Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

DATE: 7 July 2014

SUBJECT: Metrafenone. Petition to Establish Permanent Tolerances (with Section 3 

Registration) for Residues Resulting from Use of the Fungicide on Apricot,

Cherry Subgroup 12-12A, Peach Subgroup 12-12B, Fruiting Vegetables Group

8-10, Small Vine Climbing Fruit Except Fuzzy Kiwifruit Subgroup 13-07F, Hops,

Pome Fruits Group 11-10, and Cucurbit Vegetables Group 9; Evaluation of 

Conditional Data. Summary of Analytical Chemistry and Residue Data. 

PC Code: 000325 DP Barcodes: D407432, D411389, D414077, 

D416465, D417602

Decision Numbers: 472590, 476552, 480739, 484338 Registration Number: 7969-284

Petition Numbers: 3F8163, 3F8187, 3E8211 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case Number: 7052

TXR Number: NA CAS Number: 220899-03-6

MRID Numbers: 48981303, -04, -07 & -08; 

49055901 & -02; 49119101 to -09; 49145401 to -08; 

49267201 to -05

40 CFR: §180.624

FROM: William T. Drew, Chemist

Dennis McNeilly, Chemist

Risk Assessment Branch II (RAB2)

Health Effects Division (HED), 7509P

THRU: Elizabeth Holman, Physical Scientist

Michael Doherty, PhD, Senior Scientist

RAB2/HED, 7509P

TO: Tony Kish and Heather Garvie, RM Team 22

Fungicide Branch (FB)

Registration Division (RD), 7505P

and

Barbara Madden and Andrew Ertman, RM Team 5

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

RD, 7505P
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Table of Contents

1.0 Executive Summary.............................................................................................................. 4

2.0 Regulatory Recommendations.............................................................................................. 7

2.1 Data Deficiencies/Data Needs .......................................................................................... 7

2.2 Tolerance Considerations.................................................................................................. 8

2.2.1 Enforcement Analytical Method/Multiresidue Methods.......................................... 8

2.2.2 Recommended Tolerances........................................................................................ 9

2.2.3 Revisions to Petitioned-For Tolerances.................................................................... 9

2.2.4 International Harmonization ..................................................................................... 9

2.3 Label Recommendations................................................................................................ 10

2.4 Submittal of Analytical Reference Standards (860.1650) ............................................. 10

3.0 Chemical Identity............................................................................................................... 10

3.1 Nomenclature................................................................................................................. 11

3.2 Physicochemical Characteristics.................................................................................... 11

3.3 Pesticide Use Pattern/Directions for Use (860.1200) .................................................... 12

4.0 Metabolite/Degradate Residue Profile............................................................................... 13

4.1 Nature of the Residue..................................................................................................... 19

4.1.1 Summary of Plant and/or Livestock Metabolism (860.1300)................................. 24

4.1.2 Summary of Confined Rotational Crops (860.l850)............................................... 27

4.1.3 Summary of Rat Metabolism................................................................................ 279

4.1.4 Summary of Environmental Degradation ............................................................... 29

5.0 Residue Profile................................................................................................................... 30

5.1 Residue Analytical Methods (860.1340) ...................................................................... 30

5.1.1 Data Collection Methods ........................................................................................ 30

5.1.2 Multi-Residue Methods (860.1360)........................................................................ 33

5.1.3 Tolerance Enforcement Methods............................................................................ 34

5.2 Storage Stability (860.1380).......................................................................................... 38

5.3 Residue Data .................................................................................................................. 40

5.3.1 Crop Field Trials (860.1500) .................................................................................. 40

5.3.2 Field Rotational Crops (860.1900) ......................................................................... 55
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5.3.3 Processed Food and Feed (860.1520)..................................................................... 55

