Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 1 of 24 **UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY**  WASHINGTON, D.C. 20460 **OFFICE OF CHEMICAL SAFETY AND**

**POLLUTION PREVENTION MEMORANDUM**  Date: 1 2/ 1 8 /13 Subject: **Fenamidone** . Residue Chemistry Summary

Document to Support New Uses and Tolerances on Ginseng, Succulent Beans (Except Cowpea) , Bulb Onion (Subgroup 3 - 07A), and Green Onion (Subgroup 3 - 07B) . Summary of Analy tical Chemistry

and Residue Data. PC Code: 046679 DP Barcode: D 4 10422 Decision No.: 475185 Registration No. : 264 - 693 Petition No.: 3E8150 Regulatory Action: Section 3 Registration Risk Assessment T ype: NA Case No.: NA TXR No.: NA CAS No.: 161326 - 34 - 7 MRID No.: See Below 40 CFR : 180.579 **From:** Karen Milians, Ph.D. , Chemist

Ideliz Negrón- Encarnación, Ph.D., Chemist Risk Assessment Branch VII Health Effects Division (7509P) **Through** : William Donovan, Ph.D., Senior Chemist

Michael Metzger, Branch Chief Risk Assessment Branch VII Health Effects Division (7509P) **To** : Laura Nollen, Risk Manager Reviewer

Barbara Madden, Risk Manager Registration Division (7505P) Summary of Submitted Residue Chemistry Studies O C S PP 860 Series Guideline MRID Number Title 860.1500 49052101 Fenamidone: Magnitude of the Residue on Ginseng 860.1500 49052102 Fenamidone: Magnitude of the Residue on Bean (Lima) 860.1500 4905210 3 Fenamidone: Magnitude of the Residue on Bean (Snap)Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 2 of 24 **Table of Contents** 1.0 Executive Summary ................................ ................................ ................................ ............ 3 2.0 Regulatory

Recommendations ................................ ................................ ......................... 4 2.1 Data Deficiencies/Data Needs ................................ ................................ .......................... 4 2.2.1 Enforcement Analytical Method ................................ ................................ ............... 4 2.2.2 Recommended Tolerances ................................ ................................ ........................ 4 2.2.3 Revisions to Petitioned- For Tolerances ................................ ................................ .... 5 2.2.4 International Harmonization ................................ ................................ ..................... 5 3.0 Introduction ................................ ................................ ................................ ......................... 6 3.1 Chemical Identity ................................ ................................ ................................ ............. 6 3.2 Phys ical/Chemical Characteristics ................................ ................................ ................... 6 3.3 Pesticide Use Pattern/Directions for Use (860.1200) ................................ ....................... 7 4.0 Metabolite/Degradate Residue Profile ................................ ................................ .......... 8 4.1 Nature of the Residue ................................ ................................ ................................ ... 8 4.1. 1 Summary

of Plant/Livestock Metabolism (860.1300) ................................ .............. 8 4.1.2 Summary

of Confined Rotational Crops (860.l850) ................................ ................. 8 4.2 Residues of Concern Summary and Rationale ................................ ................................ . 8 5.0 Residue Profile ................................ ................................ ................................ .................... 9 5.1 Residue Analytical Methods (860.1340) ................................ ................................ .......... 9 5.1.1 Data Collection Methods ................................ ................................ .......................... 9 5.1.2 Multi - Residue Methods (860.1360) ................................ ................................ ........ 10 5.1.3 Tolerance Enforcement Methods ................................ ................................ ............ 11 5.1.4 Submittal of Analy tical Reference Standards (860.1650) ................................ ...... 11 5.2 Storage Stability

(860.1380) ................................ ................................ .......................... 11 5.3 Residue Data ................................ ................................ ................................ .................. 13 5.3.1 Crop F ield Trials (860.1500) ................................ ................................ .................. 13 5.3.2 Field Rotational Crops (860.1900) ................................ ................................ ......... 17 5.3.3 Processed Food and Feed (860.1520) ................................ ................................ ..... 17 5.3.4 Meat, Milk, Poultry and Eggs (860.1480) ................................ .............................. 17 6.0 Tolerance Derivation ................................ ................................ ................................ ........ 19 Appendix A. Field Trial Geographic Distribution ................................ ................................ ....... 20 Appendix B. International Residue Limits Table ................................ ................................ ........ 21 Appendix C. OECD MRL Calculation Procedure Inputs/Outputs ................................ .............. 22Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 3 of 24 **1.0 Executive Summary**  Fenamidone is foliar fungicide currently registered for application to a variety of field crops including, bulb vegetables, root vegetables, tuberous and corm vegetables, fruiting vegetables and leafy vegetables. In addition, fenamidone is registered for non- food uses such as cotton and tobacco. Fenamidone is a chiral compound with the technical product consisting of 98.5% Sfenamidone. Residue field trial studies were submitted by the IR- 4 Project on behalf of Bayer Crop Science , to support the registration request for the use of fenamidone ( formulated as Reason® 500 SC ) on ginseng, and succulent beans . The data in the studies are classified as scientifically acceptable with the exemption of the residue data for metabolite RPA 405862 , because frozen storage stability w as not demonstrated . Additionally, adequate analytical methods are available to enforce the proposed tolerances including the FDA multi -residue method protocol D. An adequate number of field trials with appropriate geographic representation have been provided to allow HED to establish tolerances on ginseng , and succulent beans (except cowpea) . In addition, the registrant proposed tolerances for bulb onion (subgroup 3 - 07A), and green onion (subgroup 3 - 07B) . Adequate data is available to establish tolerances on these subgroups based on residue data for bulb onions and green onions . Ginseng is ty

pically harvested after 3 - 4 ye ars growth; therefore, in order to simulate the effects of multi - ye ar applications, the registrant carried out field trials using a 3x exaggerated application rate of fenamidone (2.48 lbs a.i./A) than that stated on the label (maximum ye arly 0.80 lbs a.i./A). Based on this, f ive field trials were performed with ginseng by applying Reason® 500 SC at total rates o f 2.43 - 2.48 lbs a.i./A and one field trial with a total of 0.817 lbs a.i./A. Fenamidone residues in dried ginseng roots treated with 9 foliar broadcast applications of fenamidone at total rates of 2.43 - 2.48 lbs a.i./A ranged from 0. 02 - 0.53 ppm, when samples were harvested at 12 - 15 day

P HIs whereas, residues of metabolites RPA 408056 (DA- Fen) , and RPA 405862 ranged from <0.02 - 0.028, and from <0.02 - 0.024 ppm, respectively, while for RPA 717879 (DADK- Fen) were all <0.02 ppm . Additionally, f enamidone residues in dried ginseng roots treated with foliar broadcast applications of fenamidone at total rates of 0.817 lbs a.i./A and harvested at 14 - day

