Document ID: EPA-HQ-OPP-2007-0339-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-05-28T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	February 21, 2008

	Subject:	Fluopicolide.  PP#7E7172.  Petition for Establishment of
Tolerances for Use on Root Vegetables (Subgroup 1A), Leaves of Root and
Tuber Vegetables (Group 2), Bulb Vegetables (Group 3), and Head and Stem
Brassica (Subgroup 5A).  Summary of Analytical Chemistry and Residue
Data.  

DP#:	343471	Decision Number:	373401

PC Code:	027412	MRID Nos.:	47021701, 47021702, 47021703, 47021704,
47021705, 47021706 47021707

40 CFR 180.	627

Chemical Class:	Benzamide/pyridineFungicide

	From:	Amelia M. Acierto, Chemist

		Registration Action Branch 3

		Health Effects Division (7509P)

	

Through:		Felecia Fort, Senior Chemist

		Registration Action Branch 3

		Health Effects Division (7509P)

			and

		Chemistry Science Advisory Council

		Health Effects Division (7509P)

	To:	Janet Whitehurst/Tony Kish, RM-22

		Fungicide Branch

		Registration Division (7505P)

	This document was originally prepared under contract by Dynamac
Corporation (2275 Research Blvd, Suite 300; Rockville, MD 20850;
submitted 06/22/2007).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.

Executive Summary

The Interregional Research Project No. 4 (IR-4) on behalf of the
Agricultural Experiment Stations of AZ, CA, FL, GA, MI, ND, OR, and WA
has submitted a petition, PP#7E7172, proposing the establishment of
tolerances for residues of the fungicide fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide] in/on the following raw agricultural commodities (RAC).

Root vegetables subgroup 1-A 	0.15 ppm

Leaves of root and tuber vegetables, group 2 	13 ppm

Bulb vegetables, group 3 	6 ppm

Chive, fresh leaves 	6 ppm

Chive, Chinese, fresh leaves 	6 ppm

Daylily, bulb 	6 ppm

Elegans hosta 	6 ppm

Fritillaria, bulb 	6 ppm

Fritillaria, leaves	6 ppm

Garlic, Serpent, bulb 	6 ppm

Kurrat 	6 ppm

Lady’s leek 	6 ppm

Leek, wild 	6 ppm

Lily, bulb 	6 ppm

Onion, Beltsville bunching	6 ppm

Onion, Chinese, bulb 	6 ppm

Onion, fresh 	6 ppm

Onion, macrostem 	6 ppm

Onion, pearl	6 ppm

Onion, potato, bulb 	6 ppm

Onion, tree, tops 	6 ppm

Shallot, bulb 	6 ppm

Shallot, fresh leaves 	6 ppm

Head and stem Brassica subgroup 5-A	5 ppm

In conjunction with this petition, IR-4 is requesting an amended
registration of the Valent U.S.A Corporation end-use product, V-10161 4
SC, a 4 lb ai/gal suspension concentrate (SC) formulation which is
equivalent to a flowable concentrate (FlC) formulation of fluopicolide
with EPA File Symbol No. 59639-RUN. The product is being proposed for
use on Brassica head and stem                                           
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
        vegetables, bulb vegetables, and leaves of root and tuber
vegetables excluding potato and sweet potato.  The product is proposed
for four foliar applications at up to 0.125 lb ai/A/application at a 7
to 14-day retreatment interval (RTI) for all crops with a maximum
seasonal rate of 0.375 lb ai/A and a 2-day preharvest interval (PHI). 
The 4 lb ai/gal SC formulation is to be applied in a tank mix with
fungicides from different target site of action groups that are
registered for the same use and that are effective against the pathogens
of concern.  Under a pending petition  (PP#5F7016, DP# 327026),
fluopicolide was proposed for use on grape, potato, sweet potato,
cucurbit vegetables, fruiting vegetables, and leafy vegetables (except
Brassica), reflecting similar use patterns.  

Tolerances have been established (40 CFR §180.627) for residues of
fluopicolide in/on imported grapes at 2.0 ppm and raisins at 6.0 pm.  No
Codex, Canadian, or Mexican MRLs have been established for fluopicolide.
 

There are currently no registered uses of fluopicolide in the U.S.
although Valent U.S.A. Corporation has submitted a petition, PP#5F7016,
proposing the establishment of tolerances for residues of fluopicolide
in/on tuberous and corm vegetables subgroup 1C; vegetable, leafy, except
Brassica, group 4; vegetable, fruiting, group 8; vegetable, cucurbit,
group 9; grape; and raisins; the proposed tolerance on wheat is for
indirect and inadvertent residues in rotational wheat commodities.  HED
has considered granting the establishment of a tolerance for
fluopicolide on the raw agricultural commodities proposed except for
potato and wheat which are livestock food/feed commodities (DP#s 326080,
327026, 339155, 11/19/2007, A. Acierto).

No new metabolism data were submitted with the subject petition. 
Metabolism studies with lettuce and potato were previously submitted in
conjunction with PP#5F7016, and a metabolism study with grape was
submitted in conjunction with PP#5E6903. 

For the purposes of this petition, the nature of the residue in plants
is adequately understood.  In HED’s RARC1 meeting held on 7/19/07, HED
determined that the residue of concern for the tolerance expression for
primary crops is fluopicolide (parent).  The residues of concern for the
risk assessment for primary crops except tuberous and corm vegetables
are fluopicolide (parent) and BAM.  The RARC1 recommended that (in
addition to parent and BAM) PCA should be included in the risk
assessment for tuberous and corm vegetables 

This petition does not require tolerances in/on livestock.  However,
there are ruminant feed items (i.e., sugar beets and carrot culls)
associated with this petition for which ruminant metabolism studies are
required.  The ruminant metabolism studies submitted previously by the
Valent USA (PP#5F7016) were incomplete and required additional
information to support the ruminant metabolism studies. Based on the
decision made under PP#5F7016, HED will not consider granting the new
uses of fluopicolide associated with livestock food/feed commodities
until the requirements for livestock metabolism studies including
feeding studies with fluopicolide and BAM are fulfilled.

The LC/MS/MS method, Method RM-43C-2 (MRID 47073701) is an adequate
enforcement method for determination of fluopicolide (parent) in plants
(DP# 329578, ACB/BEAD, 3/14/07).  The LOQ for fluopicolide (parent) is
0.01 ppm.  Currently, no tolerances for ruminant, swine, or poultry
commodities are required to support the proposed uses; therefore,
enforcement methods for these livestock commodities are not required.
However, if a tolerance would be needed in the future, confirmatory
procedures or an interference study would be required for the LC/MS/MS
Method 303-02 to be considered adequate for enforcement purposes.  If it
is determined in the future that tolerances for poultry commodities are
needed, an enforcement method would be required for poultry commodities.
 

Acceptable data collection methods are available to determine the
residues of concern in both plant and livestock commodities.  

Adequate multiresidue methods testing data are also available from the
earlier petition (PP#5F7016). which indicate that the multiresidue
methods are not appropriate for determining residues of fluopicolide.

Additional storage stability data are required to support the Brassica
head and stem, bulb, and root vegetable crop field trials; maximum
storage durations for these samples ranged from 35 to 47 months.  In
support of the submitted field trial and processing studies, the
petitioner cited the available data under PP#5F7016 in which the results
of the 30-month storage stability study for cabbage, grapes, potato
tubers, and wheat grain were extrapolated to demonstrate that residues
are stable under frozen storage conditions for up to 48 months. 
However,  HED found it inappropriate to use the extrapolated data to
make conclusions regarding the stability of residues of fluopicolide,
BAM, and PCA in/on commodities following >30 months of storage.   Based
on the conclusion made under PP#5F7016, HED requires additional storage
stability data to support the full duration of the storage stability
study periods. 

Adequate field trial data for Brassica head and stem, bulb and root
vegetables are available, pending submission of additional storage
stability data.  An adequate number of geographically representative
field trials were conducted at 1x the proposed maximum seasonal rate for
each crop.  The available field trial data indicate that the proposed
tolerances for Brassica head and stem vegetables, and root vegetables
are adequate.  For bulb vegetables, the available data will support a
tolerance of 7.0 ppm.  The tolerance calculations are presented in
Appendix I.  

Adequate processing data for sugar beets are available pending
submission of additional storage stability data.  The available
processing data indicate that residues of fluopicolide are not likely to
concentrate in sugar.  Residues of fluopicolide were found to
concentrate slightly in molasses and dried pulp.  Separate tolerances
for sugar beet molasses and dried pulp are not needed because residues
in these commodities are not expected to exceed the recommended
tolerance of 0.15 ppm for the root vegetable subgroup.  However, since
sugar beet is a livestock feed item, tolerance for this crop will not be
granted at this time.

No field rotational crop data were submitted.  Based on the data
submitted in conjunction with PP#5F7016, the IR-4 petitioner has
proposed a PBI of one year for all crops other than cucurbit vegetables,
Brassica head and stem vegetables, bulb vegetables, fruiting vegetables,
grapes, leafy vegetables, root and tuber vegetables, and wheat.  Because
the confined rotational crop data indicated the potential for
quantifiable residues of fluopicolide in/on rotated crops at a one-year
PBI, additional field rotational crop data must be submitted.  Until all
field rotational crop data requirements have been satisfied, the
proposed rotational crop restrictions must be modified to state that
crops may not be rotated to any crops other than bulb vegetables,
Brassica head and stem vegetables, cucurbit vegetables, fruiting
vegetables, grapes, leafy vegetables, root vegetables, tuberous and corm
vegetables, and wheat, with a 0-day PBI for bulb vegetables, Brassica
head and stem vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables, root vegetables, and tuberous and corm
vegetables, and a 30-day PBI for wheat.

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

  SEQ CHAPTER \h \r 1 HED has examined the residue chemistry database
for fluopicolide.  Pending submission of a revised Section B and Section
F (see requirements under Directions for Use and Proposed Tolerances),
submission of the following outstanding residue chemistry data
pertaining to the storage stability; crop field trials, and field
accumulation in rotational crops, there are no residue chemistry issues
that would preclude granting a registration for the requested uses of
fluopicolide excluding sugar beet and carrot and establishment of
tolerances for fluopicolide as stated below.

 

Provided the forthcoming Human Health Risk Assessment does not identify
any risks concern, HED recommends establishment of tolerances as
follows:

Tolerances to be established under 180.627 (a) General. (1)

Tolerances are established for residues of the fungicide fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide] as an indicator of combined residues of fluopicolide and its
metabolite, 2,6-dichlorobenzamide in/on the following raw agricultural
commodities (RACs):

Vegetable, root, subgroup 1A except sugar beet and carrot 	……..0.15
ppm

Vegetable, leaves of root and tuber, group 2	…………………
…15.0 ppm

Vegetable, bulb, group 3-07 …… …………………………       
  7.0 ppm

Brassica, head and stem, subgroup 5A
........................................  5.0 ppm

DEFICIENCIES 

  SEQ CHAPTER \h \r 1 

860.1200 Directions for Use

	

The proposed PHI for root and tuber vegetables must be revised to 7
days. 