5.3.4 Meat, Milk, Poultry and Eggs (860.1480) .............................................................. 60

5.3.5. Food Handling (860.1460)...................................................................................... 61

5.3.6 Water, Fish and Irrigated Crops (860.1400)........................................................... 61

5.4 Food Residue Profile...................................................................................................... 61

6.0 Tolerance Derivation ......................................................................................................... 62

References..................................................................................................................................... 63

Attachment 1: International Residue Limit Status....................................................................... 65

Attachment 2: OECD MRL (Tolerance) Assessment Calculations..............................................66 
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1.0 Executive Summary

Metrafenone (with CAS name (3-bromo-6-methoxy-2-methylphenyl)(2,3,4-trimethoxy-6-

methylphenyl)methanone) is a benzophenone fungicide that has preventative properties for 

control of powdery mildew produced by assorted pathogens in various fruits and vegetables. 

In PP#3F8163, BASF Corporation has proposed the establishment of permanent tolerances for 

residues of the fungicide metrafenone in/on the following raw agricultural commodities (RACs), 

at the level listed below.

Fruits, pome group 11-10................................................................. 1.5 ppm

In PP#3F8187, BASF Corporation has proposed the establishment of permanent tolerances for 

residues of the fungicide metrafenone in/on the following RACs, at the level listed below. 

Vegetables, Fruiting, group 8-10 ..................................................... 1.0 ppm

In PP#3E8211, Interregional Research Project Number 4 (IR-4) has proposed the establishment 

of permanent tolerances for residues of the fungicide metrafenone in/on the following RACs, at 

the levels listed below. 

Apricot ............................................................................................. 0.7 ppm

Cherry subgroup 12-12A .................................................................... 2 ppm

Fruit, small, vine climbing, except fuzzy kiwifruit, 

subgroup 13-07F .............................................................................. 4.5 ppm

Hop, dried cones .............................................................................. 70 ppm

Peach subgroup 12-12B................................................................... 0.7 ppm

Vegetable, cucurbit, group 9............................................................ 0.5 ppm

The nature of the residue in plants is adequately understood, based on acceptable grape and 

cucumber metabolism studies. HED has previously determined that, for tolerance enforcement 

purposes, the residue of concern (ROC) in primary crops is parent metrafenone only. HED also 

concluded previously that certain unidentified and tentatively identified residues from the grape 

metabolism study should be accounted for in the dietary risk assessment. 

In conjunction with PP#3F8163, BASF submitted a FIFRA Section 3 requesting registration of a 

suspension concentrate (SC) formulation (Vivando; EPA Registration #7969-284), containing 

2.5 pounds of the active ingredient per gallon (lb ai/gal), for use on pome fruits group 11-10. 

The product is proposed for up to 3 foliar applications to pome fruits at 0.2-0.3 lb ai per acre (lb 

ai/A) per application, with a maximum seasonal application rate of 0.9 lb ai/A, a minimum retreatment interval (RTI) of 7 days, and a pre-harvest interval (PHI) of 7 days. 
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In conjunction with PP#3F8187, BASF submitted a FIFRA Section 3 requesting registration of 

the SC formulation, Vivando, for use on fruiting vegetables group 8-10. The product is proposed 

for up to 3 foliar applications to fruiting vegetables at 0.2-0.3 lb ai/A per application, with a 

maximum seasonal application rate of 0.9 lb ai/A, a minimum RTI of 7 days, and a PHI of 0

days. 

In conjunction with PP#3F8211, IR-4 submitted a FIFRA Section 3 requesting registration of the

SC formulation, Vivando, for use on apricots, cherry subgroup 12-12A, peach subgroup 12-12B 

(up to 2 foliar applications at 0.2-0.3 lb ai/A per application, with a maximum seasonal 

application rate of 0.6 lb ai/A, a minimum RTI of 7 days, and a PHI of 7 days), hops (same use 

pattern, except a PHI of 3 days), cucurbit vegetables group 9 (up to 3 foliar applications at 0.2-

0.3 lb ai/A per application, with a maximum seasonal application rate of 0.9 lb ai/A, a minimum 

RTI of 7 days, and a PHI of 0 days), and small vine-climbing fruit except fuzzy kiwifruit 

subgroup 13-07F (same use pattern, except a minimum RTI of 14 days, and a PHI of 14 days). 