P HI ranged from 0.049 - 0.059 ppm, and residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were all <0.02 ppm. Tolerance for ginseng was calculated using the highest application rate for the field trials (2.48 lbs a.i./A). Residue decline behavior was not assessed. Eight field trials were performed with snap bean s by a pplying Reason ® 500 SC to snap beans in 4 foliar broadcast or foliar directed applications at rates of 0.259 - 0.278 lbs a.i./A, RTIs of 6 - 8 days, for total application rates of 1.05 - 1.36 lbs a.i./A/season. Commercially mature snap bean pods with seeds , and plants with pods were harvested at all trial sites at 3 - 4 day P HI s. Fenamidone residues in snap bean pods with seeds ranged from 0.084 - 0.46 ppm. Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were all <0.02 ppm . Fenamidone residues decreased with increasing PHI when snap bean pods with seeds were harvested at PHIs of 1, 3, 7, and 13 days. Residues of the metabolites RPA 717879 (DADKFen) , RPA 408056 (DA- Fen) , and RPA 405862 were all <0.02 ppm in snap bean pods with seedsFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 4 of 24 at all PHIs. Residues in snap bean plants with pods ranged from 1 . 3 - 15.9 ppm. Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 ranged from <0.02 - 0.042, 0.046 - 0.17, and <0.02 - 0.094 ppm, respectively. Residue decline behavior was determined at PHI of 1, 7 and 13 days and demonstrated that residues decreased with increasing PHI . Nine field trials were performed with succulent lima beans by a pplying Reason® 500 SC as 4 foliar broadcast at 0.259 - 0.278 lbs a.i./A, RTIs of 6 - 9 days, for total application rates of 1.05 - 1.10 lbs a.i./A. Residues in succulent lima bean seeds without pods ranged from <0.02 - 0.08 ppm when samples were harvested at 2 - 4 day P HI s. Similarly, residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) RPA 405862 were all <0.02 ppm. **2.0 R** **egulatory R ecommendations**  There are no residue chemistry deficiencies that would preclude the establishment of tolerances for residues of fenamidone on the commodities below . Ginseng ..... .............................................................................. ............ 0. 80 ppm B ean , succulent , except cowpea... ................... ........................................ ..... 0. 8 0 ppm Onion, bulb, subgroup 3 - 07A ...... . . ............................................................ . 0.20 ppm Onion, green, subgroup 3 - 07B.................................................................. ... 1.5 ppm **2.1 Data**  **Deficiencies/Data Needs** None. **2.2.1 Enforcement**  **Analytical Method** The current tolerance enforcement method entitled RPA 407213: m ethod of Analysis for RPA 407213 and its Metabolites RPA 717879 (DADK -Fen), RPA 408056 (DA -Fen) and RPA 405862 (MRID No. 4 5385918), a liquid chromatographic method coupled with tandem mass spectrum detection (LC/MS/MS) has been radiovalidated. Further the method has undergone successful ILV (independent laboratory v alidation) as well as validation by the Agency

on a number o f commodities including potato, cucumber, cantaloupe, lettuce, onion, tomato (fruit, paste, and puree), spinach, and wheat (forage, hay, straw, grain, bran, flour, shorts, germ, and middlings). **Conclusion:** The data acquisition method is similar to the enforcement method. Therefore, HED concludes that the enforcement method is also suitable to enforce the new plant tolerances proposed in this petition. **2.2.2 Recommended Tolerances**  HED recommends that 40 CFR be amended by e stablishing tolerances for the plant commoditiesFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 5 of 24 listed in the **Table 1**  . Tolerances for residues on ginseng, succulent beans, bulb onion (subgroup 3 - 07A), and green onion (subgroup 3 - 07B) have been submitted to support the proposed uses of fenamidone. The tolerances for plant commodities should be defined as follows: Tolerances are established for residues of fenamidone including its metabolites and degradates, or on the commodities in the table below. C ompliance with the tolerance levels for fenamidone is to be determined by measuring only fenamidone ( (S ) - l- anilino - 4- methyl-2 -methylthio - 4- phenylimidazolin - 5- one) . **Table 1**  **. Tolerance Summary for Fenam** **idone .**  **Comm odity**  **Established** ***** **/Proposed Tolerance (ppm** **) HED**  **- Recommended**  **Tolerance (ppm) Comments** 

**( correct commodity definition**  **)** Ginseng 0.8 0.8 0 Bean, succulent 0.8 0.8 0 Bean, succulent, except cowpea Onion, bulb, subgroup 3 - 07A 0.2 0.2 0 Onion, green, subgroup 3 - 07B 1.5 1.5 Garlic 0.20* Remove These commodities are covered under the proposed / recommended onion, bulb, subgroup 3 - 07A and onion, green, subgroup 3 - 07B . Garlic, great headed 0.20* Remove Onion, dry bulb 0.20* / Remove Remove Onion, green 1.5* / Remove Remove Onion, welsh 1.5* Remove Shallot, bulb 0.20* Remove Shallot, fresh leaves 1.5* Remove * Established tolerances under the 40 CFR 180.579. **2.2.3 Revisions to Petitioned** **- For Tolerances**  The succulent bean definition includes cowpea which has forage and hay commodities that are considered significant livestock feedstuff s . The dietary

burden associated with uses on cowpea is not supported by

an appropriate feeding study ; therefore, uses on cowpea have to be excluded from succulent bean. In addition, tolerances establishe d in the 40 CFR 180.579 (see Table 1) for commodities covered under subgroups 3 - 07A and 3 - 07B should be removed. The registrant should submit a revised Section F in which the proposed tolerances are the same as those recommended b y HED. **2.2.4 Internation**  **al Harmonization** Mexican and Codex MRLs have not been established for the commodities under consideration. The recommended tolerance definition and l evels for onion, bulb, subgroup 3 - 07A , and onion, green, subgroup 3 - 07B are harmonized with established Canadian Maximum Residue Limits (MRLs) for similar commodities. Moreover, identical regulatory levels are being recommended by EPA and PMRA reviewers for ginseng and commodities under the succulent bean definition as part of this joint review.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 6 of 24 **2.3 Lab**  **el Recommendations** No recommendations are provided for the proposed new uses on ginseng, succulent beans, onion, bulb, subgroup 3 - 07A and onion, green, subgroup 3 - 07B . **3.0 Introduction**  Fenamidone is a broad- spectrum foliar fungicide currently registere d for application to a variety of field crops including bulb vegetables, tuberous and bulb vegetables, cucurbit vegetables, fruiting vegetables, leafy vegetables , potatoes, and root vegetables . F enamidone is a chiral compound with the technical product consisting of 98.5% S - fenamidone (REASON ® 500 SC) . Tolerances are established for residues of fenamidone in raw agricultural commodities, animal commodities and for inadvertent residues under 40 CFR 180.579. **3.1 Chemical Identity**  **Table 2.** below shows fenamidone nomenclature. **Table 2.**  **Fenam idone**  **Nomenclature.** Fenamidone, RPA 407213 Chemical Structure

Common name Fenamidone Com pany experimental name RPA 407213 IUPAC name (S ) - l - anilino -4 - methyl - 2 - methylthio -4 -phenylimidazolin- 5 - one CAS name (5 S ) - 3,5 - dihydro - 5 - methyl - 2 - (methylthio) - 5 -phenyl - 3 - (phenylamino) -4Himidazol -4 - one CAS # 161326 - 34 - 7 End-use product/EP REA SON ® 500 SC fungicide, PCP# 27462 **3.2 Physical/Chemical Characteristics**  Fenamidone is moderately s oluble in water (FAO, 2000 ) 1 and not likely to volatize due to low vapor pressure. Based on the octanol/water partition coefficient (Kow) fenamidone partitions to the lipophilic phase . However, it is soluble in both polar and non-polar solvents. Refer to **Table 3.**  below for the phys ic ochemical properties of fenamidone.

