Document ID: EPA-HQ-OPP-2007-0338-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-04-02T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	11/16/07.

	Subject:	Flonicamid.  IR-4 Petition for the Establishment of Permanent
Tolerances for Use on Root Vegetables (Except Sugar Beet; Subgroup 1B),
Tuberous and Corm Vegetables (Subgroup 1C), Leafy Brassica Greens
(Subgroup 5B), Turnip Greens, Hops, and Okra.  Summary of Analytical
Chemistry and Residue Data.  PP#6E7081

DP#:	332316	Decision Number:	368509

PC Code:	128016	MRID Nos.:	46867101-46867104

40 CFR 180.	613

Chemical Class:	Group 9C Insecticide

From:	Amelia M. Acierto, Chemist

Registration Action Branch 3

Health Effects Division (7509P)

Through:	Paula Deschamp, Chief

        Registration Action Branch 3

	                    Health Effects Division (7509P)

	To:	Ann Sibold, PM Team #10

        Insecticide Branch

                    Registration Division (7505P)

This document was originally prepared under contract by Dynamac
Corporation (2275 Research Blvd, Suite 300; Rockville, MD 20850;
submitted 06/18/2007).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.

Executive Summary

and Beleaf™ 50SG (EPA Reg. No. 71512-10), a soluble granule
formulation each containing 50% flonicamid, to include new uses on root
vegetables (except sugar beets), tuberous and corm vegetables, leafy
Brassica greens, turnip greens, hop, and okra.  Concurrently, IR-4
requests in the current petition, PP#6E7081, the establishment of
permanent tolerances for the combined residues of the insecticide
flonicamid [N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide]
and its metabolites TFNA (4-trifluoromethylnicotinic acid), TFNA-AM
(4-trifluoromethylnicotinamide), and TFNG
[N-(4-trifluoromethylnicotinoyl)glycine] in/on the following commodities
or subgroups:

	Vegetable, root, except sugar beet, subgroup 1B	0.45 ppm

	Radish, tops	16 ppm

	Vegetable, tuberous and corm, subgroup 1C	0.2 ppm

	Brassica, leafy greens, subgroup 5B	16 ppm

	Turnip, greens	16 ppm

	Hop, dried cones	7.0 ppm

	Okra	0.4 ppm

Flonicamid is a Group 9C insecticide (selective feeding blocker)
currently registered for the control of a variety of aphid pests and the
suppression of a variety of non-aphid pests in head and stem Brassica
vegetables, cotton, cucurbit vegetables, fruiting vegetables, leafy
vegetables, potato, pome fruit, and stone fruit.  

Tolerances have been established for residues of flonicamid under 40 CFR
180.613.  Tolerances are currently established under 180.613(a)(1) for
the combined residues of flonicamid, TFNA, TFNA-AM, and TFNG in/on head
and stem Brassica, cotton, cucurbit vegetable, fruiting vegetable, leafy
vegetable, mustard greens, potato, pome fruit, spinach and stone fruit
commodities, at 0.20 to 11 ppm.  Tolerances have also been established
for the combined residues of flonicamid, TFNA, and TFNA-AM in egg, milk,
and the fat, meat, and meat byproducts of cattle, goat, horse, poultry,
and sheep, at 0.02 to 0.08 ppm.  

The nature of the residue in plants is adequately understood for the
purposes of this petition, based on previously submitted metabolism
studies with peach, potato, and wheat.  These data indicate that
metabolism of flonicamid is similar in dissimilar crops.  The main
metabolic reactions of flonicamid in plants are the hydrolysis of the
cyano and amide functional groups and ring hydroxylation.  HED has
determined that the residues of concern in plants are flonicamid and its
metabolites TFNA-AM, TFNA, and TFNG.

The available data indicate that the metabolism of flonicamid is similar
in goats and hens.  Flonicamid was found in minor quantities in goat
(<6% TRR) and in hen matrices (<4% TRR).  The major metabolite in all
goat and hen matrices was TFNA-AM (29-97% TRR). TFNA-AM was also
identified in significant quantities (23-31% TRR) in the acid
hydrolysates of nonextractable residues in goat muscle, liver, and
kidney.  The main pathway of metabolism of flonicamid involves
hydrolysis of the amide functional group in the molecule, somewhat
similar to the plant metabolism, although in rats, flonicamid was
further metabolized by N-oxidation and hydroxylation of the pyridine
ring leading to multiple metabolites.  HED has determined that the
residues of concern in livestock are flonicamid and its metabolites TFNA
and TFNA-AM.

Adequate methods are available to enforce the proposed tolerances for
flonicamid and the major metabolites.  The method for crop commodities,
FMC No. P-3561M, utilizes LC/MS/MS to determine the residues of
flonicamid and its major metabolites, TFNA-AM, TFNA, and TFNG.  The
method has been adequately validated by an independent laboratory in
conjunction with a previous petition.  A revised version (FMC No.
P-3822) has been recently submitted (see D329381 and D379663) in
response to the conditional requirements for the earlier petition
(PP#3F6552).  The amended method includes instructions for the
determination of residues of flonicamid, TFNA, TFNA-AM, and TFNG in/on
Brassica leafy vegetables, cotton hulls, cotton gin byproducts, cotton
meal, cotton refined oil, cotton seed, cucurbits, fruiting vegetables,
leafy vegetables, pome fruits, potato chips, potato flakes, potato
tuber, potato wet peel, stone fruits, turnip roots, turnip tops, wheat
forage, wheat germ, wheat grain, wheat middlings, and wheat straw.  The
validated limits of quantitation (LOQs) for each analyte are 0.025 ppm
for Brassica leafy vegetables, 0.02 ppm for wheat straw and cotton
matrices, 0.02 ppm for apple and 0.01 ppm for all other crop
commodities.  

For enforcement of tolerances for livestock commodities, three methods
are available:  LC/MS/MS method (RCC No. 844743) for residues in eggs
and livestock tissues; LC/MS method (RCC No. 842993) for residues in
milk; and LC/MS/MS method (FMC P3580) which includes an acid hydrolysis
step for residues in cattle muscle, kidney, and liver.  The validated
LOQs are 0.01 ppm for methods RCC Nos. 844743 and 842993, and 0.025 ppm
for method FMC P3580.  

The EPA Analytical Chemistry Branch (ACB/BEAD, Fort Meade, MD) reviewed
LC/MS/MS method FMC No. P-3561M and the methods for livestock
commodities along with the supporting method validation and independent
laboratory validation data.  It was concluded that the submitted methods
were sufficiently validated by independent laboratories and that the
methods met the OPPTS 860.1340 Residue Chemistry Test Guidelines for
acceptable enforcement methods.  ACB recommended no further testing of
the methods in an Agency laboratory.   An amended method (FMC No.
P-3822) has been submitted in response to the recommendation of the
Agency, to include instructions for the types of commodities (e.g., dry
crop commodities, oily crop commodities) instead of specific crops.  

Adequate data pertaining to the testing of flonicamid and its
metabolites TFNA-AM, TFNA, and TFNG according to the FDA Multi-Residue
Method Test guidelines in the Pesticide Analytical Manual (PAM) Volume I
have been submitted with a previous petition.  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. 

Adequate cattle and hen feeding studies have been submitted with a
previous petition; these studies are supported by adequate storage
stability data.  The established tolerances for milk, the meat and fat
of cattle, goat, horse, and sheep, and all poultry commodities must be
increased slightly to account for the combined LOQs of the regulated
analytes.

Adequate field trial data are available for root vegetables, except
sugar beet, subgroup 1B (carrot and radish), leafy Brassica greens
subgroup 5B (mustard greens), and hops.  An adequate number of
geographically representative field trials were conducted at 1x the
proposed maximum seasonal rate for each crop.  The crop field trial data
are supported by adequate storage stability data.  

The available field trial data indicate that the proposed tolerance for
the root vegetable subgroup is too low; an increased tolerance of 0.60
ppm is needed.  The proposed tolerances for the leafy Brassica greens
subgroup and dried hops cones are appropriate.  When the tolerance for
leafy Brassica greens is established, the existing tolerance for mustard
greens should be removed, as residues in mustard greens will be covered
by the leafy Brassica greens tolerance.   HED has concluded that a
tolerance for radish tops is not needed for a use on subgroup 1B (root
vegetable, except sugar beet).

The available data for mustard greens are adequate to support the
proposed tolerance for turnip greens.  Adequate field trial data have
been submitted previously for potato to support the requested tolerance
for the tuberous and corm vegetables subgroup, and previously submitted
field trial data for tomato are adequate to support the requested
tolerance for okra.  The proposed tolerances for tuberous and corm
vegetables, okra, and turnip greens are adequate.  When the tolerance
for the tuberous and corm vegetables is established, the existing
tolerance for potato should be removed, as residues in potato will be
covered by the tuberous and corm vegetables tolerance.  

Adequate processing data for potato were submitted with a previous
petition.  The available data indicate that combined residues of
flonicamid, TFNA, TFNA-AM, and TFNG do not concentrate in potato wet
peel, but may concentrate in potato chips and flakes.  It was concluded
that no tolerance was needed for potato chips, but that a tolerance was
needed for potato flakes/granules at 0.40 ppm; this tolerance has since
been established.  

Confined and field rotational crop data submitted with a previous
petition indicate that a 30-day plantback interval is appropriate for
all crops not listed on the label.  HED has determined that no residues
other than flonicamid and its metabolites TFNA-AM, TFNA, and TFNG are of
concern in rotational crops.

No Codex, Mexican, or Canadian MRLs or tolerances have been established
for residues of flonicamid.  Therefore, no compatibility questions exist
with respect to Codex.

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

HED has examined the residue chemistry database for flonicamid.  
Provided a revised Setion F is submitted, there are no residue chemistry
issues that would preclude granting a registration for the requested
uses of flonicamid on root vegetables (except sugar beets), tuberous and
corm vegetables, leafy Brassica greens, turnip greens, hop, and okra, or
establishment of tolerances for flonicamid residues as follows:

Tolerances to be established under 40 CFR 180.613(a)(1):

Brassica, leafy greens, subgroup 5B …………….16 ppm

Hop, dried cones…………………………………..7.0 ppm

Okra	 …………………………………………        0.40 ppm

Turnip, greens …………………………………  .16 ppm

Vegetable, root, except sugar beet, subgroup 1B	..0.60 ppm

Vegetable, tuberous and corm, subgroup 1C	…..   . 0.20 ppm

Tolerances to be revised under 40 CFR 180.613(a)(2):

Cattle, fat	0.03 ppm

Cattle, meat	0.08 ppm

Egg	0.04 ppm

Goat, fat	0.03 ppm

Goat, meat	0.08 ppm

Horse, fat	0.03 ppm

Horse, meat	0.08 ppm

Milk	0.03 ppm

Poultry, fat	0.03 ppm

Poultry, meat	0.03 ppm

Poultry, meat byproducts	0.03 ppm

Sheep, fat	0.03 ppm

Sheep, meat	0.08 ppm

A human health risk assessment is forthcoming.  The residue chemistry
deficiency is presented below.  

