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), 

ValorTM Herbicide (59639-99), and 

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

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Executive Summary

Flumioxazin belongs to the N-phenylphthalimide class of herbicides (Group 14). It is a lightdependent 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 (ClipperTM 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)cyclohex-1-ene1-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 ValorTM Herbicide (EPA Reg. No. 59639-99) and ChateauTM 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-isoindole1,3(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 Summary of Analytical Chemistry and Residue Data DP Num: 357451

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

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

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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.

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

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 A confirmatory method is required for the proposed enforcement method for fish (GPLMTH-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-tetrahydro1H-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-prop2-ynyl-2H-1,4-benzoxazin-6-yl)cyclohex-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
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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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.

Table 1. Flumioxazin Nomenclature.

Compound

N

N

O

F

C

H2

O

O

HC C O

Common name Flumioxazin

Company experimental name VC-1152

IUPAC name N-(7-fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cyclohex-1-ene1,2-dicarboxamide

CAS name 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

CAS registry number 103361-09-7

End-use products(EPs) ClipperTM Herbicide (EPA Reg. No 59639-161), ValorTM Herbicide (EPA Reg. No 

59639-99), and ChateauTM Herbicide (EPA Reg. No 59639-119). All products are WDG 

formulations containing 51% flumioxazin. 

Table 2. Physicochemical Properties of Flumioxazin. 

Parameter Value Reference

Melting point/range 202-204°C EPA Fact Sheet for 

Flumioxazin issued April 12, 

2001.

pH 7.29 at 25°C

Density 1.51 g/mL at 20°C

Water solubility (25°C) 1079 mg/L 

Solvent solubility Not available

Vapor pressure 2.41 x10-6 mm Hg

Dissociation constant, pKa None

Octanol/water partition coefficient, Log(KOW) 2.55 at 20°C

UV/visible absorption spectrum 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 ClipperTM 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 

ValorTM Herbicide and ChateauTM 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. 
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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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

(days)

Use Directions and 

Limitations

Aquatic Use including bayous, canals, drainage ditches, lakes, marshes, ponds and reservoirs2

Broadcast 

surface 

application; 

ground or 

aerial 

equipment ClipperTM

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: 

 1.07-8.6

NS NS 28 NA

Application may include an 

approved aquatic adjuvant

when used on floating or 

emerged weeds. Apply in a 

minimum of 50 gal/A.

Cucurbit Vegetables Group 9

Ground 

equipment

ValorTM

51% WDG 

[59639-99]

ChateauTM

51% WDG 

[59639-119]

0.125 2 0.250

21±2 

after 

transpla

nt

28±2 

after 

emerge

nce

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

ValorTM

51% WDG 

[59639-99]

ChateauTM

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

ValorTM

51% WDG 

[59639-99]

ChateauTM

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 1⁄2 the water body and wait 10-14 days before treating the remaining area. 

Do not retreat the same section of water within 28 days
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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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

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-OHflumioxazin, and Metabolites B, C, and F. For poultry, the residues of concern are parent, 3-OHflumioxazin, 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)
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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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.

For Method GPL-MTH-064, water samples are analyzed directly by LC-MS/MS using separate 

samples for the analysis of flumioxazin and its metabolites. The LC-MS/MS system consists of a 

C18 column with a mobile phase gradient of water to ACN, each containing 0.2% formic acid. 

The high pressure liquid chromatograph (HPLC) is coupled to a MS/MS detector via a turbo-ion 

spray interface and uses the positive ion mode. Residues are detected and quantified using the 

m/z 355.2→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 nondetectable (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.
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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)
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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, redissolved 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, reconstituted 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
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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 
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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. 

Duplicate water samples were collected from the treated tanks pre-dose and on Study Days 0 (4 

hours post-treatment), 1, 3, 7, 14, 21 and 28, and single water samples were collected from the 

control tanks on Days 1, 3 and 21. Each water sample was split into two subsamples, one for the 

analysis of 482-HA and APF and the other for analysis of flumioxazin. The flumioxazin water 

samples were buffered to pH 5 immediately after collection, to stabilize the flumioxazin 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 
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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.
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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 
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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 
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(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 
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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.
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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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.

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

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

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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)cyclohex-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

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

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

DP Num: None
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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

Enforcement Method.

From: J. Garbus

To: J. Miller

Dated: 1/8/96

MRID(s): 43935509

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

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

DP Num: 298647

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

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

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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

Attachments: 

Appendix I: International Residue Limits Status

Appendix II: MRL Spreadsheet Results
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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Appendix I:

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 2-[7-fluoro3,4-dihydro-3-oxo-4-(2-

propynyl)-2H-1,4-benzoxazin-6-

yl]-4,5,6,7-tetrahydro-1Hisoindole-1,3(2H)-dione

Common Name: 

Flumioxazin

X Proposed tolerance

 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

PC Code: 129034

Residue definition (step 8/CXL): N/A Reviewer/Branch: W. Cutchin / RIMUERB

Residue definition: Flumioxazin per se

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

Cucurbit vegetables group 9 0.03

Leaf petioles subgroup 4B 0.02

Hops, dried cones 0.05

Limits for Canada Limits for Mexico

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

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

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Lognormal Probability Plot

0.1 1 2 5 10 20 30 50 70 80 90 95 98 99 99.9

1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156

y = 0.0587x - 3.8799

R

2

 = 0.4076

Percentiles

Concentrations

EPA Flumioxazin Cuke 6-31 Days RAW

Regulator: EPA

Chemical: Flumioxazin

Crop: Cuke

PHI: 6-31 Days

App. Rate: RAW

Submitter:

n: 15

min: 0.02

max: 0.03

median: 0.02

average: 0.02

95th Percentile 99th Percentile 99.9th Percentile

0.03 0.03 0.03

(0.03) (0.03) (--)

0.03 0.03 0.03

(0.03) (0.03) (--)

0.04

0.03

0.15

0.4076

p-value <= 0.01: Reject lognormality assumption

Would you like the above values rounded? (Y or N)==> Y

Approximate 

Shapiro-Francia

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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Regulator: EPA

Chemical: Flumioxazin

Crop: Hops

PHI: 28-30 Days

App. Rate:

Submitter:

Residues

0.020

0.020

0.020

0.020

0.024

0.040
Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

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Lognormal Probability Plot

0.1 1 2 5 10 20 30 50 70 80 90 95 98 99 99.9

1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156

y = 0.2398x - 3.7661

R

2

 = 0.6247

Percentiles

Concentrations

EPA Flumioxazin Hops 28-30 Days

Regulator: EPA

Chemical: Flumioxazin

Crop: Hops

PHI: 28-30 Days

App. Rate:

Submitter:

n: 6

min: 0.02

max: 0.04

median: 0.02

average: 0.02

95th Percentile 99th Percentile 99.9th Percentile

0.04 0.05 0.05

(0.06) (0.07) (--)

0.04 0.05 0.06

(0.07) (0.10) (--)

0.06

0.05

0.20

0.6247

p-value <= 0.01: Reject lognormality assumption

Would you like the above values rounded? (Y or N)==> Y

Approximate 

Shapiro-Francia

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD