Document ID: EPA-HQ-OPP-2008-0885-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-02-24T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	12/15/09

	Subject:	Flumioxazin.  Petition for the Establishment of Permanent
Tolerances on Fish, Cucurbit Vegetables, Leaf Petioles, and Hops. 
Summary of Analytical Chemistry and Residue Data.  PP#s 8F7438 & 8E7462.

DP Number:	357451	Decision Number:	400513

PC Code:	129034	MRID No.:	46550602, 46550604, 47581801-04

40 CFR 180.	568	Risk Assessment Type:	NA

Chemical Class:	N-phenylpthalimide derivative herbicide	CAS No.:  
103361-09-7

Regulatory Action:	Section 3 Registration	EPA Reg. No.:  	Clipper(
Herbicide (59639-161), Valor™ Herbicide (59639-99), and Chateau™
Herbicide (59639-119)

	From:	W. Cutchin, Acting Senior Branch Scientist 

		Alternative Risk Integration and Assessment (ARIA)

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

		Registration Division (RD; 7505P)

	Through:	M. Doherty, Ph.D., Chemist

		Risk Assessment Branch II (RABII)

	Health Effects Division (HED; 7509P)

	To:	J. Miller, RM 23

		Herbicide Branch

		RD (7505P)

			And

		B. Madden, 

		RIMUERB/RD (7505P)

		



Executive Summary

Flumioxazin belongs to the N-phenylphthalimide class of herbicides
(Group 14).  It is a light-dependent peroxidizing herbicide (LDPH) which
acts by blocking heme and chlorophyll biosynthesis resulting in an
endogenous accumulation of porphyrins which are known to have a
phototoxic mode of action in plants and possibly in fish.  Flumioxazin
is currently registered for pre- and post-emergence applications on a
variety of fruit, vegetable, and field crops for the control of
susceptible weeds.

Valent U.S.A Corporation has submitted a petition proposing an aquatic
use for a 51% water dispersible granular (WDG) formulation of
flumioxazin (Clipper™ Herbicide; EPA Reg. No. 59639-161) for control
of aquatic weeds in bayous, canals, fresh water ponds, lakes, marshes
and reservoirs.  The proposed use is for either a broadcast surface
application using ground or aerial equipment or a subsurface application
using ground equipment.  Flumioxazin is applied at a rate of 0.19-0.38
lb ai/A for the surface application, and at concentrations of 100-400
ppb for the subsurface application.  The subsurface concentrations are
equivalent to 0.27-1.07 lb ai/A for a water depth of 1 ft, or 2.1-8.6 lb
ai/A for a water depth of 8 ft.  A minimum retreatment interval of 28
days is specified for a given section of water, and applications are
prohibited to flowing water, intertidal or estuarine areas, and to water
used for crawfish farming.  In conjunction with this use, Valent has
proposed the following permanent tolerance for residues of flumioxazin
and its metabolites APF
(3-oxo-4-prop-2ynyl-6-amino-7-fluoro-3,4-dihydro-1,4-benzoxazin) and
482-HA
(N-(7-fluoro-3,4-dihdyro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cycl
ohex-1-ene-1-carboxamide-2-carboxylic acid):

Fish, freshwater 	1.5 ppm

The Interregional Research Project No. 4 (IR-4) is seeking the
registration of flumioxazin on cucurbit vegetables, leaf petioles, and
hops.  The end-use products (EPs) relevant to this registration request
are Valor™ Herbicide (EPA Reg. No. 59639-99) and Chateau™ Herbicide
(EPA Reg. No. 59639-119).  Both products are water-dispersible granular
(WDG) formulations containing 51% flumioxazin and are to be applied
using ground equipment.  Valor and Chateau are proposed for a
pre-emergence or pre-transplant application followed by a second
application to row middles at a total of 0.25 lb ai/A on cucurbit
vegetables, for a pre-transplant soil application at 0.094-0.188 lb ai/A
on leaf petioles, and for a directed-spray application at 0.375 lb ai/A
with a 30-day preharvest interval (PHI) on hops.  Concurrently, IR-4
requests the establishment of permanent tolerances for residues of the
herbicide flumioxazin,
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-4,5
,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, in/on the following raw
agricultural commodities:

Cucurbit vegetables group 9	0.03 ppm

Leaf petioles subgroup 4B	0.02 ppm

Hops, dried cones	0.07 ppm

With the establishment of the cucurbit vegetables tolerance, IR-4 is
requesting the removal of the following tolerance:

Melon subgroup 9A	0.02 ppm

Flumioxazin tolerances are established under 40 CFR §180.568. 
Tolerances for residues in/on plant commodities are listed in 40 CFR
§180.568[a] and are expressed in terms of flumioxazin per se. 
Tolerances ranging from 0.02 to 0.70 ppm have been established in/on the
commodities of almonds, cotton, pome fruits (group 11), stone fruits
(group 12), garlic, grape, onion, peanut, peppermint, pistachio,
shallot, soybean, spearmint, strawberry, sugarcane, and tuberous/corm
vegetables (subgroup 1C).  In HED’s review of a recent tolerance
request to the Agency, tolerances for flumioxazin residues were
recommended at 0.02 ppm in/on asparagus, fruiting vegetables, melons,
okra, tree nuts and assorted bushberries, at 0.05 ppm in/on dry beans,
and at 3.0 and 8.0 ppm, respectively, in/on alfalfa forage and hay (DP
Num: 342963, D. Rate, 11/2007). Time-limited tolerances in/on alfalfa
forage and hay, with a 12/31/09 expiration date, are also currently
listed in 40 CFR §180.568[b].  No tolerances have been established in
meat, milk, poultry, or eggs.

The nature of flumioxazin residues in plants and animals is adequately
understood based on acceptable soybean, peanut, corn, sugarcane, grape,
hen, and goat metabolism studies.  The nature of the residue in
rotational crops is also understood based on studies conducted on
carrots, lettuce, and wheat.  In primary and rotated crops, the residue
of concern is only the parent compound.  For ruminants, the residues of
concern are parent, 3-OH-flumioxazin, 4-OH-flumioxazin, plus Metabolites
B, C, and F.  For poultry, the residues of concern are parent,
3-OH-flumioxazin, 4-OH-flumioxazin, and 4-OH-S-53482-SA.  For purposes
of this petition, ARIA has waived the requirement for a fish metabolism
study and has concluded that the residues of concern in fish include
flumioxazin and its major degradates in water, APF and 482-HA.

For tolerance enforcement, Valent has submitted a liquid chromatography
with tandem mass spectroscopy/mass spectroscopy detector (LC-MS/MS)
method (GPL-MTH-066) for determining residues of flumioxazin, APF and
482-HA in fish tissues.  For this method, residues are extracted with
acetonitrile (ACN) and aqueous ACN, each containing either 1% formic
acid for extraction of parent and APF or 1% ammonium hydroxide for
extraction of 482-HA.  Extracted residues are diluted with water and
analyzed directly by LC-MS/MS using external standards for quantitation.
The validated limit of quantitation (LOQ) is 0.01 ppm for each analyte
in fish.  This method has undergone a successful independent laboratory
validation (ILV) trial and appears to be acceptable for enforcing
tolerances; however, additional information/data are required before the
method can be recommended as an enforcement method.

An adequate gas chromatography/nitrogen-phosphorus detection (GC/NPD)
method, Valent Method RM-30-A-1, is available for enforcing tolerances
for residues of flumioxazin per se in/on plant commodities.  Method
RM-30-A-1 has undergone a successful method validation by Agency
chemists at the Analytical Chemistry Branch (ACB/BEAD).  The reported
method LOQ and limits of detection (LOD) for flumioxazin in/on plant
commodities are 0.02 and 0.01 ppm, respectively.  

The available data indicate that flumioxazin could not be recovered
through application of the multiresidue protocols.  As tolerances for
livestock commodities are not required, an enforcement method for
livestock commodities is not necessary for this petition.  Analytical
standards for the parent flumioxazin are currently available in the EPA
National Pesticide Standards Repository.  However, analytical reference
standards and multiresidue method testing data are not available for APF
and 482-HA.

Residues of flumioxazin in/on cucumber, summer squash, and celery were
analyzed by using a method modified from Method RM-30A-1.  The lower
limit of method validation (LLMV) for residues of flumioxazin in/on
cucumbers, summer squash, and celery was 0.02 ppm.  The analytical
method was adequate for data collection purposes.  Residues of
flumioxazin in/on hops, dried cones were quantified by gas
chromatography with mass selective detection (GC/MSD) using Valent
Method RM-30A-3.  The residues were analyzed by GC/MSD in the selective
ion monitoring (SIM) mode.  The LLMV for residues of flumioxazin on hops
samples was 0.02 ppm. The analytical method was adequate for data
collection purposes

During the fish magnitude of residue study, tissue samples were stored
frozen for 8-14 days prior to extraction for analysis.  As samples were
stored frozen for <30 days prior to extraction and analysis, storage
stability data is not required to support the fish residue study. 
Concurrent storage stability studies were conducted along with the crop
field trials.  The available storage stability data are adequate and
support the sample storage durations incurred in the residue field
trials.  

None of the commodities in this petition, cucurbit vegetables, leaf
petioles, and hops are associated with livestock feed items of regulable
interest.  ARIA concludes that tolerances for meat, milk, poultry, and
eggs are not required for the purpose of this petition.

The submitted fish residue study is adequate and supports the proposed
aquatic use.  Juvenile bluegill sunfishes (Lepomis macrochirus) and
channel catfish (Ictalurus punctatus) were treated under static water
conditions with flumioxazin at an initial concentration of 800 ppb (2x
maximum proposed rate), and residues of flumioxazin, APF and 482-HA were
determined in the water and edible fish tissues over a 28-day period of
exposure.  Flumioxazin concentrations in the water decreased rapidly
following treatment, and reached an equilibrium with APF and 482-HA
within 1 day of treatment.  From Days 1 through 28, concentrations in
the water of the three compounds were relatively steady at 297-363 ppb
for flumioxazin, 519-638 ppb for 482-HA and 13-50 ppb for APF.  In
edible fish tissues, the distribution and decline of residues were
similar for both test species, although residue levels were generally
higher in catfish than in bluegills.  Total flumioxazin residues were
highest at the earliest sampling interval (4 hours) in both catfish
(2.52 ppm) and bluegills (0.85 ppm).  Total residues declined rapidly by
Day 3 and then remained relatively steady up to Day 28 in both bluegills
(0.063-0.075 ppm) and catfish (0.098-0.204 ppm).  At the earliest
sampling interval, total residues in both species were comprised
primarily of parent (55-65%) and 482-HA (34-45%), with trace amounts of
APF (<1%), but by Day 28, total residues were distributed equally
between parent (38-39%), 482-HA (26-27%) and APF (34-39%).  Total
flumioxazin residues did not bioaccumulate in either test species over
the 28 day study.  When extrapolated to reflect the 1x use rate, the
estimated total residues in bluegills (0.43 ppm) and catfish (1.26 ppm)
would support the proposed 1.5 ppm tolerances for freshwater fish. 
Because applications are prohibited to flowing water, intertidal or
estuarine areas, and to water used for crawfish farming, residue data
and tolerances are not required for shellfish or saltwater fishes.

Based on the rate of degradation of flumioxazin residues in aquatic
environments and the proposed 5 day restriction on the use of
flumioxazin treated water for irrigation of crops, the transfer of
quantifiable residues to irrigated crops is unlikely.  Therefore,
residue data on irrigated crops are not required for purposes of this
petition.

The submitted residue data for cucumber and summer squash are adequate. 
In addition, residue field trial data on cantaloupe, the representative
crop for muskmelon subgroup 9A were submitted previously in support of
the tolerance using the same use pattern.  The only cucurbit vegetable
residue data set containing quantifiable residues is cucumber.  The data
indicate that a tolerance for residues on cucurbits should be
established at 0.03 ppm.  ARIA recommends for the proposed flumioxazin
tolerance on cucurbit vegetables, group 9 at 0.03 ppm.  Concurrently,
with the establishment of the tolerance on cucurbit vegetables, the
existing tolerance on muskmelon subgroup 9A should be removed.

The submitted residue data for celery are adequate.  No residues of
flumioxazin above the LOQ of 0.02 ppm were found on celery.  Since
celery is the representative crop for leaf petioles, subgroup 4B, the
data are adequate to support the requested tolerance.  ARIA recommends
for the proposed flumioxazin tolerance on leaf petioles, subgroup 4B, at
0.02 ppm.

The submitted residue data for hops are adequate.  The submitted data
are adequate to support a tolerance on hops.  However, the proposed
tolerance was calculated with the MRL spreadsheet using half the LLMV
value.  Following Agency policy by using the LLMV value where
applicable, the MRL spreadsheet indicates a tolerance of 0.05 ppm would
be appropriate.  ARIA recommends for a tolerance of 0.05 ppm for the
residues of flumioxazin on hops.  A revised Section F is required. 

There are no processed food or feed items of regulable interest
associated with the raw agricultural commodities in the current
petition.

Analytical standards for flumioxazin are currently available in the EPA
National Pesticide Standards Repository.  However, standards need to be
submitted for APF and 482-HA.  

The previously submitted confined rotational crop study is adequate for
the proposed uses.  ARIA concludes that the existing rotational crop
plantback intervals (PBIs) are acceptable, and that rotational field
trials and tolerances are not necessary.

There are no Codex, Canadian or Mexican MRLs for flumioxazin; therefore,
there are no issues of international harmonization raised by this
action.

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

ARIA has examined the residue chemistry database for flumioxazin.  No
major deficiencies were noted in the current petition that would
preclude establishing a permanent tolerance for flumioxazin in
freshwater fish, cucurbit vegetables, leaf petioles and hops.  However,
until the petitioner resolves the deficiencies noted below, and pending
the results of a human health risk assessment, ARIA recommends against
the uses of flumioxazin for control of aquatic weeds. 

A confirmatory method is required for the proposed enforcement method
for fish (GPL-MTH-066).

FDA multiresidue method testing data are required for 482-HA and APF.

 

Reference standards for 482-HA and APF must be submitted to the EPA
National Pesticide Standards Repository.

The residue definition for the tolerance expression for fish should be
as follows: “Tolerances are established for residues of flumioxazin,
including its metabolites and degradates, in or on the commodities in
the table below.  Compliance with the tolerance levels specified below
is to be determined by measuring only the sum of flumioxazin,
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-4,5
,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, and its metabolites APF
(3-oxo-4-prop-2ynyl-6-amino-7-fluoro-3,4-dihydro-1,4-benzoxazin) and
482-HA
(N-(7-fluoro-3,4-dihdyro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cycl
ohex-1-ene-1-carboxamide-2-carboxylic acid), calculated as the
stoichiometric equivalent of flumioxazin, in or on the commodity.”

Assuming no risk issues are identified and pending the resolution of the
deficiencies above, ARIA recommends for establishing a permanent
tolerance for the combined residues of flumioxazin and its metabolites
482-HA and APF, expressed in parent equivalents:

Freshwater fish	1.5 ppm

Pending the results of the forthcoming risk assessment, ARIA recommends
for the uses of flumioxazin and on cucurbit vegetables, leaf petioles,
and hops.  However, the following deficiencies must be resolved as a
condition of registration:

The registrant should submit a revised Section F in which a tolerance of
0.05 ppm is proposed for hops, dried cones. 

The labels should be revised to prohibit adjuvants use on cucurbit
vegetables, leaf petioles, and hops.

The residue definition for the tolerance expression for CFR § 180.568
(a) General should be as follows: “Tolerances are established for
residues of flumioxazin, including its metabolites and degradates, in or
on the commodities in the table below. Compliance with the tolerance
levels specified below is to be determined by measuring only
flumioxazin,
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-4,5
,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione.”

Pending the resolution of the deficiencies above, ARIA recommends for
establishing a permanent tolerance for the combined residues of
flumioxazin in/on the following raw agricultural commodities:

Cucurbit vegetables group 9	0.03 ppm

Leaf petioles subgroup 4B	0.02 ppm

Hops, dried cones	0.05 ppm

With the establishment of the cucurbit vegetables tolerance, the
following tolerance should be removed:

Melon subgroup 9A	0.02 ppm

A human health risk assessment is forthcoming.