Until all field rotational crop data requirements have been satisfied,
the proposed rotational crop restrictions must be modified to state that
crops may not be rotated to any crops other than bulb vegetables,
Brassica head and stem vegetables, cucurbit vegetables, fruiting
vegetables, grapes, leafy vegetables, root vegetables, tuberous and corm
vegetables, and wheat, with a 0-day PBI for bulb vegetables, Brassica
head and stem vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables, root vegetables, and tuberous and corm
vegetables, and a 30-day PBI for wheat.  

860.1550 Proposed Tolerances

The proposed tolerance expression should be revised to reflect the
correct chemical name for fluopicolide.

The proposed tolerances should be revised to reflect the recommended
tolerance levels and correct commodity definitions as specified in Table
9.

A revised Section F should be submitted to propose for Vegetable, bulb,
group 3-07 and delete the list of individual crops under these
subgroups.  

860.1380 Storage Stability

6.	Additional storage stability data are required to support the
Brassica head and stem, bulb, and root vegetable crop field trials. 
Storage stability studies with a representative root or tuber vegetable
(reflecting analysis of roots and tops) and a Brassica vegetable must be
conducted.  The requested data for a root or tuber vegetable may be
translated to bulb vegetables.  The required studies should reflect the
storage conditions of samples from the crop field trials and should
include storage intervals of up to 47 months for the root or tuber
vegetable and 45 months for the Brassica vegetable.  If residues are
found to be unstable in any representative commodity, additional storage
stability data studies will normally be required on additional
commodities of that group [see OPPTS 860.1380(c)(5)(ii)(D)].  

860.1900 Field Accumulation in Rotational Crops

7.	As required under PP#5F7016, the petitioner must submit a limited
field rotational crop study conducted at a 12-month PBI with
representative leafy vegetable, and  root vegetable crops.  If the
results of the limited field rotational crop study indicate the
potential for quantifiable fluopicolide residues of concern in/on
rotational crops at a 12-month PBI, then extensive field rotational crop
studies will be required for all crops the petitioner wishes to allow
for rotation at a 12-month PBI.

Background

Fluopicolide is a fungicide intended for the control of plant diseases
caused by Oomycetes.  While the mode of action of disease control by
fluopicolide has not been fully determined, it has been determined to be
different from the known modes of action for other active ingredients
that are registered for control of fungal diseases.  The application by
Valent U.S.A. for registration of fluopicolide in the U.S. for use on
cucurbit vegetables, fruiting vegetables, grapes, leafy vegetables
(except Brassica), potato, and sweet potato is under consideration by
the Agency.  

The nomenclature of fluopicolide and its two metabolites BAM and PCA is
summarized in Table 1, and the physicochemical properties of the parent
fluopicolide are summarized in Table 2.  

TABLE 1.	Test Compound Nomenclature.

Compound	

Common name	Fluopicolide

Company experimental name	V-10161 (Valent); AE C638206 (Bayer)

IUPAC name
2,6-dichloro-N-[3-chloro-5-(trifluoromethyl)-2-pyridylmethyl]benzamide 

CAS name
2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzami
de 

CAS registry number	239110-15-7 

End-use products (EPs)	V-10161 4SC Fungicide (40% suspension
concentrate; 4 lb ai/gal; EPA File Symbol No. 59639-RUN) 

Compound	

Common name	BAM

Company experimental name	AE C653711

IUPAC name	2,6-dichlorobenzamide 

CAS name	2,6-dichlorobenzamide 

Compound	

Common name	PCA

Company experimental name	AE C657188

IUPAC name	3-chloro-5-trifluoromethylpyridine-2-carboxylic acid

CAS name	3-chloro-5-trifluoromethylpyridine-2-carboxylic acid

TABLE 2.	Physicochemical Properties of the Technical Grade Test Compound
Fluopicolide.

Parameter	Value	Reference 1

Melting point/range 	149 (C 	MRID 46474015

pH 	6.5 at 22.0 (C 	MRID 46474013

Density 	1.65 g/cm3 at 30 ºC  	MRID 46474016

Water solubility (20 (C) 	3.02 mg/L

2.86 mg/L at pH 4

2.80 mg/L at pH 7

2.80 mg/L at pH 9 	MRID 46474020

MRID 46474021

Solvent solubility (mg/L at 20 (C) 	n-Hexane:	200

Ethanol:	19,200

Toluene:	20,500

Ethyl acetate:	37,700

Acetone:	74,700

Dichloromethane:	126,000

Dimethylsulfoxide:	183,000 	MRID 46474022

Vapor pressure at 25 (C 	8.03 x 10-7 Pa 	MRID 46474023

Dissociation constant (pKa) 	No evidence of ionization in the pH range
of 1.9 to 9.8 	MRID 46474017

Octanol/water partition coefficient Log(KOW) 	Log POW = 3.26 at pH 7.8
and 22 ± 1 (C 	MRID 46474018

	Log POW = 2.9 at pH 4.0, 7.3 and 9.1 and 40 (C 	MRID 46474019

UV/visible absorption spectrum 	Absorption maxima wavelengths (nm): 

	In methanol:	203 and 271

	In methanol/HCl:	202 and 270

	In methanol/NaOH:	219 and 271 	MRID 46474014

1 RD Memo; DP# 318332, 10/17/06, S. Mathur

860.1200  Directions for Use

IR-4 has submitted use directions under Section B of the petition as
well as draft labeling for the 4 lbai/gal SC formulation of fluopicolide
(V-10161 4 SC; EPA File Symbol No. 59639-RUN).  The proposed use
directions for fluopicolide are presented in Table 3.

Table 3.		Summary of Directions for Use of Fluopicolide.

Trade Name	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

Brassica (head and stem):  Broccoli; Brussels Sprouts; Cabbage;
Cauliflower; Cavalo Broccolo; Chinese Broccoli; Chinese (Napa) Cabbage;
Chinese Mustard Cabbage; Kohlrabi

V-10161 4 SC	Postemergence	0.09-0.125	4	7-14	0.375	2	Application to be
made in a minimum of 20 gal/A using ground equipment or 5 gal/A using
aerial equipment.

Bulb Vegetables including:  Beltsville Bunching Onion; Chive (fresh
leaves); Chinese Chive (fresh leaves); Chinese Onion Bulb; Daylily Bulb;
Elegans Hosta; Fritillaria (bulb and leaves); Garlic Bulb; Great Headed
Garlic Bulb; Green Onion; Kurrat; Lady’s Leek; Leek; Lily Bulb;
Macrostem Onion; Onion (bulb and fresh); Pearl Onion; Potato Onion Bulb;
Shallot (bulb and fresh leaves); Serpent Garlic Bulb; Tree Onion Tops;
and Wild Leek

V-10161 4 SC	Postemergence	0.09-0.125	4	7-14	0.375	2	Application to be
made in a minimum of 20 gal/A using ground equipment or 5 gal/A using
aerial equipment.

Other Root and Tuber Vegetables2,3:  Arracacha; Arrowroot; Black
Salsify; Carrot; Cassava (bitter and sweet); Celeriac; Chayote (root);
Chicory; Chinese Artichoke; Chufa; Dasheen (taro); Edible Burdock;
Edible Canna; Garden Beet; Ginger; Ginseng; Jerusalem Artichoke; Leren;
Horseradish; Parsnip; Radish; Oriental Radish; Rutabaga; Salsify;
Skirrit; Spanish Salsify; Sugar Beet; Tanier; True Yam; Turmeric;
Turnip; Turnip-rooted Chervil; Turnip-rooted Parsley; and Yam Bean

V-10161 4 SC	Postemergence	0.09-0.125	4	7-14	0.375	2	Application to be
made in a minimum of 20 gal/A using ground equipment or 5 gal/A using
aerial equipment.

1  RTI = Retreatment interval

2  Use directions for potato and sweet potato are (DP# 327026), and
differ in the proposed RTI (10 days), PHI (7 days), and tank mix
partners. 

3 A tank mix with V-10161 4 SC with a labeled rate of either mancozeb or
other labeled product with activity on downy

mildew must be used for resistance management in leafy vegetables.  It
is recommended that V-10161 4 SC be applied on a 10 day retreatment
interval to leafy vegetables.

The proposed label for the 4 lb ai/gal SC formulation specifies that the
product must be applied in a tank mix with fungicides from different
target site of action groups that are registered for the same use and
that are effective against the pathogens of concern.  The label
specifies that the minimum labeled rate of each fungicide in the tank
mix should be used.  

Applications are to begin when crop and/or environmental conditions
favor disease development.  A maximum of two sequential fluopicolide
applications are to be made before alternating with an effective
fungicide from a different resistance management group.

The following tank mixes are recommended on the label for the 4 lb
ai/gal SC formulation:  chlorothalonil, mancozeb, or other labeled
product with activity on downy mildew and phytophthora or botrytis for
Brassica head and stem and bulb vegetables; and a labeled product with
activity on pythium for other root and tuber vegetables.

A restricted entry interval of 12 hours has been proposed.  The
following rotational crop restrictions are proposed for the 4 lb ai/gal
SC formulation:  a 0-day PBI for Brassica head and stem vegetables, bulb
vegetables, cucurbit vegetables, fruiting vegetables, grapes, leafy
vegetables, and root and tuber vegetables; a 30-day PBI for wheat; and a
12-month PBI for all other crops.

Conclusions.  The submitted use directions are sufficient to allow
evaluation of the available residue data relative to the proposed use.  

The available data will support a maximum of three applications of the
SC formulation at ~0.12 lb ai/A/application, for a total rate of ~0.36
lb ai/A, to head and stem Brassica vegetables, bulb vegetables, and root
vegetables.  The data will also support a minimum retreatment interval
of 7 days and a PHI of 2 days for Brassica and bulb vegetables, and a
minimum RTI of 7 days for root vegetables.  Based on the submitted field
trial data, the proposed PHI for other root and tuber vegetables must be
revised to 7 days.  

Until all field rotational crop data requirements have been satisfied,
the proposed rotational crop restrictions must be modified to state that
crops may not be rotated to any crops other than Brassica head and stem
vegetables, bulb vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables, root and tuber vegetables, and wheat, with a
0-day PBI for Brassica head and stem vegetables, bulb vegetables,
cucurbit vegetables, fruiting vegetables, grapes, leafy vegetables, and
root and tuber vegetables, and a 30-day PBI for wheat.

