Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 1 of 27 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date: 24-March-2011

SUBJECT: Metconazole. Petition for Registration of Use on Tuberous and Corm Vegetables Subgroup 1C and Bushberry Subgroup 13-07B (PP#0E7743). Summary of Analytical Chemistry and Residue Data.

PC Code: 125619 DP Barcode: D380990 Decision No.: 436782 Registration No.: 59639-147 Petition No.: 0E7743 Regulatory Action: Sec. 3 Registration Risk Assessment Type: N/A Case No.: N/A TXR No.: N/A CAS No.: 125116-23-6 MRID No.: See MRID Summary Table 40 CFR: §180.617

From: Amelia M. Acierto, Chemist Risk Assessment Branch III Health Effects Division (7509P)

Through: Stephen Funk, Senior Chemist Risk Assessment Branch III Health Effects Division (7509P)

To: Barbara Madden RM 5 Risk Integration, Minor Use, & Emergency Response Branch Registration Division (7505P)

Note: This document was originally prepared under contract by Versar, Inc. (6850 Versar Center, Springfield, VA 22151; submitted 1/31/11). The DER has been reviewed by the Health Effects Division (HED) and revised to reflect current Office of Pesticide Programs (OPP) policies.

MRID Summary Table MRID No. Study Type Comments 48143301 860.1500 (potato field trials) 860.1520 (potato processing study) New DER; 48143301.der1 (860.1500) New DER; 48143301.der2 (860.1520)
48143302 860.1500 (blueberry field trials) New DER; 48143302.der (860.1500)Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 2 of 27 Executive Summary

The Interregional Research Project No. 4 (IR-4), on behalf of the Agri cultural Experiment Stations of New York, New Je rsey, Ohio, Maryland, Florida,Wi sconsin, North Dakota,Texas, Colorado, California, Washington, and Idaho, ha s submitted potato field trials during the 2007 growing season, and on behalf of the agricultura l stations of New Jersey, North Carolina, Michigan, and Oregon, has submitted high bush blueberry crop field trials during the 2006 growing season in the U.S., and New Brunswick, Nova Scotia and Quebec for low bush blueberry field trials in Canada. Concomita ntly, IR-4 has submitted a petition (PP#0E7743) proposing the establishment of to lerances for the resi dues of the fungicide metconazole, 5-[(4- chlorophenyl)methyl]-2,2-dimethyl-1-(1 H -1,2,4-triazol-1-ylmethyl)c yclopentanol, in/on the following raw agricultural commodities (RAC):

Tuberous and Corm Vegetable subgroup 1C ...........0.02 ppm Bushberry subgroup 13-07B ....................................0.35 ppm

In conjunction with this petiti on, IR-4 is requesting an amende d registration of a 50% water dispersible granule formulation of metconazole to allow use on tuberous and corm vegetables and bushberries. Potato and blue berry (high and low bush) were th e representative crops used to generate data in support of the subject petition.

The end-use product (EP) relevant to this pe tition is Metconazole 50 WDG or V-10116 50 WDG registered to Valent USA Cor poration (EPA Reg. No. 59639-147). Under the proposed use, four foliar applications will be made to potato at 0.078-0.125 lb ai/A/applicat ion for a total seasonal rate of 0.500 lb ai/A and three applications will be made to blueberry at 0.078 lb ai/A/application for a total seasonal rate of 0.234 lb ai/A. For potat o, the preharvest interval (PHI) is 1-2 days; at two test sites (ID10 and ND10) additional samples were harvested at 3, 7, and 14 days for the residue decline study and at two test sites (WA3 3 and TX28) samples from added plots treated at the exaggerated rate of ≥ 5x were harvested at 1 day PHI fo r processing potato commodities. For blueberry, the PHI is 7 days and at 2 test sites (MI32 and NS01) additional samples were harvested at 0, 1, 3, and 10 days fo r residue decline determinations.

Tolerances for residues of metconazole are established under 40 CFR §180.617 and are expressed in terms of the fungi cide metconazole or in terms of the fungicide metconazole, including its metabolites and de gradates determined by measuring only metconazole as the sum of its cis - and trans - isomers [40 CFR §180.617(a)(1) and (2). Permanent tolerances have been established for a variety of raw agricultural and processed commodities including tree nuts, banana, barley, sugar beet, stone fruits, cereal gr ains, peanuts, soybean, canola, corn, and cotton commodities at tolerance levels ranging from 0.01-18 ppm. Tolerances for meat byproducts of cattle, goat, horse, and sheep, and egg are esta blished at 0.04 ppm. Section 18 time-limited tolerances are established under §180.617(b) for sugarcane ca ne and molasses at 1.6 and 3.2 ppm, respectively, and are se t to expire on 12/31/11.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 3 of 27 An adequate gas chromatography method with nitrogen-phosphorus-det ection (GC/NPD) is available for data collection and enforcement of tolerances for residues of metconazole parent isomers ( cis - and trans - metconazole) in plant commodities based on Valent Method RM-41C-1, “Determination of cis and trans –Metconazole in Crops.” An ad equate high performance liquid chromatography (HPLC) method is available for da ta collection and enforcement of tolerances for residues of 1,2,4-triazole (T), triazole alanine (TA), and tr iazole acetic acid (TAA). The method is based on Morse Laboratories, In c. analytical method, Meth-160, Rev. 2, “Determination of 1,2,4-Triazole, Tr iazole Alanine and Tr iazole Acetic Acid Residues in Plants and Animal Matrices.” The GC/N PD and HPLC methods were ade quately validated prior to and concurrently with the analyses of the crop field samples. The lowest level of method validation (LLMV) in potato was 0.02 ppm for both metconazole and the tr iazole metabolites, and in blueberry, the LLMV is 0.05 ppm for metconazole and 0.02 ppm for the triazole metabolites. For metconazole residues in potatoes, the calc ulated limits of detection (LOD) are 0.0037 and 0.0056 ppm for cis and trans -metconazole, respectively. For the triazole metabolites, the calculated LODs are 0.0052, 0.0066 and 0.0078 ppm for T, TA, and TAA, respectively. For metconazole residues in blueberries, th e calculated LODs are 0.0012 and 0.0092 ppm for cis and

trans -metconazole, respectively. For T, TA, and TAA in blueberries based on the recoveries of samples fortified at 0.02 ppm, the cal culated LODs are 0.010, 0.0042 and 0.011 ppm, respectively.

The LOQ is defined as the lowest fortification le vel of an analyte at which acceptable recovery data can be achieved. The LOQ is equivalent to the lowest level method validated (LLMV).

Additional multiresidue method te sting data required from a previous petition remain outstanding for metconazole. It was concluded (DP# 361110) that fu rther work is required to test the separation of me tconazole on OV-17 and OV-225 columns under Protocol C.

No new metabolism studies were submitted. The nature of metconazole residues in plants and animals is understood based on adequate me tabolism studies on banana, canola, mandarin oranges, pea, wheat, goats, and hens. For the to lerance expression, HED has determined that the residue of concern in plant and livestock commoditi es is metconazole (parent). For purposes of risk assessment, HED has concluded that the resi dues of concern in primary crops, except cereal grains, are metconazole (parent)

. For cereal grains, residues of metconazole and Metabolite M11 will be used for risk assessment. For livestock commodities, the residues of concern for risk assessment include metconazole and Metabolites M1 (free and conjugate d), M12, and M31 (free and conjugated).

In the potato crop field trial study, residues of the parent metc onazole, T, and TAA were not detected above the LOQ. Residues of TA we re 0.023–0.037 ppm (corrected values based on the control). Similarly, in blueberry, only the TA wa s detected over 14 days in the residue decline study with corrected residues <0.02 ppm.

The submitted field trials for potato and bluebe rry are supported by acceptable storage stability data for metconazole isomers ( cis - and trans -metconazole). Available data demonstrate that metconazole parent is relatively stable for up to 12 months in various cr op matrices; T and TAA were found stable for up to 6 months and TA was stable for up to 12 months. The currentMetconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 4 of 27 storage stability study shows that metconazole isomers ( cis - and trans -metconazole) were stable for at least 281 days (9.2 months) in blueberry fruits and 959 days (31.5 m onths) in potato tubers.

Although the samples for determina tion of triazole metabolites were stored for 875 days (28.8 months) for blueberry and 622 days (20.4 months) for potato, stability data were not submitted.

The submitted potato processing study indicate th at residues of metconazole were <LOQ in/on potato RAC samples following application of th e 50% WDG formulation at the exaggerated rates of 5x or 6.2x the maximum proposed seasonal rate. Based on this result, HED concludes that quantifiable residues of metconazole are not expected in the potato processed commodities (potato flakes/granules, potato chips and wet peel s) and tolerances are not needed for the potato processed commodities.

The ruminant feedstuffs associated with the pr oposed use of metconazole are processed potato waste and cull potatoes. However, the use of metc onazole in/on tuberous and corm vegetables is not expected to alter the dietar y exposure of ruminants based on very low (<LOQ) residues in the potato RAC samples treated at the ≥ 5x exaggerated rate. Therefor e, no changes are required in the current livestock tolerances for metconazole.

Adequate field trial data were submitted on the crop group/subgroup representative commodities to support the proposed uses of metconazole on tuberous and corm vegetables and bushberries. Based on the NAFTA tolerance spreadsheet as sp ecified by the Guidance for Setting Pesticide Tolerances, the proposed tolerances on blueberries is too low. The data will support a tolerance of 0.40 ppm for bushberries. The tolerance spread sheet was not used to calculate the tolerance for the tuberous and corm vegetables since the residues in potato were <LOQ. The tolerance should be established at 0.04 ppm, reflecti ng the combined LOQs of the metconazole enforcement method of 0.02 ppm for each metconazole isomer ( cis- and trans- metconazole).

There are no established or pr oposed Codex or Canadian maximum residue limits (MRLs) for metconazole in or on any food or feed crops; th erefore, there are no ha rmonization issues.

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry databa se for metconazole. Pending submission of a revised Section B (see requirements under Direc tion for Use) and Section F (see requirements under Proposed Tolerances), there are no residue chemistry issues that would preclude granting conditional registration and the esta blishment of a tolerance for the foliar uses of Metconazole 50 WDG Fungicide (EPA Reg. No. 59639-147) in/on ve getable, tuberous and corm and bushberry. The registration is conditional pending resolution of the issues listed under “Deficiences” below Provided the forthcoming human h ealth risk assessment does not identify any risks of concern, HED recommends for the establishment of the following tolerances:

Vegetable, tuberous a nd corm, subgroup 1C ...........0.04 ppm Bushberry subgroup 13-07B ....................................0.40 ppmMetconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 5 of 27 The remaining deficiencies regarding multires idue methods (see 860.1360 below) and storage stability (see 860.1380 below) must be reso lved as conditions of registration.

A human health risk assessment, including examin ation of potential resi dues of 1,2,4-triazole, tiazole alanine, and triazole acetic acid in/ on crops and livestock commodities is forthcoming.

Note to PM:

The tolerance expression for metconazole in 40 CFR §180.617(a)(1) should be stated according to HED’s Interim Guidance on Tolerance Expression (5/27/09, S. Knizer) as follows:

Tolerances are established for residues of metconazole , 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 onl y metconazole [5-[(4-chlorophenyl)methyl]-2,2- dimethyl-1-(1 H -1,2,4-triazol-1-ylmethyl)cyclope ntanol] as the sum of its cis - and trans -isomers.

Deficiencies:

860.1200 Directions for Use

Since no spray adjuvants were used in the residue field trials on potatoes and blueberries, the label must be amended to include a statement th at no adjuvant should be used for the tuberous and corm vegetable subgroup 1C and the bushberry subgroup 13-07B.

860.1360 Multiresidue Methods

HED has previously identified the need for me tconazole to be tested through OV-17 and OV-225 GC columns. This deficiency remains outstanding.

860.1380 Storage Stability

Storage stability data for residue s of 1,2,4-triazole, triazole acetic acid, and triazole alanine have not been submitted in conjunction with the subjec t petition . Although storage stability data for the triazoles are under revi ew by the Agency, more data may be required to support this petition.

860.1550 Proposed Tolerances

Section F should be revised to re flect the correct iden tification of the chemical being proposed. Propiconazole appears in Section F as the pesticide proposed.

The commodity definition for tuberous and corm vegetables must be changed to Vegetable, tuberous and corm, subgroup 1C as shown in Table 8.

A revised Section F should be submitted to propose a tolerance of 0.04 ppm for Vegetable, tuberous and corm, subgroup 1C and 0.40 ppm for bushberry subgroup 13-07 B . See Table 8.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 6 of 27 Background

Metconazole [5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1 H -1,2,4-triazol-1- ylmethyl)cyclopentanol] is a broad-spectrum triazo le fungicide (sterol bios ynthesis inhibitor) and acts primarily as an inhibitor of fungal ergosterol biosynthesis, th ereby interfering with synthesis of the fungal cell membrane.

The chemical structure and nomenclature of me tconazole are summarized in Table 1, and the physicochemical properties of metconazo le are summarized in Table 2.

Table 1. Metconazole Nomenclature.

Chemical structure

N N N

C H 3
C

H 3 O

H

Cl

cis -isomer N N N

C H 3
C

H 3 O

H

Cl

trans -isomer

Common name Metconazole Company experimental name V-10116 IUPAC name (1 RS ,5 RS :1 RS ,5 SR )-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1 H -1,2,4-triazol-1- ylmethyl)cyclopentanol CAS name 5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1 H -1,2,4-triazol-1- ylmethyl)cyclopentanol CAS registry number 125116-23-6 ( cis - and trans -isomers) 115850-27-6 ( cis -isomer) 115850-28-7 ( trans -isomer) End-use products (EP) 50% WG (Metconazole 50 WDG Fungicide, EPA Reg. No. 59639-147)

Table 2. Physicochemical Properties of th e Technical Grade Test Compound Metconazole.

Parameter Value Reference 1

Melting point/range 100.0-108.4 o C (using Electrothermal Digital Melting Point Apparatus) (AC900,768 technical grade) 44721505

pH No data were submitted.

Relative density at 20 o C 1.14 (relative density to water at 4 o C, using capillarystoppered, density-specific gravity bottle) (Lot No. AC 8879-140B) 44721505

Water solubility (20 ° C) Using shake flask method: 18.7±1.0 mg/L (cis-isomer, WL148271, KNF-S-474m) 13.6±1.7 mg/L (trans-isomer, WL148271, KNF-S-474m) 44721505Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 7 of 27 Table 2. Physicochemical Properties of th e Technical Grade Test Compound Metconazole.

Parameter Value Reference 1
Solvent solubility (g/L at 20 ° C) hexane: 1.40 toluene: 103 2-propanol: 132 ethyl acetate: 260 dichloromethane:481 methanol: 403 acetone: 363 44721505

Vapor pressure at 20 ° C Using gas-saturation method at 20 ° C: < 1.23x10 -5 Pa or 9.23 x 10 -8 mm Hg (AC 900,768) < 1.04x10 -5 Pa or 7.80 x 10 -8 mm Hg ( cis -isomer, CL 354,801) < 1.96x10 -6 Pa or 1.47 x 10 -8 mm Hg ( trans -isomer, CL 354,802) 44721505

Dissociation constant (pKa) 11.38±0.03 and 1.06±0.03 (in water using spectrophotometric method) (Lot No. AC 8879-140B) 44721505

Octanol/water partition coefficient Log(K
ow ) Kow (log K
ow ) = 7090±989 (3.85) (using flask shaking method) (Lot No. AC 8879-140B) (TGAI)
K ow (log K
ow ) = 7150±803 (3.85) (using flask shaking method) ( cis -isomer, CL 354,801)
K ow (log K
ow ) = 6800±1700 (3.8) (using flask shaking method) ( trans -isomer, CL 354,802) 44721505

UV/visible absorption spectrum Not required for TGAI; required for pure active ingredient

1 D256877, Shyam Mathur, 9/12/00

860.1200 Directions for Use

IR-4 has submitted use directions under Section B of the petition which include the draft labeling for the 50 % WDG formulation of metconazole (V-10116 50 WDG, EPA Reg. No. 59639-147). A summary of the proposed use directions for th e intended crops is presented in Table 3.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 8 of 27 Table 3. Summary of Directions for Use of Metconazole.

Applic. Timing, Type, and Equip. 1 Formulation [EPA Reg. No.] Applic.Rate oz/A (lb ai/A) Max. No. Applic. per

Season Max. Seasonal Applic. Rate

(lb ai/A) PHI (days) Use Directions and Limitations

Tuberous and Corm Vegetables (Subgroup 1C): arra cacha; arrowroot; artichoke, Chinese; artichoke, Jerusalem; canna (edible); cassava (b itter and sweet); chayot e (root); chufa; dasheen (taro); ginger; leren; potato; sweet potato ; tanier; turmeric; yam bean; yam true

Foliar, Broadcast, Ground (min. 10 GPA 2 ) or aerial (min. 5 GPA) 50% WG [59639-147] 2.5 - 4.0 4 (0.078- 0.125) 4 (Maximum of 2 sequential applications) 16 (0.500) 1 Use as part of an Integrated Pest Management (IPM)

program 3

. Apply when conditions favor disease development, prior to infection. Continue applications on a 7 to 14- day retreatment interval. Do not apply more than 4 applications per season. Do not make more than 2 sequential applications. Do not apply more than 16 oz/A (0.500 lb ai/A) /season. Bushberries (Subgroup 13-07B ): aronia berry; blueberry, highbush; blueberry, lowbush; buffalo currant; Chilean guava; cranberry, highbush; currant, black; currant, red; elderberry; European barberry; gooseberry; honeysuckle (e dible); huckleberry; jostaberry; june berry (Saskatoon berry); lingonberry; native currant; salal; sea bu ckthorn; cultivars, varietie s and/or hybrids of these.

Foliar, Broadcast, Ground (min. 20 GPA) or aerial (min. 10 GPA) 50% WG [59639-147] 2.5 (0.078) 3 (Maximum of 2 sequential applications) 0.234 7 Apply when conditions favor disease development, prior to infection, in sufficient water to obtain thorough coverage of blossoms, foliage, and/or fruit. Continue applications on a 7 to 14-day retreatment interval. Do not apply more than 3 applications

per season.

1 Do not apply through any type of irrigation system.

2 Gallons per acre.

3 Apply in a regularly scheduled spray program in combination and/or rotation with other effective fungicides that

have different modes of action (i.e., non Group 3 fungicides). Avoid rotating with other sterol biosynthesis inhibitors, such as Folicur®, Nova®, Procure® or Tilt®.

4 For the control of white mold ( Sclerotinia sclerotiorum ), use 4 oz /A (0.125 lb ai/A) per application. Make first

application prior to infection, generally at row closure and/or first bloom and the second application 14 days later if conditions favor white mold development.

Conclusions . The submitted use directions are sufficien t to allow for evaluation of the available residue data relative to the proposed uses. The submitted field trial data reflect the proposed directions for potat o and blueberry.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 9 of 27 Since no spray adjuvants were used in the residue field trials on potatoes and bushberries, the “Crop Specific Directions/Restrictions and Li mitations” on the 50% WDG label for Bushberry, Subgroup 13-07 B and for Vegetable, Tuberous a nd Corm ,Subgroup 1C must state that no spray adjuvant should be used for these crops.

860.1300 Nature of the Residue - Plants

DP#s 361110 and 361111, 2/26/10, D. Soderberg (PP#6F7094) DP# 348234, C. Olinger, 2/11/08 (ROCKS memo) DP#s 348168 and 348206, 2/20/08, N. Dodd (PP#6F7094 and PP#6F7095) DP# 324541, 12/14/05, N. Dodd (PP#9E5052)

No new metabolism data were submitted with the subject petition. Metabolism studies with banana, canola, mandarin, pea, and wheat were previously submitted. The metabolism of metconazole was found to be similar in all crops investigated. The ma in metabolic route of metconazole in crops is via oxidative hydroxylatio n of the methylene groups, the methyl groups on the cyclopentyl ring, and possibly the cycl opentyl ring. In addition, monohydroxylation may occur at the various pro-chiral carbons of me tconazole, giving rise to chromatographically distinguishable stereoisomeric structures. The de tection of TA and triazo le conjugates in the canola, pea, and wheat studies indicates that the methylene group between the triazole and cyclopentyl rings is susceptible to oxidat ive hydroxylation. HED has determined that metconazole (parent) is the residue of con cern for both the toleran ce expression and risk assessment purposes in plants except for cer eal grains; the residues of concern for risk assessment in small grains are metconazole and the metabolite M11.

Conclusion: For the purpose of the subject petition, th e nature of the residue in plants is adequately understood.

860.1300 Nature of the Residue - Livestock

DP# 348234, C. Olinger, 2/11/08 (ROCKS memo) DP# 348168, 2/20/08, N. Dodd (PP#6F7094 and PP#6F7095)

No new metabolism data were submitted with the subject petition. Adequate ruminant and poultry metabolism studies are av ailable, and the data indicate that the metabolism of metconazole in ruminants and poultry is generally similar. The major routes of metabolism involve oxidation and/or oxidative hydroxylati on of the methyl group at position 2 of the cyclopentyl ring and oxidative hydroxylation of the phenyl ring. Glucuronic acid conjugates were observed in the goat metabolism studies, a nd sulfate ester conjugates were observed in the hen metabolism study. In addition, in the he n metabolism study with triazole-labeled metconazole, C-N bond cleavage releasing 1,2,4-T was observed. Based on the available data, HED has determined that the residue of con cern for the tolerance expression in livestock commodities is metconazole (parent)

. The residues of concern in livestock for purposes of the risk assessment are metconazole and Metabolites M1 (free and conjugated) , M12, and M31 (free and conjugated).Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 10 of 27 860.1340 Residue Analytical Methods

An adequate gas chromatographic method with a nitrogen-phosphorous detection (GC/NPD) for determining residues of metconazole parent isomers ( cis - and trans- metconazole) and a high performance liquid chromatogra phic (HPLC) method for determin ing residues of the triazole metabolites (1,2,4-triazole, triazole acetic aci d, and triazole alanine) are available for enforcement and data collection in plant commod ities. The GC/NPD method has been reviewed by ACB/BEAD and found to be adequate for enforc ing tolerances of metconazole (parent) in/on peanuts, stone fruit, and tree nuts (DP# 339995, Paul Golden, 2/15/08). The GC/NPD method is based on Valent Method RM- 41C-1, “Determination of cis- and trans -Metconazole in Crops utilizing a gas chromatograph with a nitrogen -phosphorous detector (GC/NPD)”. The HPLC method is based on the Morse Analytical Method #160, “Determination of 1,2,4-Triazole, Triazole Alanine and Triazole Acetic Acid Residues in Plant and Animal Matrices.”

Metconazole. Briefly, 10 g. ground samples are extracted for residues of metconazole parent isomer ( cis - and trans -metconazole) with acetonitrile:wa ter (70:30, v/v), homogenized for 15 minutes and vacuum filtered through 2 layers of Whatman No. 1 in a Buchner funnel to remove solids. Transfer extract in to a round bottom flask and rem ove the acetonirile by rotary evaporation in a water bath (<35 o C) to obtain an aqueous residue. Transfer the residues to a separatory funnel. Rinse the round bottom flask 3 times with hexane and add washings to the aqueous residues in the separatory funnel. Dr ain the aqueous (lower) phase back to the round bottom flask and the hexane layer into a clean se paratory funnel. Add 150 mL acetonitrile to the hexane extract in the separatory funnel. Shake funnel to allow the phases to separate. Drain the acetonitrile layer into a clean boiling flask. A dd 100 mL acetonitrile to the separatory funnel with the hexane. Repeat partition. Drain the acetonitrile layer into the round bottom flask and evaporate just to dryness by rotary evapor ation in a heated water bath. Add 5 mL methanol:water (1:1, v/v) to the flask, sonicate briefly to dissolve the residues and transfer to a preconditioned C 18 solid phase extraction (SPE) cartridge . Rinse the flask twice with 5 mL methanol:water (1:1, v/v) , each time adding to the C 18 SPE cartridge,

Elute the cis and trans -metconazole residues into a 100 mL boiling flask by rinsing the 500 mL flask with 2 x 5 mL methanol:water (5:1) and transferring to the C 18 SPE cartridge, Add 30 mL ethyl acetate to the 100 mL flask and rotary evaporate using a heat ed water bath. Add 60 mL to the aqueous residue to azeotrope the water. Continue to rotary evaporate just to dryness. (Additional ethyl acetate may be required to remove the water). Add toluene, stopper and sonicate briefly to dissolve the residues. Bring to final volum e (typically 2.0 mL for control samples and 10 mL for the samples fortified at 0. 05 ppm). Transfer aliquots to a GC vial for analysis by GC/NPD.

The limit of quantitation (LOQ) in blueberry, based on lowest level of method validation (LLMV) was 0.05 ppm for each metconazole isomer ( cis - and trans -metconazole); corresponding limits of detection (LODs) were 0.012 and 0.0092 ppm. In potato, the LOQ based on the LLMV was 0.02 ppm for each metconazole isomer ( cis - and trans -metconazole); corresponding limits of detection (LODs ) were 0.0037 and 0.0056 ppm.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 11 of 27 Triazole metabolites. Briefly, 5.0 g macerated samples are extracted for residues of triazole metabolites with 60 mL methanol:DI water (80: 20, v/v. Add 1 gram Celite® to the crude sample, mix thoroughly and vacuum filter through Whatman GF/A filter in Buchner funnel into a 125 mL filter flask. Rinse the extraction jar an d filter cake with about 5 mL methanol:DI water (80:20, v/v) into the filter flask. This is repe ated twice. Re-rinse filter cake with 5 mL methanol:DI water (80:20, v/v). Transfer ex tracts to a 100 mL graduated mixing cylinder and bring to volume (100 mL) with methanol:DI water (80:20, v/v). Process three 1 mL aliquots of extracts separately for each of the three metabol ites through the clean-up a nd derivitization steps. The 1,2,4-triazole aliquot is direc tly derivatized with dansyl chlo ride and partitioned into ethyl acetate. The triazole alanine aliquot is pur ified through Bond Elut SPE cartridge and then subjected to two derivatizations by esterification using HCl/buta nol followed by acylation using heptafluorobutyric anhydride. The triazole acetic acid a liquot is purified through a C 18 SPE cartridge and then derivatized us ing HCl/butanol esterification. A ll the three derivatized extracts are separately evaporated to dryness, redissolved in acetonitrile:water ( 30:70, v/v), and analyzed using high performance li quid chromatography.

The limit of quantitation (LOQ) in blueberry, ba sed on the lowest leve l of method validation (LLMV) was 0.02 ppm for each triazole metabolite (1,2,4-triazole, triazole alanine and triazole acetic acid); corresponding limits of dete ction (LOD) were 0.010, 0.0042, and 0.011 ppm. In potato, the LOQ based on the LLMV was 0.02 ppm for each triazole metabolite (1,2,4-triazole, triazole alanine and triazole acetic ac id); corresponding LODs were 0.0052, 0.0066 and 0.0078

ppm.

The methods for the determination of metconazole and triazole metabolites were validated prior to and in conjunction with the anal ysis of field trial samples. C ontrol samples of blueberry were fortified at 0.05, 0.20, and 2.0 ppm or 0.020 and 0.2 ppm for concurrent recoveries of metconazole ( cis -metconazole and trans -metconazole) and triazole metabolites (1,2,4-triazole, triazole alanine, and triazole ac etic acid), respectively. In ad dition, control samples of blueberry were fortified at 0.020, 0.04, 0.05, 0.20 and 2.0 ppm or 0.020, 0.20, and 2.0 ppm prior to analysis for method validation of metconazole ( cis -metconazole and trans -metconazole) and triazole metabolites (1,2,4-triazole, triazole alanine, and triazole acetic acid), respectively.

Conclusions . The residue analytical methods are adequate for data collection based on acceptable method validation and concurrent met hod recoveries. The GC /NPD method has been reviewed by ACB/BEAD and found to be adequa te as an enforcement method for metconazole.

860.1360 Multiresidue Methods

DP#s 361110 and 361111, 2/26/10, D. Soderberg (PP#6F7094) DP# 324541, 12/14/05, N. Dodd (PP#9E5052)

The Agency previously reviewed multiresidue methods data for metconazole. Based on its chemical structure, metconazole was not tested using FDA Multiresidue Method Protocols A, B, and G. In Protocol C testing, an acceptable GC response was obtained under Level I conditions using Module DG5, although the test was not conduc ted in accordance with Protocol C; testing was not conducted on an OV-17 or OV-225 column as required in Protocol C. Subsequent testing through Protocols D and E indicated that metconazole was poorly recovered throughMetconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 12 of 27 Florisil cleanup, and was not determined by electr on capture detection (E CD) with or without cleanup. Based the results of testing under Prot ocols D and E, metcona zole was not tested through Protocol F.

Conclusions : Under DP#s 361110 and 361111, it was conclude d that further work is required to test the separation of metcon azole on OV-17 and OV-225 columns under Protocol C; no further work on other protocols is needed. This deficiency remains outstanding.

860.1380 Storage Stability

Potato RAC samples from each of the crop fi eld trials were stored frozen at <-20 o C prior to extraction and analysis for up to 126 days (4.1 months) for metconazole and up to 622 days (20.4 months for triazole metabolites. Blueberry RAC samples were stored frozen at <-20 o C up to 281 days (9.2 months) for metconazole and 875 days (29 months) for triazole metabolites. The maximum storage intervals of samples from the cr op field trial associated with this petition are presented in Table 4. Concurrent storage stab ility studies were conducted for metconazole to support the sample storage durations and conditions of the submitted crop field trials. Untreated RAC samples were fortified with cis - and trans -metconazole at 2.0 ppm for each analyte in potato in blueberry. Samples were stored at <-20°C for 959 days for potato and for 281 days for blueberry, and were analyzed concurrently with fr eshly fortified samples. The results show that residues of metconazole are stab le in frozen potato and blue berry for up to 959 and 281 days, respectively. No 0-day data were provided.

Although samples for triazole metabolites determin ation were stored for 875 days (29 months) in blueberry and 622 days (20.4 months) in potato, the stability under frozen conditions were not determined. HED has concern for residues of free 1,2,4-triazole (T) and it s conjugates, triazole alanine (TA) and triazole acetic acid (TAA), in plants and animals as a result of the use of metconazole. Storage stability data were not su bmitted with this petition. However, data on the storage stability of triazoles were received by the Agency and are currently under review.

The storage durations and conditions of samples from the crop fiel d trials and processing studies submitted to support this petition are presented in Table 4.

Table 4. Summary of Storage Conditions and Durations of Samples from Crop Field Trial and Processing Studies. Matrix Analyte Storage Temperature (°C) Actual Storage Duration Interval of Demonstrated Storage Stability

Potato RAC (field trial (1x) Metconazole ( cis - and trans

metconazole) <-20 28-126 days (1-4.1 months) 959 days (31.5 months)

Triazole metabolites

(1,2,4-Triazole, Triazole alanine, Triazole acetic acid) 426-622 days (14-20.4 months) No data available

Potato RAC Processing study/(5x) Metconazole ( cis - and trans

metconazole) <-20 126 days (4.1 months) 959 days (31.5 months)Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 13 of 27 Table 4. Summary of Storage Conditions and Durations of Samples from Crop Field Trial and Processing Studies. Matrix Analyte Storage Temperature (°C) Actual Storage Duration Interval of Demonstrated Storage Stability

Triazole metabolites

(1,2,4-Triazole, Triazole alanine, Triazole acetic acid) 622 days (20.7 months) No data available

Blueberry Metconazole(cis- and transmetconazole) <-20 231-281 days (7.6-9.4 months) 281 days

Triazole metabolites

(1,2,4-Triazole, Triazole alanine, Triazole acetic acid) 812-875 days (27-29 months) No data available

Conclusions. The submitted storage stability data fo r metconazole are ade quate to support the subject crop field trials. Storage stability data for the processed commodities were not determined since metconazole residues in the ≥ 5x-treated RAC samples were <LOQ.

Interim storage stability data for T, TA, and TA A in canola seed, turnip roots, mustard greens, wheat straw, grain, and forage were referenced in connection with a prothioconazole petition (PP#4F6830; DP#s 303508 & 314517, S. Funk, 8/21/2006) . Interim storage stability data referenced in connection with a tritic onazole petition (PP#8F7420, DP#s 325956, 353372, and 360624, A. Acierto, 6/12/2009) suggest that residue s of T, TA and TAA are reasonably stable when stored frozen for up to one year in/on apples a nd wheat flour. (Study on peanut butter was to be repeated).

860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

DP#s 350367 and 353357, 9/18/08, N. Dodd (PP#7F7292)

No livestock feed items are associated with bushb erries. The only livestock feedstuffs associated with PP#0E7743 are processed potat o waste and potato culls; these commodities are fed to beef and dairy cattle but are not fed to poultry or sw ine. The dietary burdens of metconazole to livestock, based on reasonably balanced diets, were calculated in DP # 350367. Dietary burdens were 4.2 and 6.6 ppm for beef and dairy catt le, respectively, and 1.9 and 0.64 ppm for poultry and swine, respectively, and were calculated ba sed on tolerances for cereal grain, sugarcane, cotton, and soybean commodities.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 14 of 27 Residues of metconazole from the submitted crop field studies were below the LOQ in/on potatoes following application at 5x the proposed maximum seasonal application rate; therefore, quantifiable residues of metconazole are not ex pected in potato processed commodities.

Conclusions . The addition of the use of metconazole on tuberous and corm vegetables is not expected to alter the dietary exposure of ruminants because residues of metconazole were nonquantifiable in potato treated at 1x and 5x the maximum pr oposed seasonal application rate. Therefore, no changes are required in the cu rrent livestock tolerances for metconazole.

860.1500 Crop Field Trials

: 48143301.der1 (potato) 48143302.der (blueberry)

Potato

The IR-4, on behalf of the Agricultural Sta tions of Idaho, Michigan, North Dakota, North Carolina, and Oregon has submitted field trial data for metconazole on potatoes. Seventeen potato field trials were conducted during the 2007 growing season in NAFTA Zones 1 (NY and OH; 3 trials), 2 (NJ and MD; 2 trials), 3 (FL; 1 tr ial), 5 (WI and ND; 2 trials), 6 (TX; 1 trial), 8 (CO; 1 trial), 10 (CA; 1 trial), and 11 (WA and ID; 6 trials). At each test location, there was one untreated and one treated plot. The treated plots received four foliar broadcast applications of Metconazole 50 WDG Fungicide (V-10116 50WDG), a water dispersible granule formulation containing 50% of metconazole [mixture of cis - and trans -metconazole (85:15 ratio)] as the active ingredient. Applications we re made at a target rate of 0.125 lb ai/A per application in a spray volume of 16 - 29 gal/A. The total seasona l application rate was 0.50 lb ai/A. Retreatment intervals ranged from 6 to 8 days. No adjuvant was added to the spray mixtures in any of the crop field trials.

Single untreated control and duplicat e treated potato tuber samples were collected at pre-harvest intervals (PHIs) of 1-2 days. In addition, at two of the test sites (ID10 and ND10), one control and duplicate treated potato tuber sa mples were also collected at 3 or 4, 7 or 8, and 14 or 15 days after the last application to determine residue decline.

Following four foliar broadcast a pplications of metconazole at a total rate of 0.496-0.529 lb ai/A, total metconazole residues ( cis -metconazole and trans -metconazole) in/on potatoes harvested at 1- to 2-day PHIs were below the LOQ (<0.04 ppm). Based on these low residues, the tolerance spreadsheet for estimating tole rances was not utilized.

At two test sites (ID10 and ND10), additional sample s were harvested at 3 or 4, 7 or 8, and 14 or 15 days for residue decline studies. Residue de cline for metconazole, could not be determined since the residues from PHI 0 to 15 da ys were all <LOQ (<0.02 ppm for each of cis - and trans metconazole). Residues of 1,2,4-tria zole and triazole acetic acid in potato tubers were each <0.02 ppm; triazole alanine were obs erved in one (ND10) of the tw o sites for the residue decline studies although a clear pa ttern of decline is not clear. The av erage (uncorrected) residues of TAMetconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 15 of 27 were 0,022, 0.026, 0.027 and 0.026 ppm at PHI 1, 3, 7, and 14 days, respectively. Residue in the corresponding control was reported as 0.013 ppm.

The results of the potato field tr ials are summarized in Table 5.

Table 5. Summary of Residue Data from Potato Fi eld Trials with a Metconazole Formulation (WDG). Commodity Total Applic. Rate

(lb ai/A) End-use Product PHI 2 (days) Residue Levels (ppm) 1

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

cis -Metconazole

Tuber 0.496-0.529 V-10116 50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

trans -Metconazole

Tuber 0.496-0.529 V-10116 50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

1,2,4-Triazole

Tuber 0.496-0.529 V-10116 50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

Triazole Acetic Acid

Tuber 0.496-0.529 V-10116 50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

Triazole Alanine

Tuber 0.496-0.529 V-10116 50 WDG 1-2 34 <0.020 0.075 0.075 0.031 0.016

Total 3

Tuber 0.496-0.529 V-10116 50 WDG 1-2 34 <0.040 <0.040 <0.040 <0.040 NA

1 Residues of total metconazole calculated as the sum of the cis- and trans- isomers. The LOQ was 0.04 ppm for potato

2 All studies had PHIs of 1 day except for one study with a PHI of 2 days

. 3 Residues of total metconazole calculated as the sum of the cis- and trans- isomers. The LOQ was 0.04 ppm for potato.

Conclusions: Pending review of the submitted triazole storage stability data, the submitted potato field trial data for metconazole are adequate to fulfill data requirements.

The number and locations of field trials ar e in accordance with OPP Guideline 860.1500 for potato, the representative crop for the tuberous and corm vegetable subgroup 1C, and the use pattern of the field trials ade quately reflects the proposed use pattern for tuberous and corm vegetables. Following four foliar broadcast appli cations of metconazole at a total rate of 0.496- 0.529 lb ai/A, total metconazole residues ( cis -metconazole and trans -metconazole) in/on potatoes harvested at 1- to 2-day PHIs were below the LOQ (<0.04 ppm). Residue decline could not be determined for metconazole because all cis - and trans -metconazole residues were below the LOQ. Based on these low residues, the tole rance spreadsheet for setting tolerances was not utilized. The available field trial data will suppo rt a tolerance of 0.04 ppm for tuberous and corm vegetables subgroup 1C, reflecting the combined LOQs of the enforcement method of 0.02 ppm for each of the cis- and trans- isomers of metconazole.

Residues of 1,2,4-triazole and triazole acetic acid in potato tubers were each <0.02 ppm. In 9 of the 17 field trials, residues of tr iazole alanine were detected in the treated samples at 020-0.075 ppm (uncorrected); residues in the control were 0.006-0.069 ppm. In the residue decline study, residues of triazole alanine were observed in one of two sites, although a clear pattern of declineMetconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 16 of 27 could not be determined. The average triazole alanine residues (uncor rected) over the 14-day period ranged from 0.022-0.027 ppm and 0.013 pp m in the correspond ing control.

Blueberry

The IR-4 submitted field trial data for metconazo le residues in/on blueberry. Eleven blueberry field trials were conducted duri ng the 2006 growing season; five tr ials in the United States on high bush blueberries in NAFTA Re gions 2 (NJ and NC; 3 trials), 5 (MI; 1 trial), and 12 (OR; 1 trial); six trials in Canada on low bush blue berries in NAFTA Regions 1 (New Brunswick; 1 trial), 1A (Nova Scotia; 3 trials ), 5A (Quebec; 2 trials). At each test location, there was one untreated and one treated plot. The treated plots received three foliar directed (high bush) or foliar broadcast (low bush) applications of V-10116 50WDG, a 50% water dispersible granular formulation of metconazole (a mixture of cis - and trans -metconazole (85/15 ratio) as the active ingredient). Applications were made at a target rate of 0.08 lb ai/A pe r application for a total seasonal rate of 0.24 lb ai/A. Th e first application was made at the bloom stage followed by retreatment intervals at 14 and 7 days before harvest. No adjuvant was added to the spray mixtures. Single control and duplicate treated samples of blueberries were harvested from each plot at preharvest intervals (PHI) of 6-8 days. At two of the test sites (06-MI32 and 06-NS01), one control and duplicate treated blueberry samples were al so harvested at approximately 0, 1, 3, and 10 days after the last a pplication to determine residue decline.

Following three foliar applicati ons of metconazole at a tota l rate of 0.240-0.265 lb ai/A, metconazole residues ( cis -metconazole and trans -metconazole) in/on blueberry at PHIs 6- to 8- day were <0.010-0.326 ppm. Average metconazole residues in/on blueberr y were 0.303 ppm.

In the 06-MI32 and 06-NS01 residue decline trials, total mean metconazole residues declined steadily at longer post-treatment intervals in/on blueberry. For the 06-MI32 trial, total metconazole residues declined from a mean of 0.293 ppm at 0 day PHI to 0.183 ppm by 10 day PHI in highbush blueberries. For the 06-NS01 tria l, total metconazole residues declined from a mean of 0.302 ppm at a 0-day PHI to 0.115 ppm by the 11-day PHI in lowbush blueberries Residues of the triazole metabolites were be low the LOQ (<0.02 ppm) in/on all blueberry samples.

The available field trial data will support a tolerance of 0.40 ppm for bushberry subgroup 13-07B as calculated utilizing the tolerance spreadsheet in the Agency’s Guidance for setting Pesticide Tolerances Based on Field Trial Data (Appendix I).

The results of the blueberry field tr ials are summarized in Table 6.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 17 of 27 Table 6. Summary of Residue Data from Blueberr y Field Trials with a Metconazole Formulation (WDG). Commodity Total Applic. Rate

(lb ai/A) End-use Product PHI (days) Residue Levels (ppm) 1

n Min. Max. HAFT 2 Mean 3 Std. Dev.

cis -Metconazole

Berries 0.240-0.265 V-10116 50 WDG 6-8 22 <0.05 0.263 0.246 0.110 0.1

trans -Metconazole

Berries 0.240-0.265 V-10116 50 WDG 6-8 22 <0.05 0.063 0.056 0.051 0.0

1,2,4-Triazole

Berries 0.240-0.265 V-10116 50 WDG 6-8 22 <0.02 <0.02 <0.02 <0.02 NA

Triazole Acetic Acid

Berries 0.240-0.265 V-10116 50 WDG 6-8 22 <0.02 <0.02 <0.02 <0.02 NA

Triazole Alanine

Berries 0.240-0.265 V-10116 50 WDG 6-8 22 <0.02 <0.02 <0.02 <0.02 NA

Total 4

Berries 0.240-0.265 V-10116 50 WDG 6-8 22 <0.10 0.326 0.303 0.160 0.1

1 Residues less than the LOQ were considered to be the LOQ for calculations. The lowe st level of method validation (LLMV) is 0.05 ppm for isomers of metconazole and 0.02 ppm for metabol ites. Residue levels includ e residues of metconazole and metabolites. No conversio n factors were applied.

2 HAFT = highest average field trial.

3 Mean and standard deviations were calculated by the study au thor. Does not incl ude additional sampling intervals collected fo r the residue decline study.

4 Residues of total metconazole calculated as the sum of the cis- and trans- isomers. The LOQ was 0.04 ppm 0.10 ppm for blueberry.

Conclusions : Pending review of the submitted triazole storage stability data, the submitted blueberry field trial data for metconazole are adequate to fulfill data requirements.

The number and locations of field trials are in accordance with the requirements of OCSPP Guideline 860.1500 for blueberry, the represen tative crop of the bushberry subgroup 13-07B, and the use pattern of the field tr ials adequately reflects the proposed use pattern for bushberries. Following three foliar applicati ons of metconazole at a tota l rate of 0.240-0.265 lb ai/A, metconazole residues ( cis -metconazole and trans -metconazole) in/on blueberry at PHIs 6- to 8- day were <0.010-0.326 ppm. Residues of cis - and trans -metconazole decl ined with time.

The available field trial data will support a tolerance of 0.40 ppm for bushberry subgroup 13-07B as calculated utilizing the tolerance spreadsheet in the Agency’s Guidance for setting Pesticide Tolerances Based on Field Trial Data (Appendix I).

Residues of the triazole metabolites were be low the LOQ (<0.02 ppm) in/on all blueberry samples.

860.1520 Processed Food and Feed

48143301.der2Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 18 of 27 : Potato

IR-4 submitted a processing study for metconazole on potato. In two additional plots conducted in WA and TX field sites, a 50% WG formulati on of metconazole was applied to potatoes at the exaggerated rates of 5x or 6.2x the maximum proposed seasonal application rate for tuberous and corm vegetables. Four foliar broadcast applicat ions were made at 0.625 lb ai/A per application for a total seasonal rate of 2.5 lb ai/A (5x). An additional application was made at the TX trial site with a total seasonal rate of 3.1 lb ai/A (6.2x) due to scheduling at the processing facility. Potatoes were harvested at a 1-day PHI and proc essed into flakes/granules, chips, and wet peel by the University of Idaho Food Technology Ce nter (Caldwell, ID) or the Texas A&M University Food Protein Research and Devel opment Center (Bryan, TX) using simulated commercial procedures. Adequate descriptions of the processing procedures, including material balance summaries, were provided.

Potato samples were analyzed for residues of metconazole isomers ( cis- and trans -metconazole) and the triazole metabolites (T, TA, and TAA) using adequate methods. The LOQs were 0.04 ppm for metconazole (0.02 ppm for each isomer), and 0.02 ppm for each of the triazole analytes. Sample storage conditions and durations are report ed in Table 4. Adequate concurrent storage stability data were submitted to support the samp le storage conditions and durations for analysis of metconazole; however, no storage stability data are available to support analysis for the triazole metabolites.

Total metconazole residues ( cis -metconazole and trans -metconazole) in/on pot atoes harvested at 1- to 2-day PHIs were below the LOQ (<0.04 ppm). Because residues were below the LOQ in/on potatoes treated at ~5x the maximum pr oposed seasonal application rate, processed fractions (flakes/granules, chips, and wet peel) were not analyzed

. The theoretical concentration factor (based on loss of water; OPPTS 860.1520, Table 2) is 4.7x for pot ato flakes/granules.

Residues of the triazole metabolites 1,2,4-T a nd TAA were below the LOQ (<0.02 ppm) in/on potato RAC samples from both sites; residues of TA were detected in pot ato from one site at 0.066 ppm, and were below the LOQ at the other site. The residue data from the processing study is summarized in Table 7.

Table 7. Residue Data from Potato Processing Study with Metconazole.

RAC Processed Commodity Total Rate (lb a.i./A) PHI (days) Residues (ppm) Proc e
cis

metcon azole trans

metcon azole T TAA TA TA corrected Total

metcon azole cis

metcon azole trans

metcon azole T

Prosser, WA; 2007 (07-WA33) Potato Tuber (RAC) 2.498 1 <0.020 <0.020 <0.020 <0.020 0.066 0.027 <0.040 -- -- -- Flakes NA NA NA NA NA NA NA NC NC NC Chips NA NA NA NA NA NA NA NC NC NC Wet peel NA NA NA NA NA NA NA NC NC NC Weslaco, TX; 2007 (07-TX28) Potato Tuber (RAC) 3.137 1 <0.020 <0.020 <0.020 <0.020 <0.020 -- <0.040 -- -- -- Flakes NA NA NA NA NA NA NA NC NC NC Chips NA NA NA NA NA NA NA NC NC NC Wet peel NA NA NA NA NA NA NA NC NC NC NA = Not analyzed. The LOQ was 0.020 ppm for metconazole and metabolites.

1 NC = Not calculated; processe d fractions were not analyzed.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 19 of 27 Conclusions . Residues were below the LOQ in/on pot ato tubers following application of the WDG formulation at an exaggera ted rate of 2.5 or 3.1 lb ai/A (5x or 6.2x the proposed seasonal application rate). An acceptable method was used for quantitation of resi dues in potato tubers.

Adequate storage stability are available to suppo rt the sample storage conditions and durations for samples of potato tuber (RAC) for metconazole isomers ( cis -metconazole and trans

metconazole). The stability of the metabolites 1,2 ,4-triazole, triazole acetic acid, and triazole alanine under frozen conditions was not determin ed. Potato processed fractions were not analyzed.

The submitted potato processing study is acceptabl e to satisfy data requirements. Because residues of metconazole were below the LOQ in/ on samples of potato treated with metconazole

at ≥ 5X the maximum proposed seasona l rate, analysis of processe d samples is not required. HED concludes that quantifiable residues of metconazole in pota to processed commodities are not expected, and separate tolerances are not needed.

Available potato processing data for another triazole containing fungi cide (difenoconazole) suggests that residues of difenoc onazole do not concentrate in chips or granules/flakes (<0.01 ppm; 0.5x average processing factor) but conc entrate in wet peel (<0.01 and 0.03 ppm in 1x samples, and 0.04 and 0.32 ppm in 5x samples; 4x av erage processing factor). Residues of 1,2,4- T and TAA were below the LOQ in/on all samples of potato RAC and its processed commodities. Residues of TA were 0.02 ppm in /on potato RAC samples treated at 1x, and 0.03 and 0.05 ppm in/on potato RAC samples treated at 5x. The processing data indicate that TA do not concentrate in chips (<0.01-0.02 ppm; 0.4x av erage processing factor) or wet peel (<0.01 ppm; 0.4x average processing factor) but concen trate in/on granule/fl akes (0.01-0.05 ppm; 1.2x average processing factor). No storage stability data are avai lable for the tri azoles 1,2,4-T, TA, and TAA. (PP#6F7115, DP# 371264, W. Wassell, 8/9/07).

860.1650 Submittal of Analytic al Reference Standards

An analytical standard for metconazole, with an expiration date of 9/1/2015, is currently available in the EPA National Pesticide Standa rds Repository (persona l communication between T. Cole, ACB, and Versar, e-mail, 1/25/11).

860.1900 Field Accumulation in Rotational Crops

DP#s 361110 and 361111, 2/26/10, D. Soderberg (PP#6F7094) DP#s 348168 and 348206, 2/20/08, N. Dodd (PP#6F7094 and PP#6F7095)

No new field studies have been submitted. The earlier reviews required that end-use labels include plant-back restrictions of 30 days for leafy vegetables and Brassica leafy vegetables and 120 days for all remaining crops other than those with labeled uses. This requirement has been fulfilled and the statement now a ppears in the master label.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 20 of 27 860.1550 Proposed Tolerances

Tolerances are currently established for metconazole residues on plant commodities at levels ranging from 0.01-18 ppm and for residues of me tconazole at 0.04 ppm in meat byproducts of cattle, goats, horses and sheep, and eggs [ 40 CFR §180.617]. No tolerances have been established for swine commodities.

Permanent tolerances have been proposed by IR -4 for the combined residues of the fungicide metconazole in/or on the tuberous and corm ve getables subgroup 1C at 0.02 and the bushberry subgroup 13-07B at 0.35 pp m in/on bushberries.

For purposes of the tolerance expression, HED has determined that the residue of concern is metconazole (the sum of cis- and trans- isomers) for both primary and rotational crops and for livestock commodities. The tolerance expression for metconazole in 40 CFR §180.617(a)(1) should be stated according to HED’s Interi m Guidance on Tolerance Expression (5/27/09, S. Knizer) as follows:

Tolerances are established for residues of metconazole , 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 onl y metconazole [5-[(4-chlorophenyl)methyl]-2,2- dimethyl-1-(1 H -1,2,4-triazol-1-ylmethyl)cyclope ntanol] as the sum of its cis - and trans -isomers.

Adequate crop field trial data reflecting the proposed use patterns were submitted for purposes of establishing tolerances on the tuberous and corm vegetables subgroup 1C and the bushberry subgroup 13-07B. The tolerance spreadsheet in the Agency’s Guidance for Setting Pesticide Tolerances Based on Field Trial Data was utilized in determining the appropriate tolerance level for bushberries. The tolerance spreadsheet was no t used to calculate the tolerance for tuberous and corm vegetables because residues in potato were below the LOQ (<0.04 ppm). The proposed tolerance of 0.02 ppm for tuberous and corm vegetables is too low. The tolerance should be established at 0.04 ppm, reflecti ng the combined LOQs of the metconazole enforcement method of 0.02 ppm for each of the cis - and trans - isomers of metconazole. The proposed tolerance of 0.35 ppm for bushberries is also too low; a tolerance must be proposed at 0.40 ppm.

Based on the results of the potato processing st udy, in which residues of metconazole were <LOQ in potatoes following application at ≥ 5x the maximum proposed seasonal rate, tolerances for the processed commodities of potato are not needed.

There are currently no establ ished Codex, Canadian, or Mexican maximum residue limits (MRLs) for metconazole on potato or blueberry. An International Residue Limit (IRL) status sheet is attached (Appendix I).

The proposed and recommended tolerances for metc onazole as a result of the subject action are presented in Table 8. The proposed tolerances should be revised to reflect the approved tolerance definition sp ecified above, and the correct comm odity definition and trecommended tolerance levels as specified in Table 8.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 21 of 27 Table 8. Tolerance Summary for Metconazole. Commodity Proposed Tolerance (ppm) Recommended Tolerance (ppm) Comments ( correct commodity definition ) 40 CFR §180.617(a)(2)

Tuberous and Corm Vegetable subgroup 1C 0.02 0.04 Vegetable, tuberous and corm, subgroup 1C Bushberry subgroup 13-07B 0.35 0.40

References

DP Number: 324541 Subject: Metconazole. Request for a Tole rance on Imported Bananas. Summary of Analytical Chemistry and Residue Data. Petition Number 9E05052. From: N. Dodd To: M. Waller Date: 12/14/05 MRIDs: 44721506, 44721507, 44721508, 44721509, 44721510, and 44721511

DP#s: 303508 & 314517 Subject: Prothioconazole. Pe tition for Establishment of Tolerances for Use on Barley, Oilseed (Except Sunflower and Safflo wer) Crop Group, Dried Shelled Pea and Bean (Except Soybean) Crop Subgroup, Pea nut, Rice, and Wheat. Summary of Analytical Chemistry and Residue Data. PP#4F6830. From: S. Funk To: L. Coppolino Date: 8/21/06 MRIDs: 46246139, 46246141-46246150, 46246201-46246211, 46246213-46246227, 46477701-46477704

DP Number: 371264 Subject: PP#6F7115; Difenoconazole . Petition for Establishment of Tolerances on Fruiting Vegetables, Pome Fruit, Tuberous and Corm Vegetables, and Imported Papaya. Summary of Analytical Chemistry and Residue Data. From: W. Wassell and M. Sahafeyan To: D. Rosenblatt and Shaja Brothers Dated: 8/9/07 MRID(s): 46950215-46950237Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 22 of 27 DP Number: 339992 Subject: Review of Proposed Tolerance En forcement Methods for Metconazole. ACB Project #: B07-18. From: P. Golden To: P. Deschamp Dated: 2/08/08 MRID(s): 46902216, 46902217, 46665405, and 46665407

DP Number: 339995 Subject: Review of Proposed Tolerance En forcement Methods for Metconazole. ACB Project #: B07-19. From: P. Golden To: P. Deschamp Dated: 2/15/08 MRID(s): 46901704 and 46901706

DP Number: 348234 Subject: Metconazole. Report of the Residues of Concern Knowledgebase Subcommittee. From: C. Olinger To: Risk Assessment Team, RAB3 Dated: 2/11/08 MRID(s): None

DP Numbers: 348168, 348206 Subject: Metconazole. Petition for Establishm ent of Tolerances for Use on Small Grains, Stone Fruits, Tree Nuts, Peanuts, Soyb eans, and Sugar Beets. Summary of Analytical Chemistry and Residue Data. PP#6F7094 and PP#6F7095. From: N. Dodd To: L. Coppolino/M. Waller Date: 2/20/08 MRIDs: 46665405, 46665407, 46901704-46901712, 46901717, 46901902-46901909, 46901912-46901915, 46902216-46902232, and 46902301-46902305

DP Numbers: 350367 and 353357 Subject: Metconazole. Petition for the Establ ishment of a Tolerance for Use on Canola. Summary of Analytical Ch emistry and Residue Data. From: N. Dodd To: T. Keigwin/M. Waller Date: 9/18/08 MRIDs: 47287801 and 47406901

DP Numbers: 325956, 353372, and 360624 Subject: Triticonazole. Application for New S eed Treatment Uses on Cereal Grains (Except Rice) (PP#8F7420). Summary of Analytical Chemistry and Residue
Data. From: A.M. AciertoMetconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 23 of 27 To: Shaja Joyner Date: 6/12/09

DP Numbers: 361110 and 361111 Subject: Metconazole. Response to Data Gaps for Conditional Registration on Small Grains, Stone Fruits, Tree Nuts, Peanuts, Soybeans, and Sugar Beets. Summary of Analytical Chemistry and Residue Data. From: D. Soderberg To: M. Waller Date: 2/26/10 MRIDs: 47621601, 47628002-47628006, and 47790001

F. DOCUMENT TRACKING

RDI: A. M. Acierto (3/2/2011); Chem Team (3/8/2011); S. Funk (3/24/2011) Petition Number: 0E7743 DP#: 380990 PC Code: 125619

Attachments:

Appendix I: International Resi due Limits Status Sheet Appendix II: Tolerance A ssessment Calculations.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 24 of 27 Appendix 1



### International Residue Limits

Metconazole (PC Code 125619; 03/08/11) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3
40 CFR 180.617: Plants/Livestock : Metconazole [5-[(4- chlorophenyl)methyl]-2,2-dimethyl-1- (1H-1,2,4-triazol-1- ylmethyl)cyclopentanol] as the sum of its cis- and trans- isomers None None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Vegetable, tuberous and corm, subgroup 1C 0.04

Bushberry subgroup 13-07B 0.4

Completed: M. Ne gussie; 03/10/2011

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated co mmodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 25 of 27 Appendix II. Tolerance Assessment Calculations.

The dataset used to estab lish a tolerance for metconazo le on bushberry subgroup 13-07B consisted of field trial data repr esenting application rate s of 0.240-0.265 lb ai/A (3 applications at ~0.08 lb ai/A/application) with a 6- to 8-day PHI. As specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data (SOP), the field trial a pplication rates and PHIs are generally within 25% of the maximum labe l application rate and minimum label PHI, respectively. The residue values that were entered into the tolerance spreadsheet (August 2009 version) are provided in Table II-1.

Because 4 of the 22 field trial sample results (18%) were below the LOQ (LOQ = 0.10 ppm for total metconazole residues), maximum likelihood estimation (MLE) procedures were needed to impute censored values. The dataset was larg e (>15 samples). Visual inspection of the lognormal probability plot (Figure II-1) and the results from the approximate Shapiro-Francia test statistic (Figure II-2) indicated that the dataset was reasonably lognormal.

Since the field trial data for metconazole on blue berry represent a large dataset (i.e., more than 15 samples) and are reasonably lognormal, th e minimum of the 95% upper confidence limit (UCL) on the 95 th percentile and the point estimate of the 99 th percentile should be selected as the tolerance value. Using the rounding proced ure as outlined in the SOP, the 95% UCL on the 95 th percentile and the point estimate of the 99 th percentile round to th e value 0.40 ppm (Figure II-2); therefore, 0.40 ppm is the recommended tolerance level for metconazole on bushberries.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 26 of 27 Table II-1. Residue data used to ca lculate tolerance for metconazole on blueberry. Regulator: EPA

Chemical: Metconazole Crop: Blueberry (MLE)

PHI: 7 Days App. Rate: 0.234 lb ai/A

Submitter: IR-4

MRID Citation: MRID 48143302 Residues of Metconazole (ppm)

0.072 1

0.082 1

0.124

0.137

0.204

0.180

0.089 1

0.095 1

0.156

0.244

0.140

0.140

0.326

0.280

0.170

0.142

0.141

0.143

0.170

0.191

0.126

0.115

1 Value calculated using the MLE spreadsheet.Metconazole Summary of Analytical Chemistry and Residue Data DP#: 380990

Page 27 of 27 Figure II-1. Lognormal probability plot of metconazole field trial data for blueberry.

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 y = 0.3856x - 1.917
R2 = 0.9757**Concentrations**

**Percentiles Lognormal Probability Plot** 

**EPA Metconazole Blueberries (MLE) 7 Days 0.234 lb ai/A IR-4...**

Figure II-2. Tolerance spreadsheet summary of metconazole field tria l data for blueberry.

**Regulator:** EPA

**Chemical:** Metconazole

**Crop:** Blueberries (MLE)

**PHI:** 7 Days

**App. Rate:** 0.234 lb ai/A

**Submitter:** 48143302

**n:** 22

**min:** 0.07

**max:** 0.33

**median:** 0.14

**average:** 0.16

**95th Percentile 99th Percentile 99.9th Percentile**

0.30 0.35 0.40
(0.35) (0.40) (--)

0.30 **0.40** 0.50

**(0.40)** (0.50) (--)

0.40

**0.35**

**0.80**

0.9757 p-value > 0.05 : Do not reject lognormality assumption **Approximate**
**Shapiro-Francia**
**Normality Test**

**EU Method I**

**Normal**

**UCLMedian95th**

**95/99 Rule**

**EU Method II**

**Distribution-Free**

**Mean+3SD**