.88 1.29 1.2 Apple Sauce 7.01 4.80 4.5 Canned Apples 0.204 0.140 <1 (0.1) Dried Apples 1.05 0.719 <1 (0.6) R080754 (Weiser, ID/2010) 4.53

(5.07) 6 Whole Fresh Fruit **2.17** NA

Juice (raw) 0.489 0.225 Wet Pomace 2.37 1. 09 Apple Sauce 8.94 4.12 Canned Apples 0.226 0.104 Dried Apples 0.851 0.392 1. The processing factor was calculated by dividing the residue in the apple processed commodity by the residue in the apple RAC sample ( LOQ = 0.01 ppm) . 2. NA = Not A

pplicable (whole fresh fruit , the representative apple RAC sample). Apple Conclusions: A comparison of the residues in the RAC with those in each processed fraction indicated that metrafenone residues do not concentrate appreciably (<1 X to 1.2 X onMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **57** of **78** average) in any apple processed commodities, with the exception of apple sauce, in which the processing factor was 4.5 X on average. The observed concentration factors were less than the theoretical concentration factors. An acceptable method was used for residue quantitation, and the study is supported by

adequate storage stability

data. Toma to (MRID #4911910 9 ) : Tomato processing studies were conducted to determine the potential for concentration of residues of metrafenone (BAS 560 F) in the processed fractions of tomato. During the 2010 growing season, four tomato field trials were conducte d in Germany at 04668 Motterwitz, Saxony ; 04827 Gerichshain, Saxony ; 19348 Düpow, Brandenburg; and 16248 Oderberg, Brandenburg. At each location a treated plot was established; two of the trials also included an untreated control plot. The treated plot s received two foliar applications of metrafenone (4.2 lb ai/gal SC, formulation code BAS 560 02 F) targeting 0.60 lb ai/A/application (0.675 kg ai/ha/application) with a nominal 7 - day

RTI , resulting in a total rate of 1.2 lb ai/A (1.35 kg ai/ha/season). The a ctual application rates were 0.54 - 0.65 lb ai/A/application (0.61 - 0.73 kg ai/ha/application), with 6 - 8 day RTIs, resulting in a total rate of 1.18 - 1.28 lb ai/A/season (1.32 - 1.44 kg ai/ha/season). The applications were made in 48 - 58 GPA of water (450 - 5 44 L/ha) using ground equipment , and n o adjuvant was added to the spray mixtures. At each location, tomato RAC samples (fruit) were harvested at PHIs of 0 and 3 or 4 day s. The bulk tomato samples collected at 3 - or 4 - day PHI s at each site were promptly p rocessed, according to simulated commercial procedures, into tomato processed fractions. The tomato RAC and processed commodity samples were anal yz ed for residues of metrafenone by SGS Institut Fresenius GmbH, Taunusstein, Germany , using BASF Method Number 535/1 (L 0076/01). Acceptable concurrent method recovery data for tomato RAC and processed commodity

samples were obtained for metrafenone. The validated LOQ for residues of metrafenone in tomato RAC and processed commodity samples was 0.01 ppm. As summarized below in Table 5.3.3.2, the results from the processing s tudy show that after two applications of metrafenone targeting 0.60 lb ai/A/application (0.675 kg ai/ha/application), metrafenone in treated tomato RAC samples (unwashed whole fruit) coll ected at 0 - and 3 - to 4 - day PHI s were 0.675 - 1.189 ppm and 0.40 - 0.78 ppm, respectivel y (n=4 for each sampling interval). A total of four separate treated bulk samples were processed for a total of four processing tests. The treated bulk tomato RAC sampl es harvested at 3 - or 4 - day PHI s and bearing quantifiableMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **58** of **78** metrafenone residues (levels discussed above) were separatel y processed using simulated commercial processing procedures into paste and puree, the currently EPA - regulated commodities of tomato. In addition, blanched tomatoes, blanching water, canned tomatoes, peeled tomatoes, wash water, tomato peel, wet pomace, washed tomatoes, raw juice, ketchup after pasteurization, and vegetable stock were collected for anal ys is. A comparison of the residues in the RAC with those in each processed fraction indicates that residues of metrafenone do not concentrate in tomato processed commodities with the exception of peel and wet pomace, in which residues concentrate, on average, b y factors of 6.3 X (range, 3.51 - 7.86 X , n=4) and 5.1 X (range, 3.31 - 6.16 X , n=4), respectivel y. The processing factors calculated in this study were greater than the maximum theoretical concentration factors of 1.4 X for tomato puree and 5.5 X for tomato paste (based on loss of water; O CSPP 860.1520, Table 2) and 1.4X for tomato juice (based on separation into components; OCSPP 860.1520, Table 3). The tomato RAC and processed commodity samples were stored frozen for a maximum of 165 day s (5.4 months) from collection to analy sis for residues of metrafenone. **TABLE 5.**  **3. 3.2**  **Me trafenone Residues in Tomato Processed Fractions**  **Trial Location (City, Country/**  **Year) Total Rate** 

