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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

MEMORANDUM

Date: 15-May-2020

OFFICE OF CHEMICAL SAFETY ANO POLLUTION PREVENTION

Subject: Oxathiapiprolin. Petition for the Establishment of Pennanent Tolerances and Registration for Use on Bushbeny Crop Subgroup 13-07B (Except Lowbush Bluebeny), Hops, Low Growing Beny Crop Subgroup 13-07G (Except Cranbeny), Tree Nut Crop Group 14-12, and Tropical and Subtrnpical Medium to Large Frnit with Smooth Inedible Peel Crop Subgroup 24B, as well as Tolerance Translations. Summa1y of Analytical Chemistiy and Residue Data.

PC Code: 128111 Decision Nos.: 548484, 550162 Petition Nos.: 9F8736, 9E8755 Risk Assessment Type: NA TXRNo.: NA MRID Nos: See table, page 2

DP Barcodes: D451052, D455262 Registration Nos.: 100-1571, 100-1614, 100-1612 Regulato1y Action: Section 3 Registration Case No.: NA CAS No.: 1003318-67-9 40 CFR: § 180.685

From: Jack Giordano, Chemist ,1kf). Jt~ Risk Assessment Branch II (RAB2) Health Effects Division (HED; 7509P)

Through: Michael A Doherty, Ph.D., Senior Chemist~~ Douglas Dotson, Ph.D. , Senior Chemist ,Je.~,,f .,,,,, a. JJ.t;. RAB2; HED (7509P) ~-r~~ ~ rJ,C?)

To: Laura Bacon, Acting Branch Chief ofMUERB Nancy Fitz, Minor Use Team Leader Tamica Cain, Reviewer Registration Devision (RD; 7505P)

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Oxathiapiprolin [128111] Summary of Analytical Chemistiy and Residue Data D451052, D455262

Summa1-y of Submitted Residue Chemish-y Studies OCSPP 860 Series MRID Refe1·ence Guideline Numbel'

860.1500 50683001 S, Dorsey (2017). Oxathiapiprolin (A2 l 008A) - Magnitude of the Residues in Bluebeny, USA, 2016. Analytical Bio-Chemistiy Laboratories, Inc Report Number TK024448 l. Unpublished study prepared by Syngenta Crop Protection, LLC. Greensboro, NC, USA. 176 p.

860.1500 50683002 S, Dorsey (2018) Magnitude of Residues ofOxathiapiprolin OD (A20941A) and Mefenoxam SL (A13947A) in Tree Nuts - Pecans and Almonds, USA, 2016. Analytical Bio-Chemistiy Laboratories. Analytical Bio-Chemistiy Laboratories, Inc Report Number TK0244482. Unpublished study prepared by Syngenta Crop Protection, LLC. Greensboro, NC, USA. 346 p.

860.1500 50615201 Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on Sti·a:wbeny. Study Numbers : 11719; ll 719.15-MIR16. Unpublished study prepared and submitted by Inten-egional Research Project Number 4. 198 p.

860.1500 50615202 Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on Avocado. Study Numbers : 11795; l l 795.16-MIR09. Unpublished study prepared and submitted by Inten-egional Research Project Number 4. 153 p.

860.1500/860.1520 50615203 Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on Pomegranate. Study Numbers : 10915; 10915.15-MIR16; 10915.15-IDP07. Unpublished study prepared and submitted by Intel1'egional Research Project Number 4. 201 p.

860.1500 50615204 Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on Hops. IR-4 Project Number: 117 59, Analytical Laborat01y Identification Number: 11759. 16-CARl 7. Unpublished Study Prepared by IR-4, Princeton, NJ, USA. 230 p.

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Oxathiapiprolin [128111] Summary of Analytical Chemistry and Residue Data D451052, D455262

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Table of Contents 1.0 Executive Summary ............................................................................................................ 4 2.0 Regulatory Recommendations ............................................................................................ 5

2.1 Data Deficiencies/Data Needs .......................................................................................... 5 2.2 Tolerance Considerations ................................................................................................. 5

2.2.1 Enforcement Analytical Method ............................................................................... 5 2.2.2 Recommended Tolerances ........................................................................................ 6 2.2.3 Revisions to Petitioned-For Tolerances .................................................................... 8 2.2.4 International Harmonization ..................................................................................... 8

3.0 Introduction ......................................................................................................................... 9 3.1 Chemical Identity ............................................................................................................. 9 3.2 Physical/Chemical Characteristics ................................................................................. 10 3.3 Pesticide Use Pattern/Directions for Use (860.1200) ..................................................... 10

4.0 Metabolite/Degradate Residue Profile .............................................................................. 13 4.1 Nature of the Residue ..................................................................................................... 13

5.0 Residue Profile .................................................................................................................. 13 5.1 Residue Analytical Methods (860.1340) ........................................................................ 13

5.1.1 Data Collection Methods ........................................................................................ 13 5.1.2 Multi-Residue Methods (860.1360) ........................................................................ 14 5.1.3 Tolerance Enforcement Methods ............................................................................ 14 5.1.4 Submittal of Analytical Reference Standards (860.1650) ...................................... 14

5.2 Storage Stability (860.1380) .......................................................................................... 14 5.3 Residue Data .................................................................................................................. 15

5.3.1 Crop Field Trials (860.1500) .................................................................................. 15 5.3.2 Field Rotational Crops (860.1900) ......................................................................... 21 5.3.3 Processed Food and Feed (860.1520) ..................................................................... 22 5.3.4 Meat, Milk, Poultry and Eggs (860.1480) .............................................................. 22 5.3.5 Food Handling (860.1460) ...................................................................................... 22 5.3.6 Water, Fish, and Irrigated Crops (860.1400) .......................................................... 23

5.4 Food Residue Profile ...................................................................................................... 23 6.0 Tolerance Derivation ........................................................................................................ 23 7.0 References ......................................................................................................................... 24 Appendix A. Field Trial Geographic Distribution ........................................................................ 25 Appendix B. International Residue Limits Table ......................................................................... 26 Appendix C. OECD MRL Calculation Procedure Inputs/Outputs ............................................... 27 Appendix D. Anticipated Residues in Livestock Tissues ............................................................. 32

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1.0 Executive Summary Oxathiapiprolin (with CAS name 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone) is a piperidinyl thiazole isoxazoline fungicide for control of crop diseases caused by oomycetes (downy mildew and late blight). Oxathiapiprolin acts as an oxysterol-binding protein modulator in fungal cells. Syngenta is proposing new uses and establishment of tolerances for the active ingredient (ai) on bushberry crop subgroup 13-07B (except lowbush blueberry) and tree nut crop group 14-12 under petition #9F8736. Simultaneously, the Interregional Research Project #4 (IR-4) is proposing new uses and establishment of tolerances for the ai on hops, low growing berry crop subgroup 13-07G (except cranberry), and tropical and subtropical medium to large fruit with smooth inedible peel crop subgroup 24B under petition #9E8755. Furthermore, IR-4 is requesting translation of existing tolerances for residues in edible podded peas and succulent shelled peas to individual edible podded pea and succulent shelled pea commodities that are to be included in the forthcoming edible podded pea and succulent shelled pea subgroups of the legume vegetables crop group. HED is assessing the new use for hops as a work-share with Canada’s Pest Management Regulatory Agency (PMRA). Three registered end-use products are proposed for use on the various crops requested by the petitioners. Orondis® (EPA registration # 100-1571) is a suspension concentrate (SC) formulation containing 1.67 pounds of the active ingredient per gallon (lb ai/gal), equal to 200 grams of the ai per liter (g ai/L), and is alternatively sold as Orondis® Gold 200. Orondis® Gold (EPA registration # 100-1614) is a dispersable concentrate (DC) formulation containing 0.29 lb ai/gal (35 g ai/L). Orondis® Ultra (EPA registration # 100-1612) is an SC formulation containing 0.25 lb ai/gal (30 g ai/L). Nature of the Residue: The sole residue of concern for tolerance enforcement is oxathiapiprolin. Residues of concern for risk assessment are unnecessary due to the low toxicity of the compound. Residue Analytical Methods: There are adequate analytical methods available for enforcement and data gathering purposes for oxathiapiprolin. Crop Field Trial and Processing Studies: Field trials and a processing study were conducted in accordance with the proposed labels and on appropriate commodities to support the petitioned-for uses and tolerances. Storage Stability: Adequate storage stability data are available for oxathiapiprolin that support the storage durations and conditions of samples from the submitted field trials and processing study. Meat, Milk, Poultry, and Eggs: There is no expectation of quantifiable residues in livestock tissues (i.e., §180.6(a)(3) situation).

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International Harmonization: There are no international harmonization issues associated with the petitioned-for tolerances. 2.0 Regulatory Recommendations HED examined the residue chemistry database for oxathiapiprolin. Provided that Syngenta and IR-4 each submit a revised Section F in order to propose correct commodity definitions as recommended by HED, there are no residue chemistry issues that would preclude granting the requested registrations and establishing the recommended tolerances for oxathiapiprolin. Specific commodity definition recommendations are discussed in Section 2.2, and label modifications are discussed in Section 2.3. Note to RD: Upon establishment of the tolerances in/on individual edible podded pea commodities at 0.1 ppm (dwarf pea, edible podded pea, green pea, snap pea, snow pea, sugar snap pea, grass-pea, lentil, pigeon pea, and chickpea), the currently established tolerance for Pea, edible-podded should be removed. Note to RD: Upon establishment of the tolerances in/on individual succulent shelled pea commodities at 0.05 ppm (chickpea, English pea, garden pea, green pea, pigeon pea, and lentil), the currently established tolerance for Pea, succulent shelled should be removed. Note to RD: The individual edible podded pea and succulent shelled pea commodities align with commodities in HED’s Chemistry Science Advisory Council (ChemSAC)-approved updates to the legume vegetables groups/subgroups; specifically the forthcoming subgroups consisting of edible podded peas and succulent shelled peas. 2.1 Data Deficiencies/Data Needs None. 2.2 Tolerance Considerations 2.2.1 Enforcement Analytical Method Residue Chemistry Summary Document D426128, E. Holman, 29-APR-2015 Tolerance Enforcement Method For Crops Analytical method DuPont-30422, Supplement 1 is a high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method available for the quantitation of oxathiapiprolin residues in plant matrices. Method DuPont 30422, Supplement 1 underwent successful independent laboratory validation (ILV). The solvent used for extraction was shown to efficiently extract incurred residues in the metabolism studies. Briefly, residues of oxathiapiprolin are extracted from crop samples using a solution of formic acid, water, and acetonitrile, and diluted with aqueous formic acid solution and methanol. An aliquot of supernatant is filtered, centrifuged, and analyzed by reverse-phase HPLC-MS/MS in positive ion mode. The limit of quantitation (LOQ), defined as the lowest level of method validation (LLMV), was determined to be 0.02 ppm for hops and 0.01 ppm for all other matrices.

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5.1.2 Multi-Residue Methods (860.1360) See Section 2.2.1 5.1.3 Tolerance Enforcement Methods See Section 2.2.1. 5.1.4 Submittal of Analytical Reference Standards (860.1650) The analytical standard for oxathiapiprolin, with an expiration date of 30 June 2024, is currently available in the EPA’s National Pesticide Standards Repository (NPSR), via electronic communication between G. Verdin of the Analytical Chemistry Branch of the Biological and Economic Analysis Division (ACB/BEAD) and J. Giordano on 27-Nov-2019. The registrant is required to maintain reasonable amounts of the analytical reference standard for oxathiapiprolin in the NPSR. When necessary, a new reference standard or updated certificate of analysis (COA) should be sent to 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 will 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 analytical method used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for safe handling. Replacement of standards may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage. Material Safety Data Sheets (MSDSs) must accompany all analytical standards as specified in 29CFR§1910.1200 by the Occupational Safety and Health Administration (OSHA). 5.2 Storage Stability (860.1380) Residue Chemistry Summary Document D426128, E. Holman, 29-APR-2015

Low Growing Berries (Strawberries): 50615201.der Tropical and Subtropical Fruits (Avocados and Pomegranates): 50615202.der and 50615203.der

Adequate storage stability data were previously submitted that show that oxathiapiprolin residues are stable for at least 18 months in various crop commodities (high-water content, high-starch content, high-acid content, high-protein content, high-oil content, and very dry content) when maintained under frozen storage conditions (D426128, E. Holman, 29-APR-2015). Additional concurrent storage stability data were generated for strawberry, avocado, pomegranate fruit, and pomegranate juice along with the field trials and processing study.

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The crop field trials were conducted at approximately the maximum seasonal application rate, minimum RTI, and minimum PHI specified on the proposed labels. The OD formulation is adequate for the proposed use on the SC and DC labels because Syngenta previously submitted residue bridging studies on broccoli, cauliflower, cucumber, potato, and tobacco showing equivalence of residues after application of an OD and SC formulation (D434522, W. Drew, 14-OCT-2016). As such, the submitted field trials are appropriate for tolerance establishment. Pomegranate - 50615203.der IR-4 submitted field trial data for oxathiapiprolin on pomegranate from four field trials conducted in the U.S. during the 2015 and 2016 growing seasons. See Appendix A for field trial locations. Each trial was treated with a 0.83 lb ai/gal (100 g ai/L) OD formulation of oxathiapiprolin. All trials received a combination of two soil applications (directed spray or drench) followed by two foliar directed applications. At one trial location, an additional treated plot received only two soil applications. Soil applications were made at 0.125-0.128 lb ai/A/application (140-143 g ai/ha/application), at an RTI of 27-31 days, for total soil application rates of 0.250-0.255 lb ai/A (280-286 g ai/ha). Foliar applications were made 27-31 days after the second soil application. Foliar applications were made at a rate of 0.0308-0.0318 lb ai/A/application (34.5-35.6 g ai/ha/application) and with an RTI of 13-14 days between applications. Total application rates for the soil and foliar applications were 0.313-0.318 lb ai/A (351-356 g ai/ha). An adjuvant was added to the spray mixture for the foliar applications at three of the four trials; no adjuvant was used for soil applications at all trials or for the foliar applications at the fourth trial. Duplicate treated samples of pomegranate were harvested at a PHI of 27-29 days following the second soil application (prior to foliar applications), and at a 1-day PHI following the second foliar application. At one trial location, additional samples were collected at PHIs of 9, 15, and 20 days from the soil application plot and PHIs of 0, 3, 7, and 9 days from the soil plus foliar application plot to assess residue decline. The maximum storage intervals for samples between harvest and extraction for analysis were 650 days (21 months). Samples were analyzed within 6 days of extraction. Although samples were stored for 2.0 months longer than the concurrent storage stability study for pomegranates, given that good recoveries were observed after 19 months of frozen storage, it is not anticipated that residues in pomegranate matrices would have degraded below acceptable levels during the additional storage sample time. Therefore, storage stability data support the storage durations and conditions. Following the last of four applications (combination of soil and foliar applications) and a 1-day PHI, residues of oxathiapiprolin in/on individual samples of pomegranate were 0.0239-0.0371 ppm, corresponding to per-trial average residues of 0.0261-0.0356 ppm. For pomegranate harvested at a PHI of 27-29 days following the second soil application (prior to foliar applications), all residues were below the LOQ (<0.01 ppm). In the decline trial, average oxathiapiprolin residues generally declined in/on pomegranate with increasing PHI following combined soil and foliar applications. Residues were below the LOQ at