Crop Field Trials: The number and geographic distribution of the field trials are adequate, and 

the use patterns are consistent with the maximum proposed use pattern regarding application 

rate, PHI, and minimum RTIs. 

Adequate pome fruit field trial data were submitted in support of the proposed use. The 

submitted data support the proposed tolerance of 1.5 ppm in pome fruits (group 11-10). 

Adequate fruiting vegetable field trial data were submitted in support of the proposed use. The 

submitted data support a recommended tolerance of 0.90 ppm, rather than the proposed tolerance 

of 1.0 ppm, in fruiting vegetables (group 8-10). 

Adequate cucurbit vegetable field trial data were submitted in support of the proposed use. The 

submitted data support the proposed tolerance of 0.5 ppm in cucurbit vegetables (group 9); HED 

recommends that the tolerance be established at 0.50 ppm. 

Adequate cherry field trial data were submitted in support of the proposed use. The submitted 

data support the proposed tolerance of 2 ppm in the cherry subgroup (12-12A); HED 

recommends that the tolerance be established at 2.0 ppm. 

Adequate peach field trial data were submitted in support of the proposed use. The submitted 

data support the proposed tolerance of 0.7 ppm in the peach subgroup (12-12B); HED 

recommends that the tolerance be established at 0.70 ppm. 

Adequate hops field trial data were submitted in support of the proposed use. The submitted data 

support the proposed tolerance of 70 ppm in hops. 
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The proposed tolerance of 4.5 ppm in small vine climbing fruits except fuzzy kiwifruit (subgroup 

13-07F) is based upon existing data for grapes (the representative commodity for the subgroup). 

Upon establishment of the tolerance in subgroup 13-07F, the existing tolerance in grapes should 

be removed. 

The proposed tolerance of 0.7 ppm in apricots is based upon the submitted data for peaches. 

HED recommends that the tolerance be established at 0.70 ppm. 

Processing Studies: The apple processing study data indicated that residues of metrafenone do 

not concentrate appreciably in any apple processed commodities, with the exception of apple 

sauce, in which the processing factor was 4.5X. Processing factors ranged from <1X to 1.2X

(average of 2 trials for each commodity) for the other processed commodities. 

The tomato processing study data indicated that residues of metrafenone do not concentrate in 

tomato processed commodities, with the exception of peel and wet pomace, in which residues 

concentrate, on average, by factors of 6.3X and 5.1X, respectively. The mean transfer factor of 

tomato peel and wet pomace (>1) indicates that the metrafenone residues are mainly located in 

the tomato peels. 

Residue Analytical Methods: There is an adequate enforcement method available for the 

quantitation of metrafenone in plant commodities (Method FAMS 105-01). Additionally, BASF 

has proposed the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method as a 

new enforcement method for metrafenone residues in plant commodities, and DFG Method S19 

(extended revision) as the new enforcement method for metrafenone residues in livestock 

commodities. 

Storage Stability: Adequate storage stability data are available to support the storage durations 

and conditions of samples from the submitted field trial, metabolism and processing studies. 

Meat, Milk, Poultry and Eggs: The only livestock feed item associated with the proposed new 

uses is apple wet pomace, and it is fed only to dairy cattle. Based on the dietary burden to dairy

cattle of metrafenone residues in apple wet pomace, and the results of the goat metabolism study, 

it is not expected that detectable residues would be found in cattle commodities. Therefore, 

tolerances in livestock commodities are not required. 