**lbs ai/A (kg ai/ha)**  **Processed**

**Comm odity**  **PHI (D**  **ays) 1**  **Me trafenone**  **Processing Factor**  **2** 04668 Motterwitz, Saxony , Germany/2010 ( L100261 ) 1.26 (1.41) Fruit, 0 PHI **3** 0 0.675 --- Fruit, 3 PHI **3** 3 0.401 --- Fruit, RAC **4** 0.423 1.0 Blanched tomatoes 0.353 0.83 Blanching water < 0.01 0.02 Canned tomatoes < 0.01 0.02 Peeled tomatoes < 0.01 0.02 Wash water 0.066 0.16 Tomato peel 3.184 **7.53** Wet pomace 2.034 **4.81** Washed tomatoes 0.382 0.90 Raw juice 0.168 0.40 Ketchup after pasteurization 0.177 0.42

Paste 0.225 0.53 Puree 0.335 0.79 Vegetable stock < 0.01 0.02Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **59** of **78 TABLE**  **5. 3.**  **3.2 Me** **trafenone Residues in Tomato Processed Fractions Trial Location**  **(City, Country/ Year)**  **Total Rate**

**lbs ai/A (kg ai/ha)**  **Processed**

**Comm odity**  **PHI (D**  **ays) 1**  **Me trafenone**  **Processing Factor**  **2** 04827 Gerichshain, Saxony , Germany/2010 ( L100262 ) 1.28 (1.44) Fruit, 0 PHI **3** 0 0.962 --- Fruit, 3 PHI **3** 3 0.778 --- Fruit, RAC **4** 0.775 1.0 Blanched tomatoes 0.352 0.45 Blanching water 0.013 0.02 Canned tomatoes 0.015 0.02 Peeled tomatoes < 0.01 0.01 Wash water 0.507 0.65 Tomato peel 4.807 **6.20** Wet pomace 2.567 **3.31** Washed tomatoes 0.477 0.62 Raw juice 0.198 0.26 Ketchup after pasteurization 0.327 0.42

Paste 0.207 0.27 Puree 0.501 0.65 Vegetable stock < 0.01 0.01 19348 Düpow , Brandenburg , Germany/2010 ( L100263 ) 1.18 (1.32) Fruit, 0 PHI **3** 0 1.189 --- Fruit, 4 PHI **3** 4 0.782 --- Fruit, RAC **4** 0.583 1.0 Blanched tomatoes 0.528 0.91 Blanching water 0.017 0.03 Canned tomatoes < 0.01 0.02 Peeled tomatoes 0.013 0.02 Wash water 0.218 0.37 Tomato peel 4.585 **7.86** Wet pomace 3.592 **6.16** Washed tomatoes 0.488 0.84 Raw juice 0.194 0.33 Ketchup after pasteurization 0.219 0.38

Paste 0.174 0.30 Puree 0.487 0.84 Vegetable stock < 0.01 0.02Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **60** of **78 TABLE**  **5. 3.**  **3.2 Me** **trafenone Residues in Tomato Processed Fractions Trial Location**  **(City, Country/ Year)**  **Total Rate**

**lbs ai/A (kg ai/ha)**  **Processed**

**Comm odity**  **PHI (D**  **ays) 1**  **Me trafenone**  **Processing Factor**  **2** 16248 Oderberg, Brandenburg , Germany/2010 ( L100264 ) 1.18 (1.32) Fruit, 0 PHI **3** 0 0.925 --- Fruit, 3 PHI **3** 3 0.435 --- Fruit, RAC **4** 0.452 1.0 Blanched tomatoes 0.398 0.88 Blanching water 0.012 0.03 Canned tomatoes < 0.01 0.02 Peeled tomatoes 0.01 0.02 Wash water 0.152 0.34 Tomato peel 1.588 **3.51** Wet pomace 2.679 **5.93** Washed tomatoes 0.242 0.54 Raw juice 0.149 0.33 Ketchup after pasteurization 0.211 0.47

