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                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                       
                                                  OFFICE OF CHEMICAL SAFETY AND
                                                                                               POLLUTION PREVENTION
                                                                               

MEMORANDUM
  
Date:	23-October-2014   				

Subject:	Metconazole.  Petition for the Establishment of Permanent Tolerances and Registration for Use on the Pea and Bean, Dried Shelled, except Soybean, Subgroup 6C and the Sunflower Subgroup 20B; Expansion of the Canola Tolerance to the Rapeseed Subgroup 20A; and Conversion of the Established Stone Fruit and Tree Nut Crop Groups to the Stone Fruit Group 12-12 and the Tree Nut Group 14-12.  Summary of Analytical Chemistry and Residue Data.

PC Code: 125619
DP Barcode: D419223
Decision No.: 487580
Registration No.: 59639-147
Petition No.: 4E8244
Regulatory Action: Section 3 Registration
Risk Assessment Type: NA
Case No.: NA 
TXR No.: NA
CAS No.: 125116-23-6 
MRID No.: See Below
40 CFR: 180.617

From:	Nancy Dodd, Chemist
	Risk Assessment Branch III (RAB3) 
	Health Effects Division (HED; 7509P)

Through:	Steve Funk, Senior Chemist
	RAB3/HED (7509P)
	
To: 	Barbara Madden, RM#05
	Registration Division (7505P)





Summary of Submitted Residue Chemistry Studies
OCSPP 860 Series Guideline
MRID Number
Title
860.1500 
49297801
Corley, J. (2013) Metconazole:  Magnitude of the Residue on Bean (Dry).  Laboratory Project ID:  10388.10-JRF02.  Unpublished study prepared by IR-4 Project.  201 p.
860.1500
49297802
Corley, J. (2013) Metconazole:  Magnitude of the Residue on Pea (Dry).  Laboratory Project ID:  10389.10-JRF03.  Unpublished study prepared by IR-4 Project.  173 p.
860.1500
860.1520
49297803
Corley, J. (2013) Metconazole:  Magnitude of the Residue on Sunflower.  Laboratory Project ID:  10390.10-JRF01.  Unpublished study prepared by IR-4 Project.  237 p.


                               Table of Contents

1.0	Executive Summary	5
2.0	Regulatory Recommendations	8
2.1	Data Deficiencies/Data Needs	9
2.2	Tolerance Considerations	9
2.2.1	Enforcement Analytical Method	9
2.2.2	Recommended Tolerances	9
2.2.3	Revisions to Petitioned-For Tolerances	10
2.2.4	International Harmonization	10
3.0	Introduction	11
3.1	Chemical Identity	12
3.2	Physical/Chemical Characteristics	12
3.3	Pesticide Use Pattern/Directions for Use (860.1200)	14
4.0	Metabolite/Degradate Residue Profile	19
4.1	Nature of the Residue	19
4.1.1 	Summary of Plant Metabolism (860.1300)	19
4.1.2	Summary of Livestock Metabolism (860.1300)	20
4.1.3	Summary of Confined Rotational Crops (860.l850)	20
4.1.4	Summary of Metabolites and Degradates	21
4.2	Comparison of Metabolic Pathways	21
4.3	Residues of Concern Summary and Rationale	22
5.0	Residue Profile	24
5.1	Residue Analytical Methods (860.1340)	24
5.1.1	Data Collection Methods	24
5.1.2	Multi-Residue Methods (860.1360)	25
5.1.3	Tolerance Enforcement Methods	26
5.1.4	Submittal of Analytical Reference Standards (860.1650)	28
5.2	Storage Stability (860.1380)	29
5.3	Residue Data	32
5.3.1	Crop Field Trials (860.1500)	32
5.3.2	Field Rotational Crops (860.1900)	38
5.3.3	Processed Food and Feed (860.1520)	39
5.3.4	Meat, Milk, Poultry and Eggs (860.1480)	42
5.3.4.1	Dietary Burden	44
5.3.4.2	Estimated Secondary Residues in Livestock	45
5.3.5	Food Handling (860.1460)	46
5.3.6	Water, Fish, and Irrigated Crops (860.1400)	46
5.4	Food Residue Profile	46
6.0	Tolerance Derivation	47
Appendix A.  Tabular Summary of Metabolites	50
Appendix B.  Field Trial Geographic Distribution	52
Appendix C.  International Residue Limits Table	53
Appendix D.  OECD MRL Calculation Procedure Inputs/Outputs	55

  
1.0	Executive Summary

Metconazole [5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol] is a broad-spectrum triazole fungicide that works systemically by preventing spore formation and inhibiting mycelial growth.  Metconazole acts primarily as an inhibitor of ergosterol biosynthesis, thereby interfering with synthesis of fungal cell membranes and providing systemic seed and seedling protection.  

The Interregional Research Project No. 4 (IR-4), on behalf of the IR-4 Project and the Agricultural Experiment Stations of Montana, South Dakota, North Dakota, and Colorado (dry bean), Montana, South Dakota, Idaho, and North Dakota (dry pea), and Kansas, Montana, South Dakota and North Dakota (sunflower), requested the establishment of permanent tolerances and registration for use on the pea and bean, dried shelled, except soybean, subgroup 6C, and the sunflower subgroup 20B; expansion of the canola tolerance to the rapeseed subgroup 20A; and conversion of the established stone fruit crop group 12 and tree nut crop group 14 to the stone fruit crop group 12-12 and the tree nut crop group 14-12. 

Proposed Uses:  Metconazole 50 WDG Fungicide (EPA Reg. No. 59639-147) is a water-dispersible granule formulation containing 50% active ingredient (ai).  It is to be applied to crops in the pea and bean, dried shelled, except soybean, subgroup 6C; the sunflower subgroup 20B; the rapeseed subgroup 20A; the stone fruit crop group 12-12, and the tree nut crop group 14-12. 
Applications are to be made as broadcast foliar sprays in sufficient water for thorough coverage using ground equipment (including chemigation) or aerial equipment.  Depending on the crop and the targeted fungal disease, single application rates range from 0.0625-0.125 lb ai/A.  Depending on the crop, a maximum of one to four applications can be made with minimum retreatment intervals (RTIs) ranging from 7 to 14 days except for pecan (interval not specified) and pistachio (2-3 week interval); the yearly application rates range from 0.125 to 0.500 lb ai/A.  Preharvest intervals (PHIs) range from 14-35 days.  Immediate plant-back is allowed for barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, and those crops listed on the label.  A 30-day plant-back interval (PBI) is required for Brassica leafy vegetables and leafy vegetables.  A 120-day PBI applies to other crops.

Nature of the Residue in Primary Plants: The nature of the residue in crops in the pea and bean, dried shelled, except soybean, subgroup 6C; the sunflower subgroup 20B, the rapeseed subgroup 20A, the stone fruit crop group 12-12, and the tree nut crop group 14-12 is adequately understood based on metabolism studies on banana, canola, mandarin, pea, and wheat.  The metabolism of metconazole was similar in all crops investigated.  Metconazole (parent) is the residue of concern for the tolerance expression for primary and rotational crops.  Metconazole is the residue of concern for risk assessment purposes in primary and rotational crops except for cereal grains; the residues of concern for risk assessment in cereal grains (as both primary and rotational crops) are metconazole and the metabolite M11.  (See Section 4.3 and Appendix A.) 

HED also has concern for residues of free 1,2,4-triazole and its conjugates, triazolylalanine (TA) and triazolylacetic acid (TAA), in plants as a result of the use of metconazole.  However, because separate endpoints for these compounds have been established, exposure and risks from free triazole and its conjugates will be addressed separately.


Nature of the Residue in Livestock:  The nature of the residue in livestock (ruminants and poultry) is adequately understood.  The residue of concern for the tolerance expression in livestock commodities is metconazole.  The residues of concern in livestock for purposes of the risk assessment are metconazole and metabolites M1 (free and its glucuronic acid conjugate), M12, and M31 (free and its glucuronic acid conjugate).  (See Section 4.3 and Appendix A.)

HED also has concern for residues of 1,2,4-triazole, TA, and TAA in livestock as a result of the use of metconazole.  However, because separate endpoints for these compounds have been established, exposure and risks from free triazole and its conjugates will be addressed separately.

Enforcement Methods: An adequate gas chromatography method with nitrogen-phosphorus-detection (GC/NPD), Valent Method RM-41C-1-1, is available for enforcement of tolerances for residues of metconazole (cis- and trans- isomers) in plant commodities from the pea and bean, dried shelled, except soybean, subgroup 6C; the sunflower subgroup 20B, the rapeseed subgroup 20A, the stone fruit crop group 12-12, and tree nut crop group 14-12.  A confirmatory liquid chromatography/tandem mass spectrometry (LC/MS/MS) method, Method RM-41C-4, is available.  For both methods, the reported limit of quantitation (LOQ) is 0.02 ppm for each isomer in each matrix.
  
An adequate GC/NPD method is available for enforcement of tolerances for residues of metconazole (cis- and trans-isomers) in livestock commodities.  The enforcement method is a modified version of the German multiresidue method DFG S19.  An acceptable confirmatory procedure, gas chromatography/mass spectrometry (GC/MS), is included for the method.  The LOQ is 0.01 ppm for each isomer in each matrix, for an LOQ of 0.02 ppm for total metconazole residues.

Multiresidue Methods: Multiresidue methods data have been submitted for metconazole.  The multiresidue methods are not adequate for determining residues of metconazole for dietary exposure assessment.  The data (MRIDs 44721509 and 47790001) will be forwarded to the US FDA.

Storage Stability: Adequate storage stability data for cis- and trans-metconazole were previously submitted to support the storage conditions and durations of samples of raw agricultural and processed commodities from the previously submitted crop field trials and processing studies on stone fruit, tree nuts, and canola.  The currently submitted storage stability data for dry bean, dry pea, and sunflower are adequate to support the intervals of frozen storage from harvest to analysis for dry bean, dry pea, and sunflower seed, meal, and oil.  No corrections of residue values from the field trials or processing studies for loss of metconazole or triazole residues (TA in sunflowers and dry shelled beans/peas; 1,2,4-triazole, TA, and TAA in canola) are necessary.

Meat, Milk, Poultry, and Eggs: Based on the cattle feeding study and the calculated dietary burden based on the maximum reasonably balanced diet (Table 1 Feedstuffs, June 2008), no changes are required in the established livestock tolerances as a result of the proposed/expanded uses.  The established tolerances for meat byproducts of cattle, goat, horse, and sheep at 0.04 ppm and for egg at 0.04 ppm are adequate.  No tolerances are established for milk; fat and meat of cattle, goat, hog, horse, poultry, and sheep; or meat byproducts of hog and poultry since residues are not expected to occur in those commodities.  If additional uses increase the dairy cattle dietary burden, additional ruminant feeding studies conducted at higher rates may be needed.

Crop Field Trials: Adequate field trial data have been submitted for the pea and bean, dried shelled, except soybean, subgroup 6C and the sunflower subgroup 20B.  Field trials were conducted on dry beans, dry peas, and sunflowers.  The studies adequately reflect the proposed use patterns.  The number of field trials and geographic representations are adequate.  The residue data are supported by adequate storage stability data.  The analytical methods (the GC/NPD method adapted from Valent Method RM-41C-1 for metconazole and the LC/MS/MS method adapted from Morse Laboratories Meth-160 for TA) are adequate for analysis of the residues of concern.  Although triazole fungicides are typically monitored for residues of all three triazole metabolites (i.e., 1,2,4-triazole, TA, and TAA), HED previously concluded that only analysis for TA need be conducted in the subject studies (refer to HED's Chemistry Science Advisory Council minutes, 8/11/2010 meeting).

The previously submitted field trial data on canola, cherry, peach, plum, almond, and pecan are adequate to support the rapeseed subgroup 20A, the stone fruit subgroup 12-12, and the tree nut group 14-12.  The studies adequately reflect the proposed use patterns.  The number of field trials and geographic representation are adequate.  Adequate storage stability data are available to support the field trial data.  An adequate data collection method, the GC/NPD method RM-41C-1, was used to determine metconazole (cis- and trans- isomers) in canola, stone fruit, and tree nuts.  Residues of 1,2,4-triazole, TA, and TAA were determined in canola seed using an adequate LC/MS/MS method (Morse Laboratories Method 160).  Although stone fruit and tree nut samples were not analyzed for the triazole metabolites, field trial data for triazoles are not required for those petitions submitted in 2006.

Processing Studies:  Adequate processing studies have been conducted on canola, plums, and sunflowers. 

Canola:  Metconazole (the sum of cis- and trans-isomers) was non-detectable in/on canola seed, meal and refined oil samples reflecting treatment at a 5x rate; therefore, separate tolerances are not required for canola meal and oil.  Residues of 1,2,4-triazole were also not detectable in canola seed, meal and refined oil reflecting treatment at 5x.  Residues of TA and TAA do not concentrate in oil.  However, residues of TA and TAA concentrated in canola meal by 2.1x and 1.4x, respectively.

Plum:  Metconazole (the sum of cis- and trans-isomers) concentrates 2.3x in prunes.

Sunflower:  Metconazole (the sum of cis- and trans-isomers) does not concentrate in sunflower meal and oil.  Residues of TA concentrate 2.9x in sunflower meal, but do not concentrate in oil.  

Confined Accumulation in Rotational Crops:  The nature of the residue in rotational crops is adequately understood.   The metabolism of metconazole appears to proceed in rotational crops via similar mechanisms as in primary crops and to be more extensive than that observed in primary crops (banana, canola, mandarin, pea, and wheat).  The residue of concern for the tolerance expression in rotational crops is metconazole. The residue of concern for the risk assessment in rotational crops except small grains is metconazole; the residues of concern for the risk assessment in small grains as rotational crops is metconazole and the metabolite M11.

Since the confined study indicated the potential for quantifiable metconazole residues in rotated crop commodities, limited field rotational crop trials were conducted.  

Field Accumulation in Rotational Crops: Adequate limited field rotational crop studies have previously been submitted.  Based on the limited field rotational crop trials, rotational crop restrictions are included on the registered Metconazole 50 WDG labels (EPA Reg. No. 59639-147).  The same rotational crop restrictions on the proposed Metconazole 50 WDG label (as shown in Section 3.3) are adequate.

International Tolerances: There are no Codex maximum residue limits (MRLs) established for metconazole.
 
Residue definitions are harmonized with Canada.  Tolerances in the US are established for residues of metconazole, including its metabolites and degradates.  In both the US and Canada, compliance with the tolerance/MRL levels is determined by measuring only metconazole.
  
The recommended tolerance levels are harmonized with Canada.
  
A human health risk assessment is forthcoming.

2.0	Regulatory Recommendations

Provided the Section B/label is revised as requested, there are no residue chemistry considerations that would preclude granting the requested registration and establishing the recommended tolerances for metconazole on the pea and bean, dried shelled, except soybean, subgroup 6C and the sunflower subgroup 20B; expansion of the canola tolerance to the rapeseed subgroup 20A; and conversion of the established tolerances and registrations for the stone fruit crop group 12 and tree nut crop group 14 to the stone fruit crop group 12-12 and the tree nut crop group 14-12.  The specific tolerance recommendations are discussed in Section 2.2, and label modifications are discussed in Section 2.3.


2.1	Data Deficiencies/Data Needs

Data gaps to be addressed prior to a tolerance being established/registration allowed

Refer to Section 2.3 for label modifications.

Data that may be required for future uses

If additional uses increase the dairy cattle dietary burden, additional ruminant feeding studies conducted at higher rates may be needed.

2.2	Tolerance Considerations

2.2.1	Enforcement Analytical Method

An adequate GC/NPD method, Valent Method RM-41C-1-1, is available for enforcement of tolerances for residues of metconazole (cis- and trans- isomers) in plant commodities.  A confirmatory LC/MS/MS method, Method RM-41C-4, is available.  For both methods, the reported LOQ is 0.02 ppm for each isomer in each matrix.  The method has been validated by the ACB/BEAD and was found adequate for enforcing tolerances for residues of metconazole per se in plant commodities.  No radiovalidation data were submitted for method RM-41C-1-1; however, HED has concluded that because the extraction solvent used for the proposed enforcement method is similar to the aqueous organic solvent mixtures used in the plant metabolism studies, radiovalidation of the method is not required.

An adequate GC/NPD method is available for enforcement of tolerances for residues of metconazole (cis- and trans-isomers) in livestock commodities.  The enforcement method is a modified version of the German multiresidue method DFG S19.  The LOQ is 0.01 ppm for each isomer in each matrix, for an LOQ of 0.02 ppm for total metconazole residues.  An acceptable confirmatory procedure (GC/MS) is included for the method.  The method has been validated by ACB/BEAD and was found adequate for enforcing tolerances for residues of metconazole (cis- and trans-isomers) in/on livestock commodities.  No radiovalidation data were submitted; however, because DFG S19 is an established multiresidue method, these data are not required.

