Document ID: EPA-HQ-OPP-2017-0224-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2018-07-23T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                               WASHINGTON, D.C.  20460
                                       
                                       
                                                      OFFICE OF CHEMICAL SAFETY
                                                       AND POLLUTION PREVENTION
	

MEMORANDUM

Date:		09-MAY-2018

Subject:	Flonicamid (128016); Petition for the Establishment of Uses and Permanent Tolerances for Clover, Crop Group Conversions to Brassica, Head and Stem Vegetable, Group 5-16; Brassica, Leafy Greens, Subgroup 4-16B, Leaf Petiole Vegetable, Subgroup 22B; Leafy Greens, Subgroup 4-16A, Except Spinach; Celtuce; Florence Fennel; and Kohlrabi; Expansion of Cottonseed Tolerances to Cottonseed Subgroup 22B Tolerance (sub BEAN DP440462) 
	Revised Use Directions for Citrus (sub BEAN DP447010)
	Summary of Analytical Chemistry and Residue Data.  

PC Code:  128016
DP Barcodes:  D440462, D447010
Decision Nos.:  526902, 530022 (citrus)
Registration No.:  71512-9, 71512-10, 71512-7
Petition No.:  7E8556, none (citrus)
Regulatory Action:  Section 3 registration, Revised Label 
Risk Assessment Type:  not applicable
Case No.:  7436
TXR No.:  not applicable
CAS No.:  158062-67-0
MRID No:  see below
40 CFR:  §180.613

From:		William D. Wassell, Chemist
      Health Effects Division/Risk Assessment Branch 3 (HED/RAB3, 7509P)

Through:		George F. Kramer, Ph.D., Senior Chemist
	HED/RAB1 (7509P)

To: 		Sidney Jackson/Carmen Rodia, RM 05
		Registration Division (7505P)

Summary of Submitted/Reviewed Residue Chemistry Studies
                                OCSPP Guideline
                                   Reference
                                   860.1500
50151701.  Kenneth S. Samoil (2016) Flonicamid: Magnitude of the Residue on Clover (Seed Crop).  Report Number:  A9943.  Analytical Laboratory Identification Number A9943.14-FLR03.  Unpublished study prepared by IR-4 Project.  165 pages.
                                   860.1500
50292501.  Thomas Schreier (2017) Flonicamid: Magnitude of the Residue of Beleaf 50 SG Insecticide in/on Orange.  Study Number:  PSM-16-06-02.  Analytical Laboratory Identification Number 160682.  Unpublished study prepared by Precision Study Management, LLC.  241 pages.

TABLE OF CONTENTS

1.0 Executive Summary	3
2.0 Recommendations	5
2.1 Data Deficiencies/Data Needs	5
2.2 Tolerance Considerations	6
2.2.1 Enforcement Analytical Method	6
2.2.2 Recommended Tolerances	6
2.2.3 Revisions to Petitioned-For Tolerances	8
2.2.4 International Harmonization	8
2.3 Label Recommendations	8
3.0 Introduction	8
3.1 Chemical Identity	8
3.2 Physical/Chemical Properties	8
3.3 Pesticide Use Pattern/Directions	10
4.0 Metabolism/Degradate Residue Profile	11
5.0 Residue Profile	13
5.1 Residue Analytical Methods	13
5.1.1 Data-Collection Methods	13
5.1.2 Food and Drug Administration (FDA) Multiresidue Methods (MRMs)	13
5.1.3 Tolerance-Enforcement Method	14
5.1.4 Submittal of Analytical Reference Standards	14
5.2 Storage Stability	15
5.3 Residue Data	15
5.3.1 Crop Field Trials	15
5.3.2 Magnitude of the Residue - Rotational Crops	18
5.3.3 Processed Food/Feed	19
5.3.4 Meat, Milk, Poultry, and Eggs	19
5.4 Food Residue Profile	19
6.0 Tolerance Derivation	19
Attachment 1:  International Residue Limits	21
Attachment 2:  OECD MRL Calculation Procedure Inputs/Outputs	23

1.0 Executive Summary

Background:  Flonicamid [N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide] is a systemic insecticide that immediately suppresses the feeding of sucking insects on plants.  From its chemical structure (including the nicotinic acid structure), it would be expected to exhibit the same mode of action as similarly structured neo-nicotinoid pesticides.  However, flonicamid has not been found to activate acetylcholine esterase (e.g., organophosphates and carbamates), or nicotinic acetylcholine receptors (neo-nicotinoids).  Flonicamid is a member of the pyridinecarboxamide class of insecticides.  It is a Group 9C (selective feeding blocker) insecticide that controls pests by contact and ingestion provoking rapid and irreversible feeding cessation.

Permanent tolerances have been established under 40 CFR §180.613(a)(1) for the combined residues of the insecticide flonicamid and its metabolites TFNA (4-trifluoromethylnicotinic acid), TFNA-AM (4-trifluoromethylnicotinamide), and TFNG, N-(4-trifluoromethylnicotinoyl)glycine, calculated as the stoichiometric equivalent of flonicamid in/on various plant commodities at levels ranging from 0.20 ppm (tuberous and corm vegetables, subgroup 1C) to 20 ppm (dried hop cones).  Additionally, permanent tolerances have been established under 40 CFR §180.613(a)(2) for the combined residues of the insecticide flonicamid and its metabolites TFNA and TFNA-AM, calculated as the stoichiometric equivalent of flonicamid in/on various livestock commodities at levels ranging from 0.03 ppm for fat of cattle, goats, hog, horse, poultry, and sheep and meat of hogs & poultry to 0.08 ppm for meat and meat byproduct of cattle, goat, horse, and sheep.  Flonicamid is currently registered to ISK Biosciences Corporation as a water-dispersible granular (WG) formulation (Flonicamid 50 WG, EPA REG. No. 71512-9) and as a solid granular (SG) formulation (Beleaf 50 SG Insecticide, EPA Reg. No. 71512-10.  Both formulations contain 50% ai by weight.

Under action DP439902, the Interregional Research Project No. 4 (IR-4) has proposed uses and tolerances (40 CFR §180.613(a)) for residues of flonicamid, including its metabolites and degrades, in or on the following commodities:

Raw Agricultural Commodities/Crop Group
                              Proposed Tolerance
                                     (ppm)
Vegetable, Brassica, head and stem, group 5-16
                                      1.5
Brassica, leafy greens, subgroup 4-16B
                                      16
Cottonseed, subgroup 20C
                                    0.60[1]
Leaf Petiole vegetable, subgroup 22B
                                      4.0
Leafy greens, subgroup 4-16A, except spinach
                                      4.0
Celtuce
                                      4.0
Florence fennel
                                      4.0
Kohlrabi
                                      1.5
1 Tolerance level is based on Codex cottonseed MRL at 0.60 ppm.

Additionally under DP439902, IR-4 has proposed uses and tolerances (40 CFR §180.613(c)) for residues of flonicamid, including its metabolites and degrades, in or on the following commodities:

Raw Agricultural Commodities/Crop Group
                              Proposed Tolerance
                                     (ppm)
Clover, forage[1]
                                      0.9
Clover, hay[1]
                                      4.0
1 Tolerance for regional registration (west of Rocky Mountains).  

IR-4 further proposes under DP439902, upon establishment of the requested tolerances, to remove established tolerances for residues of the flonicamid, including its metabolites and degrades, in or on the commodities listed in the following table:

Raw Agricultural Commodities/Crop Group
                                Tolerance Level
                                     (ppm)
Vegetable, leafy, except Brassica, group 4, except spinach
                                      4.0
Brassica, head and stem, subgroup 5A
                                      1.5
Brassica, leafy greens, subgroup 5B
                                      16
Radish, tops
                                      16
Turnip, greens
                                      16
Cotton, undelinted seed
                                     0.50
Turnip Greens
                                      3.0

Under action DP441385, IR-4 has proposed revised use directions for Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) on citrus.  Specifically, the registrant has proposed reducing the pre-harvest interval (PHI) from 14-days to 0-days.

