UNITED STA TES ENVIRONMENTA L PROTECTION AGENCY WA SHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM Date: 1 2 / 15 /0 9 Subject: Flumioxazin. Petition for the Establishment of Permanent Tolerances on Fish,

Cucurbit Vegetables, Leaf Petioles, and Hops . Summary of Analy tical Chemistry and Residue Data. P P# s 8F7438 & 8 E7 462 . DP Number : 357451 Decision Number: 400513 PC Code: 129034 MRID No.: 465506 0 2, 46550604, 47581801 - 04 40 CFR 180. 568 Risk Assessment Ty pe: 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 (RAB II) Health Effects Division (HED ; 7509 P ) 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

2 of 29 Executive Summary Flumioxazin belongs to the N - phenylphthalimide class of herbicide s (Group 14) . It is a light dependent peroxidizing herbicide (LDPH) which acts by blocking heme and chlorophyll biosy nthesis resulting in an endogenous accumulation of porphy rins 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 applic ation 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 subsurf ace 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. Inconjunction with this use, Valent has proposed the following permanent tolerance for residues of flumioxazin and its metabolites APF ( 3 - oxo - 4 - prop - 2y nyl - 6 - amino - 7 - fluoro - 3,4 - dihydro - 1,4 - benzoxazin ) and 482 - HA (N - (7 - fluoro - 3,4 - dihdy ro - 3 - oxo - 4 - prop - 2 - ynyl - 2H - 1,4 - benzoxazin - 6 - yl )cyclohex - 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 product s (EP s ) 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 - disper sible granular (WDG) formulation s 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 0.0 94 - 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 - propy nyl) - 2H - 1,4 - benzoxazin - 6 - yl ] - 4,5,6,7 - tetrahydro - 1 H - isoindole 1,3(2H ) - dione , in/on the following raw agricultural commodities: C ucurbit vegetabl es group 9 ................................ ............................ 0.03 ppm Leaf petioles subgroup 4B ................................ ............................... 0.02 ppm Hops, dried cones ................................ ................................ ............. 0.0 7 ppm With the establishment of the cucurbit vegetables tolerance, IR - 4 is requesting the removal of the following tolerance: Melon subgroup 9A ................................ ................................ ......... 0.02 ppmFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

3 of 29 Flumioxazin t olerances 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, soy bean, 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 alfalf a forage and hay (DP Num: 342963, D. Rate , 11/2007 ) . T ime - limited tolerance s in/on alfalfa forage and hay , w ith a 12/ 31 /0 9 expiration date , are also currently listed in 40 CFR §180.568[b]. No tolerances have been established in meat, milk, poultry , or egg s. The nature of flumioxazin residues in plants and animals is adequately understood b ased on a cceptable soy

bean, 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. Inprimary 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 - 06 6 ) 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 e i ther 1% formic acid for extraction of parent and APF or 1% ammonium hydroxide for extraction of 482 - HA. Extracte d r esidues are d iluted with water and analy zed directly

by L C - MS/MS using extern al standards for quantitation. The validated limit of quantitation (L OQ) is 0.01 ppm for each analy te in fish. This method has undergone a successful independent laboratory va lidation (ILV) trial and appears to be accept able 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/N PD) method , Valent Method RM - 30 - A - 1, is available for enforcing tolerances f or 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 Analy

tical Chemistry

Branch (ACB /BEAD). The reported method LOQ and limits of detection (L OD) 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 proto cols. As tolerances for livestock commodities are not required, an enforcement method for livestock commodities is not necessary for this petition. Analy

tical standards for the parent flumioxazin are currently available in the EPA National PesticideFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

4 of 29 Stan dards Repository . However, analy tical 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 analy zed by using a method modified from Method RM - 30A - 1. The lower limit of method validation (LLM V) for residues of flumioxazin in/on cucumbers, summer squash , and celery was 0.02 ppm. The analy tical method was adequate for data collection purposes . Res idues of flumioxazin in/on hops, dried cones wer e quantified by gas chromatography

with mass selective detection (GC/MSD) using Valent M ethod RM - 30A - 3 . The residues were analy zed by GC/MSD in the selective ion monitoring (SIM) mode. The LLM V for residues of flumioxazin on hops samples was 0.02 ppm. Th e analy tical 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, s torage stability

data is not required to support the fish residue study . C oncurrent 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 th is 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 unde r static wat er 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 co ncentrations 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 catfi sh (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 shellf ish or saltwater fishes.Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