1 FAO, 2000. Food and Agriculture Organization of the United Nations. FAO Pesticide Disposal Series 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence processes in the soil. Editorial Group, FAO Information Division: Rome, 2000. http://www.fao.org/docrep/003/X2570E/X2570E00.htm . N N C H 3 O S C H 3 N HFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 7 of 24 **Table 3**  **. Physicochemical Properties of the Technical Grade**  **Fenam idone**  Parameter Value Reference (MRID) Form ula/Molecular weight (g/mole) C 17H 17N 3 OS - 311.401 NA Melting point/range (°C) 135.5 45385708 pH 5.7 45385714 Density (g/cm3 ) 1.288 45385708 Water solubility ( mg/L at 20 °C) 7.8 45385712 Solvent solubility (mg/L at RT ) 330,000 methylene chloride 250,000 acetone 106,000 ethyl acetate 86,000 acetonitrile 43,000 methanol 40,000 toluene 300 heptane 45385712

Vapor pressure at 20 °C (Pa) 2.60X10 - 9 MRID 45385711 Dissociation constant (pKa) No measurable dissociation constants in the pH range of 1 to 13 MRID 45385714 Octanol/water partition coefficient Log(KOW) 631 (2.8) MRID 45385713 **3.3 Pesticide**  **Use Pattern/ Directions for Use**  **(860.1200)** Fenamidone can be applied by ground, aerial or chemigation on ginseng , succulent beans and bulb vegetables . The maximum seasonal application for these crops is 0.80 lbs a.i./A and the application rate is 0.178 - 0.267 lbs a.i./A (Refer to **Table 4**  ) . The pre -harvest interval (PHI) is 14 days for ginseng and 3 days for lima and snap beans. However, the maximum number of application s per season is not specified for these crops on the label. **Table 4**  **. Summary of**  **Proposed Directions for Use of**  **Fenamidone .**  Applic. Timing, T ype, and Equip. Form

ulation [EPA Reg. No.] Applic. Rate

(lb a . i . /A) Max. No.

Applic. per Season Max. Seasonal

Applic. Rate (lb a . i . /A) PHI

(days) Use Directions and

Limitations Ginseng Reason® 500 SC fungicide, ground, aerial, chemigation 264 - 695 0.178 - 0.267 Not Specified 0.80 14 14 day RTI Succulent Beans Reason® 500 SC fungicide, ground, aerial, chemigation 264 - 695 0.178 - 0.267 Not Specified 0.80 3 7 day RTI Bulb Vegetables Reason® 500 SC fungicide, ground, aerial, chemigation 264 - 695 0.178 Not Specified 0. 71 7 5 - 10 days RTI **Conclusions:** The proposed use directions are sufficient to allow evaluation of the crop field trial studies. The proposed use pattern is supported by the crop field trial data in succulent beans (lima beans and snap beans) and bulb vegetables . The use pattern applied in the ginseng cropFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 8 of 24 field trials was selected to reflect multi - ye ar applications; therefore, it differs to the yearly use pattern described in the label. This is considered adequate for ginseng, see further discussion in the crop field trial section. **4.0 Metabolite/Degradate Residue Profile**  **4.1 Nature of the Residue**  **4.1.1 Summary of Plant/Livestock**  **Metabolism (860.1300)** D314318, 6/14/2007 , T. Bloem No new metabolism studies were submitted for this petition. B ased on data submitted on the metabolism of fenamidone on potatoes, tomatoes, lettuce, grapes and carrots, HED concludes that the nature of the residue in plants has been adequately delineated to support this request for crop use on ginseng, succulent beans and bulb onion (subgroup 3 - 07A), and green onion (subgroup 3 - 07B) . The HED Metabolism Assessment Review Committee (MARC) has reviewed metabolism studies, rotational crop studies and environmental fate data (MARC memos - T. Bloem et al., 11 - July- 2002; T. Bloem et al., 25 - May- 2004). The residue of concern (ROC) for tolerance enforcement in plants is parent fenamidone. The ROC for risk assessment in all plant commodities except carrot is parent fenamidone and the metabolites RPA 717879 (DADK- Fen), RPA 408056 (DA- Fen), and RPA 405862 . HED reconsidered the ROC definition for root vegetables. Inorder to account for the major metabolites observed in the carrot and potato metabolism studies HED recommends that for future field trial data with root vegetables parent f enamidone, RPA 413255 , RPA 717879 (DADK- Fen) and RPA 408056 (DA- Fen), RPA 405862 are measured and that the residues of concern for risk assessment are considered on a case by c ase basis . For ginseng, based on the lack of information pertaining to the absence/presence of RPA 413255 in the crop field trials, a metabolite ratio 0 . 6X will be used for dietary assessment purposes. This ratio is based on the carrot metabolism study (D314318, T. Bloem, 06/0 7/2007 ). The residues of concern for tolerance setting and risk assessment purposes are summarized in Table 5 . **4.1. 2**  **Summary of Confined Rotational Crops (860 .l850)**  D314318, T. Bloem, 6/14/2007 Confined rotational crop data on lettuce, turnip and barley w ere previously

submitted to the Agency . The Agency

has determined that the residue of concern in rotational crops for purposes of tolerance setting is fenamidone and its metabolite, RPA 717879 (DADK- Fen) . The residue of concern in rotational crops for purposes of risk assessment is fenamidone, and its metabolites RPA 717879 (DADK- Fen) , and RPA 408056 (DA- Fen) (free and conjugated). **4. 2**  **Residues of Concern Summary and Rationale** MARC memos - T. Bloem et al , 2002; T. Bloem et al., 25 -May- 2004. The residues of concern for tolerance setting and risk assessment purposes are summarized in **Table 5** .Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 9 of 24 **Table 5 .**  **Summary of Metabolites and Degradates to be included in th e Risk Assessment**  **and Tolerance Ex** **pression** Matrix Residues included in Tolerance Expression Residues included in Risk Assessment

Plants Primary Crop

(excluding carrot) Fenamidone Fenamidone, RPA 717879 (DADK- Fen) , RP A 408056 (DA -Fen), and RP A 405862 Carrot 1 Fenamidone Fenamidone, and RP A 413255 Rotational Crop Fenamidone, RPA 71787 9 (DADK- Fen) Fenamidone, RPA 717879 (DADK- Fen) and RPA 408056 (DA-Fen) (free and conjugated) Livestock Ruminant Fenamidone, RPA 717879 (DADK- Fen) Fenamidone, RPA 717879 (DADK- Fen) and RPA 408056 (DA-Fen) (free and conjugated) Poultry Drinking Water Not Applicable 1 For future field trials with the root vegetables, HED recommends that parent f enamidone, and the metabolites RP A 413255, RPA 717879 (DADK-Fen) and RPA 408056 (DA- Fen), and RPA 405862 are measured. **5.0 Residue Profile**  **5.1 Residue Analytical Methods (860.1340)**  **5.1 .1**  **Data Collection Methods** 49052101, 49052102, 49052103, Fenamidone: Magnitude of the Residue on ginseng, Lima and Snap Bean , respectively. Residues of fenamidone and the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were determined using the analy tical method entitled “RPA 407213: Method of Analysis for RPA 407213 and its Metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DAFen) , and RPA 40586 2 in Plants”. This method has been assessed previously and is acceptable for data gathering purposes. The reference method was modified slightly f or the current study