Proposed Use:  IR-4 has submitted proposed use directions for Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) and Flonicamid 50 WG (EPA Reg. No. 71512-9) which include instructions for applications to clover grown for seed west of the Rockies.  For clover, up to 2 applications may be made at 0.089 lb ai/A for control of aphids and plant bugs.  A re-treatment interval (RTI) of 7 days between applications and a PHI of 60 days are specified.  A maximum of 0.18 lb ai/A may be applied per year.  The use directions include the following restriction:  For use on clover grown for seed.  Do not allow foraging of fields or harvesting of hay within 60 days of the last application.  

Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) is registered for use on the citrus fruit group for applications at the rate of 0.089 to 0.178 lb ai/A.  The directions specify:  do not apply more than 3 applications at 0.089 lb ai/A; do not apply more than 2 applications at 0.133 lb ai/A; and do not apply more than one application at 0.178 lb ai/A.  Allow a minimum of 7 days between applications.  A PHI of 0 days is specified.

The proposed application scenarios are supported by the submitted residue chemistry data.  

Nature of the Residue - Primary Crops/Rotational Crops/Livestock:  The nature of the residue in plants is adequately understood based on the available metabolism studies on potato, peach, and wheat.  The metabolism studies on these crops combined with the confined rotational crop data provide adequate information to define the metabolic profile across numerous crops.

Based on the available data, HED determined that the residues of concern for the tolerance expression and risk assessment in primary and rotational crops are flonicamid and its metabolites TFNA, TFNA-AM, TFNG, expressed as flonicamid.

The nature of the residue in livestock is adequately understood based on acceptable ruminant (goat) and poultry (laying hen) metabolism studies.  HED has determined that the residues of concern for the tolerance expression and risk assessment in meat, milk, poultry, and eggs are flonicamid and its metabolites TFNA and TFNA-AM, expressed as flonicamid.

Based on these data, HED concluded that the residues of concern, for tolerance enforcement and risk assessment, are as defined in Table 4.0.1.  

Magnitude of the Residue - Proposed Crops:  The number and geographical representation of the submitted clover field trial data are adequate.  All samples were analyzed using adequately validated methods and sufficient storage stability data are available.  Based on these field trial data, HED concludes that the tolerances for residues of flonicamid and its metabolites in clover commodities listed in Table 2.2.2.1 are appropriate.  

The number and geographical representation of the submitted orange field trial data are adequate.  All samples were analyzed using adequately validated methods and sufficient storage stability data are available.  Based on these field trial data, HED concludes that a PHI of 0 days is adequate for oranges and grapefruit, but not lemons.  

Magnitude of the Residue - Rotational Crops:  Additional field rotational crop data are not required.  A limited field rotational crop study was previously submitted and reviewed.  The study was found to be acceptable.  The results of the limited field rotational crop studies indicate that rotational crop tolerances are not required, and that the 30-day plantback interval (PBI) for all crops not listed on the label, is appropriate.  

Magnitude of the Residue  -  Livestock:  Livestock tolerances for residues of flonicamid and its metabolites TFNA and TFNA-AM in/on livestock commodities are currently established.  Clover and citrus pulp are ruminant feed items, but are not fed to poultry or swine.  The use of flonicamid on clover was originally proposed in conjunction with PP#2E8137.  In conjunction with this petition, the contribution of citrus pulp and clover forage and hay to the livestock diet was evaluated.  The calculated dietary burden based on the maximum reasonably balanced diets for dairy and beef cattle were 1.3 and 3.4 ppm, respectively.  It was concluded that the established tolerances for residues in fat, meat, and meat by product of cattle, goat, horse, and sheep are adequate.  Additionally, it was concluded a tolerance of 0.05 ppm for residues of flonicamid and its metabolites TFNA and TFNA-AM in milk should be established.  HED concludes that the current petition does not alter the previous decisions concerning the magnitude of the residue in/on livestock.

2.0 Recommendations

Provided the petitioner submits a revised Section F/proposed tolerances and an analytical grade standard for TFNG, HED concludes that the residue chemistry database supports the establishment of the permanent tolerances listed in Section 2.2.2.  A human health risk assessment is forthcoming.  

Additionally, HED concludes the petitioner has submitted adequate data to show that the PHI for the orange and grapefruit subgroups may be reduced to 0-days; however, the 14-day PHI for lemons should be retained.  A revised label is required.  

2.1 Data Deficiencies/Data Needs

 Submission of analytical grade standard (TFNG).
 Revised Section F/proposed tolerances.
 Revised label for citrus.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method
References:
Memo, 09/29/2016, J. Smith, D435472

Plant Commodities:  FMC Method No. P-3561M, a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method, is an acceptable enforcement method for flonicamid and its metabolites in plant commodities.  The method determines residues of flonicamid and its metabolites TFNA-AM, TFNA, and TFNG.  The method has been sufficiently validated in five diverse crops.  Depending on the matrix, the limit of quantitation (LOQ) is 0.01 or 0.02 ppm. The limit of detection (LOD) can be estimated as one-third the LOQ.

Livestock Commodities:  Three enforcement methods are used for livestock commodities: an LC/MS/MS method RCC No. 844743 for determination of residues in eggs, poultry tissues, and fat of cattle, goat, hog, horse, and sheep; LC/MS method RCC No. 842993 for determination of residues in milk; and LC/MS/MS method FMC No. P-3580, which includes an acid hydrolysis step, for determination of residues in meat and meat by-products (kidney and liver) of cattle, goat, hog, horse, and sheep.  All three methods determine flonicamid and the metabolites OH-TFNA-AM (6-hydroxy-4-trifluoromethylnicotinamide), TFNA-AM, TFNG, and TFNA.  The LOQs for each analyte in each matrix (based on the lowest level of method validation (LLMV)) are 0.01 ppm for Methods RCC No. 844743 and RCC No. 842993, and 0.025 ppm for FMC No. P-3580.  The LODs are all 0.005 ppm.

2.2.2 Recommended Tolerances

HED has reviewed the available residue data and has determined the appropriate tolerance levels for residues of flonicamid and its metabolites (Table 2.2.2.1.).  Note:  Tolerances established in 40 CFR §180.613 (a)(1) are for residues in/on plant commodities.  Tolerances established in 40 CFR §180.613 (a)(2) are for residues in/on livestock commodities.  The tolerance expressions are as follows:

 General. (1) Tolerances are established for the residues of the insecticide flonicamid, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of flonicamid, N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide, and its metabolites, TFNA (4-trifluoromethylnicotinic acid), TFNA-AM (4-trifluoromethylnicotinamide), and TFNG, N-(4-trifluoromethylnicotinoyl)glycine, calculated as the stoichiometric equivalent of flonicamid, in or on the following commodities. 
   
 (2) Tolerances are established for the residues of the insecticide flonicamid, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of flonicamid, N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide, and its metabolites, TFNA (4-trifluoromethylnicotinic acid), and TFNA-AM (4-trifluoromethylnicotinamide), calculated as the stoichiometric equivalent of flonicamid, in or on the following commodities.

HED concludes the tolerance expression is in compliance with current guidance and does not need to be revised.  