860.1550 Proposed Tolerances

1.	The proposed tolerances should be revised in Section F to reflect the
recommended tolerance levels as specified above and in Table 10.  

Background

Flonicamid is a Group 9C insecticide (selective feeding blocker)
registered for the control of a variety of aphid pests and the
suppression of a variety of non-aphid pests in head and stem Brassica
vegetables, cotton, cucurbit vegetables, fruiting vegetables, leafy
vegetables, potato, pome fruit, and stone fruit.  ISK Biosciences
Corporation, the basic producer of flonicamid, previously proposed, in
PP#3F6552, the establishment of permanent tolerances for the combined
residues of flonicamid and its metabolites TFNA, TFNA-AM, and TFNG 
in/on various plant and livestock commodities, in conjunction with an
application for Section 3 registration of a 50% WG formulation of
flonicamid for use on cotton, cucurbit vegetables, fruiting vegetables,
leafy vegetables, potato, pome fruit, and stone fruit.  In review of the
petition, HED concluded that submitted data were adequate to support
conditional registration of the 50% WG formulation (DP# 290386,
4/22/2005, A. Acierto).  The registrant subsequently submitted a
petition, PP#4F6832, for the establishment of permanent tolerances for
residues of flonicamid, TFNA, TFNA-AM, and TFNG in/on head and stem
Brassica and mustard greens, in conjunction with an application for
Section 3 registration of the 50% WG formulation for use on head and
stem Brassica and mustard greens.  In review of the petition, HED
concluded that conditional registration of the requested uses could be
granted (DP# 301415, 8/23/2005, A. Acierto).  

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 1 and 2.  

Table 1.		Flonicamid and Metabolites 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 registry number	158062-67-0

End-use product (EP)	Flonicamid 50WG (EPA Reg. No. 71512-9);

™ 50SG (EPA Reg. No. 71512-10)

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

Table 2.		Physicochemical Properties of 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

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 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.

860.1200  Directions for Use

% SG formulation (Beleaf™ 50 SG; EPA Reg. No. 71512-10).  A summary of
the proposed use patterns is detailed in Table 3.  HED notes that the
draft labels included new proposed use directions, for root vegetables
(except sugar beets), tuberous and corm vegetables, leafy Brassica
greens, hops, and okra, as well as the currently registered use
directions (for cotton, cucurbit vegetables, fruiting vegetables, head
and stem Brassica, leafy vegetables, pome fruit, and stone fruit).  Only
the new proposed use directions are included in Table 3.

Table 3.		Summary of Proposed Directions for Use of Flonicamid.

Formulation

[EPA Reg. No.]	Application Timing	Application Rate 

(lb ai/A)	Max. No. Applic. per Season	RTI1

(days)	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and other Limitations

Root Vegetables (except sugar beets) including:  garden beet; edible
burdock; carrot; celeriac; turnip-rooted chervil; chicory; ginseng;
horseradish; turnip-rooted parsley; parsnip; radish; oriental radish;
rutabaga; salsify; black salsify; Spanish salsify; skirret; turnip

50% WG

[71512-9]	Postemergence Broadcast	0.036-0.089	3	7	0.267	3	Applications
are to be made in a minimum of 10 gal/A using ground equipment or 3
gal/A using aerial equipment.

50% SG

[71512-10]

	Tuberous and Corm Vegetables including:  arracacha; arrowroot; Chinese
artichoke; Jerusalem artichoke; edible canna; bitter and sweet cassava;
chayote (root); chufa; dasheen (taro); ginger; leren; potato;2 sweet
potato; tanier; turmeric; yam bean; yam (true)

50% WG

[71512-9]	Postemergence Broadcast	0.036-0.089	3	7	0.267	7	Applications
are to be made in a minimum of 10 gal/A using ground equipment or 3
gal/A using aerial equipment.

50% SG

[71512-10]

	Leafy Brassica Greens including:  broccoli raab (rapini); Chinese
cabbage (bok choy); collards; kale; mizuna; mustard greens;3 mustard
spinach; rape greens; turnip greens

50% WG

[71512-9]	Postemergence Broadcast	0.036-0.089	3	7	0.267	0	Applications
are to be made in a minimum of 10 gal/A using ground equipment or 3
gal/A using aerial equipment.

50% SG

[71512-10]

	Hop

50% WG

[71512-9]	Postemergence Broadcast or banded	0.054-0.089	3	7	0.267	10
Applications are to be made in a minimum of 10 gal/A using ground
equipment or 3 gal/A using aerial equipment.

50% SG

[71512-10]

	Okra 4

50% WG

[71512-9]	Postemergence Broadcast	0.036-0.089	3	7	0.267	0	Applications
are to be made in a minimum of 10 gal/A using ground equipment or 3
gal/A using aerial equipment.

50% SG

[71512-10]	Postemergence Broadcast or banded

1  RTI = Retreatment interval

2  Uses on potato have been registered previously.

3  Uses on mustard greens have been registered previously.

4  Uses on okra are included under Fruiting Vegetables on the proposed
labels.

The following rotational crop restrictions are proposed: a 0-day
plantback interval for any registered crop listed on the label; and a
30-day plantback interval for all other crops.

The proposed labels specify that the product may be tank mixed with
products approved for use on the crops listed on the label, with the
instructions that all manufacturer’s label recommendations for the
companion product must be read and followed.  The labels also specify
that the products may not be used with spray adjuvants.

Conclusions.  The proposed use directions for the 50% WG and 50% SG
formulations are adequate to allow an assessment as to whether the
submitted residue data reflect the maximum residues likely to occur
in/on root vegetables (except sugar beet), tuberous and corm vegetables,
leafy Brassica greens, hops, and okra.  

The crop field trial data submitted with this petition reflect
application of the 50% WG formulation only.  The basic producer of
flonicamid, ISK Biosciences Corporation, has previously submitted
side-by-side crop field trial data for the 50% WG and 50% SG
formulations of flonicamid on tomato and leaf lettuce.  These data have
been reviewed DP# 304829, 1/9/2006, A. Acierto).  It was concluded that
combined residues of flonicamid and its metabolites TFNA-AM, TFNA and
TFNG in/on tomato and leaf lettuce were comparable whether the 50% WG or
50% SG  formulation was applied, and that previously submitted data for
the 50% WG formulation could be used to support registration of the 50%
SG formulation on the same crops.  Therefore, the data for the 50% WG
formulation submitted with the current petition may be used to support
uses of the 50% SG formulation on the same crops at the same rates.

860.1300 Nature of the Residue - Plants

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

No new plant metabolism studies were submitted with this petition. 
Adequate plant metabolism studies with flonicamid on peach, potato, and
wheat were submitted in conjunction with PP#3F6552.  Flonicamid was
found to be a major component of the residue in peach fruit and leaves
(30-33% TRR) and wheat forage, hay, straw, chaff, and grain (22-51%),
but accounted for a smaller portion of the residues in potato tubers and
leaves (6-10% TRR).  The major identified metabolites were TFNA in peach
fruit (49% TRR), TFNA and TFNG in potato tubers (39% and 34% TRR,
respectively), TFNG in wheat matrices (19-53% TRR) and TFNG-AM in forage
and hay (11% and 13% TRR, respectively); TFNG was found to be a minor
residue in peaches, and TFNA was found in small quantities in wheat
matrices (<10% TRR).  TFNA-AM was a minor component of the residue in
potatoes, peaches, and wheat.  Based on the results of the plant
metabolism studies, 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-AM, TFNA, and TFNG. 

The nature of the residue in plants is adequately understood for the
purposes of this petition.

860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

No new livestock metabolism studies were submitted with this petition;
metabolism studies with goat and hen were submitted previously
(PP#3F6552).  In the goat study, lactating goats were dosed with
[14C]flonicamid (labeled at the 3 position of the pyridine ring) at 10
ppm (10x the dietary burden to beef cattle and 20x the dietary burden to
dairy cattle; see Table 6) in the diet for five consecutive days. 
Flonicamid was found in minor quantities in all goat matrices (<6% TRR)
and in the acid hydrolysates of liver.  TFNA-AM was the major (29-97%
TRR) residue in milk, kidney, liver, fat, and muscle; TFNA-AM was also
identified in significant quantities (23-31% TRR) in the acid
hydrolysates of kidney, liver and muscle.  The metabolite GT-1,
determined to be an unstable conjugate of TFNA, was identified in goat
kidney at ~12% TRR, and the metabolite OH-TFNA-AM was identified in
liver acid hydrolysate at 11% TRR.  

In the hen study, laying hens were dosed with [14C]flonicamid (labeled
at the 3 position of the pyridine ring) at 10 ppm (50x the dietary
burden to poultry; see Table 6) in the diet for five consecutive days. 
Flonicamid was found in minor quantities in all hen matrices at <4% TRR.
 TFNA-AM was the major (>90% TRR) metabolite in all hen matrices. 
TFNA-AM was identified in minor amounts in the protease hydrolysate of
liver nonextractable residues at <2% TRR.  All other metabolites
including OH-TFNA-AM were found at 0.1-1.3% TRR in liver, muscle, skin,
and fat, TFNG-AM in muscle, skin, and fat, and TFNA in muscle.  

HED concluded that pending submission of additional information
pertaining to the conditions and parameters used in the goat and hen
metabolism studies, the nature of the residue in livestock is adequately
understood.  The studies indicate that the metabolism of flonicamid is
similar in goats and hens.  The residues of concern in livestock
commodities for the tolerance expression  and risk assessment were
determined to be flonicamid, TFNA and TFNA-AM.

ISK Biosciences Corporation has submitted the requested additional
information (MRID Nos. 46824301 and 46824302) for the goat and hen
metabolism studies, which is being reviewed separately (see DP# 329381).
 HED has concluded that with the exception of the information pertaining
to metabolite confirmation, the additional information is adequate and
supports the results reported in the original submission.  ISK
Biosciences reported that for both the goat and hen metabolism studies,
the identification of the major metabolites (those found to be present
at >10% TRR and >0.05 ppm) in all matrices was made by comparison of
retention times with the metabolite isolated from urine or excreta using
one HPLC method; the metabolites in urine or excreta were identified
using multiple chromatographic systems.  