Background

The nomenclature and physicochemical properties of flumioxazin are
presented below in Tables 1 and 2.

Clipper™ Herbicide (EPA Reg. No 59639-161), Valor™ Herbicide (EPA
Reg. No 59639-99), and Chateau™ Herbicide (EPA Reg. No 59639-119). 
All products are WDG formulations containing 51% flumioxazin. 

λ218,  ε = 14700 (pH  1.9)

λ216,  ε = 43600 (pH  6.8)

λ216, ε = 51200 (pH 10.0)	MRID No. 44295004

860.1200  Directions for Use

Valent is proposing use of Clipper™ Herbicide for control of aquatic
weeds in bayous, canals, fresh water ponds, lakes, marshes and
reservoirs.  IR-4 wishes to amend the product labels for Valor™
Herbicide and Chateau™ Herbicide to incorporate new uses.  All
products are WDG formulations containing 51% flumioxazin.  A summary of
the proposed use directions is presented in Table 3.  

Table 3.	Summary of Proposed Use Pattern of Flumioxazin. 

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

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

(lb ai/A)	RTI 1 (days) 	PHI

™

51% WDG [59639-161]

	0.19-0.38	NS	NS	283	NA	Apply in a minimum volume of 30 and 5 gal/A for
ground and aerial applications, respectively.  

Subsurface application; ground equipment under water surface (weighted
trailing hoses)

100 ppb4: 

          0.27-2.1

200 ppb: 

          0.55-4.3

400 ppb: 

™

51% WDG [59639-99]

Chateau™

51% WDG [59639-119]	0.125	2	0.250	21±2 after transplant

28±2 after emergence	NS2	First shielded application to row middles
14±2 before crop emergence or transplant. Apply at 10-40 gal/A.

Leaf Petioles Subgroup 4B

Ground equipment	Valor™

51% WDG [59639-99]

Chateau™

51% WDG [59639-119]	0.094-0.188	1	0.094-0.188	NA	NS	Apply to soil
surface before transplant. Apply at 20-40 gal/A.

Hops

Ground equipment	Valor™

51% WDG [59639-99]

Chateau™

51% WDG [59639-119]	0.375	2	0.750	30±3	30±3	Apply to lower 30in of
plant extending to 18in from row. Apply at 10-40 gal/A.

1  Retreatment Interval.  

2  Do not apply to flowing water, intertidal or estuarine areas. Do not
use treated water for irrigation purposes until at least 5 days after
application.  Do not use in water used for crawfish farming.  

3   Where vegetation is dense, treat up to ½ the water body and wait
10-14 days before treating the remaining area.     Do not retreat the
same section of water within 28 days

	4  For subsurface uses, the reported rate is the lb ai/A necessary to
achieve the given concentration in a column of      water 1-8 feet in
depth

.  		NS = Not Specified 

	NA = Not applicable.

Conclusions:  The label directions are adequate to allow evaluation of
the field trial data relative to the proposed uses.  However, since
adjuvants were not used in the submitted residue field trials, the
labels should prohibit such uses on cucurbit vegetables, leaf petioles,
and hops.

860.1300 Nature of the Residue – Plants.

DP Num: 272652, R. Loranger, 3/12/01

DP Num: 259493, D. Dotson, 3/12/01

MRID 45888501, -03-04, M. Doherty, 7/1/04

  SEQ CHAPTER \h \r 1 Adequate plant metabolism studies are available
depicting the uptake and metabolism of [14C]flumioxazin following
preemergence or soil-directed applications to soybean, peanut, corn,
sugarcane, and grapes.  Based on these studies, HED determined that the
parent compound only is the residue of concern to be used in risk
assessments and the tolerance expression for primary and rotated crops. 
The crops and use patterns utilized in the available metabolism studies
adequately cover the proposed uses.

860.1300 Nature of the Residue – Livestock.

DP Num: 272652, R. Loranger, 3/12/01

DP Num: 194594, J. Garbus, 9/21/94

DP Num: 259493, D. Dotson, 3/12/01

Fish

HED’s ChemSAC agreed to waive the fish metabolism study with the
proviso that the fish be analyzed for residues of parent plus the two
major water degradates 482-HA and APF (Minutes, 5/9/07).  The registrant
has fulfilled that requirement.  No flumioxazin fish metabolism study is
required.

Livestock

Adequate ruminant and poultry metabolism studies are available depicting
the metabolism of flumioxazin radiolabeled in either the phenyl or
tetrahydrophthaloyl (THP) ring.  The metabolism of flumioxazin is
similar in both ruminants and poultry, involving the hydroxylation and
reduction of the cyclohexene ring in the THP moiety, hydrolytic cleavage
of the imide and amide linkages, and incorporation of sulfonic acid into
the THP moiety.  HED has determined that the residues of concern for
ruminants should include parent, 3-OH-flumioxazin, 4-OH-flumioxazin, and
Metabolites B, C, and F.  For poultry, the residues of concern are
parent, 3-OH-flumioxazin, 4-OH-flumioxazin, and 4-OH-S-53482-SA.  

860.1340 Residue Analytical Methods.

47550602.der (ILV trial)

MRID 47892901 (Method GPL-MTH-066)

MRID 47892902 (Method GPL-MTH-066 Discussion and ILV)

Water and Fish 

Valent has submitted method descriptions and validation data for two
LC-MS/MS methods for determining residues of flumioxazin and its
metabolites APF and 482-HA in water (Method GPL-MTH-064) and fish
tissues (Method GPL-MTH-066).  These methods were used for data
collection in the fish residue study, and Method GPL-MTH-066 is also
being proposed as a tolerance enforcement method for residues of
flumioxazin, APF and 485-HA in fish.

→327.2 transition for flumioxazin, the m/z 221.1→163.1 transition
for APF, and the m/z 373.2→221.0 transition for 482-HA.  Residues are
quantified using external standards, and residue values are expressed in
terms of each analyte.  The LOQ for each analyte is 1 ppb in water.

For Method GPL-MTH-066 (MRID 47892901; Amended Method, 10/22/09),
residues of flumioxazin and APF are sequentially extracted with ACN and
then ACN:water (1:1, v:v), each containing 1% formic acid.  The extracts
are combined and centrifuged, and residues are then analyzed by
LC-MS/MS.  Residues of 482-HA are sequentially extracted with ACN and
then ACN:water (1:1, v:v), each containing 1% ammonium hydroxide.  The
extracts are combined and centrifuged, and residues of 482-HA are then
analyzed by LC-MS/MS.  The results of the analysis are then used to
determine total flumioxazin residues (flumioxazin, APF and 482-HA) in
terms of parent equivalents.  The LC-MS/MS parameters for this method
are the same as for Method GPL-MTH-064, and the LOQ for each analyte is
10 ppb in fish tissues.

Both methods were adequately validated in conjunction with the analysis
of samples from the fish residue study.  For water samples fortified
with each analyte at 1 and 1000 ppb, average recoveries (±CV) were 100
± 8% for flumioxazin, 103 ± 10% for APF, and 86 ± 9% for 482-HA. For
catfish tissue samples fortified with all three analytes at 10 and 1000
ppb and with parent and 482-HA at 2000 ppb, average recoveries (±CV)
were 96 ± 14% for flumioxazin, 94 ± 14% for APF, and 87 ± 9% for
482-HA.  For bluegill tissue samples fortified at 10 and 1000 ppb,
average recoveries (±CV) were 96 ± 13% for flumioxazin and 83 ± 6%
for 482-HA.  APF recoveries from bluegill were also adequate at the 1000
ppb level (94 ± 3%), but were consistently low at the 10 ppb level (52
± 7%).  Apparent residues of flumioxazin and its metabolites were
non-detectable (ND) in/on all control samples of water and fish tissues.
 

In addition, a successful ILV trial was conducted for Method GPL-MTH-066
using five replicate samples of catfish tissue fortified with each
analyte at 10 and 100 ppb.  The ILV was successfully completed on the
first try, and recoveries of each analyte were adequate at both
fortification levels.  Average recoveries (±CV) were 102 ± 11% for
flumioxazin, 92 ± 15% for APF, and 97 ± 11% for 482-HA.  No major
modifications were made to the method for the ILV trial, and a set of 12
samples could be extracted and prepared for LC-MS/MS analysis within 4
hours.