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5.3.3 Processed Food and Feed (860.1520) Pomegranate Juice 50615203.der IR-4 submitted a study investigating the concentration of oxathiapiprolin residues in pomegranates when processed into juice. At one trial location, pomegranates were treated with a 0.83 lb ai/gal (100 g ai/L) OD formulation of oxathiapiprolin in a combination of two soil applications (directed spray or drench) followed by two foliar directed applications. Soil applications were made at 0.128 lb ai/A/application (143 g ai/A/application) at an RTI of 30 days. The first foliar application was made 31 days after the second soil application. Foliar applications were made at a rate of 0.0310-0.0318 lb ai/A/application (34.7-35.6) and with an RTI of 14 days. The total application rate for the soil and foliar applications was 0.318 lb ai/A (356 g ai/ha). Pomegranate samples were harvested with a 1-day PHI. Samples were processed into juice within two days of harvest. The maximum storage interval for samples between harvest and extraction for analysis was 588 days (19 months). Samples were analyzed within 6 days of extraction. Adequate data are available to support the sample storage conditions and durations from the processing study. Oxathiapiprolin residues were 0.0207 ppm in/on fruit collected prior to processing and <0.01 ppm in processed juice. Residues did not concentrate in pomegranate juice (processing factor of <0.5x). There are no theoretical concentration factors listed in OCSPP 860.1520 for pomegranate. 5.3.4 Meat, Milk, Poultry and Eggs (860.1480) Residue Chemistry Summary Document D426128, E. Holman, 29-APR-2015 Almond hulls are considered a major livestock feedstuff. As such, HED recalculated the livestock maximum reasonable dietary burdens (MRDBs), including all existing and proposed tolerances on livestock feedstuffs, including the tolerance of 0.10 ppm for inadvertent residues in/on all rotational crops. The resulting MRDBs were 0.37 ppm for beef cattle, 0.4 ppm for dairy cattle, 0.1 ppm for poultry, and 0.1 ppm for swine. The previously submitted livestock metabolism studies show that oxathiapiprolin residues do not tend to transfer to livestock tissues (D426128, E. Holman, 29-APR-2015). Due to the low MRDBs and low tissue to feed transfer ratios, livestock feeding studies and tolerances for residues in livestock tissues are not needed at this time. See Appendix D for the MRDB diets, the tissue to feed transfer factor calculations, and the anticipated residues in livestock tissues. Conclusions: Due to the low MRDBs and tissue to feed ratios, there is no expectation of quantifiable residues in livestock tissues (i.e., §180.6(a)(3)). 5.3.5 Food Handling (860.1460) There are no proposed uses that are relevant to this guideline topic.

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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 The submitted field trials and processing study are adequate for supporting regulatory conclusions and for establishing appropriate tolerance levels for enforcement. Analysis of residues can be accomplished through standard analytical techniques, and residues do not show any trends for dissipation during frozen storage. One or more of the samples from all submitted field trials contained quantifiable oxathiapiprolin residues, with the exception of tree nut nutmeats, which all contained residues less than the LOQ (<0.01 ppm). The registrant submitted residue decline data that generally demonstrated that residues of oxathiapiprolin decrease with an increasing PHI. All field trial and processing study results are supported by adequate storage stability data, and the studies were conducted using the validated analytical enforcement method. Oxathiapiprolin translocation appears to occur following foliar and soil applications, as there is uptake of oxathiapiprolin by both foliage and roots. In general, oxathiapiprolin residues do not tend to concentrate in processed fractions, other than via dehydration or from surface residues. Residues are not expected in livestock tissues. 6.0 Tolerance Derivation HED used field trial data and the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedure to determine recommended tolerance levels for almond hulls (0.05 ppm), bushberry crop subgroup 13-07B except lowbush blueberry (0.5 ppm), hops (5 ppm), low growing berry crop subgroup 13-07G except cranberry (0.4 ppm), and tropical and subtropical medium to large fruit with smooth inedible peel crop subgroup 24B (0.1 ppm). See Appendix C for field trial residue values and OECD tolerance calculations. For tree nut crop group 14-12, the HED-recommended tolerance is the LOQ (0.01 ppm), because all field trial residue values were below the LOQ. HED’s ChemSAC recently concurred with proposed revisions to the legume crop group (Crop Group 6). Part of that revision includes establishing separate edible podded, succulent shelled, and dried subgroups each, for beans and peas. As the crop group update has not become officially established, HED concurs with the petitioner’s request to translate the currently established tolerance for residues of oxathiapiprolin on edible podded peas (1 ppm) to the members of the HED-approved subgroup for edible podded peas. Similarly, HED concurs to translate the established tolerance for residues of oxathiapiprolin on succulent shelled peas (0.05 ppm) to the HED-approved subgroup for succulent shelled peas. HED is not establishing a separate tolerance for pomegranate juice, as the processing data demonstrate that the 0.1 ppm tolerance for crop subgroup 24B is adequate to cover residues in pomegranate juice.

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7.0 References Drew, W. 14-OCT-2016. D434522. Oxathiapiprolin. Petition Proposing the Establishment of

Permanent Tolerances and Section 3 Registration for New Uses of the Fungicide on Various Crops. Summary of Analytical Chemistry and Residue Data.

Holman, E. 29-APR-2015. D426128. Oxathiapiprolin. Petition for the Establishment of

Permanent Tolerances and Registration for Use of the New Active Ingredient on a Number of Crops. Summary of Analytical Chemistry and Residue Data.

Negrón-Encarnación, I., 29-APR-2015. D425280. Oxathiapiprolin. Report of the Residues of

Concern Knowledgebase Subcommittee (ROCKS).

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Oxathiapiprolin [PC Code 128111]/ Interregional Research Project Number 4

EPA MRID #: 50615201 Page 1 of 11

DATA EVALUATION RECORD

OXATHIAPIPROLIN

Study Type: OCSPP 860.1500, Crop Field Trial/Residue Decline

EPA Contract No. EP-W-16-018 Task Assignment Form No. 23-2-012 (MRID 50615201)

Prepared for Health Effects Division

Office of Pesticide Programs U.S. Environmental Protection Agency

2777 South Crystal Drive Arlington, VA 22202

Prepared by

10560 Arrowhead Dr., Suite 500

Fairfax, VA 22030

Primary Reviewer: Signature: Tara K. B. Johnson, M.E.A. Date: 9/10/19 Secondary Reviewer: Signature: Sandra Hastings Date: 9/11/19 Quality Assurance: Signature: Kelly Luck, M.Sc. Date: 9/24/19 Project Manager: Signature:

Jack D. Early, M.S. Date: 9/25/19

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B.7.6 Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IIIA 8.3) B.7.6.1 Residues in Target Crops B.7.6.1.1 Strawberry Document ID: MRID No. 50615201 Report: Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on Strawberry.

Study Numbers: 11719; 11719.15-MIR16. Unpublished study prepared and submitted by Interregional Research Project Number 4. 198 p.

Guidelines: EPA OCSPP Harmonized Test Guideline 860.1500 Crop Field Trials (August 1996)

PMRA Regulatory Directive DIR98-02 – Residue Chemistry Guidelines, Section 9 – Crop Field Trials

PMRA Regulatory Directive DIR2010-05 – Revisions to the Residue Chemistry Crop Field Trial Requirements

OECD Guideline 509 Crop Field Trial (September 2009) GLP Compliance: No deviations from regulatory requirements were reported which would

have an impact on the validity of the study. Acceptability: The study is considered scientifically acceptable. The acceptability of this

study for regulatory purposes is addressed in the forthcoming U.S. EPA Residue Chemistry Summary Document, DP#s D451052, D455262.