860.1340 Residue Analytical Methods

Plant commodities

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

Enforcement method:  ISK Biosciences Corporation had previously proposed
an LC/MS/MS method for the enforcement of tolerances for residues of
flonicamid and its metabolites TFNA, TFNA-AM, and TFNG in/on crop
commodities.  The method, FMC No. P-3561M, has been reviewed by HED in
conjunction with PP#3F6552.  It was concluded that the method would be
adequate for enforcement purposes provided additional information/data
and a revised method were submitted.  Additional method validation data
at the stated method LOQ and at expected residue levels were required
for the processed commodities of apple, plum, potato, and tomato, and
additional method validation data at the stated LOQ were required for
cotton gin byproducts.  In addition, an explanation for the low
recoveries of TFNA-AM and correspondingly high recoveries of TFNA in
wheat straw in the radiovalidation study was required.  Finally, an
amended method, to include instructions for the analyses of all crops
(and their associated processed commodities) for which tolerances were
requested was required.

IR-4 has proposed that LC/MS/MS method FMC No. P-3561M be used for the
enforcement of the requested tolerances for flonicamid residues in/on
root vegetables (except sugar beets), tuberous and corm vegetables,
leafy Brassica greens, hop, and okra commodities.  

ACB/BEAD reviewed the proposed enforcement method and the supporting
method validation data for plant commodities.  ACB concluded that the
submitted method was sufficiently validated by an independent laboratory
and that the method met the OPPTS 860.1340 Residue Chemistry Test
Guidelines for acceptable enforcement methods.  ACB recommended no
further testing of the proposed plant method in an Agency laboratory.

ISK Biosciences Corporation has submitted the requested additional
information and data for the enforcement method for plant commodities,
which are being reviewed separately (see DP# 329381, 11/16/2007, A.
Acierto).  An amended method, FMC No. P-3822, was submitted, along with
additional validation data for several commodities.  For the purposes of
the current petition, the submitted data satisfy the requirements of the
previous review.  

For method FMC No. P-3822, homogenized samples, other than samples of
oil, are extracted with acetonitrile (ACN) and water.  The extracts of
oily samples (cotton seed, cotton hulls, cotton meal, potato chips, and
wheat germ) are partitioned with hexane, discarding the hexane phase. 
Samples of oil are mixed with hexane and partitioned with ACN/water. 
Concentrated HCl is added to the extracts (all samples), and the
extracts are cleaned up by C-18 solid-phase extraction (SPE; wheat straw
and middlings samples only) and/or ethyl acetate partitioning (all
samples).  The ethyl acetate phases are concentrated and redissolved in
ACN/water for analysis by LC/MS/MS.  The validated LOQs for each analyte
are 0.025 ppm for Brassica leafy vegetables, 0.02 ppm for wheat straw
and cotton matrices, and 0.01 ppm for all other crop commodities.  

Data collection methods:  Samples of carrot, radish root and top,
mustard greens, and dried hop cones were analyzed for residues of
flonicamid and its metabolites TFNA, TFNA-AM, and TFNG using methods
similar to LC/MS/MS method FMC No. P-3561M.  The methods were adequate
for data collection based on acceptable method recoveries.  

Samples of carrots were analyzed using an LC/MS method similar to
LC/MS/MS method FMC No. P-3561M.  The lower level of method validation
(LLMV) for this method was 0.020 ppm for flonicamid and 0.050 ppm for
TFNA, TFNA-AM, and TFNG in/on carrots.  The average concurrent
recoveries (and standard deviations) were 92% (8%), 96% (8%), 85% (6%),
and 78% (8%) for samples of untreated carrots fortified with flonicamid,
TFNA-AM, TFNA, and TFNG, respectively, at 0.050 and 0.20 ppm.  

Samples of radish roots and tops were analyzed using an LC/MS method
similar to LC/MS/MS method FMC No. P-3561M; the C-18 SPE cleanup step
was used for radish tops.  The LLMV for this method was 0.020 ppm for
flonicamid, TFNA, TFNA-AM, and TFNG in/on radish roots and 0.050 ppm for
each analyte in/on radish tops.  The average concurrent recoveries (and
standard deviations) were 89% (6%), 87% (7%), 71% (3%), and 79% (7%) for
samples of untreated radish roots fortified with flonicamid, TFNA-AM,
TFNA, and TFNG, respectively, at 0.020-2.0 ppm, and were 86% (11%), 81%
(18%), 82% (7%), and 74% (13%) for samples of untreated radish tops
fortified with flonicamid, TFNA-AM, TFNA, and TFNG, respectively, at
0.050-2.0 ppm.  

Samples of mustard green leaves were analyzed using a modified version
of LC/MS/MS method FMC No. P-3561M.  The validated LOQ was 0.01 ppm. 
The average recoveries (and standard deviations) were 98% (9%), 93%
(7%), 89% (10%), and 92% (9%) for samples of untreated mustard greens
fortified with flonicamid, TFNA-AM, TFNA, and TFNG, respectively, at
0.01-15 ppm.  

Samples of dried hop cones were analyzed using a modified version of
LC/MS/MS method FMC No. P-3561M; the C-18 SPE cleanup step was used for
dried hop cones and extracts were cleaned up on a second column prior to
ethyl acetate partitioning.  The LLMV for this method was 0.020 ppm for
each analyte.  The average concurrent recoveries (and standard
deviations) were 81% (7%), 89% (14%), 89% (10%), and 98% (14%) for
samples of untreated dried hop cones fortified with flonicamid, TFNA-AM,
TFNA, and TFNG, respectively, at 0.020-4.00 ppm.  

Conclusions.  An adequate method exists for the enforcement of the
proposed tolerances for crop commodities.   The revised LC/MS/MS Method
FMC No. P-3822 will be forwarded to FDA for publication in PAM Volume
II.

Adequate methods, similar to the existing enforcement method, were used
for data collection for the crop field trial studies submitted in
conjunction with this petition.

Livestock commodities

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

Enforcement methods:  ISK Biosciences had previously proposed three
methods for the enforcement of tolerances for residues of flonicamid and
its metabolites in livestock commodities (PP#3F6552).  The first is an
LC/MS/MS method, RCC No. 844743, used to determine residues of
flonicamid and its metabolites in eggs and livestock tissues.  The
second is an LC/MS method, RCC No. 842993, used to determine residues of
flonicamid and its metabolites in milk.  The third is an LC/MS/MS
method, FMC No. P-3580, which includes an acid hydrolysis step and is
used to determine residues of flonicamid and its metabolites in cattle
muscle, kidney, and liver.   

ACB/BEAD has reviewed the proposed enforcement methods and concluded
that the methods appear to meet the OPPTS 860.1340 Residue Chemistry
Test Guidelines for an acceptable enforcement method.  The ACB concluded
that the methods do not need to be tested in an Agency laboratory based
on the adequate method validation and independent laboratory validation
data provided for the methods.  

The three livestock methods recommend the use of calibration standards
prepared using control matrix extracts for all or some of the
analyte/matrix combinations to remove matrix enhancement effects.  While
OPPTS 860.1340 guidelines do not currently allow enforcement methods to
use clean control materials within an analytical procedure, this is
primarily because of the potential difficulty for a FIFRA enforcement
laboratory to quickly and easily obtain clean control commodities to
perform analysis.  HED has concluded that the use of standards in matrix
would be allowed in the case of flonicamid because animal commodities
are easily obtained and residues are not generally found in animal
commodities.

Conclusions.  Adequate methods exist for the enforcement of tolerances
for flonicamid residues in livestock commodities.  LC/MS/MS method RCC
No. 844743, LC/MS method RCC No. 842993, and LC/MS/MS method FMC No.
P-3580 will be forwarded to FDA for publication in PAM Volume II.

860.1360 Multiresidue Methods

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

Adequate multiresidue method data for flonicamid and its metabolites
were submitted previously in conjunction with PP#3F6552.  The compounds
were evaluated using the FDA Multi-Residue Method Test guidelines in PAM
Volume I.  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.

860.1380 Storage Stability

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

Storage stability data have been submitted previously which demonstrate
that flonicamid and its metabolites TFNA-AM, TFNA, and TFNG are stable
in/on cotton seed, potatoes, spinach, tomatoes, and wheat grain, forage,
and straw for up to 23 months of frozen storage (PP#3F6552).  Because
these data represent five diverse crops (an oilseed, root or tuber crop,
leafy vegetable, fruiting vegetable, and non-oily grain), it was
concluded that the data would be acceptable for translation of
demonstrated storage stability to other crops.  

IR-4 conducted concurrent storage stability studies with the carrot,
hop, and radish crop field trials submitted with this petition.  Samples
were fortified with flonicamid, TFNA, TFNA-AM, and TFNG at 0.20 ppm each
and stored frozen.   SEQ CHAPTER \h \r 1 Although zero-day data were not
provided, the storage stability data suggest that residues of
flonicamid, TFNA, TFNA-AM, and TFNG are stable in/on fortified samples
of carrot stored frozen up to 462 days (15.2 months), in/on fortified
samples of dried hops cones stored frozen up to 299 days (9.8 months),
and in/on fortified samples of radish root and top stored frozen up to
463 and 464 days, respectively (15.2 months).  

The concurrent storage stability studies adequately covered the storage
durations of samples from the carrot field trials, but were ~50 days
short of covering all of the storage durations from the hop and radish
field trials.  However, the available storage stability data for five
diverse crops are adequate to support the storage conditions and
durations of samples from the submitted hop and radish field trials.

The storage durations and conditions of samples from the crop field
trials submitted to support this petition are presented in Table 5.  

Table 5.		Summary of Storage Conditions and Durations of Samples from
the Crop Field Trial Studies.  

Matrix 	Storage Temperature

 (°C)	Actual Storage Duration	Interval of Demonstrated Storage
Stability

Carrot	-21 ± 7	115-386 days

(3.9-12.7 months)	Residues of flonicamid, TFNA, TFNA-AM, and TFNG are
stable in/on carrots stored frozen for up to 462 days.

Hop, dried cones	<-20	302 - 347 days

(9.9 - 11.4 months)	Residues of flonicamid, TFNA, TFNA-AM, TFNG are
stable in/on dried hops stored frozen for up to 299 days, and are stable
under frozen storage conditions in/on five diverse crops for up to ~23
months.

Mustard greens	-18	64-218 days 

(2.1-7.2 months)	Residues of flonicamid, TFNA-AM, TFNA, and TFNG are
stable under frozen storage conditions in/on five diverse crops for up
to ~23 months.

Radish, roots	-21 ± 7	258 - 434 days

(8.5 - 14.3 months)	Residues of flonicamid, TFNA, TFNA-AM, and TFNG are
stable in/on radish roots for up to 463 days.