by not filtering extracts after the initial extractions, and by omitting the use of clean-up cartridges as they were not required. However, this did not appear to affect the analyses as the chromatograms of the samples matched those of the controls. Briefly, residues were extracted twice with acetonitrile:water (80:20; v/v), the extracts were combined, and then diluted at least 10 times with methanol:water (10:90; v/v). Residues were then determined by l iquid chromatography/mass spectroscop y/mass spectroscopy (LC/MS/MS). The LLMV for all analytes in all matrices was 0.02 ppm. The calculated LOQ was determined to be 0.03, 0.008, 0.009, and 0.012 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPAFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 10 of 24 405862 in dried ginseng roots, respectively. The calculated LOD was determined to be 0.009, 0.003, 0.003, and 0.004 ppm for residues of fenamidone, and metabolites RPA 717879 (DADKFen) , RPA 408056 (DA- Fen) , and RPA 405862 in dried ginseng roots, respectively. The LLMV was 0.02 ppm for all analytes in dried ginseng roots. Similarly, the LOQ was determined to be 0.00972, 0.01102, 0.00557, and 0.01065 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 in succulent lima bean seeds without pods, respectively. The calculate d LOD was determined to be 0.00324, 0.00367, 0.00186, and 0.00355 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 in succulent lima bean seeds without pods, respectively . The LLMV was 0.02 ppm for all analytes in succulent lima bean seeds without pods. The method was validated prior to sample analysis by spiking control lima bean seeds without pods with 0.02, 0.2, and 2.0 ppm fenamidone, and its 3 metabolites. Adequacy

o f the method was also confirmed by spiking control samples with 0.02 and 0.2 ppm of each analy te, and determining recoveries concurrently with analys is of treated sample sets. Finally, for snap beans in pods with seeds, the LOQ was calculated to be 0.020, 0.019, 0.006, and 0.005 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , RPA 405862 , respectively. The LO D was calculated to be 0.007, 0.006, 0.002, and 0.002 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , RPA 405862 , respectively . On the contrary, snap bean plants with pods, the LOQ was calculated to be 0.033, 0.025, 0.013, and 0.012 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , RPA 405862 , respective ly . Also, in snap bean plants with pods, the LOD was calculated to be 0.011, 0.008, 0.004, and 0.004 ppm for residues of fenamidone, and metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DAFen) , RPA 405862 , respectively . **Conclusions :**  All method validation and concurrent recoveries were within the acceptable 70 - 120% range. Therefore, the reference method, is adequate for the determination of fenamidone, and the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 in ginseng roots and succulent beans in the studies . **5.1.2 Multi** **- Residue Methods (860.1360)**  D314318, T. Bloem, 6/14/2007 Fenamidone, RPA 408056 (DA- Fen) , RPA 717879 (DADK- Fen) , and RPA 405862 were tested through FDA multi -residue methods. Residues of fenamidone and all three metabolites were completely

recovered from fortified lettuce during Protocol D. Low recoveries of fenamidone were observed from Protocols E (31%) and F (54%). M etabolites RPA 408056 (DA- Fen) , RPA 717879 (DADK- Fen) , and RPA 405862 were not recovere d using Protocols E and F. Protocol B was not tested because fenamidone and its metabolites are not acids or phenols, and Protocol A was not fully

tested because the compounds were not found to naturally fluoresce. **Conclusions :**  The multi -residue metho d (Protocol D) is adequate for determining residues for dietary exposure assessment and has the potential to be the primary enforcement method.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 11 of 24 **5.1 .3**  **Tolerance Enforcement Methods** D357372, 2/24/09 , A. LaMay The current tolerance enforcement method entitled RPA407213: m ethod of Analysis for RPA 407213 and its Metabolites RPA 717879, RPA 408056 and RPA 405862 (MRID No. 45385918), a liquid chromatographic method coupled with tandem mass spectrum detection (LC/MS/MS) has been radiovalidated. Further the method has undergone successful ILV (independent laboratory

validation) as well as validation by the Agency

on a number of commodities including potato, cucumber, cantaloupe, lettuce, onion, tomato (fruit, paste, and puree), spinach, and wheat (forage, hay, straw, grain, bran, flour, shorts, germ, and middlings). HED concludes that this method is also suitable to enforce the new tolerances proposed in this petition. HED notes that since residues of fenamidone are detected through FDA Multi - Residue Method Protocol D, this protocol can also serve as an enforcement methodology . Field trial data were generated using the enforcement method. The method has been adequately validated and acceptable for determining residues of fenamidone, and its metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA - Fen) , and RPA 405862 in/on the commodities under consideration. The method extraction efficiency was validated by spiking control samples of each analy

te which resulted in acceptable recoveries (70 - 120% range). The lowe st level of method validation (LLMV) was 0.02 ppm for all analytes in all matrices. **Conclusions :**  The ILV and radiolabeled method validation were found adequate; therefore, the method is adequate for enforcement of the proposed new tolerance s as it has met Agency ’s standards. . **5.1.4 Submittal of**  **Analytical Reference Standards (860. 1650)**  The analytical reference standards for fenamidone (expiration date: 7/20/2014 ) and RPA 717879 (expiration date: 1/29/2016 ) have been submitted to the Agency ’s Pesticide Repository (Email correspondence with Theresa M. Cole, US EPA National Pesticide Standard Repository, 09/23/14 ). **5.2 Storage Stability (860.1380)**  MRIDs: 49052101, 49052102 and 49052103 : “Fenamidone: Magnitude of the Residue on Ginseng, Lima, and snap beans, respectively”. New storage stab ility

studies were submitted for the tolerance petition on ginseng, lima and snap beans. In previously submitted and reviewed data (MRID 45385914), residues of f enamidone and metab olite s have been shown to be stable in various matrices. The submitted storage stability data have been validated and indicate that residues of fenamidone, RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 are each relatively stable under frozen storage conditions for ~7 months in/on cottonseed and cotton gin by products, ~6 months in cottonseed hulls and meal, ~1 month in cottonseed oil, ~14 months in/on cucumber, ~13 months in/on leaf lettuce, ~12 months in/on bulb onions, ~13 months in/on potato tubers and in potato chips, ~12 months in potato flakes and potato wet peel, ~12 months in/on tomatoes, ~13 months in tomato paste and tomato puree, and ~13 months in/on wheat forage, grain, hay, and straw (45385914.der.doc).Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 12 of 24 The freezer storage stability study f or ginseng indicated that fenamidone, and metabolites RPA 717879 (DADK- Fen) and RPA 408056 (DA- Fen) were stable when stored frozen for 650 days. However, c oncurrent freezer storage stability data were not provided for metabolite RPA 405862 . Therefore, the data presented is considered as supplemental only. For snap beans samples stored frozen for 360 - 361 and 830 - 831 days were within the acceptable 70 - 120% range for all analy tes except fenamidone in pod with seeds. Similarly, mean freezer storage recoveries in lima bean samples stored frozen for 250 and 804 days were within the acceptable 70 - 120% range for all analytes, indicating residues were stable for this time period. These data are adequate to support the residue studies ginseng, lima and snap beans that are subject of this petition. **TABLE 6.**  **Summary of Storage Conditions.** Matrix (RAC) Storage