Paste 0.201 0.44 Puree 0.478 1.06 Vegetable stock < 0.01 0.02 1 . The pre - harvest interval (PHI) for the bulk tomato RAC sample. 2 . The processing factor is calculated by dividing the residue in the processed fraction by the mean residue in the tomato RAC sample. Processing factor is equivalent to “transfer factor”. 3 . Result from the analysis of the smaller tomato fruit RAC samp le . 4 . Result from the representative “fresh fruit” sample collected at the processing facility. Tomato Conclusions: A comparison of the residues in the RAC with those in each processed fraction indicated that residues of metrafenone do not concentrate in tomato processed commodities with the exception of peel and wet pomace, in which residues concentrate, on average, b y factors of 6.3 X and 5.1 X , respectivel y. The mean transfer factor of tomato peel and wet pomace (>1 ) indicates that the metrafenone residues are mainl y located in the peel of the tomatoes. An acceptable method was used for residue quantitation, and the study is supported by

adequate storage stability

data. **5.3.4 Meat, Milk, Poultry and Eggs (860.1480)**  **Me tabolism** **DER for MRID #49267201 (Goat)**  The only livestock feed item associated with the proposed metrafenone new uses is apple wet pomace, and it is fed only to dairy cattle , at a mazimum of 10% of the diet . Twelve apple field trials were conducted , with a HAFT value of 0.760 ppm . An average processing factor of 1.2 was determined for apple wet pomace in the apple processing study (MRID # 49055902). Therefore, the adjusted metrafenone residues in apple pomace are 0.76 0 ppm x 1.2 PF = 0.912 ppm.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **61** of **78** When goats in the metabolism study were dosed at 87 pp m in the feed , the highest metrafenone residue in tissues was in liver at 0.269 ppm. Scaling down to the anticipated dietary burden to dairy cattle of 0.228 mg/kg in feed, anticipated metrafenone residues are not expect ed to exceed 0.000705 ppm in liver, well below the LOD. Residues would occur at lower levels in muscle, fat and milk. Ergo , there is no reasonable expectation of residues above the LOQ of 0.01 ppm in the milk or tissues of ruminant animals. **TABLE 5.3.4**  **Dietary Burden to**  **Dairy Cattle fr**  **om Metrafenone**  **. Feedstuff**  **Feedstuff**

**Type 1**  **% Dry**

**Matter 2**  **% Diet 2**  **Feeding Level (ppm)**  **Dietary Contribution**

**(ppm) 3**  **Dairy Cattle** Apple wet pomace CC 4 0 10 0.912 0.228 TO TAL BURDEN -- -- 10 4 0.912 **0.228** 1. CC = Carbohydrate C oncentrate. 2. OCSPP Residue Chemistry Test Guideline 860.1000 , Table 1 Feedstuffs ( 30 June 2008 ). 3. Contribution = (tolerance ÷ % DM x % diet) for beef and dairy cattle. 4. The remainder of the diet will be composed of feedstuffs ( roughage and protein concentrate sources) derived from crops that do not have registered metrafenone uses or tolerances. Conclusion s : Based on the dietary burden to dairy

cattle of metrafenone residues in apple wet pomace, and the results of the goat m etabolism study , it is not expected that detectable residues would be found in cattle commodities. Therefore, tolerances in livestock commodities are not required , nor is a livestock feeding study required . **5.3.5 Food Handling (860.1460)**  There are no proposed uses that are relevant to this guideline topic. **5.3.6 Water, Fish, and Irrigated Crops (860.1400)**  There are no proposed uses that are relevant to this guideline topic. **5.4 Food Residue Profile**  Residues of metrafenone from the new uses proposed in the current action are expected to vary from low (up to 0. 7 0 ppm in apricot and peache s) to high levels (up to 7 0 ppm in dried hops cones ).Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **62** of **78 6.0**  **Tolerance Derivation** Adequate pome fruit field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 1.5 ppm in pome fruits (group 11 - 10). Adequate fruiting vegetable field trial data were submitted in support of the proposed use. The submitted data support a recommen ded tolerance of 0.90 ppm, rather than the proposed tolerance of 1.0 ppm, in fruiting vegetables (group 8 - 10). Adequate cucurbit vegetable field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 0.5 ppm in cucurbit vegetables (group 9); HED recommends that the tolerance be established at 0.50 ppm. Adequate cherry

