Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

MEMORANDUM

Date: October 2, 2012

SUBJECT: REVISED. Flonicamid. Petition for the Establishment of Permanent Tolerances 

and Registration for Use on Berry Low-Growing Subgroup 13-07G, Cucumber for 

Greenhouse Use Only, and Rapeseed Sub-group 20A. Summary of Analytical 

Chemistry and Residue Data.

PC Code: 128016 DP Barcode: D396902

Decision No.: 457726 Registration No.: 71512-10, 71512-9

Petition No.: 1E7942 Regulatory Action: Section 3 Registration

Assessment Type: Single Chemical Case No.: NA

TXR No.: NA CAS No.: 158062-67-0

MRID No.: See Table Below 40 CFR: 180.613

 

FROM: Amelia M. Acierto, Chemist

Risk Assessment Branch III (RAB3)

Health Effects Division (HED; 7509P)

THROUGH: Stephen Funk, Senior Scientist

Risk Assessment Branch III (RAB3)

Health Effects Division (HED; 7509P)

TO: Barbara Madden/Sydney Jackson, RM #5

Risk Integration, Minor Use and Emergency Response Branch (RIMUERB)

Registration Division (7505P)

Note: The DER for greenhouse use on cucumber was originally prepared by the Pest Management Regulatory 

Agency (PMRA) of Health Canada and DERs for berry and canola were originally prepared under contract by 

Versar, Inc. (6850 Versar Center, Springfield, VA 22151; submitted 4/3/12). The DERs have been reviewed by 

HED and revised to reflect current Office of Pesticide Programs (OPP) policies.

MRID Summary Table

MRID No. Study Type Comments

48657101 860.1500 New DER; 48657101.der.doc Strawberry

48657102 860.1500 New DER; 48657102.der.doc Cucumber

48657103 de.1 860.1500 New DER; 48657103.de.1.doc Canola

48657103 de.2 860.1520 New DER; 48657103.de.2.doc Canola processed food
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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Table of Contents

Executive Summary........................................................................................................................ 3

Regulatory Recommendations........................................................................................................ 5

Pre-Registration Data Needs....................................................................................................... 6

Condition-of-Registration Data Needs........................................................................................ 6

Tolerance Considerations................................................................................................................ 6

Analytical Method....................................................................................................................... 6

Recommended Tolerances.......................................................................................................... 6

International Harmonization ....................................................................................................... 7

Revisions to Petitioned-For Tolerances...................................................................................... 7

Residue Profile................................................................................................................................ 7

Residue Chemistry Guidelines........................................................................................................ 9

Directions for Use (860.1200) .................................................................................................... 9

Nature of the Residue in Plants and Livestock (860.1300)....................................................... 10

Residue Analytical Methods (860.1340) .................................................................................. 11

Multiresidue Methods (860.1360) ............................................................................................ 11

Storage Stability (860.1380) ..................................................................................................... 11

Food Handling (860.1460)........................................................................................................ 12

Meat, Milk, Poultry, and Eggs (860.1480)................................................................................ 12

Crop Field Trials (860.1500) .................................................................................................... 13

Strawberry ................................................................................................13

Cucumber................................................................................................ 15

Canola ................................................................................................................................... 16

Processed Food and Feed (860.1520) ....................................................................................... 18

Canola ................................................................................................................................... 18

Confined Accumulation in Rotational Crops (860.1850)......................................................... 20

Field Accumulation in Rotational Crops (860.1900)................................................................ 20

Proposed Tolerances (860.1550)............................................................................................... 20

Appendix I .................................................................................................................................... 23

International Residue Limits................................................................................................. 23

Appendix II................................................................................................................................... 24

Tolerance Assessment Calculations.......................................................................................... 24

Berry, Low growing, Subgroup 13-07G ............................................................................... 24

Cucumber (Greenhouse, Foliar)............................................................................................ 24

Cucumber (Greenhouse, Chemigation)............................................................ 24

Rapeseed, Subgroup 20A...................................................................................................... 25
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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Executive Summary

Flonicamid 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 (OP's and 

carbamates), or nicotinic acetylcholine receptors (neo-nicotinoids). Flonicamid has been 

described as a new chemistry (cyanomethyl trifluoromethyl nicotinamide) with a novel (but 

undefined) mode of action, different from other commercially available products. 

The Interregional Research Project No. 4 (IR-4) has submitted crop field trial and greenhouse 

data generated during 2008 and 2009 growing season from the North American Free Trade 

Agreement (NAFTA) Growing Zones in support of the petition for the establishment of 

permanent tolerances for the combined residues of flonicamid [N-(cyanomethyl)-4-

trifluoromethylnicotinamide] and its metabolites TFNA (4-trifluoromethylnicotinic acid), TFNAAM (4-trifluoromethylnicotinamide), and TFNG [N-(4-trifluoromethylnicotinoyl)glycine], in or 

on the following raw agricultural commodities (RACs):

Berry low-growing subgroup 13-07G ....... . .... ...1.4 ppm

Cucumber * ....................................... ......1.3 ppm

Rapeseed subgroup 20A ......................... .......1.5 ppm

 * To increase tolerance on cucumber for greenhouse use only. 

The petitioner proposes Section 3 registration of BeleafTM 50SG (EPA Reg. No. 71512-10) and 

Flonicamid 50WG (EPA Reg. No. 71512-9) for use on the berry subgroup 13-07G, cucumber for 

greenhouse use, and the rapeseed subgroup 20A. BeleafTM 50SG and Flonicamid 50WG are 50% 

water soluble granule (SG) formulations of flonicamid (containing 0.5 pound active ingredient 

per pound of formulated product).

The end-use products can be applied with ground, aerial and chemigation equipment at the total 

rate of 0.267- 0.269 lb ai/acre (equivalent rate calculated/plant for greenhouse use). A non-ionic 

surfactant was used in the crop trials except for canola and for greenhouse cucumber treated by

chemigation. The proposed pre-harvest intervals (PHIs) range from 0-days for strawberry and 

cucumber to 6-8 days for canola.

Tolerances are established for residues of flonicamid under 40 CFR §180.613(a)(1) on various 

raw agricultural commodities (RACs) at levels ranging from 0.2 ppm on fruit, pome, group 11 

and vegetable, tuberous and corm, subgroup 1C to 16.0 ppm on turnip greens; Brassica leafy

greens subgroup 5B; and raddish, tops. Tolerance on cucumber is currently included in the 

vegetable, cucurbit, group 9 at 0.40 ppm. Tolerances have also been established under 

§180.613(a)(2) on livestock commodities including egg and milk at levels ranging from 0.03 

ppm on fat of cattle, goat, horse, poultry, and sheep to 0.08 ppm on meat byproducts of cattle, 

goat, horse, poultry, and sheep.
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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The nature of the residue in plants and livestock is adequately understood for purposes of this 

petition. The metabolism of flonicamid in plant and livestock are identical. The main pathway

of metabolism involves hydrolysis of the cyano and amide functional groups in the molecule.

The residues of concern in plants for the tolerance expression and risk assessment are flonicamid, 

TFNA, TFNA-AM and TFNG (D290386, A.M. Acierto, 4/22/2005). The HED’s RARC (RARC 

Sec. 3.0, 4/20/05) has determined that the residues of concern in livestock commodities for the 

tolerance expression and risk assessment are flonicamid, TFNA and TFNA-AM.

An adequate enforcement method is available which uses high performance liquid 

chromatography with tandem mass spectrometric detection (LC/MS/MS) adapted from FMC No. 

P-3561M. The method has been used for data collection and enforcement for plant 

commodities. The method determines flonicamid and its metabolites TFNA, TFNA-AM and 

TFNG and has been sufficiently validated in five diverse crops. A number of minor 

modifications to the method were made for the petitioned crops including changes in clean-up 

procedures, reagents, and sample sizes. An LC-MS method similar to the LC/MS/MS method 

was used for cucumber. Method validation and concurrent recoveries in strawberry, cucumber 

and canola were conducted using untreated control samples fortified separately with flonicamid 

and its metabolites at 0.02, 0.20 and 2.0 ppm. The fortification levels were adequate to bracket 

expected residue levels in the strawberry and cucumber. The quantifiable residues were 

converted to parent equivalents by the study reviewer using molecular weight conversion factors 

of 1.20, 1.21, and 0.92 for TFNA, TFNA-AM, and TFNG, respectively. The LOQ (determined 

as the LLMV) was 0.02 ppm for each analyte and the LOD was calculated as 1/3 the LOQ.