Tem perature (°C) Maximum Actual

Storage Duration ( days) 1 Interval of Demonstrated Storage Stability ( days) Dried ginseng roots < - 20 658 Dried ginseng roots were spiked with 0.2 ppm fenamidone, 0.4 ppm metabolite RPA 717879 (DADK- Fen) , and 0.2 ppm RPA 408056 (DAFen) and stored f

rozen for 650 days . The data indicated that fenamidone, and metabolites RP A 717879 (DADK-Fen) and RP A 408056 (DA-Fen) were stable when stored frozen for 650 days. Concurrent freezer storage stability data were not provided for metabolite RP A 405862 . Snap bean pods with seeds and snap bean plants with pods ≤ - 20 835 Snap bean pods with seeds and plants with pods were spiked with 0.2 ppm fenamidone or metabolite s RPA 4 08056 (DA-Fen) , RPA 717879 (DADK- Fen) , and RPA 405862 . S am ples were stored frozen for a minimum of 835 days, and there are no concerns regarding the stab ility of residues in snap bean pods with seeds, and snap bean plants with pods in this study. Lima bean, s eeds without pods ≤ - 20 682 Lima bean seeds were spiked with 0.2 ppm fenamidone or metabolites RPA 4 08056 (DAFen), RPA 717879 (DADK- Fen) , and RPA 405862 . S amples were stored frozen for a maximum of 682 days, there are no concerns regarding the stability of residues in lima bean seeds without pods in this study. 1 From start of storage period to residue extraction. Residues were determined within 1 day of extraction. **Conclusions:** The submitted storage stability results are adequate to support the storage duration for samples of lima and snap beans . S torage stabi lity data for the degradate RPA 405862 were not submitted and data in other root vegetables is not sufficient to support the storage duration of the ginseng crop field trial samples. However, since all the residues of concern other than RPA 405862 were shown to be stable in ginseng, and RPA 405862 was shown to be stable in/on succulent beans samples which were stored for a longer period than the ginseng samples, additional residue data will not be required at this time .Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 13 of 24 **5.3 Residue Data**  **5.3.1 Crop**  **Field Trials (860.1500)** Ginseng (MRID 49052101 ) Five residue field trial studies were conducted to support the registration request for the use of fenamidone on ginseng. These studies were conducted in the 2007 growing season in the US and Canada. Fenami done residues in dried ginseng roots treated with 9 foliar broadcast applications of fenamidone at total rates of 2.43 - 2.48 lbs a.i./A ranged from 0.02 - 0.53 ppm, when samples were harvested at 12 - 15 day P HI s and retreatment intervals from 12 - 15 days . Ginseng is a three to four ye ars crop and therefore, in order to simulate the effects of multi - year applications on the residues, field trials were carried out using higher total application rate of fenamidone (2.48 lbs a.i./A) than that stated on the label (maximum yearly 0.80 lbs a.i./A). Residue decline data for carrot (representative commodity o f ginseng crop subgroup) shows that residues of fenamidone increased as the PHIincreased from 3 to 15 days and then drop sl ightly as the PHIincreased to 29 days (T. Bloem, D314118, 06/ 14/2007) . Inaddition, the confined rotational study showed the presence of RPA 408056 (DA- Fen) and RPA 717879 (DADK- Fen). Turnips planted 30, 120, and 365 days following treatment of C -phenylring radiolabeled fenamidone at 1.80 lb ai/acre showed TRRs of 0.2501 ppm at 30 days, 0.1488 at 120 days, and 0.1381 ppm at 365 days in turnip roots (T. Bloem, D281887, see 45385902.der.wpd). In mature turnip root samples, RPA 717879 (DADK- Fen) decreased from 0.0359 ppm at 30 day to 0.0204 ppm at 365 days, RPA 408056 (DA- Fen) conjugate decreased from 0.3437 ppm at 30 - days to 0.0857 ppm at 365 days. Actual uptake of residues of fenamidone from the soil may b e lower as suggested by two field rotational studies with radish (T. Bloem, D281887, 07/1 /2002). However, based on the confined rotational study

with turnip and the decline data with carrot showing some persistence of residues of fenamidone, the crop field trial use pattern used on ginseng will be accepted at this time. The ginseng field trials showed that residues of metabolites RPA 408056 (DA- Fen) , and RPA 405862 ranged from <0.02 - 0.028, and from <0.02 - 0.024 ppm, respectively, while for RPA 717879 (DADK- Fen) were all <0.02 ppm. Fenamidone residues in dried ginseng roots treated with 3 foli ar broadcast applications of fenamidone at total rates of 0.817 lbs a.i./A ranged from 0.049 - 0.059 ppm, when samples were harvested at a 14 - day P HI . Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were all <0.02 ppm and harvested at a 14 - day

PHI. Residue decline behavior was not assessed. **T able**  **7. Summary of Residue Data from Crop Field Trials with Fenamidone**  **on Ginseng**  **1 .**  Commodity Total Applic.

Rate lb a.i./A PHI

(days) Residue Levels (ppm) n2 Min. Max. LAFT * HAFT * Median (STMdR) Mean

(STMR) Std. Dev. **Fenam idone**  Dried Ginseng Roots 2.43 - 2.48 12 - 15 10 0.02 0.53 -- -- 0.15 0.19 0.16 5 -- -- 0.027 0.35 0.17 0.19 0.13Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 14 of 24 **Me tabolite**  **RPA 717879 (DADK -** **Fen)** Dried Ginseng Roots 2.43 - 2.48 12 - 15 10 <0.02 <0.02 -- -- <0.02 <0.02 0 5 -- -- <0.02 <0.02 <0.02 <0.02 0 **Me tabolite**  **RPA 408056 (DA -** **Fen)** Dried Ginseng Roots 2.43 - 2.48 12 - 15 10 <0.02 0.028 -- -- <0.02 <0.021 0.0027 5 -- -- <0.02 <0.024 <0.02 <0.021 0.0018 **Me tabolite**  **RPA 405862** Dried Ginseng Roots 2.43 - 2.48 12 - 15 10 <0.02 0.024 -- -- <0.02 <0.021 0.0015 5 -- -- <0.02 <0.022 <0.02 <0.021 0.0011 **Total Residues**  Dried Ginseng Roots 10 0.08 0.62 0.02 0.06 5 0.087 0.02 0.06 1 Summary statistics do not include data from Trial ID # MI29 - 03 since it was the only plot treated at a different total application rate. RPA 413255 was not measured in this study. 2 Where n=10, statistics are based on trial samples; where n=5, statistics are based on trial averages. * LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial. Lima Beans (MRID 4905210 2 ) Nine trials were conducted in the US in the 2008 growing season. Fenamidone, formulated as Reason 500 SC, was applied to succulent lima beans in 4 foliar broadcast applications at all trial sites at rates 0.259 - 0.278 lbs a.i./A, and RTIs of 6 - 9 days, for total application rates of 1.05 - 1.10 lbs a.i./A. At the trial conducted in North Carolina (NC30), pods were slow to mature , so a fifth application was applied to lima beans to enable pod harvest at the requested PHI; therefore, the total application rate was 1.34 lbs a.i./A. Fenamidone residues in succulent lima bean seeds without pods treated at total rates of 1.05 - 1.10 lbs a.i./A ranged from <0.02 - 0.08 ppm when samples were harvested at 2 - 4 day P HIs. Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA - Fen) , and RPA 405862 were all <0.02 ppm in lima bean seeds without pods treated at the same rate and harvested at the same PHI . At the trial conducted in North Carolina, residues of fenamidone, and metabolites RPA 408056 (DA- Fen) and RPA 405862 were all <0.02 ppm in lima bean seeds without pods treated foliarly with a total of 1.34 lbs a.i./A when samples were harvested at a 4 - day PHI . Residues of the metabolite RPA 717879 (DADK- Fen) were 0.04 ppm in both samples harvested from the North Carolina trial site. Residue decline behavior was not assessed. **TABLE 8**  **. Summary of Residue Data from Crop Field Trials with**  **Fenamidone on Lima**  **Beans 1**  **.** Commodity Total Applic.