5 of 29 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 irrigate d 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 representati ve 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 L OQ of 0.02 ppm were found on celery . Since celery is the representative crop for leaf petioles, subgroup 4B, the data are a dequate 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 ho ps. 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 MRLspreadsheet indicates a tolerance of 0.05 ppm would be appropriate. ARIA rec ommends 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. Anal yt ical 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 propose d uses. ARIA concludes that the existing rotational crop plantback intervals (PBI s) are acceptable, and that rotational field trials and tolerances are not necessary . There are no Codex, Canadian or Mexican MRL s for flumioxazin; therefore, there are no i ssues 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 cur

rent 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 h ealth 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

6 of 29  A confirmatory

method is required for th e 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 s hould be as follows: “ Tolerances are established for residues of flumi oxazin , 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 - propy nyl) - 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 - 2y nyl - 6 - amino - 7 - fluoro - 3,4 - dihydro - 1,4 - benzoxazin) and 482 - HA (N - (7 - fluoro - 3,4 - dihdy ro - 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 .” Assuming no risk issues are identified and p ending 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 cuc urbit vegetables, leaf petioles, and hops. However, the following deficienc ies 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 labe ls 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 s hould 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 - propy nyl) - 2H - 1,4 - benzoxazin - 6 - yl ] - 4,5,6,7 - tetrahydro - 1H - isoindole - 1,3(2H) - dione . ” P ending the resolution of the deficienc ies above , ARIA recommends for establishing a permanent tolerance for the combined residues of flumioxazin in/on the following raw agricultural commodities: C ucur bit vegetables group 9 ................................ ............................ 0.03 ppm Leaf petioles subgroup 4B ................................ ............................... 0.02 ppm Hops, dried cones ................................ ................................ ............. 0.0 5 ppmFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

7 of 29 With the establishment of the cucurbit vegetables tolerance, the following tolerance should be removed: Melon subgroup 9A ................................ ................................ ......... 0.0 2 ppm A human health risk assessme nt is forthcoming. Background The nomenclature and physicochemical properties of flumioxazin are presented below in Tables 1 and 2. Table 1. Flumioxazin Nom enclature. Compound N N O F

C H 2 O

O O C C H 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 - ene 1,2 - 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 - 1 H

- isoindole - 1,3(2H

) - dione CAS registry number 103361 - 09 - 7 End - use product s (EP s) 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, mar shes 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 direction s is presented in Tabl e 3.Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

8 of 29 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 reservoirs 2 Broadcast surface application; ground or aerial equipment ClipperTM

51% WDG [59639 - 161] 0. 19 - 0. 38 NS NS 28 3 NA A pply in a minimum volume of 30 and 5 gal/A for ground and aerial applications, respectively. Subsurface application; ground equipment under water surface (weighted tr a iling hoses) 100 ppb 4 : 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 floati ng or emerged weeds. Apply in a minimum of 5 0 gal/A . Cucurbit Vegetables Group 9

Ground equipment ValorTM

51% WDG [59639 - 99] ChateauTM 51% WDG [59639 - 119] 0.12 5 2 0. 250 21±2 after transpla nt 28±2 after emerge nce NS 2 Fi r st shielded application to

row middles 14±2 before crop emergence or transplant. Apply at 1 0 - 40 gal/A . Leaf Petioles Subgroup 4B Ground equ ipment 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. 7 50 30±3 30±3 Apply to lower 30in of plant extending to 18 in 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 daysFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