Table 2.2.2.1.  Tolerance Summary for Flonicamid.
                                   Commodity
                           Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments
                        (correct commodity definition)
Vegetable, Brassica, head and stem, group 5-16
                                      1.5
                                       
                                       
Brassica, leafy greens, subgroup 4-16B
                                      16
                                       
                                       
Cottonseed, subgroup 20C
                                     0.60
                                       
                                       
Leaf petiole vegetable, subgroup 22B
                                      4.0
                                       
                                       
Leafy greens, subgroup 4-16A, except spinach
                                      4.0
                                       
                                       
Celtuce
                                      4.0
                                       
                                       
Florence fennel
                                      4.0
                                       
                                       
Kohlrabi
                                      1.5
                                       
                                       

Additionally, IR-4 has proposed uses and tolerances (40 CFR §180.613(c)) for residues of flonicamid, including its metabolites and degrades, in or on the following commodities:

Table 2.2.2.2.  Tolerance Summary for Flonicamid.
                                   Commodity
                           Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments
                        (correct commodity definition)
Clover, forage
                                      0.9
                                     0.90
                                       
Clover, hay
                                      4.0
                                      5.0
                                       
1 Tolerance for regional registration (west of Rocky Mountains).  

IR-4 further proposes, upon establishment of the requested tolerances, to remove established tolerances for residues of the flonicamid, including its metabolites and degrades, in or on the commodities listed in the following table:

Table 2.2.2.3.  Raw Agricultural Commodities/Crop Group
                                Tolerance Level
                                     (ppm)
Vegetable, leafy, except Brassica, group 4, except spinach
                                      4.0
Brassica, head and stem, subgroup 5A
                                      1.5
Brassica, leafy greens, subgroup 5B
                                      16
Radish, tops
                                      16
Turnip, greens
                                      16
Cotton, undelinted seed
                                     0.50
Turnip Greens
                                      3.0

Revised use directions for citrus:  The registrant has submitted field trial data for oranges to demonstrate that tolerances for residues in/on citrus will not be exceeded if the PHI is reduced from 14 days to 0 days.  An examination of the petition for the establishment of tolerances for residues of flonicamid and its metabolites in/on citrus reveals that the tolerance level is based on residue levels in/on lemons.  Residue levels for flonicamid and its metabolites in/on grapefruit (highest-average field trial (HAFT):  0.137 ppm) were lower than that of oranges (HAFT:  0.254 ppm); however, residue levels for lemons (HAFT:  0.804 ppm) were approximately four times higher than the values for oranges.  The submitted data are adequate to show that tolerances levels will not be exceeded for grapefruit and orange when the PHI is reduced from 14 days to 0 days, but the data are not adequate to show that residues in/on lemons will not exceed the established tolerance level when the PHI is reduced to 0 days.  A revised label is requested in which the PHI is reduced to 0 days for the orange and grapefruit subgroups, but the 14-day PHI is retained for the lemons subgroup.

2.2.3 Revisions to Petitioned-For Tolerances

The proposed tolerance levels were not revised with the exception of the tolerance for residues in clover hay.  The reason why the petitioned for tolerance and the HED-recommended tolerance levels for clover hay are not the same is because some of the residue data that IR-4 used was not converted to parent equivalents while all of the residue data used by HED were converted to parent equivalents.  A revised Section F/proposed tolerances is required.  

2.2.4 International Harmonization

There are no Codex, Canadian or Mexican maximum residue limits (MRLs) for flonicamid and its metabolites in/on clover hay and forage.  Thus, harmonization of tolerances/MRLs are not an issue for clover.  There are Canadian MRLs, but no Codex MRLs for flonicamid in/on commodities of the Brassica, head and stem, group 5-16.  These Canadian MRLs are established at 1.5 ppm and are harmonized.  There are Canadian MRLs and one Codex MRL for flonicamid in/on commodities of the Brassica, leafy greens, subgroup 4-16B.  For most commodities, the Canadian MRLs are established at 16 ppm and are harmonized with the exception of MRLs for arugula (4 ppm), Chinese broccoli (1.5 ppm), garden and upland cress (4.0 ppm).  Additionally, the Codex MRL is established for flonicamid in/on radish tops at 20 ppm.  This tolerance/MRL is not harmonized.  There is a Codex MRL established for flonicamid residues in/on cottonseed at 0.60 ppm, but not a Canadian MRL.  Thus, the tolerance/MRL for flonicamid residues in/on cottonseed is harmonized with Codex and harmonization with Canada is not an issue.  There are Canadian MRLs established for residues in/on members of the leaf petiole vegetable, subgroup 22B.  These MRLs are established at 4.0 ppm and are harmonized.  There is a Codex MRL for residues of flonicamid in/on celery at 1.5 ppm; this tolerance/MRL is not harmonized.  There are Canadian MRLs established for members of the leafy greens, subgroup 4-16A.  These MRLs are established at 4.0 ppm and are harmonized.  There are Codex MRLs established for residues of flonicamid in/on head lettuce and leaf lettuce at 1.5 and 8.0 ppm, respectively; these tolerances/MRLs are not harmonized.  There are Canadian MRLs for flonicamid in/on celtuce, Florence fennel, and kohlrabi.  These Canadian MRLs are established at the same levels as the U.S. tolerances and are harmonized.  

2.3 Label Recommendations

A revised label is requested in which the PHI is reduced to 0 days for the orange and grapefruit subgroups, but the 14-day PHI is retained for the lemons subgroup.  A revised Section B is required.  

3.0 Introduction

3.1 Chemical Identity

The chemical structure and nomenclature of flonicamid and its metabolites TFNA, TFNA-AM, and TFNG are presented in Table 3.1.  

Table 3.1.  Flonicamid Nomenclature.
Compound
                                       
Common name
Flonicamid
Company experimental name
IKI-220
IUPAC name
N-cyanomethyl-4-(trifluoromethyl)nicotinamide
CAS name
N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide
CAS #
158062-67-0
End-use products (EP)
Beleaf(TM) 50 SG (EPA Reg. No. 71512-10) and Flonicamid 50 WG (EPA Reg. No. 71512-9)
Compound
                                       
Common name
TFNA
Chemical name
4-trifluoromethylnicotinic acid
Compound
                                       
Common name
TFNA-AM
Chemical name
4-trifluoromethylnicotinamide
Compound
                                       
Common name
TFNG
Chemical name
N-(4-trifluoromethylnicotinoyl)glycine

3.2 Physical/Chemical Properties

Table 3.2 is a summary of the physical/chemical properties for flonicamid.  

Table 3.2.  Physicochemical Properties of Technical Grade Flonicamid.
Parameter
Value
Reference[1]
Molecular weight (g/mole)
229.16

Melting point
157.5 C
MRID 45854601 
pH
4.5 (25 C)

Density (g/cm[3]) 
1.531 (20 C)

Water solubility
5.2 g/L (20 C)

Solvent solubility
Solvent	g/100 mL (20 C)
acetone	17.32
acetonitrile	12.04
dichloromethane	0.40
ethyl acetate	3.57
hexane	0.00003
isopropyl alcohol	1.46
methanol	9.76
n-octanol	0.26
toluene	0.03
MRID 45656705
Vapor pressure
9.43 x 10[-7] Pa (20 C)
2.55 x 10[-6] Pa (25 C)
MRID 45854601
Dissociation constant, pKa
11.60 +- 0.03 (20 +- 1 C)
MRID 45656705
Octanol/water partition coefficient, Log(KOW)
1.9 (Log POW = 0.3) (29.8 C)
MRID 45854601
UV/visible absorption spectrum
Acidic and neutral aqueous solutions exhibited similar spectra with an absorption maximum near 265 nm and a molar absorptivity of 3,900 L/cm mol. A basic solution exhibited two absorption peaks. The peak observed in acidic and neutral solutions was present at a slightly longer wavelength, 270 nm, with an absorptivity of 4,200 L/cm mol. The second peak had absorption maxima at 204 nm with an absorptivity of 13,200 L/cm mol.