Rate lb a.i./A PHI

(days) Residue Levels (ppm) n2 Min. Max. LAFT * HAFT * Median (STMdR) Mean

(STMR) Std. Dev. **Fenam idone**  Lima bean seeds without pods 1.05 - 1.10 2 -4 16 <0.02 0.08 -- -- <0.02 <0.04 0.024 8 -- -- <0.02 0.08 <0.03 <0.04 0.026 **Me tabolite**  **RPA 717879 (DADK -** **Fen)** Lima bean seeds without pods 1.05 - 1.10 2 -4 16 <0.02 <0.02 -- -- <0.02 <0.02 0 8 -- -- <0.02 <0.02 <0.02 <0.02 0Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 15 of 24 **Me tabolite**  **RPA 408056 (DA -** **Fen)** Lima bean seeds without pods 1.05 - 1.10 2 -4 16 <0.02 <0.02 -- -- <0.02 <0.02 0 8 -- -- <0.02 <0.02 <0.02 <0.02 0 **Me tabolite**  **RPA 405862** Lima bean seeds without pods 1.05 - 1.10 2 -4 16 <0.02 <0.02 -- -- <0.02 <0.02 0 8 -- -- <0.02 <0.02 <0.02 <0.02 0 **Total Residues** Lima bean seeds without pods 16 0.02 0.035 0.02 0.025 8 0.02 0.035 0.02 0.025 1 Summary statistics do not include data from Trial ID # NC30 since an additional application was applied resulting in a different total application rate. 2 Where n=1 6 , statistics are based on trial samples; where n= 8 , statistics are based on trial averages. * LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial. Snap Beans (MRID 49052103) Eight trials were conducted in the US in the 2008 growing season. Fenamidone, formulated as Reason 500 SC, was applied to snap beans in 4 foliar broadcast or foliar directed applications, with RTIs of 6 - 8 days, for total application rates of 1.05 - 1.36 lbs a.i./A. A fifth application was added at the trial conducted in California (Trial ID # CA86) due to slow pod maturation; therefore, the total application rate was 1.36 lbs a.i./A. Fenamidone residues in snap bean pods with seeds ranged from 0.084 - 0.46 ppm when snap beans were treated with 4 foliar applications o f fenamidone and samples were harvested at 3 - 4 day P HI s. Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were all <0.02 ppm. Fenamidone residues decreased with increasing PHI when snap bean pods with seeds were harvested at PHIs of 1, 3, 7, and 13 days. Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were all <0.02 ppm in snap bean pods with seeds at all PHIs. At the trial conducted at the higher rate of 1.52 kg a.i./ha (1.36 lbs a.i./A) (Trial ID#CA86), fenamidone residues in snap bean pods with seeds ranged from 1.07 - 1.52 ppm when samples were harvested at a 3 - day P HI . Residues of the metabolites were all <0.02 ppm at this trial site. Fenamidone residues in snap bean p lants with pods ranged from 2.0 - 15.9 ppm when snap beans were treated with 4 foliar applications and samples were harvested at 3 - 4 day P HI s. Residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 ranged from <0.02 - 0.042, 0.046 - 0.17, and <0.02 - 0.094 ppm, respectively. Fenamidone residues decreased with increasing PHI when snap bean plants with pods were harvested at PHIs of 1, 3, 7, and 13 days (decline study). Residues of the metabolite RPA 717879 (DADK- Fen) were all <LOQ in residue decline samples. Average residues of the metabolite RPA 408056 (DA- Fen) were higher at the 13 - day PHIthan they were in the samples harvested at the 1 - day PHI. Average residues of the metabolite RPA 405862 appeared to stay about the same. At the trial cond ucted at the higher rate of 1.36 lbs a.i./A (Trial ID # CA86), fenamidone residues in snap bean pods with seeds ranged from 24 - 25 ppm when samples were harvested at a 3 - day PHI . Average residues of the metabolites RPA 717879 (DADK- Fen) , RPA 408056 (DA- Fen) , and RPA 405862 were 0.037, 0.096, and 0.11 ppm, respectively at the CA86 trial site.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 16 of 24 **TABLE 9.**  **Summary of Residue Data from Crop Field Trials with Fenamidone on Snap**  **Beans 1**  **.** Commodity Total Applic.

Rate (kg a.i./ha) [lb a.i./A] PHI

(days) Residue Levels (ppm) n2 Min. Max. LAFT * HAFT * Median (STMdR) Mean

(STMR) Std. Dev. **Fenam idone**  Snap bean pods with seeds 1.05 - 1.36 3 -4 14 0.084 0.46 -- -- 0.19 0.23 0.13 7 -- -- 0.097 0.46 0.19 0.23 0.13 Snap bean plants with pods 14 2.0 15.9 -- -- 7.58 8.09 4.47 7 -- -- 2.3 15.9 7.58 8.09 4.63 **Me tabolite**  **RPA 717879 (DADK -** **Fen)** Snap bean pods with seeds 1.05 - 1.36 3 -4 14 <0.02 <0.02 -- -- <0.02 <0.02 0 7 -- -- <0.02 <0.02 <0.02 <0.02 0 Snap bean plants with pods 14 <0.02 0.042 -- -- <0.02 < 0.023 0.008 7 -- -- <0.02 0.042 <0.02 0.023 0.008 **Me tabolite**  **RPA 408056 (DA -** **Fen)** Snap bean pods with seeds 1.05 - 1.36 3 -4 14 <0.02 <0.02 -- -- <0.02 <0.02 0 7 -- -- <0.02 <0.02 <0.02 <0.02 0 Snap bean plants with pods 14 0.046 0.17 -- -- 0.11 0.11 0.036 7 -- -- 0.047 0.17 0.11 0.11 0.037 **Me tabolite**  **RPA 405862** Snap bean pods with seeds 1.05 - 1.36 3 -4 14 <0.02 <0.02 -- -- <0.02 <0.02 0 7 -- -- <0.02 <0.02 <0.02 <0.02 0 Snap bean plants with pods 14 <0.02 0.094 -- -- 0.039 0.042 0 7 -- -- <0.02 0.094 0.039 0.043 0.025 1 Summary statistics do not include data from Trial ID # CA86 since an additional application was applied resulting in a different total application rate. 2 Where n=14, statistics are based on trial samples; where n=7, statistics are based on trial averages. * HAFT = Highest Average Field Trial. Onion, bulb, subgroup 3 - 07A (T. Bloem, D297216, 05/25/04) T olerances are established for garlic, bulb; garlic, great headed; onion, dry bulb; and shallot, bulb at 0.20 ppm. These are based on eight dry bulb onion trials in which fenamidone was foliarly applied six times at a single application rate of 0.178 lb ai/A, 5 - 9 day RTIf or a total rate of 1.05 - 1.09 lb ai/A . S amples were pulled at 3 to 7 days post treatment and cured in the field for 0 - 6 days prior to collection. The registrant proposes to use this data to establish a tolerance for onion, bulb, subgroup 3 - 07 A. B ased on the similarity o f the use pattern and adequacy o f the data the registrant proposal is appropriate.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 17 of 24 Onion, green, subgroup 3 - 07B (T. Bloem, D297216, 05/25/04) T olerances are established for onion, green; onion, welsh; leek; and shallot, fresh leaves at 1.5 ppm. These are based on four green onion trials in which fenamidone was foliarly applied six times at a single application rate of 0.178 lb ai/A, 6 - 8 day RTI for a total rate of 1.06 - 1.08 lb ai/A. Samples were harvested at a 7 - day PHI. The registrant proposes to use this data to esta blish a tolerance for onion, green , subgroup 3 - 07 B . Based on the similarity of the use pattern and adequacy