Evaluator: Jack Giordano, Chemist, RAB2 Note: This Data Evaluation Record (DER) was prepared under contract by CDM/CSS-Dynamac Joint Venture (submitted 25-Sep-2019). The CDM/CSS-Dynamac Joint Venture role does not include establishing Agency policies. The DER has been reviewed by HED and revised as necessary to reflect current Office of Pesticide Programs (OPP) policies. EXECUTIVE SUMMARY Interregional Research Project Number 4 (IR-4) and Agriculture and Agri-Food Canada (AAFC) submitted field trial data for oxathiapiprolin on strawberry from 10 field trials conducted in the United States and Canada during the 2016 and 2017 growing seasons. Trials were conducted in North American Free Trade Agreement (NAFTA) Growing Zones 1 (NY; 1 trial), 1A (NS; 1 trial), 3 (FL; 1 trial), 5 (OH; 1 trial), 5B (QC; 1 trial), 10 (CA; 3 trials), and 12 (BC and OR; 2 trials). Each trial consisted of one untreated plot and one treated plot reflecting a combination of two soil applications (directed spray or drip/chemigation) followed by two foliar applications (broadcast or directed spray) of a 0.83 lb ai/gal (100 g ai/L) oil dispersion (OD) formulation of oxathiapiprolin, made at 6- to 9-day retreatment intervals (RTIs). The soil applications were made at 0.141-0.148 lb ai/A/application (158-166 g ai/ha/application) and the foliar applications were made at 0.0305-0.0334 lb ai/A/application (34.2-37.4 g ai/ha/application) for total seasonal rates of 0.350-0.356 lb ai/A (392-399 g ai/ha). Applications were made using ground equipment in volumes of 32-66 gal/A (299-617 L/ha) for spray applications; application volumes were not

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reported for drip/chemigation applications. An adjuvant (nonionic surfactant or citrus oil solution) was added to the spray mixture for each application at all trials. Duplicate treated samples of strawberry were harvested at a preharvest interval (PHI) of 0 days. In one trial, samples were collected at additional PHIs of 1, 3, 6, and 10 days to assess residue decline. Samples were maintained frozen at the field sites, during shipping, and at the laboratory prior to analysis. The maximum storage interval for samples between harvest and extraction for analysis was 12.0 months. Samples were analyzed within 7 days of extraction. To support sample storage durations, a concurrent storage stability study was conducted using untreated samples of strawberry. The data demonstrate that residues of oxathiapiprolin are stable during frozen storage in strawberry for at least 11.0 months. In addition, acceptable storage stability data are available demonstrating the stability of oxathiapiprolin residues in all OECD representative crop commodities (high water content, high oil content, high protein content, high starch content, and high acid content) during frozen storage for at least 18 months (D426128; 29-Apr-2015; E. Holman). These data are acceptable to support the storage conditions and durations of the samples from the submitted field trials. Samples were analyzed for residues of oxathiapiprolin using a working method based on DuPont-30422, Supplement No. 1, a high-performance liquid chromatography method with tandem mass spectrometry detection (LC-MS/MS). Method DuPont-30422, Supplement No. 1, is the tolerance enforcement method for plant commodities (D426128; 29-Apr-2015; E. Holman). The limit of quantitation (LOQ), determined as the lowest level of method validation (LLMV), was 0.01 ppm. Acceptable method validation and concurrent recoveries were obtained from samples of strawberry fortified with oxathiapiprolin at 0.01-1.0 ppm. The fortification levels adequately bracketed measured residue levels. Following the last of four applications (combination of soil and foliar applications) totaling 0.350-0.356 lb ai/A (392-399 g ai/ha), residues of oxathiapiprolin in/on individual samples of strawberry were 0.0489-0.213 ppm at a 0-day PHI, and the corresponding per-trial average residues were 0.0508-0.207 ppm. In the residue decline trial, oxathiapiprolin residues declined in/on strawberry as the PHIs increased.

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field sites prior to shipment by freezer truck to the analytical laboratory, IR-4 North Central Region Laboratory (Lansing, MI). At the laboratory, samples were homogenized in the presence of dry ice and stored frozen (ca. <-20°C) until extraction for analysis. 2. Description of Analytical Procedures Samples were analyzed for residues of oxathiapiprolin by LC-MS/MS using a working method based on DuPont-30422, Supplement No. 1, titled “Analytical Method for the Determination of DPX-QGU42 and Metabolites in Crops Using LC-MS/MS.” Method DuPont-30422, Supplement No. 1, is the tolerance enforcement method for plant commodities (D426128; 29-Apr-2015; E. Holman). Modifications to the cited method included substitutions for the final dilution solvent and LC-MS/MS mobile phases. A complete description of the working method was included in the submission. Briefly, samples were soaked in water for 5 minutes then extracted (3x) with water:acetonitrile (ACN):1% formic acid (4:12:0.1, v:v:v for extractions 1 and 2, and 3:9:0.1, v:v:v for extraction 3). The extracts were isolated by centrifugation, combined, and adjusted to volume with ACN. An aliquot of the extract was filtered through a 0.2-µm PTFE membrane filter, adjusted to volume with 1% formic acid, and applied to an Envi-Carb solid phase extraction column. The column was rinsed with 1% formic acid:ACN (75:25, v:v) followed by ACN, then residues were eluted with acetone followed by toluene:methanol:1% formic acid (90:10:1, v:v:v). The eluate was evaporated to dryness under nitrogen, and residues were reconstituted in methanol and adjusted to volume with 1% formic acid for LC-MS/MS analysis. The following transitions were monitored: m/z 540 → 499.9 for quantitation and m/z 540 → 163.1 for confirmation. The LOQ (determined as the LLMV) was 0.01 ppm; a limit of detection was not reported. II. RESULTS AND DISCUSSION Method performance was evaluated by use of method validation and concurrent recovery samples of strawberry fortified with oxathiapiprolin at 0.01-1.0 ppm. Individual recoveries were within the acceptable range of 70-120%; therefore, the method is considered valid for the determination of residues of oxathiapiprolin in/on strawberry (Table B.7.6.1.1-4). The fortification levels adequately represented the measured residues. Concurrent recoveries were not corrected for apparent residues in/on controls. The detector response was linear (coefficient of determination, r2 ≥0.9935) within the range of 0.07-7.0 ng/mL. Representative chromatograms of control samples, fortified samples, and treated samples were provided. The control chromatograms generally had no peaks of interest above the chromatographic background. The fortified sample chromatograms contained only the analyte of interest, and peaks were symmetrical and well defined. Apparent residues in/on controls were below the LOQ (0.01 ppm).

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Appendix I. Soil Characteristics for Strawberry Field Trials with Oxathiapiprolin.

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Oxathiapiprolin [OXP]/ Syngenta Canada Inc. [SYZ]

MRID #: 50615204 Page 1 of 8 PMRA #: 2999325

B.7.6 Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IIIA 8.3) B.7.6.1 Residues in Target Crops B.7.6.1.1 Hops Document ID: MRID 50615204

PMRA No. 2951332 Report: Jolly, C. (2018) “OXATHIAPIPROLIN: MAGNITUDE OF THE

RESIDUE ON HOPS,” IR-4 Project Number: 11759, Analytical Laboratory Identification Number: 11759.16-CAR17. Unpublished Study Prepared by IR-4, Princeton, NJ, USA. 230 pgs.

Guidelines: EPA OCSPP Harmonized Test Guideline 860.1500 Crop Field Trials (August 1996) PMRA Regulatory Directive DIR98-02 – Residue Chemistry Guidelines, Section 9 – Crop Field Trials

PMRA Regulatory Directive DIR2010-05 – Revisions to the Residue Chemistry Crop Field Trial Requirements OECD Guideline 509 Crop Field Trial (September 2009)

GLP Compliance: No deviations from regulatory requirements were reported which would have an impact on the validity of the study.