2.2.2	Recommended Tolerances
 
The petitioner's proposed residue definition (tolerance expression) is adequate and is consistent with the S. Knizner memo dated 5/27/09.  The petitioner requested the establishment of tolerances for residues of metconazole, including its metabolites and degradates.  Compliance with the tolerance levels specified below is to be determined by measuring only 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.


Table 2.2.2.  Tolerance Summary for Metconazole.
Commodity
                     Established/Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments 
                        (correct commodity definition)
 Pea and bean, dried shelled, except soybean, subgroup 6C
                                     0.15
                                     0.15
The 0.15 ppm level harmonizes with the Canadian MRL. Based on calculations using the OECD calculator for dry pea (0.08 ppm) and <0.04 ppm residues for dry bean, a tolerance of 0.08 ppm would have been recommended.
 Sunflower subgroup 20B
                                      0.9
                                      0.7

 Rapeseed subgroup 20A
                                     0.04
                                     0.08
The 0.08 ppm level harmonizes with the Canadian MRL. 
 Fruit, stone, group 12-12
                                      0.2
                                      0.2

 Nut, tree, group 14-12
                                     0.04
                                     0.04

 Canola seed
                                     0.04
                                     None
Remove upon establishment of rapeseed subgroup 20A tolerance.
 Fruit, stone, group 12
                                     0.20
                                     None
Remove upon establishment of fruit, stone, group 12-12 tolerance.
 Nut, tree, group 14
                                     0.04
                                     None
Remove upon establishment of nut, tree, group 14-12 tolerance
 Pistachio
                                     0.04
                                     None
Remove upon establishment of nut, tree, group 14-12 tolerance


2.2.3	Revisions to Petitioned-For Tolerances

The proposed tolerance on the sunflower subgroup 20B is 0.9 ppm; HED is recommending a decrease to 0.7 ppm based on the OECD tolerance calculation procedures with two studies combined as not independent.

The proposed tolerance for the rapeseed subgroup 20A is 0.04 ppm.  HED is recommending an increase to 0.08 ppm to harmonize with the Canadian MRL. Based on calculations using the OECD calculator for canola, a tolerance of 0.04 ppm would have been recommended.

2.2.4	International Harmonization

There are no Codex maximum residue limits (MRLs) established for metconazole.
 
Residue definitions are harmonized with Canada.  Tolerances in the US are established for residues of metconazole, including its metabolites and degradates.  In both the US and Canada, compliance with the tolerance/MRL levels is determined by measuring only metconazole.
  
The recommended tolerance levels are harmonized with Canada.
  
Refer to the International Residue Limits (IRL) table in Appendix C.

2.3	Label Recommendations

860.1200 Directions for Use

The Section B/label must be revised to include the following statement for the dried shelled pea and bean, except soybean, subgroup 6C:  "Do not apply to cowpea or field pea used for livestock feed."

The Section B/label should be revised to include the interval between applications for pecan and pistachio.

3.0	Introduction

Metconazole is a broad-spectrum triazole fungicide that works systemically by preventing spore formation and inhibiting mycelial growth.  Metconazole acts primarily as an inhibitor of ergosterol biosynthesis, thereby interfering with synthesis of fungal cell membranes and providing systemic seed and seedling protection.


3.1	Chemical Identity

Table 3.1.  Metconazole Nomenclature.
Chemical Structure

 
                  cis-isomer                                                trans-isomer

Common name
Metconazole
Company experimental name
KNF-S-474m (Kureha); BAS 555 F (BASF); V-10116 (Valent)
IUPAC name
(1RS,5RS;1RS,5SR)-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol
CAS name
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol
CAS #
125116-23-6 (cis- and trans-isomers)
115850-27-6 (cis-isomer)
115850-28-7 (trans-isomer)
End-use product/EP
Metconazole 50 WDG Fungicide (EPA Reg. No. 59639-147), a water-dispersible granule formulation containing 50% active ingredient.
Quash 50 WDG (EPA Reg. No. 59639-147), also known as V-10116 50 WDG


3.2	Physical/Chemical Characteristics

Metconazole is a granule formulation with a low vapor pressure.  It is more soluble in organic solvents than in water.  The physicochemical properties are reported in Table 3.2 below.
 
Table 3.2. Physicochemical Properties of the Technical Grade Metconazole
Parameter
Value
Reference*
(MRID)	
Molecular weight (g/mole)
319.8
--
Melting point/range (°C)
100.0-108.4°C (using Electrothermal Digital Melting Point Apparatus) (AC900,768 technical grade)
44721505
pH
5.81 at 25ºC (1% aqueous suspension)
46808402
Relative density (20°C)
Asked for Density (g/cm[3])
1.14 (relative density to water at 4°C, using capillary-stoppered, density-specific gravity bottle)    (Lot No. AC 8879-140B)
44721505
Water solubility (mg/L at 20ºC)
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)
44721505
Solvent solubility (g/L at 20ºC)
Solvent
                                  Metconazole
                                      cis
                                     trans
44721505

acetone
                                      363
                                      251
                                      117


methanol
                                      403
                                      294
                                      117


dichloromethane
                                      481
                                      343
                                      141


ethyl acetate
                                      260
                                      173
                                     90.0


propanol
                                      132
                                     86.6
                                     46.7


toluene
                                      103
                                     66.2
                                     38.0


hexane
                                     1.40
                                     0.929
                                     0.483

Vapor pressure at 20°C (Pa)
Using gas-saturation method:
< 1.23x10[-][5] Pa or 9.23 x 10[-][8] mm Hg (metconazole)
< 1.04x10[-][5] Pa or 7.80 x 10[-][8] mm Hg (cis-isomer)
< 1.96x10[-][6] Pa or 1.47 x 10[-][8] mm Hg (trans-isomer)
44721505
Dissociation constant (pKa)
11.38+-0.03 and 1.06+-0.03 (in water at 29.1°C using spectrophotometric method; Lot No. AC 8879-140B) 
44721505
Octanol/water partition coefficient, Log(KOW)
At 20 ºC (using flask shaking method):
 Kow (log Kow) = 7090+-989 (3.85) (Lot No. AC 8879-140B)  (TGAI)
 Kow (log Kow) = 7150+-803 (3.85) (cis-isomer, CL 354,801)
 Kow (log Kow) = 6800+-1700 (3.8) (trans-isomer, CL 354,802)
44721505
* DP #256877, Shyam Mathur, Ph.D., 9/12/2000 and DP #329168, Shyam Mathur, Ph.D., 7/13/07.


3.3	Pesticide Use Pattern/Directions for Use (860.1200)

Table 3.3.  Summary of Proposed Directions for Use of Metconazole.
Applic. Timing, Type, and Equip.
                                  Formulation
                                [EPA Reg. No.]
                                 Applic. Rate 
                                   (lb ai/A)
                           Max. No. Applic. per Year
                           Max. Yearly Applic. Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                       Use Directions and Limitations[1]
            Dried Shelled Pea and Bean, Except Soybean, Subgroup 6C
[Dried cultivars of bean (Lupinus); bean (Phaseolus) (includes field bean, kidney bean, lima bean (dry), navy bean, pinto bean, tepary bean); bean (Vigna) (includes adzuki bean, blackeyed pea, catjang, cowpea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean); broad bean (dry); chickpea; guar; lablab bean; lentil; pea (Pisum) (includes field pea); pigeon pea]
Postemergence; Broadcast foliar sprays;
Ground or aerial equipment; Chemigation
                                    50% WDG
                                  [59639-147]
                                 0.08 - 0.125
                                       2
                                     0.25
                                      21
Apply when conditions favor disease development and prior to infection. 
A second application may be made at a 7- to 10-day interval.  
Apply in sufficient water to obtain thorough coverage of the plant.
Apply with ground equipment in a minimum of 20 gallons per acre (GPA) or by air in a minimum of 5 GPA.
Two applications may be made sequentially.  Use a non-group 3 fungicide in alternation with Metconazole 50 WDG Fungicide.  
                             Rapeseed Subgroup 20A
(Borage; crambe; cuphea; exchium; flax seed; gold of pleasure; hare's ear mustard; lesquerella; lunaria; meadowfoam; milkweed; mustard seed; oil radish; poppy seed; rapeseed (canola varieties only); sesame; sweet rocket; cultivars, varieties and/or hybrids of these)
Broadcast foliar spray during flowering; ground or aerial equipment.
                                    50% WDG
                                  [59639-147]
                                 0.0625-0.125
                                       1
                                       
                                       
                                       
                                       
                                       
                                     0.125
                                      35
Make application between 20% and 50% bloom.  Apply in sufficient water to obtain thorough coverage of the plant.  Apply with ground equipment in 10-20 GPA or by air in a minimum of 5 GPA.
                         Stone Fruit, Crop Group 12-12
(Black cherry; capulin; Chinese Jujube; Nanking cherry; sweet cherry; tart cherry; cultivars, varieties and/or hybrids of these)
Broadcast foliar spray; 
ground  or 
aerial equipment

                                    50% WDG
                                  [59639-147]
                                  0.078-0.125
                                       3
                                       
                                     0.375
                                      14
Timing: 
For brown rot/blossom blight, green fruit rot/jacket rot, or cherry leaf spot, begin applications at green tip.  If conditions are favorable for disease development, make additional applications at full bloom and at petal fall.  

For fruit brown rot, make applications 14 to 21 days prior to harvest.  

For powdery mildew, follow the brown rot/blossom blight schedule; make additional applications on a 10-14 day interval until terminal growth ceases; application can be made after harvest.

Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage, and or fruit.

Apply with ground equipment in 100-400 GPA or by air in a minimum of 20 GPA.

Do not make more than 2 applications after petal fall.  
                         Stone Fruit, Crop Group 12-12
               (Apricot; Japanese apricot; nectarine and peach)
Broadcast foliar sprays; 
ground  or 
aerial equipment

                                    50% WDG
                                  [59639-147]
                                  0.078-0.125
                                       3
                                       
                                     0.375
                                      14
Timing: 
For brown rot/blossom blight, green fruit rot/jacket rot, scab, or shot hole, begin applications at early pink bud stage before infection occurs.  If conditions are favorable for disease development, make additional applications at full bloom and at petal fall.

For fruit brown rot, make applications 14-21 days prior to harvest.  

For powdery mildew, follow the brown rot/blossom blight schedule; make additional applications on a 10-14 day interval until terminal growth ceases.  Begin applications prior to disease development and continue at a 7-10 day interval.

For rust, begin application when bud tissue is susceptible to disease development (i.e., pink, white, or red bud).  If conditions are favorable for disease development, make a second application at full bloom or at petal fall.

Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage, and or fruit.

Apply with ground equipment in 100-400 GPA or by air in a minimum of 20 GPA.

Do not make more than 2 applications after petal fall.  
                         Stone Fruit, Crop Group 12-12
(American plum; beach plum; Canada plum; cherry plum; Chickasaw plum; Damson plum; Japanese plum; Klamath plum; plum; plumcot; prune plum; sloe)
Broadcast foliar spray; 
ground  or 
aerial equipment

                                    50% WDG
                                  [59639-147]
                                  0.078-0.125
                                       3
                                       
                                     0.375
                                      14
Timing: 
For brown rot/blossom blight and rust, begin applications at green tip.  If conditions are favorable for disease development, make additional applications at full bloom and at petal fall. 

For powdery mildew, follow the brown rot/blossom blight schedule; make additional applications on a 10-14 day interval until terminal growth ceases.

Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage, and or fruit.

Apply with ground equipment in 100-400 GPA or by air in a minimum of 20 GPA.

Do not make more than 2 applications after petal fall

Do not apply Metconazole 50 WDG Fungicide to "Stanley" type plums."  
                            Sunflower Subgroup 20B
(Calendula; castor oil plant; Chinese tallowtree; euphorbia; evening primrose; jojoba; niger seed; rose hip; safflower; stokes aster; sunflower; tallowwood; tea oil plant; vernonia; cultivars, varieties, and/or hybrids of these)
Postemergence; Broadcast foliar spray;
Ground or aerial equipment 
                                    50% WDG
                                  [59639-147]
                                 0.078 - 0.125
                                       2
                                     0.25
                                      21
Apply when conditions favor disease development and prior to infection. 
A second application may be made on a 7- to 14-day interval.  
Apply as a foliar spray in sufficient water to obtain thorough coverage of leaves.
Apply by ground in a minimum of 20 GPA or by air in a minimum of 5 GPA.
Two applications may be made sequentially.
Use a non-group 3 fungicide in alternation with Metconazole 50 WDG Fungicide.  
       Tree Nuts, Crop Group 14-12, Except Filbert, Pecan, and Pistachio
(African nut-tree; almond; beechnut; black walnut; Brazil nut; Brazilian pine; bunya; bur oak; butternut; Cajou nut; candlenut; cashew; chestnut; chinquapin; coconut; coquito nut; dika nut; English walnut; ginkgo; Guiana chestnut; heartnut; hickory nut; Japanese horse-chestnut; macadamia nut; mongongo nut; monkey-pot; monkey  puzzle nut; Okari nut; Pachira nut; peach palm nut; pequi; Pili nut; pine nut; Sapucaia nut; tropical almond; yellowhorn; cultivars, varieties and/or hybrids of these)
Broadcast foliar spray;
Ground or aerial equipment
                                    50% WDG
                                  [59639-147]
                                  0.078-0.11 
                                       
                                       4
                                       
                                     0.44
                                       
                                       
                                      25
Begin applications prior to disease development and continue at a 7 to 14 day interval throughout the year.

Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage and/or fruit.

Apply in 100-400 GPA with ground equipment or in a minimum of 20 GPA by air.

Do not make more than 2 applications after petal fall.
                              Filbert (Hazelnut)
Broadcast foliar spray;
Ground or aerial equipment
                                    50% WDG
                                  [59639-147]
                                     0.11 
                                       
                                       4
                                       
                                     0.44
                                       
                                       
                                      25
Begin applications starting at bud swell to bud break and continue at 10 or 14-day intervals.

Apply as a foliar spray in sufficient water to obtain thorough coverage of all branches.  

Apply in 100-400 GPA with ground equipment or in a minimum of 20 GPA by air.

Do not make more than 2 sequential applications before switching to a non-Group 3 fungicide for resistance management.
                                     Pecan
Broadcast foliar spray;
Ground or aerial equipment
                                    50% WDG
                                  [59639-147]
                                  0.078-0.11 
                                       
                                       4
                                       
                                     0.44
                                       
                                       
                                      25
Begin applications when leaves reach one-half mature size.  Continue to make scab applications if scab model predicts need.

Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage and/or fruit.

Apply in 100-400 GPA with ground equipment or in a minimum of 20 GPA by air.

Do not make more than 2 sequential applications before switching to a non-Group 3 fungicide for resistance management.
                                   Pistachio
Broadcast foliar spray;
Ground or aerial equipment
                                    50% WDG
                                  [59639-147]
                                     0.125
                                       4
                                       
                                    0.500 
                                      25
Apply prior to onset of disease development and continue on a 2 to 3 week interval.

Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage and/or fruit.

Apply in 100-400 GPA with ground equipment or in a minimum of 20 GPA by air.

Do not make more than 2 sequential applications before switching to a non-Group 3 fungicide for resistance management.
1 Rotational Crop Restrictions: 
Immediate plant-back is allowed for barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, and those crops listed on the label.
A 30-day plant-back interval is required for Brassica Leafy Vegetables and Leafy Vegetables.
Do not plant any crop, except barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, Brassica Leafy Vegetables, Leafy Vegetables and those crops listed on the label, earlier than 120 days after applying Metconazole 50 WDG Fungicide.

Conclusions.  Metconazole 50 WDG Fungicide (EPA Reg. No. 59639-147) is to be applied to crops in the pea and bean, dried shelled, except soybean, subgroup 6C; the sunflower subgroup 20B; the rapeseed subgroup 20A; the stone fruit crop group 12-12, and the tree nut crop group 14-12.  Applications are to be made as broadcast foliar sprays in sufficient water for thorough coverage using ground equipment (including chemigation) or aerial equipment.  Depending on the crop and the targeted fungal disease, single application rates range from 0.0625-0.125 lb ai/A.  Depending on the crop, a maximum of one to four applications can be made with minimum RTIs ranging from 7 to 14 days except for pecan (interval not specified) and pistachio (2-3 week interval); the yearly application rates range from 0.125 to 0.500 lb ai/A.  PHIs range from 14-35 days.  Immediate plant-back is allowed for barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, and those crops listed on the label.  A 30-day plant-back interval (PBI) is required for Brassica leafy vegetables and leafy vegetables.  A 120-day PBI applies to other crops.

Pending the following revisions, the Section B/label is adequate to allow evaluation of the residue data relative to the proposed use:

The Section B/label must be revised to include the following statement for the dried shelled pea and bean, except soybean, subgroup 6C:  "Do not apply to cowpea or field pea used for livestock feed."

The Section B/label should be revised to include the interval between applications for pecan.

4.0	Metabolite/Degradate Residue Profile

4.1	Nature of the Residue

4.1.1 	Summary of Plant Metabolism (860.1300)
DP# 403859, S. Funk, 2/14/13
DP# 348168, N. Dodd, 2/20/08
DP# 348234, C. Olinger, 2/11/08 (Report of the Residues of Concern Knowledgebase Subcommittee; ROCKS memo)
DP# 324541, N. Dodd, 12/14/05

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 main metabolic route of metconazole in crops is via oxidative hydroxylation of the methylene groups, the methyl groups on the cyclopentyl ring, and possibly the cyclopentyl ring.  In addition, monohydroxylation may occur at the various pro-chiral carbons of metconazole, giving rise to chromatographically distinguishable stereoisomeric structures.  The detection of TA and triazole conjugates in the canola, pea, and wheat studies indicates that the methylene group between the triazole and cyclopentyl rings is susceptible to oxidative hydroxylation.  HED determined that metconazole (parent) is the residue of concern for both the tolerance expression and risk assessment purposes in plants except for cereal grains; the residues of concern for risk assessment in cereal grains are metconazole and the metabolite M11.  

Conclusions.  The nature of the residue in crops in the pea and bean, dried shelled, except soybean, subgroup 6C; the sunflower subgroup 20B, the rapeseed subgroup 20A, the stone fruit crop group 12-12, and the tree nut crop group 14-12 is adequately understood based on metabolism studies on banana, canola, mandarin, pea, and wheat.  The metabolism of metconazole was similar in all crops investigated.  Metconazole (parent) is the residue of concern for the tolerance expression for primary and rotational crops.  Metconazole is the residue of concern for risk assessment purposes in primary and rotational crops except for cereal grains; the residues of concern for risk assessment in cereal grains (as both primary and rotational crops) are metconazole and the metabolite M11.

HED also has concern for residues of 1,2,4-triazole, TA, and TAA in plants as a result of the use of metconazole.  However, because separate endpoints for these compounds have been established, exposure and risks from free triazole and its conjugates will be addressed separately.

4.1.2	Summary of Livestock Metabolism (860.1300)
DP# 403859, S. Funk, 2/14/13
DP# 348234, C. Olinger, 2/11/08 (ROCKS memo)
DP# 348168, N. Dodd, 2/20/08

No new metabolism data were submitted with the subject petition.  Adequate ruminant and poultry metabolism studies are available.  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 hydroxylation 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, and sulfate ester conjugates were observed in the hen metabolism study.  In addition, in the hen metabolism study with triazole-labeled metconazole, C-N bond cleavage releasing 1,2,4-T was observed.  Based on the available data, HED determined that the residue of concern 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).  

Conclusions.  The nature of the residue in livestock (ruminants and poultry) is adequately understood.  The residue of concern for the tolerance expression in livestock commodities is metconazole.  The residues of concern in livestock for purposes of the risk assessment are metconazole and metabolites M1 (free and its glucuronic acid conjugate), M12, and M31 (free and its glucuronic acid conjugate).

HED also has concern for residues of 1,2,4-triazole, TA, and TAA in livestock as a result of the use of metconazole.  However, because separate endpoints for these compounds have been established, exposure and risks from free triazole and its conjugates will be addressed separately.

4.1.3	Summary of Confined Rotational Crops (860.l850)
DP# 403859, S. Funk, 2/14/13
DP# 348168, N. Dodd, 2/20/08 
DP# 348234, C. Olinger, 2/11/08 (ROCKS memo)

The nature of the residue in rotational crops is adequately defined.  The metabolism of metconazole appears to proceed in rotational crops via similar mechanisms as in primary crops and to be more extensive than that observed in primary crops (banana, canola, mandarin, pea, and wheat).  Two metabolites were identified in rotational crops that were not identified in primary crops, the stereoisomers M12 and M13.  HED noted that these metabolites reflect further oxidation of the methyl groups on the cyclopentyl ring of metconazole.  HED determined that the residues of concern for rotational crops are the same as for primary crops.  The residue of concern for the tolerance expression in rotational crops is metconazole. The residue of concern for the risk assessment in rotational crops except small grains is metconazole; the residues of concern for the risk assessment in small grains as rotational crops is metconazole and the metabolite M11.

The confined study indicated the potential for quantifiable metconazole residues in rotated crop commodities at 30- and 120-day plant-back intervals based on total radioactive residue (TRR) levels.  Metconazole was quantifiable (>0.01 ppm) at both PBIs in all rotational crop matrices except wheat grain.  Therefore, limited field rotational crop trials were conducted.

Conclusions.  The nature of the residue in rotational crops is adequately understood.  The metabolism of metconazole appears to proceed in rotational crops via similar mechanisms as in primary crops and to be more extensive than that observed in primary crops (banana, canola, mandarin, pea, and wheat).  The residue of concern for the tolerance expression in rotational crops is metconazole. The residue of concern for the risk assessment in rotational crops except small grains is metconazole; the residues of concern for the risk assessment in small grains as rotational crops is metconazole and the metabolite M11.

Since the confined study indicated the potential for quantifiable metconazole residues in rotated crop commodities, limited field rotational crop trials were conducted.

HED also has concern for residues of 1,2,4-triazole, TA, and TAA in rotational crops as a result of the use of metconazole.  However, because separate endpoints for these compounds have been established, exposure and risks from free triazole and its conjugates will be addressed separately.
  
4.1.4	Summary of Metabolites and Degradates

Refer to Appendix A for the summary table of chemical names and structures of parent and metabolites.  

4.2	Comparison of Metabolic Pathways
DP#441926, Y. Donovan, 3/12/08

The metabolism of metconazole was found to be similar in all crops investigated.  The main metabolic route of metconazole in crops is via oxidative hydroxylation of the methylene groups, the methyl groups on the cyclopentyl ring, and possibly of the cyclopentyl ring.  In addition, monohydroxylation may occur at the various pro-chiral carbons of metconazole, giving rise to chromatographically distinguishable stereoisomeric structures.  Further oxidation of the hydroxylated metabolites to form dihydroxylated or carboxylated derivatives was also observed in the mandarin study.  Finally glucose conjugation of the mono- and/or dihydroxylated metabolites was observed in all crops, yielding glucosides as terminal residues.  The detection of TA and triazole conjugates in the canola, pea, and wheat studies indicates that the methylene group between the triazole and cyclopentyl rings is susceptible to oxidative hydroxylation. 

The metabolism of metconazole appears to proceed in rotational crops via similar mechanisms as in primary crops and to be more extensive than that observed in primary crops (banana, canola, mandarin, pea, and wheat).

The metabolism of metconazole in ruminants and poultry was generally similar.  The major routes of metabolism involved oxidation and/or oxidative hydroxylation 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, and sulfate ester conjugates were observed in the hen metabolism study.  In addition, in the hen metabolism study with triazole-labeled metconazole, C-N bond cleavage releasing 1,2,4-T was observed.  
 
Based on the above descriptions, it is concluded that there are significant similarities in plant and livestock metabolism.  Metconazole was metabolized primarily through oxidative hydroxylation of the benzylic methylene and the methyl groups on the cyclopentyl ring, followed by conjugation with glucose.  The triazole metabolites (1,2,4-triazole, TA, and TAA) are also residues of concern.  

4.3	Residues of Concern Summary and Rationale
DP# 348234, C. Olinger, 2/11/08 (ROCKS memo)

A summary of the metabolites and degradates to be included in the risk assessment and tolerance expression are presented below in Table 4.3, followed by the rationale.  

Table 4.3.  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression
Matrix
Residues Included In Risk Assessment
Residues Included In Tolerance Expression
Plants


Primary and Rotational Crops, except Cereal Grains
Metconazole
Metconazole

Primary and Rotational Crops, Cereal Grains only
Metconazole and M11
Metconazole
Livestock
Ruminant
Metconazole; M1 and its glucuronic acid conjugate; M12; M31 and its glucuronic acid conjugate
Metconazole

Poultry


Drinking Water

Metconazole
Not Applicable
Note:  For all triazole-containing pesticides, the triazole-containing metabolites 1,2,4-T, TA, and TAA should also be included as residues of concern for risk assessment purposes only for plant and livestock commodities. Since these metabolites are common to the entire class of triazole-derivative fungicides and because of differential toxicity between the metabolites and the various parent compounds, risks associated with exposure to 1,2,4-T and to TA/TAA are addressed in separate risk assessment documents.

M1 = 5-[(4-chlorophenyl)methyl]-2-methoxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol;  M11 = 5-[(4-chlorophenyl)methoxyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M12 = 5-[(4-chlorophenyl)methyl]-2-carboxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M31 = (1S*,3R*,5S*)-3-hydroxy-cis-metconazole; 1,2,4-T = 1H-1,2,4-triazole; TAA = 1H-1,2,4-triazol-1-yl acetic acid; TA = 2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acid.  (See Appendix A.)

Rationale:

Plants
Metconazole is the major residue in plant commodities based on the nature of the residue and magnitude of residue studies in numerous crops, and is, therefore, a residue of concern for both tolerance expression and risk assessment purposes.  The registrant analyzed for residues of three metabolites, M11, M21, and M30, in cereal grain magnitude of residue studies.  M11 was found at levels exceeding 1 ppm in oat and wheat straw at the proposed application rate, and at higher relative amounts than observed in the nature of the residue studies.  Toxicity data are not available for M11, but it has a very similar chemical structure to the parent compound; therefore, without empirical data, it is assumed to have equal toxicity to the parent.  M11 needs to be included as a residue of concern for risk assessment purposes in cereal grains only.  M12 was a major residue in one of the rotational crop studies.  For any future uses with higher application rates that result in the need for rotational crop tolerances, HED should consider inclusion of the M12 metabolite for risk assessment purposes.

Livestock
The major residues observed in the ruminant and poultry metabolism studies were metconazole, M1, M12, and the glucuronic acid conjugates of M1 and M31.  Since the parent compound is the major residue in many of the livestock commodities, it is the only residue that needs to be included in the tolerance expression.  M1 is very similar to the parent with an additional hydroxyl group in the cyclopentanol ring, and M12 has a carboxylic acid group in the same ring.  The analytical method used in the feeding study is able to quantify the parent compound, M12, M1, and the glucuronic acid conjugate of M1.  Due to the chemical structural similarity to the parent and assumed equivalent toxicity, they should be included in the risk assessment.  The conjugated nature of the M31 metabolite mitigates the hazard concern to some extent; however, in the absence of toxicity data for the M31 metabolite, and the chemical structural similarity to the parent and assumed equivalent toxicity to the parent compound, HED recommends that M31 be included in the risk assessment only.

Triazoles
Metconazole is a member of the triazole-containing class of pesticides.  HED generally includes 1,2,4-T, TA, and TAA as residues of concern for risk assessment purposes for most triazole-containing pesticides.  1,2,4-T was a major residue found in some livestock commodities, and TA and TAA were significant residues in some plant metabolism studies.  Since these metabolites are common to the entire class of triazole-derivative fungicides and because of differential toxicity between the metabolites and the various parent compounds, risks associated with exposure to 1,2,4-T and to TA/TAA are addressed in separate risk assessment documents.

Water
In addition to the parent compound, three degradates were observed at greater than 10% of the applied dose in laboratory fate studies:  M30, hydroxymetconazole, and M13.  Metconazole is generally slow to degrade in the environment, and the environmental fate data suggest that microbial-mediated degradation is likely the major degradation pathway for the proposed terrestrial agricultural uses.  Although M30 was a major soil aerobic transformation product in

laboratory studies (approximately 13% of the applied dose), it was a not a significant degradation product in field dissipation studies (approximately 5% of the applied dose).  Hydroxymetconazole was a major photolysis product, but photolysis would not be a significant route of dissipation in the environment for the existing and proposed uses.  In addition, the loss of the chlorine in hydroxymetconazole lessens the hazard concern for the degradate.  M13 was observed in only one water soil system of the two tested and at a level barely over 10%, and is, therefore, not considered to be a significant degradate.  HED recommends only the parent compound be included in the drinking water exposure and risk assessments since exposure is not likely to be significantly different if the major degradates were included in the assessment.

5.0	Residue Profile

5.1	Residue Analytical Methods (860.1340) 

5.1.1	Data Collection Methods
49297801.der (dry bean)
49297802.der (dry pea)
49297803.de1 (sunflower)
49297803.de2 (sunflower processed commodities)

Dry Shelled Beans, Dry Shelled Peas, and Sunflower Seeds

Dry beans, dry peas, sunflower seeds, and sunflower processed commodities (meal and oil) were analyzed for residues of metconazole, determined as cis- and trans-metconazole, using a GC/NPD method adapted from Valent Method RM-41C-1 (dated 11/13/03).  For determination of cis- and trans-metconazole, samples were extracted with acetonitrile (ACN):water (70:30, v:v), filtered, and concentrated to remove the ACN.  Residues were partitioned into hexane and then into ACN.  The resulting ACN phases were combined with ethyl acetate, concentrated to dryness, and redissolved in methanol (MeOH):water (1:1, v:v), then subjected to solid phase extraction (SPE) through a C18 cartridge.  Residues were eluted with MeOH:water (5:1, v:v).  The eluate was evaporated to an aqueous remainder, combined with ethyl acetate, and evaporated to dryness.  Residues were then redissolved in toluene for GC/NPD analysis.  The validated LOQ is 0.02 ppm for each isomer.

Samples were analyzed for residues of the triazole metabolite triazole alanine (TA) using an LC/MS/MS method adapted from Morse Laboratories Meth-160 (dated 6/27/03).  For determination of TA, samples were extracted with methanol:water (80:20, v:v).  Following the addition of Celite, the extracts were vacuum filtered, rinsed, and brought to volume with methanol:water (80:20, v:v).  The resulting extract was purified by elution through a Bond Elut Certify II SPE cartridge.  The resulting eluate was reduced to dryness then subjected to two derivatizations:  an esterification using hydrochloric acid (HCl)/butanol and an acylation using heptafluorobutyric anhydride (HFBA).  The resulting extract was evaporated to dryness, and redissolved in ACN/water for analysis by LC/MS/MS.  The LOQ (determined as the LLMV) was 0.02 ppm. The limits of detection (LODs) were not reported.

Acceptable method validation and concurrent recovery data were reported for dry bean, dry pea, sunflower, and sunflower processed commodities at fortification levels of 0.02 and 0.2 ppm, thus validating the methods.  The fortification levels were adequate to bracket expected residue levels.  Although triazole fungicides are typically monitored for residues of all three triazole metabolites (i.e., 1,2,4-triazole, TA, and TAA), HED previously concluded that only analysis for TA need be conducted in the subject study (refer to HED's Chemistry Science Advisory Council minutes, 8/11/2010 meeting).

Canola

Samples of canola seed, meal, and oil were analyzed for residues of cis- and trans-metconazole using an adequate GC/NPD method (RM-41C-1).  The validated LOQ is 0.02 ppm for each metconazole isomer; the LOQ for total metconazole residues (cis- + trans-isomers) is 0.04 ppm.  Residues of 1,2,4-triazole, TA, and TAA were determined in canola seed, meal, and oil using an adequate LC/MS/MS method (Morse Laboratories Method 160).  The validated LOQ of the LC/MS/MS method in canola matrices was 0.01 ppm for triazole and TAA and 0.03 ppm for TA.  

Almond, Pecan, Cherry, Peach, and Plum

Samples were analyzed for residues of cis- and trans-metconazole using an adequate GC/NPD method (RM-41C-1).  The validated LOQ is 0.02 ppm for each metconazole isomer; the LOQ for total metconazole residues (cis- + trans-isomers) is 0.04 ppm.  

Conclusions.  An acceptable data collection method was used for determination of metconazole.  The method used for determination of metconazole (as cis- and trans-metconazole) in dry beans, dry peas, sunflower seeds, sunflower processed commodities (meal and refined oil), canola seed, canola processed commodities (meal and refined oil), almond nutmeat and hulls, cherries, peaches, plums, and prunes is a GC/NPD method adapted from Valent Method RM-41C-1.  The method has been adequately validated as a data collection method based on acceptable method validation and concurrent recovery data.  The LOQ of the method is 0.02 ppm for each analyte (cis- and trans-metconazole) in each matrix.

An acceptable data collection method was used for determination of triazoles.  Samples of dry beans, dry peas, sunflower seeds, and sunflower processed commodities (meal and oil) were analyzed for residues of TA using an LC/MS/MS method adapted from Morse Laboratories Meth-160 (dated 6/27/03).  Residues of 1,2,4-triazole, TA, and TAA were determined in canola seed using Method 160.  The method has been adequately validated as a data collection method based on acceptable concurrent recovery data.  The validated LOQ for dry beans, dry peas, and sunflower seeds, meal, and oil is 0.02 ppm.  The validated LOQ of the LC/MS/MS method in canola matrices was 0.01 ppm for triazole and TAA and 0.03 ppm for TA.  
 
5.1.2	Multi-Residue Methods (860.1360)
DP# 361110, D. Soderberg, 2/26/10 (MRID 47790001)
DP# 324541, N. Dodd, 12/14/05 (MRID 44721509)

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.  Testing of metconazole through protocols A, B and G is unnecessary because metconazole is not naturally fluorescent, is neither an N-methyl carbamate nor a substituted urea, nor does it possess a phenol or carboxylic acid group. 

An acceptable GC response (Protocol C) was obtained under Level I conditions using Module DG5, with a DB-1 (100% methyl siloxane) GC column.

Metconazole in peach (a non-fatty food) was tested through Protocol D using electron capture detection (ECD).  Metconazole could not be seen in the extract when tested using ECD without a cleanup step.  When tested through Fluorisil cleanup protocols C1 and C5, the residues appeared to be poorly recoverable through a Fluorisil column, but the recovery was largely obscured when residues were determined by ECD.  Thus, protocol D cannot be used with ECD, but a more selective NPD was not tried, so results were equivocal for possibilities with that or other more selective detectors.  

Metconazole in peach was also tested through Protocol E without cleanup.  Results again showed that a cleanup was needed when using an ECD.  Because of the previous results using protocol D, no attempt was made to try the Protocol E extract through a Fluorisil cleanup.  Because of these poor results, no attempt was made to test metconazole through Protocol F (for fatty foods).  

Conclusions.  Multiresidue methods data have been submitted for metconazole.  The multiresidue methods are not adequate for determining residues of metconazole for dietary exposure assessment.  The data (MRIDs 44721509 and 47790001) will be forwarded to the US FDA.
 
5.1.3	Tolerance Enforcement Methods
DP# 348168, N Dodd, 2/20/08
DP# 350367, N. Dodd, 9/18/08
DP# 389556, N. Dodd, 9/29/11
 
Plants

An adequate GC/NPD method, Valent Method RM-41C-1-1, is available for enforcement of tolerances for residues of metconazole parent isomers (cis- and trans- metconazole) in plant commodities from dry bean, dry pea, sunflower, canola, stone fruit and tree nuts.  A confirmatory LC/MS/MS method, Method RM-41C-4, is available. 

In Method RM-41C-1-1, homogenized samples are extracted with ACN:water (70:30, v:v) and filtered.  The extract is concentrated to remove ACN and partitioned with hexane (2x).  The resulting hexane phases are combined and partitioned with ACN (2x), and the ACN phases are combined with ethyl acetate, concentrated to dryness, and redissolved in MeOH:water (1:1, v:v).  The reconstituted extract is applied to a C18 SPE cartridge, and residues are eluted with MeOH:water (5:1, v:v).  The eluate is evaporated to aqueous, combined with ethyl acetate, evaporated to dryness, and then redissolved in toluene for GC/NPD analysis.  The reported LOQ is 0.02 ppm for each isomer.

In the confirmatory method RM-41C-4, homogenized samples are extracted with ACN/water, filtered, and concentrated to aqueous as above, then partitioned with hexane:ethyl acetate (9:1, v:v; 2x).  The resulting hexane/ethyl acetate phase is partitioned with ACN (2x) and the combined ACN phases are concentrated, mixed with ethyl acetate, and evaporated to dryness.  The residues are dissolved in MeOH:water (1:1, v:v) and subjected to C18 SPE cleanup as described above.  The resulting eluate is diluted with aqueous formic acid for LC/MS/MS analysis.  The LOQ, based on the submitted method validation data, is 0.02 ppm for metconazole (total of cis and trans-isomers).

Method RM-41C-1-1 has undergone an acceptable independent laboratory validation (ILV) with almond nutmeat fortified at 0.02-0.2 ppm.  Adequate recoveries were obtained for almond nutmeat, ranging from 93.5 to 111% for cis-metconazole and from 88.6 to 112% for trans-metconazole.  

No radiovalidation data were submitted for method RM-41C-1-1; however, HED has concluded that because the extraction solvent used for the proposed enforcement method is similar to the aqueous organic solvent mixtures used in the plant metabolism studies, radiovalidation of the method is not required.

Method RM-41C-1-1 was forwarded to ACB/BEAD for petition method review (DP #339994, N. Dodd, 5/29/07).  ACB/BEAD (DP# 339995, Paul Golden, ACB Project #B07-19, 2/15/08) reviewed the method and found it adequate as an enforcement method for determination of residues of metconazole (cis- and trans-isomers).  

Livestock

An adequate method is available for enforcement of tolerances for residues of metconazole (cis- and trans-isomers) in livestock commodities.  The enforcement method is a modified version of the German multiresidue method DFG S19.  The LOQ is 0.01 ppm for each isomer, for an LOQ of 0.02 ppm for total metconazole residues.  The method has been validated by ACB/BEAD and was found adequate for enforcement.

For milk, bovine muscle, and egg, samples are homogenized with water:acetone (1:2, v:v), then combined with ethyl acetate:cyclohexane (1:1, v:v), and sodium chloride.  An aliquot of the resulting organic phase is filtered through sodium sulfate and concentrated by evaporation, then reconstituted in ethyl acetate.  Sodium sulfate:sodium chloride (1:1, w:w) and cyclohexane are added, and the salts are allowed to precipitate.  For fat, samples are blended with ACN:acetone (9:1, v:v) and Calflo E and Celite as adsorbents, filtered, and combined with isooctane.  The extract is concentrated and redissolved in ethyl acetate:cyclohexane (1:1, v:v) as above.  For all matrices, the resulting ethyl acetate/cyclohexane fractions are subjected to sequential cleanup on a GPC column (residues eluted with ethyl acetate/cyclohexane) and a silica gel mini-column (residues eluted with acetone).  The resulting eluate is concentrated by rotary evaporation and reconstituted in ethyl acetate for GC/NPD or GC/MS (confirmatory procedure) analysis.  The method LOQ is 0.01 ppm for each isomer.

Method DFG S19 with modified extraction has undergone an acceptable ILV with grape, pea, wheat grain, rapeseed, milk, bovine muscle, egg, and bovine fat fortified with each isomer at 0.01 and 0.10 ppm.  Adequate recoveries, generally within the acceptable range of 70-120%, were obtained for all matrices at both fortification levels.

An acceptable confirmatory procedure (GC/MS) was included for the method.  No radiovalidation data were submitted; however, because DFG S19 is an established multiresidue method, these data are not required.

The method based on the German multiresidue method DFG S19 was forwarded to ACB/BEAD for a petition method review (DP #339992, N. Dodd, 5/29/07).  ACB/BEAD (Paul Golden, ACB Project #B07-18, 2/8/08) conducted a successful petition method review, indicating that the method is adequate for enforcing tolerances for residues of metconazole (cis- and trans-isomers) in/on livestock commodities.    

Conclusions.  An GC/NPD method, Valent Method RM-41C-1-1, is available for enforcement of tolerances for residues of metconazole (cis- and trans- isomers) in plant commodities from the pea and bean, dried shelled, except soybean, subgroup 6C; the sunflower subgroup 20B, the rapeseed subgroup 20A, the stone fruit crop group 12-12, and tree nut crop group 14-12.  A confirmatory LC/MS/MS method, Method RM-41C-4, is available.  For both methods, the reported LOQ is 0.02 ppm for each isomer in each matrix.  The method has been validated by ACB/BEAD and was found adequate for enforcing tolerances for residues of metconazole per se in plant commodities.  No radiovalidation data were submitted for method RM-41C-1-1; however, HED has concluded that because the extraction solvent used for the proposed enforcement method is similar to the aqueous organic solvent mixtures used in the plant metabolism studies, radiovalidation of the method is not required.

An adequate GC/NPD method is available for enforcement of tolerances for residues of metconazole (cis- and trans-isomers) in livestock commodities.  An acceptable confirmatory procedure, GC/MS, is included for the method.  The enforcement method is a modified version of the German multiresidue method DFG S19.  The LOQ is 0.01 ppm for each isomer in each matrix, for an LOQ of 0.02 ppm for total metconazole residues.  The method has been validated by ACB/BEAD and was found adequate for enforcing tolerances for residues of metconazole (cis- and trans-isomers) in/on livestock commodities.  No radiovalidation data were submitted; however, because DFG S19 is an established multiresidue method, these data are not required.

5.1.4	Submittal of Analytical Reference Standards (860.1650)
DP# 386784, A. Acierto, 7/27/11

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

5.2	Storage Stability (860.1380)
DP# 403859, S. Funk, 2/14/13
DP# 363016, D. Drew, 1/12/12 (47606601.der).
DP# 350367, N. Dodd, 9/18/08
DP# 348168, N. Dodd, 2/20/08.
49297801.der (dry bean)
49297802.der (dry pea)
49297803.de1 (sunflower)
49297803.de2 (sunflower processed commodities)

Rapeseed Subgroup 20A, Stone Fruit, and Tree Nuts 

The previously submitted storage stability data for cis- and trans-metconazole are adequate to support the storage conditions and durations of samples of raw agricultural and processed commodities from the previously submitted crop field trials and processing studies on stone fruit and tree nuts (DP# 348168, N. Dodd, 2/2/08) and canola (DP# 350367, N. Dodd, 9/18/08).  

Dry Bean, Dry Pea, and Sunflower

Storage stability data submitted for dry peas and sunflower meal and oil are reported in Table 5.2.1 below.

Table 5.2.1.	Stability of Metconazole in Frozen Dry Peas and Sunflower Meal and Oil.
Analyte
                                     Spike
                                     Level
                                     (ppm)
                              Storage interval[1]
                                    (days)
                      Fresh Fortification Recoveries (%)
                           Recovered Residues (ppm)
                            Mean Recovered Residues
                                     (ppm)
                               Mean Recovery (%)
                            Corrected % recovery[2]
                                   Dry Peas
                                cis-metconazole
                                      0.2
                                      419
                                      83
                                     NR[3]
                                      NR
                                      88
                                      106
                               trans-metconazole
                                      0.2
                                      419
                                      92
                                      NR
                                      NR
                                      79
                                      86
                                Sunflower Meal
                                cis-metconazole
                                      0.2
                                      306
                                     72.5
                            0.1791, 0.1494, 0.1545
                                    0.1610
                                     80.5
                                      111
                               trans-metconazole
                                      0.2
                                      306
                                     70.5
                            0.1507, 0.1406, 0.1459
                                    0.1457
                                     72.8
                                      103
                                 Sunflower Oil
                                cis-metconazole
                                      0.2
                                      305
                                      117
                            0.2347, 0.1972, 0.2233
                                    0.2184
                                      109
                                     93.2
                               trans-metconazole
                                      0.2
                                      305
                                     89.7
                            0.1951, 0.2060, 0.2437
                                    0.2149
                                      107
                                      119
[1] Interval from fortification to extraction.
[2] Corrected for recovery of freshly fortified samples.
[3] NR = not reported. 

The storage durations and conditions of samples from the crop field trials and sunflower processing study are presented in Table 5.2.2.  

Dry bean samples were stored frozen from harvest to extraction for a maximum of 258 days (8.5 months) prior to analysis for cis- and trans-metconazole and for a maximum of 192 days (6.3 months) prior to analysis for TA (Table 5.2.2).  Samples were analyzed within 1-5 days of extraction.  The available freezer storage stability data indicate that residues of cis- and trans-metconazole were stable when stored frozen at <=-20 °C in/on dry pea for up to 419 days (13.8 months), and residues of TA were stable when stored frozen in/on canola seed and wheat grain for up to 4 years.  

Dry pea samples were stored frozen from harvest to extraction for a maximum of 376 days (12.4 months) prior to analysis for cis- and trans-metconazole and for a maximum of 417 days (13.7 months) prior to analysis for TA (Table 5.2.2).  Samples were analyzed within 2-14 days of extraction.  The available freezer storage stability data indicate that residues of cis- and trans-metconazole were stable when stored frozen at <=-20 °C in/on dry pea for up to 419 days (13.8 months), and residues of TA were stable when stored frozen in/on canola seed and wheat grain for up to 4 years.  

Sunflower seed samples were stored frozen from harvest to extraction for a maximum of 423 days (13.9 months) prior to analysis for cis- and trans-metconazole and for a maximum of 472 days (15.5 months) prior to analysis for TA (Table 5.2.2).  Samples were analyzed with 1-18 days of extraction.  The available storage stability data indicate that residues of cis- and trans-metconazole were stable under frozen storage conditions for up to 26 months in/on soybean seed.  Residues of TA have been shown to be stable in/on canola seed and wheat grain under frozen conditions for up to 4 years.

In the sunflower processing study, samples were stored frozen from harvest/processing to extraction for 389-403 days (12.8-13.2 months) for sunflower seed (RAC) and 141-149 days (4.6-4.9 months) for meal and oil (Table 5.2.2).  Samples were analyzed within 1-14 days of extraction.  Processing took place within 290-293 days (9.5-9.6 months) of harvest.  The available storage stability data indicate that residues of cis- and trans-metconazole were stable under frozen storage conditions for up to 26 months in/on soybean seed.  To support the sample storage intervals for sunflower meal and oil, a concurrent storage stability study was conducted with the field trial study; the results are presented in Table 5.2.1.  The data demonstrate that residues of metconazole, determined as cis- and trans-metconazole, were stable in/on samples of sunflower meal and oil stored frozen for up to 306 and 305 days; no 0-day data were provided.  These data are acceptable to support the storage conditions and durations of samples from the submitted field trials; however, storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].  Residues of TA have been shown to be stable in/on canola seed, meal, and wheat grain under frozen conditions for up to 4 years and up to 8 months in canola oil.

Table 5.2.2.  Summary of Storage Conditions.
Matrix
                                    Analyte
                           Storage Temperature (°C)
                          Actual Storage Duration[1]
                                 (days/months)
                  Interval of Demonstrated Storage Stability
                                       
Bean, dry
                                  Metconazole
                                     ~-20
                                 148-258 days
                               (4.9-8.5 months)
Residues are stable for up to 419 days (13.8 months) in dry pea.[2]

                                      TA
                                       
                                  88-192 days
                               (2.9-6.3 months)
Residues are stable for up to 4 years in/on canola seed and wheat grain.[3]
Pea, dry
                                  Metconazole
                                     ~-20
                                       
                                 312-376 days 
                              (10.3-12.4 months)
Residues are stable for up to 419 days (13.8 months) in dry pea.[2]

                                      TA
                                       
                                 350-417 days 
                              (11.5-13.7 months)
Residues are stable for up to 4 years in/on canola seed and wheat grain.[3]
Sunflower seed

                                  Metconazole
                                     ~-20
                                 355-423 days 
                              (11.7-13.9 months)
Residues of cis- and trans-metconazole were stable under frozen storage conditions for up to 22 months in/on almond nutmeat.[4] 

                                      TA
                                     ~-20
                                 388-472 days 
                              (12.8-15.5 months)
Residues are stable for up to 4 years in/on canola seed and wheat grain.[3]
Sunflower, seed (for processing)
Metconazole
                                     ~ -20
                                   389 days 
                                 (12.8 months)
Residues of cis- and trans-metconazole were stable under frozen storage conditions for up to 22 months in/on almond nutmeat.[4] 
Sunflower, meal
                                       
                                       
                                   142 days 
                                 (4.7 months)
                           306 days (10.1 months)[5]
Sunflower, oil
                                       
                                       
                                   141 days
                                 (4.6 months)
                           305 days (10.0 months)[5]
Sunflower, seed
                                      TA
                                     ~ -20
                                   403 days
                                 (13.2 months)
Residues of TA are stable for up to 4 years in/on canola seed, meal, and wheat grain.[3]
Sunflower, meal
                                       
                                       
                                   149 days
                                 (4.9 months)
                                       
Sunflower, oil
                                       
                                       
                                   148 days 
                                 (4.9 months)
        Residues of TA are stable for up to 8 months in canola oil.[3]
[1] Field trial studies: Interval from harvest to extraction.  Dry bean samples were analyzed within 1-5 days of  extraction.  Dry pea samples were analyzed within 2-14 days of extraction.  Sunflower seed samples were analyzed within 1-18 days of extraction.  
  Sunflower processing study: Interval from harvest/processing to extraction.  In the processing study, samples were analyzed within 1-14 days of extraction.  Processing took place within 290-293 days (9.5-9.6 months) of harvest.
[2] Based on concurrent dry pea storage stability study (MRID 4929780).
[3] DP# 363016, D. Drew, 1/12/12 (47606601.der).
4  DP# 348168, N. Dodd, 2/20/08.
[5] Based on concurrent sunflower storage stability study (MRID 49297803).

Conclusions: The currently submitted storage stability data are adequate to support the intervals of frozen storage from harvest to analysis for dry bean, dry pea, and sunflower seed, meal, and oil.  The previously submitted storage stability data for cis- and trans-metconazole are adequate to support the storage conditions and durations of samples of raw agricultural and processed commodities from the previously submitted crop field trials and processing studies on stone fruit, tree nuts, and canola.  No corrections of residue values from the field trials or processing studies for loss of metconazole residues are necessary.

5.3	Residue Data

5.3.1	Crop Field Trials (860.1500)

DP# 350367, N. Dodd, 9/18/08; 47287801.de1 (Rapeseed subgroup 20A: canola)
DP# 371571, A. Acierto, 8/20/10 (Rapeseed subgroup 20A: canola)
DP# 348168, N. Dodd, 2/20/08 (stone fruits: cherry, peach, and plum; and tree nuts: almond and pecan)
DP# 361110, D. Soderberg, 2/26/10 (stone fruits: cherry, peach, and plum; and tree nuts: almond and pecan)
49297801.der (dry bean)
49297802.der (dry pea)
49297803.de1 (sunflower)

Shelled Dry Bean, Shelled Dry Pea, and Sunflower

As shown in Table 5.3.1, field trials were conducted on dry beans, dry peas, and sunflowers.  Refer to the geographic distribution tables in Appendix B.

As discussed in Section 5.1.1, samples from all field trials were analyzed for residues of metconazole, determined as cis- and trans-metconazole, using a GC/NPD method adapted from Valent Method RM-41C-1 (dated 11/13/03).  Samples were analyzed for residues of the triazole metabolite TA using an LC/MS/MS method adapted from Morse Laboratories Meth-160 (dated 6/27/03).  The LOQ (determined as the lowest level of method validation, LLMV) was 0.02 ppm for each analyte.  Acceptable method validation and concurrent recovery data (with recoveries generally within the acceptable range of 70-120%) were reported for dry bean, dry pea, and sunflower samples at fortification levels of 0.02 and 0.2 ppm, thus validating the methods as adequate data collection methods.  The fortification levels were adequate to bracket expected residue levels.  Although triazole fungicides are typically monitored for residues of all three triazole metabolites (i.e., 1,2,4-triazole, TA, and TAA), HED previously concluded that only analysis for TA need be conducted in the subject studies (refer to HED's Chemistry Science Advisory Council minutes, 8/11/2010 meeting).

As discussed in Section 5.2, the available storage stability data are adequate to support the storage conditions and intervals of samples from the field trials. All samples were maintained frozen at the testing facility, during shipping to the laboratory, and were stored frozen until analysis.  

Dry Bean

IR-4 has submitted field trial data for metconazole on dry beans.  Thirteen field trials were conducted in the United States during the 2010 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (NY; 1 trial), 5 (MI, NE, OH and WI; 6 trials), 7 (ND; 1 trial), 8 (KS; 1 trial), 9 (NM; 1 trial), 10 (CA; 1 trial) and 11 (ID and WA; 2 trials).  

Each trial consisted of one untreated plot and one treated plot.  Each treated plot received two foliar broadcast applications of the 50% water dispersible granule (WG) formulation of metconazole (Quash 50 WDG) at 0.119-0.133 lb ai/A/application for a total seasonal rate of 0.245-0.259 lb ai/A.  Applications were made at RTIs of 6-8 days using ground equipment in spray volumes of 15-51 gal/A.  A nonionic surfactant (NIS) was included in the spray mixtures for all applications.  Samples of dry bean were harvested at PHIs of 19-23 days.  At seven trials, samples were allowed to dry in the field for 3-12 days between harvest and collection.  No residue decline trials were conducted.
                                       
Individual sample (and per-trial average) total residues of metconazole (determined as the sum of cis- and trans-metconazole) were below the LOQ (<0.04 ppm) in/on all samples.  Corresponding residues of TA were <0.02-0.348 ppm (<0.02-0.346 ppm).  

Dry Pea

IR-4 has submitted field trial data for metconazole on dry peas.  Five field trials were conducted in the United States during the 2010 growing season in the NAFTA Growing Zones 5 (NE; 1 trial), 7 (ND; 1 trial), 10 (AZ; 1 trial) and 11 (ID and WA; 2 trials).  One pair of trials conducted in Velva, ND (Zone 7) are separated by <20 miles and have been assessed for independence; HED has concluded that these trials should be considered replicates.  The above field trial distribution incorporates this conclusion.

Each trial consisted of one untreated plot and one treated plot.  Each treated plot received two foliar broadcast applications of the 50% WG formulation of metconazole (Quash 50 WDG) at 0.124-0.131 lb ai/A/application for a total seasonal rate of 0.250-0.258 lb ai/A.  Applications were made at RTIs of 7-8 days using ground equipment in spray volumes of 15-31 gal/A.  An NIS was included in the spray mixtures for all applications.  Samples of dry pea were harvested at PHIs of 20-22 days.  At two trials, samples were allowed to dry in the field for 2-8 days between harvest and collection.  At one trial, additional samples were collected to assess residue decline at PHIs of 9, 14, and 28 days.

Individual sample (and per-trial average) total residues of metconazole (determined as the sum of cis- and trans-metconazole) were <0.04-<0.062 ppm (<0.04-<0.0562 ppm).  Corresponding residues of TA were 0.155-3.16 ppm (0.187-2.38 ppm).  In the residue decline trial, average total residues of metconazole (determined as the sum of cis- and trans-metconazole) were below the LOQ at the 9-day PHI, increased at the 14-day PHI (<0.0546 ppm), and then decreases to at or below the LOQ with increasing PHIs.  Corresponding average residues of TA were constant (0.172-0.202 ppm) at all sampling intervals.

Sunflower

IR-4 has submitted field trial data for metconazole on sunflowers.  Ten field trials were conducted in Canada and the United States during the 2010 growing season in the NAFTA Growing Zones 5 (ND and SD; 3 trials), 7 (ND and NE; 3 trials), 8 (NM; 1 trial) and 14 (SK; 3 trials).  One pair of trials conducted in Velva, ND were treated with the same spray solution, and, therefore, have been assessed for independence; it was concluded that these trials should be considered replicates.  The above field trial distribution incorporates this conclusion.

Each trial consisted of one untreated plot and one treated plot.  Each treated plot received two foliar broadcast applications of the 50% WG formulation of metconazole (Quash 50 WDG) at 0.121-0.130 lb ai/A/application for a total seasonal rate of 0.245-0.259 lb ai/A.  Applications were made at RTIs of 7-8 days using ground equipment in spray volumes of 10-35 gal/A.  An NIS was included in the spray mixtures for all applications.  Samples of sunflower were harvested at PHIs of 20-21 days.  At three trials, samples were allowed to dry in the field or were bagged and hung to dry for 6-17 days between harvest and collection.  At one trial, additional samples were collected to assess residue decline at PHIs of 7, 14 and 27 days.

Individual sample (and per-trial average) total residues of metconazole (determined as the sum of cis- and trans-metconazole) were <0.04-0.968 ppm (<0.04-0.440 ppm).  Corresponding residues of TA were <0.02-0.252 ppm (<0.02-0.148 ppm).  In the residue decline trial, total residues of metconazole (determined as the sum of cis- and trans-metconazole) and corresponding residues of TA in seed were at or below the LOQ in/on all samples; therefore, residue decline could not be determined.

Table 5.3.1.  Summary of Residues from Field Trials with Metconazole.
Crop Matrix
Analyte
                            Total Application Rate
                                   (lb ai/A)
                                  PHI (days)
                                     n[1]
                                Residues (ppm)
                                       
                                       
                                       
                                       
                                       
                                    Min.[2]
                                    Max.[2]
                                    LAFT[3]
                                    HAFT[3]
                                   Median[3]
                                    Mean[3]
                                     SD[3]
 BEAN, DRY (Proposed Use = 0.25 lb ai/acre total application rate, 21-day PHI)
Bean, dry
Metconazole (sum of cis- and trans-isomers)
                                  0.245-0.259
                                     19-23
                                      13
                                   <0.04
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      N/A

TA
                                  0.245-0.259
                                     19-23
                                      13
                                   <0.02
                                     0.348
                                   <0.02
                                     0.346
                                     0.021
                                     0.048
                                     0.090
 PEA, DRY (Proposed Use = 0.25 lb ai/acre total application rate, 21-day PHI)
Pea, dry
Metconazole (sum of cis- and trans-isomers)
                                  0.250-0.258
                                     20-22
                                       5
                                   <0.04
                                  <0.0620
                                   <0.04
                                  <0.0562
                                     0.040
                                     0.043
                                     0.007
Pea, dry
TA
                                  0.250-0.258
                                     20-22
                                       5
                                     0.155
                                     3.16
                                     0.187
                                     2.38
                                     0.591
                                     0.864
                                     0.869
 SUNFLOWER (Proposed Use = 0.25 lb ai/acre total application rate, 21-day PHI)
Sunflower seed
Metconazole (sum of cis- and trans-isomers)
                                  0.245-0.259
                                     20-21
                                      10
                                   <0.04
                                     0.968
                                   <0.04
                                     0.440
                                     0.067
                                     0.127
                                     0.131
Sunflower seed
TA
                                  0.245-0.259
                                     20-21
                                      10
                                   <0.02
                                     0.252
                                   <0.02
                                     0.148
                                     0.049
                                     0.054
                                     0.039
[1] n = number of field trials.
[2] Values based on total number of samples.
[3] Values based on per-trial averages.  LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard deviation.  For computation of the LAFT, HAFT, median, mean, and standard deviation, values <LOQ are assumed to be at the LOQ (0.04 ppm for total metconazole and 0.02 ppm for TA).  N/A = Not applicable.

Rapeseed Subgroup 20A

Valent previously submitted field trial data for canola, the representative crop for the rapeseed subgroup 20A.  The field trials are adequate in number and geographic representation.  Samples of canola seed were analyzed for residues of cis- and trans-metconazole using an adequate GC/NPD method (RM-41C-1).  The validated LOQ is 0.02 ppm for each metconazole isomer; the LOQ for total metconazole residues (cis- + trans-isomers) is 0.04 ppm.  Residues of 1,2,4-triazole, TA, and TAA were determined in canola seed using an adequate LC/MS/MS method (Morse Laboratories Method 160).  The validated LOQ of the LC/MS/MS method in canola matrices was 0.01 ppm for triazole and TAA and 0.03 ppm for TA.  Adequate storage stability data are available supporting the storage duration prior to analysis of metconazole (parent) and triazole metabolites (1,2,4-triazole, TA, and TAA) in canola seed.  The field trial residues for metconazole and the triazoles are summarized below in Tables 5.3.2 and 5.3.3, respectively.

Table 5.3.2.	Summary of Residue Data from Crop Field Trials with Metconazole (WDG).
Crop matrix
                         Total Applic. Rate  (lb ai/A)
                                  PHI (days)
                           Residue Levels (ppm) [1]

                                       
                                       
                                       n
                                     Min.
                                     Max.
                                   HAFT [2]
                                    Median
                                     Mean
                                   Std. Dev.
   Canola (proposed use = 0.125 lb ai/A total application rate, 35-day PHI)
Canola seed
                                 0.124-0.130 
                                     35-49
                                      14
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      NA

                                  0.245-0.250
                                     37-49
                                       4
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      NA

                                     0.632
                                      35
                                       3
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      NA
[1] 	The LOQ is 0.02 ppm for each isomer, for a combined LOQ of 0.04 ppm.  For calculation of the median, mean, and standard deviation, the LOQ was used for samples with residues <LOQ.
[2]	HAFT = Highest Average Field Trial.

Table 5.3.3.	Summary of Residue Data for the Triazole Metabolites from Canola Field Trials with Metconazole (WDG).
Commodity
                              Total Applic. Rate
                                   (lb ai/A)
                                  PHI (days)
                                    Analyte
                           Residue Levels (ppm) [1]

                                       
                                       
                                       
                                     n [2]
                                     Min.
                                     Max.
                                   HAFT [3]
                                    Median
                                     Mean
                                   Std. Dev.
   Canola (proposed use = 0.125 lb ai/A total application rate, 35-day PHI)
Canola seed
                                  0.124-0.130
                                     35-49
                                    1,2,4-T
                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      NA

                                       
                                       
                                    TA [4]
                                       6
                                     0.18
                                     0.50
                                     0.49
                                     0.28
                                     0.31
                                     0.14

                                       
                                       
                                      TAA
                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      NA
[1] 	The LOQ is 0.01 ppm for each triazole analyte.  For calculation of the median, mean, and standard deviation, the LOQ was used for samples with residues <LOQ. 		
[2]	For triazole analysis, seed samples were pooled by growing region to yield 3 pooled samples that were each analyzed in duplicate.  Seeds from Trial F were not included in the pool samples as they were not of commercial quality.
[3]	HAFT = highest average residues from pooled regional samples.
[4]	TA residues were found in all control samples at 0.22-0.27 ppm and averaged 0.24 ppm.

Stone Fruit Crop Group 12-12

Valent previously submitted field trials on cherries, peaches, and plums, which are the representative crops of the stone fruit crop group 12-12.  The field trials are adequate in number and geographic representation.  Samples of stone fruit were analyzed for residues of cis- and trans-metconazole using an adequate GC/NPD method (RM-41C-1).  The validated LOQ is 0.02 ppm for each metconazole isomer; the LOQ for total metconazole residues (cis- + trans-isomers) is 0.04 ppm.  Adequate storage stability data are available supporting the storage duration prior to analysis of metconazole (parent) in stone fruit.  The field trial residues are summarized in Table 5.3.4 below.
 
Table 5.3.4.	Summary of Residue Data from Stone Fruit Crop Field Trials with Metconazole
Crop matrix
                              Total Applic. Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                                    Analyte
                            Residue Levels (ppm)[1]




                                       n
                                     Min.
                                     Max.
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
 STONE FRUIT (proposed use = 0.375 lb ai/A total application rate, 14-day PHI)
                          1.81 lb/gal FlC formulation
Cherry
                                  0.405-0.416
                                     0.538
                                   (1 trial)
                                     13-14
cis-Metconazole
                                      16
                                   <0.02
                                     0.134
                                     0.119
                                     0.041
                                     0.048
                                     0.032

                                       
                                       
trans-Metconazole
                                      16
                                   <0.02
                                     0.028
                                     0.025
                                     0.020
                                     0.021
                                     0.002

                                       
                                       
Metconazole
                                      16
                                   <0.04
                                     0.162
                                     0.143
                                     0.061
                                     0.068
                                     0.033
Peach
                                  0.403-0.417
                                     0.545
                                   (1 trial)
                                     13-14
cis-Metconazole
                                      18
                                   <0.020
                                     0.073
                                     0.066
                                     0.027
                                     0.030
                                     0.015

                                       
                                       
trans-Metconazole
                                      18
                                   <0.020
                                   <0.020
                                     0.020
                                   <0.020
                                   <0.020
                                     0.00

                                       
                                       
Metconazole
                                      18
                                   <0.040
                                   <0.093
                                     0.086
                                     0.047
                                     0.050
                                     0.015
Plum
                                  0.405-0.412
                                     0.538
                                   (1 trial)
                                     13-14
cis-Metconazole
                                      12
                                   <0.020
                                     0.04
                                     0.06
                                     0.020
                                     0.024
                                     0.008

                                       
                                       
trans-Metconazole
                                      12
                                   <0.020
                                   <0.020
                                   <0.020
                                   <0.020
                                   <0.020
                                      --

                                       
                                       
Metconazole
                                      12
                                   <0.040
                                   <0.060
                                     0.060
                                     0.040
                                     0.044
                                     0.008
                              50% WDG formulation
Cherry
                                  0.407-0.410
                                      14
cis-Metconazole
                                       4
                                     0.027
                                     0.056
                                     0.052
                                     0.039
                                     0.040
                                     0.014

                                       
                                       
trans-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                     0.02
                                     0.020
                                     0.020
                                     0.020

                                       
                                       
Metconazole
                                       4
                                     0.049
                                   <0.076
                                     0.076
                                     0.068
                                     0.065
                                     0.011
Peach
                                     0.418
                                      14
cis-Metconazole
                                       2
                                   <0.02
                                     0.020
                                     0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                       2
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                       2
                                   <0.04
                                   <0.040
                                     0.04
                                     0.04
                                     0.04
                                      --
Plum
                                     0.408
                                      14
cis-Metconazole
                                       2
                                   <0.02
                                     0.020
                                     0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                       2
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                       2
                                   <0.04
                                   <0.040
                                     0.04
                                     0.04
                                     0.04
                                      --
1   Values for "Metconazole" and "Total Residues" are reported on a sample basis and are therefore not summations of tabulated data.
[2]  HAFT = Highest average field trial result.

Tree Nut Group 14-12
D348168, N. Dodd, 2/20/08 (almonds and pecans)

Valent previously submitted field trials for metconazole on almonds and pecans, the representative commodities of the tree nut crop group 14-12.  The field trials are adequate in number and geographic representation.  Samples of stone fruit were analyzed for residues of cis- and trans-metconazole using an adequate GC/NPD method (RM-41C-1).  The validated LOQ is 0.02 ppm for each metconazole isomer; the LOQ for total metconazole residues (cis- + trans-isomers) is 0.04 ppm.  Adequate storage stability data are available supporting the storage duration prior to analysis of metconazole (parent) in stone fruit.  The field trial residues are summarized in Table 5.3.5 below.

Table 5.3.5.	Summary of Residue Data from Tree Nut Crop Field Trials with Metconazole[1]
Crop matrix
                              Total Applic. Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                                    Analyte
                             Residue Levels (ppm)




                                       n
                                     Min.
                                     Max.
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
TREE NUTS (proposed use = 0.44 or 0.50 lb ai/A total application rate, 25-day PHI)
                          1.81 lb/gal FlC formulation
Almond, 
hulls
                                  0.543-0.570
                                      25
cis-Metconazole
                                      10
                                     0.42
                                     3.04
                                     2.49
                                     0.65
                                     1.05
                                     0.84

                                       
                                       
trans-Metconazole
                                      10
                                     0.08
                                     0.65
                                     0.50
                                     0.13
                                     0.22
                                     0.19

                                       
                                       
Metconazole
                                      10
                                     0.50
                                     3.69
                                     2.82
                                     0.78
                                     1.27
                                     1.03

                                  0.394-0.408
                                      25
cis-Metconazole
                                       4
                                     0.30
                                     0.62
                                     0.62
                                     0.48
                                     0.47
                                     0.17

                                       
                                       
trans-Metconazole
                                       4
                                     0.07
                                     0.15
                                     0.14
                                     0.11
                                     0.11
                                     0.04

                                       
                                       
Metconazole
                                       4
                                     0.37
                                     0.76
                                     0.76
                                     0.59
                                     0.58
                                     0.21
Almond, nutmeat
                                  0.543-0.570
                                      25
cis-Metconazole
                                      10
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                      10
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                      10
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      --

                                  0.394-0.408
                                      25
cis-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                       4
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      --
Pecan,
nutmeat
                                  0.502-0.537
                                     25-32
cis-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                       6
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      --
                              50% WDG formulation
Almond, 
hulls
                                  0.402-0.407
                                      25
cis-Metconazole
                                       4
                                   <0.02
                                     1.69
                                     1.51
                                     0.68
                                     0.77
                                     0.87

                                       
                                       
trans-Metconazole
                                       4
                                   <0.02
                                     0.33
                                     0.31
                                     0.15
                                     0.16
                                     0.17

                                       
                                       
Metconazole
                                       4
                                   <0.04
                                     2.02
                                     1.82
                                     0.83
                                     0.93
                                     1.04
Almond, nutmeat
                                  0.402-0.407
                                      25
cis-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                       4
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                       4
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      --
Pecan,
nutmeat
                                     0.529
                                      26
cis-Metconazole
                                       2
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
trans-Metconazole
                                       2
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      --

                                       
                                       
Metconazole
                                       2
                                   <0.04
                                   <0.04
                                   <0.04
                                     0.04
                                     0.04
                                      --
1   Values for "Metconazole" and "Total Residues" are reported on a sample basis and are therefore not summations of tabulated data.
[2]  HAFT = Highest average field trial result.

Conclusions.  Adequate field trial data have been submitted for the pea and bean, dried shelled, except soybean, subgroup 6C and the sunflower subgroup 20B.  Field trials were conducted on dry beans, dry peas, and sunflowers.  The studies adequately reflect the proposed use patterns.  The number of field trials and geographic representations are adequate.  The residue data are supported by adequate storage stability data.  The analytical methods (the GC/NPD method adapted from Valent Method RM-41C-1 for metconazole and the LC/MS/MS method adapted from Morse Laboratories Meth-160 for TA) are adequate for analysis of the residues of concern.  

In samples of dry bean harvested 19-23 days after two applications of the 50% WG formulation of metconazole at a seasonal rate of 0.245-0.259 lb ai/A, individual sample (and per-trial average) residues of total metconazole (determined the sum of cis- and trans-metconazole) were below the LOQ (<0.04 ppm) in/on all samples.  Corresponding residues of TA were <0.02-0.348 ppm (<0.02-0.346 ppm).  

In samples of dry pea harvested 20-22 days after two applications of the 50% WG formulation of metconazole at a seasonal rate of 0.250-0.258 lb ai/A, individual sample (and per-trial average) residues of total metconazole (determined as the sum of cis- and trans-metconazole) were <0.04-<0.0620 ppm (<0.04-<0.0562 ppm).  Corresponding residues of TA were 0.155-3.16 ppm (0.187-2.38 ppm).  In the residue decline trial, average total residues of metconazole (determined as the sum of cis- and trans-metconazole) were below the LOQ at the 9-day PHI, increased at the 14-day PHI (<0.0546 ppm), and then decreased to at or below the LOQ with increasing PHIs.  Corresponding average residues of TA were constant (0.172-0.202 ppm) at all sampling intervals.

In samples of sunflower seed harvested 20-21 days after two applications of the 50% WG formulation of metconazole at a seasonal rate of 0.245-0.259 lb ai/A, individual sample (and per-trial average) residues of total metconazole (determined as the sum of cis- and trans-metconazole) were <0.04-0.968 ppm (<0.04-0.440 ppm).  Corresponding residues of TA were <0.02-0.252 ppm (<0.02-0.148 ppm).  In the residue decline trial, total residues of metconazole (determined as the sum of cis- and trans-metconazole) and corresponding residues of TA in seed were at or below the LOQ in/on all samples; therefore, residue decline could not be determined.

The previously submitted field trial data on canola, cherry, peach, plum, almond, and pecan are adequate to support the rapeseed subgroup 20A, the stone fruit subgroup 12-12, and the tree nut group 14-12.  The number of field trials and geographic representations are adequate.  Adequate storage stability data are available to support the field trial data.  An adequate data collection method, the GC/NPD method RM-41C-1, was used to determine metconazole (cis- and trans- isomers) in canola, stone fruit, and tree nuts.  Residues of 1,2,4-triazole, TA, and TAA were determined in canola seed using an adequate LC/MS/MS method (Morse Laboratories Method 160).  Although stone fruit and tree nut samples were not analyzed for the triazole metabolites, field trial data for triazoles are not required for those petitions submitted in 2006.

5.3.2	Field Rotational Crops (860.1900)
DP# 380990, 3/24/11, A. Acierto 
DP# 361110, 2/26/10, D. Soderberg
DP# 348168, 2/20/08, N. Dodd 

No new field rotational crop studies have been submitted.  Limited field rotational crop studies were previously submitted for the rotational crops radish, spinach, wheat, and lettuce after seasonal application rates of approximately 0.50 lb ai/A to soybeans, tomatoes, or wheat.  Based on that data, HED 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.

Rotational crop restrictions on both the current label dated 8/12/13 and the proposed label (Metconazole 50 WDG Fungicide, EPA Reg. No. 59639-147) are shown below:

● Immediate plant-back is allowed for barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, and those crops listed on the label. [Note: Peanut is included on the Metconazole 50 WDG label; barley, corn, cotton, oat, rye, soybean, sugar beet, triticale, and wheat are on the Caramba(R) Fungicide label (EPA Reg. No. 7969-246, dated 6/13/13)].
● A 30-day plant-back interval is required for Brassica Leafy Vegetables and Leafy Vegetables.
● Do not plant any crop, except barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, Brassica Leafy Vegetables, Leafy Vegetables and those crops listed on the label, earlier than 120 days after applying Metconazole 50 WDG Fungicide.

Conclusions.  Adequate limited field rotational crop studies have previously been submitted.  The rotational crop restrictions on the proposed label (Metconazole 50 WDG Fungicide, EPA Reg. No. 59639-147) are adequate. 


Note:  To support the field rotational crop studies, additional storage stability data were requested for cis- and trans-metconazole reflecting storage for up to 18 months for wheat grain and straw, 19 months for lettuce and wheat hay, and 21 months for radish roots and tops and wheat forage (DP# 348168 (N. Dodd, 2/20/08).

This deficiency has been resolved.  HED has accepted the available storage stability data, including data showing storage stability data for potato for 31.5 months (DP# 380990, A. Acierto, 3/24/11); almond nutmeat for 22 months and almond hulls for 26 months (DP# 348168, N. Dodd, 2/20/08); and radish root, wheat hay, and soybean seed for 26 months (DP# 361110, D. Soderberg, 2/26/10). 

5.3.3	Processed Food and Feed (860.1520)
DP# 350367, N. Dodd, 9/18/08 (canola)
DP# 348168, N. Dodd, 2/20/08 (plum)
49297803.de2 (sunflower)

Canola

A processing study on canola was previously submitted.  Metconazole (50% WDG) was applied to canola as a single broadcast foliar application during flowering at 0.632 lb ai/A (5x rate the proposed rate).  Samples of canola seed, meal and oil were analyzed for residues of cis- and trans-metconazole using an adequate GC/NPD method (RM-41C-1).  Residues of 1,2,4-triazole, TA, and TAA were determined using an adequate LC/MS/MS method (Morse Laboratories Method 160).  Adequate storage stability data are available supporting the storage duration prior to analysis of metconazole (parent) and triazole metabolites (1,2,4-triazole, TA, and TAA) in canola seed, meal, and oil.  The processing factors for metconazole and the triazole-related residues are discussed in Table 5.3.3.1 below.

Plum

A processing study on plum was previously submitted.  Metconazole (1.81 lb ai/gal FlC formulation) was applied three times for a total application rate of 2.04 lb ai/A/season (5.4x the maximum proposed seasonal application rate for stone fruits).  Residues of metconazole in/on plum samples were quantitated using GC/NPD method RM-41C-1.  The method was adequate for data collection based on acceptable method validation and concurrent method recoveries.  Adequate storage stability data on cherries are available to support the storage conditions and durations of samples from the plum processing study.  The processing factor for metconazole was determined to be 2.3x as shown in Table 5.3.3.1 below.

Sunflower

IR-4 submitted a processing study for metconazole on sunflower seed.  The processed commodities of sunflower seed are meal and refined oil.

In one trial conducted in ND during the 2010 growing season, a 50% WG formulation of metconazole (Quash 50 WDG) was applied as two foliar broadcast applications to sunflower at an exaggerated rate of 0.630-0.635 lb ai/A/application for a total seasonal rate of 1.265 lb ai/A (5.1x the proposed total application rate).  Applications were made at a 7-day RTI using ground equipment in spray volumes of 12 gal/A.  An NIS was added to the spray mixture for each of the applications.  Samples of sunflower seed were harvested at a PHI of 21 days and processed into meal and oil by GLP Technologies (Navasota, TX) using simulated commercial procedures.  Adequate descriptions were provided of the processing procedures, including material balance summaries.

As discussed in Section 5.2, the available storage stability data are adequate to support the storage conditions and intervals of samples from the processing study.  All samples were frozen at the testing facility and remained frozen during shipping and storage prior to processing and analysis.

Samples were analyzed for residues of metconazole, determined as cis- and trans-metconazole, using a GC/NPD method adapted from Valent Method RM-41C-1 (dated 11/13/03).  Samples were analyzed for residues of the triazole metabolite triazole alanine (TA) using an LC/MS/MS method adapted from Morse Laboratories Meth-160 (dated 6/27/03).  The LOQ (determined as the lowest level of method validation, LLMV) was 0.02 ppm for each analyte.  Acceptable method validation and concurrent recovery data were reported for sunflower samples at fortification levels of 0.02-0.2 ppm, thus validating the methods.  The fortification levels were adequate to bracket expected residue levels.  Although triazole fungicides are typically monitored for residues of all three triazole metabolites (i.e., 1,2,4-triazole, TA, and TAA), HED previously concluded that only analysis for TA need be conducted in the subject study (refer to HED's Chemistry Science Advisory Council minutes, 8/11/2010 meeting).

Following two foliar broadcast applications of the 50% WG formulation at total application rates of 1.265 lb ai/A, quantifiable residues of total metconazole (determined as the sum of cis- and trans-metconazole) were observed in/on sunflower seed (RAC), but were below the combined LOQ (<0.04 ppm) in meal and oil.  Corresponding residues of TA were 0.0200 ppm in/on sunflower seed, 0.0580 ppm in meal, and below the LOQ (<0.02 ppm) in oil.

A comparison of the residues in sunflower seed (RAC) with those in each processed sunflower fraction indicated that total residues of metconazole (determined as the sum of cis- and trans-metconazole) do not concentrate (processing factors <1x) in meal and oil.  Residues of TA concentrate in sunflower meal (processing factor of 2.9x), but do not concentrate in oil.  These processing factors are less than or close to the theoretical concentration factors. The theoretical concentration factors for sunflower are 4.5x for meal and 2.5x for oil (Table 3, OCSPP 860.1520).

Residues found in samples and processing factors are given in Table 5.3.3.2 below.

Table 5.3.3.1.	Summary of Processing Factors for Metconazole (cis-and trans-isomers) in Canola.
                                      RAC
Processed Commodity
                            Processing Factors [1]
                                       

                                  Metconazole
                                1,2,4-triazole
                                      TA
                                      TAA
Canola seed
Meal
                                      NC
                                      NC
                                     2.07x
                                     1.43x

Refined oil
                                      NC
                                      NC
                                    0.005x
                                     1.0x
Plum
Prune
                                     2.3x
                                     NA[2]
                                      NA
                                      NA
[1]  NC = Not calculated; residues were below the LOQ in the RAC and the processed commodity.
2  NA = Not analyzed since analysis is not required for data submitted in 2006.

Table 5.3.3.2.  Residue Data from Sunflower Processing Study with cis- and trans-Metconazole and TA.
                                       
                            RAC/Processed Commodity
                                       
                                  Total Rate
                                    lb ai/A
                                       
                                     PHI 
                                     (day)
                                    Analyte
                               Residues (ppm)[1]
                               Processing Factor
                           Median Processing Factor
                                Sunflower, seed
                                     1.265
                                      21
                                cis-metconazole
                                     0.170
                                      --
                                      --
                                       
                                       
                                       
                               trans-metconazole
                                    0.0362
                                      --
                                      --
                                       
                                       
                                       
                               Total metconazole
                                     0.206
                                      --
                                      --
                                       
                                       
                                       
                                      TA
                                    0.0200
                                      --
                                      --
                                Sunflower, meal
                                       
                                       
                                cis-metconazole
                                   <0.02
                                   <0.1x
                                      --
                                       
                                       
                                       
                               trans-metconazole
                                   <0.02
                                   <0.6x
                                      --
                                       
                                       
                                       
                               Total metconazole
                                   <0.04
                                   <0.2x
                                      --
                                       
                                       
                                       
                                      TA
                                    0.0580
                                     2.9x
                                      --
                                Sunflower, oil
                                       
                                       
                                cis-metconazole
                                   <0.02
                                   <0.1x
                                      --

                                       
                                       
                               trans-metconazole
                                   <0.02
                                   <0.6x
                                      --

                                       
                                       
                               Total metconazole
                                   <0.04
                                   <0.2x
                                      --

                                       
                                       
                                      TA
                                      ND
                                   <1.0x
                                      --
[1] ND = Not detected (<LOD).  For seed, meal, and oil, respectively, the LODs were 0.00601, 0.00615, and 0.01330 ppm for cis-metconazole and 0.00864, 0.01533, and 0.00589 ppm for trans-metconazole, and the LOQ was 0.02 ppm for each analyte, for a combined LOQ of 0.04 ppm.  For TA, the LODs were 0.00356, 0.02229, and 0.01207 ppm for seed, meal, and oil, respectively, and the LOQ was 0.02 ppm.  Combined residues and per trial averages were calculated by the study reviewer using the LOQ for all residues reported as <LOQ.

Conclusions.  Adequate processing studies have been submitted on canola, plum, and sunflower.
(Refer to Section 6.0 for a discussion of recommended tolerances for processed commodities.)

Canola:  Metconazole residues (cis- and trans-metconazole) were non-detectable in/on seed, meal and refined oil samples from a field trial treated at an exaggerated 5x rate.   Residues of 1,2,4-triazole were also not detectable in the RAC treated at 5x and processed commodities (meal and refined oil).  The data indicate that residues of TA and TAA do not concentrate in oil.  However, residues of TA and TAA concentrated in canola meal by 2.1x and 1.4x, respectively.

Plum:  The processing study on plums treated at a 5.4x rate indicate that metconazole residues (cis- and trans-metconazole) concentrate 2.3x in prunes. 
 
Sunflower:  Following two foliar broadcast applications of the 50% WG formulation at total application rates of 1.265 lb ai/A (5.1x the proposed total application rate), quantifiable residues of metconazole (cis- and trans-metconazole) were observed in/on sunflower seed (RAC).  Metconazole residues (cis- and trans-metconazole) were below the combined LOQ (<0.04 ppm) in sunflower meal and oil, indicating that metconazole residues do not concentrate (processing factors <1x) in meal and oil.  Corresponding residues of TA were 0.0200 ppm in/on sunflower seed, 0.0580 ppm in meal, and below the LOQ (<0.02 ppm) in oil; these data indicate that residues of TA concentrate in sunflower meal (processing factor of 2.9x), but do not concentrate in oil.  

Adequate storage stability data are available to support sample storage durations and conditions for these processing studies.  The data collection methods (the GC/NPD method adapted from Valent Method RM-41C-1 for metconazole and the LC/MS/MS method adapted from Morse Laboratories Meth-160 for 1,2,4-triazole, TA, and TAA) are adequate for analysis of the residues of concern. 

The observed processing factors in these processing studies are less than the theoretical concentration factors.  The theoretical processing factor is 3.5x for prunes (OCSPP 860.1520, Table 1).  The theoretical processing factors are 1.9x for canola meal, 3.0x for canola oil, 4.5x for sunflower meal, and 2.5x for sunflower oil (based on separation into components; OCSPP 860.1520, Table 3). 

5.3.4	Meat, Milk, Poultry and Eggs (860.1480)
DP# 348168, N. Dodd, 2/20/08 (cattle feeding study)
DP# 350367, N. Dodd, 9/18/08 (poultry feeding study)
DP# 399057, N. Dodd, 7/19/12

Adequate cattle and poultry feeding studies were previously submitted and are summarized below.  Maximum residues of metconazole (sum of cis- and trans-isomers) and 1,2,4-triazole are reported below in Tables 5.3.4.1 and 5.3.4.2, respectively.

Cattle

In the cattle feeding study (MRID 46901914), cattle were dosed orally with metconazole at 4.73, 14.6, and 45.7 ppm (low, mid, and high dose) in the diet via capsules for 28 consecutive days.  These dose levels are respectively equivalent to 2.0x, 6.1x, and 19x the dietary burden for beef cattle and 0.56x, 1.7x, and 5.4x the dietary burden for dairy cattle.  Residues of cis- and trans-metconazole were determined in milk using method RM-41M-1 (GC/NPD) and in tissues using method RM-41M-2 (LC/MS/MS).  The validated LOQs for RM-41M-1 were 0.02 ppm for each analyte in milk and 0.04 ppm for each analyte in cream.  The validated LOQ for RM-41M-2 was 0.02 ppm for each analyte in tissues.  Low- and mid-dose samples were not analyzed for cis- and trans-metconazole except for mid-dose liver, which had residues of <0.02 ppm for each isomer.  In high-dose liver, residues of cis- and trans-metconazole were <0.02-0.021 ppm and <0.02 ppm, respectively; maximum total metconazole residues (sum of cis- and trans-isomers) were <0.041 ppm in liver.  Residues of cis- and trans-metconazole were <LOQ in all samples of whole milk, skim milk, cream, fat, muscle, and kidney from the high-dose group.  The triazole metabolites (1,2,4-triazole, TA, and TAA) were not determined in the cattle feeding study.

Poultry

In the poultry feeding study (MRID 47406901), laying hens were dosed orally with metconazole at 2.05, 6.24, and 20.3 ppm (low, mid, and high dose) in the diet via capsules for 28 consecutive days.  The dose levels are respectively equivalent to 5.4x, 16x, and 53x the dietary burden for poultry.  Residues of cis- and trans-metconazole were separately determined in eggs and tissues using the LC/MS/MS method RM-41M-2.  The validated LOQ for RM-41M-2 is 0.02 ppm for each analyte in eggs and tissues.  Residues of cis- and trans-metconazole were <LOQ in eggs from the low- and mid-dose groups, but quantifiable metconazole residues were found in eggs from the high-dose group, with total residues of cis- and trans-metconazole in eggs ranging from <0.04-<0.085 ppm.  Residues of cis- and trans-metconazole were <LOQ in all samples of muscle, fat, and liver from all three dose groups.

Residues of 1,2,4-triazole in egg and poultry tissue samples were determined using the LC/MS/MS method (Morse Laboratories Method 160, Revision 2).  The validated LOQ is 0.01 ppm for triazole in eggs and tissues.  Triazole residues were <LOQ (<0.01 ppm) in selected egg samples from the 1x and 3x groups, with the exception of one sample from the 3x group on Day 28, which had triazole residues of 0.011 ppm.  In the 10x dose group, triazole residues were quantifiable in all analyzed egg samples.  Triazole residues plateaued in eggs by Day 7 and were 0.015-0.026 ppm between Days 7-28 and averaged 0.02 ppm.  In poultry tissues, triazole residues were <LOQ in fat from the 10x dose group and in muscle and liver from the 1x dose groups; however, triazole residues were quantifiable in muscle and liver from the 3x and 10x dose groups and increased with dose level.  For both muscle and liver, triazole residues averaged 0.01 ppm for the 3x dose group and 0.029 ppm for the 10x dose group.  TA and TAA were not determined in eggs and poultry tissues.

Table 5.3.4.1.  Summary of Livestock Feeding Studies with Metconazole 
Commodity
                              Feeding Level, ppm
                           Residue in Tissue, ppm[1]
                            Tissue-to-Feed Ratio[2]
Milk (whole and skim)
                                     45.7
                              <0.04 (<LOQ)
                                      --
Cream
                                     45.7
                              <0.08 (<LOQ)
                                      --
Muscle (cattle)
                                     45.7
                                   <0.04
                                      --
Fat (cattle)
                                     45.7
                                   <0.04
                                      --
Liver (cattle)
                                     14.6
                                   <0.04
                                      --

                                     45.7
                                   <0.041
                                    0.00090
Kidney (cattle)
                                     45.7
                                   <0.04
                                      --
Eggs
                                     2.05
                                   <0.04
                                      --

                                     6.24
                                   <0.04
                                      --

                                     20.3
                                   <0.085
                                    0.0042
Muscle (poultry)
                                     2.05
                                   <0.04
                                      --

                                     6.24
                                   <0.04
                                       -

                                     20.3
                                   <0.04
                                      --
Fat (poultry)
                                     2.05
                                   <0.04
                                      --

                                     6.24
                                   <0.04
                                      --

                                     20.3
                                   <0.04
                                      --
Liver (poultry)
                                     2.05
                                   <0.04
                                      --

                                     6.24
                                   <0.04
                                      --

                                     20.3
                                   <0.04
                                      --
[1] Maximum residues of metconazole (sum of cis- and trans-isomers).are reported.  The LOQ is 0.04 ppm (0.02 ppm for each isomer) in all commodities except cream.  The LOQ in cream is 0.08 ppm.  Tissue-to-feed ratios were not calculated for matrices with residues of <LOQ.
2 Tissue-to-feed ratios were not calculated for matrices with residues of <LOQ.


Table 5.3.4.2.  Summary of 1,2,4-Triazole Residues from Poultry Feeding Studies with Metconazole
Commodity
                              Feeding Level, ppm
                           Residue in Tissue, ppm[1]
                            Tissue-to-Feed Ratio[2]
Eggs
                                     2.05
                                   <0.01
                                      --

                                     6.24
                                     0.011
                                    0.0018

                                     20.3
                                     0.026
                                    0.0013
Muscle (poultry)
                                     2.05
                                   <0.01
                                      --

                                     6.24
                                     0.011
                                    0.0018

                                     20.3
                                     0.031
                                    0.0015
Fat (poultry)
                                     20.3
                                   <0.01
                                      --
Liver (poultry)
                                     2.05
                                   <0.01
                                      --

                                     6.24
                                     0.011
                                    0.0018

                                     20.3
                                     0.032
                                    0.0016
[1] Maximum residues of 1,2,4-triazole, expressed as 1,2,4-triazole, are reported.  The LOQ is 0.01 ppm.
2 Tissue-to-feed ratios were not calculated for matrices with residues of <LOQ.

5.3.4.1	Dietary Burden

Livestock feed items associated with the proposed/expanded uses are sunflower meal, safflower meal, canola meal, flax meal, and almond hulls.

There are no livestock feed items associated with stone fruits or tree nuts other than almonds.

There are no livestock feed items associated with dried shelled peas and beans except for cowpeas (seed, forage, and hay) and field peas (seed, vines/silage, and hay) (Table 1 Feedstuffs, June 2008).  To avoid the need for residue data on livestock feed items of cowpea and field pea, the label should be revised to include the following statement for the dried shelled pea and bean, except soybean, subgroup 6C:  "Do not apply to cowpea or field pea used for livestock feed."

The dietary burdens for metconazole residues are based on the maximum reasonably balanced diets (Table 1 Feedstuffs, June 2008).  The dietary burdens for metconazole residues are calculated to be 2.4 ppm for beef cattle, 8.5 ppm for dairy cattle, 0.38 ppm for poultry, and 0.14 ppm for swine. 

Table 5.3.4.1.	Calculation of Dietary Burdens of Metconazole Residues to Livestock.
Feedstuff
                                    Type[1]
                                % Dry Matter[2]
                                   % Diet[2]
                          HAFT[4] or Median[5,6][,7] 
                                       
                                Residue Level 
                                     (ppm)
                         Dietary Contribution (ppm)[3]
Beef Cattle (R = 15%; CC = 80%; PC = 5%)
Wheat hay
                                       R
                                      88
                                      15
                                     HAFT
                                     12.6
                                     2.15
Barley grain
                                      CC
                                      88
                                      50
                                    Median
                                     0.48
                                     0.27
Wheat, milled byproducts
                                      CC
                                      88
                                      30
                                  Median x PF
                                     0.063
                                     0.021
Sunflower meal
                                      PC
                                      92
                                       5
                                    Median
                                     0.067
		0.0036
                                                                   TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                      --
                                      2.4
Dairy Cattle (R = 45%; CC = 45%; PC = 10%)
Oat hay
                                       R
                                      90
                                      10
                                     HAFT
                                     11.24
                                     1.25
Wheat hay
                                       R
                                      88
                                      20
                                     HAFT
                                     12.6
                                     2.86
Corn, sweet, stover
                                       R
                                      83
                                      15
                                     HAFT
                                     22.7
                                     4.10
Barley grain
                                      CC
                                      88
                                      45
                                    Median
                                     0.48
                                     0.25
Sunflower meal
                                      PC
                                      92
                                      10
                                    Median 
                                     0.067
                                    0.0073
                                                                   TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                      --
                                      8.5
Swine (CC = 85%; PC = 15%)
Barley grain
                                      CC
                                      88
                                      20
                                    Median
                                     0.48
                                     0.096
Wheat, milled byproducts
                                      CC
                                      88
                                      50
                                  Median x PF
                                     0.063
                                     0.032
Corn, field, grain
                                      CC
                                      88
                                      15
                                    Median
                                     0.01
                                    0.0015
Sunflower meal
                                      PC
                                      92
                                      15
                                    Median
                                     0.067
                                     0.010
                                                                   TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                      --
                                     0.14
Poultry (CC = 75%; PC = 25%)
Barley grain
                                      CC
                                      88
                                      75
                                    Median
                                     0.48
                                     0.36
Sunflower meal
                                      PC
                                      92
                                      25
                                    Median
                                     0.067
                                     0.017
                                                                   TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                      --
                                     0.38
[1]  R:  Roughage; CC:  Carbohydrate concentrate; PC:  Protein concentrate.
[2]  Table 1 Feedstuffs (June 2008).  
[3]  Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle; contribution = ([tolerance] X % diet) for     poultry and swine.
4 The HAFT (highest average field trial) was used for sweet corn stover, oat hay, and wheat hay. 
[5] The median was used for the blended commodities field corn grain and barley grain.
[6] The median times the processing factor (PF) was used for wheat milled byproducts (PF = 2.1x based on shorts, which had the highest PF considering bran, middlings, shorts).
7  The median was used for sunflower meal (OECD's "Guidance on Residues in Livestock,"  ENV/JM/MONO(2013)8, 9/4/13).

5.3.4.2	Estimated Secondary Residues in Livestock 

The secondary residue levels of metconazole in livestock commodities in Table 5.3.4.2 below were estimated using tissue-to-feed ratios from Table 5.3.4 above and the calculated dietary burden from Table 5.3.4.1 above. 

Table 5.3.4.2. Estimation of Secondary Residues from Use of Metconazole (sum of cis- and trans-isomers).
Commodity
Tissue-to-Feed Ratio
Dietary Burden (ppm)
Expected Residue
Liver (cattle)
                                    0.00090
                                      8.5
                                    0.0076
Eggs
                                    0.0042
                                     0.38
                                    0.0016

Tolerances for metconazole are established in 40 CFR §180.617 at 0.04 ppm for meat byproducts of cattle, goat, horse, and sheep.  No tolerances are established for milk, meat, or fat of cattle, goat, horse, and sheep.  A tolerance of 0.04 ppm is established in egg; no other tolerances are established for poultry.  No tolerances are established for swine. 

Conclusions.  Based on the cattle feeding study and the calculated dietary burden based on the maximum reasonably balanced diet (Table 1 Feedstuffs, June 2008), no changes are required in the established livestock tolerances as a result of the proposed/expanded uses.  The established tolerances for meat byproducts of cattle, goat, horse, and sheep at 0.04 ppm and for egg at 0.04 ppm are adequate.  No tolerances are established for milk; fat and meat of cattle, goat, hog, horse, poultry, and sheep; or meat byproducts of hog and poultry since residues are not expected to occur in those commodities.  If additional uses increase the dairy cattle dietary burden, additional ruminant feeding studies conducted at higher rates may be needed.

5.3.5	Food Handling (860.1460)

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

5.3.6	Water, Fish, and Irrigated Crops (860.1400)

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

5.4	Food Residue Profile

Crop Field Trials:  Adequate field trial data have been submitted on dry beans, dry peas, sunflowers, canola, almonds, pecans, cherries, peaches, and plums.  The studies adequately reflect the proposed use patterns.  The number of field trials and geographic representations are adequate.  The residue data are supported by adequate storage stability data.  The analytical methods (the GC/NPD method adapted from Valent Method RM-41C-1 for metconazole and the LC/MS/MS method adapted from Morse Laboratories Meth-160 for triazoles) are adequate for analysis of the residues of concern. 

The residue data on canola, almonds, pecans, cherries, peaches, and plums support the established tolerance levels. 

Metconazole residues (the sum of cis- and trans-isomers) in dry beans were all below the LOQ (<0.04 ppm).  Metconazole residues in dry pea were generally <LOQ.  Metconazole residues sunflower seeds were generally quantifiable but low.  Residues of TA were quantifiable (>0.02 ppm) in 54% of the dry bean samples.  TA was generally quantifiable in dry pea and sunflower seeds.

In the dry pea residue decline trial, average total residues of metconazole were below the LOQ at the 9-day PHI, increased at the 14-day PHI (<0.0546 ppm), and then decreased to at or below the LOQ with increasing PHIs.  Corresponding average residues of TA were constant (0.172-0.202 ppm) at all sampling intervals.

In the sunflower residue decline trial, residue decline could not be determined because all residues were <=LOQ.

Processing Studies: Adequate processing studies have been conducted on canola, plums, and sunflowers. 

Canola:  Metconazole (the sum of cis- and trans-isomers) was non-detectable in/on canola seed, meal and refined oil samples reflecting treatment at a 5x rate; therefore, separate tolerances are not required for canola meal and oil.  Residues of 1,2,4-triazole were also not detectable in canola seed, meal and refined oil reflecting treatment at 5x.  Residues of TA and TAA do not concentrate in oil.  However, residues of TA and TAA concentrated in canola meal by 2.1x and 1.4x, respectively.

Plum:  Metconazole (the sum of cis- and trans-isomers) concentrates 2.3x in prunes.

Sunflower:  Metconazole (the sum of cis- and trans-isomers) does not concentrate in sunflower meal and oil.  Residues of TA concentrate 2.9x in sunflower meal, but do not concentrate in oil.  

Storage Stability:  The storage stability data are adequate to support the intervals of frozen storage from harvest to analysis for dry bean, dry pea, sunflower (seed, meal, and refined oil), canola (seed, meal and refined oil), cherry, peach, plum, and prune.  No corrections of residue values from the field trials or processing studies for loss of metconazole or TA residues are necessary.

Meat, Milk, Poultry, and Eggs: Based on the cattle feeding study and the calculated dietary burden based on the maximum reasonably balanced diet (Table 1 Feedstuffs, June 2008), no changes are required in the established livestock tolerances as a result of the proposed/expanded uses.  No residues are expected to occur in milk, fat, and meat, and residues in liver are not expected to exceed the established tolerance of 0.04 ppm.  

Rotational Crops: Since the confined study indicated the potential for quantifiable metconazole residues in rotated crop commodities, limited field rotational crop trials were conducted.  Based on the limited field rotational crop trials, rotational crop restrictions are included on the registered label (Metconazole 50 WDG Fungicide, EPA Reg. No. 59639-147).  The same rotational crop restrictions on the proposed label are adequate.

6.0	Tolerance Derivation

The established tolerances for canola, the stone fruit crop group 12, and the tree nut crop group 14 are adequate for the rapeseed subgroup 20A, the stone fruit crop group 12-12, and the tree nut crop group 14-12, respectively.  However, to harmonize with Canada, HED is recommending a tolerance of 0.08 ppm for the rapeseed subgroup 20A.

As shown in Appendix D, the Office of Economic Cooperation and Development (OECD) tolerance calculation procedures were used for calculating a tolerance for metconazole in sunflower.  The statistical goal of the tolerance calculation procedures is to produce a maximum residue limit MRL) proposal in the region of the 95[th] percentile of the underlying residues distribution. 

The OECD tolerance procedures were used for calculating a tolerance for dry pea.  However, to harmonize with Canada, HED is recommending a tolerance of 0.15 ppm on the pea and bean, dried shelled, except soybean, subgroup 6C.

The OECD tolerance calculation procedures were not used for metconazole in dry beans since all residues of metconazole (MRID 49297801) were <LOQ (<0.04 ppm) in dry beans.

Separate tolerances are not required for canola meal and oil since metconazole residues were non-detectable in/on seed, meal and refined oil samples from a field trial treated at an exaggerated 5x rate.  Residues of 1,2,4-triazole were also not detectable in canola seed treated at 5x and processed commodities (meal and refined oil).  The data indicate that residues of TA and TAA do not concentrate in oil.  However, residues of TA and TAA concentrated in canola meal by 2.1x and 1.4x, respectively.

Residues of metconazole concentrate 2.3x in prunes.  Based on the HAFT residues in plum (0.06 ppm) and the processing factor (2.3x), expected residues in prune would be 0.14 ppm.  This value is less than the established/recommended 0.20 ppm tolerance for the stone fruit group; therefore, a separate tolerance for prune is not required.

Residues of metconazole do not concentrate in sunflower meal and oil; therefore, separate tolerances are not needed for sunflower meal and oil.  Residues of TA concentrate in sunflower meal (processing factor of 2.9x), but do not concentrate in oil.  

Dry Pea (MRID 49297802)

The dataset for metconazole on dry pea consisted of data from five field trials representing foliar broadcast applications at the rate of 0.250-0.258 lb ai/A/season with PHIs of 20-22 days.  The field trial application rates are within 25% of the maximum label application rate.  The average field trial residue values used to calculate the tolerance are provided in Appendix D.  Residues of metconazole were quantifiable in only one of five field trials.  Using the OECD tolerance calculation procedures, the tolerance for the residues of metconazole in dry bean would be 0.08 ppm, which is the higher result of dry bean (0.04 ppm) and dry pea (0.08 ppm).  However, to harmonize with Canada, HED is recommending a tolerance of 0.15 ppm for the pea and bean, dried shelled, except soybean, subgroup 6C.  

Sunflower (MRID 49297803)

The dataset used to determine a tolerance for metconazole on sunflower consisted of data from ten field trials representing foliar broadcast applications at the rate of 0.245-0.259 lb ai/A/season with PHIs of 20-21 days.  The field trial application rates are within 25% of the maximum label application rate.  The average field trial residue values used to calculate the tolerance are provided in Appendix D.  Residues of metconazole were quantifiable in eight of ten field trials.  Using the OECD tolerance calculation procedures, the recommended tolerance for the residues of metconazole in sunflower is 0.7 ppm.


Appendix A.  Tabular Summary of Metabolites 

Table A.1.  Structures and Names of  Metconazole and Metabolites
Common name/code
ID No.
Chemical name
Chemical structure
Metconazole
(AC 900768)
(CL 900768)

5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol

Cis-isomer


Trans-isomer

M1
(CL 359451)

5-[(4-chlorophenyl)methyl]-2-methoxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol

M11
(CL 382390)

5-[(4-chlorophenyl)methoxyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol

M12
(CL 359138)
5-[(4-chlorophenyl)methyl]-2-carboxyl-2-methyl-1-(1H-1,2,4-
triazol-1-ylmethyl)-1-cyclopentanol


M13 
(CL359139)
3-(4-chlorobenzyl)-2-hydroxy-1-methyl-2-[1,2,4]triazol-1-ylmethyl-cyclopentanecarboxylic acid
                                       
M21
(CL 382391)
5-[(4-chlorophenyl)methoxyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol


  
M30
(CL 382389)
5-[(4-chlorophenyl)keto]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol


M31
(CL 359139)

(1S*,3R*,5S*)-3-hydroxy-cis-metconazole

1,2,4-Triazole
(1,2,4-T; free triazole)
1H-1,2,4-triazole

Triazolylalanine
(Triazole alanine)
(TA)
(M35)
(CL 147267)

2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acid



Triazolylacetic acid
(Triazole acetic acid)
(TAA)

1H-1,2,4-triazol-1-yl acetic acid


Hydroxymetconazole
(1RS,5RS,1RS,5SR)-5-(4-hydroxybenzyl)-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol 








Appendix B.  Field Trial Geographic Distribution

Table C.1.	Dry Bean Trial Numbers and Geographical Locations.
Crop
                                  No. Trials
                              NAFTA Growing Zone
                                     Total

                                       
                                       1
                                       2
                                       3
                                       4
                                       5
                                       6
                                       7
                                       8
                                       9
                                      10
                                      11
                                      12
                                       
Bean, dried
                                     Sub.
                                       1
                                      --
                                      --
                                      --
                                       6
                                      --
                                       1
                                       1
                                       1
                                       1
                                       2
                                      --
                                      13
                                       
                                     Req.1
                                      1/0
                                      --
                                      --
                                      --
                                      5/4
                                      --
                                      2/1
                                      1/1
                                      1/1
                                      1/1
                                      1/1
                                      --
                                     12/9
1 As per Table 5 of 860.1500 for bean, dried; the second number reflects a 25% reduction in the number of field trials allowed for the crop as a representative commodity in support of a crop group/subgroup tolerance or when application results in no quantifiable residues.

Table C.2.	Dry Pea Trial Numbers and Geographical Locations.
Crop
                                  No. Trials
                              NAFTA Growing Zone
                                     Total

                                       
                                       1
                                       2
                                       3
                                       4
                                       5
                                       6
                                       7
                                       8
                                       9
                                      10
                                      11
                                      12
                                       
Pea, dried
                                     Sub.
                                      --
                                      --
                                      --
                                      --
                                       1
                                      --
                                     1[2]
                                      --
                                      --
                                       1
                                       2
                                      --
                                       5
                                       
                                     Req.1
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                       5
[1] As per Table 1 of OCSPP 860.1500 for peas (dried shelled); requested 5 trials, regions are not specified.
[2] HED has concluded that two trials conducted in ND (Zone 7) are replicate trials for purposes of OCSPP 860.1500 data requirements.

Table C.3.	Sunflower Trial Numbers and Geographical Locations.
Crop
                                  No. Trials
                              NAFTA Growing Zone
                                     Total

                                       
                                       1
                                       2
                                       3
                                       4
                                       5
                                       6
                                       7
                                       8
                                       9
                                      10
                                      11
                                      12
                                      13
                                      14
                                       
Sunflower
                                     Sub.
                                      --
                                      --
                                      --
                                      --
                                       3
                                      --
                                     3[3]
                                       1
                                      --
                                      --
                                      --
                                      --
                                      --
                                       3
                                      10
                                       
                                     Req.1
                                      --
                                      --
                                      --
                                      --
                                      3/2
                                      --
                                      4/3
                                      1/1
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                      8/6
                                       
                                     Req.2
                                      --
                                      --
                                      --
                                      --
                                       2
                                      --
                                       1
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
                                       2
                                       5
1 As per Table 5 of 860.1500 for sunflower; the second number reflects a 25% reduction in the number of field trials allowed for the crop as a representative commodity in support of a crop group/subgroup tolerance or when application results in no quantifiable residues.
2 As per Table 1.2 of PMRA Directive DIR98-02 for sunflower.
[3]  HED has concluded that two trials conducted in Velva, ND (Zone 7) are replicate trials for purposes of OCSPP 860.1500 data requirements.




Appendix C.  International Residue Limits Table

                       Metconazole (125619; 08/27/2014)
Summary of US and International Tolerances and Maximum Residue Limits 
Residue Definition:
US
Canada
Mexico[2]
Codex
40 CFR §180.617
Metconazole [5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol]
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl) cyclopentanol

None
Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US
Canada
Mexico[2]
Codex
Fruit, stone, group 12-12
0.2
0.2 American plums, apricots, beach plums, black cherries, Canada plums, capulins, cherry plums, chicksaw plums, damson plums, fresh prune plums, Japanese apricots, Japanese plums, klamath plums, nanking cherries, nectarines, peaches, plumcots, plums, sloes, sweet cherries, tart cherries


Nut, tree, group 14-12
0.04
0.04 African tree nuts, almond nuts, beechnuts, black walnuts, Brazil nuts, Brazilian pine nuts, bunya nuts, bur oak nuts, butternuts, Cajou nuts, candlenuts, cashew nuts, chestnuts, chinquapin nuts, coconuts, coquito nuts, dika nuts, English walnuts, ginkgo nuts, Guiana chestnuts, hazelnuts (filbert), heartnuts, hickory nuts, Japanese horse-chestnuts, macadamia nuts, mongongo nuts, monkey-pot nuts, monkey puzzle nuts, Okari nuts, Pachira nuts, peach palm nuts, peanuts, pecan nuts, pequi nuts, Pili nuts, pine nuts, pistachio nuts, Sapucaia nuts, tropical almond nuts, yellow horn nuts


Pea and bean, dried shelled, except soybean, subgroup 6C
0.15
0.15 Dry (adzuki beans, beans, blackeyed peas, 
 broad beans, catjang seeds, chickpeas, cowpea seeds, field peas, guar seeds, kidney beans, lablab beans, lentils, lima beans, moth beans, mung beans, navy beans, pigeon peas, pink beans, pinto beans, rice beans, southern peas, tepary beans, urd beans, grain lupin
0.05 dry soybeans


Rapeseed subgroup 20A
0.08
0.08 Seeds (borage, cuphea, echium, flax, gold of pleasure, hare's ear mustard, milkweed, mustard (oilseed type), oil radish, poppy, rapeseed (canola), sesame, sweet rocket 


Sunflower subgroup 20B
0.7













Completed:  M. Negussie; 08/27/2014
[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.




Appendix D.  OECD MRL Calculation Procedure Inputs/Outputs

Sunflower Seeds (MRID 49297803) - Metconazole

0.245-0.259 lb ai/A; 20-21 day PHI
                               Residues (mg/kg)
                                       n
                                   < 0.04 
                                       2
                                    0.0402
                                       1
                                     0.043
                                       1
                                     0.045
                                       1
                                    0.0883
                                       1
                                    0.0957
                                       1
                                     0.196
                                       1
                                     0.237
                                       1
                                     0.44
                                       1


                                  Metconazole
                                Sunflower Seeds
                                  USA, Canada
                      0.245-0.259 lb ai/A; 20-21 day PHI
 
 
Total number of data (n)
                                      10
Percentage of censored data
                                      20%
Number of non-censored data
                                       8
Lowest residue
                                     0.040
Highest residue
                                     0.440
Median residue
                                     0.067
Mean
                                     0.127
Standard deviation (SD)
                                     0.131
Correction factor for censoring (CF)
                                     0.867
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                     0.440
- Mean + 4 SD
                                     0.649
- CF x 3 Mean
                                     0.329
Unrounded MRL
                                     0.649
 
                                       
Rounded MRL
                                      0.7
 
                                       
 
 




Sunflower (MRID 49297803)  -  TA

0.245-0.259 lb ai/A; 20-21 day PHI
                               Residues (mg/kg)
                                       n
                                   < 0.02 
                                       1
                                    0.0213
                                       1
                                    0.0243
                                       1
                                    0.0253
                                       1
                                     0.042
                                       1
                                    0.0562
                                       1
                                    0.0654
                                       1
                                    0.0663
                                       1
                                     0.073
                                       1
                                     0.148
                                       1



                                      TA
                                Sunflower Seeds
                                  USA, Canada
                      0.245-0.259 lb ai/A; 20-21 day PHI
 
 
Total number of data (n)
                                      10
Percentage of censored data
                                      10%
Number of non-censored data
                                       9
Lowest residue
                                     0.020
Highest residue
                                     0.148
Median residue
                                     0.049
Mean
                                     0.054
Standard deviation (SD)
                                     0.039
Correction factor for censoring (CF)
                                     0.933
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                     0.148
- Mean + 4 SD
                                     0.209
- CF x 3 Mean
                                     0.152
Unrounded MRL
                                     0.209
 
                                       
Rounded MRL
                                      0.2
 
                                       
 
 



Dry Bean (MRID 49297801)  -  TA

0.245-0.259 lb ai/A; 19-23 day PHI
                               Residues (mg/kg)
                                       n
                                   < 0.02 
                                       6
                                    0.0208
                                       1
                                    0.0218
                                       1
                                    0.0236
                                       1
                                    0.0242
                                       1
                                    0.0275
                                       1
                                    0.0369
                                       1
                                     0.346
                                       1

                                      TA
                                   Dry bean
                                      USA
                      0.245-0.259 lb ai/A; 19-23 day PHI
 
 
Total number of data (n)
                                      13
Percentage of censored data
                                      46%
Number of non-censored data
                                       7
Lowest residue
                                     0.020
Highest residue
                                     0.346
Median residue
                                     0.021
Mean
                                     0.048
Standard deviation (SD)
                                     0.090
Correction factor for censoring (CF)
                                     0.692
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                     0.346
- Mean + 4 SD
                                     0.407
- CF x 3 Mean
                                     0.099
Unrounded MRL
                                     0.407
 
                                       
Rounded MRL
                                      0.4
 
                                       
 
 


Dry Pea (MRID 49297802)  -  Metconazole

0.250-0.258 lb ai/A; 20-22 day PHI
                               Residues (mg/kg)
                                       n
                                   < 0.04 
                                       4
                                    0.0562
                                       1

                                  Metconazole
                                    Dry Pea
                                      USA
                      0.250-0.258 lb ai/A; 20-22 day PHI
 
 
Total number of data (n)
                                       5
Percentage of censored data
                                      80%
Number of non-censored data
                                       1
Lowest residue
                                     0.040
Highest residue
                                     0.056
Median residue
                                     0.040
Mean
                                     0.043
Standard deviation (SD)
                                     0.007
Correction factor for censoring (CF)
                                     0.467
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                     0.056
- Mean + 4 SD
                                     0.072
- CF x 3 Mean
                                     0.061
Unrounded MRL
                                     0.072
 
                                       
Rounded MRL
                                     0.08
 
                                       
 High uncertainty of MRL estimate.
[Small dataset and high level of censoring]



Dry Pea (MRID 49297802) - TA

0.250-0.258 lb ai/A; 20-22 day PHI
                               Residues (mg/kg)
                                       n
                                     0.187
                                       1
                                     0.459
                                       1
                                     0.591
                                       1
                                     0.701
                                       1
                                     2.38
                                       1


                                      TA
                                    Dry Pea
                                      USA
                      0.250-0.258 lb ai/A; 20-22 day PHI
 
 
Total number of data (n)
                                       5
Percentage of censored data
                                      0%
Number of non-censored data
                                       5
Lowest residue
                                     0.187
Highest residue
                                     2.380
Median residue
                                     0.591
Mean
                                     0.864
Standard deviation (SD)
                                     0.869
Correction factor for censoring (CF)
                                     1.000
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                     2.380
- Mean + 4 SD
                                     4.340
- CF x 3 Mean
                                     2.591
Unrounded MRL
                                     4.340
 
                                       
Rounded MRL
                                       5
 
                                       
 High uncertainty of MRL estimate.
[Small dataset]