9 of 29 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 fiel d trial data relative to the proposed use s . However, since ad j uvants were not used in the submitted residue field trials, the label s should prohibit such uses on cucurbit vegetables, leaf petioles, and hops. 860 . 1300 Nature of the Residue – Plants. D P 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 [ 14 C]flumioxazin following preemergen ce or soil - directed applications to soy bean, peanut, corn, sugarcane, and grape s . 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 ro tated crops. The crops and use patterns utilized in the available metabolism studies adequately

cover the proposed uses. 860.1300 Nature of the Residue – Livestock. D P 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 analy zed for residues of parent plus the two major water degradates 482 - HA and APF (Minutes, 5/9/07). The registrant has fulfilled that requ irement. 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 metabol ism of flumioxazin is similar in both ruminants and poultry , involving the hydroxylation and reduction of the cyclohexene ring in the THP moiety , hydroly tic 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 4789290 2 (Method GPL - MTH - 066 Discussion and ILV )Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

10 of 29 Wa ter and Fish Valent has submitted method descriptions and validation data for two L C - MS/MS meth ods 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 analy zed directly

by L C - MS/MS using separate samples for the analysis of flumioxazin and its metabolites. The L C - MS /MS sy stem consists of a C 18 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 . R esidues 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 analy te. The LOQ for each analy t e is 1 ppb in water. For Method GPL - MTH - 066 (MRID 47892901 ; Amended Method, 10/22/09) , r esidues 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 centri fuged, and residues are then analy zed by L C - 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 ana ly zed by L C - 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 L OQ for each analy te 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 analy te at 1 and 1000 ppb, average recoveries (±CV) were 10 0 ± 8% for flumioxazin, 103 ± 10% for APF, and 86 ± 9% for 482 - HA. For catfish tissue samples fortified with all three analy tes 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. Inaddition, a successful ILV trial was conducted for Method GPL - MTH - 06 6 using five replicate samples of catfish tissue fortified with each analy te at 10 and 100 ppb. The ILV was successfully completed on the first try , and recoveries of each analy te 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 L C - MS/MS analysis within 4 hours.Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

11 of 29 No confirmatory

method h as 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 withi n the parameters expe cted for these ty pes 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 analy

te ; 3) since the three analy tes were found together in the m agnitude of the residue study

in fish, the presence of each of the three analy tes 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 obt ained from analy

tical standards; 6) the APF transition (221 to 163 m/z) still appears very ac ceptable 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 L OQ, Method GPL - MTH - 06 6 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 accept able for tolerance enforcement. However, the ILV, confirmatory method , and rad iovalidation 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 me thod 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 re quirements . An acceptable confirmatory method is required before the method can be recommended as an enforcement method. Since the proposed enforcement m ethod uses an MS/MS detector, it can be amended to include additional ion transitions for each analy te or some other confirmatory aspect such as retention time on a different L C column . Although radiovalidation data are ty pically 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

– Li vestock, above) . Plant commo dities An adequate GC/NPD method is available for enforcing tolerances f or 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 ha s undergone a successful independent laboratory

validation ( ILV ) trial and a successful petition method validation ( PMV )Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

12 of 29 trial by the Agency . The reported method L OQ and LOD for flumioxazin are 0.020 and 0.010 ppm, respectively . However, the validated L O Q was 0.010 ppm for residues in soy bean seed, forage, and hay

in the PMV trial, and the L OD was 0.005 ppm. Residues of flumioxazin in/on cucumber, summer squash, and celery were quantitated by GC/NPD . The harvested RAC samples were analy zed by Cornell An aly

tical L aboratory

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 Januar y 1996).” Residues were extracted with acetone:water (4:1, v:v). The residues were partitioned into dichloromethane (DCM), concentrated to dry ness, and further purified by partitioning in hexane/acetonitrile (ACN). The residues in the ACN phase were eva porated to dry

ness, 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 dry ness, re - constituted in acetone, and analy zed by GC/NPD. The LLMV for residues of flumioxazin in/on cucumbers, summer squash , and celery was 0.02 ppm. The analy

tical 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 analy tical laboratory , IR - 4 Western Region L eader Laboratory , University of California, Department of Environmental Toxicology , Davis, CA. The residues were partitioned into DCM, concentrated to dry ness, 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 dry ness, re - dissol ved in hexane:ethyl acetate (1:1, v:v) and further purified on a tandem NH 2 carbon SPE column eluted with hexane:ethyl acetate (1:1, v:v). The residues in the eluate were evaporated to dry ness, re constituted in acetone, and analy zed by GC/MSD in the sele ctive 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 . Ho wever, 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 L C/MS/MS methods, Valent Methods RM - 30MK for milk and RM - 30T for tissues. T he methods were adequately validated in conjunction with the analysis of the feeding study samples using control samples of milk and tissues fortified with each analy te at 0.02 and 0.1 ppm. For both methods, the validated LOQ is 0.02 ppm for each analy te, and the reported LOD is 0.01 ppm. Conclusion s : There are adequate enforcement methods to determine flumioxazin residues on plants. The analy

tical 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 comm odities is required. 860.1360 Multiresidue Methods DP Num: 259493, D. Dotson , 3/12 /01Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