No confirmatory method has been submitted for the proposed enforcement
method for fish (GPL-MTH-066).  The registrant indicates that for the
following reasons, no further confirmatory method is required: 1) the
recoveries obtained in the magnitude of the residues study were within
the parameters expected for these types of studies; 2) the data does not
reveal any tendency for either suppression or false positives due to the
use of a single parent ion to daughter ion transition for each analyte;
3) since the three analytes were found together in the magnitude of the
residue study in fish, the presence of each of the three analytes is
confirmatory for the others when used as an enforcement method; 4)
analyses in these studies were performed with two different LC/MS-MS
detectors; 5) the primary transitions from both flumioxazin and 482-HA
(masses of 355 and 373) result in daughter ions that are unique (327 and
221, respectively), with daughter ions above 200 m/z giving sample
chromatograms that are very similar to those obtained from analytical
standards; 6) the APF transition (221 to 163 m/z) still appears very
acceptable in these chromatograms; and 7) with the APF daughter ion of
only 163 m/z, it seems unlikely that a lower mass ion could reliably be
used since, the use of ions less than about 200 m/z can result in lower
method sensitivity.

Conclusions:  Method GPL-MTH-064 is adequate for collecting data on
residues of flumioxazin, APF and 482-HA in water samples.  Although low
recoveries were obtained from bluegill tissues fortified at the LOQ,
Method GPL-MTH-066 is also adequate for collecting data on residues of
flumioxazin, APF and 482-HA in fish samples.

Method GPL-MTH-066 for fish appears to be acceptable for tolerance
enforcement.  However, the ILV, confirmatory method, and radiovalidation
requirements have not been fulfilled.  The 860.1340 Guidelines require
that the ILV be conducted at the proposed tolerance level.  In this
case, the ILV was conducted at a level lower than the proposed tolerance
(100 ppb vs 1.5 ppm).  Since method performance at low levels is usually
the limiting factor, and once a method works at low levels it also works
at higher levels (C. Stafford, e-mail, 11/24/09), the ILV as submitted
is acceptable. 

The registrant’s contention that there is sufficient information
available to negate the requirement for a confirmatory method does not
meet the Agency requirements.  An acceptable confirmatory method is
required before the method can be recommended as an enforcement method. 
Since the proposed enforcement method uses an MS/MS detector, it can be
amended to include additional ion transitions for each analyte or some
other confirmatory aspect such as retention time on a different LC
column.  

Although radiovalidation data are typically required to demonstrate that
the residues of concern are adequately extracted by the enforcement
method, radiovalidation data will not be required for method GPL-MTH-066
as HED has waived the requirement for a fish metabolism study (See
860.1300 – Livestock, above).

Plant commodities

An adequate GC/NPD method is available for enforcing tolerances for
residues of flumioxazin in/on plant commodities (MRID 43935509, Valent
Residue Method #RM-30A-1, Determination of Flumioxazin Residues in
Crops, J. Garbus, 1/8/96).  This method has undergone a successful
independent laboratory validation (ILV) trial and a successful petition
method validation (PMV) trial by the Agency.  The reported method LOQ
and LOD for flumioxazin are 0.020 and 0.010 ppm, respectively.  However,
the validated LOQ was 0.010 ppm for residues in soybean seed, forage,
and hay in the PMV trial, and the LOD was 0.005 ppm.

Residues of flumioxazin in/on cucumber, summer squash, and celery were
quantitated by GC/NPD.  The harvested RAC samples were analyzed by
Cornell Analytical Laboratory using the Method, “Residue Analysis of
Flumioxazin on Cucumber by GC/NPD Detection, Version #6,” adapted and
modified from “Determination of Flumioxazin Residues in Crops; Residue
Method RM-30A-1.  Valent USA Corporation (Revised January 1996).” 
Residues were extracted with acetone:water (4:1, v:v).  The residues
were partitioned into dichloromethane (DCM), concentrated to dryness,
and further purified by partitioning in hexane/acetonitrile (ACN).  The
residues in the ACN phase were evaporated to dryness, re-dissolved in
hexane:ethyl acetate (2:1, v:v), and cleaned up on a Florisil column
eluted with hexane:ethyl acetate (2:1, v:v). The residues were
evaporated to dryness, re-constituted in acetone, and analyzed by
GC/NPD.  The LLMV for residues of flumioxazin in/on cucumbers, summer
squash, and celery was 0.02 ppm.  The analytical method was adequate for
data collection purposes.

Residues of flumioxazin in/on hops RAC samples (dried cones) were
quantified by gas chromatography with mass selective detection (GC/MSD)
using Valent method RM-30A-3, “Determination of Flumioxazin Residues
in Crops,” modified by the analytical laboratory, IR-4 Western Region
Leader Laboratory, University of California, Department of Environmental
Toxicology, Davis, CA.  The residues were partitioned into DCM,
concentrated to dryness, re-dissolved in hexane:ethyl acetate (2:1,
v:v), and cleaned up on a Florisil column eluted with hexane:ethyl
acetate (2:1, v:v).  The residues were evaporated to dryness,
re-dissolved in hexane:ethyl acetate (1:1, v:v) and further purified on
a tandem NH2 carbon SPE column eluted with hexane:ethyl acetate (1:1,
v:v).  The residues in the eluate were evaporated to dryness,
re-constituted in acetone, and analyzed by GC/MSD in the selective ion
monitoring (SIM) mode.  The LLMV for residues of flumioxazin on hops
samples was 0.02 ppm.  

Livestock commodities  

As tolerances for livestock commodities are not required, an enforcement
method for livestock commodities is not necessary.  However, adequate
data collection methods were submitted in conjunction with the cattle
feeding study (PP#s 6F7092 and 6E7151; DP Num: 342963, D. Rate,
11/20/07).  Residues of flumioxazin and its two hydroxy metabolites
(3-OH-flumioxazin and 4-OH-flumioxazin) were determined in milk and
tissues using two related LC/MS/MS methods, Valent Methods RM-30MK for
milk and RM-30T for tissues.  The methods were adequately validated in
conjunction with the analysis of the feeding study samples using control
samples of milk and tissues fortified with each analyte at 0.02 and 0.1
ppm.  For both methods, the validated LOQ is 0.02 ppm for each analyte,
and the reported LOD is 0.01 ppm.  

Conclusions:  There are adequate enforcement methods to determine
flumioxazin residues on plants.  The analytical methods used to
determine residues of flumioxazin in/on cucumber, summer squash, celery,
and hops are adequate for data collection purposes.  No further
information for the determination of flumioxazin residues on livestock
commodities is required.

860.1360 Multiresidue Methods

DP Num: 259493, D. Dotson, 3/12/01

  SEQ CHAPTER \h \r 1 Data depicting the analysis of flumioxazin through
FDA Multiresidue Protocols were submitted to FDA for review.  The
multiresidue method testing data indicate that flumioxazin is not
recovered through Sections 304 and 402 of PAM, Vol. I.

860.1380 Storage Stability

MRID 47550604, W. Cutchin, in process

MRID 47581801-04, W. Cutchin, in process

During the fish magnitude of residue study, the test water and tissue
samples were stored frozen for 8-14 days prior to extraction for
analysis.  As samples were stored frozen for <30 days prior to
extraction and analysis, storage stability data is not required to
support the fish residue study.

Concurrent storage stability studies were conducted along with the crop
field trials.  Control samples were fortified with flumioxazin at 0.20
ppm.  The fortified samples were then stored under conditions similar to
those under which the field trial samples were stored (~ -20ºC).  The
results indicate that flumioxazin is reasonably stable under frozen
storage conditions for up to 480 days in/on the various commodities. 
The actual durations of sample storage from the residue field trials are
presented in Table 4. 

Table 4.   Summary of Storage Conditions and Intervals.  

Matrix 	Storage Temperature

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

Cucumber	~-20	146	203

Summer squash

90-330	480

Celery

278	298

Hops

330	300

Additional storage stability data for flumioxazin residues in/on various
plant commodities are available from several earlier petitions.  These
data indicate that flumioxazin is reasonably stable under frozen
(-20ºC) storage for at least the following intervals: 13 months in
sugarcane; 12 months in cherries and soybean forage, hay, and seed; 10
months in peanut forage, hay, hulls, and nutmeats; 9 to 11 months in
mint tops and oil; 9 months in prunes, wet apple pomace, potatoes, and
potato processed fractions; 6 months in apple juice, grapes, raisins,
and almond nutmeats and hulls; 4 months in dry bulb onions; 3 months in
cotton seed, gin byproducts, hulls, and meal; and 2 to 3 months in grape
juice, and sugarcane molasses and refined sugar.  

Conclusions:  The available storage stability data are adequate and
support the sample storage durations incurred in the residue field
trials.  

860.1400 Water, Fish, and Irrigated Crops

Water and Fish

MRID 47550604, W. Cutchin, in process

In two tests using static water conditions, the residues of flumioxazin
and its two major water degradates (482-HA and APF) were examined in
water and in the edible tissues of bluegill sunfishes (Lepomis
macrochirus) and channel catfish (Ictalurus punctatus) for up to 28 days
following a single application of flumioxazin at an initial
concentration of 800 ppb (2x the maximum proposed rate).  The test
included one control and one treated tank (900 L/tank) for each species,
and the tanks contained either 185 juvenile bluegill sunfishes or 92
juvenile catfish at the start of the study.  The test substance was
diluted with water and applied to the treated tanks at a nominal
concentration of 800 ppb.  Water quality parameters and fish health were
determined daily, and the water volumes in each tank were maintained at
a constant level.  Flumioxazin treatment had no adverse effects on
either water quality or fish health during the 28-day study.  

 which degrades rapidly at pHs of ≥7.  Single treated samples of each
fish species were also collected on Days 0 (4 hours post-dose), 1, 3, 7,
14, 21 and 28, and control samples of fish were collected on Days 1, 3
and 21.  The fish were separated into non-edible and edible tissues, and
the edible tissue samples were frozen, homogenized, and divided into
triplicate subsamples for analysis.  During the study, additional
control samples of water and tissues were collected and fortified with
each analyte to assess recovery from “field” fortified samples.  All
samples were stored frozen and were analyzed within 8-14 days of
collection; therefore, additional supporting storage stability data are
not required.

Residues of flumioxazin, APF and 482-HA were determined using two
LC-MS/MS methods, one for analysis of water (GPL-MTH-064) and one for
analysis of fish tissues (GPL-MTH-066).  These methods are described in
the above Residue Analytical Methods section, and were adequately
validated in conjunction with the analysis of the study samples. 
Residues are expressed in terms of the individual analytes, and the
validated LOQs are 1 ppb for each analyte in water and 10 ppb for each
analyte in fish tissues.  For calculating the total combined residues,
482-HA and APF were converted to parent equivalent using conversion
factors of 0.95 and 1.61, respectively.

Following application of flumioxazin at 800 ppb (2x rate), the
concentration of flumioxazin in the water decreased rapidly in both
tanks to 310-313 ppb within 1 day of dosing, and then remained steadily
(297-363 ppb) throughout the remainder of the 28-day study.  There was a
proportional increase in 482-HA residues in the water to 558-604 ppb
within 1 day of dosing, after which 482-HA concentrations also remained
steady at 519-638 ppb.  Residues of APF in the water were considerably
lower than the other two analytes, but were also steady throughout the
study at 13-28 ppb, with the exception of a slight increase in the
catfish tank on Day 28 (50 ppb).  Total combined residues in water
(expressed in parent equivalents) were steady through the study at
725-973 ppb or 91-121% of the nominal dose, and the concentrations of
flumioxazin and the two metabolites appeared to reach equilibrium in
both tanks within 1 day of dosing, with flumioxazin accounting for
34-40% of the total combined residues, 482-HA accounting for 57-63%, and
APF accounting for 2-5%. 

In bluegill tissues, residues of both parent and 482-HA were highest at
the first sampling interval (4 hours) at 552 and 307 ppb, respectively,
and then declined rapidly to 42.4 and 33.9 ppb by Day 3.  Residue levels
were then relatively steady from 7 to 28 days at 26.4-33.3 ppb for
flumioxazin and 20.5-25.2 ppb for 482-HA.  Residues of APF were ND-18
ppb and showed a slight increase over time.  Flumioxazin and 482-HA did
not bioaccumulate in bluegills, and APF accumulated only slightly in
tissues at the 28-day interval (bioconcentration factor (BCF) = 1.29). 
Combined residues, expressed in parent equivalents, showed the same
pattern of decline as for the two major residues.  Combined residues
were highest at 4 hours post-treatment (852 ppb), declined rapidly to 90
ppb by Day 3, and then remained relatively steady at 63-75 ppb from Days
7 to 28.  Combined residues did not bioaccumulate in bluegill tissues
during the 28 day study.

The distribution and decline of residues in catfish tissues were similar
to the patterns observed for bluegills, although residue levels were
generally higher in catfish.  Residues of parent and 482-HA in catfish
tissues were 1390 and 1186 ppb, respectively, at 4 hours post-treatment,
and then declined rapidly by Day 3, after which residue levels were
relatively steady for flumioxazin (53.6-96.7 ppb) and 482-HA (36.8-81.9
ppb).  Residues of APF were also relatively steady from Day 0 to 21 at
13.4-23.5 ppb and then increased slightly to 43.1 ppb by Day 28.  None
of the three analytes appeared to bioaccumulate in catfish tissues. 
Combined residues, expressed in parent equivalents, were highest at 4
hours post-treatment (2525 ppb) and declined rapidly by Day 3 and
remained relatively steady at 98-204 ppb for the remainder of the study.
 Combined residues did not bioaccumulate in catfish tissues during the
28 day study.

Conclusions:  The flumioxazin residue data for sunfish and catfish are
adequate and support the proposed aquatic use of flumioxazin as a
subsurface application at concentrations up to 400 ppb. Following an
application of flumioxazin at 800 ppb (2x rate), the maximum total
flumioxazin residues (parent, 482-HA and APF) in edible tissues occurred
shortly after application (4 hours) and were 0.85 ppm for bluegill
sunfish and 2.52 ppm for catfish.  When extrapolated to a 1x use rate,
the maximum expected residues would be 0.43 ppm for bluegill sunfish and
1.26 ppm for catfish.  These data support the proposed 1.5 ppm tolerance
of freshwater fish.

Because the proposed label prohibits applications to flowing water,
intertidal or estuarine areas and to water used for crawfish farming,
residue data and tolerances are not required for shellfish or saltwater
fishes.

Irrigated Crops

In assessing the need for residue data on irrigated crops, ARIA
considered the available environmental fate data for flumioxazin.  For
flumioxazin, aqueous hydrolysis is rapid and pH dependent with a
half-life of 3.4-5.1 days at pH 5, 0.9-1 days at pH 7, and 0.2-0.4 hours
at pH 9.  The aqueous photolysis half-life is 1 day for flumioxazin, and
the anaerobic aquatic half-life is 3 to 4 hours (DP Num: 359097& 362612,
L. Liu, 7/24/09).

Conclusions: Based on the rapid degradation of flumioxazin in aquatic
environments, the proposed 5 day restriction on the use of flumioxazin
treated water for irrigation of crops is adequate and will preclude the
transfer of quantifiable residues to irrigated crops.  Therefore,
residue data on irrigated crops are not required to support the proposed
aquatic use.

860.1460 Food Handling

There are no proposed uses in the current petition that are relevant to
this guideline topic.

860.1480 Meat, Milk, Poultry, and Eggs

DP Num: 342963, D. Rate, 11/20/07

ARIA has previously concluded that there is no reasonable expectation of
quantifiable residues of flumioxazin in livestock commodities [40 CFR
§180.6(a)(3)] from the proposed uses associated with previous
flumioxazin petitions.  This determination was based on the results of
poultry and goat metabolism studies, which were conducted at >1800x and
6.3x the theoretical dietary burdens (TDB), based on a recently reviewed
ruminant feeding study (DP Num: 342963, D. Rate, 11/20/07).  The results
of the cattle feeding study show that no residues of flumioxazin nor its
two hydroxy metabolites were found at the method LOD (0.01 ppm) in any
of the samples of milk and tissues from cattle dosed for 28 days at a
level equivalent to 20 ppm (6.3x TDB).