field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 2 ppm in th e cherry subgroup (12 - 12A); HED recommends that the tolerance be established at 2.0 ppm. Adequate peach field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 0.7 ppm in the peach subgroup ( 12 - 12B); HED recommends that the tolerance be established at 0.70 ppm. Adequate hops field trial data were submitted in support of the proposed use. The submitted data support the proposed tolerance of 70 ppm in hops. The proposed tolerance of 4.5 ppm in small vine climbing fruits except fuzzy kiwifruit (subgroup 13 - 07F) is based upon existing data for grapes (the representative commodity for the subgroup). Upon establishment of the tolerance in subgroup 13 - 07F, the existing tolerance in grapes should be removed. The proposed tolerance of 0.7 ppm in apricots is based upon the submitted data for peaches. HED recommends that the tolerance be established at 0.70 ppm. The rationales for the establishment and concurrent removal of tolerances associated with the current action are listed in Table 6, below. An International Residue Limit Status s heet is appended as Attachment 1 . Data sets and results from the OECD tolerance calculation procedure for the various commodities are appended as Attachment 2.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **63** of **78 TABLE**  **6 Tolerance Summary for Metrafenone**  **( 40CFR §**  **624[a]) .** 

**Comm odity**  **Existing Tolerance (ppm)**  **Recommended**

**Tolerance (ppm) Rationale**  Apricot None 0.70 Based on submitted peach data. Cherry subgroup 12 - 12A None 2.0 Based on submitted cherry data. Fruit, pome, group 11 - 10 None 1.5 Based on submitted pome fruits data. Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F None 4.5 Based on data supporting the existing tolerance in grape. Grape 4.5 Remove Covered by the subgroup 13 - 07F tolerance to be established. Hop, dried cones None 70 Based on submitted hops data. Peach subgroup 12 - 12B None 0.70 Based on submitted peach data. Vegetable, cucurbit, group 9 None 0.50 Based on submitted cucurbit data. Vegetable, fruiting, group 8 - 10 None 0.90 Based on submitted fruiting vegetable data. **References** Metrafenone. Petition for the Establishment of Tolerances on Imported Grapes. Summary of Analytical Chemistry and Residue Data. PP#4E6884. ; D312307; D. McNeilly . 24 August 2006 . Metrafenone: Human Health Risk Assessment for Foliar Use on Grapes. ; D354166; D. McNeilly ; 1 March 2010 . Metrafenone. Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS). ; D370903; G.F. Kramer; 18 Nov 2009. Metrafenone: Chronic Aggregate Dietary Exposure (Food and Drinking Water) and Risk Assessment for the Section 3 Registration on Grapes. ; D371367; D. McNeilly ; 18 February 2010 . Metrafenone. Application for Section 3 Registration for Use on Grape. Summary of Analytical Chemistry and Residue Data. ; D331685; D. McNeilly ; 18 February 20 10. PP#4E6884. New Chemical, Food Use of Metrafenone on Table and W ine Grapes. Request for Petition Method Validation (PMV) of the Proposed Tolerance Enforcement Methods. ; D331185; D. McNeill y ; 3 August 2006 . Review of Proposed Tolerance Enforcement Method for Metrafenone. ; ACB Project #B06 - 38. D. Wright , D. McNeill y; 29 September 20 08. Drinking W

ater Assessment for the Proposed Uses of Metrafenone [ (3 - bromo - 6- methyoxy - 2 - methylphenyl) (2,3,4 - trimethoxy- 6- methylphenyl) methanone ] on Pome Fruits, FruitingMetrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **64** of **78** Vegetables, Peach Subgroup 12 - 12B, Apricot, Cherry Subgroup 12 - 12A , Cucurbit Vegetables (Group 9), and Fruit, Small, Vine Climbing (except Fuzzy Kiwifruit) Subgroup 13 - 07F; D411540, D414403, D416312; J.A. Hetrick; 25 November 2013 . Metrafenone. Review of Residue Data from Hops Field Trials