[1] RD Memo, 09/30/2003, S. Mathur, D285457

3.3 Pesticide Use Pattern/Directions

Proposed Use:  IR-4 has submitted proposed use directions for Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) and Flonicamid 50 WG (EPA Reg. No. 71512-9) which include instructions for applications to clover grown for seed west of the Rockies.  For clover, up to 2 applications may be made at 0.089 lb ai/A for control of aphids and plant bugs.  A RTI of 7 days between applications and a PHI of 60 days are specified.  A maximum of 0.18 lb ai/A may be applied per year.  The use directions include the following restriction:  For use on clover grown for seed.  Do not allow foraging of fields or harvesting of hay within 60 days of the last application.  

Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) is registered for use on the citrus fruit group for applications at the rate of 0.089 to 0.178 lb ai/A.  The directions specify:  do not apply more than 3 applications at 0.089 lb ai/A; do not apply more than 2 applications at 0.133 lb ai/A; and do not apply more than one application at 0.178 lb ai/A.  Allow a minimum of 7 days between applications.  A PHI of 0 days is specified.

The proposed application scenarios are supported by the submitted residue chemistry data.  

Table 3.3.1.  Summary of End-Use Product.
                                  Trade Name
                                     Conc.
                                 Formulation 
                                  Label Date
                                 Target Crops
                                 Target Pests
                               Flonicamid 50 WG
                             EPA Reg. No. 71512-9
                      0.5 lb ai/lb of formulated product
                                      WG
                 02/22/2017 (date of cover letter for clover)
                                    Clover
                             Aphids and plant bugs
                           Beleaf 50 SG Insecticide
                             EPA Reg. No. 71512-10
                      0.5 lb ai/lb of formulated product
                                      SG
                 07/29/2016 (date of cover letter for clover)
                 05/30/2017 (date of cover letter for citrus)
                               Clover and Citrus
                             Aphids and plant bugs

Table 3.3.2.  Summary of Proposed Use Directions.
                                 App. Timing; 
                               Type; and Equip.
                                  Formulation
                                 Single App. 
                                     Rate 
                            Max. # App. per Season
                            Max. Seasonal App. Rate
                                      PHI
                                    (days)
                        Use Directions and Limitations
                             Clover grown for seed
Begin applications before populations begin to build or at economic thresholds/ ground or aerial equipment may be used
                                      WG
                       (0.5 lb ai/lb formulated product)
                      2.8 oz./A for aphids and plant bugs
                                (0.089 lb ai/A)
                                       2
                                   5.6 oz./A
                                (0.18 lb ai/A)
                                      60
Apply in a minimum of 20 gallons per acre (GPA) for ground applications or a minimum of 10 GPA for aerial applications.  Finished spray volume should be increased under extreme pest populations or dense plant foliage.  Allow a minimum of 7 days between applications.  Do not apply more than 2.8 oz./A (0.089 lb ai/A) per application; do not apply more than 5.6 oz./A per year.  Do not allow foraging of fields or harvesting of hay within 60 days of application.  
Begin applications before populations begin to build or at economic thresholds/ ground or aerial equipment may be used
                                      SG
                       (0.5 lb ai/lb formulated product)
                      2.8 oz./A for aphids and plant bugs
                                (0.089 lb ai/A)
                                       2
                                   5.6 oz./A
                                (0.18 lb ai/A)
                                      60
Apply in a minimum of 20 GPA for ground applications or a minimum of 10 GPA for aerial applications.  Finished spray volume should be increased under extreme pest populations or dense plant foliage.  Allow a minimum of 7 days between applications.  Do not apply more than 2.8 oz./A (0.089 lb ai/A) per application; do not apply more than 5.6 oz./A per year (0.18 lb ai/A).  Do not allow foraging of fields or harvesting of hay within 60 days of application.  
                                    Citrus
Begin applications before populations begin to build or at economic thresholds/ ground or aerial equipment may be used
                                      SG
                       (0.5 lb ai/lb formulated product)
             2.8 to 5.7 oz./A for Asian citrus psyllid and aphids
                           (0.089 to 0.178 lb ai/A)
                         1, 2, or 3 depending on rate
                                   8.4 oz./A
                                (0.267 lb ai/A)
                                       0
Apply in a minimum of 50 GPA by ground and 10 GPA by air.  Do not apply more than 3 applications at 0.089 lb ai/A; do not apply more than 2 applications at 0.133 lb ai/A; and do not apply more than one application at 0.178 lb ai/A.  Allow a minimum of 7 days between applications.  Do not apply more than a total of 0.267 lb ai/A per year.

Use directions for Brassica (cole) leafy vegetables fruiting vegetables have been modified to indicate that the use directions apply to the commodities of the Brassica head and stem vegetables, crop group 5-16 and to kohlrabi.  Use directions for leafy vegetables (except Brassica) have been modified to indicate that the use directions apply to the commodities of the leaf petiole vegetables, subgroup 22A, celtuce, Florence fennel, and the leafy vegetables (except Brassica) crop group 4-16A.  Use directions for cottonseed have been expanded to indicate the use directions apply to the cottonseed, subgroup 20C.

Conclusions:  The proposed use directions are adequate except for citrus.  For citrus, the use directions should indicate that for the grapefruit and orange subgroups, fruits may be harvested after a PHI of 0 days.  For lemons, the use directions should indicate samples may be harvested after a PHI of 14 days.  

4.0 Metabolism/Degradate Residue Profile
References:  
Memo, 04/22/2005, A. Acierto, D290386
Memo, 05/25/2005, J. Arthur, D289592

Table 4.0.7 and the following text are summaries of the residues of concern in plants (primary and rotational crops), poultry, and ruminants.  

Plants:  No new plant metabolism data were submitted in support of this petition.  The nature of the residue in plants is adequately understood.  Adequate metabolism studies are available on potato, peach, and wheat.  Based on the metabolism studies conducted in plants, the major metabolic pathway of flonicamid in plants involves hydrolysis of the cyano (-CN) and amide (-CONH-) functional groups and ring hydroxylation.  The residues of concern in plants for tolerance and risk assessment are flonicamid and its metabolites TFNA, TFNA-AM, and TFNG.  

Livestock:  No new livestock metabolism data were submitted in support of this petition.  The nature of the residue in livestock is adequately understood.  Metabolism studies using [[14]C]flonicamid are available on goats and hens.  HED has determined that the residues of concern in livestock commodities for the tolerance expression and risk assessment are flonicamid, TFNA and TFNA-AM.

Conclusions:  HED has determined that the residues of concern in plant commodities for tolerance and risk assessment are flonicamid and its metabolites TFNA, TFNA-AM, and TFNG and the residues of concern in livestock commodities for tolerance setting and risk assessment are flonicamid, TFNA and TFNA-AM.

Based on the previously submitted metabolism data, the HED concluded that the residues of concern, for tolerance enforcement and risk assessment, are as defined in Table 4.0.  