Acceptability: The study is considered scientifically acceptable. Evaluator: Jack Giordano, Chemist EXECUTIVE SUMMARY Interregional Research Project Number 4 (IR-4) and Agriculture and Agri-Food Canada (AAFC) Canada submitted six field trials for oxathiapiprolin on hops in Canada and the United States during the 2016 growing season. Trials were conducted in North American Free Trade Agreement (NAFTA) Growing Regions 5/5B (1 trial in WI, 1 trial in QC), 11 (1 trial in ID, 1 trial in WA), and 12 (1 trial in BC, 1 trial in OR) during the 2016 growing season. At each trial location, oxathiapiprolin formulated as an oil dispersion (Oxathiapiprolin 100 OD; 10.2% w/w; 100 g ai/L; 0.83 lb ai/gal) was applied as a single soil directed application at a rate of 280-292 g ai/ha (0.250-0.260 lb ai/A) followed by 3 foliar directed applications at a rate of 35-37 g ai/ha (0.031-0.033 lb ai/A). All applications were made with a retreatment interval (RTI) of 5-8 days. The total seasonal application rates ranged from 388-398 g ai/ha (0.346-0.355 lb ai/A). An adjuvant was added to the spray mixture for all applications at one trial site (BC16) and for all foliar applications at the other 5 trial sites. Hops were harvested at a preharvest interval (PHI) of 6-8 days. In one trial, samples were collected at different time intervals (PHIs of 1, 3, 10, and 14 days) to monitor residue decline. All samples were maintained frozen at the testing facility, during shipping to the laboratory, and until arrival at the analytical laboratory. The maximum storage interval for samples between

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harvest and extraction was 480 days (~15.8 months). Samples were analyzed on the same day as extraction. Residues of oxathiapiprolin have been shown to be stable in 5 crop categories according to OECD Guidance Document 506 (2007) (wheat and potato [high starch], tomato [high water], grape [high acid], dry beans [high protein], and soybean [high oil]) for up to 18 months under frozen conditions. Adequate storage stability data are therefore available to support the storage conditions and intervals for samples in the current trials. Samples in the current study were analyzed using a working Method based on DuPont-30422, a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to determine residues of oxathiapiprolin. Acceptable method validation and concurrent recoveries were reported for dried hop cone samples fortified with oxathiapiprolin at 0.02 mg/kg (ppm), 0.10 ppm, 1.0 ppm, and 10 ppm. The limit of quantitation (LOQ) was 0.02 ppm. Individual sample (and per-trial average) residues of oxathiapiprolin in dried hop cones following treatment at a total rate of 388-398 g ai/ha (0.346-0.355 lb ai/A) and harvested at a PHI of 6-8 days ranged from 0.30-2.5 ppm (0.33-2.1 ppm). Residue decline data show that residues of oxathiapiprolin decrease slightly in hops with increasing PHIs.

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Sample Handling and Preparation Samples of hop cones were collected from control plots followed by treated plots to avoid sample contamination. Hop bines were cut with a knife, machete, or pruning shears, and placed on a clean tarp. Samples of hop cones were then collected by hand from the bines, or the bines were fed through a picker to remove the hop cones. After sample collection, the hop cones were dried for 2.5 to 26 hours at temperatures ranging from 55-63°C (131-145°F). Dried hop cones were placed in frozen storage (generally at <-20°C [-4°F]) within 57 minutes after drying. Samples of dried hop cones were shipped frozen via ACDS freezer truck to the analytical laboratory (University of California, Davis, Davis, CA, USA) where they arrived frozen and in good condition. Upon arrival, samples of dried hop cones were processed with dry ice in a Robot Coupe Food chopper, sub-sampled, and returned to the freezer until extraction and analysis. 2. Description of Analytical Procedures Samples of dried hop cones were analyzed for residues of oxathiapiprolin using a working method based on the DuPont-30422, Supplement No. 1, titled Analytical Method titled “Analytical Method for the Determination of DPX-QGU42 and Metabolites in Crops Using LC/MS/MS.” This method is on file (PMRA #2365222, MRID 49011136) and has been previously deemed acceptable for the data gathering and enforcement purposes (Submission 2013-6410; PMRA #2410098; Review EPA DP# D426128). The modifications to the reference method include:

1. Reduced sample weight to improve extraction efficiency. 2. Addition of a cleanup step solid phase extraction (SPE) columns to reduce sample

suppression. 3. Matrix-matched standards were used to analyze metabolites at 0.01 ppm.

Briefly, samples were extracted with a mixture of acetonitrile, water, and formic acid, and were homogenized and centrifuged. The supernatant was decanted and the extraction step was repeated twice more. The pooled supernatants were cleaned up using liquid/liquid partition with hexane. The aqueous portion was decanted, and the liquid/liquid partition with hexane was repeated. Extracts were cleaned up using two SPE columns (strong cation exchange [SCX] SPE column and Envi-Carb SPE). Oxathiapiprolin was eluted from the column first with acetone and then with toluene/methanol (90:10, v/v). The eluate was evaporated to dryness and reconstituted in acetone/ water (50:50, v/v). The final residue extracts were analyzed for oxathiapiprolin by LC-MS/MS. The LOQ was 0.02 ppm and the limit of detection (LOD) was calculated to be 0.002 ppm. II. RESULTS AND DISCUSSION Method performance was evaluated during method validation and by use of concurrent recovery samples by fortifying dried hop cones with oxathiapiprolin at 0.02 ppm (n=9), 0.1 ppm (n=3; method validation only), 1.0 ppm (n=6), and 10 ppm (n=3; concurrent recoveries only).

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2.5 ppm (0.33-2.1) ppm. A residue decline study indicates that the level of oxathiapiprolin residues in hops decreases slightly with time. Adequate storage stability data are available to support sample storage durations and conditions. REFERENCES PMRA #2365222, MRID 49011136 Henze, R.M., Stry, J.J. (2011) “Analytical method for the determination of DPX-QGU42 and metabolites in crops using LC/MS/MS,” Report No: DuPont-30422, Suppl. No. 1. Unpublished Study Prepared by DuPont Crop Protection, Wilmington, Delaware, USA. 198 pgs. PMRA #2364992, MRID 49011204: Vincent, T. (2013) “Stability of DPX-QGU42 and metabolites in crop matrices stored frozen,” DuPont Study Number: DuPont-30046. ABC Laboratories, Inc. Project No. 66399. Unpublished Study Prepared by DuPont Crop Protection, Wilmington, Delaware, USA. 299 pgs.

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B.7.6 Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IIIA 8.3) B.7.6.1 Residues in Target Crops B.7.6.1.1 Blueberry Document ID: MRID No. 50683001 Report: S, Dorsey (2017). “Oxathiapiprolin (A21008A) – Magnitude of the

Residues in Blueberry, USA, 2016.” Analytical Bio-Chemistry Laboratories, Inc Report Number TK0244481. Unpublished study prepared by Syngenta Crop Protection, LLC. Greensboro, NC, USA. 176 pages.

Guidelines: EPA OCSPP Harmonized Test Guideline 860.1500 Crop Field Trials (August 1996) OECD Guideline 509 Crop Field Trial (September 2009)


Acceptability: The study is considered scientifically acceptable. Evaluator: Jack Giordano, Chemist EXECUTIVE SUMMARY Eight field trials for oxathiapiprolin on blueberries were conducted in the United States encompassing North American Free Trade Agreement (NAFTA) Growing Regions I (1 trial in NY), II (2 trials in GA; 1 trial in PA), V (2 trials in OH; 1 trial in MI), and XII (1 trial in OR) during the 2016 growing season. At each trial location, oxathiapiprolin, formulated as a suspension concentrate (SC) containing 1.67 pounds of the active ingredient per gallon (lb ai/gal), was applied to blueberries as two soil directed applications at rates ranging from 0.245-0.262 pounds of active ingredient per acre (lb ai/A), equal to 274-293 grams of active ingredient per hectare (g ai/ha). Oxathiapiprolin was applied with a 6-7 day re-treatment interval (RTI), and the total seasonal application rate ranged from 0.493-0.515 lb ai/A (553-577 g ai/ha). No adjuvant was added to the spray mixture in any of the trials. Blueberries were harvested at a preharvest interval (PHI) of 1 day. For two trials, samples were collected at different time intervals (PHIs of 4, 7, 10, and 14 days) to monitor residue decline. All samples were maintained frozen at the testing facility, during shipping, and at the laboratory until analysis. The maximum storage interval for samples between harvest and extraction was 146 days (4.8 months). Residues of oxathiapiprolin have been shown to be stable in representative crop matrices including high water content, high oil content, high protein content, high starch content, and high acid content matrices for at least 18 months under frozen conditions. Adequate storage stability data are therefore available to support the storage durations and conditions for samples in the current trials.

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Oxathiapiprolin (128111)


Samples in the current study were analyzed using DuPont Method-30422, Supplement No 1, a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to determine residues of oxathiapiprolin. Acceptable method validation and concurrent recoveries were reported for blueberry samples at fortification levels of 0.01, 0.1, and 1 mg/kg (ppm), thus validating the method. The limit of quantitation (LOQ) was established at 0.01 ppm in blueberry matrices. Individual sample (and per-trial average) residues in blueberries ranged from <0.01 ppm to 0.42 ppm (<0.01 ppm to 0.27 ppm). Residue decline data could not be assessed, as all residues in the decline trials were below the LOQ.