860.1300 Nature of the Residue - Plants

DER Reference:	None

Residue Chemistry Memo DP# 326080, 8/20/07, A.Acierto (PP#5F7016)

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo DP# 321209, 1/23/2007, A.
Acierto (PP#5E6903) 

No new plant metabolism data were submitted with this subject IR-4
petition.  Based on the acceptable grape, lettuce, and potato metabolism
studies submitted under PP#5E6903 and PP#5F7016, the qualitative nature
of the residues in primary plants is adequately understood for the
purposes of this petition.  HED has determined that the tolerance
expression for all primary crops is fluopicolide per se as an indicator
of combined residues of fluopicolide and its metabolite,
2,6-dichlorobenzamide (BAM).  For risk assessment purposes, the residue
of concern for the tuberous and corm vegetables includes the parent
compound, fluopicolide, and its metabolites,
3-chloro-5-trifluoromethylpyridine-2-carboxylic acid (PCA) and BAM.  For
all other primary crops, the residue of concern for risk assessment
purposes includes the parent compound and the metabolite, BAM.  

In grape, lettuce, and potato metabolism studies reported in PP#5F7016,
the majority of radioactivity was found to be on the surface of foliage
samples (all studies) and fruit samples (grape study).  Fluopicolide
appeared to be metabolized slowly in these crops to BAM and PCA via
cleavage of the bond between the carbon attached to the pyridine ring
and the amide nitrogen of the parent compound, and AE C643890 (an
additional metabolite identified in grape, lettuce and potato
commodities which is present at <3% TRR) is produced by the
hydroxylation of the phenyl ring in the parent compound.  BAM, a common
metabolite of fluopicolide and dichlobenil, is included in the tolerance
expression for dichlobenil because it is a major metabolite of
dichlobenil.  The metabolism of fluopicolide in rotational crops
appeared to be more extensive than that observed in primary crops.  In
addition to fluopicolide, BAM, and PCA, four other metabolites [AE
C657378 (3-OH-BAM), AE 1344122 (P1X), AE C653598, and AE B102859] were
observed in the confined rotational crop studies that were not observed
in the primary crop metabolism studies.  The confined rotational crop
data indicate the potential for quantifiable fluopicolide and
metabolites in rotated crop commodities. 

860.1300 Nature of the Residue - Livestock

DER References: 46708514.der.doc (Cow; phenyl label)

		46708518.der.doc (Cow; pyridinyl label)

Residue Chemistry Memo DP# 326080, 8/20/07, A.Acierto (PP#5F7016)

No new livestock metabolism data were submitted with the subject
petition.  Metabolism studies with dairy cows and laying hens were
previously submitted in conjunction with PP#5F7016.  Only the results of
the ruminant metabolism studies are relevant for this petition because
there are no poultry feedstuffs associated with the proposed uses on
Brassica, bulb, and root and tuber vegetables.  

 In ruminants,  fluopicolide appears to be metabolized via hydroxylation
of the chlorophenyl ring in two positions to form AE 0712556 and AE
C643890; these metabolites were found in liver and kidney at <7% TRR
each.  Each of these metabolites is then conjugated with sulfate or
glucuronic acid, or hydroxylated in a second position and then
conjugated with sulfate or glucuronic acid.  A small amount of BAM was
found in milk (4% TRR), and no PCA was found in any cattle matrix.  HED
has tentatively determined that the residue of concern for a tolerance
expression in livestock commodities is fluopicolide per se.  For the
risk assessment, the residues of concern are parent fluopicolide and
BAM.  

As stated in the Executive Summary, the ruminant metabolism studies
submitted previously by the Valent USA (PP#5F7016) are incomplete and
numerous deficiencies have been noted.  HED will not consider granting
the new uses of fluopicolide associated with livestock food/feed
commodities until the requirements for livestock metabolism studies
including feeding studies with fluopicolide and BAM are fulfilled.

860.1340 Residue Analytical Methods

Plant commodities

DER Reference:  None 

Residue Chemistry Memo DP# 326080, 8/20/07, A.Acierto (PP#5F7016)

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo DP# 321209, 1/23/2007, A.
Acierto (PP#5E6903)

Residue Chemistry Memo DP# 329686, A. Acierto, 6/8/2006

Enforcement methods:  An acceptable enforcement method (Method RM-43C-2)
is available.  The LC/MS/MS method has a  LOQ for parent of 0.01 ppm. 
For Method RM-43C-2, the primary analytical column is a reversed-phase
C18 packing while the alternative column is a mixed phase of C18 plus a
strong cation exchange packing material.  The difference of polarity
between the primary and alternate columns provides an additional degree
of method selectivity which satisfies the guideline requirement for a
confirmatory method (Memo, DP #329578, Charles Stafford, 3/14/07). 

Data collection methods:  Samples of crop commodities from the crop
field trial and processing studies associated with this petition were
analyzed for residues of fluopicolide and metabolites BAM and PCA by
LC/MS/MS using Pyxant methods 1611-00.02 or 1629-00.00.  Method
1629-00.00 is a revision of method 1611-00.02 reflecting minor changes
to the HPLC conditions, including changes to the mobile phase gradient
program, and addition of a solvent exchange step following extraction. 
Although not stated by the petitioner, these methods are clearly
modified versions of Method 00782/M001.

Samples of broccoli, cabbage, bulb onion, and green onion from the
submitted crop field trials were analyzed for residues of fluopicolide,
BAM, and PCA using Method 1611-00.02, and samples of carrot, radish and
sugar beet commodities from the root vegetable field trials and sugar
beet molasses, sugar, and oil from the processing study were analyzed
for residues of fluopicolide, BAM, and PCA using Method 1629-00.00.  

Briefly, homogenized crop samples were extracted (2x) from samples with
water:acetone (75:25, v:v).  The extracts were centrifuged and brought
to volume with extraction solvent, and an aliquot was diluted with 0.2%
acetic acid in water for LC/MS/MS analysis.  The validated LOQ was 0.01
ppm for each analyte in all matrices tested, and the estimated limit of
detection (LOD) was 0.003 ppm for each analyte in carrots, radish roots
and tops, and sugar beet roots, tops, molasses, dried pulp, and oil; or
0.008 ppm for each analyte in broccoli, cabbage, bulb onion and green
onion.  Adequate method validation and concurrent method recoveries,
within 70-120%, were obtained for samples of broccoli, cabbage, bulb
onion, green onion, carrot, radish roots, radish tops, and sugar beet
roots, tops, molasses, dried pulp, sugar, and oil fortified with
fluopicolide, BAM, or PCA at 0.01 and up to 15 ppm.  The fortification
levels encompassed the residues found in these crop matrices.

HED notes that for the crop field trials and processing studies
associated with this petition, residues of each analyte were reported in
terms of the analyte (i.e., residues of metabolites were not converted
to parent equivalents). 

Conclusions.  The residue analytical method data are adequate to satisfy
data requirements for the subject petition.

Livestock commodities

DER Reference None

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo DP# 326080, 8/20/07,
A.Acierto (PP#5F7016)

Residue Chemistry Memo DP# 329686, 6/8/06, A. Acierto 

The available livestock commodity method, LC/MS/MS Method 303-02
described in PP#5F7016 is adequate for data collection purposes. 
Currently, no tolerances for ruminant or swine commodities are required
to support the proposed uses; therefore, an enforcement method for these
commodities is not required.  For LC/MS/MS method 303-02 to be
considered adequate for enforcement purposes, confirmatory procedures or
an interference study would be required.

860.1360 Multiresidue Methods

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo DP# 321209, 1/23/2007, A.
Acierto (PP#5E6903)

Adequate multiresidue method testing data for fluopicolide and its
metabolites BAM, PCA, P1X, and BAM-OH were submitted in conjunction with
PP#5E6903.  Based on the results of the testing, the multiresidue
methods are not appropriate for determining residues of fluopicolide or
its metabolites (BAM, PCA, P1X, and BAM-OH).

860.1380 Storage Stability

Plant commodities

DER Reference:	None

Residue Chemistry Memo DP# 326080, 8/20/07, A.Acierto (PP#5F7016) 

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo DP# 321209, 1/23/2007, A.
Acierto (PP#5E6903)

to be ≤20 (C.

The maximum storage intervals of samples from the crop field trial and
processing studies associated with this petition are presented below in
Table 4.

Table 4.		Summary of Storage Conditions and Durations of Samples from
Crop Field Trial and Processing Studies.  

Matrix 	Storage

Temperature

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

Broccoli	≤-20	1065 days (35.0 months)	30 months for residues of
fluopicolide, BAM and PCA in/on frozen cabbage leaves

Cabbage

1225 days (40.3 months)

	Carrot, root	≤-20	1415 days (46.5 months)	30 months for residues of
fluopicolide, BAM, and PCA in/on frozen potato tuber

Onion, bulb

1248 days (41.1 months)

	Onion, green

1159 days (38.1 months)

	Radish, root

1374 days (45.2 months)

	Sugar beet, root

1192 days (39.2 months)

	Radish, tops	≤-20	1379 days (45.4 months)	30 months for residues of
fluopicolide, BAM, and PCA in/on frozen cabbage leaves

Sugar beet, tops

1208 days (39.7 months)

	Sugar beet, molasses	≤-20	1157 days (38.1 months)	30 months for
residues of fluopicolide, BAM and PCA in/on sugar beet dried pulp,
molasses and refined sugar

Sugar beet, dried pulp

1168 days (38.4 months)

	Sugar beet, sugar

1196 days (39.3 months)

	

No new storage stability data were submitted with the subject petition. 
 Instead, the petitioner cited the available 30-month storage stability
data from PP#5F7016 for cabbage leaves, grape, potato tuber, and wheat
grain in support of the submitted field trials as well as the results of
the extrapolation study.  In support of the sugar beet processing study,
the petitioner cited the 30-month storage stability data for potato
tuber and the 30-month data for sugar beet refined sugar, molasses, and
dried pulp as well as the results of the extrapolation study.  The
petitioner stated that based on the available storage stability data for
sugar beet processed commodities, it is unlikely residues would further
degrade after the 30-month storage interval.  

	

ients were determined to be ≤0.48.  Because the proposed extrapolation
represents a much longer interval (1.6x) than is supported by actual
storage stability data and in consideration of the low correlation
coefficients, HED did not believe it would be appropriate to use the
extrapolated data to make conclusions regarding the stability of
residues of fluopicolide and PCA in cabbage and potato tuber, residues
of fluopicolide in grape, or residues of BAM in wheat grain following 48
months of storage.