Table 4.0.  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression.
Matrix
Residues included in Risk Assessment
Residues included in Tolerance Expression
Plants
Primary Crop
Flonicamid, TFNA, TFNA-AM, and TFNG
Flonicamid, TFNA, TFNA-AM, and TFNG

Rotational Crop
Flonicamid, TFNA, TFNA-AM, and TFNG
Flonicamid, TFNA, TFNA-AM, and TFNG
Livestock
Ruminant
Flonicamid, TFNA and TFNA-AM
Flonicamid, TFNA and TFNA-AM

Poultry
Flonicamid, TFNA and TFNA-AM
Flonicamid, TFNA and TFNA-AM
Drinking Water
Flonicamid, TFNA, TFNG-AM, TFNG, TFNA-OH, TFNA-AM
Not Applicable

5.0 Residue Profile

5.1 Residue Analytical Methods

5.1.1 Data-Collection Methods 
Reference:
MRID 50151701
MRID 50292501

Clover samples were analyzed for residues of flonicamid and its three major metabolites using a working method very similar to the reference method, Analytical Methodology for IKI-220 (F1785) and its Major Metabolites in/on Peach, Potato Tuber, and Wheat Straw. FMC Corp. P-3561M.  August 2002.  FMC Corp. P3561M is the enforcement method for flonicamid.  The metabolites analyzed were TFNA, TFNA-AM and TFNG.  Method suitability was evaluated on clover forage and hay, both prior to and concurrently with sample analysis.  Recoveries were in the ranges of 74-96% (flonicamid), 66-89% (TFNA-AM), 73-92% (TFNA), and 62-86% (TFNG).  

Orange samples were analyzed for flonicamid and its three major metabolites using a working method very similar to the reference method, Analytical Methodology for Flonicamid and Its Major Metabolites on Various Crop Matrices and Their Associated Processed Products.  FMC Corp. Report Number P-3822.  The metabolites analyzed were TFNA, TFNA-AM and TFNG.  Method suitability was evaluated on whole oranges, both prior to and concurrently with sample analysis.  Concurrent recoveries were in the ranges of 76-106% (flonicamid), 71-105% (TFNA-AM), 77-112% (TFNA), and 70-115% (TFNG).  

The two methods are essentially identical.  Samples were homogenized with dry ice using a Robot Coupe chopper.  Subsamples were extracted in acetonitrile (ACN)/water using two rounds of shaking on a mechanical shaker.  The extracts were centrifuged to remove most of the solids from solution, and the extracts from the two shaking periods were combined.  The extract was evaporated using a rotary evaporator to remove the ACN.  Concentrated hydrochloric acid (HCl) was added to the extract, which was then filtered and brought to volume with water.  An aliquot of the extract was filtered and extracted two (forage) or three (hay) times with ethyl acetate.  The ethyl acetate fractions were combined and evaporated to near dryness on a nitrogen evaporator.  The extracts were brought to the final volume in 3:7 ACN/water, then analyzed via LC/MS/MS.  Analytical sets typically consisted of calibration standards, unfortified controls, fortified controls, and treated samples.  

The LOQ, based on the LLMV, was 0.010 ppm for all analytes in clover hay, forage and oranges.  The LOD for this method was reported to be 0.005 ppm for each analyte.

5.1.2 Food and Drug Administration (FDA) Multiresidue Methods (MRMs)
Reference:
Memo, 04/22/2005, A. Acierto, D290386

The requirements for data pertaining to multiresidue methods are fulfilled.  ISK Biosciences Corporation has previously submitted multiresidue method data for flonicamid and its metabolites.  Flonicamid and its metabolites were not found to be naturally fluorescent; therefore, further testing under Protocol A was not required.  Flonicamid and TFNA-AM were completely recovered using Protocol D (with no cleanup) but were not recovered using Protocols E and F.  TFNA and TFNG were not recovered using Protocols B, D, E, and F.  The testing data have been forwarded to FDA for inclusion in Pesticide Analytical Method (PAM), Vol. I.  HED concludes the FDA MRMs are not adequate for enforcement of flonicamid tolerances.  

5.1.3 Tolerance-Enforcement Method
Reference:
Memo, 09/29/2016, J. Smith, D435472

Plant Commodities:  FMC Method No. P-3561M, a LC/MS/MS method, is an acceptable enforcement method for flonicamid and its metabolites in plant commodities.  The method determines residues of flonicamid and its metabolites TFNA-AM, TFNA, and TFNG.  The method has been sufficiently validated in five diverse crops.  Depending on the matrix, the LOQ is 0.01 or 0.02 ppm.  The LOD can be estimated as one-third the LOQ.

Livestock Commodities:  Three enforcement methods are used for livestock commodities:  an LC/MS/MS method RCC No. 844743 for determination of residues in eggs, poultry tissues, and fat of cattle, goat, hog, horse, and sheep; LC/MS method RCC No. 842993 for determination of residues in milk; and LC/MS/MS method FMC No. P-3580, which includes an acid hydrolysis step, for determination of residues in meat and meat products (kidney and liver) of cattle, goat, hog, horse, and sheep.  All three methods determine flonicamid and the metabolites OH-TFNA-AM (6-hydroxy-4-trifluoromethylnicotinamide), TFNA-AM, TFNG, and TFNA.  The LOQs for each analyte in each matrix (based on the LLMV) are 0.01 ppm for Methods RCC No. 844743 and RCC No. 842993, and 0.025 ppm for FMC No. P-3580.  The LODs are all 0.005 ppm.

5.1.4 Submittal of Analytical Reference Standards
Reference:
Correspondence with G. Verdin, BEAD/ACL, 08/14/2017

The EPA National Pesticide Standards Repository has analytical standards of flonicamid with an expiration date of 12/18/2018; TFNA with an expiration date of 11/17/2020; TFNA-AM with an expiration date of 11/19/2020; and TFNG with an expiration date of 03/31/2017.  The TFNG standard has expired and submission of a new standard is required.  

If a new standard is being submitted, it should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of Gregory Verdin at the following address:

	USEPA
	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP
	701 Mapes Road
	Fort George G. Meade, MD  20755-5350

Please note:  the mail will be returned if the extended zip code is not used.

The letter of transmittal should include information on the assay of the standards, names of the analytical methods 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 or if decomposition occurs during storage.  Material Safety Data Sheets (MSDSs) must accompany all analytical standards as specified by Occupational Safety and Health Administration (OSHA) in 29 CFR §1910.1200.

5.2 Storage Stability
References:
MRID 50151701
Memo, 9/29/2016, J. Smith, D435472

Table 5.2.1 is a summary of the maximum storage intervals for samples between harvest and extraction for the clover and orange field trials.  To support sample storage durations, freezer storage stability data were generated concurrently with the clover field trials.  The maximum storage durations for samples between harvest and analysis were 542 days for forage and 540 days for hay.  Residues of parent flonicamid and its metabolites have been shown to be stable in clover forage and hay for intervals of up to 492 days (forage), and 491 days (hay), when stored frozen at -38 to -2ºC (see Table 5.2.1, below). 

TABLE 5.2.1.  Summary of Storage Conditions.
                                    Matrix
                                    Analyte
                           Storage Temperature (°C)
                        Actual Storage Duration (Days)*
               Interval of Demonstrated Storage Stability (Days)
                                 Clover forage
                                  Flonicamid
                                   -38 to -2
                                      542
                                      492
                                       
                                    TFNA-AM
                                       
                                       
                                       
                                       
                                     TFNA
                                       
                                       
                                       
                                       
                                     TFNG
                                       
                                       
                                       
                                  Clover Hay
                                  Flonicamid
                                   -38 to -2
                                      540
                                      491
                                       
                                    TFNA-AM

                                       
                                     TFNA

                                       
                                     TFNG

                                    Oranges
                                  Flonicamid
                                   -38 to -2
                                   268 days
                                  (~9 months)
                                   ~690 days
                                 (~23 months)
                                       
                                    TFNA-AM

                                       
                                     TFNA

                                       
                                     TFNG

* Maximum storage duration between harvest and analysis.  

To support sample storage durations for the orange field trials, freezer storage stability data were previously submitted.  The maximum storage durations for samples between harvest and analysis was 268 days (~9 months) for oranges.  Previously submitted storage stability data demonstrate that flonicamid and its metabolites TFNA, TFNA-AM, and TFNG are stable when stored frozen for ~23 months in/on five diverse crops including an oil seed (cottonseed), a non-oily grain (wheat grain), a root and tuber crop (potatoes), a leafy vegetable (spinach), and a fruiting vegetable (tomatoes).  HED concludes the available storage stability data are adequate to support the frozen storage intervals in the current study.  

Conclusions:  Although the forage and hay storage stability samples were only stored for roughly 91% of the maximum duration of the field trial samples, the data are adequate to support the storage durations and conditions of the samples from the clover field trials.  Adequate storage stability data are available to support the orange field trials.  

5.3 Residue Data

5.3.1 Crop Field Trials

Clover:
Reference:
MRID 50151701

IR-4 has submitted field trial data for flonicamid on clover (grown for seed) were conducted in the US, encompassing North American Free Trade Agreement (NAFTA) Growing Zones 11 (WA, 1 trial) and 12 (OR, 1 trial) during the 2014 growing season.  

At each trial site, two foliar broadcast applications of flonicamid, at RTIs of 6-7 days, were made to the treated plots.  The flonicamid end-use product (EP) applied was Carbine 50 WG (EPA Reg. No. 71512-9), a WG formulation containing 50% of the ai by weight.  Application rates ranged from 0.088 to 0.094 lb ai/A per application, for a total use rate of 0.178-0.188 lb ai/A per season.  Applications were made using either a tractor-pulled CO2 boom sprayer (OR trial) or a CO2 backpack sprayer (WA trial), in spray volumes of 22-31 GPA, which were sufficient to provide adequate dispersal of the test substance.  An adjuvant was added to the spray mixture for all applications.  Samples of clover forage and hay were collected at a PHI of 53 days.  The forage samples were collected on the day of harvest, while the hay samples were allowed to dry for one day (OR) or nine days (WA) in a protected area before collection.  Residue decline was not investigated.  

Individual sample (and per-trial average) combined residues of flonicamid and its metabolites in clover forage ranged from 0.067 to 0.174 ppm (0.068 to 0.168 ppm).  Individual sample (and per-trial average) combined residues of flonicamid and its metabolites in clover hay ranged from 0.248 to 0.584 ppm (0.256 to 0.506 ppm).  

The clover field trial data are acceptable.  The data were entered in to the Organization for Economic Co-operation and Development (OECD) tolerance calculator.  The OECD tolerance calculator recommends tolerance levels of 6.0 and 0.90 ppm for residues of flonicamid and its metabolites in/on clover forage and clover hay, respectively.  The clover residue data submitted with this petition are summarized in Table 5.3.1.1. 

Table 5.3.1.1.  Summary of Residues from Clover Field Trials with Flonicamid.
Crop Matrix
                            Total Application Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                                       N
                        Total Combined Residues[1] of 
                   Flonicamid + TFNA-AM + TFNA + TFNG (ppm)
                                       
                                       
                                       
                                       
                                    Min.[2]
                                    Max.[2]
                                    LAFT[3]
                                    HAFT[3]
                                   Median[3]
                                    Mean[3]
                                     SD[3]
                                    Forage
                                  0.178-0.188
                                      53
                                       4
                                     0.067
                                     0.174
                                     0.068
                                     0.168
                                     0.118
                                     0.118
                                      NA
                                      Hay
                                  0.178-0.188
                                      53
                                       4
                                     0.248
                                     0.584
                                     0.256
                                     0.506
                                     0.381
                                     0.381
                                      NA
1 Residues levels are expressed in terms of flonicamid equivalents.  
[2] Values based on total number of samples.  Two field trials were conducted, with 2 samples collected from each trial (n = number of individual samples).
[3] Values based on per-trial averages.  LAFT = lowest average field trial; HAFT = highest average field trial; SD = standard deviation.  
[4] NA = not applicable (standard deviation is not calculated for n < 3).  

Orange:
Reference:
MRID 50292501

Three field trials for flonicamid on oranges were conducted in the US, encompassing NAFTA Growing Zones 3 (FL, 2 trials) and 10 (CA, 1 trial) during the 2016 growing season.  

At each trial site, an untreated plot and 3 treated plots were maintained.  The first treated plot (TRT-2) received an airblast application of Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) at a target rate of 0.178 lb ai/A (200 g/ha).  Beleaf is formulated as a SG formulation which contains 50% ai by weight.  Applications were made in spray volumes of approximately 100 GPA.  Actual application rates varied from 0.177 to 0.179 lb ai/A or 99 to 101% of the target rate.

The second treated plot (TRT-3) received two airblast applications of Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) at a target rate of 0.134 lb ai/A (150 g/ha).  Applications were made in spray volumes of approximately 100 GPA with a 6 to 7-day interval between applications.  Actual application rates varied from 0.133 to 0.135 lb ai/A or 99 to 101% of the target rate.
The third treated plot (TRT-4) received three airblast applications of Beleaf 50 SG Insecticide (EPA Reg. No. 71512-10) at a target rate of 0.089 lb ai/A (100 g/ha).  Applications were made in spray volumes of 100 GPA with a 7 +- 1-day interval between applications.  Actual application rates varied from 0.088 to 0.090 lb ai/A or 99 to 101% of the target rate.

For all plots, samples (whole oranges) were collected from each plot at intervals of 0, 7, 14, and 21 days after the final application.  

In samples collected from the TRT-2 plot at day 0, flonicamid residues ranged from 0.018 to 0.119 ppm in whole orange samples.  Metabolite residues were all <LOD in all orange samples collected at day 0 from TRT-2 plot.  Total residues of flonicamid and its metabolites as parent equivalents ranged from 0.018 to 0.119 ppm at day 0.  In samples collected from the TRT-2 plot at day 7, flonicamid residues ranged from <LOQ to 0.124 ppm.  Metabolite residues were all <LOD in all orange samples collected at day 7.  Total residues of flonicamid and its metabolites as parent equivalents ranged from <LOQ to 0.124 ppm at day 7.  In samples collected from the TRT-2 plot at day 14, flonicamid residues ranged from <LOD to 0.050 ppm.  Residues of TFNG ranged from <LOD to <LOQ.  Metabolite residues were either <LOQ or <LOD in all orange samples collected at day 14.  Total residues of flonicamid plus metabolites as parent equivalents ranged from <LOD to 0.057 ppm at day 14.  In samples collected from the TRT-2 plot at day 21, flonicamid residues ranged from <LOD to 0.052 ppm.  Residues of TFNG were <LOQ.  Residues of TFNA ranged from <LOD to 0.011 ppm.  TFNA-AM was not detected at this sampling interval.  Total residues of flonicamid plus metabolites as parent equivalents ranged from <LOD to 0.070 ppm at day 21.

In samples collected from the TRT-3 plot at day 0, flonicamid residues ranged from 0.031 to 0.307 ppm in whole orange samples.  Metabolite TFNG residues ranged from <LOD to 0.011 ppm.  Metabolites TFNA and TFNA-AM were <LOD in all orange samples collected at day 0 from TRT-3 plot.  Total residues in flonicamid equivalents ranged from 0.031 to 0.318 ppm at day 0.  In samples collected from the TRT-3 plot at day 7, flonicamid residues ranged from 0.075 to 0.140 ppm.  Residues of metabolite TFNG ranged from <LOD to 0.011 ppm.  Residues of metabolite TFNA and TFNA-AM were not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.075 to 0.151 ppm.  In samples collected from the TRT-3 plot at day 14, flonicamid residues ranged from 0.013 to 0.059 ppm.  Residues of metabolite TFNG and TFNA ranged from <LOD to <LOQ.  Residues of metabolite TFNA-AM were not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.075 to 0.151 ppm.  In samples collected from the TRT-3 plot at day 21, flonicamid residues ranged from 0.012 to 0.057 ppm.  Residues of metabolite TFNG ranged from <LOD to 0.012 ppm.  Residues of metabolite TFNA ranged from <LOD to 0.010 ppm.  Metabolite TFNA-AM was not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.012 to 0.078 ppm.  

In samples collected from the TRT-4 plot at day 0, flonicamid residues ranged from 0.078 to 0.207 ppm in whole orange samples.  Residues of metabolites TFNG, TFNA, and TFNA-AM were not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.078 to 0.207 ppm.  In samples collected from the TRT-4 plot at day 7, flonicamid residues ranged from 0.055 to 0.086 ppm.  Residues of metabolite TFNG ranged from <LOD to 0.010 ppm.  Residues of metabolites TFNA and TFNA-AM were not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.055 to 0.093 ppm.  In samples collected from the TRT-4 plot at day 14, flonicamid residues ranged from 0.017 to 0.072 ppm.  Residues of metabolite TFNG and TFNA ranged from <LOD to <LOQ (0.009 ppm).  Residues of metabolite TFNA-AM were not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.017 to 0.090 ppm at day 14.  In samples collected from the TRT-4 plot at day 21, flonicamid residues ranged from <LOQ (0.009 ppm).  Residues of metabolite TFNG ranged from <LOD to <LOQ (0.009 ppm).  Residues of metabolite TFNA ranged from <LOD to <LOQ (0.007 ppm).  Residues of metabolite TFNA-AM were not detected at this interval.  Total residues in flonicamid equivalents ranged from 0.015 to 0.069 ppm at day 21.  

The orange residue data submitted with this petition are summarized in Table 5.3.1.2. 

Table 5.3.1.2.  Summary of Residues from Orange Field Trials with Flonicamid.
                                  Crop Matrix
                                Total Use Rate 
                                   (lb ai/A)
                                  PHI (Days)
                                     n[2]
                          Total Combined Residues of 
                  Flonicamid + TFNA-AM + TFNA + TFNG (ppm)[1]
                                       
                                       
                                       
                                       
                                    Min.[2]
                                    Max.[2]
                                    LAFT[3]
                                    HAFT[3]
                                   Median[3]
                                    Mean[3]
                                     SD[3]
                                    Oranges
                                     0.178
                                       0
                                       6
                                     0.018
                                     0.119
                                    0.0411
                                     0.104
                                     0.080
                                     0.070
                                     0.038
                                    Oranges
                                     0.178
                                       6
                                       6
                                     0.009
                                     0.124
                                    0.0152
                                     0.109
                                     0.020
                                     0.046
                                     0.049
                                    Oranges
                                     0.178
                                      14
                                       6
                                      ND
                                     0.057
                                    <LOQ
                                     0.053
                                     0.009
                                     0.020
                                     0.025
                                    Oranges
                                     0.178
                                      20
                                       6
                                      ND
                                     0.070
                                    <LOQ
                                     0.062
                                     0.003
                                     0.022
                                     0.032
                                    Oranges
                                  0.134 (x2)
                                       0
                                       6
                                     0.031
                                     0.318
                                    0.0355
                                     0.266
                                     0.053
                                     0.118
                                     0.120
                                    Oranges
                                  0.134 (x2)
                                       7
                                       6
                                     0.075
                                     0.151
                                    0.1055
                                     0.121
                                     0.104
                                     0.107
                                     0.026
                                    Oranges
                                  0.134 (x2)
                                      14
                                       6
                                     0.013
                                     0.067
                                    0.0151
                                     0.066
                                     0.018
                                     0.033
                                     0.026
                                    Oranges
                                  0.134 (x2)
                                      21
                                       6
                                     0.012
                                     0.078
                                    0.0126
                                     0.077
                                     0.015
                                     0.035
                                     0.033
                                    Oranges
                                  0.089 (x3)
                                       0
                                       6
                                     0.078
                                     0.207
                                    0.0827
                                     0.172
                                     0.091
                                     0.114
                                     0.050
                                    Oranges
                                  0.089 (x3)
                                       7
                                       6
                                     0.055
                                     0.093
                                    0.0705
                                     0.088
                                     0.081
                                     0.079
                                     0.013
                                    Oranges
                                  0.089 (x3)
                                      14
                                       6
                                     0.017
                                     0.090
                                    0.0186
                                     0.079
                                     0.027
                                     0.041
                                     0.031
                                    Oranges
                                  0.089 (x3)
                                      21
                                       6
                                     0.015
                                     0.069
                                    0.0161
                                     0.058
                                     0.030
                                     0.035
                                     0.020
[1] Expressed as parent equivalents.
[2] Values based on total number of samples.  Two field trials were conducted, with 2 samples collected from each trial (n = number of individual samples).
[3] Values based on per-trial averages.  LAFT = lowest average field trial; HAFT = highest average field trial; SD = standard deviation.  

5.3.2 Magnitude of the Residue - Rotational Crops
Reference:
Memo, 04/22/2005, A. Acierto, D290386

Additional field rotational crop data are not required.  A limited field rotational crop study was previously submitted and reviewed.  The study was found to be acceptable.  The results of the limited field rotational crop studies indicate that rotational crop tolerances are not required, and that the 30-day PBI for all crops not listed on the label, is appropriate.  

5.3.3 Processed Food/Feed
Reference:
Memo, 09/29/2016, J. Smith, D435472.

Processed food/feed commodities are not of concern for clover.  Processed food/feed commodities are of concern for citrus.  Data concerning the processing of citrus were previously submitted.  The previously submitted data show that residues of flonicamid slightly concentrated in orange pulp, but not in other processed commodities.  It was determined that tolerances for residues of flonicamid and its metabolites were not required for citrus processed commodities.  

5.3.4 Meat, Milk, Poultry, and Eggs
References:  
Memo, 08/14/2013, N. Dodd, D413404
Memo, 09/29/2016, J. Smith, D435472

Livestock tolerances for residues of flonicamid and its metabolites TFNA and TFNA-AM in/on livestock commodities are currently established.  Clover and citrus pulp are ruminant feed items, but are not fed to poultry or swine.  In conjunction with a previous petition, the contribution of citrus pulp, clover forage and hay to the livestock diet was evaluated.  The calculated dietary burden based on the maximum reasonably balanced diets for dairy and beef cattle were 1.3 and 3.4 ppm, respectively.  It was concluded that the established tolerances for residues in fat, meat and meat by product of cattle, goat, horse, and sheep are adequate.  Additionally, it was concluded a tolerance of 0.05 ppm for residues of flonicamid and its metabolites TFNA and TFNA-AM in milk should be established.  HED concludes that the current petition does not alter the previous decisions concerning the magnitude of the residue in/on livestock.

5.4 Food Residue Profile

Based on the proposed/registered application scenarios, flonicamid and its metabolites may be found in drinking water and crop and livestock commodities.  

6.0 Tolerance Derivation

Clover forage and hay:  The clover field trial data are acceptable.  The data from the field trials of this petition and the previous petition (PP#2E8137) were entered into the OECD tolerance calculator.  The OECD tolerance calculator recommends tolerance levels of 6.0 and 0.90 ppm for residues of flonicamid and its metabolites in/on clover forage and clover hay, respectively. A revised Section F/proposed tolerances is required.  

Brassica head and stem vegetables, crop group 5-16:  The tolerance level for residues of flonicamid in/on Brassica head and stem vegetables, crop group 5-16 and kohlrabi are based upon the established tolerance for flonicamid residues in/on Brassica (cole) leafy vegetables.

Leaf petiole vegetables, subgroup 22A:  The tolerance level for residues of flonicamid in/on leaf petiole vegetables, subgroup 22A, celtuce, Florence fennel, and the leafy vegetables (except Brassica) crop group 4-16A are based upon the established tolerance for flonicamid residues in/on leafy vegetables (except Brassica).