13 of 29 Data depicting the analysis of flumioxazin through FDA Multiresidue Protocols were submitted to FDA for review. The multiresidue method testing d ata 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 wat er 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, s torage stability data is not required to support the fish residue study . C oncurrent sto rage stability stud ies w ere conducted along with the crop field trials. C ontrol samples were fortified with flumioxazin at 0. 2 0 ppm . The fortified samples were then stored under conditions similar to those under which the field trial samples were stored ( ~ - 20oC). Th e results indicate that flumioxazin is reasonably stable under frozen storage conditions for up to 480 days in/on the vario us c ommodities . The actual duration s of sample storage from the residue field trials are presented in Table 4. T able 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 Add itional storage stability data for flumioxazin residues in/on various plant commodities are available from several earlier petitions . These data indicate that flumioxazin is reas onably stable under frozen ( - 20 oC) storage for at least the following interva ls: 13 months in sugarcane; 12 months in cherries and soy bean 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 by products, 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 Intwo tests using static wate r 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 a n initial concentration of 800 ppb (2x the maximum proposed rate). The test included one control and one treated tank (900 L /tank) forFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

14 of 29 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 eac h 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 t issue s amples were frozen, homogenized, and divided into triplicate sub samples for analysis. During the study , additional control samples of water and tissues were collected and fortified with each analy

te to ass ess recovery

from “field” fortified samples. All samples were stored frozen and were analy

zed within 8 - 14 days of collection; therefore, additional supporting storage stability data are not required. Residues of flumioxazin, APF and 482 - HA were determine d using two L C - MS/MS methods, one for analysis of water ( GPL - MTH - 064 ) and one for analysis of fish tissues ( GPL - MTH - 066 ) . These methods are describe d in the above Residue Analy tical Methods section, and were adequately

validated in conjunction with the an alysis of the study samples. Residues are expressed in terms of the individual analy tes, and the validated L OQs are 1 ppb for each analy te in water and 10 ppb for each analy te in fish tissues. For calculating the total combined residues, 482 - HA and APF w ere 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 st eady at 519 - 638 ppb. Residues of APF in the water were considerably lower than the other two analy tes, 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 dosin g, with flumioxazin accounting for 34 - 40% of the total combined residues, 482 - HA accounting for 57 - 63%, and APF accounting for 2 - 5%. Inbluegill 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 increaseFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

15 of 29 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 sam e 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 bio accumulate 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 a lso 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 analy

tes appeared to bioaccumulate in catfish tissues. Combined residues, expressed in parent equivalents, were highest at 4 hour s 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 resid ue 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 residu es (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 Inassessing the need for residue data on irrigated crops, ARIA considered the available environmental fate data for flumioxazin. For flumioxazin, aqueous hydrolysis is ra pid 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 aq uatic half - life is 3 to 4 hours ( DP Num: 359097 & 362612 , L . L iu, 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.Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

16 of 29 860.1480 Meat, Mi lk, 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 pre vious 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: 34 2963, 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 L OD (0.01 ppm) in any of the samples of milk and tissues from cattle dosed for 28 days at a lev el equivalent to 20 ppm (6.3x TDB). Conclusions : None of the commodities in th is 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 tri a l data on cucumber, summer squash, celery , and hops . T he results from this study are d iscussed 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: MIand 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 appl ied 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, shie lded 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 applic ation. Residues of flumioxazin in/on cucumber were quantitated by GC/NPD using an analy

tical method that was adequate for data collection purposes. The harvested RAC samples were analy zed by Cornell Analy

tical L aboratory

using the Method, “Residue Analys is 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 LLM V for residues of flumioxazin in/on cucumbers was 0.02 ppm. The L OD and LOQ wereFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