– Statistical Test for Outlier. ; D421923; Bayazid Sarkar; 21 August 2014. **Attachments** Attachment 1: International Residue Limit Status sheet. Attachment 2: OECD MRL(Tolerance) Assessment Calculations.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **65** of **78 Attachment 1:**  **International Residue Limit Status**  **Me trafenone**  **(PC Code 0**  **00 32**  **5 )**  **Summary of US Tolerances and International Maxim um Residue Limits.**  **Residue Definitions US (40CFR §180.6**  **24 )**  **Canada Codex**  **Plants:** M etrafenone (3 -bromo - 6 - methoxy - 2 - methylphenyl)(2,3,4 - trimethoxy - 6 - methylphenyl)methanone . Metrafenone (3 -bromo - 6 - methoxy - 2 - methylphenyl)(2,3,4 - trimethoxy - 6 - methylphenyl)methanone . **Comm odity**  **2 Tolerance**  **(ppm) 3**  **Comm odity**  **MRL (m**  **g/kg) Comm**  **odity MRL**  **(m g/kg)**  Apricot 0.70 Cherry subgroup 12 - 12A 2.0 Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F 4.5 Grapes Raisins 4.5 17 Fruits, pome , group 11 - 10 1.5 Hop, cones , dried 70 Peach subgroup 12 - 12B 0.70 Vegetable, cucurbit, group 9 0.50 Vegetables, fruiting, group 8 - 10 0.90

**Completed:** M. Negussie, 1 2 November 2013. 1. Mexico adopts US tolerances, and/or Codex MRLs, for its export purposes. 2. Includes only commodities of interest for this action. 3. Tolerance values are those recommended by HED, not those proposed by the petitioner.Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **66** of **78 Attachment 2: OECD MRL (Tolerance) Assessment Calculations.**  Apple **Residues (mg/kg)** 0.218 0.158 0.492 0.446 0.360 0.230 0.214 0.314 0.141 0.155 0.165 0.078 0.536 0.760 0.392Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **67** of **78 Metrafenone**  **Apple USA**  **0.90 lb ai/A, 7 -**  **day PHI Total number of data (n)**  15 **Percentage of censored data** 0% **Number of non -**  **censored data** 15 **Lowest residue** 0.078 **Highest residue** 0.760 **Median residue** 0.230 **Mean** 0.311 **Standard deviation (SD)** 0.187 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.760

**- Mean + 4 SD**  1.058

**- CF x 3 Mean**  0.932 **Unrounded MRL** 1.058 **Rounded MRL 1.5** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **68** of **78** Pear **Residues (mg/kg)** 0.405 0.409 0.189 0.141 0.160 0.477 0.392 **Metrafenone Pear**  **USA 0.90 lb ai/A, 7**  **- day PHI**  **Total number of data (n)**  7 **Percentage of censored data** 0% **Number of non -**  **censored data** 7 **Lowest residue** 0.141 **Highest residue** 0.477 **Median residue** 0.392 **Mean** 0.310 **Standard deviation (SD)** 0.141 **Correction factor for censoring (CF)**  1.000 **Proposed MRL estimate**

**- Highest residue**  0.477

**- Mean + 4 SD**  0.874

**- CF x 3 Mean**  0.931 **Unrounded MRL** 0.931 **Rounded MRL 1**  High uncertainty of MRL estimate. [Small dataset]Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **69** of **78** Tomato **Residues (mg/kg)** 0.101 0.228 0.079 0.110 0.170 0.105 0.176 0.246 0.088 0.285 0.109 0.095 0.103 0.234 0.427 0.099 0.041 0.222Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **70** of **78 Metrafenone**  **Tomatoes USA**  **0.90 lb ai/A, 0**  **- day PHI**  **Total number of data (n)** 18 **Percentage of censored data** 0% **Number of non -**  **censored data** 18 **Lowest residue** 0.041 **Highest residue** 0.427 **Median residue** 0.110 **Mean** 0.162 **Standard deviation (SD)** 0.096 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.427

**- Mean + 4 SD**  0.547

**- CF x 3 Mean**  0.486 **Unrounded MRL** 0.547 **Rounded MRL 0.6** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **71** of **78** Pepper **Residues (mg/kg)** 0.417 0.402 0.148 0.248 0.270 0.353 0.081 0.498 **Metrafenone**

**Bell/non -**  **bell peppers**

**USA 0.90 lb ai/A, 0**  **- day PHI**  **Total number of data (n)** 8 **Percentage of censored data** 0% **Number of non -**  **censored data** 8 **Lowest residue** 0.081 **Highest residue** 0.498 **Median residue** 0.312 **Mean** 0.302 **Standard deviation (SD)** 0.142 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.498