In canola, poor method validation recoveries and poor concurrent recoveries were reported using 

the HPLC/MS/MS method for each analyte at the 0.02 ppm fortification level. The petitioner 

noted that this is caused by ion suppression due to matrix interference. HED recommends raising

the limit of quantitation (LOQ) for each analyte to 0.2 ppm or about 0.9 ppm for the combined 

residues of flonicamid and its metabolites, calculated as flonicamid

(ChemSAC Minutes, 4/2/12).

Three enforcement methods are used for livestock commodities: an LC/MS/MS method RCC 

No. 844743 (for the determination of residues in eggs and livestock tissues), LC/MS method 

RCC No. 842993 (for determination of residues in milk) and LC/MS/MS method FMC No. P3580, which includes an acid hydrolysis step (for determination of residues in meat and meat 

products (muscle, kidney and liver) of cattle, goat, hog, horse, and sheep.

The multi-residue methods requirement has been fulfilled. Flonicamid and TFNA-AM were 

completely recovered using Protocol D (with no cleanup) but were not recovered using Protocols

E and F. Metabolites TFNA and TFNG were not recovered using Protocols B, D, E and F. 

Available storage stability data demonstrate that flonicamid and its metabolites TFNA, TFNAAM, and TFNG are relatively stable in/on oil seed, non-oily grain, root and tuber crops, leafy

vegetables, and fruiting vegetables in frozen storage for ~23 months. Storage stability data 

demonstrate that processed commodities are also stable for ~23 months. The current storage 

stability data demonstrate that residues of flonicamid, TFNA, TFNA-AM, and TFNG are stable 

in/on the RAC samples of berry, cucumber and canola stored frozen for up to 460, 336 and 735 

days, respectively. The available data on the five diverse crops (oil seed, non-oily grain, root and 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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tuber crop, leafy vegetables, and fruiting vegetables) are adequate to support the storage 

conditions and durations of the RAC samples from the submitted field trials.

Adequate field trial data were submitted supporting the use of the flonicamid 50SG formulation 

on the proposed crop/crop groups. An adequate number of field trials were conducted on the 

required representative crops in the appropriate geographic regions. The crop field trial data 

reflect the proposed multiple application rates and pre-harvest intervals (PHIs). The 

Organization of Economic Cooperation and Development (OECD) spreadsheet calculation 

procedure was used to determine appropriate tolerance levels. The proposed tolerance for berry,

low-growing, subgroup 13-07G is 1.4 ppm; the proposed tolerance for greenhouse cucumber is

1.3 ppm. Based on the OECD spreadsheet calculation procedure, the proposed tolerances for 

berry and cucumber as a member of the cucurbit vegetable group should be raised to 1.5 ppm.

Therefore, a revised Section F is required to reflect this determination. The recommended 

tolerance of 1.5 ppm will replace the existing tolerance of 0.40 ppm for the cucurbit vegetable 

group 9 under 40 CFR §180.613 (a)(1). The proposed tolerance of 1.5 ppm for rapeseed is

appropriate.

Field trial decline studies demonstrate that the combined residues of flonicamid and its 

metabolites in strawberry decline with increasing pre-harvest intervals. Residue decline was 

observed in greenhouse grown cucumber treated by foliar spray but not in crops treated by

chemigation where the residues increased from the 0- to 7-day PHIs. No decline study was 

reported for canola.

Adequate processing studies in/on canola are available. The processing data indicate that the 

combined residues of flonicamid, TFNG, TFNA, and TFNA-AM do not concentrate in canola 

meal and canola oil (each have 0.27x average processing factor). The reported processing factors 

do not exceed the theoretical concentration factor of 1.0x for canola meal and 3.0x for canola oil

(OCSPP §860.1520, Table 3). Based on these results, the tolerances for livestock commodities

will not change.

 

No new rotational crop data were submitted and none are required with the use of flonicamid on 

rapeseed, cucumber and berry (OCSPP 860.1850). 

There are currently no Codex or Canadian maximum residue limits (MRLs) established for 

residues of flonicamid in crop or livestock commodities. 

The analytical standards for flonicamid, and its metabolites (TFNA, TFNA-AM and TENG) are

available at the EPA National Pesticide Standards Repository with expiration dates from 2014 -

2016.

Regulatory Recommendations 

Provided the revisions to the Section B/label and Section F are made as requested below (in the 

Pre-Registration Data Needs section), the available residue chemistry data are adequate to 

support registration of the crop/crop group commodities requested by the petitioner at the 

tolerance levels recommended in Table 1 below (in the Recommended Tolerances section).
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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Pre-Registration Data Needs

The submitted labels for BeleafTM 50SG Insecticide and Flonicamid 50WG have a restriction 

prohibiting greenhouse use. The labels should be revised to: “Do not use this product in 

greenhouses, except on cucumbers”.

The registrant needs to submit a revised section F in which the recommended tolerances and 

commodity definitions listed in Table 1 are proposed. 

Condition-of-Registration Data Needs

No residue chemistry conditional registration data needs are associated with this tolerance 

petition.

Tolerance Considerations

Analytical Method

Adequate enforcement methods are available to enforce the proposed tolerances for flonicamid 

and the major metabolites in plants and livestock. The proposed method for plants uses 

LC/MS/MS (FMC No. P-3561M) to determine the residues of flonicamid and its major 

metabolites, TFNA-AM (4-trifluoromethylnicotinamide), TFNA (4-trifluoromethylnicotinic 

acid), and TFNG [N-(4-trifluoromethylnicotinoyl)glycine]. The reported LOQ was 0.02 ppm and 

the reported LOD was calculated as 1/3 the LOQ. This LOQ was demonstrated for cucumber 

and strawberry, but not for canola. Based on the poor results in the method validation and 

concurrent recoveries for canola at 0.02 ppm fortifications per analyte, it is required to raise the 

LOQ to 0.2 ppm per each analyte (3/14/12). Recoveries were consistently acceptable at the 0.2 

ppm per analyte fortification level.

Recommended Tolerances

Tolerances should be established in 40 CFR §180.613 with the following tolerance expression, as 

per the Steve Knizner memo dated 5/27/09:

Tolerances are established for the residues of the insecticide flonicamid including its 

metabolites and degradates, in or on the commodities in the following table. Compliance 

with the tolerance levels specified in the following table 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.

HED recommends for establishment of tolerances on the commodities in Table 1 using the same 

tolerance expression as above at the tolerance levels recommended in Table 1 below:
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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Table 1. Tolerance Summary for Flonicamid

Commodity Established/Proposed 

Tolerance

(ppm)

Recommended 

Tolerance 

(ppm)

Comments (correct 

commodity definition)

Berry, low growing, subgroup 13-07G 1.4 1.5

1

Cucumber for greenhouse use only 9 1.3 1.52 Vegetable, cucurbit, 

group 9

Rapeseed subgroup 20A 1.5 1.53

1

The representative commodity for the berry, low growing, subgroup 13-07G is strawberry. The Organization of 

Economic Coordination and Development (OECD) spreadsheet calculation procedure gave a value of 1.5 ppm for

strawberry.

2 A tolerance was established on cucumber at 0.4 ppm (as a member of the cucurbit vegetable group 9). The current 

petition is to increase the tolerance to 1.3 ppm for cucumber grown in greenhouse only. The OECD spreadsheet 

calculation procedure gave a value of 1.5 ppm for cucumber grown in the greenhouse treated at the proposed label 

rate by foliar spray. The OECD spreadsheet calculation procedure gave a value of 0.7 ppm for cucumber treated by 

chemigation. This tolerance value and the existing tolerance of 0.40 ppm in 40 CFR §180.613 will be covered under 

the foliar spray treatment in greenhouse.

3

The representative commodity for the rapeseed, subgroup 20A is canola. The OECD spreadsheet calculation 

procedure gave a value of 1.5 ppm for canola.

No tolerances are required for the processed commodities of canola based on the demonstrated 

processing factor of <0.27x for each canola meal and canola oil. The maximum theoretical 

concentration factors for canola meal and canola oil are 1.9x and 3.0x, respectively (OCSPP

860.1520, Table 3). 

International Harmonization

There are no Codex or Canadian maximum residue limits (MRLs) on the proposed crops. 