As required in the cited petition, additional storage stability data are
required to support the Brassica head and stem, bulb, and root vegetable
field trials.  Storage stability studies with a representative root or
tuber vegetable (reflecting analysis of roots and tops) and a Brassica
vegetable must be conducted.  The requested data for a root or tuber
vegetable may be translated to bulb vegetables.   The required studies
should reflect the storage conditions of samples from the crop field
trials and should include storage intervals of up to 47 months for the
root or tuber vegetable, and 45 months for the Brassica vegetable.  The
petitioner is advised that, per OPPTS 860.1380(c)(5)(ii)(D), if residues
are found to be unstable in any representative commodity, additional
storage stability data studies will normally be required on additional
commodities of that group.  

The available storage stability data for fluopicolide, BAM, and PCA
in/on potato tuber and sugar beet molasses, dried pulp, and sugar may be
translated to support the sugar beet processing study; however, these
data are not sufficient to support the storage durations of samples from
the submitted study.

The requested storage stability study for a root or tuber vegetable will
be adequate to support the storage duration for the RAC sample from the
sugar beet processing study.  HED concurs that no additional storage
stability data are required for the processed commodities of sugar
beets, provided the required data indicate that residues are stable in
sugar beets. 

Livestock commodities

Residue Chemistry Memo DP# 326080, 8/20/07, A.Acierto (PP#5F7016)

No new livestock data were submitted in association with this petition. 
In support of the previous petition (PP#5F7016), Valent U.S.A. submitted
the results of a storage stability study with fluopicolide and its
metabolites in cattle commodities.  The results indicate that under
these conditions, residues of fluopicolide and its metabolites BAM and
PCA are stable for up to 83 days in milk, for up to 4 months in muscle
and fat, and for up to 9 months in liver and kidney.  

In the cattle feeding study, milk and tissue samples were stored frozen
prior to analysis; maximum storage intervals were 30 days for milk, 20
days for cream, 13 days for skim milk, 66 days for muscle, 95 days for
fat, and 277-280 days for liver and kidney.  

Conclusions.  Although it is not relevant to this subject petition at
this time, the storage stability data was found adequate to support the
storage intervals and conditions of samples from the cattle feeding
study reported in PP#5F7016.  

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

No poultry feeding studies are required for either fluopicolide or BAM
based on the available metabolism studies and the calculated dietary
burdens.  There is no reasonable expectation of finite residues of
fluopicolide (parent) in poultry commodities [40 CFR §180.6(a)(3)].

860.1500 Crop Field Trials

Root vegetable, subgroup 1A 

Leaves of root and tuber vegetable, group 2

DER Reference:	47021704.der.doc (includes review of MRIDs 47021705 and
47021706)

IR-4 has submitted field trial data for fluopicolide on carrot, radish,
and sugar beet as representative commodities of the root vegetable
subgroup 1A; radish and sugar beet tops were included as representative
commodities of the leaves of root and tuber vegetable group 2.  HED has
concluded that radish tops may be substituted for turnip tops for
purposes of this petition.  The results from these field trials are
discussed below and summarized in Table 5.1.  

Table 5.1.	Summary of Residue Data from the Root Vegetable Crop Field
Trials with Fluopicolide.

Matrix	Total Applic. Rate

(lb ai/A)	PHI (days)	Residue Levels  (ppm)

	n	Min.	Max.	HAFT 1	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Root & Tuber Vegetables, other than potato and sweet potato

(proposed use = 0.375 lb ai/A total application rate, 7-day minimum RTI,
2-day PHI)

Fluopicolide

Carrot	0.353-0.362	7	14	<0.01	0.144	0.125	0.030	0.050	0.043

Radish, root	0.353-0.363	7	12	0.017	0.103	0.086	0.028	0.039	0.026

Radish, top	0.353-0.363	7	12	2.32	10.2	8.76	4.73	4.95	2.45

Sugar beet, root	0.355 - 0.367	7	20	<0.01	0.061	0.054	0.029	0.031	0.017

Sugar beet, tops	0.355 - 0.367	7	20	3.61	11.20	10.51	5.47	6.21	2.27

BAM

Carrot	0.353-0.362	7	14	<0.01	<0.01	<0.01	NA	NA	NA

Radish, root	0.353-0.363	7	12	<0.01	<0.01	<0.01	NA	NA	NA

Radish, top	0.353-0.363	7	12	0.012	0.163	0.156	0.045	0.063	0.051

Sugar beet, root	0.355 - 0.367	7	20	<0.01	0.0162	0.0131	0.010	0.0105
0.001

Sugar beet, tops	0.355 - 0.367	7	20	0.014	0.121	0.107	0.021	0.033	0.029

PCA

Carrot	0.353-0.362	7	14	<0.01	<0.01	<0.01	NA	NA	NA

Radish, root	0.353-0.363	7	12	<0.01	0.011	0.011	<0.01	<0.01	<0.001

Radish, top	0.353-0.363	7	12	<0.01	0.028	0.023	0.014	0.015	0.005

Sugar beet, root	0.355 - 0.367	7	20	<0.01	<0.01	<0.01	NA	NA	NA

Sugar beet, tops	0.355 - 0.367	7	20	<0.01	0.027	0.022	0.010	0.012	0.004

1  HAFT = Highest Average Field Trial

Twenty-three field trials were conducted in the United States during the
2002-2003 growing seasons.  Seven carrot field trials were conducted in
Zones 3 (GA; 1 trial), 5 (OH; 1 trial), 6 (TX; 1 trial), and 10 (CA; 4
trials).  Six radish field trials were conducted in Zones 1 (NY; 1
trial), 3 (FL; 3 trials), 5 (WI; 1 trial), and 10 (CA; 1 trial).  Ten
sugar beet field trials were conducted in Zones 5 (MN, ND, and WI; 5
trials), 7 (ND; 1 trial), 8 (TX; 1 trial), 10 (CA; 1 trial), and 11 (ID
and OR; 2 trials).  

Each field trial consisted of one untreated plot and one treated plot. 
At each trial site, three broadcast foliar applications of a 4 lb ai/gal
suspension concentrate formulation [equivalent to a flowable concentrate
(SC) formulation] of fluopicolide were made at 4- to 7-day retreatment
intervals to carrot, radish, or sugar beet plants at ~0.12 lb
ai/A/application for a total seasonal rate of 0.35-0.37 lb ai/A (~1x the
maximum proposed seasonal rate for root and tuber vegetables). 
Applications were made using ground equipment in spray volumes of 15-39
gal/A with a spreader/sticker added to the tank mixture.

Mature carrot roots, radish roots and tops, and sugar beet roots and
tops were harvested 7 days after the last application.  Additional
samples were collected from one trial for each crop at 2, 4/5, 10, and
14 days following the last application to generate residue decline data.

The collected samples were analyzed for residues of fluopicolide, BAM,
and PCA using LC/MS/MS Method 1629-00.00.  The validated LOQ was 0.01
ppm for each analyte in carrot, radish roots and tops, and sugar beet
roots and tops.  The method was adequate for data collection based on
acceptable method validation and concurrent method recoveries.  

Samples were stored frozen (<-20 (C) prior to analysis.  The maximum
storage durations from harvest to analysis were 1415 days (47 months)
for carrots, 1379 days (45 months) for radish roots and tops, and 1208
days (40 months) for sugar beet roots and tops.  The available storage
stability data indicate that residues of fluopicolide, BAM, and PCA are
reasonably stable under frozen storage conditions for a maximum of 30
months in/on cabbage, potato tuber, wheat grain, and grapes.  Although
the storage stability data for cabbage leaves and potato tuber may be
translated to root vegetables, the available data are not sufficient to
support the storage durations of samples from the subject field trials. 

Maximum residues of fluopicolide were 0.14 ppm in/on carrots, 0.10 ppm
in/on radish roots, and 0.061 ppm in/on sugar beet roots.  Maximum
residues of BAM were <0.01 ppm in/on all samples of carrots and radish
roots, and 0.016 ppm in/on sugar beet roots, and maximum residues of PCA
were <0.01 ppm in/on all samples of carrots and sugar beet roots, and
0.011 in/on radish roots.  Maximum residues of fluopicolide were 10.2
ppm in/on radish tops and 11.20 ppm in/on sugar beet tops.  Maximum
residues of BAM were 0.163 ppm in/on radish tops and 0.121 ppm in/on
sugar beet tops, and maximum residues of PCA were 0.028 ppm in/on radish
tops and 0.027 ppm in/on sugar beet tops.

Based on the residue decline data, fluopicolide residues generally
decreased in/on samples of carrot, radish root and tops, and sugar beet
tops after the proposed 7-day PHI.  Residues of fluopicolide in sugar
beet roots generally did not increase from the 2-day to the 14-day
sampling interval; however, the highest residues were observed in
samples from the 10-day interval.  Residues of BAM and PCA were both
either nondetectable or below the LOQ in/on carrots, and radish and
sugar beet roots, and residues of PCA were nondetectable in/on sugar
beet tops from all sampling intervals.  Residues of BAM and PCA
generally decreased from the 2-day sampling interval to the 14-day
sampling interval in/on radish tops, and residues of BAM appeared to
increase slightly from the 2-day to the 14-day sampling interval in/on
sugar beet tops. 

Conclusions.  Pending submission of additional storage stability data,
the submitted carrot, radish and sugar beet field trial data are
adequate to satisfy data requirements.  The number and locations of the
field trials are in accordance with OPPTS Guideline 860.1500 for root
vegetable, subgroup 1A.  The use pattern of the field trials adequately
reflects the use pattern proposed for root and tuber vegetables other
than potato and sweet potato.

The available field trial data will support a tolerance for residues of
fluopicolide in/on root vegetables, subgroup 1A at 0.15 ppm; the
tolerance calculation for root vegetables is presented in Appendix I. 
Although the residue decline data for sugar beet roots indicate a slight
increase in residues at a 10-day sampling interval, based on the
submitted data, residues are not likely to exceed the recommended
tolerance of 0.15 ppm.

Data submitted for the tops of radish and sugar beet are adequate to
support the proposed tolerance for the leaves of root and tuber
vegetable, group 2 at 15 ppm; this exceeds the proposed tolerance of 13
ppm.  The tolerance calculation for leaves of root and tuber vegetables
is presented in Appendix I.

Vegetable, bulb, group 3-07

DER Reference:	47021703.der.doc 

IR-4 has submitted field trial data for fluopicolide on bulb and green
onions, the representative crops of the bulb vegetable crop group 3-07. 
The results from these field trials are discussed below and summarized
in Table 5.2.  

Table 5.2.	Summary of Residue Data from the Bulb Vegetable Crop Field
Trials with Fluopicolide.