of the data the registrant proposal is appropriate. **Conclusions** The data presented here for the tolerance petition on ginseng, succulent beans, bulb onion (subgroup 3 - 07A), and green onion (subgroup 3 - 07B) are adequate. The residue data are supported by

the storage stability

and the analytical methods which were validated in the studies for both the parent and residues of concern s . Additionally, the number, geographical location and distribution of these crops were adequate to satisfy this tolerance petition. **5.3.2 Field**  **Rotational Crops (860.1900 )**  D357372, 2/24/09 , A. LaMay Rotational crop data have been submitted for field corn, sweet corn and soy beans and tolerances for inadvertent residues have been established. The rotational crop trials were considered adequate to support a plant back interval (PBI) of 30 days. Residues of conjugated RPA 405862 were not reported for fi eld corn, sweet corn, or soy bean rotation crops, but are a residue of concern in rotational crops for risk assessment purposes. In the absence of data on conjugated RPA 405862 , HED translate d information on the relative ratios of residues of conjugated RPA 405862 to RPA 717879 (DADK- Fen) from related crops to derive a conservative risk assessment. **5.3.3 Processed Food and Feed (860.1520)**  Field ginseng and lima/snap beans processing data were not submitted with this petition. For the purpose of this request for use on ginseng and lima/snap beans, detectable residues are not expected in processed commodities and tolerances for processed fiel d ginseng and lima/snap beans commodities are not required. **5.3.4 Meat, Milk, Poultry and Eggs**  **(860.1480)** D314318, 6/14/2007, T. Bloem Tolerances are currently established for livestock commodities. Cowpea forage and hay can be used as feed items to dairy cattle consisting of up to 20% of the diet . These feed items may contribute to the roughage content of the diet. To maintain a reasonably balanced diet, the constructed diet for dairy cattle includes 45% roughage, 45% carbohydrate, and 10% protein concentrate, consistent with the diet described in the Table 1 (June 2008) guidance. HED has previously

calculated a dietary

burden for dairy

cattle to support new uses in several crops including turnip (D352806, D. Davis, 12/18/2008). A dietary burden of 30.17 ppm wasFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 18 of 24 estimated for dairy

cattle ; however, the highest dose tested in the feeding study was 7.9 ppm which did not supported the new use in turnip . Considering the residue levels of fenamidone, RPA 717879 and RPA 408056 in/on cowpea hay and forage a dietary

burden of 22. 1 ppm is estimated , see Table 5 . **Table 4. Residue estimates for cowpea feedstuff comm odities.**  **Comm odity**  **Fenam idone**  **RPA 717879 RPA 408056**  **Residue (ppm)** Cow pea, hay 1 15.9 ppm * 86/30 0.042 ppm * 86/30 0.17 ppm * 86/30 46.19 Cow pea, forage 15.9 ppm 0.042 ppm 0.17 ppm 16.11 1 Residue data for cowpea hay is not available; therefore, the maximum residues in/on snap bean forage were translated to cowpea forage and then adjusted by the % of dry matter to estimate the residues in/on cowpea hay. **Table 5 .**  **Dietary Burden Calculations for Dairy Cattle** 

Crop 1 ,3 Residue

(ppm) 2 %Dry

Matter2 % Diet Residue in Diet (ppm)

Dairy Cattle Dairy Cattle Cowpea hay (R) 46.19 86 20 10.74 Cowpea forage (R) 16.11 30 20 10.74 Wheat hay (R) 3.16 88 5 0.18 Wheat milled byproducts (CC) 0.62 88 3 5 0. 24 Carrot (CC) 0.17 12 10 0.14 Cottonseed meal (PC) 0.08 89 10 0.01 Total **22. 1**  1 R= roughage; PC = protein concentrate; CC = carbohydrate concentrate. 2 For wheat, combined fenamidone, RPA 717879, and RPA 408056 (free and conjugated); inadvertent residues in wheat as a result of crop rotation; for calculation see D297216 , T. Bloem, 25 -May- 2004); for the other crops, combined fenamidone, RPA 717879, RPA 408056, and RPA 405862

– highest field trial value used for combined residues. 3 Turnip roots and tops are not included based on a label restriction for the use of turnip commodities to fed livestock (D366172, D. Davis, 06/16/2009 ). A l actating dairy

cattle feeding study was previously submitted and reviewed by HED (D297216, T. Bloem, 25 - May- 2004). The cattle were dosed with fenamidone for 35 days at dietary feeding levels of 0.8 ppm, 2.3 ppm , and 7.9 ppm. Milk was collected throughout the study and muscle, fat, liver, and kidney

were collected at sacrifice. Because of low residue levels, only samples from the 7.9 ppm dosing group were analyz ed. Following dosing of cattle with fenamidone for 35 days at 7.9 ppm , residues of fenamidone and its metabolites RPA 717879 and RPA 408056 were below the limit of detection (LOD = <0.0033 ppm each) in milk samples collected over the course of the dosing period and were <LOD (<0.017 ppm each) in samples of muscle, fat, liver, and kidney

collected at sacrifice. Quantifiable residues of fenamidone were observed in one sample of milk fat at 0.011 ppm; the other two samples bore detectable residues of fenamidone at levels below the LOQ (<0.01 ppm). Residues of RPA 717879 and RPA 408056 were <LOD (<0.0033 ppm each) in the milk fat samples. The current dietary

burden for dairy

cattle including the newly proposed use on succulent beans (i.e. including cowpea) would results in a dietary burden of 22 .1 ppm which exceeds the highe st dose tested in the lactating dairy cattle study

by 2. 8 - fold. HED concludes that it is not possible to determine if revised milk and meat tolerances might be required as a result of feeding dairy cattle cowpeas treated with fenamidone ; therefore, HED does not consider the cowpea use adequately supported b y residue data.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 19 of 24 **Conclusions:** A cowpea hay and forage feeding restriction is not considered practical. A ruminant feeding study reflecting a concentration in the diet which brackets the newly calculated MRBD would be required to support a use on cowpeas. In the absence of an appropriate feeding study, HED would recommend to establish a tolerance for bean, succulent, except cowpea. **6.0 Tolerance**  **Derivation** The Organization for the Economical Cooperation and Development (OECD) MRLc alculation procedures were used to determine the tolerances for ginseng and succulent beans . The procedures generate tolerances bas ed on mean field trial values . The spreadsheets for the various commodities can be found in Appendix C . The tolerance for ginseng was determined by using the crop field trial representing the multi - ye ar application. A tolerance of 0.8 ppm is recommended. For snap beans with seeds, the residue level from one field trial (CA86 Holtville, CA) was not included in the calculation for tolerance , mainly because an additional application was added to the crop due to slow pod maturation (1. 36 lbs a.i./A) . A tolerance of 0.8 ppm is recommended. For lima beans , the residue level from one field trial (NC30 ) was not included in the calculation for tolerance , mainly because an additional application was added to the crop due to slow pod maturation (1. 34 lbs a.i./A) . The tolerance for snap beans (po ds with seeds) and lima beans was estimated separately as 0.15 ppm and 0.8 ppm, respectively. S ince these estimated tolerances differ by a 5 x factor, HED is in favor of establishing a tolerance of 0.8 ppm for succulent beans (except cowpea) . HED rec ommends that the tolerances for onion, bulb, subgroup 3 - 07A and onion, green, subgroup 3 - 07B are established based on the current tolerances for the commodities under the respective groups in order to maintain harmonization with Canada; therefore, a reevaluation using the OECD procedures is not recommended at this time. **References** 49052102.der.doc . , Corley, J. (2012), Fenamidone: Magnitude of the Residue on Bean (Lima) . 49052103 .der.doc, Corley, J. (2012), Fenamidone: Magnitude of the Residue on Bean (Snap) . 49052101.der.doc , Corley, J. (2010), Fenamidone: Magnitude of the Residue on Ginseng. **Attachments** Appendix A. Field Trial Geographic Distribution Appendix B. International Residue Limits Table Appendix C. OECD MRL Calculation Procedure Inputs/OutputsFenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 20 of 24 **Appendix A**  **. Field Trial Geographic Distribution**  **TABLE 1 Trial Numbers and Geographical Locations**  . NAFTA Growing Zones Ginseng