Revisions to Petitioned-For Tolerances

Based on the OECD spreadsheet calculation procedure, HED recommends increasing the 

proposed tolerance from 1.4 ppm to 1.5 ppm for berry, low growing, subgroup 13-07G and from 

1.3 ppm to 1.5 ppm for greenhouse grown cucumber (as a member of the cucurbit vegetable 

group).

Residue Profile

The chemical structure and nomenclature of flonicamid and its metabolites TFNA, TFNA-AM, 

and TFNG, and the physicochemical properties of the technical grade of flonicamid are presented 

in Tables 2 and 3. 
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TABLE 2. Test Compound Nomenclature.

Compound

N

CF3

N

H

O

CN

Common name Flonicamid

Company experimental name IKI-220

IUPAC name N-cyanomethyl-4-(trifluoromethyl)nicotinamide

CAS name N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide

CAS registry number 158062-67-0

End-use product (EP) 50% SG formulation; Beleaf 50 SG (EPA Reg. No. 71512-10)

Compound

N

CF3

OH

O

Common name TFNA

Chemical name 4-trifluoromethylnicotinic acid

Compound

N

CF3

NH2

O

Common name TFNA-AM

Chemical name 4-trifluoromethylnicotinamide

Compound

N

CF3

N

H

O

OH

O

Common name TFNG

Chemical name N-(4-trifluoromethylnicotinoyl)glycine

TABLE 3. Physicochemical Properties of the Technical Grade Test Compound Flonicamid.

Parameter Value Reference1

Melting point 157.5 C MRID 45854601 

pH 4.5 (25 C)

Density 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
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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TABLE 3. Physicochemical Properties of the Technical Grade Test Compound Flonicamid.

Parameter Value Reference1

Vapor pressure 9.43 x 10-7

Pa (20 C)

2.55 x 10-6Pa (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 

an absorption maxima at 204 nm with an absorptivity 

of 13,200 L/cm mol.

1 RD Memo, DP# 285457, 9/30/2003, S. Mathur

Residue Chemistry Guidelines

Directions for Use (860.1200)

The petitioner has submitted amended labels for a 50SG formulation (Beleaf 50SG Insecticide,

EPA Reg. No. 71512-10) and for the 50WG formulation (Flonicamid 50WG, EPA Reg. No. 

71512-9). A summary of the proposed use patterns on berry, low growing (subgroup 13-07G), 

greenhouse grown cucumbers, and rapeseed (subgroup 20B) is detailed in Table 4.

Table 4. Summary of Directions for Use of Flonicamid

Application, 

Timing, 

Type and 

Equipment

Formulation 

(EPA Reg. 

Nos.).

App. Rate 

(lb ai/A)

[fl oz /A]

Max. No. 

App. per 

Season

RTI

(days)

Max. 

Seasonal 

App. 

Rate

(lb ai/A)

[fl oz /A]

PHI

(days) Use Directions and other Limitations

Berry, low growing, subgroup 13-07G [Bearberry, bilberry, blueberry, lowbush, cloudberry, cranberry, lingonberry, muntries 

partridgeberry, strawberry, cultivars, varieties, and/or hybrids of these]1.

Foliar spray

ground or air

Beleaf 50SG

(EPA Reg.

No. 71512-10)

or

Flonicamid 

50WG (EPA 

Reg. No. 

71512-9)

0.089

[2.8]

3 7 0.267

[8.4]

0 Apply when Aphids or Lygus first appear in the field 

and before populations reach high levels. Flonicamid

will stop Aphids or Lygus feeding rapidly but it may 

take several days to see reduction in Aphids or Lygus 

numbers. Reapply when new insects are detected. 

Two sequential applications of flonicamid result in 

better Aphids or Lygus control than a single 

application. Do not make more than 2 applications of 

flonicamid without rotating to an insecticide with a 

different mode of action. 

Greenhouse Cucumbers
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Table 4. Summary of Directions for Use of Flonicamid

Application, 

Timing, 

Type and 

Equipment

Formulation 

(EPA Reg. 

Nos.).

App. Rate 

(lb ai/A)

[fl oz /A]

Max. No. 

App. per 

Season

RTI

(days)

Max. 

Seasonal 

App. 

Rate

(lb ai/A)

[fl oz /A]

PHI

(days) Use Directions and other Limitations

Foliar 

directed

Beleaf 50SG

(EPA Reg.

No. 71512-10)

or

Flonicamid 

50WG (EPA 

Reg. No. 

71512-9)

0.089

[2.8]

2 7 4.28 oz/A 

or 0.1 oz

per 1000 

ft2

0 1) For Aphids Plant Bugs. Begin applications before 

populations begin to build and before damage is 

evident, according to local pest management 

guidelines. Use LOWER RATE for building 

populations and HIGHER RATE for greater 

populations and/or dense foliage. Rapidly growing 

plants may need retreatment. Check plants often and 

retreat as necessary to maintain population below 

damaging levels.

2) For Greenhouse Whitefly. Apply when adult 

whiteflies first appear. Do not allow population to 

increase unchecked before making the first application.

Application provides SUPPRESSION only. Apply in 

combination with other effective products for control. 

Check plants often and retreat as necessary to maintain 

population below damaging levels. 

Chemigation

(to soil or 

growth 

media)

Beleaf 50SG

(EPA Reg.

No. 71512-10)

or

Flonicamid 

50WG (EPA 

Reg. No. 

71512-9)

0.089

[2.8]

2 7 4.28 oz/A 

or 2.8 

g/1000 ft2

0 Begin applications before populations begin to build 

and before damage is evident according to local pest 

management guidelines. Apply using a drench by 

hand, drip irrigation or with motorized calibrated 

irrigation equipment to the base of the plants.2

Rapeseed Subgroup 20A [Borage, crambe, cuphea, echium, flax seed, gold of pleasure, hare’s ear mustard, lesquerella, lunaria, meadowfoam, 

milkweed, mustard seed, oil raddish, poppy seed, rapeseed, sesame, sweet rocket, cultivars varieties, and/or hybrids of these].

Foliar spray 

ground or air

Beleaf 50SG

(EPA Reg.

No. 71512-10)

or

Flonicamid 

50WG (EPA 

Reg. No. 

71512-9)

0.089

[2.8]

3 7 0.267

[8.4]

7 Apply when Aphids or Lygus first appear in the field 

and before populations reach high levels. Flonicamid

will stop Aphids or Lygus feeding rapidly but it may 

take several days to see reduction in Aphids or Lygus 

numbers. Reapply when new insects are detected. 

Two sequential applications result in better Aphids or 

Lygus control than a single application. Do not make 

more than 2 applications of flonicamid without 

rotating to an insecticide with a different mode of 

action.3

1

Spray adjuvants may improve coverage but do not use binder or sticker-type surfactants. Only use adjuvants known to be safe on strawberries.

2 Use a minimum of 25 gal/1000 plants but do not exceed the holding capacity of soil or growth media. Do not apply more than 4.28 oz/A (0.44

oz/1000 plants based on 1 plant/4.5 ft2or 9712 plants/A) of flonicamid per application. 

3

Spray adjuvants may improve coverage but do not use binder or sticker-type surfactants. Only use adjuvants known to be safe on canola

The submitted labels for BeleafTM 50SG Insecticide and Flonicamid 50WG have a restriction for 

greenhouse use. The labels should be revised to change the statement “Do not use this product in 

greenhouses” to “Do not use this product in greenhouses, except for cucumber”.

Conclusions. The submitted labels (EPA Reg. Nos. 71512-10 and 71512-9) are adequate to 

allow evaluation of the residue data relative to the proposed use. Revised labels are required to

delete the restriction for greenhouse use for cucumber.

Nature of the Residue in Plants and Livestock (860.1300)

No new metabolism data were submitted in support of this petition and none are required. The 

nature of the residue in plants and livestock is adequately understood. 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. 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

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The residues of concern in plants for tolerance and risk assessment are flonicamid and its 

metabolites TFNA, TFNA-AM, and TFNG (D290386, A.M. Acierto, 4/22/2005). In livestock 

commodities, HED has determined that the residues of concern for the tolerance expression and 

risk assessment are flonicamid, TFNA and TFNA-AM (HED/RARC Sec. 3.0, 4/20/05).