17 of 29 0.010 and 0.031 ppm, respectively . In these tri als , 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/ap plication, 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 Califor

nia 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 mad e 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 Analy tical L aboratory

Method, “Residue Analysis of Flumioxazin on Squash by GC/NPD Detection, Version #4.” This method was adapted with minor modific ation 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 LLM V for residues of flumioxazin in/on summer squash samples was 0.02 ppm. The L OD and LOQ were 0.007 and 0.021 ppm, respectively . Residues of flumioxazin were below the LLM V (<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 wer e conducted in the United States encompassing NAFTA Zone 3: FL (2 trials); Zone 5: MI (1 trial); and Zone 10: CAFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

18 of 29 (5 trials) during the 2004 and 2005 growing seasons. At each test location, one broadcast preplant application of flumioxazin (51% WDG) was ma de 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 Analy tical 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 fort ified 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 LLM V 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 analy tical method is avail able 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 - 0.19 7 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 eac h 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 lowe r 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 analy tical laboratory , IR - 4 Western Region L e ader Laboratory , University of California, Department of Environmental Toxicology , Davis, CA. The LLM V 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 ofFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

19 of 29 0.02 and 0.2 ppm. An acceptable analy tical method is available for enforcement purposes. In these trials , flumioxazin residues in/on hops ranged from <0.02 to 0.04 ppm h arvested 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 numb er of trials were conducted in the appropriate geographic regions for the squash/cucumber subgroup 9B , and samples were analy zed for the residue of concern using validated data - collection methods. Inaddition, residue field trial data on cantaloupe, the r epresentative crop for muskmelon subgroup 9A were submitted previously

in support of the tolerance using the same use pattern . Inthat 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 MRLspreadsheet 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 0.0 3 ppm. Concurrently , with the establishment of the tolerance on cucurbit vegetables, the existing tolerance on muskmelon subgroup 9A should b e 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 analy

zed for the residue of concern using validated data - collection methods. No residues of flumioxazin above the L OQ of 0.02 ppm were found on celery ; therefore, the data would not be analy

zed using the MRL

spreadsheet . Since celery is the representative crop for leaf petioles, subgroup 4 B, 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 analy

zed 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 MRLspreadsheet indicates a tolerance of 0.0 5 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. S ince ad j uvants were not used in the submitt ed residue field trials, the label s should prohibit such uses on cucurbit vegetables, leaf petioles, and hops.Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

20 of 29 Table 5. Sum mary of Residue Data from Field T rials 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, F ruit 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 L LMV 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 Analy tical 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 Analy tical Chemistry

L aboratory

to the attention of Theresa Cole or Thuy Nguyen at the following address: U.S. EPA National Pesticide Standards Repository / Analy tical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350. Ple ase 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 D P Num: 259493 , D. Dotson , 3/12 /01 D P Num: 272652, R. L oranger , 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 conclude d that the existing rotational crop plantback intervals (PBI s) 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 fo llowing general rotational crop restriction: Do not plant any crop except cotton, peanut, soy bean and sugarcane earlier than 30 days after application of flumioxazin. In addition, the labels also specify a variety of PBI s for different field crops depending on the application rate. For theFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

21 of 29 highest use rate on any

rotated crop (0.38 lb ai/A), the specified PBI s are 9 months for cotton, field corn, peanut, rice, sorghum, soy bean, 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. T olerances 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 re sidues 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 dat a 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 establis hment 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 L OQ of 0.02 ppm were found on celery ; therefore, th e MRLspreadsheet 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 u s i ng the LLMV value where applicable , the MRLspreadsheet 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 accept able 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 MRL s for flumioxazin (see Appendix I); therefore, there are no issues of international harmonizati on raised by this action. The residue definition for the tolerance expression for fish s hould be as follows: “ Tolerances are established for residues of flumioxazin , including its metabolites and degradates, in or on the commodities in the table below. C ompliance with the tolerance levels specified below is to beFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