Submitted Requested

Canada * U.S. 5 1 1 5A 3 -- 11 -- 1 12 1 -- **Total 5**  **2** * According to DIR98 - 02. **TABLE 2**  **Trial Numbers and Geographical Locations** . NAFTA Growing Zones Snap beans

Submitted Requested

Canada * U.S. 1 1 -- 1A -- 1 2 1 -- 3 1 -- 5 -- 2 5A 3 -- 5B -- 2 10 1 1

-- 12 1 -- **Total 8**  **5** * Trial requirements in DIR98 - 02 are listed for “green or wax beans”. 1 The trial at this site was conducted at a higher rate than the other trials. **TABLE 3**  **Trial Numbers and Geographical Locations** . NAFTA Growing Zones Lima beans

Submitted Requested

Canada * U.S. 1A -- 1 2 5 1

-- 5 -- 2 5A 1 -- 5B -- 2 10 2 -- 11 1 -- **Total 9**  **5** * Trial requirements in DIR98 - 02 are listed for “green or wax beans”. 1 An additional application was applied at one trial site resulting in a different total application rate compared to all other trials.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 21 of 24 **Appendix B**  **. International Residue Limits Table** Table B1. Summary of US and International Tolerances and Maximum Res idue Limits for Fenamidone (PC Code: 046679 ) Residue Definition : US Canada Mexico 2 Codex 40 CFR 180.579: Plants: fenamidone (4H - Imidazol -4 - one, 3,5 - dihydro - 5 - methyl - 2 - (methylthio) - 5 -phenyl - 3 (phenylamino) - , (S) - ) Livestock: fenamidone (4H - imidazol -4 - one, 3,5 - dihydro 5 - methyl - 2 - (methylthio) - 5 -phenyl - 3 - (phenylamino), (S) - ) and its metabolite RPA 717879 (DADK-Fen) (2,4 - imidazolidinedione, 5 - methyl - 5 -phenyl), expressed as parent compound Indirect or inadvertent residues: . fenamidone (4 - H imidazol -4 - one, 3,5 - dihydro - 5 - methyl - 2 - (methlthio) - 5 - phenyl - 3 - (phenylamino, (S) - ) and its metabolite RPA 717879 (DADK-Fen) (2,4 - imidazolidinedione, 5 - methyl 5 -phenyl) (5 S ) - 3,5 - dihydro - 5 - methyl - 2 - (methylthio) - 5 - phenyl - 3 - (phenylamino) -4 H imidazol -4 - one None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Ginseng 0. 8 0.15 ginseng roots 3 Beans, Succulent , except cow pea 0.8 Onion, bulb, subgroup 03 - 07A 0.20 0.2 Chinese, onions; Daylilies; dry bulb onions; fritillaria, bulbs; garlic; great-headed garlic; lilies; pearl onions, potato onions; serpent garlic, shallot bulbs onion, green, subgroup 03 - 07B 1.5 1.5 Beltsville bunching onions, elegans hosta, fresh (Chinese chive leaves, chive leaves), fresh onions, fritillaria leaves, green onions, kurrats, lady's leek, leeks, macrostem onions, shallot leaves, tree onion tops, Welsh onion tops, wild leeks Com pleted: M. Negussie; 09/16/2013 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 3 Identical regulatory levels are recommended by EPA and PMRA as part of this joint review (0.08 ppm).Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 22 of 24 **Appendix C**  **. OECD MRL Calculation Procedure**  **Inputs/Outputs Compound**  **Fenamidone Fenamidone**  **Fenamidone Fenamidone**  **Crop Ginseng**  **Lima Beans Snap beans**  **(pots with seeds)**  **Snap Beans**

**(plants with pods)**  **Region / Country USA**  **USA USA**  **USA GAP**  **2.78 1.1**  **1.36 1.36**  **Total number of data (n)**  5 8 7 7 **Percentage of censored data**  0% 5 0 % 0% 0% **Number of non**   ** censored data** 5 4 7 7 **Lowest residue** 0.027 0.020 0.100 2.300 **Highest residue** 0.350 0.080 0.460 15.900 **Median residue** 0. 1 70 0.020 0.190 7.580 **Mean** 0. 1 86 0.0 39 0.234 8.101 **Standard deviation (SD)**  0. 13 4 0.02 6 0.132 4.647 **Correction factor for**  **censoring (CF)** 1.000 0.667 1.000 1.000 **Proposed MRL estimate** 

**- Highest**  **residue** 0.350 0.080 0.460 15.900

**- Mean + 4 SD**  0. 721 0.1 44 0.764 26.690

**- CF x 3 Mean**  0. 559 0. 078 0.703 24.304 **Unrounded MRL** 0. 721 0.1 44 0.764 26.690 **Rounded MRL 0.**  **8 0.15**  **0.8 30**  High uncertainty of MRL estimate due to small dataset. High

uncertainty of MRL estimate due to high level of censoring. High

uncertaint y of MRL estimate due to small dataset. High

uncertaint y of MRL estimate due to small dataset.Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 23 of 24 **Residues (mg/kg)**  **Residues**

**(mg/kg) Residues** 

**(mg/kg) Residues** 

**(mg/kg)** 0.170 0.020 0.110 2.300 0.095 0.020 0.280 5.600 0.027 0.080 0.460 15.900 0.290 0.040 0.160 11.000 0.350 0.080 0.100 4.130

0.020 0.340 7.580 0.020 0.190 10.200 0.0 30 **Note:** If an acceptable feeding study is submitted a tolerance of 30 ppm would be appropriate for cowpea forage based on the data for snap beans (plants with pods).Fenamidone Summary of Analytical Chemistry and Residue Data Barcode D 4 10422

Page 24 of 24 **Appendix D : Chemical Structures** 

**Nam e**  **Structure Fenamidone**  ; RPA 407213 (5 S ) - 3,5 - dihydro - 5 -methyl - 2 - (methylthio) - 5 -phenyl - 3 - (phenylamino) - 4H

- imidazol - 4 - one

**DA -** **Fen;** RPA 408056 (racemic mixture) 5 -methyl - 2 - methylthio - 5 -phenyl - 3,5 - dihydroimidazol - 4 - one RPA 405862 (racemic mixture) RPA 410193 (S enantiomer) 5 -methyl - 5 -phenyl - 3 -phenylamino - imidazolidin-2,4 - dione

**DADK -** **Fen ;**  RPA 717879 (racemic mixture) 5 -methyl - 5 -phenylimidazolidine-2,4 - dione RPA 413255 (5 S ) - 5 -methyl - 2 - (methylthi o ) - 3 - [(2 -nitrophenyl)amino] - 5 - phenyl - 3,5 - dihydro - 4H

- imidazol -4 - one RPA 410914 (racemic mixture) N N C H3 O S C H 3 N H

N N CH 3 O S C H 3 H

N H N C H 3 O O N H

N

H N C H 3 O O H