Commodity	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels  (ppm)

	n	Min.	Max.	HAFT1	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Bulb Vegetables

(proposed use = 0.375 lb ai/A total application rate, 7-day minimum RTI,
2-day PHI)

Fluopicolide

Bulb Onion	0.355-0.366	2	14	0.013	2.522	1.57	0.052	0.3282	0.664

Green Onion	0.355-0.361	2	6	1.49	4.50	4.49	1.90	2.64	1.44

BAM

Bulb Onion	0.355-0.366	2	14	<0.01	<0.01	<0.01	NA	NA	NA

Green Onion	0.355-0.361	2	6	<0.01	0.014	0.014	0.011	0.012	0.002

PCA

Bulb Onion	0.355-0.366	2	14	<0.01	<0.01	<0.01	NA	NA	NA

Green Onion	0.355-0.361	2	6	<0.01	<0.01	<0.01	NA	NA	NA

1  HAFT = Highest Average Field Trial

2  Initial analysis results were confirmed with a second analysis; the
average value is reported.  The petitioner noted that based on the color
of the sample homogenate and high residues, it is believed that some
onion top material was in the bulb samples (see MRID 47021703).

Ten field trials were conducted in the United States during the
2002-2003 growing seasons.  Seven bulb onion trials were conducted in
Zones 1 (PA; 1 trial), 6 (TX; 1 trial), 8 (NM; 1 trial), 10 (CA; 2
trials), and 11 (OR; 2 trials).  Three green onion trials were conducted
in Zones 6 (TX; 1 trial), and 10 (CA; 2 trials).

Each field trial consisted of one untreated plot and one treated plot. 
At each trial site, three broadcast foliar applications of a 4 lb ai/gal
suspension concentrate formulation [equivalent to a flowable concentrate
(SC) formulation] of fluopicolide were made at 4- to 6-day retreatment
intervals to bulb and green onions at ~0.12 lb ai/A/application, for a
total seasonal rate of 0.36-0.37 lb ai/A (~1x the maximum proposed
seasonal application rate for bulb vegetables).  Applications were made
using ground equipment in spray volumes of 18-23 gal/A with a
spreader/sticker added to each tank mixture.

Bulb and green onions were harvested 2 days after the last application. 
Additional samples were collected from 2 trials (one bulb onion and one
green onion) at 1, 3, 5, and 7 days following the last application to
generate residue decline data. 

The collected samples were analyzed for residues of fluopicolide, BAM,
and PCA using LC/MS/MS Method 1611-00.02.  The validated LOQ was 0.01
ppm for each analyte in bulb and green onions.  The method was adequate
for data collection based on acceptable method validation and concurrent
method recoveries.  

Samples were stored frozen (<-20 (C) prior to analysis.  The maximum
storage durations from harvest to analysis were 1248 days (41 months)
for bulb onions and 1159 days (38 months) for green onions.  The
available storage stability data indicate that residues of fluopicolide,
BAM, and PCA are reasonably stable under frozen storage conditions for a
maximum of 30 months in/on cabbage leaves, grape, potato tuber, and
wheat grain.  Although the storage stability data for potato tuber may
be translated to bulb vegetables, the available data are not sufficient
to support the storage durations of samples from the subject field
trials.

Maximum residues including all 7 trials were 2.52 ppm in bulb, onions. 
Maximum residues of fluopicolide were 0.582 ppm in/on bulb onions from
six trials; residues of 0.617 and 2.52 ppm (confirmed by sample
re-analysis) were observed in samples from a single bulb onion trial
conducted in CA.  The petitioner noted that, based on the color of the
sample homogenate and the high residues, some onion top material may
have been included in the bulb samples for this trial.  Maximum residues
of fluopicolide were 4.50 ppm in/on green onions.  Residues of BAM and
PCA were each below the LOQ (<0.01 ppm) in/on bulb onions.  Maximum
residues of BAM were 0.014 ppm in/on green onions, and residues of PCA
were <0.01 ppm.

In the residue decline trials, residues of fluopicolide residues
generally decreased with increasing sampling interval in/on bulb and
green onions.  Residues of BAM and PCA were nondetectable in/on bulb
onions from all sampling intervals.  Residues of BAM in/on green onions
increased slightly from the 1-day sampling interval to the 7-day
sampling interval; residues of PCA in/on the respective samples were
nondetectable.

Conclusions.   The submitted bulb and green onion field trial data
reflect the use of three broadcast foliar applications of a 4 lb ai/gal
SC formulation of fluopicolide at total seasonal rates of 0.355-0.366 lb
ai/A, with a 2-day PHI.  An acceptable method was used for quantitation
of residues in/on bulb and green onions; however, the available storage
stability data do not support the study storage durations for bulb and
green onions.  The maximum storage durations from harvest to analysis
were 1248 days (41 months) for bulb onions and 1159 days (38 months) for
green onions.  The available storage stability data (DP# 321209,
1/23/07, A. Acierto) indicate that residues of fluopicolide, BAM, and
PCA are reasonably stable under frozen storage conditions for a maximum
of 30 months in/on cabbage leaves, grape, potato tuber, and wheat grain.
 Although the storage stability data for potato tuber may be translated
to bulb vegetables, the available data are not sufficient to support the
full storage durations of samples from the field trials for the subject
petition.  Pending submission of additional storage stability data, the
submitted bulb vegetable field trial data are adequate to satisfy data
requirements.

The residues of fluopicolide generally decreased with increasing
sampling interval in/on bulb and green onions.  Residues of BAM and PCA
were nondetectable in/on bulb onions from all sampling intervals. 
Residues of BAM in/on green onions increased slightly from the 1-day
sampling interval to the 7-day sampling interval; residues of PCA in/on
the respective samples were nondetectable.

Because the calculated tolerance for green onion do not exceed that for
bulb onion by more than 5x, HED has determined that a crop group
tolerance for bulb vegetables is appropriate.  The available field trial
data will support tolerances for residues of fluopicolide in/on bulb
vegetables at 7.0 ppm.  The tolerance calculations for bulb vegetables
are presented in Appendix I. 

Brassica, head and stem, subgroup 5A

DER Reference:	47021701.der.doc (includes review of MRID 47021702)

IR-4 has submitted field trial data for fluopicolide on broccoli and
cabbage, the representative crops of the head and stem Brassica subgroup
5A.  The results from these field trials are discussed below and
summarized in Table 5.3.  

Table 5.3.	Summary of Residue Data from the Brassica Vegetable Field
Trials with Fluopicolide.

Commodity	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels (ppm)

	n	Min.	Max.	HAFT1	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Brassica, Head & Stem 

(proposed use = 0.375 lb ai/A total application rate, 7-day minimum RTI,
2-day PHI)

Fluopicolide

Broccoli head & stem	0.353-0.364	2	12	0.122	0.690	0.601	0.373	0.360
0.176

Cabbage w/ wrapper leaves	0.352-0.359	2	14	0.056	3.93	3.77	0.71	1.24
1.24

Cabbage w/o wrapper leaves	0.352-0.359	2	14	<0.01	2.63	2.36	0.104	0.532
0.852

BAM

Broccoli head & stem	0.353-0.364	2	12	<0.01	<0.01	<0.01	NA	NA	NA

Cabbage w/ wrapper leaves	0.352-0.359	2	14	<0.01	0.017	0.016	0.010	0.011
0.002

Cabbage w/o wrapper leaves	0.352-0.359	2	14	<0.01	0.011	0.011	0.010
0.010	0.000

PCA

Broccoli head & stem	0.353-0.364	2	12	<0.01	0.017	0.016	0.010	0.011
0.002

Cabbage w/ wrapper leaves	0.352-0.359	2	14	<0.01	0.020	0.018	0.010	0.011
0.003

Cabbage w/o wrapper leaves	0.352-0.359	2	14	<0.01	0.015	0.013	0.010
0.010	0.001

1  HAFT = Highest Average Field Trial.

Thirteen field trials were conducted in the United States during the
2002 growing season.  Six broccoli trials were conducted in Zones 6 (TX;
1 trial), 10 (CA; 4 trials), and 12 (OR; 1 trial).  Seven cabbage trials
were conducted in Zones 1 (NY; 1 trial), 2 (GA and NC; 2 trials), 3 (FL;
1 trial), 5 (WI; 1 trial), 6 (TX; 1 trial), and 10 (CA; 1 trial).  

Each field trial consisted of one untreated plot and one treated plot. 
At each trial site, three broadcast foliar applications of a 4 lb ai/gal
suspension concentrate formulation [equivalent to a flowable concentrate
(SC) formulation] of fluopicolide were made at 4- to 6-day retreatment
intervals to broccoli and cabbage at ~0.12 lb ai/A/application, for a
total seasonal rate of 0.35-0.36 lb ai/A (~1x the maximum proposed
seasonal rate for Brassica vegetables).  Applications were made using
ground equipment in 15-21 gal/A spray volumes with a spreader/sticker
added to each tank mixture.

Head and stem Brassica were harvested 2 days after the last application 
 Additional samples were collected from 2 trials (one broccoli and one
cabbage) at 1, 3, 5, and 7 days following the last application to
generate residue decline data.  Data were provided to determine the
impact of removal of the outer wrapper leaves on the treated cabbage. 

The collected samples were analyzed for residues of fluopicolide, BAM,
and PCA using LC/MS/MS Method 1611-00.02.  The validated LOQ was 0.01
ppm for each analyte in broccoli and cabbage.  The method was adequate
for data collection based on acceptable method validation and concurrent
method recoveries.

Samples were stored frozen (<-20 (C) prior to analysis.  The maximum
storage duration from harvest to analysis was 1065 days (35 months) for
broccoli and 1225 days (40 months) for cabbage.  The available storage
stability data indicate that residues of fluopicolide, BAM, and PCA are
reasonably stable under frozen storage conditions for a maximum of 30
months in/on cabbage leaves, grape, potato tuber, and wheat grain. 
Although the storage stability data for cabbage leaves would support
Brassica vegetables, the available data are not sufficient to support
the storage durations of samples from the subject field trials.  

Maximum residues of fluopicolide were 0.69 ppm in/on broccoli, 3.93 ppm
in/on cabbage with wrapper leaves, and 2.63 ppm in/on cabbage without
wrapper leaves.  Maximum residues of BAM were <0.01 ppm (LOQ) in/on
broccoli, and 0.02 ppm and 0.01 ppm in/on cabbage with and without
wrapper leaves, respectively.  Maximum residues of PCA were 0.02 ppm
in/on all samples of broccoli and cabbage.