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REFERENCES S, Dorey (2017). “Oxathiapiprolin (A21008A) – Magnitude of the Residues in Blueberry, USA, 2016.” Analytical Bio-Chemistry Laboratories, Inc Report Number TK0244481. Unpublished study prepared by Syngenta Crop Protection, LLC. Greensboro, NC, USA. 176 pages. Oxathiapiprolin. Petition for the Establishment of Permanent Tolerances and Registration for Use of the New Active Ingredient on a Number of Crops. Summary of Analytical Chemistry and Residue Data.; D426128; E. Holman; 29-Apr-2015.

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B.7.6 Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IIIA 8.3) B.7.6.1 Residues in Target Crops B.7.6.1.2 Avocado Document ID: MRID No. 50615202 Report: Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on Avocado.

Study Numbers: 11795; 11795.16-MIR09. Unpublished study prepared and submitted by Interregional Research Project Number 4. 153 p.







Evaluator: Jack Giordano, Chemist, RAB2 Note: This Data Evaluation Record (DER) was prepared under contract by CDM/CSS-Dynamac Joint Venture (submitted 25-Sep-2019). The CDM/CSS-Dynamac Joint Venture role does not include establishing Agency policies. The DER has been reviewed by HED and revised as necessary to reflect current Office of Pesticide Programs (OPP) policies. EXECUTIVE SUMMARY Interregional Research Project Number 4 (IR-4) has submitted field trial data for oxathiapiprolin on avocado from five field trials conducted in the United States and Puerto Rico during the 2016 and 2017 growing seasons. Trials were conducted in North American Free Trade Agreement (NAFTA) Growing Zones 3 (FL; 1 trial), 10 (CA; 3 trials), and 13 (PR; 1 trial). Each trial consisted of one untreated plot and one treated plot reflecting a combination of two soil applications (directed spray or chemigation) followed by two foliar directed applications of a 0.83 lb ai/gal (100 g ai/L) oil dispersion (OD) formulation of oxathiapiprolin. The soil applications were made at 0.125-0.146 lb ai/A/application (140-164 g ai/ha/application), at a retreatment interval (RTI) of 27-33 days, for total soil application rates of 0.250-0.291 lb ai/A (280-326 g ai/ha). The first foliar applications was made 27-45 days after the second soil application. Foliar application rates ranged from 0.0311-0.0325 lb ai/A/application (34.9-36.4 g ai/ha/application), with an RTI of 13-14 days between the foliar applications, for a total foliar application rate of 0.0628-0.0640 lb ai/A (70.4-71.7 g ai/ha). Total application rates for the soil and foliar applications were 0.314-0.355 lb ai/A (352-398 g ai/ha). Applications were made

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using ground equipment in volumes of 20-33 gal/A (187-309 L/ha) for soil spray applications and 53-193 gal/A (496-1800 L/ha) for foliar spray applications; application volumes were not reported for chemigation applications. An adjuvant (nonionic surfactant) was added to the spray mixture for each application. Duplicate treated samples of avocado were harvested at a preharvest interval (PHI) of 27-31 days following the second soil application (prior to foliar applications), and at a 1-day PHI following the second foliar application. In one trial, samples were collected at additional PHIs of 0, 3, 7, and 10 days following the second foliar application to assess residue decline. Samples were maintained frozen at the field sites, during shipping, and at the laboratory prior to analysis. The maximum storage interval for samples between harvest and extraction for analysis was 14.5 months. Samples were analyzed within 7 days of extraction. To support sample storage durations, a concurrent storage stability study was conducted using untreated samples of avocado. The data demonstrate that residues of oxathiapiprolin are stable during frozen storage in avocado for at least 13.4 months. In addition, acceptable storage stability data are available demonstrating the stability of oxathiapiprolin residues in representative crop commodities (high water, high starch, high acid, high protein, high oil, and very dry matrices) during frozen storage for at least 18 months (D426128, 29-April-2015; E. Holman). These data are acceptable to support the storage conditions and durations of the samples from the submitted field trials. Samples were analyzed for residues of oxathiapiprolin using a working method based on DuPont-30422, Supplement No. 1, a high-performance liquid chromatography method with tandem mass spectrometry detection (LC-MS/MS). Method DuPont-30422, Supplement No. 1, is the tolerance enforcement method for plant commodities (D426128). The limit of quantitation (LOQ), determined as the lowest level of method validation (LLMV), was 0.01 ppm. Acceptable method validation and concurrent recoveries were obtained from samples of avocado fortified with oxathiapiprolin at 0.01-1.0 ppm. The fortification levels adequately represented measured residue levels. Following four applications (two soil and two foliar applications) at a 1-day PHI, residues of oxathiapiprolin in/on individual samples of avocado were <0.01-0.0392 ppm, corresponding to per-trial average residues of <0.01-0.0391 ppm. For avocadoes harvested at a PHI of 27-31 days following the second soil application (prior to foliar applications), all residues were below the LOQ (<0.01 ppm). In the decline trial, average oxathiapiprolin residues following soil and foliar applications were relatively consistent over the sampling period, but did increase slightly in/on avocado between the 0- and 10-day PHIs.

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Sample Handling and Preparation Duplicate treated samples of avocado were harvested from all trials at a PHI of 27-31 days following the second soil application (prior to foliar applications), and duplicate untreated and treated samples were harvested from all trials at a 1-day PHI following the second foliar application. At Trial CA94, additional treated samples were harvested at PHIs of 0, 3, 7, and 10 days following the second foliar application to assess residue decline. Pits and stems were removed from all samples prior to collection. Samples were placed into frozen storage within ~3 hours of harvest and were stored frozen (<-17°C) at the field sites prior to shipment by freezer truck or overnight courier (on dry ice) to the analytical laboratory, IR-4 North Central Region Laboratory (Lansing, MI). At the laboratory, samples were homogenized in the presence of dry ice and stored frozen (ca. <-20°C) until extraction for analysis. 2. Description of Analytical Procedures Samples were analyzed for residues of oxathiapiprolin by LC-MS/MS using a working method based on DuPont-30422, Supplement No. 1, titled “Analytical Method for the Determination of DPX-QGU42 and Metabolites in Crops Using LC-MS/MS.” Method DuPont-30422, Supplement No. 1, is the tolerance enforcement method for plant commodities (D426128). Modifications to the cited method included substitutions for the final dilution solvent and LC-MS/MS mobile phases. A complete description of the working method was included in the submission. Briefly, samples were soaked in water for 5 minutes and extracted (3x) with water:acetonitrile (ACN):1% formic acid (4:12:0.1, v:v:v for extractions 1 and 2; and 3:9:0.1, v:v:v for extraction 3). The extracts were isolated by centrifugation, combined, and adjusted to volume with ACN. An aliquot of the extract was filtered through a 0.2-µm PTFE membrane filter, adjusted to volume with 1% formic acid, and applied to an Envi-Carb solid phase extraction column. The column was rinsed with 1% formic acid:ACN (75:25, v:v) followed by ACN. Residues were eluted with acetone followed by toluene:methanol:1% formic acid (90:10:1, v:v:v). The eluate was evaporated to dryness under nitrogen, and residues were reconstituted in methanol and adjusted to volume with 1% formic acid for LC-MS/MS analysis. The following transitions were monitored: m/z 540 → 499.9 for quantitation and m/z 540 → 163.1 for confirmation. The LOQ (determined as the LLMV) was 0.01 ppm; a limit of detection was not reported. II. RESULTS AND DISCUSSION Method performance was evaluated by use of method validation and concurrent recovery samples of avocado fortified with oxathiapiprolin at 0.01-1.0 ppm. Individual recoveries were within the acceptable range of 70-120%; therefore, the method is considered valid for the determination of residues of oxathiapiprolin in/on avocado (Table B.7.6.1.2-4). The fortification levels adequately bracketed the measured residues. The detector response was linear (coefficient of determination, r2 ≥0.9914) within the range of 0.07-7.0 ng/mL. Representative chromatograms of control samples, fortified samples, and treated samples were provided. The control chromatograms generally had no peaks of interest above the

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Appendix I. Soil Characteristics for Avocado Field Trials with Oxathiapiprolin.