**- Mean + 4 SD**  0.869

**- CF x 3 Mean**  0.906 **Unrounded MRL** 0.906 **Rounded MRL 0.9** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **72** of **78** Cherry **Residues (mg/kg)** 0.699 0.393 0.429 0.494 0.317 0.738 0.368 0.438 1.160 0.492 0.334 0.596 0.647 0.547 **Metrafenone Cherry**  **USA 0.60 lb ai/A, 7**  **- day PHI**  **Total number of data (n)** 14 **Percentage of censored data** 0% **Number of non -**  **censored data** 14 **Lowest residue** 0.317 **Highest residue** 1.160 **Median residue** 0.493 **Mean** 0.547 **Standard deviation (SD)** 0.221 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  1.160

**- Mean + 4 SD**  1.430

**- CF x 3 Mean**  1.640 **Unrounded MRL** 1.640 **Rounded MRL 2** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **73** of **78** Hops **Residues (mg/kg)** 16.870 21.890 21.120 23.520 21.300 22.800 13.300 19.700 34.400 33.100

**Metrafenone Hops**  **USA 0.60 lb ai/A, 3**  **- day PHI**  **Total number of data (n)** 10 **Percentage of censored data** 0% **Number of non -**  **censored data** 10 **Lowest residue** 13.300 **Highest residue** 34.400 **Median residue** 21.595 **Mean** 22.800 **Standard deviation (SD)** 6.516 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  34.400

**- Mean + 4 SD**  48.863

**- CF x 3 Mean**  68.400 **Unrounded MRL** 68.400 **Rounded MRL 70** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **74** of **78** Peach **Residues (mg/kg)** 0.211 0.247 0.227 0.185 0.166 0.489 0.208 0.139 0.208 0.136 0.051 0.289 0.222 0.186Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **75** of **78 Metrafenone**  **Peach USA**  **0.60 lb ai/A, 7 -**  **day PHI Total number of data (n)**  14 **Percentage of censored data**  0% **Number of non -**  **censored data** 14 **Lowest residue** 0.051 **Highest residue** 0.489 **Median residue** 0.208 **Mean** 0.212 **Standard deviation (SD)** 0.098 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate** 

**- Highest residue**  0.489

**- Mean + 4 SD**  0.604

**- CF x 3 Mean**  0.635 **Unrounded MRL** 0.635 **Rounded MRL 0.7** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **76** of **78** Cantaloupe **Residues (mg/kg)** 0.154 0.226 0.133 0.088 0.282 0.177 0.132 0.038 0.132 0.209 0.178 0.080 **Metrafenone Cantaloupe**  **USA 0.90 lb ai/A, 0**  **- day PHI**  **Total number of data (n)** 12 **Percentage of censored data** 0% **Number of non -**  **censored data** 12 **Lowest residue** 0.038 **Highest residue** 0.282 **Median residue** 0.144 **Mean** 0.152 **Standard deviation (SD)** 0.068 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.282

**- Mean + 4 SD**  0.423

**- CF x 3 Mean**  0.457 **Unrounded MRL** 0.457 **Rounded MRL 0.5** Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **77** of **78** Cucumber **Residues (mg/kg)** 0.100 0.142 0.084 0.157 0.053 0.097 **Metrafenone Cucumber**  **USA 0.90 lb ai/A, 0**  **- day**  **PHI Total number of data (n)**  6 **Percentage of censored data** 0% **Number of non -**  **censored data** 6 **Lowest residue** 0.053 **Highest residue** 0.157 **Median residue** 0.099 **Mean** 0.106 **Standard deviation (SD)** 0.038 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.157

**- Mean + 4 SD**  0.258

**- CF x 3 Mean**  0.317 **Unrounded MRL** 0.317 **Rounded MRL 0.4**  High uncertainty of MRL estimate. [Small dataset]Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

Page **78** of **78** Summer Squash **Residues (mg/kg)** 0.305 0.294 0.125 0.129 0.101 0.174 0.072 0.137 0.216 0.105 0.100 0.113 0.277 0.124 **Metrafenone Summer squash**  **USA 0.90**  **lb ai/A, 0 -**  **day PHI Total number of data (n)**  14 **Percentage of censored data** 0% **Number of non -**  **censored data** 14 **Lowest residue** 0.072 **Highest residue** 0.305 **Median residue** 0.127 **Mean** 0.162 **Standard deviation (SD)** 0.079 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.305

**- Mean + 4 SD**  0.476

**- CF x 3 Mean**  0.487 **Unrounded MRL** 0.487 **Rounded MRL 0.5**