Residue Analytical Methods (860.1340)

The method entitled “Analytical Methodology for IKI-220 (F1785) and its Major Metabolites 

in/on Peach, Potato Tuber, and Wheat Straw” (FMC No. P-3561M) was used with some 

modifications to determine residues of flonicamid and its metabolites TFNA-AM (4-

trifluoromethylnicotinamide), TFNA (4-trifluoromethylnicotinic acid), and TFNG [N-(4-

trifluoromethylnicotinoyl)glycine] in/on strawberry and canola. Cucumber fruit samples were 

analyzed for the residues of flonicamid and the three major metabolites, using a liquid 

chromatography with mass spectroscopic detection (LC-MS) working method entitled “Residue 

Analysis of Flonicamid, TFNA, TFNG, TFNA-AM by LC/MS, Version #3”. A number of 

minor modifications to the methods were made, including changes in clean-up procedures, 

reagents, and sample sizes. To calculate the total of all flonicamid, TFNA, TFNA-AM and 

TFNG residues (the residue definition in plant matrices), residues of the 3 metabolites above the 

lowest level of method validation (LLMV) were converted to flonicamid equivalents (MW 

flonicamid = 229.17 g/mol) prior to summing using the following conversion factors: 1.2 for 

TFNA (MW = 191.11 g/mol), 1.21 for TFNA-AM (MW = 190.12 g/mol); and, 0.92 for TFNG 

(MW = 248.2 g/mol). The LOQ (determined as the LLMV) was 0.02 ppm for each analyte, 

except in canola. For canola matrices, poor recoveries were obtained at the 0.02 ppm 

fortification for canola matrices. Satisfactory recoveries were obtained at a fortification level of 

0.2 ppm for each of the four analytes. The limit of detection (LOD) was calculated as 1/3 the 

LOQ.

Multiresidue Methods (860.1360)

The multi-residue method (MRM) data were reviewed previously and the testing data have been 

forwarded to FDA for inclusion in PAM, Vol. I. The multi-residue methods requirement has 

been fulfilled. Flonicamid and TFNA-AM were completely recovered using Protocol D (with no 

cleanup) but were not recovered using Protocols E and F. Metabolites TFNA and TFNG were 

not recovered using Protocols B, D, E and F.

Flonicamid and its metabolites TFNA (4-trifluoromethylnicotinic acid), TFNA-AM (4-

trifluoromethylnicotinamide), and TFNG [N-(4-trifluoromethylnicotinoyl)glycine] were analyzed 

according to the FDA Multi-Residue Method Test guidelines in PAM, Vol. I (dated 1/94). 

Flonicamid and its metabolites were tested through Protocols A and C, and as a result of Protocol 

C testing, all compounds were tested through Protocols D and E. Based on the results of 

Protocol E testing, testing under Protocol F was not required. Since methylated TFNA and 

TFNG provided good response on at least one of the column/detector combinations outlined in 

Protocol C, additional testing was performed with these compounds under Protocol B. 

Storage Stability (860.1380)

DER Reference: 48657101 der doc (strawberry)

 48657102 der.doc (cucumber)
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 12 of 28

 48657103 de 1.doc (canola)

 48657103 de 2 doc (canola processed commodities)

To support the sample storage intervals, untreated control RAC samples (strawberry, cucumber

and canola) and processed canola commodities (canola meal and oil) were fortified with each 

analyte (flonicamid, TFNA, TFNA-AM and TFNG) at 0.2 ppm. The samples were extracted 

according to the method described under the analytical method and stored at <-15 to ~-21oC from 

collection to extraction. Samples were analyzed within 1- 14 days of extraction. The data 

demonstrate that residues of flonicamid, TFNA, TFNA-AM, and TFNG are stable in/on the RAC 

samples of strawberry, cucumber and canola stored frozen for up to 460, 336 and 735 days, 

respectively. The available data on five diverse crops (oil seed, non-oily grain, root and tuber 

crop, leafy vegetables, and fruiting vegetables) are adequate to support the storage conditions and 

durations of the RAC samples for the subject petition. Results of the storage study are 

summarized in Table 5. 

TABLE 5. Stability of Flonicamid and its Metabolites in Strawberry, Cucumber and Canola,

Strawberry

Matrix Analyte Spike 

Level

(ppm)

Storage 

interval1

(days)

Fresh 

Fortification 

Recoveries 

(%) 

Recovered Residues 

(ppm)

Mean 

Recovered 

Residues 

(ppm)

Mean 

Recovery 

(%)

Corrected 

% 

Recovery2,3

Strawberry

Flonicamid 0.20 460 100 0.19, 0.20, 0.20 0.20 98 98

TFNA 0.20 460 90 0.17, 0.18, 0.18 0.18 88 98

TFNA-AM 0.20 460 80 0.16, 0.17, 0.17 0.17 83 104

TFNG 0.20 460 80 0.15, 0.16, 0.16 0.16 78 98

Cucumber

Flonicamid 0.2 336 90, 90, 105 0.18, 0.18, 0.21 0.19 95 100

TFNA 0.2 336 80, 85, 95 0.16, 0.17, 0.19 0.17 85 102

TFNA-AM 0.2 336 80, 80, 90 0.16, 0.16, 0.18 0.17 85 104

TFNG 0.2 336 75, 80, 90 0.15, 0.16, 0.18 0.16 84 103

Canola 

(seed)

Flonicamid 0.2 735 82 0.16, 0.16, 0.17 0.16 81 98

TFNA 0.2 735 74 0.12, 0.15, 0.16 0.14 72 97

TFNA-AM 0.2 735 82 0.16, 0.16, 0.16 0.16 81 99

TFNG 0.2 735 85 0.15, 0.17, 0.16 0.16 79 93

1

Interval from fortification to extraction. Samples were analyzed within 0 - 14 days of extraction.

2 Corrected for mean recovery in freshly fortified samples.

3 Corrected by dividing the mean freezer storage stability recoveries by the corresponding concurrent recovery.

Conclusions. The submitted storage stability data demonstrate that residues of flonicamid, 

TFNA, TFNA-AM, and TFNG are stable in/on the RAC samples of strawberry, cucumber and 

canola stored frozen for up to 460, 336 and 735 days, respectively. The available data on five 

diverse crops (oil seed, non-oily grain, root and tuber crop, leafy vegetables, and fruiting 

vegetables) support the storage conditions and durations on strawberry, cucumber and canola. 

Food Handling (860.1460)

There are no proposed uses that are relevant to this guideline topic.

Meat, Milk, Poultry, and Eggs (860.1480)
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 13 of 28

There are no proposed uses that are relevant to this guideline topic.

Crop Field Trials (860.1500)

Strawberry

DER Reference: 48657101

The IR-4 has submitted field trial data for flonicamid on strawberries. Eight field trials were 

conducted in the United States during the 2008 growing season in the North American Free 

Trade Agreement (NAFTA) Growing Zones 1 (NY; 1 trial), 2 (NC; 1 trial), 3 (FL; 1 trial), 5 (WI; 

1 trial), 10 (CA; 3 trials), and 12 (OR; 1 trial). 

Two trials [CA*59 and CA*60 (Salinas, CA)] were conducted at the same location by the same 

field research director (FRD). The differences between the trials were: use of different tank 

mixes for all applications; a 60- to 62-day off-set in application dates; and use of different 

application equipment (in two of three applications). HED has concluded that the differences are

insufficient to classify the trials as two separate trials (ChemSAC, 11/2/2011). The number of 

independent trials is seven.

Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated 

plot received three foliar broadcast or directed applications of a 50% water soluble granule (SG) 

formulation of flonicamid (Beleaf 50 SG) at 0.086-0.094 lb ai/A/application, for a total seasonal 

rate of 0.263-0.280 lb ai/A. Applications were made at the blooming to mature fruit stage with 

retreatment intervals (RTI) between 6- to 8-days, except at trials OR12 and FL24, where one 

application at each trial was made at an RTI of 10-11 days due to rain. Applications were made

using ground equipment in spray volumes of 27-53 gal/A. Except for one trial, a nonionic 

surfactant (NIS) was added to the spray mixture for each of the applications.

Samples were harvested from all trials at a 0-day pre-harvest interval (PHI); additional samples 

of strawberries were collected at PHIs of 3, 5, and 7 days from one trial (NC13) to assess residue 

decline. 

Samples were analyzed for residues of flonicamid and metabolites TFNA, TFNA-AM, and 

TFNG using a high performance liquid chromatography method with tandem mass spectrometric 

detection (LC/MS/MS) adapted from FMC No. P-3561M. The quantifiable residues of TFNA, 

TFNA-AM, and TFNG were converted to parent equivalents using molecular weight conversion 

factors of 1.20, 1.21, and 0.92, respectively (MW of flonicamid 229.17 ÷ MW of TFNA 191.11, 

MW of TFNA-AM 190.12, or MW of TFNG 248.2). The limit of quantitation (LOQ; 

determined as the lowest level of method validation, LLMV) was 0.02 ppm for each analyte. The

method was adequate for data collection based on acceptable method validation and concurrent 

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

recovery were adequate to bracket expected residue levels. Concurrent recoveries and residues in 

the treated samples were not corrected for residues in controls. The LOD for each matrix was 

calculated by multiplying the standard deviation of recovery measurements at the LLMV by the 

one-tailed t-statistic (confidence level not reported) for six to seven replicates, and the LOQ was 

defined as 3x the LOD. The calculated LOQs in strawberries were 0.0094, 0.0153, 0.0134, and 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 14 of 28

0.0104 ppm, respectively, for flonicamid, TFNA, TFNA-AM, and TFNG; corresponding 

calculated LOD values were 0.0031, 0.0051, 0.0045, and 0.0035 ppm. 

Following three foliar broadcast or directed applications of the 50% SG formulation of 

flonicamid at 0.263-0.280 lb ai/A, residues (and per trial averages) of flonicamid, metabolites 

TFNA, TFNA-AM, TFNG, and combined residues of the four analytes, respectively, in/on 

strawberries harvested at a 0-day PHI were: 0.11-0.66 (0.13-0.54), <0.02-0.12 (<0.02-0.12), 

<0.02 (<0.02), <0.02-0.083 (<0.02-0.080), and <0.17-<0.79 (<0.19-<0.73) ppm. 

Data from the residue decline trial showed that residues of flonicamid and combined residues

decreased in strawberries with increasing PHIs; however, residues of TFNA increased with 

increasing PHIs. Residue decline could not be assessed for TFNA-AM and TFNG because 

residues were below the LOQ in/on all samples.

A summary of residue data from the strawberry field trials is presented in Table 6.

TABLE 6. Summary of Residue Data from Strawberry Field Trials with Flonicamid.

Commodity Analyte Total

Rate

(lb ai/A)

PHI 

(days)

Residue Levels (ppm flonicamid equivalents)

n Sample 

Min.

Sample 

Max.

LAFT1 HAFT1 Media

n

Mean Std. 

Dev.

Strawberry, 

Berries with 

caps 

removed

Flonicamid

0.263-0.280 0 7

0.11 0.66 0.13 0.54 0.34 0.34 0.16

TFNA <0.02 0.12 <0.02 0.12 0.052 0.051 0.035

TFNA-AM <0.02 <0.02 <0.02 <0.02 0.02 0.02 N/A

TFNG <0.02 0.083 <0.02 0.080 0.026 0.036 0.022

Combined2<0.17 <0.79 <0.19 <0.73 0.41 0.45 0.20

1

LAFT: Lowest average fielt trial; HAFT: highest average field trial

2

 Combined residues of flonicamid, TFNA, TFNA-AM, and TFNG

Conclusions. The submitted strawberry field trial data are adequate. Following three foliar 

broadcast or directed applications of the 50% SG formulation of flonicamid at 0.263-0.280 lb 

ai/A, residues (and per trial averages) of flonicamid, metabolites TFNA, TFNA-AM, TFNG, and 

combined residues of the four metabolites, respectively, in/on strawberries harvested at a 0-day

PHI were: 0.11-0.66, <0.02-0.12, <0.02, <0.02-0.083, and <0.17-<0.79 ppm. Data from the 

residue decline trial showed that residues of flonicamid and total residues decreased in 

strawberries with increasing PHIs; however, residues of TFNA increased with increasing PHIs. 

Residue decline could not be assessed for TFNA and TFNG because residues were below the 

LOQ in/on all samples.

An acceptable method was used for residue quantitation, and adequate data were submitted to 

support sample storage intervals and conditions.
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 15 of 28

Cucumber

DER Reference: 48657102

Four greenhouse cucumber trials were conducted in zones 2 (1 trial each in MD and TN), 5 (1 

trial in ON) and 9 (1 trial in CO) during 2008 and 2009. Each trial site consisted of two treated 

plots and one untreated control plot. At one of the treated plots, two foliar ground applications of 

flonicamid (Beleaf 50SG insecticide) were applied 6-7 days apart at rates ranging from 0.129-

0.147 lb a.i./A (0.145-0.165 kg a.i./ha) per application for total rates of 0.262-0.291 lb a.i./A 

(0.294-0.326 kg a.i./ha) per season. A nonionic surfactant was included in the tank mix for the 

second foliar application at trial CO06 (Activator 90; 0.25% v/v) and in both foliar applications 

at trials TN04 (Co-Op; 0.25% v/v) and ON03 (Agral 90; 0.25% v/v). The second treated plot 

received two simulated chemigation applications of flonicamid to the rock wool substrate in 

which the cucumber plants were grown using a syringe, 6-7 days apart. The rates (per acre 

[hectare]) determined using an average plant density of 2.4 plants per square meter, ranged from 

0.130-0.134 lb a.i./A (0.146-0.150 kg a.i./ha) per application for total rates of 0.264-0.269 lb 

a.i./A (0.296-0.302 kg a.i./ha) per season. No adjuvants were included in any of the chemigationapplied mixtures. Mature cucumber fruit samples were harvested from all treated plots on the 

day of the last application, after the foliar spray had dried (i.e., 0-day PHI). At the ON03 trial, 

samples were harvested from both treated plots at additional PHIs of 3, 5, and 7 days to evaluate 

any residue decline.

Cucumber fruit samples were analyzed for the combined residues of flonicamid and the three 

major metabolites, 4-trifluoromethylnicotinic acid (TFNA), 4-trifluoromethylnicotinamid 

(TFNA-AM), and N-(4-trifluoro- methylnicotinoyl)glycine (TFNG), using a liquid 

chromatography with mass spectroscopic detection (LC-MS) working method entitled “Residue 

Analysis of Flonicamid, TFNA, TFNG, TFNA-AM by LC/MS, Version #3”. This method is 

similar to the previously reviewed reference method No. P-3561 entitled “Analytical 

Methodology for IKI-220 (F1785) and its Major Metabolites in/on Peach, Potato Tuber, and 

Wheat Straw, FMC Corp. P-3561M”. The calculated limit of quantitation (LOQ) was 0.017 ppm 

for flonicamid, 0.0094 ppm for TFNA, 0.011 ppm for TFNA-AM, and 0.0081 ppm for TFNG. 

The limit of detection (LOD) was calculated to be 0.0056, 0.0031, 0.0036 and 0.0027 ppm for 

flonicamid, TFNA, TFNA-AM and TFNG, respectively. The LLMV for cucumber was 

determined to be 0.020 ppm for flonicamid and each of the metabolites. Based on acceptable 

method validation and concurrent recoveries within the range of 70-120%, the method is 

adequate for data gathering purposes in cucumber fruit matrices in this study.

The maximum storage interval for treated cucumber samples was 329 days from harvest to 

extraction. All extracted samples were analyzed within 14 days. Concurrent freezer storage 

stability tests conducted as part of the trial study demonstrated that residues of flonicamid, 

TFNA, TFNA-AM and TFNG are stable in cucumbers for up to 336 days of frozen storage, 

which adequately covers the frozen storage interval for treated cucumber samples in this study. 

In cucumbers harvested at a 0-day PHI, total residues of flonicamid and the TFNA, TFNA-AM 

and TFNG metabolites were <0.203-<0.208 ppm following two foliar spray applications at total 

rates of 0.264 lb a.i./A (0.296 kg a.i./ha) without an adjuvant in the spray mixture and <0.106-

<0.775 ppm following two foliar applications at rates totaling 0.262-0.291 lb a.i./A (0.294-0.326 

kg a.i./ha) including an adjuvant in one or both of the spray mixtures. In cucumbers harvested at 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 16 of 28

a 0-day PHI following two simulated chemigation applications to the growth medium at total 

rates of 0.264-0.269 lb a.i./A (0.296-0.302 kg a.i./ha), total residues were <0.079-<0.341 ppm. 

Residue decline data indicated that following foliar applications, residues in cucumber fruit 

decreased with increasing PHIs from 0-7 days; the residues increased slightly with increasing 

PHIs from 0-7 days in cucumber fruit following simulated chemigation applications to the 

growth medium. 

A summary of residue data from the cucumber greenhouse trials is presented in Table 7.