In the residue decline trials, residues of fluopicolide generally
decreased with increasing sampling interval after the 2-day PHI in/on
broccoli, cabbage (with wrapper leaves), and  cabbage (without wrapper
leaves).  Because no detectable residues of BAM and PCA were found in/on
any of the broccoli samples and were variable or nondetectable in/on the
cabbage samples, the potential for residue decline could not be
assessed.

Conclusions.  The submitted broccoli and cabbage field trial data
reflect the use of three broadcast foliar applications of a 4 lb ai/gal
SC formulation of fluopicolide at total seasonal rates of 0.352-0.364 lb
ai/A, with a 2-day PHI.  An acceptable method was used for quantitation
of residues in/on broccoli and cabbage.

Maximum residues of fluopicolide were 0.69 ppm in/on broccoli, 3.93 ppm
in/on cabbage with wrapper leaves, and 2.63 ppm in/on cabbage without
wrapper leaves.  Maximum residues of BAM were <0.01 ppm (LOQ) in/on
broccoli, and 0.02 ppm and 0.01 ppm in/on cabbage with and without
wrapper leaves, respectively.  Maximum residues of PCA were 0.02 ppm
in/on all samples of broccoli and cabbage.

In the residue decline trials, residues of fluopicolide generally
decreased with increasing sampling interval after the 2-day PHI in/on
broccoli, cabbage (with wrapper leaves), and  cabbage (without wrapper
leaves).  Because no detectable residues of BAM and PCA were found in/on
any of the broccoli samples and were variable or nondetectable in/on the
cabbage samples, the potential for residue decline could not be
assessed.

The available storage stability data (DP# 321209, 1/23/07, A. Acierto)
indicate that residues of fluopicolide, BAM, and PCA are reasonably
stable under frozen storage conditions for a maximum of 30 months in/on
cabbage leaves, grape, potato tuber, and wheat grain.  The maximum
storage duration from harvest to analysis for the current petition was
35 months for broccoli and 40 months for cabbage.  Although the storage
stability data for cabbage leaves would support Brassica vegetables, the
available data are not sufficient to support the full storage durations
of the study period.  Additional data to support the full duration of
the storage stability study period should be submitted. 

The available field trial data will support a tolerance for residues of
fluopicolide in/on broccoli at 1.2 ppm and cabbage at 5.0 ppm.  Although
the maximum residues of fluopicolide in broccoli and cabbage differ by
slightly more than 5x, HED concludes that a crop subgroup tolerance at
5.0 ppm is appropriate for head and stem Brassica.  The tolerance
calculation for Brassica head and stem vegetables is presented in
Appendix I.  

860.1520 Processed Food and Feed

DER Reference:	47021707.der.doc 

Sugar Beet

IR-4 has submitted a processing study for fluopicolide on sugar beets. 
The sugar beet samples used for processing were generated from one trial
conducted in NE during the 2002 growing season.  Sugar beets were
harvested 7 days following the last of three broadcast foliar
applications of a 4 lb ai/gal suspension concentrate formulation
[equivalent to a flowable concentrate (SC) formulation] of fluopicolide
at ~0.59 lb ai/A/application, for a total seasonal rate of 1.79 lb ai/A
(5x the maximum proposed seasonal rate for sugar beet).  Applications
were made using ground equipment in 20 gal/A spray volumes with a
spreader/sticker added to the tank mixture.  Sugar beet roots were
processed into molasses, dry pulp, and sugar using simulated commercial
processes.

Samples of sugar beet roots (RAC) and the processed commodities
(molasses, dried pulp and sugar) were analyzed for residues of
fluopicolide, BAM, and PCA using LC/MS/MS method 1629-00.00.  The
validated LOQ was 0.01 ppm for each analyte in each matrix.  The method
was adequate for data collection based on acceptable method validation
and concurrent method recoveries.

Samples were stored frozen (<-20 (C) prior to analysis.  The maximum
storage durations from harvest to analysis were 1234 days (41 months)
for sugar beet roots (RAC) and 1196 days (39 months) for the processed
commodities.  The available storage stability data indicate that
residues of fluopicolide, BAM, and PCA are reasonably stable under
frozen storage conditions for a maximum of 30 months in/on cabbage
leaves, grape, potato tuber, and wheat grain.  Additional storage
stability data are available which demonstrate that residues are
reasonably stable under frozen storage conditions for a maximum of 30
months in/on potato, sugar beet, tomato and wheat processed commodities.
 The petitioner stated that based on the available storage stability
data for processed commodities, it is unlikely that residues would
further degrade after the 30-month storage interval in processed sugar
beet commodities.  HED concurs that no additional storage stability data
are required for processed commodities based on the OECD guidance that
storage stability data are not required for processed commodities as
long as there are data to support stability of compounds in the RAC (See
ChemSAC minutes, 5/29/07).  Therefore,  the processed commodity residue
data are tentatively classified as scientifically acceptable pending
submission of storage stability data demonstrating the stability of
fluopicolide and its metabolites BAM and PCA in/on RAC of sugar beet
stored frozen for up to 41 months.

Residues of fluopicolide were 0.060-0.088 ppm in/on sugar beet root
(RAC) harvested 7 days following foliar treatment with the 4 lb ai/gal
SC formulation for a seasonal rate of 1.79 lb ai/A.  Residues of BAM and
PCA were each below the LOQ (<0.01 ppm) in the RAC samples.

The processing factors for sugar beet processed commodities are
presented in Table 7.  Following processing, residues of fluopicolide
were 0.112-0.115 ppm in molasses, 0.090-0.110 ppm in dried pulp, and
below the LOQ (<0.01 ppm) in sugar.  Residues of fluopicolide appear to
concentrate slightly in molasses (1.6x average processing factor) and
dried pulp (1.4x), but do not concentrate in sugar (<0.1x).  Residues of
PCA were 0.020-0.023 ppm in molasses, indicating PCA residues may
concentrate in molasses (>2.1x).  Residues of PCA in dried pulp and
sugar, and residues of BAM in molasses, dried pulp, and sugar were below
the LOQ; processing factors could not be calculated because residues
were nonquantifiable in both the RAC and processed commodity. 

The calculated processing factors for sugar beet molasses, dried pulp,
and sugar do not exceed the theoretical concentration factors (OPPTS
860.1520) of 12.5x for sugar (Table 2, based on separation) and 20x for
dried pulp (Table 4, experimental maximum observed).  

  SEQ CHAPTER \h \r 1 Table 6.		Summary of Processing Factors for
Fluopicolide.

RAC	Processed Commodity	Average Processing Factor 1

Fluopicolide	BAM	PCA

Sugar beet	Dried pulp	1.4x	NC	NC

	Molasses	1.6x	NC	>2.1x

	Sugar	<0.1x	NC	NC

1  NC = Not calculated; a processing factor could not be calculated for
this matrix because residues were below the LOQ in both the RAC and the
processed commodity.  NA = Not applicable.  Estimated processing factors
were calculated when residues were reported below the LOQ in the RAC or
the processed matrix.

Conclusions.  Pending submission of additional storage stability data,
the submitted sugar beet processing data are adequate to satisfy data
requirements.  

The sugar beet processing data indicate that fluopicolide residues do
not concentrate in sugar.  A tolerance for fluopicolide residues in
sugar is not required.  The sugar beet processing data indicate that
fluopicolide residues may concentrate slightly in molasses and dried
pulp.  Based on the HAFT residue for sugar beet (0.054 ppm) and the
average processing factors for molasses (1.6x) and dried pulp (1.4x),
expected residues would be 0.09 ppm in molasses and 0.08 ppm in pulp. 
Because these values are below the proposed 0.15 ppm tolerance for root
vegetables, no tolerances for processed sugar beet molasses and dried
pulp are needed.  Residues of PCA in dried pulp and sugar, and residues
of BAM in molasses, dried pulp and sugar were below the LOQ; therefore,
the processing factors could not be calculated. 

An acceptable method was used for quantitation of residues in/on sugar
beet roots, dried pulp, molasses and sugar; however, the available
storage stability data do not support the study storage durations for
sugar beet roots and its processed commodities.  The processed commodity
residue data are tentatively classified as scientifically acceptable
pending submission of storage stability data demonstrating the stability
of fluopicolide and its metabolites BAM and PCA in/on the RAC of sugar
beet or root and tuber vegetables stored frozen for up to 41 months.

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

An analytical standard for fluopicolide, with an expiration date of
8/16/2008, is currently available in the National Pesticide Standards
Repository (personal communication with Dallas Wright, ACB, 2/15/2007). 

860.1850 Confined Accumulation in Rotational Crops

Residue Chemistry Memo DP# 326080, 327026, 339155 (PP#5F7016).

A confined rotational crop study was previously submitted in conjunction
with PP#5F7016 with [U-14C-phenyl]fluopicolide (PH label) and
[2,6-14C-pyridinyl]fluopicolide (PY label).  Each radiolabeled test
substance was combined with nonlabeled fluopicolide, formulated as a
suspension concentrate, mixed with adjuvant, and applied to bare sandy
loam soil at a rate equivalent to 0.36 lb ai/A (~1x the proposed maximum
seasonal rate to annual crops); the specific activity of the applied
test substances ranged 39.6-41.5 µCi/mg.  Rotational crops of lettuce,
radish, and wheat, were planted 29, 133, and 365 days after soil
treatment.  

TRR accumulated at ≥0.01 ppm in all rotated crop matrices planted at
the 29-, 133-, or 365-day PBIs.  Fluopicolide and seven discrete
metabolites were identified in rotational crops by HPLC analysis. 
Because of the double-ring structure of fluopicolide, metabolites
resulting from cleavage of the amide bond were identified in either PH
samples (BAM and 3-OH-BAM) or PY samples (PCA, AE C653598, P1X, and AE
B102859).  Fluopicolide and the double-ring metabolite AE C643890 were
identified in both PH and PY samples.  

Fluopicolide was identified in all rotational crop matrices at all PBIs,
at 2.1-55.8% TRR in PH label samples and 1.8-79.9% TRR in PY label
samples.  BAM, 3-OH-BAM, PCA, and P1X were all major metabolites in
rotational crops.  BAM was identified in all rotational crop matrices at
all PBIs at 3.4-87.9% TRR, and 3-OH-BAM was identified in wheat forage,
grain, and straw at all PBIs at 13.6-59.3% TRR.  Metabolites PCA and P1X
were identified in all rotational crop matrices at all PBIs except that
PCA was not found in 133-day lettuce and 133- and 365-day wheat straw,
and P1X was not found in 133-day lettuce; residues of PCA and P1X ranged
5.4-69.6% and 2.9-66.6% TRR, respectively.  Metabolites AE 653598 and AE
B102859 were also identified in all rotational crop matrices except
wheat grain, at up to 9.5% and 21.5% TRR, respectively.  Metabolite AE
653598 was primarily identified at the 365-day PBI, while AE B102859 was
represented in selected samples across all PBIs.  Metabolite AE C643890
was identified at the 29-day PBI only at <2% TRR in wheat forage and
13.10% in 29-day wheat grain.  A number of minor metabolites,
characterized as hydroxylated or sulfhydrylated versions of fluopicolide
or its metabolite with or without conjugation to glucose, malonic acid,
glyconic acid, or amino acid, were found in 29-day wheat forage and
straw at ≤6.2% TRR each in forage and ≤8.6% TRR each in straw.