Radish, tops	-21 ± 7	305 - 517 days

(10.0 - 17.0 months)	Residues of flonicamid, TFNA, TFNA-AM, and TFNG are
stable in/on radish tops for up to 464 days, and are stable under frozen
storage conditions in/on five diverse crops for up to ~23 months.

Conclusions.  Adequate storage stability data are available to support
the storage intervals and durations of samples of carrot, hop, mustard
greens, and radish commodities from the crop field trials submitted with
this petition.  No corrections for decline during storage are needed.  

860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

The cattle feedstuffs associated with the proposed uses are carrot
culls, potato culls, and processed potato waste.  There are no poultry
or swine feedstuffs associated with the proposed uses.  The dietary
burdens of flonicamid to livestock are calculated in Table 6 below.  The
Agency has recently prepared a draft revision to Table 1 of OPPTS
860.1000, including modifications to the amounts of various feedstuffs
fed to livestock; the revised calculations of dietary burdens in Table 6
include these revisions.  The dietary burdens are 1.01 ppm for beef
cattle, 0.50 ppm for dairy cattle, 0.20 ppm for poultry, and 0.15 ppm
for swine.  

Table 6.		Calculation of Dietary Burdens of Flonicamid Residues to
Livestock.

Feedstuff	Type1	% Dry Matter2	% Diet2	Established/ Recommended Tolerance
(ppm)	Dietary Contribution (ppm)3

Beef Cattle

Cotton seed, hulls	R	90	20	2.0	0.44

Other R not treated with flonicamid	R	N/A4	5	N/A	--

Potato, processed waste	CC	15	30	0.20	0.40

Other CC not treated with flonicamid	CC	N/A	30	N/A	--

Cotton seed, meal	PC	89	15	1.0	0.17

TOTAL BURDEN	--	--	100	--	1.01

Dairy Cattle

Cotton seed, hulls	R	90	15	2.0	0.33

Other R not treated with flonicamid	R	N/A	30	N/A	--

CC not treated with flonicamid	CC	N/A	40	N/A	--

Cotton seed, meal	PC	89	15	1.0	0.17

TOTAL BURDEN	--	--	100	N/A	0.50

Poultry

Cotton seed, meal	PC	89	20	1.0	0.20

CC not treated with flonicamid	CC	N/A	80	N/A	--

TOTAL BURDEN	--	--	100	--	0.20

Swine

Cotton seed, meal	PC	89	15	1.0	0.15

CC not treated with flonicamid	CC	N/A	85	N/A	--

TOTAL BURDEN	--	--	100	--	0.15

1  R:  Roughage; CC:  Carbohydrate concentrate; PC:  Protein
concentrate.

2  Revision of feedstuffs in OPPTS 860.1000 Table 1 referenced as
“Table 1 Feedstuffs (October 2006)”.  

3  Contribution = ([tolerance /% DM] X % diet) for beef and dairy
cattle; contribution = ([tolerance] X % diet) for poultry and swine. 

4  N/A:  Not applicable.  

Note: The above dietary burden calculations have been reviewed by J.
Stokes (personal communication, 5/29/2007). 

No feeding studies were submitted with this petition.  Feeding studies
with cattle and hens were submitted with the previous petition
(PP#3F6552).  At that time, the dietary burdens to livestock were
calculated to be 2.2-2.3 ppm to beef and dairy cattle, 0.20 ppm to
poultry, and 0.25 ppm to swine.  The revisions to Table 1 have resulted
in a large decrease in the dietary burdens to cattle.

In the cattle feeding study, three groups of dairy cattle (3 cows per
group) were dosed orally with gelatin capsules containing a 1:1 mixture
of flonicamid and TFNG at levels equivalent to 2.50, 6.89, and 23.69 ppm
(flonicamid and TFNG combined) in the diet for 28 consecutive days.  The
dosing levels are equivalent to 2.5x, 6.8x, and 23x the dietary burden
to beef cattle and 5x, 14x, and 47x the dietary burden to dairy cattle. 

Milk samples were analyzed for residues of flonicamid and its
metabolites OH-TFNA-AM, TFNA-AM, TFNG, and TFNA using LC/MS method RCC
No. 842993; muscle samples were analyzed for residues of flonicamid and
its metabolites using LC/MS/MS method FMC No. P-3580; fat samples were
analyzed for residues of flonicamid and its metabolites using LC/MS/MS
method RCC No. 844743; and separate analyses of liver and kidney samples
were conducted using methods FMC P-3580 and RCC No. 844743.  These
methods are the enforcement methods for livestock commodities.  For
methods RCC Nos. 842993 and 844743, the validated LOQ was 0.01 ppm for
each analyte in milk, liver, kidney, and fat.  For method FMC No.
P-3580, the validated LOQ was 0.025 ppm for each analyte in muscle,
liver, and kidney.  

The maximum combined residues of flonicamid, TFNA-AM, and TFNA in cattle
commodities are summarized in Table 7 below.  Combined residues of
flonicamid, TFNA-AM, and TFNA appeared to increase with increased
feeding level in all tissues; linear regression analyses could not be
conducted because all residues in all matrices from the lowest dosing
level were below the LOQ.  Combined residues of flonicamid, TFNA-AM, and
TFNA were higher in cattle liver and kidney samples analyzed using FMC
No. P-3580, which includes an acid hydrolysis step, than in samples
analyzed using RCC No. 844743, which does not include acid hydrolysis. 
This is in agreement with the ruminant metabolism study, in which acid
hydrolyses were required to release significant portions of the
radioactivity

In the poultry feeding study, four groups of laying hens (10 hens per
group) were dosed orally with gelatin capsules containing a 1:1 mixture
of flonicamid and TFNG at levels equivalent to 0.2593, 2.514, 7.473, and
25.83 ppm (flonicamid and TFNG combined) in the diet for 28 consecutive
days.  The dosing levels are equivalent to 1.3x, 13x, 37x, and 130x the
dietary burden to poultry.  Poultry eggs and tissues were analyzed for
residues of flonicamid and its metabolites OH-TFNA-AM, TFNA-AM, TFNG,
and TFNA using LC/MS/MS method RCC No. 844743, the proposed enforcement
method for poultry commodities.  The validated LOQ was 0.01 ppm for each
analyte in all matrices.  

The maximum combined residues of flonicamid, TFNA-AM, and TFNA in
poultry commodities are summarized in Table 8 below.  TFNA-AM residues
were generally found to have a linear relationship with the dosing level
in poultry muscle, liver, and fat; flonicamid and TFNA residues were
below the LOQ in all tissue samples at all dosing levels.  

HED has determined that the residues of concern in livestock commodities
are flonicamid, TFNA-AM, and TFNA.  The maximum combined residues of
flonicamid, TFNA-AM, and TFNA in livestock commodities are summarized
below.  

Table 7.		Summary of Maximum Residue Levels of Flonicamid and its
Metabolites in Cattle Matrices.

	Matrix	Maximum Combined Residues of Flonicamid, TFNA-AM, and TFNA by
Feeding Level (ppm)

	2.50 ppm	6.89 ppm	23.69 ppm

Milk	<0.03	<0.0620	<0.1313

Muscle	<0.075	<0.0796	<0.1552

Fat	<0.03	<0.03	<0.0410

Liver - RCC No. 844743	<0.03	<0.0390	<0.0765

Liver - FMC No. P-3580	<0.075	<0.0917	<0.1742

Kidney - RCC No. 844743	<0.0393	<0.0755	<0.2881

Kidney - FMC No. P-3580	<0.075	<0.1055	<0.3212

Table 8.		Summary of Maximum Residue Levels of Flonicamid and its
Metabolite in Poultry Matrices.

Matrix	Maximum Combined Residues of Flonicamid, TFNA-AM, and TFNA by
Feeding Level.

	0.2593 ppm	2.514 ppm	7.473 ppm	25.83 ppm

Eggs	<0.0343	<0.1441	<0.3956	<1.2675

Muscle	<0.03	<0.0815	<0.2066	<0.7381

Liver	<0.03	<0.0849	<0.2071	<0.8057

Fat	<0.03	<0.0511	<0.0996	<0.3726

Note:  The values in the above tables for cattle milk, muscle, and fat
and all poultry commodities have been revised from the values reported
in Tables 8 and 9 of DP# 290386 to include residues of TFNA (in the
previous petition, combined residues of flonicamid and TFNA-AM were
reported for cattle milk, muscle, and fat, and for all poultry
commodities as these were the residues the petitioner had proposed to
regulate in these commodities).  Residues of TFNA were below the LOQ
(0.01 ppm for cattle milk and fat and all poultry commodities, and 0.025
ppm for cattle muscle) in/on all samples of cattle milk, muscle, and
fat, and all poultry commodities.  

Conclusions.  The available data indicate that tolerances are needed for
the combined residues of flonicamid, TFNA-AM, and TFNA in livestock
commodities, other than swine commodities.  With the exception of eggs,
the tolerances should be set at the combined LOQs of the enforcement
methods.  For eggs, the feeding study data indicate that a tolerance is
needed at 0.04 ppm.  For the remaining commodities, tolerances are
needed at 0.03 ppm for milk and the fat of cattle, goat, horse, and
sheep; 0.03 ppm for the fat, meat, and meat byproducts of poultry; and
0.08 ppm for the meat and meat byproducts of cattle, goat, horse, and
sheep.  The established tolerances for milk, the meat and fat of cattle,
goat, horse, and sheep, and all poultry commodities must be increased
slightly to account for the combined LOQs of the regulated analytes.

Based on the cattle feeding study, residues of flonicamid, TFNA and
TFNA-AM would be expected to be below the LOQ when the swine are fed a
diet corresponding to 10x the dietary burden.  Therefore, no tolerances
for residues in hog commodities are needed.

860.1500 Crop Field Trials

DER Reference:	46867101.der.doc (Hops)

		46867102.der.doc (Radish)

		46867103.der.doc (Carrot)

		46867104.der.doc (Mustard greens)

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

Residue Chemistry Memo DP# 301415, 8/23/2005, A. Acierto (PP#4F6832)

In support of the proposed uses on hops and crop subgroups 1B and 5B,
IR-4 has submitted magnitude of the residue studies for hops, radish and
carrot (representative commodities of subgroup 1B), and mustard greens
(representative commodity of subgroup 5B).  The results from these field
trials are discussed below and summarized in Table 9.  

Table 9.		Summary of Residue Data from Crop Field Trials with
Flonicamid.

Commodity	Analyte	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels1

 (ppm)

n	Min.	Max.	HAFT2	Median	Mean	Std. Dev.3

ROOT VEGETABLE EXCEPT SUGAR BEET, SUBGROUP 1B (proposed use = 0.267 lb
ai/A total application rate, 3-day PHI)

Carrot	Flonicamid	0.264-0.277	6-8	16	<0.020	<0.020	<0.020	<0.020	<0.020
NA

	TFNA

	16	<0.050	0.122	0.100	0.055	0.065	0.022

	TFNA-AM

	16	<0.050	<0.050	<0.050	<0.050	<0.050	NA

	TFNG

	16	<0.050	0.178	0.163	0.050	0.066	0.039

	Total

	16	<0.170	<0.298	<0.283	0.185	0.201	0.039

Radish roots	Flonicamid	0.263-0.274	2-4	10	<0.020	0.25	0.21	0.10	0.11
0.070

	TFNA

	10	<0.020	0.088	0.078	0.035	0.041	0.022

	TFNA-AM

	10	<0.020	<0.020	<0.020	<0.020	<0.020	NA

	TFNG

	10	<0.020	0.066	0.056	<0.020	0.027	0.016

	Total

	10	<0.080	<0.40	<0.36	0.18	0.20	0.10

Radish tops	Flonicamid	0.263-0.274	2-4	10	0.18	8.8	8.5	5.2	4.6	3.0

	TFNA

	10	<0.050	0.22	0.17	0.051	0.096	0.065

	TFNA-AM

	10	<0.050	0.48	0.47	0.098	0.20	0.17

	TFNG

	10	0.063	0.71	0.70	0.20	0.28	0.24

	Total

	10	0.343	10.1	9.8	5.7	5.1	3.3

LEAFY BRASSICA GREENS, SUBGROUP 5B (proposed use = 0.267 lb ai/A total
application rate, 0-day PHI)

Mustard greens	Flonicamid	0.264-0.269	0	6	4.334	5.123	4.909	4.622	4.696
0.335

	TFNA-AM

	6	<0.01	<0.01	<0.01	<0.01	<0.01	NA

	TFNA

	6	<0.01	0.096	0.084	0.072	0.066	0.029

	TFNG

	6	0.413	0.496	0.482	0.448	0.448	0.032

	Total

	6	4.789	5.620	5.484	5.182	5.220	0.360

HOPS (proposed use = 0.267 lb ai/A total application rate, 10-day PHI)

Dried hop cones 	Flonicamid	0.261-0.272	9-11	6	0.561	2.85	2.82	1.15	1.51
1.05

	TFNA

	6	0.302	0.470	0.456	0.335	0.366	0.072

	TFNA-AM

	6	0.038	0.177	0.171	0.146	0.118	0.063

	TFNG

	6	0.098	0.204	0.204	0.162	0.157	0.045

	Total

	6	1.09	3.45	3.40	1.96	2.15	1.04

1  For the calculation of total residues and determination of the HAFT,
median, mean, and standard deviation values, the LOQ or                 
                                                                        
LLMV (lowest level of method validation) was used for residues reported
as <LOQ or <LLMV.

2  HAFT = Highest Average Field Trial. 

3  NA = Not applicable.

Root vegetable, except sugar beet, subgroup 1B

Carrot:  IR-4 has submitted field trial data for flonicamid on carrot. 
Eight carrot field trials were conducted during the 2003-2004 growing
seasons in Zones 3 (FL; 1 trial), 5 (OH; 1 trial), 6 (TX; 1 trial), 10
(CA; 4 trials), and 11 (WA; 1 trial).  The number and locations of field
trials are in accordance with OPPTS Guideline 860.1500 for carrot as an
individual crop and also as a representative commodity of the root
vegetable, except sugar beet, subgroup 1B.

At each test location, three foliar broadcast spray applications of the
50% WG formulation were made to carrots at ~0.089 lb ai/A/application,
with 6- to 8- day retreatment intervals, for a total seasonal rate of
~0.267 lb ai/A (1x the proposed maximum seasonal rate).  At one site
(FL), applications were made as foliar directed sprays instead of
broadcast sprays.  Applications were made in spray volumes of 22-58
gal/A without an adjuvant.  Carrot samples were collected 6-8 days after
the final application; the PHI proposed for the root vegetable subgroup
is 3 days.  Additional samples were collected from two trials (CA and
TX) at 0, 1, 3, and 10 days following the last application to evaluate
residue decline.

Samples of carrots were analyzed for residues of flonicamid and its
metabolites TFNA, TFNA-AM, and TFNG using an LC/MS method similar to
LC/MS/MS method FMC No. P-3561M.  The LLMV for this method was 0.020 ppm
for flonicamid and 0.050 ppm for TFNA, TFNA-AM, and TFNG in/on carrots. 
The petitioner used the LLMV as the LOQ for reporting residue results. 
This method is adequate for data collection based on acceptable method
recoveries.  

The maximum storage duration for carrot samples was 386 days (12.7
months).  The storage conditions and durations are supported by adequate
storage stability data generated concurrently with the field trials.  

The results from the carrot field trials are presented in Table 9.  The
maximum combined residues of flonicamid, TFNA, TFNA-AM, and TFNG were
<0.298 ppm in/on carrots.  The maximum individual residues were 0.12 ppm
for TFNA and 0.18 ppm for TFNG; residues of flonicamid and TFNA-AM were
below the LLMV (<0.020 ppm and <0.050 ppm, respectively) in/on all
samples.

Residues of flonicamid and TFNA-AM were near or below the LLMV in/on all
samples from both decline trials.  In the CA decline trial, residues of
TFNA increased (from an average of 0.054 ppm at the 1-day PHI to an
average of 0.106 at the 13-day PHI) and residues of TFNG increased
slightly (from <0.052 at the 1-, 3-, and 6-day PHIs to an average of
0.070 ppm at the 13-day PHI) with increasing sampling intervals.  The
average combined residues from the CA decline trial were 0.176 ppm at
the 1-day PHI, 0.193 ppm at the 3-day PHI, 0.214 ppm at the 6-day PHI,
and 0.246 ppm at the 13-day PHI.  In the TX trial, residues of TFNA were
at or near the LLMV in/on all samples except those from the 6-day PHI
(in which average residues were 0.061 ppm) and residues of TFNG
increased (from an average of 0.086 ppm at the 3-day PHI to an average
of 0.124 ppm at the 13-day PHI) with increasing sampling intervals.  The
average combined residues from the TX decline trial increased from the
1-day PHI (0.206 ppm) to the 7-day PHI (0.283 ppm) but declined at the
13-day PHI (0.244 ppm).  Based on these data, combined residues of
flonicamid, TFNA, TFNA-AM, and TFNG appeared to generally increase in
carrots with later sampling intervals.  However, HED notes that residues
in/on TFNA and TFNG increased only marginally with increasing sampling
intervals, and residues of each analyte were generally ≤2xLLMV in/on
each sample.  In addition, the variation in residues for TFNA and TFNG
over the sampling intervals tested was less than the variation in
residues for these analytes across all carrot field trial results.  

Radish:  IR-4 has submitted field trial data for flonicamid on radish. 
Five radish field trials were conducted during the 2003 growing season
in Zones 1 (NJ; 1 trial), 3 (FL; 2 trials), 5 (OH; 1 trial), and 10 (CA;
1 trial).  The number and locations of field trials are in accordance
with OPPTS Guideline 860.1500 for radish as an individual crop and also
as a representative commodity of the root vegetable, except sugar beet,
subgroup 1B.

At each test location, three foliar broadcast or directed spray
applications of the 50% WG formulation were made to radishes at ~0.089
lb ai/A/application, with a 6- to 8- day retreatment interval, for a
total seasonal rate of ~0.267 lb ai/A (1x the proposed maximum seasonal
rate).  Directed applications were made at two of the sites and
broadcast applications were made at three of the sites.  Applications
were made in spray volumes of 26-58 gal/A without an adjuvant.  Samples
of radish roots and tops were collected 2-4 days after the final
application.

Samples of radish roots and tops were analyzed for residues of
flonicamid and its metabolites TFNA, TFNA-AM, and TFNG using an LC/MS
method similar to LC/MS/MS method FMC No. P-3561M.  The LLMV for this
method was 0.020 ppm for flonicamid, TFNA, TFNA-AM, and TFNG in/on
radish roots and 0.050 ppm for each analyte in/on radish tops.  The
petitioner used the LLMV as the LOQ for reporting residue results.  This
method is adequate for data collection based on acceptable method
recoveries. 

The maximum storage duration of crop samples was 434 days (14.3 months)
for radish roots and 517 days (17.0 months) for radish tops.  The
storage conditions and durations are supported by adequate storage
stability data generated concurrently with the field trials, and
previously submitted storage stability data.   

The results from the radish field trials are presented in Table 9.  The
maximum combined residues of flonicamid, TFNA, TFNA-AM, and TFNG were
<0.40 ppm in/on radish roots and 10.1 ppm in/on radish tops harvested 2
to 4 days after final application.  Maximum individual residues of
flonicamid, TFNA, and TFNG in/on radish roots were 0.25 ppm, 0.088 ppm,
and 0.066 ppm, respectively.  TFNA-AM residues were below the LLMV
(<0.020 ppm) in/on all radish root samples.  For radish tops, the
maximum individual residues were 8.8 ppm for flonicamid, 0.22 ppm for
TFNA, 0.48 ppm for TFNA-AM, and 0.71 ppm for TFNG.

No decline trial was conducted for radish; however, no decline trial
will be required as two decline trials were conducted with the other
root vegetable subgroup representative crop, carrot.

Conclusions.  The submitted residue data for root vegetables are
adequate to fulfill data requirements.  The number and locations of
field trials are in accordance with OPPTS Guideline 860.1500 for the
root vegetable, except sugar beet, subgroup 1B.  

The use pattern of the radish field trials adequately reflects the use
pattern proposed for root vegetables, except sugar beets.  The
application rates used in the carrot field trials reflects the proposed
maximum rate; however, carrots were harvested 7 days after final
application, which does not reflect the proposed PHI of 3 days. 
Although the carrot data do not reflect the requested PHI, the data are
acceptable for the purposes of the petition.  The residue decline data
for carrot indicate that combined residues do not decrease with
increasing sampling intervals, indicating that combined residues of
flonicamid, TFNA, TFNA-AM, and TFNG in carrots harvested 3 days after
final application are not likely to be greater than the residues
observed in/on samples harvested 7 days following last application. 
Therefore, HED has determined that it is appropriate to use the 7-day
carrot data to set a tolerance for the subgroup to support the proposed
use with a 3-day PHI.  

The available field trial data will support a tolerance for combined
residues of flonicamid, TFNA, TFNA-AM, and TFNG in/on the root
vegetable, except sugar beet, subgroup at 0.60 ppm; the tolerance
calculation for root vegetables is presented in Appendix I.

h analyte were generally ≤2x the LLMV in/on each sample from the
decline study.  HED concludes that if combined residues were to increase
in radish with increasing sampling interval, it is unlikely that
residues would exceed the recommended tolerance of 0.60 ppm.