22 of 29 determined by

measuring only

the sum of flumioxazin, 2 - [7 - fluoro - 3,4 - dihydro - 3 - oxo - 4 - (2 - propy nyl) - 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 - 2y nyl - 6 - amino - 7 - fluoro - 3,4 - dihydro - 1,4 - benzoxazin) and 482 - HA (N - (7 - fluoro - 3,4 - dihdy ro - 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 s hould 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 - propy

nyl) - 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 c ones 0.07 0.0 5 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. Peti tions 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 Analy tical 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 Soy beans. Evaluation of Analy

tical 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: NoneFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

23 of 29 Subject: PP# 3 G4250: New Chemic al 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 o n

Peanuts, Soy

beans, and Sugarcane. Evaluation of Residue Chemistry and Analy tical 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, Soy beans and Sugarcane. Conclusions of the 12/20/2000 Meeting of the Metabolism Assessment Review Committee. From: R. L oranger 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 Analy tical 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 Bu lb Onion/Garlic/Shallot. Summary of Analy tical 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, 45375 507, 45888501, 46109201,

46114601, 46133901 DP Num: 310408 and 313783Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

24 of 29 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 Analy tical 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 Subj ect: Crop Grouping

– Part I II: 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 Amen ded Use on Garlic. Summary

of Analy tical 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 L imits Status Appendix I I: MRLSpreadsheet ResultsFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

25 of 29 Appendix I : INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 2 - [7 - fluoro 3,4 - dihydro - 3 - oxo - 4 - (2 - propynyl) - 2H

- 1,4 - benz oxazin - 6 - yl] - 4,5,6,7 - tetrahydro - 1 Hisoindole - 1,3(2H

) - dione Common Name:

Flumioxazin X Proposed tolerance Reevaluated tolerance Other Date: 4/29/09 

### Codex Status (Maximum Residue L imits) 

### 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

26 of 29 A 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 0.027Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

27 of 29 Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156 y = 0.0587x - 3.8799 R 2 = 0.4076

PercentilesConcentrations EPA Flumioxazin Cuke 6-31 Days RAW

Reg ulat or: EP A Ch emic al: Fl umio xazin Cr op: Cu ke PH I: 6- 31 D ays App . Ra te: RA W Sub mitt er:

n: 15 mi n: 0.0 2 ma x: 0.0 3 medi an: 0.0 2 avera ge: 0.0 2 95th Per centi le 99 th P erce ntile 99.9 th Pe rcen tile 0. 03 0.0 3 0.03 (0 .03) (0.0 3) (--) 0. 03 0.0 3 0.03 (0 .03) (0.0 3) (--) 0.0 4 0.0 3 0.1 5 0.40 76 p-va lue < = 0. 01: Rejec t lo gnorm alit y ass umpt ion

Wou ld y ou l ike t he a bove valu es r ounde d? ( Y or N)== > Y Appr oxima te Sh apir o-Fra ncia Norm alit y Tes t EU M ethod I Norm al

UC LMe dian9 5th 95 /99 Rule EU Meth od II Dis trib ution -Fre e Me an+ 3SDFlumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

28 of 29 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. 0 40Flumioxazin Summary of Analytical Chemistry and Residue Data DP Num: 357451

29 of 29 Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156 y = 0.2398x - 3.7661 R 2 = 0.6247

PercentilesConcentrations EPA Flumioxazin Hops 28-30 Days

Reg ulat or: EP A Ch emic al: Fl umio xazin Cr op: Ho ps PH I: 28 -30 Days App . Ra te: Sub mitt er:

n: 6 mi n: 0.0 2 ma x: 0.0 4 medi an: 0.0 2 avera ge: 0.0 2 95th Per centi le 99 th P erce ntile 99.9 th Pe rcen tile 0. 04 0.0 5 0.05 (0 .06) (0.0 7) (--) 0. 04 0.0 5 0.06 (0 .07) (0.1 0) (--) 0.0 6 0.0 5 0.2 0 0.62 47 p-va lue < = 0. 01: Rejec t lo gnorm alit y ass umpt ion

Wou ld y ou l ike t he a bove valu es r ounde d? ( Y or N)== > Y Appr oxima te Sh apir o-Fra ncia Norm alit y Tes t EU M ethod I Norm al

UC LMe dian9 5th 95 /99 Rule EU Meth od II Dis trib ution -Fre e Me an+ 3SD