Conclusions: None of the commodities in this petition, cucurbit
vegetables, leaf petioles, and hops are associated with livestock feed
items of regulable interest.  ARIA concludes that tolerances for meat,
milk, poultry, and eggs are not required for the purpose of this
petition.

860.1500 Crop Field Trials

MRID 47581801-04, W. Cutchin, in process

IR-4 has submitted residue field trial data on cucumber, summer squash,
celery, and hops.  The results from this study are discussed below and
summarized in Table 5.  

Cucumber

IR-4 has submitted field trial data for flumioxazin on cucumber.  Eight
trials were conducted in the United States encompassing NAFTA Zone 2: 
MD, SC, GA, and NC (1 trial, each); Zone 3: FL (1 trial); Zone 5: MI and
WI (1 trial, each); and Zone 6: TX (1 trial) during the 2005 growing
season.  The number and geographic distribution of the supervised crop
field trials on cucumber are adequate.  

At each test location, flumioxazin (Valor 51% WDG) was applied to the
treated plot two times, once as a banded, shielded application to the
row middles 14 ± 2 days before crop emergence (if the cucumber crop was
seeded) or before crop transplanting (if cucumber transplants were
used). The second was a banded, shielded application to the row middles
at either 21 ± 2 days after cucumber transplanting or 28 ± 2 days
after the crop emergence of a seeded cucumber crop (at the South
Carolina site the first application was 10 days before planting).  The
individual application rates ranged from 0.122-0.154 lb flumioxazin/A,
and totaled 0.244-0.279 lb ai/A per season.  The applications were made
in a spray volume of 20-34 gal/A, and did not include an adjuvant. 
Cucumber samples were harvested 6-31 days after the last application.

Residues of flumioxazin in/on cucumber were quantitated by GC/NPD using
an analytical method that was adequate for data collection purposes. 
The harvested RAC samples were analyzed by Cornell Analytical Laboratory
using the Method, “Residue Analysis of Flumioxazin on Cucumber by
GC/NPD Detection, Version #6,” adapted and modified from
“Determination of Flumioxazin Residues in Crops; Residue Method
RM-30A-1.  Valent USA Corporation (Revised January 1996).”  Concurrent
recoveries from control cucumber samples fortified at 0.02 ppm and 0.2
ppm were 80-120% (95 ± 15%, n = 6) and 70-85% (78 ± 8%, n = 3),
respectively.  The LLMV for residues of flumioxazin in/on cucumbers was
0.02 ppm.  The LOD and LOQ were 0.010 and 0.031 ppm, respectively.  In
these trials, flumioxazin residues ranged from <0.02 to 0.027 ppm in/on
cucumbers harvested 6-31 days after two banded, shielded applications to
row middles at 0.244-0.279 lb ai/A.

A freezer storage stability study was conducted in conjunction with this
study.  Flumioxazin residues were stable in/on cucumbers when stored
frozen for up to 203 days.  The maximum storage interval for cucumber
samples in this study was 146 days.

Summer Squash

IR-4 has submitted field trial data for flumioxazin on summer squash. 
Eight trials were conducted in the United States encompassing NAFTA Zone
1: NY (1 trial); Zone 2: MD and GA (1 trial, each); Zone 3: FL (1
trial); Zone 5: MI (1 trial); Zone 6: TX (1 trial); Zone 10: CA (1
trial); Zone 11: WA (1 trial) during the 2004 growing season.  The
number and geographic distribution of the supervised crop field trials
on squash are adequate.  

At each test location, two shielded applications of flumioxazin (51%
WDG) were made to the row middles of summer squash at 0.124-0.134 lb
ai/A/application, with a 33-45 day retreatment interval, for a total
rate of 0.250-0.263 lb ai/A.  At three of the sites, the first
application was made preplanting or preemergence.  In Georgia, the first
application was at 10 days prior to seeding and in California and
Washington at 1 day after seeding.  The second application was made
29-30 days after crop emergence.  At the five other sites, NY, MD, FL,
MI, and TX, the first application was made 14-15 days before
transplanting and the second application was made 20-26 days after
transplanting.  The applications were made with ground equipment using a
spray volume of 14-32 gal/A, and did not include an adjuvant in the
spray mixture.  Summer squash samples were harvested at commercial
maturity, 7-34 days after the last application. 

Residues of flumioxazin in/on summer squash were quantitated by GC/NPD
using Cornell Analytical Laboratory Method, “Residue Analysis of
Flumioxazin on Squash by GC/NPD Detection, Version #4.”  This method
was adapted with minor modification from Valent method RM-30A-1.  For
method validation, control samples of summer squash were fortified with
flumioxazin at 0.02 and 0.2 ppm; all recoveries from summer squash were
70-110% (88 ± 14%, n = 6).  Concurrent recoveries from summer squash
samples fortified at 0.02 ppm were 90-130% (110 ± 13%, n = 8).  The
LLMV for residues of flumioxazin in/on summer squash samples was 0.02
ppm.  The LOD and LOQ were 0.007 and 0.021 ppm, respectively.  Residues
of flumioxazin were below the LLMV (<0.02 ppm) in/on all summer squash
samples harvested 7-34 days after the second of two shielded
applications of flumioxazin to row middles totaling 0.250-0.263 lb
ai/A/season.

A freezer storage stability study was conducted in conjunction with this
study.  Flumioxazin residues were stable in/on summer squash when stored
frozen for up to 16 months.  The maximum storage interval for summer
squash samples in this study was 11 months.

Celery

IR-4 has submitted field trial data for flumioxazin on celery.  Eight
trials were conducted in the United States encompassing NAFTA Zone 3: FL
(2 trials); Zone 5: MI (1 trial); and Zone 10: CA (5 trials) during the
2004 and 2005 growing seasons.  At each test location, one broadcast
preplant application of flumioxazin (51% WDG) was made to the soil
surface 0-2 days before transplanting celery at rates of 0.093-0.100 lb
ai/A (low rate) or 0.182-0.197 lb ai/A (high rate).  The applications
were made in a spray volume of 20-39 gal/A, and did not include an
adjuvant in the spray mixture.  Celery RAC samples were harvested at
commercial maturity, 73-127 days after treatment.  The number and
geographic distribution of the supervised crop field trials on celery
are adequate

Residues of flumioxazin in/on celery were quantitated by GC/NPD using
the Cornell Analytical Laboratory Method entitled, “Residue Analysis
of Flumioxazin on Celery by GC/NPD, Version #5.”  This method was
adapted with minor modification from Valent method RM-30A-1.  For Method
Validation, control samples of celery were fortified with flumioxazin at
0.02 and 0.2 ppm.  Recoveries from all method validation celery samples
were 90-150% (113 ± 17%, n = 13), with three recoveries outside the
range of 70-120%.  Concurrent recoveries from control celery samples
fortified at 0.02 ppm were 95-150% (114 ± 13%, n = 17) with one
recovery outside the range of 70-120%.  The LLMV for residues of
flumioxazin in/on celery samples was 0.02 ppm.  The LOD and LOQ were
0.007 ppm and 0.02 ppm, respectively.  An acceptable analytical method
is available for enforcement purposes.  In these trials, flumioxazin
residues in/on celery were <0.02 ppm in/on all celery samples harvested
73–127 days after one pre-transplanting application of flumioxazin at
rates of 0.093–0.100 lb ai/A (low rate) or 0.182-0.197 lb ai/A (high
rate).  

A freezer storage stability study was conducted in conjunction with this
study.  Flumioxazin residues were stable in/on celery when stored frozen
for up to 10 months.  The maximum storage interval for celery samples in
this study was 9 months.

Hops

IR-4 has submitted field trial data for flumioxazin on hops.  Three
trials were conducted in the United States encompassing NAFTA Zone 11:
ID (1 trial) and WA (1 trial); and Zone 12: OR (1 trial) during the 2005
growing season.  At each test location, two directed foliar applications
of flumioxazin (51% WDG) were made to hops at a rate of 0.358-0.408 lb
ai/A/application, with a 29-33 day retreatment interval, for a total
rate of 0.729-0.808 lb ai/A.  The sprays were directed to the lower
30-40 inches of the hops plants, extending out 18-24 inches from the
vine row.  The applications were made in a spray volume of 32-47
gallons/A, and included crop oil concentrate as an adjuvant in the spray
mixture.  Commercially mature hops samples were harvested at a 28 or
30-day preharvest interval (PHI) and immediately dried according to
actual or simulated commercial practices.  The number and geographic
distribution of the supervised crop field trials on hops are adequate.  