The petitioner proposed a tolerance for radish tops.  HED does not
require a tolerance for radish tops to support use on the root
vegetable, except sugar beet, subgroup (Bernard Schneider, email
6/7/07).

Tuberous and corm vegetable, subgroup 1C

IR-4 did not submit any crop field trial data for the tuberous and corm
vegetable crop subgroup and instead referenced crop field trial data
previously submitted for potato, the representative crop of the
subgroup.  Adequate crop field trial data for potato were submitted in
conjunction with PP#3F6552.  Seventeen potato field trials were
conducted during the 2001 growing season in Regions 1 (NY and PA; 2
trials), 2 (VA; 1 trial), 3 (FL; 1 trial), 5 (MN, ND, and WI; 4 trials),
9 (CO; 1 trial), 10 (CA; 1 trial), and 11 (ID and WA; 7 trials).  The
number and locations of field trials are in accordance with OPPTS
Guideline 860.1500 for potatoes as an individual crop and as a
representative crop of subgroup 1C.  Combined residues of flonicamid,
TFNA-AM, TFNA, and TFNG were 0.050-0.139 ppm in/on potato tubers
harvested 7 days following the last of three broadcast foliar
applications of the 50% WG formulation at ~0.089 lb ai/A/application,
for a total seasonal rate of ~0.276 lb ai/A (1x the proposed maximum
seasonal rate to tuberous and corm vegetables).

Conclusions.  The previously submitted data for potato are adequate to
support use on the tuberous and corm vegetable subgroup.  The proposed
use on the tuberous and corm vegetable subgroup is identical to the
registered use on potato.  The available data will support a tolerance
for the combined residues of flonicamid, TFNA, TFNA-M, and TFNG in/on
the tuberous and corm vegetable subgroup at 0.20 ppm, the current
tolerance level for potato.  

Leafy Brassica greens, subgroup 5B

FMC Corporation has submitted field trial data for flonicamid on mustard
greens.  Three trials were conducted in Zones 2 (GA; 1 trial), 3 (FL; 1
trial) and 10 (CA; 1 trial) during the 2004 growing season.  The number
and locations of field trials are not in accordance with OPPTS Guideline
860.1500 for establishing a group tolerance for crop subgroup 5B leafy
Brassica greens; 8 trials are needed to support a subgroup 5B tolerance.

At each test location, three broadcast foliar spray applications of the
50% WG formulation were made to mustard greens at ~0.089 lb ai/A, with
6- to 7-day retreatment intervals, for a total seasonal rate of ~0.267
lb ai/A (1x the proposed maximum seasonal rate).  Applications were made
in spray volumes of 10-11 gal/A without an adjuvant.  The mustard greens
were harvested on the day of the final application.

Samples of mustard green leaves were analyzed for residue of flonicamid
and its metabolites TFNA-AM, TFNA, and TFNG using a modified version of
LC/MS/MS method FMC No. P-3561M.  The validated LOQ was 0.01 ppm.  This
method is adequate for data collection based on acceptable concurrent
method recovery data. 

The maximum storage duration of crop samples from harvest to analysis
was 218 days (7.2 months).  The available storage stability data are
adequate to support the storage conditions and durations of samples from
the mustard greens field trials.

The results from the mustard greens field trials are presented in Table
9.  The maximum combined residues of flonicamid, TFNA-AM, TFNA, and TFNG
were 5.620 ppm in/on mustard greens.  Maximum individual residues of
flonicamid, TFNA, and TFNG were 5.123 ppm, 0.096 ppm, and 0.496 ppm,
respectively.  Residues of TFNA-AM were below the LOQ (<0.01 ppm) in/on
all samples. 

Conclusions.  The submitted residue data for mustard greens are adequate
to fulfill data requirements.  The use pattern of the field trials
adequately reflects the use pattern proposed for leafy Brassica greens. 

A total of eight field trials on mustard greens are required to
establish a tolerance for crop subgroup 5B.  The three field trials
submitted with this petition were performed in addition to five other
mustard greens field crop trials submitted in conjunction with
PP#4F6832, in order to meet the requirements under OPPTS Guideline
860.1500 to establish a group tolerance for leafy Brassica greens,
subgroup 5B.  In the previous submission, five mustard greens field
trials were conducted in Zones 2 (VA; 1 trial), 4 (MS; 1 trial), 5 (MN;
1 trial), 6 (OK; 1 trial), and 10 (CA; 1 trial).  The number and
locations of the current and previously submitted field trials are in
accordance with OPPTS Guideline 860.1500 for establishing a group
tolerance for crop subgroup 5B.  

In the previous submission, combined residues of flonicamid, TFNA-AM,
TFNA, and TFNG were <2.132-10.113 ppm in/on mustard greens harvested 0
days following the last of three broadcast foliar applications of the
50% WG formulation at ~0.089 lb ai/A/application, for a total seasonal
rate of ~0.276 lb ai/A (1x the proposed maximum seasonal rate to leafy
Brassica greens). 

The available field trial data will support a tolerance for combined
residues of flonicamid, TFNA, TFNA-AM, and TFNG in/on the leafy Brassica
greens subgroup 5B at 16 ppm; the tolerance calculation for leafy
Brassica greens is presented in Appendix I.

HED has recently concluded that turnip greens will be moved from the
leaves of root and tuber vegetables crop group (group 2) to the Brassica
leafy vegetables crop group (group 5); turnip greens will also be a
member of the leafy Brassica greens subgroup.  Therefore, crop field
trial data for mustard greens as the representative commodity of the
leafy Brassica greens subgroup are sufficient to support the proposed
use on turnip greens.  Until the regulations have been finalized in the
Federal Register, a separate tolerance must be established for turnip
greens, at the same level as the leafy Brassica greens tolerance.  

Okra

IR-4 did not submit any crop field trial data for okra, and instead
referenced crop field trial data previously submitted for the fruiting
vegetable crop group (crop group 8).  Adequate crop field trial data for
fruiting vegetables were submitted in conjunction with PP#3F6552. 
Combined residues of flonicamid, TFNA-AM, TFNA, and TFNG were
<0.049-<0.304 ppm in/on tomatoes, <0.141-<0.205 ppm in/on bell peppers,
and <0.282-<0.300 ppm in/on non-bell peppers harvested 0 days following
the last of three broadcast foliar applications of the 50% WG
formulation at ~0.089 lb ai/A/application, for a total seasonal rate of
~0.276 lb ai/A (1x the proposed maximum seasonal rate to okra).

Conclusions.  The previously submitted data for the fruiting vegetable
crop group are adequate to support use on okra.  The proposed use on
okra is identical to the registered use on fruiting vegetables.  HED has
recommended inclusion of okra in crop group 8.  

The available data will support a tolerance for the combined residues of
flonicamid, TFNA, TFNA-M, and TFNG in/on okra at 0.40 ppm, the current
tolerance level for fruiting vegetables.

Hop

IR-4 has submitted field trial data for flonicamid on dried hops.  Three
field trials were conducted in the U.S. during the 2003 growing season
in Zones 11 (ID and WA; 2 trials) and 12 (OR; 1 trial).  The number and
locations of field trials are in accordance with OPPTS Guideline
860.1500 for hops. 

At each test location, three foliar directed spray applications of the
50% WG formulation were made to hops at ~0.089 lb ai/A/application, with
7- to 8-day retreatment intervals, for a total seasonal rate of ~ 0.267
lb ai/A (1x the proposed maximum seasonal rate).  Applications were made
in spray volumes of 85-144 gal/A without an adjuvant.  Fresh hop cones
were harvested 9-11 days after the final application and then dried in a
crop dryer for 3-24 hours. 

Samples of dried hop cones were analyzed for residues of flonicamid and
its metabolites TFNA, TFNA-AM, and TFNG using a modified version of
LC/MS/MS method FMC No. P-3561M.  The LLMV for this method was 0.020 ppm
for flonicamid and its metabolites.  The petitioner used the LLMV as the
LOQ for reporting residue results.  This method is adequate for data
collection based on acceptable method recoveries.  

The maximum storage duration of dried hop samples was 347 days (11
months).  The storage conditions and durations are supported by adequate
storage stability data generated concurrently with the field trials, and
previously submitted storage stability data.  

The results of the hops field trials are presented in Table 9.  Maximum
combined residues of flonicamid, TFNA, TFNA-AM, and TFNG were 3.45 ppm
in/on dried hop cones.  Maximum individual residues of flonicamid, TFNA,
TFNA-AM, and TFNG were 2.85, 0.470, 0.177, and 0.204 ppm, respectively.

Conclusions.  The submitted residue data for dried hop cones are
adequate to fulfill data requirements.  The number and locations of
field trials are in accordance with OPPTS Guideline 860.1500 for hops,
and the use pattern of the field trials adequately reflects the use
pattern proposed for hops.  

The available field trial data will support a tolerance for residues of
the combined residues of flonicamid, TFNA, TFNA-M, and TFNG in/on dried
hop cones at 7.0 ppm; the tolerance calculation for hops is presented in
Appendix I.

860.1520 Processed Food and Feed

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

HED does not require residue data for any processed commodities
associated with crop subgroup 1B, crop subgroup 5B, hops, or okra.  Data
are required for the processed commodities of potato.  These data have
been submitted previously, in association with PP#3F6552.  

The potato processing data indicated that the combined residues of
flonicamid, TFNA-AM, TFNA, and TFNG do not concentrate in potato wet
peel (0.3x average processing factor), but may concentrate in potato
chips (1.6x average processing factor) and flakes (2.85x average
processing factor).  Based on the average processing factors and the
HAFT residue of 0.123 ppm for potato, the expected residues in potato
chips and flakes following treatment of potato plants at 1x would be
0.20 and 0.35 ppm, respectively.  It was concluded that no tolerance was
needed for potato chips, but that a tolerance was needed for potato
flakes/granules at 0.40 ppm; this tolerance has since been established. 

It was also concluded that because limited validation data were provided
to support the potato processing study, validation data for potato
processed commodities at the stated LOQ and at expected residue levels
was required.  ISK Biosciences has submitted these data, which are being
reviewed separately (see DP# 329381, 11/16/2007, A. Acierto); adequate
validation data were provided for flonicamid and its metabolites in/on
potato tuber, chips, flakes, and wet peel at the LOQ (0.01 ppm) and at
the levels which bracket the observed residues in potato processed
commodities.  

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

Analytical standards for flonicamid and its metabolites TFNA, TFNA-AM,
and TFNG are available in the EPA National Pesticide Standards
Repository with expiration dates of 2008 and 2011 (Charles Stafford,
e-mail, 11/15/07).  Therefore, the requirement for additional standard 
has been satisfied.