TABLE 7. Summary of Residue Data from GreenhouseTrials with Flonicamid.

Commodity Analyte Total Rate

lb ai/A

[kg ai/ha]

PHI 

(days)

Residue Levels

(ppm)

n Min. Max. LAFT* HAFT* Median

(STMdR)

Mean

(STMR)

Std. 

Dev.

Foliar

Cucumber 

fruit

Flonicamid 0.262-

0.291 

[0.294-

326]

0 4

<0.046 0.69 0.054 0.54 0.101 0.2 0.23-

TFNA <0.02 0.034 <0.02 0.031 0.02 0.23 0.005

TFNA-AM <0.02 <0.02 <0.02 <0.02 0.02 0.02 0

TFNG <0.02 0.03 <0.02 0.028 0.02 0.23 0.004

Chemigation

Cucumber 

fruit

Flonicamid 0.264-

0.269 

[0.296-

0.302]

0 4

0.012 0.2 0.013 0.2 0.112 0.11 0.073

TFNA <0.02 0.023 0.02 0.023 0.02 0.021 0.001

TFNA-AM <0.02 <0.02 <0.02 <0.02 0.02 0.02 0

TFNG <0.02 0.11 <0.02 0.11 0.02 0.043 0.04

*LAFT = Lowest average field trial; HAFT = Highest average field trial.

Conclusion. The cucumber greenhouse trials are considered scientifically acceptable. In cucumbers 

harvested at a 0-day PHI, total residues of flonicamid and the TFNA, TFNA-AM and TFNG metabolites 

were <0.203-<0.208 ppm following two foliar spray with adjuvant added in both first and second spray

mixtures, <0.106-<0.775 ppm following two foliar applications with adjuvant added in the first spray

mixtures. Total residues in cucumbers harvested at a 0-day PHI following two simulated chemigation 

applications were <0.079-<0.341 ppm. 

Residue decline was observed with increasing PHI in cucumber treated by foliar spray. The residues in the 

chemigation treatment increased with increasing PHI from 0 to 7 days.

Canola

DER Reference: 48657103.de.1

The IR-4 has submitted field trial data for flonicamid on canola. Nine field trials were conducted 

in the United States during the 2007-2008 growing seasons in the North American Free Trade 

Agreement (NAFTA) Growing Zones 2 (NJ; 1 trial), 5 (SD; 3 trials), 7 (ND; 2 trials), and 11 (ID 

and WA; 3 trials).

Two WA trials (WA05 and WA10) were conducted by different Principal Field Investigators 

(PFIs) at the same trial location; examination of the field trial records indicates that there are 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 17 of 28

sufficient differences between the trials, including a 372- to 373-day offset in application dates, 

for the trials to constitute separate trials for purposes of OCSPP 860.1500 data requirements. 

Three of the SD trials (SD02, SD03, and SD05) were conducted by the same PFI. Careful 

examination of the field trial records indicates that the only differences between trials 

SD02/SD03 were: use of different tank mixes for all applications, a ~7-mile separation between 

the two trial locations, and a 1-day off-set in application dates (application 1 only). HED has

concluded that the differences between the trials (SD02 and SD03) are insufficient to classify

them as separate trials; therefore, these trials constitute a single trial with replicate samples for 

purposes of OCSPP 860.1500 data requirements. Examination of the field trial records indicates 

that there are sufficient differences between trials SD05 and SD02/SD03, including a 377 to 380-

day offset in application dates for this trial to constitute a separate trial. The adjustment in trial 

numbers results in a total of eight field trials, with two trials conducted in NAFTA Zone 5.

Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated 

plot received three foliar broadcast applications of a 50% water soluble granule (SG) formulation 

of flonicamid (Beleaf 50 SG) at 0.085-0.092 lb ai/A/application, for a total seasonal rate of

0.261-0.272 lb ai/A. Applications were made at 6- to 8-day RTIs using ground equipment in 

spray volumes of 10-20 gal/A. No adjuvants were added to the spray mixtures at any trial site. 

Samples of canola seed were harvested from all trials at a 6- to 8-day PHI) seed samples from 

four trial sites were dried in the field or greenhouse for 1-10 days prior to collection. 

Samples were analyzed for residues of flonicamid and its metabolites (TFNA, TFNA-AM, and 

TFNG) using the high performance liquid chromatography with tandem mass spectrometric 

detection (LC/MS/MS) adapted from FMC No. P-3561M. The limit of quantitation (LOQ; 

determined as the lowest level of method validation, LLMV) was 0.02 ppm for each analyte. 

Variable recoveries were obtained in method validation and concurrent method validation 

reflecting fortification with each analyte at 0.020, 0.20, and 2.0 ppm. Method validation 

recoveries were generally slightly low (flonicamid, TFNA, and TFNA-AM) to very low (TFNG) 

for all analytes at all fortification levels except flonicamid at 2.0 ppm and TFNA-AM at 0.20 and 

2.0 ppm, for which recoveries were acceptable (mean 78-84%). Concurrent recoveries for all 

analytes were generally acceptable at the 0.20 and 2.0 ppm fortification levels: mean recoveries 

were 72-85% with standard deviations of 4-12%. However, low concurrent recoveries were 

obtained at 0.020 ppm: 53% for flonicamid, 68% for TFNA, 62% for TFNA-AM, and 41% for 

TFNG. The petitioner noted that the lower than expected recoveries were caused by ion 

suppression due to matrix interference. Several approaches were taken to reduce the ion 

suppression, including additional cleanups and different elution programs, but the problem could 

not be eliminated. The ChemSAC reviewed the situation and concluded that the LOQ is 0.2 ppm 

for each analyte in canola matrices (03/14/2012). The fortification levels used in method 

validation and concurrent method recovery were adequate to bracket expected residue levels. 

Concurrent recoveries were corrected for residues in the controls; residues in the treated samples

were not corrected for residues in controls. Quantifiable residues of TFNA, TFNA-AM, and 

TFNG were converted to parent equivalents by the study reviewer using molecular weight 

conversion factors of 1.20, 1.21, and 0.92, respectively (MW of flonicamid 229.17 ÷ MW of 

TFNA 191.11, MW of TFNA-AM 190.12, or the MW of TFNG 248.2).

Samples were stored frozen (< -15 °C) from collection to analysis for 311-748 days (10.2-24.6 

months). Samples were analyzed within 0-3 days of extraction. Storage stability data generated 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 18 of 28

concurrently with the field trial study demonstrate that residues of flonicamid, TFNA, TFNAAM, and TFNG were stable in/on samples of canola stored frozen for up to 735 days (24.2 

months). 

Residue decline data on canola were not submitted. Since sufficient data have been reported on 

residue decline of residues in a variety of crops, further study on canola is necessary (See 

D290386, 4/22/2005). 

A summary of the residue data is presented in Table 8. The combined residues of flonicamid and 

metabolites TFNA, TFNA-AM, TFNG following three foliar broadcast applications of the 50% 

SG formulation of flonicamid at 0.261-0.272 lb ai/A, residues (per trial averages, calculated as 

flonicamid equivalents) are: <0.2-0.333 and <0.18-0.287 ppm for flonicamid and metabolite 

TFNG, respectively; residues of TFNA and TFNA-AM are below the LOQ (<0.24 ppm). The 

combined residues of flonicamid and the three metabolites are <086-1.10 ppm.

TABLE 8. Summary of Residue Data from Canola Field Trials with Flonicamid.

Commodity Analyte Total

Rate

(lb ai/A)

PHI 

(days)

Residue Levels (ppm flonicamid equivalents)1,2

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Media

n

Mean Std. 

Dev.

Canola seed

Flonicamid

0.261-0.272 6-8 8

<0.2 0.333 <0.2 0.333 0.2 0.215 0.048

TFNA <0.24 <0.24 <0.24 <0.24 0.24 0.24 0

TFNA-AM <0.24 <0.24 <0.24 <0.24 0.24 0.24 0

TFNG <0.18 0.287 <0.18 0.287 0.18 0.195 0.039

Combined3<0.86 1.10 <0.86 1.1 0.86 0.650 0.245

1 The LOQ was 0.2 ppm for all analytes. Values reflect per trial averages; n = no. of field trials. Data reflect conversion of 

quantifiable residues of TFNA, TFNA-AM, and TFNG to parent equivalents by the study reviewer.