HED notes that in general, the levels of fluopicolide were found to
decrease significantly with increasing PBI in the phenyl-label (PH)
samples.  The same trend was not observed in the pyridinyl label (PY)
samples; fluopicolide levels in PY samples were generally the same at
all three PBIs.  

The metabolism of fluopicolide in rotational crops appeared to be more
extensive than that observed in primary crops (grapes, lettuce, and
potato); four rotational crop metabolites, 3-OH-BAM, P1X, AE C653598,
and AE B102859, were not observed in the primary crop metabolism
studies.  

Conclusions.  The available confined rotational crop studies indicate
the potential for quantifiable fluopicolide and metabolite residues in
rotated crop commodities.  In HED’s RARC1 meeting held on 7/19/07, HED
determined that the residue of concern for the tolerance expression for
rotational crops is fluopicolide (parent).  The residues of concern for
the risk assessment for cereal grains as rotational crops are
fluopicolide (parent), BAM, PCA, and P1X in grain for human food, and
fluopicolide (parent) and BAM in forage/hay/straw and grain for
livestock feed.  The residues of concern for the risk assessment for all
rotational crops except cereal grains are fluopicolide (parent) and BAM.
 

860.1900 Field Accumulation in Rotational Crops

Residue Chemistry Memo DP# 326080, 327026, 339155 (PP#5F7016).

The petitioner cited the study reported in PP#5F7016 where a  SEQ
CHAPTER \h \r 1 n extensive field rotational crop study was submitted on
wheat.  Broadcast foliar applications of a 4 lb ai/gal SC formulation of
fluopicolide were made to a primary crop of potatoes or to bare ground
for total application rates of 0.346-0.372 lb ai/A (~1x the proposed
maximum seasonal rate to annual crops).  A spreader/sticker adjuvant was
added to the spray mixtures.  Potatoes were harvested ~7 days after the
last application, and the rotational wheat crop was planted 29-37 days
after the last application (22-30 days after potato harvest).  Wheat
forage, hay, grain, and straw were collected at normal commercial
harvest.

  SEQ CHAPTER \h \r 1 Maximum residues of fluopicolide, BAM, 3-OH-BAM,
PCA, and P1X were, respectively, 0.213, 0.123, 0.050, 0.043, and 0.064
ppm in/on wheat forage; 0.501, 0.102, 0.160, 0.064, and 0.073 ppm in/on
hay; 0.014, <0.01, <0.01, 0.062 and 0.075 ppm in/on grain; and 0.350,
0.050, 0.081, 0.043, and 0.055 ppm in/on straw planted 29 to 37 days
following the last application of fluopicolide to a primary crop of
potatoes at 0.346-0.372 lb ai/A.

Conclusions.  The available field rotational crop data were determined
in PP#5F7016 to be adequate pending submission of additional storage
stability information and data.  Tolerances were recommended for
indirect or inadvertent residues of fluopicolide in/on wheat forage at
0.20 ppm, wheat grain at 0.02 ppm, and wheat hay and straw at 0.50 ppm. 

In the confined rotational crop study, residues of fluopicolide >0.01
ppm were observed in/on all rotational crop commodities at all PBIs,
with the exception of wheat grain at the 133- and 365-day PBIs.  Based
on these results and the proposed rotational crop restrictions, limited
field rotational crop studies must be conducted at a 12-month PBI with
representative leafy vegetable, and  root vegetable crops.  If the
results of the limited field rotational crop study indicate the
potential for quantifiable fluopicolide residues of concern in/on
rotational crops at a 12-month PBI, then extensive field rotational crop
studies will be required for all crops the petitioner wishes to allow
for rotation at a 12-month PBI.

Conclusions.  It was concluded in the cited petition that until all
field rotational crop data requirements have been satisfied, the
proposed rotational crop restrictions must be modified to state that
crops may not be rotated to any crops other than bulb vegetables,
Brassica head and stem vegetables, cucurbit vegetables, fruiting
vegetables, grapes, leafy vegetables, root vegetables, tuberous and corm
vegetables, and wheat, with a 0-day PBI for bulb vegetables, Brassica
head and stem vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables, root vegetables, and tuberous and corm
vegetables, and a 30-day PBI for wheat.  

860.1550 Proposed Tolerances

HED has determined that the terminal residue of concern in plant
commodities for the tolerance expression is fluopicolide per se
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide].  The tolerance expression proposed in this petition is
appropriate; however, HED notes that the chemical name for fluopicolide
provided by the petitioner in Section F
[3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,
6-dinitro-p-toluidine] is not the preferred name. 

No Codex, Canadian, or Mexican MRLs have been established for
fluopicolide.

Pending submission of the requested storage stability data, adequate
field trial data are available for Brassica head and stem vegetables
(subgroup 5A), root vegetables (subgroup 1A), and leaves of root and
tuber vegetables (group 2).  The available field trial data indicate
that the proposed tolerances for the Brassica head and stem and root
vegetables subgroups are adequate, but that the proposed tolerance for
leaves of the root and tuber vegetables group should be increased to
15.0 ppm.

The available data for bulb and green onions support a bulb vegetable
group tolerance because residues do not differ by >5x between the
representative crops, bulb and green onions.  A tolerance of 7.0 ppm is
approriate.

The tolerance calculations for Brassica head and stem, bulb, and root
vegetable are presented in Appendix I. 

Adequate processing data for sugar beets are available pending
submission of the requested storage stability data.  The available
processing data indicate that residues of fluopicolide are not likely to
concentrate in sugar.  Residues of fluopicolide were found to
concentrate slightly in molasses and dried pulp.  Separate tolerances
for sugar beet molasses and dried pulp are not needed because residues
in these commodities are not expected to exceed the recommended
tolerance of 0.15 ppm for the root vegetable group.

The available cattle feeding study data indicate that tolerances for
ruminant and swine commodities are not needed to support the requested
fluopicolide uses pending confirmatory information related deficiencies
found in the livestock metabolism studies.  There are no poultry
feedstuffs associated with the proposed uses.

The proposed tolerances should be revised to reflect the recommended
tolerance levels and correct commodity definitions as specified in Table
7.  HED notes that individual tolerances for the members of the Bulb
Vegetables, group 3 will not be needed since a crop group tolerance
would be appropriate.  Please note the pre-existing Crop Group 3 is now
titled Crop Group 3-07 (Pesticide Tolerance Crop Group Program, Federal
Register, Vol. 72, No. 235, 12/7/2007).

  

Table 7. 	Tolerance Summary for Fluopicolide.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;
Correct Commodity Definition

Tolerances to be established under “(a) General”:

Root vegetable subgroup 1-A	0.15	0.15	Vegetable, root, subgroup 1A

Leaves of root and tuber vegetables, group 2	13	15	Vegetable, leaves of
root and tuber, group 2

Bulb vegetables, group 3	6	Remove	Tolerances should be proposed for
Vegetable, bulb, group 3-07

Bulb vegetables, group 3-07	None proposed	7.0	Vegetable, bulb, group
3-07

Daylily, bulb 	6	Remove

	Individual tolerances are not required for members of the Vegetable,
bulb, group 3-07

Garlic, Serpent, bulb	6

Lily, bulb	6

Onion, Chinese, bulb	6

Onion, pearl	6

Onion, potato, bulb	6

Shallot, bulb	6

Chive, fresh leaves 	6

Chive, Chinese, fresh leaves	6

Elgans hosta	6

Fritillaria, bulb	6

Fritillaria, leaves	6

Kurrat	6

Lady’s leek	6

Leek, wild	6

Onion, Beltsville bunching	6

Onion, fresh	6

Onion, macrostem	6

Onion, tree, tops	6

Shallot, fresh leaves	6

Head and stem Brassica subgroup 5-A 	5	5	Brassica, head and stem,
subgroup 5A

References

DP#:	329686

Subject:	Fluopicolide (AE C638206) in/on imported grapes, domestic use
in/on food crops and ornamental turf.  Request for Petition Method
Validation.

From:	A. Acierto

To:	F. Siegelman

Date:	6/8/06   

MRIDs:	46474027-46474031, 46708522-46708525 and 46708516

DP#:	318332

Subject:	FEE.  Secondary Product Chemistry Review on Fluopicolide
technical (Import Tolerance)

From:	S. Mathur

To:	J. Whitehurst/T. Kish

Date:	10/17/2006   

MRIDs:	46474001-46474023, 46478409, and 46478410

DP#:	321209

Subject:	Fluopicolide.  PP#5E6903; Petition for Tolerances on Imported
Grapes and Raisins.  Summary of Analytical Chemistry and Residue Data.  

From:	A. Acierto

To:	J. Whitehurst/T. Kish

Date:	1/23/2007   

MRIDs:	46474025-46474045; 46474101-46474106; 46708525

DP#:	327026

Subject:	Fluopicolide.  PP#5F7016; Petition for Establishment of
Tolerances for Use on Tuberous and Corm Vegetables, Leafy
Vegetables,(except Brassica), Fruiting Vegetables, Cucurbit Vegetables,
and Grapes.  Summary of Analytical Chemistry and Residue Data.  

From:	A. Acierto

To:	J. Whitehurst/T. Kish

Date:	8/20/07 

MRIDs:	46708418, 46708514-46708524, 46708526-46708541, 46708543-46708547

  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: 
2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]-benzam
ide	Common Name:  Fluopicolide	 □Proposed tolerance

 xReevaluated tolerance

 □ Other	Date:  6/11/2007

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

√ No Codex proposal step 6 or above

⁯No Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#7E7172

DP Barcode:  336216

√ No Limits

⁯No Limits for the crops requested	√ 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, 02/20/2007 under petition PP#7E7172.

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.

Vegetable, Root, Subgroup 1A

The dataset used to establish a tolerance for fluopicolide on the
vegetable, root, subgroup 1A consisted of field trial data for radishes.
 Data were submitted for the representative crops of the vegetable,
root, subgroup 1A (carrot, radish, and sugar beet).  The field trial
data for carrots, radish, and sugar beets represent application rates of
0.35-0.36 lb ai/A (3 applications at 0.12 lb ai/A/application) with a
7-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 I.

                                                                        
                                                      

The dataset for each crop was entered into the tolerance spreadsheet. 
Visual inspection of the lognormal probability plots for radish root and
carrot (Figure I-1a and 3a) provided in the spreadsheet indicated that
the datasets were reasonably lognormal. The results from the approximate
Shapiro-Francia test statistic (Figure I-1b and I-3b) confirmed that the
assumption of lognormality should not be rejected for both radish roots
and carrots.  For sugar beets, the result from the Shapiro-Francia test
statistics (Figure  I-2a) indicated that the data set is not lognormal. 

Using the tolerance spreadsheet, the recommended tolerance is 0.20 ppm
for carrots and 0.15 ppm for radish roots.  A tolerance of 0.09 ppm for
sugar beets was selected using the California Method (Figure I-2b).  The
maximum observed residue value for carrot was 0.14 ppm and for sugar
beet root was 0.06 ppm.  Because these values differ by less than 5x, a
crop subgroup tolerance is appropriate for root vegetables.  The
petitioner has proposed a tolerance of 0.15 ppm; the available data
indicate that 0.20 ppm is an appropriate value for the tolerance for the
subgroup 1A..  

Table I.	Residue data used to calculate tolerance for fluopicolide on
radish root, sugar beet root and carrot.

Regulator:	EPA	EPA	EPA

Chemical:	Fluopicolide	Fluopicolide	Fluopicolide

Crop:	Radish root	Sugar beet root 	Carrot

PHI:	7 days	7 days	7 days

App. Rate:	3 at 0.12 lb ai/A/Application	3 at 0.12 lb ai/A/Application	3
at 0.12 lb ai/A/Application

Submitter:	IR-4	IR-4	IR-4

MRID Citation:	47021704	47021704	47021704

0.051	0.042	0.008

	0.055	0.052	0.008

	0.031	0.049	0.144

	0.032	0.032	0.106

	0.017	0.004	0.028

	0.017	0.004	0.047

	0.020	0.042	0.011

	0.025	0.028	0.033

	0.025	0.016	0.029

	0.022	0.009	0.025

	0.103	0.007	0.029

	0.069	0.02	0.012

0.03	0.031

0.021	0.003

0.06

	0.039

	0.02

	0.019

	0.061

	0.047

	

Figure I-1a.  Lognormal probability plot of fluopicolide field trial
data for radish root.

Figure I-1b.   Tolerance spreadsheet summary of fluopicolide field trial
data for radish root.

Figure I-2a.  Lognormal probability plot of fluopicolide field trial
data for sugar beet root

Figure I-2b.   Tolerance spreadsheet summary of fluopicolide field trial
data for sugar beet root



Figure I-3a.  Lognormal probability plot of fluopicolide field trial
data for carrot

Figure I-3b.   Tolerance spreadsheet summary of fluopicolide field trial
data for carrot

Vegetable, Leaves of Root and Tuber, group 2

The dataset used to establish a tolerance for fluopicolide on the
vegetable, leaves of root and tuber, group 2, consisted of field trial
data for radish and sugar beet tops (the representative crops of the
vegetable, leaves of root and tuber, group 2 are turnip and sugar beet;
radish tops may be substituted for turnip tops), representing
application rates of 0.35-0.37 lb ai/A (~3 applications at 0.12 lb
ai/A/application) with a 7-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.

All field trial sample results were above the LOQ.  Because there were
no values reported below the LOQ, maximum likelihood estimation (MLE)
procedures were not needed to impute censored values. The radish tops
dataset was small (12 samples).  The sugar beet tops dataset was not
small (20 samples).  The dataset for each crop was entered into the
tolerance spreadsheet.  Visual inspection of the lognormal probability
plots for radish and sugar beet tops (Figures I-3 and I-5) provided in
the spreadsheet indicated that both were reasonably lognormal. The
results from the approximate Shapiro-Francia test statistic (Figures I-4
and I-6) confirmed that the assumption of lognormality should not be
rejected for radish and sugar beet tops.

Using the tolerance spreadsheet, the recommended tolerances are 15 ppm
for radish tops and 14.0 ppm for sugar beet tops (Figures II-1b and
II-2b).  Because the minimum and maximum recommended tolerances differ
by less than 5x, a crop group tolerance is appropriate for leaves of
root and tuber vegetables.  The recommended value is 15 ppm, the maximum
of the recommended individual tolerances.

Table II.	Residue data used to calculate tolerance for fluopicolide on
vegetable, leaves of root and tuber, group 2.

Regulator:	EPA	EPA

Chemical:	Fluopicolide	Fluopicolide

Crop:	Radish top	Sugar beet top

PHI:	7 days	7 days

App. Rate:	3 at 0.12 lb ai/A/Application	3 at 0.12 lb ai/A/Application

Submitter:	IR-4	IR-4

MRID Citation:	47021704	47021706

	Residues of fluopicolide (ppm)

	5.490	5.720

	7.030	5.480

	3.710	3.610

	3.970	4.380

	2.330	9.820

	2.980	11.200

	2.390	5.860

	2.320	5.230

	10.200	3.790

	7.320	8.410

	6.030	5.460

	5.580	4.790

3.750

5.320

4.290

3.910

7.250

9.180

8.290

8.440

Figure II.1a.  Lognormal probability plot of fluopicolide field trial
data for radish tops.

Figure II-1b.   Tolerance spreadsheet summary of fluopicolide field
trial data for radish tops.

Figure II-2a.  Lognormal probability plot of fluopicolide field trial
data for sugar beet tops.

Figure II-2b.   Tolerance spreadsheet summary of fluopicolide field
trial data for sugar beet tops.

Bulb vegetables, Crop Group 3-07

The dataset used to establish a tolerance for fluopicolide on the bulb
vegetables, crop group 3-07 consisted of field trial data for bulb and
green onion (belonging to the bulb onion subgroup 3-07A and green onion
subgroup 3-07B, respectively), representing application rates of
0.36-0.37 lb ai/A (3 applications at ~0.12 lb ai/A/application) with a
2-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 III.

All field trial sample results were above the LOQ.  Because there were
no values reported below the LOQ, maximum likelihood estimation (MLE)
procedures were not needed to impute censored values. The bulb and green
onion datasets were small (14 and 6 samples, respectively).  The dataset
for each crop was entered into the tolerance spreadsheet.  However,
visual inspection of the lognormal probability plot for green onion
(Figure III-1a) provided in the spreadsheet indicated that it may not be
lognormal.  The spreadsheet recommended tolerance of 7.0 ppm for green
onions based on the California Method.

The spreadsheet selected the UPLMedian 95th  for bulb onion based on the
small data set (i.e., <15) and assignment of lognormality.  However,
inspection of the probability plot (Figure III-2a) indicate that the
data may not be lognormal.  Therefore, the California Method was chosen
which recommended  a tolerance of 2.5 ppm for bulb onion (Figure
III-2b).

The recommended tolerances are 2.5 ppm for bulb onion and 7.0 ppm for
green onion. Because recommended tolerances do not differ by more than
5x, a crop group tolerance of 7.0 ppm is  appropriate for bulb
vegetables.  

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Bulb Onion	Green Onion

PHI:	2 days	2 days

App. Rate:	3 at 0.12 lb ai/A/Application	3 at 0.12 lb ai/A/Application

Submitter:	IR-4	IR-4

MRID Citation:	47021703	47021703

	Residues of fluopicolide (ppm)

	0.013	4.500

	0.013	4.470

	0.029	1.710

	0.048	1.490

	0.071	2.080

	0.050	1.610

	0.617

2.520

0.582

0.408

0.045

0.046

0.100

0.053

	

Figure III-1a.  Lognormal probability plot of fluopicolide field trial
data for bulb onion.

Figure III-1b.   Tolerance spreadsheet summary of fluopicolide field
trial data for bulb onion.

Figure III-2a.  Lognormal probability plot of fluopicolide field trial
data for green onion.

Figure III-2b.   Tolerance spreadsheet summary of fluopicolide field
trial data for green onion.

Head and Stem Brassica, Subgroup 5A

The dataset used to establish a tolerance for fluopicolide on the head
and stem Brassica crop subgroup consisted of field trial data for
broccoli and cabbage (the representative crops of the head and stem
Brassica subgroup), representing application rates of 0.35-0.36 lb ai/A
(3 applications at ~0.12 lb ai/A/application) with a 2-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 IV.

All field trial sample results were above the LOQ.  Because there were
no values reported below the LOQ, maximum likelihood estimation (MLE)
procedures were not needed to impute censored values. The broccoli and
cabbage datasets were small (12 and 14 samples, respectively).  The
dataset for each crop was entered into the tolerance spreadsheet. 
Visual inspection of the lognormal probability plots for broccoli and
cabbage (Figures IV-1a and IV-2a) provided in the spreadsheet indicated
that both were reasonably lognormal. The results from the approximate
Shapiro-Francia test statistic (Figures IV-2b and IV-2b) confirmed that
the assumption of lognormality should not be rejected for broccoli and
cabbage.

Using the tolerance spreadsheet, the recommended tolerances are 1.2 ppm
for broccoli, and 5.0 ppm for cabbage.  Because the minimum and maximum
recommended tolerances differ by less than 5x, a crop subgroup tolerance
is appropriate for head and stem Brassica.  The recommended value is 5.0
ppm, the maximum of the recommended individual tolerances.

Table IV.	Residue data used to calculate tolerance for fluopicolide on 

	head and stem Brassica, subgroup 5A.

Regulator:	EPA	EPA

Chemical:	Fluopicolide	Fluopicolide

Crop:	Broccoli	Cabbage (w/wrapper leaves)

PHI:	2 days	2 days

App. Rate:	3 at 0.12 lb ai/A/Application	3 at 0.12 lb

ai/A/Application

Submitter:	IR-4	IR-4

MRID Citation:	47021701	47021702

	Residues of fluopicolide (ppm)

	0.503	0.544

	0.480	0.614

	0.454	0.383

	0.428	1.220

	0.218	0.810

	0.317	1.910

	0.511	0.056

	0.690	0.310

	0.207	0.360

	0.206	0.334

	0.178	0.966

	0.122	2.290

3.930

3.600

Figure IV-1a.  Lognormal probability plot of fluopicolide field trial
data for broccoli.

Figure IV.1b.   Tolerance spreadsheet summary of fluopicolide field
trial data for broccoli.

Figure IV-2a.  Lognormal probability plot of fluopicolide field trial
data for cabbage.

Figure IV-2b.   Tolerance spreadsheet summary of fluopicolide field
trial data for cabbage.

Fluopicolide	Summary of Analytical Chemistry and Residue Data	DP#: 
343471

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