860.1850 Confined Accumulation in Rotational Crops

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

No confined rotational crop data were submitted with this petition.  An
adequate confined rotational crop study was submitted in conjunction
with PP#3F6552.  The radiolabeled test substance,
[pyridyl-14C]flonicamid, was formulated as a WG formulation and applied
twice to bare loamy sand soil in planting containers at 0.089 lb
ai/A/application for a total rate of 0.179 lb ai/A.  Rotational carrot,
lettuce, and wheat were planted at plantback intervals (PBIs) of 30,
120, and 361 days.  

The 30-day PBI wheat matrices were the only rotational crop commodities
in which individual identified components accounted for ≥0.01 ppm. 
Total identified residues were 62.1-85.6% TRR.  Flonicamid was a minor
residue in all wheat matrices.  Metabolite TFNG was the major residue in
wheat grain and chaff and was a significant residue in wheat forage and
straw.  TFNA-OH, the only metabolite identified in rotational crops that
was not found in primary crops, was the major residue in forage and a
minor residue straw, chaff, and grain.  Metabolite TFNA was a
significant residue in forage, chaff, and grain but was a minor residue
in straw.  TFNG-AM was a significant residue in forage, straw, and chaff
but was a minor residue in grain.  TFNA-AM was also identified in 30-day
PBI wheat matrices at minor levels.

Flonicamid and metabolites TFNG, TFNA, TFNG-AM, TFNA-AM, and TFNA-OH
were identified in 30-day PBI mature carrot roots and tops and immature
and mature lettuce and in 120-day PBI immature carrot, mature carrot
tops, and wheat forage, straw, chaff, and grain.  In 30-day PBI carrot
roots and tops and immature and mature lettuce and 120-day PBI immature
carrot and carrot tops, no individual identified metabolite was present
at >0.005 ppm, and in 120-day PBI wheat matrices, no individual
identified metabolite was present at >0.008 ppm.  TFNG-AM was the major
compound identified in 30-day PBI carrot and lettuce matrices, except
immature lettuce, and in 120-day PBI wheat straw and chaff.  TFNG was a
significant residue in 30-day PBI immature lettuce and 120-day PBI
immature carrot and wheat forage, straw, grain, and chaff.  Flonicamid
was a minor component in all of these matrices.  

HED has determined that no residues other than flonicamid and its
metabolites TFNA-AM, TFNA, and TFNG are of concern in rotational crops. 

860.1900 Field Accumulation in Rotational Crops

Residue Chemistry Memo DP# 290386, 4/22/2005, A. Acierto (PP#3F6552)

No field rotational crop data were submitted with this petition.  An
adequate limited field rotational crop study was submitted in
conjunction with PP#3F6552.  The study was conducted on the
representative crops turnips and wheat; leafy vegetables were not
included in the limited field trial study because low residues (<0.01
ppm) were observed in lettuce from the confined rotational crop study. 
A total of six field rotational crop trials (two turnip and four wheat
trials) were conducted at five field sites in cotton growing regions: AR
(Region 4), CA (Region 10), OK (Region 6), SC (Region 2), and TX (Region
8).  At each trial site, a primary cover crop of cotton received three
broadcast foliar applications of a 50% WG formulation at ~0.089 lb
ai/A/application for total seasonal rates of ~0.267 lb ai/A (1x the
proposed maximum seasonal rate).  Cotton was harvested 29-30 days after
the last application, the soil was disced or cultivated, and rotational
crops (turnips and wheat) were planted 30-32 and 58-63 days after the
last application and grown to maturity.  

Individual residues of flonicamid and its metabolites TFNA-AM, TFNA, and
TFNG were each below the method LOQ (<0.01 ppm for turnip roots and tops
and wheat forage and grain; <0.02 ppm for wheat straw) in all samples of
rotational crop commodities from both PBIs.

Although the harvest and analysis of wheat hay samples was not included
in the limited field rotational crop study, HED concluded that these
data would not be required because residues were not quantifiable in
wheat forage and straw.  The results of the limited field rotational
crop studies indicate that rotational crop tolerances are not required,
and that the proposed 30-day plantback interval, for all crops not
listed on the label, is appropriate.  

860.1550 Proposed Tolerances

IR-4 has proposed permanent tolerances for the combined residues of the
insecticide flonicamid  and its metabolites TFNA, TFNA-AM, and TFNG
in/on the commodities listed in Table 10.  HED has determined that the
residues of concern in plant commodities are flonicamid and its
metabolites TFNA-AM, TFNA, and TFNG.  The proposed tolerance expression
is adequate.

There are currently no established Codex, Canadian, or Mexican MRLs for
flonicamid.  An International Residue Limit Status sheet is attached to
this review.

Adequate field trial data are available for root vegetables subgroup 1B
(carrot and radish), leafy Brassica greens subgroup 5B (mustard greens),
and hops.  The tolerance calculations for the root vegetable subgroup,
the leafy Brassica greens subgroup, and dried hop cones are presented in
Appendix I.  

The available field trial data indicate that the proposed tolerances for
the root vegetable subgroup is too low; an increased tolerance of 0.60
ppm is needed.  The proposed tolerances for the leafy Brassica greens
subgroup and dried hops cones are appropriate.  When the tolerance for
leafy Brassica greens is established, the existing tolerance for mustard
greens should be removed, as residues in mustard greens will be covered
by the leafy Brassica greens tolerance.  

HED has recently concluded that turnip greens will be moved from the
leaves of root and tuber vegetables crop group (group 2) to the Brassica
leafy vegetables crop group (group 5); turnip greens will also be a
member of the leafy Brassica greens subgroup.  Until the regulations
have been finalized in the Federal Register, a separate tolerance is
needed for turnip greens, at the same level as the leafy Brassica greens
tolerance, 16 ppm; the proposed tolerance for turnip greens is
appropriate.  

HED has concluded that a tolerance for radish tops is not needed for a
use on the root vegetable, except sugar beet, subgroup.  

Adequate field trial data have been submitted previously to support the
requested tolerances for the tuberous and corm vegetables subgroup and
okra.  The proposed tolerances for tuberous and corm vegetables and okra
are adequate.  When the tolerance for the tuberous and corm vegetables
is established, the existing tolerance for potato should be removed, as
residues in potato will be covered by the tuberous and corm vegetables
tolerance.  

The available feeding study data indicate that tolerances are needed for
the combined residues of flonicamid, TFNA-AM, and TFNA in livestock
commodities, other than swine commodities; tolerances are not needed for
swine commodities.  With the exception of eggs, the tolerances should be
set at the combined LOQs of the enforcement methods.  For eggs, the
feeding study data indicate that a tolerance is needed at 0.04 ppm.  For
the remaining commodities, tolerances are needed at 0.03 ppm for milk
and the fat of cattle, goat, horse, and sheep; 0.03 ppm for the fat,
meat, and meat byproducts of poultry; and 0.08 ppm for the meat and meat
byproducts of cattle, goat, horse, and sheep.  Tolerances were
established previously for the combined residues of flonicamid, TFNA,
and TFNA-AM in egg, milk, and the fat, meat, and meat byproducts of
cattle, goat, horse, poultry, and sheep.  The established tolerances for
milk, the meat and fat of cattle, goat, horse, and sheep, and all
poultry commodities must be increased slightly to account for the
combined LOQs of the regulated analytes.

A summary of the recommended tolerances for the current petition is
presented in Table 10.  The proposed tolerances should be revised to
reflect the recommended tolerance levels as specified in Table 10.  

Table 10. 	Tolerance Summary for Flonicamid

Commodity or Subgroup	Proposed Tolerance (ppm)	Established Tolerance
(ppm)	Recommended Tolerance (ppm)	Comments; Correct Commodity Definition

Tolerances for combined residues of flonicamid and its metabolites TFNA,
TFNA-AM, and TFNG

[40 CFR 180.613(a)(1)]:

Brassica, leafy greens, subgroup 5B	16	--	16

	Hop, dried cones	7.0	--	7.0

	Mustard greens	--	11

Residues in/on mustard greens will be covered by the tolerance for leafy
Brassica green, subgroup 5B.

Okra	0.4	--	0.40

	Potato	--	0.20

Residues in/on potato will be covered by the tolerance for tuberous and
corm vegetables, subgroup 1C.

Radish, tops	16	--

A tolerance for radish tops is not needed to support the proposed uses.

Turnip, greens	16	--	16

	Vegetable, root, except sugar beet, subgroup 1B	0.45	--	0.60

	Vegetable, tuberous and corm, subgroup 1C	0.2	--	0.20

	Tolerances for combined residues of flonicamid and its metabolites
TFNA-AM and TFNA in/on livestock commodities [40 CFR 180.613(a)(2)]:

Cattle, fat	--	0.02	0.03	Increased tolerances are needed to reflect
combined limits of quantitation for all regulated residues.

Cattle, meat	--	0.05	0.08

	Cattle, meat byproducts	--	0.08	0.08	No change needed.

Egg	--	0.03	0.04	An increased tolerance is needed to account for all
regulated residues.

Goat, fat	--	0.02	0.03	Increased tolerances are needed to reflect
combined limits of quantitation for all regulated residues.

Goat, meat	--	0.05	0.08

	Goat, meat byproducts	--	0.08	0.08	No change needed.

Horse, fat	--	0.02	0.03	Increased tolerances are needed to reflect
combined limits of quantitation for all regulated residues.

Horse, meat	--	0.05	0.08

	Horse, meat byproducts	--	0.08	0.08	No change needed.

Milk	--	0.02	0.03	Increased tolerances are needed to reflect combined
limits of quantitation for all regulated residues.

Poultry, fat	--	0.02	0.03

	Poultry, meat	--	0.02	0.03

	Poultry, meat byproducts	--	0.02	0.03

	Sheep, fat	--	0.02	0.03

	Sheep, meat	--	0.05	0.08

	Sheep, meat byproducts	--	0.08	0.08	No change needed.

References

DP#:	290386

Subject:	Flonicamid.  Petition for the Establishment of Permanent
Tolerances for Use on Cotton, Cucurbit Vegetables, Fruiting Vegetables,
Leafy Vegetables, Pome Fruit, Potato, and Stone Fruit.  Summary of
Analytical Chemistry and Residue Data.  PP#3F6552.  

From:	A. Acierto

To:	A. Sibold

Dated:	4/22/2005

MRIDs:	45854704-45854718, 45854801-45854811, 45863800, 45863806,
45863807, & 46242803

  SEQ CHAPTER \h \r 1 DP#:	301415

Subject:	Flonicamid.  Petition for the Establishment of Permanent
Tolerances for Use on Head and Stem Brassica and Mustard Greens. 
Summary of Analytical Chemistry and Residue Data.  PP#4F6832.  

From:	A. Acierto

To:	A. Sibold

Dated:	8/23/2005

MRID:	46242804

DP#:	304829

Subject:	Flonicamid.  EPA File Symbol No. 71512-RN.  Bridging Study for
the 50% Water-Dispersible Granule (50 WG) and 50% Soluble Granule (50
SG) Formulations.  

From:	A. Acierto

To:	A. Sibold/M. Johnson

Dated:	1/9/2006

MRID:	46271202

DP#:	329381

Subject:	Flonicamid 50WG Insecticide (EPA Reg. No. 71512-9). 
Conditional Registration Follow-Up Data.

From:	A. Acierto

Dated:	11/16/07

MRIDs:	46824301-46824304

  SEQ CHAPTER \h \r 1 Attachments:  

International Residue Limit Status sheet

Appendix I - Tolerance Assessment Calculations

Template Version September 2005



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:  N-(cyanomethyl)-4-trifluoromethyl)-3-pyridinecarboximide
Common Name:

Flonicamid	X Proposed tolerance

( Reevaluated tolerance

( Other	Date: 4/24/2007

Codex Status (Maximum Residue Limits)	U. S. Tolerances

X No Codex proposal step 6 or above

⁯Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#6E7081

DP#:  329381

Other Identifier:  Decision #368509

Residue definition (step 8/CXL):  N/A	Reviewer/Branch:  Amelia Acierto,
RAB3

	Residue definition:  Flonicamid and metabolites TFNA
(4-trifluoromethylnicotinic acid), TFNA-AM
(4-trifluoromethylnicotinamide), and TFNG
[N-(4-trifluoromethylnicotinoyl) glycine]  SEQ CHAPTER \h \r 1   SEQ
CHAPTER \h \r 1 

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Vegetable, root, except sugar beet, subgroup 1B	0.45

Radish, tops	16

Vegetable, tuberous and corm, subgroup 1C	0.2

Brassica, leafy greens, subgroup 5B	16

Turnip, greens	16

Hop, dried cones	7.0

Okra	0.4

	Limits for Canada	Limits for Mexico

X   No Limits

   No Limits for the crops requested	X   No Limits

   No Limits for the crops requested

Residue definition  N/A	Residue definition:  N/A

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

	Notes/Special Instructions:  S. funk, 04/25/2007.

Appendix I.  Tolerance Assessment Calculations.

For each of the crops listed below, the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data (SOP), along with the tolerance
spreadsheet, was used for calculating recommended tolerances.  As
specified in the SOP, the minimum of the 95% upper confidence limit
(UCL) on the 95th percentile and the point estimate of the 99th
percentile was selected as the tolerance value in cases when the dataset
was large (greater than 15 samples) and reasonably lognormal.  For
datasets that were small (≤15 samples) and reasonably lognormal, the
upper bound estimate of the 95th percentile based on the median residue
value was compared to the minimum of the 95% UCL on the 95th percentile
and the point estimate of the 99th percentile, and the minimum value was
selected as the tolerance value.  For datasets that were not lognormal,
the upper bound on the 89th percentile was selected as the tolerance
value (distribution-free method).  The rounding procedures specified in
the SOP were also used.

Root vegetable, except sugar beet, subgroup 1B

The dataset used to establish a tolerance for flonicamid on the root
vegetable subgroup consisted of field trial data for carrot and radish
(the representative crops of subgroup 1B), representing application
rates of 0.267 lb ai/A (3 applications at 0.089 lb ai/A/application)
with a 2- to 4-day PHI for radish and a 6- to 8-day PHI for carrot.  As
specified by the SOP, the results used for tolerance calculation
represented field trial application rates within 25% of the maximum
label application rate, respectively.  The results used for radish for
the tolerance calculation represent PHIs within 25% of the minimum label
PHI.  The results used for carrot represent PHIs (6-8 days) greater than
the minimum label PHI (3 days).  However, HED has determined that
residues in/on carrot at a 3-day PHI are not likely to be greater than
the residues found at the ~7-day PHI (see 860.1500).  The residue values
used to calculate the tolerance are provided in Table I.

For carrot, all field trial sample results for flonicamid and TFNA-AM
were below the LOQ, results for TFNA were below the LOQ in/on 6 of 16
samples, and results for TFNG were below the LOQ in/on 11 of 16 samples.
 For radish root, residues of TFNA-AM were below the LOQ in/on all
samples and residues of TFNG were below the LOQ in/on 8 of 10 samples;
residues of flonicamid were below the LOQ in/on 2 samples and residues
of TFNA were above the LOQ in/on all samples.  Because no radish root
samples had combined residues below the combined LOQ, and combined
residues were below the LOQs in/on only three carrot samples, maximum
likelihood estimation (MLE) procedures were not needed to impute
censored values. 

The carrot dataset was not small and the radish dataset was small (16
and 10 samples, respectively).  The dataset for each crop was entered
into the tolerance spreadsheet.  Visual inspection of the lognormal
probability plots for carrot and radish root (Figures I-1 and I-3)
provided in the spreadsheet indicated that radish root dataset was
reasonably lognormal, but that the carrot dataset was not.  The results
from the approximate Shapiro-Francia test statistic (Figures I-2 and
I-4) confirmed that the assumption of lognormality should not be
rejected for radish root but should be rejected for carrot.  

Using the tolerance spreadsheet, the recommended tolerances are 0.35 ppm
for carrot and 0.60 ppm for radish root.  Because the minimum and
maximum recommended tolerances differ by less than 5x, a crop group
tolerance is appropriate for fruiting vegetables.  The recommended value
is 0.60 ppm, the maximum of the recommended individual tolerances.

Table I.	Residue data used to calculate tolerance for flonicamid on root
vegetable, except sugar beet, subgroup 1B.

Regulator:	EPA	EPA

Chemical:	Flonicamid	Flonicamid

Crop:	Carrot	Radish root

PHI:	6-8 days	2-4 days

App. Rate:	0.267 lb ai/A	0.267 lb ai/A

Submitter:	IR-4	IR-4

MRID Citation:	MRID 46867103	MRID 46867102

	Combined Residues of Flonicamid, TFNA, TFNA-AM, and TFNG (ppm)

	<0.184	<0.210

	<0.176	<0.214

	<0.242	<0.403

	<0.197	<0.324

	<0.234	<0.165

	<0.194	<0.132

	<0.1701	<0.148

	<0.1701	<0.190

	<0.172	<0.080

	<0.1701	<0.084

	<0.178

<0.180

<0.298

<0.268

<0.186

<0.197

	1  All analytes were below the LOQ in/on this sample (<0.020 ppm for
flonicamid and <0.050 ppm for each of the metabolites).

Figure I-1.	Lognormal probability plot of flonicamid field trial data
for carrot.

Figure I-2.	Tolerance spreadsheet summary of flonicamid field trial data
for carrot.

Figure I-3.	Lognormal probability plot of flonicamid field trial data
for radish root.

Figure I-4.	Tolerance spreadsheet summary of flonicamid field trial data
for radish root.

Dried hop cones

The dataset used to establish a tolerance for flonicamid on dried hop
cones consisted of field trial data representing application rates of
0.267 lb ai/A (3 applications at 0.089 lb ai/A/application) with a 9- to
11-day PHI.  As specified by the SOP, the results used for tolerance
calculation represented field trial application rates and PHIs within
25% of the maximum label application rate and minimum label PHI,
respectively.  The residue values used to calculate the tolerance are
provided in Table II.

The dataset was small (6 samples).  Residues of flonicamid, TFNA,
TFNA-AM, and TFNG were above the LOQ in/on all field trial samples. 

The dataset was entered into the tolerance spreadsheet.  Visual
inspection of the lognormal probability plot (Figure II-1) provided in
the spreadsheet indicated that the dataset was reasonably lognormal,
which was confirmed by the approximate Shapiro-Francia test statistic
(Figure II-2).

Using the tolerance spreadsheet, the recommended tolerance for dried hop
cones is 7.0 ppm.  

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Figure II-1.	Lognormal probability plot of flonicamid field trial data
for dried hop cones.

Figure  II-2.	Tolerance spreadsheet summary of flonicamid field trial
data for dried hop cones.

Leafy Brassica greens, subgroup 5B

The dataset used to establish a tolerance for flonicamid on the leafy
Brassica greens crop subgroup consisted of field trial data for mustard
greens (the representative crop of the leafy Brassica greens subgroup),
representing application rates of 0.267 lb ai/A (3 applications at 0.089
lb ai/A/application) with a 0-day PHI.  As specified by the SOP, the
results used for tolerance calculation represented field trial
application rates and PHIs within 25% of the maximum label application
rate and minimum label PHI, respectively.  The data were obtained from
the DER for MRID 46867104, as well as a previous mustard greens review
(46242804.der.F.wpd; DP# 301415, 8/23/2005, A. Acierto).  The residue
values used to calculate the tolerance are provided in Table  III.

The dataset was not small (16 samples).  Residues of flonicamid and TFNG
were above the LOQ in/on all field trial samples, residues of TFNA were
above the LOQ in/on 15 of 16 samples, and residues of TFNA-AM were above
the LOQ in/on 8 of 16 samples.  Because no samples had combined residues
below the combined LOQ, MLE procedures were not needed to impute
censored values. 

The dataset was entered into the tolerance spreadsheet.  Visual
inspection of the lognormal probability plot (Figure III-1) provided in
the spreadsheet indicated that the dataset was reasonably lognormal,
which was confirmed by the approximate Shapiro-Francia test statistic
(Figure III-2.

Using the tolerance spreadsheet, the recommended tolerance for the leafy
Brassica greens subgroup is 16 ppm.  

Table III.	Residue data used to calculate tolerance for flonicamid on
leafy Brassica greens, subgroup 5B.

Regulator:	EPA

Chemical:	Flonicamid

Crop:	Mustard greens

PHI:	0 days

App. Rate:	0.267 lb ai/A

Submitter:	ISK Biosciences/IR-4

MRID Citation:	MRIDs 46242804 and 46867104

	Combined Residues of Flonicamid, TFNA, TFNA-AM, and TFNG (ppm)

	8.161

	8.314

	9.596

	10.113

	<2.132

	<2.405

	4.233

	4.956

	2.258

	3.197

	5.015

	4.789

	5.617

	4.928

	5.620

	5.348

Figure III-1.	Lognormal probability plot of flonicamid field trial data
for mustard greens.

Figure III-2.	Tolerance spreadsheet summary of flonicamid field trial
data for mustard greens.

Page   PAGE  34  of   NUMPAGES  39 

Flonicamid	Summary of Analytical Chemistry and Residue Data	DP#:  332316