2 LAFT = lowest average field trial; HAFT = highest average field trial.

3 Combined residues of flonicamid, TFNA, TFNA-AM, and TFNG calculated using molecular weight conversion factors of 1.20, 

1.21, and 0.92, respectively.

Conclusion. The submitted canola field trial data are acceptable. The residues of flonicamid, 

TFNA, TFNA-AM and TFNG in/on canola seed harvested at a 6- to 8-day PHI following three 

foliar broadcast applications of the 50% SG formulation of flonicamid at 0.261-0.272 lb ai/A

were <0.2-0.333 ppm and <0.2-0.287 ppm for flonicamid and TFNG, respectively. The 

residues were <LOQ (<0.2 ppm) for TFNA and TFNA-AM in all trials. The combined residues 

of flonicamid and the three metabolites are <086-1.10 ppm.

Processed Food and Feed. 860.1520

Canola

DER Reference: 48657103.de.2

A processing study was carried out to determine the magnitude of flonicamid, TFNA, TFNA-AM 

and TFNG residues in canola seed (RAC) and processed canola commodities. In one field trial,

Beleaf 50SG was applied as three foliar broadcast applications in/on canola at an exaggerated 

rate ( ~3x ) of 0.272-0.276 lb ai/A/application for a total rate of 0.821 lb ai/A. Applications 

were made at 6-day RTIs using ground equipment in spray volumes of 15-20 gal/A. No 

adjuvants were added to the spray mixture. 
Flonicamid Summary of Analytical Chemistry and Residue Data DP# D396902

Page 19 of 28

Canola seed was harvested at an 8-day PHI and stored frozen within 29 minutes of collection and 

were shipped frozen within 28 days of harvest via ACDS truck to the processing facility. 

Processing was completed within 195 days of harvest, and the samples were placed in frozen 

storage (~-18 °C) for up to 6 days prior to shipment via overnight air express to the analytical 

laboratory, the Food and Environmental Quality Laboratory at Washington State University

(FEQL; Richland, WA) for analysis. At the analytical laboratory, samples were stored frozen (<-

15 °C) until analysis.

The processing procedures simulated commercial operations to generate the required fractions of 

canola seed (RAC) into meal and oil.

Samples were analyzed for residues of flonicamid and metabolites TFNA, TFNA-AM, and 

TFNG using the LC/MS/MS method FMC No. P-3561M as described under analytical methods. 

A number of minor modifications to the method were specified, including changes in clean-up 

procedures, reagents, and sample sizes. Conversion to parent equivalents was not necessary

because residues of the metabolites in canola meal and oil were below the LOQ in/on all 

samples. 

Briefly, samples of seed were extracted twice with acetonitrile (ACN):water (1:1, v:v), then 

centrifuged and filtered. The combined extract was acidified with concentrated HCl and cleaned 

up using C18 solid phase extraction (SPE), then evaporated to remove ACN. The sample was 

partitioned with ethyl acetate four times; and the ethyl acetate fractions were combined, reduced 

by evaporation, and applied to a Carbograph SPE cartridge. The resulting eluate was evaporated 

to dryness and re-suspended in 1% formic acid for LC/MS/MS analysis. 

Samples of meal were extracted with ACN/water as above. The combined aqueous extract was 

adjusted to volume with water and evaporated to remove ACN, then partitioned with hexane and 

evaporated to remove hexane. The resulting extract was acidified with concentrated HCl and 

subjected to partitioning with ethyl acetate followed by Carbograph SPE cleanup as above. The 

resulting eluate was evaporated to dryness and re-suspended in 1% formic acid for LC/MS/MS 

analysis. 

Samples of oil were extracted with ACN/water, partitioned with hexane, and acidified as for 

meal, then subjected to C18 SPE clean-up as for seed. The eluate was partitioned with ethyl 

acetate four times, and the ethyl acetate fractions were combined, reduced by evaporation and 

adjusted to volume with 1% formic acid for LC/MS/MS analysis.

The LOQ (determined as the LLMV) was 0.02 ppm for each analyte. The LODs were calculated

as 1/3 the LOQs.

Residue data from the canola processing study are reported in Table 9. Residues of flonicamid 

were 0.232 ppm in/on canola seed (RAC) and below the LOQ (<0.02 ppm) in meal and oil. 

Residues of TFNA, TFNA-AM, and TFNG were each below the LOQ (<0.02 ppm) in/on canola 

seed, meal, and oil. Combined residues of flonicamid, TFNA, TFNA-AM, and TFNG were 

<0.292 ppm in/on seed and <0.08 ppm in meal and oil. The processing data indicate that 

combined residues of flonicamid, TFNA, TFNA-AM, and TFNG do not concentrate in meal or 

oil (processing factor <0.27x).
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The processing factors calculated in this study were less than the maximum theoretical 

concentration factors for canola of 1.9x for meal and 3.0x for oil (based on separation into 

components; OCSPP 860.1520, Table 3).

TABLE 9. Residue Data from Canola Processing Study with Flonicamid.

RAC Processed 

Commodity

Total 

Rate

(lb ai/A)

PHI Residues (ppm)

1

[Average] Processing Factor2

FlonicamidTFNA TFNAAM TFNG Combined3FlonicamidTFNA TFNAAMTFNG Combined3

Canola

Seed

(RAC)

0.821 8

--

4

,

0.232

[0.232]

<0.02,

<0.02

[<0.02]

<0.02,

<0.02

[<0.02]

<0.02,

<0.02

[<0.02]

<0.292

[<0.292]

NA5- NA -- -- --

Meal

<0.02,

<0.02

[<0.02]

<0.02,

<0.02

[<0.02]

<0.02,

<0.02

[<0.02]

<0.02,

<0.02

[<0.02]

<0.08,

<0.08

[<0.08]

<0.09x NC5 NC NC <0.27x

Oil <0.02 <0.02 <0.02 <0.02 <0.08 <0.09x NC NC NC <0.27x

1 The LOQ was 0.02 ppm for all analytes. Averages and combined residues were calculated by the study reviewer using the LOQ 

for values reported as <LOQ. The second value for seed and meal reflects the results of redilution (seed) or reinjection (meal). 

Residues of the metabolites were <LOQ in/on all samples and therefore were not converted to parent equivalents.

2

Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the RAC]. 

3 Combined residues of flonicamid, TFNA, TFNA-AM, and TFNG.

4 The first value obtained for seed (0.143 ppm) was rejected by the study director because it was outside the linearity range.

5 NC = Not calculated; residues were below the LOQ (<0.02 ppm for all in analytes) in the RAC and processed fraction; NA= not 

available

Conclusions. The processing study is acceptable to satisfy data requirements. Adequate 

processing studies on canola are available. The observed processing factors for canola meal and 

canola oil were each <0.27x. Therefore, tolerances for residues on meal and oil are not needed.

Submittal of Analytical Reference Standards (860.1650)

As of April 26, 2012, the analytical reference standards for flonicamid and the metabolites 

TFNA, TFNA-AM and TFNG including TFNA-OH and TFNG-AM are available at the EPA 

National Pesticide Standards Repository with expiration dates ranging from 2014 – 2016 

(personal communication, Dallas Wright and Theresa Cole, ACB, 05/26/2012).

Confined Accumulation in Rotational Crops (860.1850)

No new study was conducted under this guideline and none is required.

Field Accumulation in Rotational Crops (860.1900)

No new data was submitted for this guideline and none is required in support of the current 

petition.

Proposed Tolerances (860.1550)

The IR-4 has proposed the establishment of permanent tolerances for berry low growing 

subgroup 13-07G, cucumber for greenhouse use, and rapeseed, subgroup 20A.
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According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizer), the 

tolerance expression should be stated as follows:

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.

The submitted magnitude of the residue data for the RACs of the representative crops 

(strawberry, cucumber, and canola) are adequate to support the tolerance and registration 

requests for berry, low growing, subgroup13-07G, cucumber for greenhouse use, and rapeseed 

subgroup 20A. The OECD spreadsheet calculation procedure was used to determine appropriate 

tolerance levels; see Appendix II.

HED recommends for establishment of tolerances using the same tolerance expression and at the 

tolerance levels listed in Table 10 below. The petitioner should submit a revised section F

reflecting the tolerances and commodity definitions as recommended.

Table 10. Tolerance Summary for Flonicamid

Commodity Established/Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance 

(ppm)

Comments (correct 

commodity definition)

Berry, low growing, subgroup 13-07G 1.4 1.5

1

Cucumber for greenhouse use only 1.3 1.52 Vegetable, cucurbit, 

group 92

Rapeseed subgroup 20A 1.5 1.53

1

The representative commodity for the berry, low growing, subgroup 13-07G is strawberry. The OECD spreadsheet 

calculation procedure gave values of 1.5 ppm for strawberry.

2 A tolerance was currently established on cucumber at 0.4 ppm, as a member of the cucurbit vegetable group. The 

current petition is to increase the tolerance to 1.3 ppm for cucumber grown in greenhouse only. The OECD 

spreadsheet calculation procedure gave values of 1.5 ppm for cucumber grown in the greenhouse treated at the 

proposed label rate by foliar spray. The OECD spreadsheet calculation procedure gave a value of 0.7 ppm for 

cucumber treated by chemigation in the greenhouse. This tolerance value and the existing tolerance of 0.40 ppm in 

40 CFR §180.613 will be covered under the foliar spray treatment in greenhouse.

3

The representative commodity for the rapeseed, subgroup 20A is canola. The OECD spreadsheet calculation 

procedure gave values of 1.5 ppm for canola. 

No tolerances are required for the processed commodities of canola based on the demonstrated

processing factor of <0.27x for each canola meal and canola oil. The maximum theoretical 

concentration factors for canola meal and canola oil are 1.9x and 3.0x, respectively (OCSPP 

§860.1520, Table 3). 
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The tolerance expression under §180.613(a)(2) for livestock commodities should be stated as:

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.

The existing livestock commodity tolerances are adequate.

There are currently no Codex or Canadian maximum residue limits (MRLs) established for 

residues of flonicamid in crop or livestock commodities. An International Residue Limit Status 

sheet (IRL) is attached to this Summary Document (APPENDIX I).

Attachments: 

Appendix I - International Residue Limit Status sheet

Appendix II - Tolerance Assessment Calculations

Template Version September 2005
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Appendix I

International Residue Limits

Flonicamid (PC Code 128016; 04/26/2012)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.613:

Plant : flonicamid [N -(cyanomethyl)-4-

(trifluoromethyl)-3-pyridinecarboxamide] and its 

metabolites TFNA [4-trifluoromethylnicotinic acid], 

TFNA-AM [4-trifluoromethylnicotinamide], and TFNG 

[N -(4-trifluoromethylnicotinoyl)glycine]

Livestock: residues of flonicamid [N -(cyanomethyl)-4-

(trifluoromethyl)-3-pyridinecarboxamide], and its 

metabolites TFNA [4-trifluoromethylnicotinic acid] and

TFNA-AM [4-trifluoromethylnicotinamide] 

None None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Berry, low growing, subgroup 

13-07G 1.5

Vegetable, cucurbit, group 9 1.5

Rapeseed Subgroup 20A 1.5

Completed: M. Negussie; 05/01/2012

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.
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Appendix II

Tolerance Assessment Calculations

For each of the crops listed below, the OECD calculator was used for calculating recommended 

tolerances. As specified in the OECD document, the average residue value was used 

The rounding procedures specified in the OECD guideline were also used.

For each of the crops listed below, the field trials reflect the proposed application rates and 

samples were collected at the proposed pre-harvest intervals. 

Berry, Low Growing, Subgroup 13-07G

The dataset used to establish a tolerance for residues of flonicamid in/on berry, low growing 

consisted of field trial data representing total application rate of 0.263-0.280 lb ai/A (3

applications at 0.086-0.094 lb ai/A/application) with a 0-day PHI. The representative crop of the

low growing berry is strawberry. The average residue values for strawberry crop field trial used 

to calculate the tolerances are provided in Table II-1 and these values were entered in the OECD 

calculator. Using the OECD calculator, the recommended tolerance is 1.5 ppm. A crop group 

tolerance is appropriate for berry low growing subgroup 13-07G. The recommended tolerance is 

slightly higher than the proposed (1.4 ppm).

Cucumber (Greenhouse)

The dataset used to establish a tolerance for residues of flonicamid in/on greenhouse grown 

cucumber consisted of greenhouse trial data representing two methods of application: (a) foliar 

application rates of 0.262-0.291lb ai/A (2 foliar applications at 0.129-0.147 lb ai/A/application) 

with a 6-7-days RTI and 0-days PHI) and (b) application by simulated chemigation to the rock 

wool substrate in which the cucumber plants were grown using syringe) at rates of 0.264-0.269 lb 

ai/A (2 chemigation application at 0.130-0.134 lb ai/A/application) with a 6- to 7-day RTI and 0-

days PHI.

The average residue values for cucumber greenhouse trial (a) and (b) used to calculate the 

tolerances are provided in Table II-1 and these values were entered in the OECD calculator. 

Using the OECD calculator, the recommended tolerance is 1.5 ppm. The recommended 

tolerance for cucurbit vegetables, group 9, is higher than the proposed (1.3 ppm) for greenhouse 

cucumbers.

The existing tolerance for cucurbit vegetables is 0.4 ppm. This is based on the evaluation of 

crop field trial data for summer squash, cantaloupe, and cucumber (D290386, A. Acierto, 

04/22/2005). The highest residues were 0.17 ppm on squash, 0.34 ppm on cucumber, and 0.25 

ppm on cantaloupe. The recommended tolerance of 1.5 ppm for cucurbit vegetables is 

appropriate for the representative commodities.
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Rapeseed, Subgroup 20A

The dataset used to establish a tolerance for residues of flonicamid in/on rapeseed consisted of 

field trial data representing total application rate of 0.261-0.272 lb ai/A (3 applications at 0.085-

0.092 lb ai/A/application) with 6- to 8-day RTI and 6- to 8-day and 6- to 8-day PHI. The 

representative crop is canola. The average residue values for the canola field trial used to 

calculate the tolerances are provided in Table II-1 and these values were entered in the OECD 

calculator. Using the OECD calculator, the recommended tolerance is 1.5 ppm. A crop group 

tolerance is appropriate for rapeseed subgroup 20A. The proposed tolerance of 1.5 ppm is 

appropriate.

Flonicamid

Strawberry

USA

0.258-0.282 lb ai/A

Total number of data (n) 7

Percentage of censored data 0%

Number of non-censored data 7

Lowest residue 0.200

Highest residue 0.710

Median residue 0.410

Mean 0.446

Standard deviation (SD) 0.193

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.710

- Mean + 4 SD 1.219

- CF x 3 Mean 1.337

Unrounded MRL 1.337

Rounded MRL 1.5

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

0.2 1

0.25 1

0.36 1

0.41 1

0.56 1

0.63 1

0.71 1
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Flonicamid

Cucumber (Member of Cucurbit Crop Group)

USA/Canada

Foliar,0.262-0.291lb ai/A, 0-day PHI

Total number of data (n) 4

Percentage of censored data 0%

Number of non-censored data 4

Lowest residue 0.114

Highest residue 0.619

Median residue 0.164

Mean 0.265

Standard deviation (SD) 0.240

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.619

- Mean + 4 SD 1.224

- CF x 3 Mean 0.795

Unrounded MRL 1.224

Rounded MRL 1.5

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

0.114 1

0.121 1

0.206 1

0.619 1
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Flonicamid

Cucumber (Member of Cucurbit Crop Group)

USA and Canada

Chemigation 0.264-0.269 lb ai/A (0.296-0.302 kg/ha, 0-day 

PHI

Total number of data (n) 4

Percentage of censored data 0%

Number of non-censored data 4

Lowest residue 0.079

Highest residue 0.341

Median residue 0.175

Mean 0.192

Standard deviation (SD) 0.110

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.341

- Mean + 4 SD 0.633

- CF x 3 Mean 0.577

Unrounded MRL 0.633

Rounded MRL 0.7

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

0.079 1

0.154 1

0.195 1

0.341 1
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Flonicamid

Canola

Region / USA

0.261-0.272 lb ai/A PHI = 6-8 days

Total number of data (n) 8

Percentage of censored data 75%

Number of non-censored data 2

Lowest residue 0.860

Highest residue 1.100

Median residue 0.860

Mean 0.895

Standard deviation (SD) 0.084

Correction factor for censoring (CF) 0.500

Proposed MRL estimate

- Highest residue 1.100

- Mean + 4 SD 1.231

- CF x 3 Mean 1.343

Unrounded MRL 1.343

Rounded MRL 1.5

High uncertainty of MRL estimate.

[High level of censoring]

Residues (mg/kg) n

< 0.86 6

0.9 1

1.1 1