Residues of flumioxazin in/on hops RAC samples (dried cones) were
quantified by gas chromatography with mass selective detection (GC/MSD)
using Valent method RM-30A-3, “Determination of Flumioxazin Residues
in Crops,” modified by the analytical laboratory, IR-4 Western Region
Leader Laboratory, University of California, Department of Environmental
Toxicology, Davis, CA.  The LLMV for residues of flumioxazin on hops
samples was 0.02 ppm. The calculated LOD and LOQ were 0.0071 and 0.0213,
respectively.  Method validation recoveries of flumioxazin from hops
were 93-129% (109 ± 13%, n = 6) at fortification levels of 0.02 and 0.2
ppm.  An acceptable analytical method is available for enforcement
purposes.  In these trials, flumioxazin residues in/on hops ranged from
<0.02 to 0.04 ppm harvested 28–30 days after two directed foliar
applications of flumioxazin totaling 0.729–0.808 lb ai/A/season.

A freezer storage stability study was conducted in conjunction with this
study.  Flumioxazin residues were stable in/on hops when stored frozen
for up to 10 months.  The maximum storage interval for hops samples in
this study was 11 months.

Conclusions:  The submitted residue data for cucumber and summer squash
are adequate.  The field trial data reflect the proposed use pattern, an
adequate number of trials were conducted in the appropriate geographic
regions for the squash/cucumber subgroup 9B, and samples were analyzed
for the residue of concern using validated data-collection methods.  In
addition, residue field trial data on cantaloupe, the representative
crop for muskmelon subgroup 9A were submitted previously in support of
the tolerance using the same use pattern.  In that study, no residues
were detected above the reported LOD, 0.008 ppm (PP#s: 6F7092 and
6E7151, DP Num: 342963, D. Rate, 11/20/07).  The only cucurbit vegetable
residue data set containing quantifiable residues is cucumber.  Using
the MRL spreadsheet for that data set indicates that a tolerance for
residues on cucurbits should be established at 0.03 ppm.  ARIA finds
that there are no residue chemistry issues that would preclude a
flumioxazin tolerance on cucurbit vegetables, group 9 at 0.03 ppm.
Concurrently, with the establishment of the tolerance on cucurbit
vegetables, the existing tolerance on muskmelon subgroup 9A should be
removed.

The submitted residue data for celery are adequate.  The field trial
data reflect the proposed use pattern, an adequate number of trials were
conducted in the appropriate geographic regions, and samples were
analyzed for the residue of concern using validated data-collection
methods.  No residues of flumioxazin above the LOQ of 0.02 ppm were
found on celery; therefore, the data would not be analyzed using the MRL
spreadsheet.  Since celery is the representative crop for leaf petioles,
subgroup 4B, the data is adequate to support the requested tolerance. 
ARIA finds no residue chemistry issues to preclude establishing a
flumioxazin tolerance on leaf petioles, subgroup 4B, at 0.02 ppm.

The submitted residue data for hops are adequate.  The field trial data
reflect the proposed use pattern, an adequate number of trials were
conducted in the appropriate geographic regions, and samples were
analyzed for the residue of concern using validated data-collection
methods.  The submitted data is adequate to support a tolerance on hops.
 However, the proposed tolerance was calculated with the MRL spreadsheet
using half the LLMV value.  Following Agency policy by using the LLMV
value where applicable, the MRL spreadsheet indicates a tolerance of
0.05 ppm would be appropriate.  ARIA had determined that the appropriate
tolerance for residues in/on hops is 0.05 ppm.  A revised Section F is
required. 

Adjuvants were not used in any of the submitted residue field trials. 
Since adjuvants were not used in the submitted residue field trials, the
labels should prohibit such uses on cucurbit vegetables, leaf petioles,
and hops.

Table 5.    Summary of Residue Data from Field Trials with Flumioxazin.

Matrix	Total Applic. Rate  (lb ai/A)	PHI (days)	Residue Levels (ppm) 1

	n	Min.	Max.	HAFT 2	Median	Mean	Std. Dev.

Cucumber,

Fruit	0.244-0.279	7-31	16	<0.02	0.027	0.026	0.020	0.021	0.0020

Summer squash, fruit	0.250–0.263	7-34	16	<0.02	<0.02	<0.02	<0.02	<0.02
-

Celery, 

Stalks and leaves	0.093-0.100	73-127	16	<0.02	<0.02	<0.02	<0.02	<0.02	-

	0.182-0.197	73-127	16	<0.02	<0.02	<0.02	<0.02	<0.02	-

Hops,

(Dried cones)	0.729–0.808	28–30	6	<0.02	0.04	0.032	0.02	0.024	0.01

1	The LLMV is 0.02 ppm  For calculation of the median, mean, and
standard deviation, the LLMV was used for samples with residues <LOQ.

2	HAFT = Highest Average Field Trial.

860.1520 Processed Food and Feed

There are no processed food or feed items of regulable interest
associated with the raw agricultural commodities in the current
petition.

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

Analytical standards for flumioxazin are currently available in the EPA
National Pesticide Standards Repository.  However, standards need to be
submitted for APF and 482-HA.  These should be sent to the Analytical
Chemistry Laboratory to the attention of Theresa Cole or Thuy Nguyen at
the following address:  

U.S. EPA

National Pesticide Standards Repository/ Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD  20755-5350.

Please note that mail will be returned if the entire extended zip code
is not used when addressing correspondence to the Repository.

860.1850/860.1900 Confined and Field Accumulation in Rotational Crops

DP Num: 259493, D. Dotson, 3/12/01

DP Num: 272652, R. Loranger, 3/12/01

The previously submitted confined rotational crop study is adequate for
the proposed uses.  HED has concluded that the residue of concern in
rotational crops is the parent compound only.  Based on the results of
the confined accumulation study, HED concluded that the existing
rotational crop plantback intervals (PBIs) are acceptable, and that
field trials and tolerances in rotated crops are not necessary.

Current label directions for both 51% WDG formulations of flumioxazin
specify the following general rotational crop restriction:  Do not plant
any crop except cotton, peanut, soybean and sugarcane earlier than 30
days after application of flumioxazin.  In addition, the labels also
specify a variety of PBIs for different field crops depending on the
application rate.  For the highest use rate on any rotated crop (0.38 lb
ai/A), the specified PBIs are 9 months for cotton, field corn, peanut,
rice, sorghum, soybean, sunflower, tobacco and wheat, and 18 months for
all other field crops. 

860.1550 Proposed Tolerance

HED previously determined that the residue of concern in crops for the
purposes of risk assessment and tolerance expression should include only
parent flumioxazin.  

Flumioxazin tolerances are established under 40 CFR §180.568. 
Tolerances for residues in/on plant commodities are listed in 40 CFR
§180.568[a] and are expressed in terms of flumioxazin per se.  The
tolerance expression proposed by Valent USA in the current petition is
consistent with the tolerance definition for plant commodities.  

The flumioxazin residue data for sunfish and catfish are adequate and
support the proposed aquatic use of flumioxazin as a subsurface
application at concentrations up to 400 ppb.  When extrapolated to a 1x
use rate, the maximum expected residues would be 0.43 ppm for bluegill
sunfish and 1.26 ppm for catfish.  These data support the proposed 1.5
ppm tolerance of freshwater fish.

The submitted residue data for cucumber and summer squash are adequate. 
The only cucurbit vegetable residue data set containing quantifiable
residues is cucumber.  Using the MRL spreadsheet for that data set
indicates that the appropriate tolerance for residues on cucurbits is
0.03 ppm, which is in agreement with the proposed value.  Concurrently,
with the establishment of the tolerance on cucurbit vegetables, the
existing tolerance on muskmelon subgroup 9A should be removed.