Use directions for leafy vegetables (except Brassica) have been modified to indicate that the use directions apply to the commodities of the leaf petiole vegetables, subgroup 22A, celtuce, Florence fennel, and the leafy vegetables (except Brassica) subgroup 4-16A, except spinach.  

Cottonseed, subgroup 20C:  The tolerance level for residues of flonicamid in/on cottonseed, subgroup 20C is based upon the established Codex cottonseed MRL for flonicamid and its metabolites. 

Table 6.0.1 is a summary of the proposed and HED recommended tolerances.  

Table 6.0.1.  Tolerance Summary for Flonicamid.
                                   Commodity
                           Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments
                        (correct commodity definition)
Vegetable, Brassica, head and stem, group 5-16
                                      1.5
                                       
                                       
Brassica, leafy greens, subgroup 4-16B
                                      16
                                       
                                       
Cottonseed, subgroup 20C
                                    0.60[1]
                                       
                                       
Leaf Petiole vegetable, subgroup 22B
                                      4.0
                                       
                                       
Leafy greens, subgroup 4-16A, except spinach
                                      4.0
                                       
                                       
Celtuce
                                      4.0
                                       
                                       
Florence fennel
                                      4.0
                                       
                                       
Kohlrabi
                                      1.5
                                       
                                       
1 Tolerance level is based on Codex cottonseed MRL at 0.60 ppm.

Additionally, IR-4 has proposed uses and tolerances (40 CFR §180.613(c)) for residues of flonicamid, including its metabolites and degrades, in or on the following commodities:

Table 6.0.2.  Tolerance Summary for Flonicamid.
                                   Commodity
                           Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments
                        (correct commodity definition)
Clover, forage
                                      0.9
                                     0.90
                                       
Clover, hay
                                      4.0
                                      5.0
                                       
1 Tolerance for regional registration (west of Rocky Mountains).  

IR-4 further proposes, upon establishment of the requested tolerances, to remove established tolerances for residues of flonicamid, including its metabolites and degrades, in or on the commodities listed in the following table:

Table 6.0.3.  Raw Agricultural Commodities/Crop Group
                                Tolerance Level
                                     (ppm)
Vegetable, leafy, except Brassica, group 4, except spinach
                                      4.0
Brassica, head and stem, subgroup 5A
                                      1.5
Brassica, leafy greens, subgroup 5B
                                      16
Radish, tops
                                      16
Turnip, greens
                                      16
Cotton, undelinted seed
                                     0.50
Turnip Greens
                                      3.0

7.0.	REFERENCES

Memo, 09/29/2016, J. Smith, D435472
RD Memo, 09/30/2003, S. Mathur, D285457
Memo, 04/22/2005, A. Acierto, D290386
Memo, 05/25/2005, J. Arthur, D289592
MRID 50151701
MRID 50292501
Memo, 04/22/2005, A. Acierto, D290386
Correspondence with G. Verdin, BEAD/ACL, 08/14/2017
Memo, 08/14/2013, N. Dodd, D413404

Attachment 1:  International Residue Limits.
Attachment 2:  OECD MRL Calculation Procedure Inputs/Outputs

Attachment 1:  International Residue Limits.

                        Flonicamid (128016, 09/05/2017)
Summary of US and International Tolerances and Maximum Residue Limits 
Residue Definition:
US
Canada
Mexico[2]
Codex
Plant:  Flonicamid and its metabolites TFNA, TFNA-AM, and TFNG, expressed as flonicamid 

None
Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US
Canada
Mexico
Codex
Clover forage
                                      0.9
--
--
--
Clover hay
                                      4.0
--
--
--
Vegetable, Brassica, head and stem, group 5-16
                                      1.5
Broccoli  -  1.5
Brussels Sprouts  -  1.5
Cabbage  -  1.5
Cabbage, Chinese napa  -  1.5
Cauliflower  -  1.5
--
--
Brassica, leafy greens, subgroup 4-16B
                                      16
Arugula  -  4
Broccoli, raab  -  16
Broccoli, Chinese  -  1.5
Collards  -  16
Garden cress  -  4
Upland cress  -  4
Kale  -  16
Mustard greens  -  16
Radish tops  -  16
Rape leaves - 16
--
Radish tops - 20
Cottonseed, subgroup 20C
                                     0.60
--
--
Cottonseed - 0.60
Leaf petiole vegetable, subgroup 22B
                                      4.0
Cardoon  -  4
Celery  -  4
Chinese celery  -  4
Rhubarb - 4
--
Celery - 1.5
Leafy greens, subgroup 4-16A
                                      4.0
Amaranth, leafy  -  4
Chervil  -  4
Chrysanthemum, garland  -  4
Corn salad  -  4
Dandelion leaves  -  4
Dock  -  4
Endive  -  4
Head lettuce  -  4
Leaf lettuce  -  4
Orach  -  4
Parsley, fresh leaves  -  4
Garden purslane  -  4
Winter purslane  -  4
Radicchio  -  4
Swiss chard - 4
--
Head lettuce  -  1.5
Leaf lettuce  -  8
Celtuce
                                      4.0
Celtuce - 4
--
--
Florence fennel
                                      4.0
Florence fennel - 4
--
--
Kohlrabi
                                      1.5
Kohlrabi  -  1.5
--
--
Completed:  W. Wassell; 09/05/2017
[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.

Attachment 2:  OECD MRL Calculation Procedure Inputs/Outputs

Clover Hay:

Flonicamid
 
Clover hay
 
US
 
0.89 lb ai/A x 2
 
 
 
Residues (mg/kg)
2.045
 
0.506
 
0.256
 
 

 
 
 
 
 
 
                                  Flonicamid
                                       
 
                                  Clover hay
                                       
 
                                      US
                                       
 
                               0.89 lb ai/A x 2
                                       
 
 
 
 
 
 
Total number of data (n)
                                       3
                                       
 
 
 
                                       
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                       3
                                       
 
 
 
                                       
                                       
 
Lowest residue (LR)
                                     0.256
                                       
 
Highest residue (HR)
                                     2.045
                                       
 
Median residue (STMR)
                                     0.506
                                       
 
 
 
                                       
                                       
 
Mean
 
                                     0.936
                                       
 
Standard deviation (SD)
                                     0.969
                                       
 
 
 
                                       
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
 
 
 
 
Unrounded
 
                                     4.811
                                       
 
Rounded to the next MRL class
                                       5
                                       
 
 
 
                                       
                                       
 
High uncertainty of MRL estimate due to small dataset.
                                       
                                       
 
 
 
 
 

Clover forage:

Flonicamid
 
Clover forage
US
 
0.89 lb ai/A x 2
 
 
 
Residues (mg/kg)
0.377
 
0.168
 
0.068
 

 
 
 
 
 
 
                                  Flonicamid
                                       
 
                                 Clover forage
                                       
 
                                      US
                                       
 
                               0.89 lb ai/A x 2
                                       
 
 
 
 
 
 
Total number of data (n)
                                       3
                                       
 
 
 
                                       
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                       3
                                       
 
 
 
                                       
                                       
 
Lowest residue (LR)
                                     0.068
                                       
 
Highest residue (HR)
                                     0.377
                                       
 
Median residue (STMR)
                                     0.168
                                       
 
 
 
                                       
                                       
 
Mean
 
                                     0.204
                                       
 
Standard deviation (SD)
                                     0.158
                                       
 
 
 
                                       
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
 
 
 
 
Unrounded
 
                                     0.835
                                       
 
Rounded to the next MRL class
                                      0.9
                                       
 
 
 
                                       
                                       
 
High uncertainty of MRL estimate due to small dataset.