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Oxathiapiprolin [128111]


B.7.6 Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IIIA 8.3) B.7.6.1 Residues in Target Crops B.7.6.1.2 Crop Group 14-12 Document ID: MRID No. 50683002 Report: S, Dorsey (2018) “Magnitude of Residues of Oxathiapiprolin OD

(A20941A) and Mefenoxam SL (A13947A) in Tree Nuts – Pecans and Almonds, USA, 2016. Analytical Bio-Chemistry Laboratories.” Analytical Bio-Chemistry Laboratories, Inc Report Number TK0244482. Unpublished study prepared by Syngenta Crop Protection, LLC. Greensboro, NC, USA. 346 pages.

Guidelines: EPA OCSPP Harmonized Test Guideline 860.1500 Crop Field Trials (August 1996) OECD Guideline 509 Crop Field Trial (September 2009)


Acceptability: The study is considered scientifically acceptable. Evaluator: Jack Giordano, Chemist EXECUTIVE SUMMARY Ten independent field trials for oxathiapiprolin on tree nuts (5 on almonds and 5 on pecans) were conducted in the United States encompassing North American Free Trade Agreement (NAFTA) Growing Regions II (2 trials in GA), IV (1 trial in LA), VI (1 trial in TX), VIII (1 trial in TX), and X (4 trials in CA) during the 2016 growing season. At each trial location, oxathiapiprolin, formulated as an oil dispersion (OD) containing 0.83 pounds of the active ingredient per gallon (lb ai/gal), was applied to almonds or pecans as two soil directed applications at rates ranging from 0.113-0.128 pounds of active ingredient per acre (lb ai/A), equal to 127-143 grams of active ingredient per hectare (g ai/ha). Oxathiapiprolin was applied with a 28-33 day re-treatment interval (RTI), and the total seasonal application rate ranged from 0.239-0.253 lb ai/A (268-283 g ai/ha). No adjuvant was added to the spray mixture for any of the trials. Almonds and pecans were harvested at a preharvest interval (PHI) of 26-31 days. For two trials, samples were collected at different time intervals (PHIs of 20, 25, 35, and 40 days) to monitor residue decline. All samples were maintained frozen at the testing facility, during shipping, and at the laboratory until analysis. Samples were stored frozen a maximum of 87 days (2.9 months) for almonds and 146 days (4.8 months) for pecans from harvest to extraction. Residues of oxathiapiprolin have been shown to be stable in representative commodities of wheat forage, tomato, potato tuber, wheat grain, grapes, dry bean seed, soybean seed, grape dry pomace, and wheat straw for at least

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18 months under frozen conditions. Adequate storage stability data are therefore available to support the storage durations and conditions for samples in the current trials. Samples in the current study were analyzed using DuPont Method 30422, Supplement No. 1, a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to determine residues of oxathiapiprolin. Acceptable method validation and concurrent recoveries were reported in almond nutmeat, almond hull, and pecan nutmeat matrices at fortification levels of 0.0100 and 0.100 mg/kg (ppm), and additionally in almond nutmeat at 2.00 ppm, thus validating the method. The limit of quantitation (LOQ) was established at 0.01 ppm in almond nutmeat, almond hull, and pecan nutmeat matrices. Individual sample (and per-trial average) residues in almond nutmeat and pecan nutmeat were all below the LOQ. Individual sample (and per-trial average) residues in almond hulls ranged from <0.01 ppm to 0.029 ppm (<0.01 ppm to 0.024 ppm). Residue decline data could not be assessed, as all residues in the decline trials were below the LOQ.

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Sample Handling and Preparation Single control and duplicate treated almond and pecan samples were collected from all trials 26-31 days after the last treatment application. At trial Sites TK0244482-01 and TK0244482-06, additional duplicate treated samples were collected at 20, 25, 35, and 40 days after the last application. Multiple nuts were sampled from a minimum of four trees to obtain the required sample weights of approximately 1.0 kg for almond nutmeat, pecan nutmeat, and almond hulls. All samples were collected starting with the untreated plot and ending with the treated plot. After collection, the raw agricultural commodity samples were frozen and stored at the field trial sites until shipment. Samples were shipped via freezer truck or by FedEx from the field trial sites to EAG Laboratories (Columbia, MO). All samples were received frozen at EAG Laboratories, except one pecan nutmeat control sample from trial 06 that was received cold. All samples were stored frozen at approximately -20°C. 2. Description of Analytical Procedures Almond nutmeat, almond hulls, and pecan nutmeat were analyzed for residues of oxathiapiprolin using the analytical method DuPont 30422, Supplement No. 1, titled “Analytical Method for the Determination of DPX-QGU42 and Metabolites in Crops Using LC/MS/MS.” EAG laboratories verified the analytical method on almond nutmeat, almond hulls, and pecan nutmeat as part of this study. Oxathiapiprolin residues were extracted from almond and pecan samples with acetonitrile/water/formic acid (12/4/0.1, v/v/v) via triplicate homogenization using a Genogrinder®. After each homogenization, samples were centrifuged and the supernatants decanted into the same collection tube. The extracts were diluted to a known volume with acetonitrile. An aliquot of each extract was diluted with acetonitrile/1% formic acid (30/70, v/v) for LC-MS/MS analysis. The method LOQ was established at 0.01 ppm. II. RESULTS AND DISCUSSION Method performance was evaluated during method validation and by use of concurrent recovery samples. Four almond nutmeat samples were fortified at 0.0100 ppm and individual recoveries ranged from 95% to 109% with a standard deviation of 5.9%. Four almond nutmeat samples were fortified at 0.100 ppm and individual recoveries ranged from 96% to 102% with a standard deviation of 2.8%. One almond nutmeat sample was fortified at 2.00 ppm and displayed 104% recovery. Four almond hull samples were fortified at 0.0100 ppm and individual recoveries ranged from 79% to 104% with a standard deviation of 11%. Four almond hull samples were fortified at 0.100 ppm and individual recoveries ranged from 90% to 99% with a standard deviation of 4.4%. Five pecan nutmeat samples were fortified at 0.0100 ppm and individual recoveries ranged from 80% to 103% with a standard deviation of 9.2%. Four pecan nutmeat samples were fortified at 0.100 ppm and individual recoveries ranged from 84% to 99% with a standard deviation of 6.7%. All recoveries were within the acceptable range of 70% to 120%; therefore, the method was considered valid for the analysis of oxathiapiprolin residues in almond nutmeat, almond hull, and pecan nutmeat matrices (Table B.7.6.1.1-4). The fortification levels

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B.7.6 Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IIIA 8.3) B.7.6.1 Residues in Target Crops B.7.6.1.3 Pomegranate, Including Pomegranate Juice Document ID: MRID No. 50615203 Report: Jolly, C. (2018) Oxathiapiprolin: Magnitude of the Residue on

Pomegranate. Study Numbers: 10915; 10915.15-MIR16; 10915.15-IDP07. Unpublished study prepared and submitted by Interregional Research Project Number 4. 201 p.