The submitted residue data for celery are adequate.  No residues of
flumioxazin above the LOQ of 0.02 ppm were found on celery; therefore,
the MRL spreadsheet was not used.  Since celery is the representative
crop for leaf petioles, subgroup 4B, the data is adequate to support the
requested tolerance at 0.02 ppm.

The submitted residue data for hops are adequate.  Following Agency
policy by using the LLMV value where applicable, the MRL spreadsheet
indicates a tolerance at the proposed level of 0.05 ppm would be
appropriate.  

Tolerances for rotational crop commodities are not needed.  The existing
rotational crop plantback intervals are acceptable to preclude the need
for rotational crop trials.

A summary of the proposed tolerances is presented in Table 6.

There are no Codex, Canadian or Mexican MRLs for flumioxazin (see
Appendix I); therefore, there are no issues of international
harmonization raised by this action.

The residue definition for the tolerance expression for fish should be
as follows: “Tolerances are established for residues of flumioxazin,
including its metabolites and degradates, in or on the commodities in
the table below.  Compliance with the tolerance levels specified below
is to be determined by measuring only the sum of flumioxazin,
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-4,5
,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, and its metabolites APF
(3-oxo-4-prop-2ynyl-6-amino-7-fluoro-3,4-dihydro-1,4-benzoxazin) and
482-HA
(N-(7-fluoro-3,4-dihdyro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cycl
ohex-1-ene-1-carboxamide-2-carboxylic acid), calculated as the
stoichiometric equivalent of flumioxazin, in or on the commodity.”

The residue definition for the tolerance expression for CFR § 180.568
(a) General should be as follows: “Tolerances are established for
residues of flumioxazin, including its metabolites and degradates, in or
on the commodities in the table below. Compliance with the tolerance
levels specified below is to be determined by measuring only
flumioxazin,
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-4,5
,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione.”

Table 6.   Tolerance Summary for Flumioxazin.

Commodity	Proposed/Existing Tolerance (ppm)	Recommended Tolerance (ppm)
Comments;

Correct Commodity Definition

Fish, freshwater	1.5	1.5

	Cucurbit vegetables group 9	0.03	0.03

	Leaf petioles subgroup 4B	0.02	0.02

	Hops, dried cones	0.07	0.05

	Melon subgroup 9A	0.02	remove	With the establishment of the tolerance
on cucurbit vegetables, the existing tolerance on muskmelon subgroup 9A
should be removed.

References

  SEQ CHAPTER \h \r 1 DP Num:	342963

Subject:	Flumioxazin.  Petitions for Tolerances on Alfalfa, Asparagus,
Dry Beans, Fruiting Vegetables (Group 8, including Okra), Melons
(subgroup 9A), Bushberries (subgroup 13B), and Tree Nuts (group 14), and
a Request for an Amended Use on Garlic.  Summary of Analytical Chemistry
and Residue Data.  PP#s: 6F7092 and 6E7151.	

From:		D. Rate

To:		D. Rosenblatt, J. Miller and J. Stone

Dated:		11/20/07

MRID(s):	46889603 -04, 47005101-07

  SEQ CHAPTER \h \r 1 DP Num:	194594

Subject:	PP# 3G4250: New Chemical EUP:   V-53482, Flumioxazin on
Soybeans.  Evaluation of Analytical Methods and of Residue Data.

From:		J. Garbus

To:		J. Miller, D. Kenny and A. Koscialski

Dated:		9/21/94

MRID(s):	42884011-42884014, 42884016-42884019

  SEQ CHAPTER \h \r 1 DP Num:	None

Subject:	PP# 3G4250:  New Chemical EUP: Flumioxazin:  Revised Tolerance
Enforcement Method.

From:		J. Garbus

To:		J. Miller

Dated:		1/8/96

MRID(s):	43935509

  SEQ CHAPTER \h \r 1 DP Num:	259493 and 268181

Subject:	PP#s 7F4841 and 0F6171.  Tolerance Petitions for the Use of
Flumioxazin on Peanuts, Soybeans, and Sugarcane.  Evaluation of Residue
Chemistry and Analytical Methodology

From:		D. Dotson

To:		D. Kenny and J. Miller

Dated:		3/12/01

MRID(s):	44013001, 44013002, 44295049 - 44295057

  SEQ CHAPTER \h \r 1 DP Num:	272652

Subject:	PP# 7F4841/0F6171; Flumioxazin in/on Peanuts, Soybeans and
Sugarcane.  Conclusions of the 12/20/2000 Meeting of the Metabolism
Assessment Review Committee.

From:		R. Loranger

To:		Y. Donovan

Dated:		3/12/01

MRID(s):	None

  SEQ CHAPTER \h \r 1 DP Num:	298647

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Subject:	Flumioxazin.  Tolerance Petition Requesting Section 3
Registration for Food Use of Flumioxazin on Cotton.  Summary of
Analytical Chemistry and Residue Data.  Petition Number 1F06296.

From:		W. Drew

To:		J. Miller

Dated:		2/17/04

MRID(s):	45375506

  SEQ CHAPTER \h \r 1 DP Num:	301247

Subject:	Flumioxazin.  Tolerance Petition Requesting Section 3
Registration for Food Use of the Herbicide Flumioxazin on Sugarcane,
Grape, Almond/Pistachio, Mint, Tuberous/Corm Vegetables (Crop Subgroup
1C), and Dry Bulb Onion/Garlic/Shallot.  Summary of Analytical Chemistry
and Residue Data.  Petitions Numbered 0F06171, 1F06296, 3E06777,
3E06779, 3E6788.

From:		W. Drew

To:		Joanne Miller/James Stone

Dated:		7/23/04

MRID(s):	45244801, 45375503, 45375504, 45375505, 45375507, 45888501,
46109201, 46114601, 46133901

DP Num:	310408 and 313783

Subject:	Flumioxazin.  Tolerance Petitions Requesting Section 3
Registration for Food Use of the Herbicide Flumioxazin on Pome Fruit
(Crop Group 11), Stone Fruit (Crop Group 12), and Strawberries.  Summary
of Analytical Chemistry and Residue Data.	

From:		W. Drew

To:		J. Stone, J. Miller and D. Rosenblatt,

Dated:		3/15/06

MRID(s):	46229401, 46229402, 46229403, 46229404, 46229405, 46229406,
46229407, 46229408, 46292501

DP Num:	None	

Subject:	Crop Grouping – Part III:  Analysis of the USDA IR-4 Petition
to Amend the Crop Group Regulation 40 CFR §180.41 (c)(13) and Commodity
Definitions [40 CFR §180.1(h)] Related to Crop Group Berry. 

From:		B. Schneider

To:		B. Madden

Dated:		3/28/06

MRID(s):	None

DP Num:	342963	

Subject:	Flumioxazin.  Petitions for Tolerances on Alfalfa, Asparagus,
Dry Beans, Fruiting Vegetables (Group 8, including Okra), Melons
(subgroup 9A), Bushberries (subgroup 13B), and Tree Nuts (group 14), and
a Request for an Amended Use on Garlic.  Summary of Analytical Chemistry
and Residue Data.  PP#s: 6F7092 and 6E7151.

From:		D. Rate

To:		D. Rosenblatt, J. Miller, J. Stone

Dated:		11/20/07

MRID(s):	46889603, 46889604, 47005101, 47005102, 47005103, 47005104,
47005105, 47005106, 47005107

  SEQ CHAPTER \h \r 1 Attachments:  

Appendix I: International Residue Limits Status

Appendix II: MRL Spreadsheet Results 



Appendix I:

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benz硯穡湩㘭礭
嵬㐭㔬㘬㜬琭瑥慲票牤ⵯ䠱椭潳湩潤敬ㄭ㌬㈨⥈搭潩敮
䌇浯潭⁮慎敭›䘠畬業硯穡湩堇†牐灯獯摥琠汯牥湡散

 Reevaluated tolerance

 Other	Date: 4/29/09

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:  8E7462

DP#:  359142

√ 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, 04/29/2009.

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ppendix II:

EPA

Flumioxazin

Cuke

6-31 Days

Raw Data

 

Residues

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.020

0.024

0.027



 PAGE   

 PAGE   1  of   NUMPAGES  29 

Flumioxazin	Summary of Analytical Chemistry and Residue Data	DP Num: 
357451

 PAGE   29  of   NUMPAGES  29