Evaluator: Jack Giordano, Chemist, RAB2 Note: This Data Evaluation Record (DER) was prepared under contract by CDM/CSS-Dynamac Joint Venture (submitted 25-Sep-2019). The CDM/CSS-Dynamac Joint Venture role does not include establishing Agency policies. The DER has been reviewed by HED and revised as necessary to reflect current Office of Pesticide Programs (OPP) policies. EXECUTIVE SUMMARY Interregional Research Project Number 4 (IR-4) submitted field trial data for oxathiapiprolin on pomegranate from four field trials conducted in the United States during the 2015 and 2016 growing seasons. Trials were conducted in North American Free Trade Agreement (NAFTA) Growing Zones 3 (FL; 1 trial) and 10 (CA; 3 trials). Each trial consisted of one untreated plot and one or two treated plots reflecting applications of a 0.83 lb ai/gal (100 g ai/L) oil dispersion (OD) formulation of oxathiapiprolin. At all trials, a treated plot received a combination of two soil applications (directed spray or drench) followed by two foliar directed applications. At one trial (in CA), an additional treated plot received only two soil applications. Soil applications were made at 0.125-0.128 lb ai/A/application (140-143 g ai/ha/application), at a retreatment interval (RTI) of 27-31 days, for total soil application rates of 0.250-0.255 lb ai/A (280-286 g ai/ha). Foliar applications were made 27-31 days after the second soil application. Foliar applications were made at a rate of 0.0308-0.0318 lb ai/A/application (34.5-35.6 g ai/ha/application) and with an RTI of 13-14 days between applications. Total

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application rates for the soil and foliar applications were 0.313-0.318 lb ai/A (351-356 g ai/ha). Applications were made using ground equipment in volumes of 10-42 gal/A (93.5-393 L/ha) for soil applications and 50-91 gal/A (468-851 L/ha) for foliar applications. An adjuvant (nonionic surfactant) was added to the spray mixture for the foliar applications at three of the four trials; no adjuvant was used for soil applications at all trials, or for the foliar applications at the fourth trial. Duplicate treated samples of pomegranate were harvested at a preharvest interval (PHI) of 27-29 days following the second soil application and at a 1-day PHI following the second foliar application. At the CA trial with two treated plots, soil application samples were collected from one plot, and soil plus foliar application samples were collected from the other plot. Additional samples were collected at this trial at PHIs of 9, 15, and 20 days from the soil applications plot and PHIs of 0, 3, 7, and 9 days from the soil plus foliar applications plot to assess residue decline. At a different CA trial, bulk samples of pomegranate were harvested at a 1-day PHI following soil and foliar applications for processing into pomegranate juice. Samples, except for bulk samples for processing, were maintained frozen at the field sites, during shipping, and at the laboratory prior to analysis. Bulk samples were maintained and shipped from the field sites under ambient temperatures, stored cool prior to processing, and stored frozen following processing, which was completed within 2 days of harvest; samples from the processor were stored frozen during shipping and at the laboratory prior to analysis. The maximum storage intervals for samples between harvest/collection and extraction for analysis were 21.4 months for pomegranate fruit and 19.3 months for juice. Samples were analyzed within 6 days of extraction. To support sample storage durations, a concurrent storage stability study was conducted using untreated samples of pomegranate fruit and juice; no 0-day data were provided. The data demonstrate that residues of oxathiapiprolin are stable during frozen storage for at least 18.7 months in pomegranate fruit and 17.7 months in juice. In addition, acceptable storage stability data are available demonstrating the stability of oxathiapiprolin residues in representative crop commodities (high water, high starch, high acid, high protein, and high oil matrices) during frozen storage for at least 18 months (D426128; 29-Apr-2015; E. Holman). These data are considered adequate to support the sample storage conditions and durations from the submitted field trials. Samples were analyzed for residues of oxathiapiprolin using a working method based on DuPont-30422, Supplement No. 1, a high-performance liquid chromatography method with tandem mass spectrometry detection (LC-MS/MS). Method DuPont-30422, Supplement No. 1, is the tolerance enforcement method for plant commodities (D426128). The limit of quantitation (LOQ), determined as the lowest level of method validation (LLMV), was 0.01 ppm. Acceptable method validation and concurrent recoveries were obtained from samples of pomegranate fruit and juice fortified with oxathiapiprolin at 0.01-1.0 ppm. The fortification levels adequately represented measured residue levels. Following the last of four applications (combination of soil and foliar applications) with a 1-day PHI, residues of oxathiapiprolin in/on individual samples of pomegranate were 0.0239-0.0371 ppm, corresponding to per-trial average residues of 0.0261-0.0356 ppm. For pomegranate harvested at a PHI of 27-29 days following the second soil application, all residues were below the LOQ (<0.01 ppm). For pomegranate harvested at a 1-day PHI following soil and foliar

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applications and processed into juice, oxathiapiprolin residues were 0.0207 ppm in/on fruit collected prior to processing and <0.01 ppm in processed juice. In the decline trial, average oxathiapiprolin residues generally declined in/on pomegranate with increasing PHI following soil and foliar applications. Residues were below the LOQ at all sampling intervals in/on samples harvested following soil only applications; therefore, residue decline could not be evaluated. Based on residues in/on pomegranate fruit and juice, residues of oxathiapiprolin did not concentrate in pomegranate juice (processing factor of <0.5x). There are no theoretical concentration factors listed in OCSPP 860.1520 for pomegranate.

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collected at the processor was analyzed. Samples were shipped frozen via freezer truck from the processor to the analytical laboratory where they were stored frozen (ca. <-20°C) until homogenization (RAC only) and extraction for analysis. 2. Description of Analytical Procedures Samples were analyzed for residues of oxathiapiprolin by LC-MS/MS using a working method based on DuPont-30422, Supplement No. 1, titled “Analytical Method for the Determination of DPX-QGU42 and Metabolites in Crops Using LC/MS/MS.” Method DuPont-30422, Supplement No. 1, is the tolerance enforcement method for plant commodities (D426128). Modifications to the cited method included substitutions for the final dilution solvent and LC-MS/MS mobile phases, and addition of procedures for liquid (juice) matrices. A complete description of the working method was included in the submission. Briefly, pomegranate fruit samples were soaked in water for 5 minutes and extracted (3x) with water:acetonitrile (ACN):1% formic acid (4:12:0.1, v:v:v, for extractions 1 and 2, and 3:9:0.1, v:v:v, for extraction 3). The extracts were isolated by centrifugation, combined, and adjusted to volume with ACN. For extraction of residues from juice, samples were mixed with water:ACN:1% formic acid (11:32:0.3, v:v:v) and adjusted to volume with ACN. For both matrices, an aliquot of the extract was filtered through a 0.2-µm PTFE membrane filter, adjusted to volume with 1% formic acid, and applied to an Envi-Carb solid phase extraction column. The column was rinsed with 1% formic acid:ACN (75:25, v:v) followed by ACN, and residues were eluted with acetone followed by toluene:methanol:1% formic acid (90:10:1, v:v:v). The eluate was evaporated to dryness under nitrogen, and residues were reconstituted in methanol and adjusted to volume with 1% formic acid for LC-MS/MS determination. The following transitions were monitored: m/z 540 → 499.9 for quantitation and m/z 540 → 163.1 for confirmation. The LOQ (determined as the LLMV) was 0.01 ppm; a limit of detection was not reported. II. RESULTS AND DISCUSSION Method performance was evaluated by use of method validation and concurrent recovery samples of pomegranate fruit and juice fortified with oxathiapiprolin at 0.01-1.0 ppm. Individual recoveries were within the acceptable range of 70-120%; therefore, the method is considered valid for the determination of residues of oxathiapiprolin in/on pomegranate fruit and juice (Table B.7.6.1.3-4). The fortification levels adequately bracketed the measured residues. The detector response was linear (coefficient of determination, r2 ≥0.9892) within the range of 0.07-7.0 ng/mL. Representative chromatograms of control samples, fortified samples, and treated samples were provided. The control chromatograms generally had no peaks of interest above the chromatographic background. The fortified sample chromatograms contained only the analyte of interest, and peaks were symmetrical and well defined. Apparent residues in/on controls were below the LOQ (<0.01 ppm).

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Based on residues in/on pomegranate fruit and juice, residues of oxathiapiprolin did not concentrate in pomegranate juice (processing factor of <0.5x). There are no theoretical concentration factors listed in OCSPP 860.1520 for pomegranate. An acceptable method was used for residue quantitation, and adequate storage stability data were submitted and are available to support sample storage durations and conditions. REFERENCES D426128, D417280, D417281, and D422595; 29-Apr-2015; E. Holman

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Appendix I. Soil Characteristics for Pomegranate Field Trials with Oxathiapiprolin.

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