Conditional Data: Additional method validation data were requested for the analytical Method 

FAMS 105-01. In addition, radiovalidation data were required to demonstrate that Method 

FAMS 105-01 adequately recovers weathered residues of metrafenone from grapes. BASF 

submitted the information requested to satisfy the conditions of registration (MRIDs #48981305,

48981306 and 48981307). 
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HED accepts the cucumber metabolism and other extraction efficiency data which show 

adequate extractability using the 4:1 n-heptane/acetone solvent. This resolves HED concerns

about the analytical Method FAMS 105-01 adequately recovering weathered residues of 

metrafenone from grapes, and the issue of accounting for aged residues in the grape metabolism 

study. It also resolves the issue of the extraction solvent used in the data collection method, 

BASF Method 535/0, being different than that used in the proposed enforcement method. 

Therefore, all of HED’s previously identified conditional data requirements have been 

sufficiently addressed. 

MRL Harmonization: The proposed uses in IR-4’s petition (PP#3E8211) are also being 

reviewed by Canada’s Pest Management Regulatory Agency (PMRA). EPA and PMRA have 

agreed to harmonize (wherever possible) the recommended tolerances and maximum residue 

limits (MRLs), based on use of the Organization for Economic Cooperation and Development 

(OECD) tolerance calculation procedure. Harmonization of EPA’s recommended tolerances 

with PMRA’s recommended MRLs has been agreed upon for all commodities requested in 

PP#3E8211 except apricot. PMRA has decided against translating the peach field trial data to 

apricot, and will therefore not be establishing an MRL in apricot. 

2.0 Regulatory Recommendations

HED has examined the residue chemistry database for metrafenone. Pending submission of a 

revised Section F (to propose tolerance levels in accordance with those recommended by HED, 

and to correct some of the commodity definitions), there are no residue chemistry issues that 

would preclude establishing tolerances in the requested commodities. HED recommends in 

favor of establishing tolerances for residues of metrafenone as specified in Section 2.2.2, below.

2.1 Data Deficiencies/Data Needs

No additional data are required to support HED’s currently recommended tolerances in pome 

fruits, fruiting vegetables, cucurbit vegetables, the cherry subgroup (12-12A), the peach 

subgroup (12-12B), hops, small vine climbing fruits except fuzzy kiwifruit subgroup (13-07F), 

and apricots. 

HED previously recommended that the following actions be required as a condition of 

registration (D331685; D. McNeilly; 18 February 2010). The conditional data (MRIDs 

#48981305, 48981306 and 48981307) were submitted in response to the data deficiencies listed 

below. 
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1. Additional method validation data should be submitted for Method FAMS 

105-01 reflecting fortifications at 4.5 ppm for grapes, and at both 0.05 

ppm, the limit of quantitation (LOQ), and 17 ppm for raisins. 

2. Radiovalidation data are required to demonstrate that Method FAMS 105-

01 adequately recovers weathered residues of metrafenone from grapes. 

HED is willing to accept cucumber data currently being collected, as 

proposed by the registrant, provided such data show adequate 

extractability by the 4:1 n-heptane/acetone solvent mixture. 

3. Because the extraction solvent used in the data collection method is 

different than that used in the proposed enforcement method, 

radiovalidation data are required to support the data collection method, 

BASF Method 535/0. Samples from the cucumber metabolism study may

also be used to generate these data. 

These conditional data submissions (D407462) have been reviewed, and have adequately 

resolved all of HED’s previously identified issues. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method/Multiresidue Methods

There is an adequate enforcement method available for the quantitation of metrafenone in plant 

commodities (Method FAMS 105-01). Additionally, BASF has proposed the QuEChERS

method as a new enforcement method for metrafenone that will cover fortifications at 4.5 ppm in 

grapes, and at both the LOQ (0.05 ppm) and 17 ppm in raisins. QuEChERS stands for “Quick, 

Easy, Cheap, Effective, Rugged and Safe.” The method that was initially submitted for 

enforcement (Method FAMS 105-01) of metrafenone in grapes is an older gas chromatography 

(GC) method that was developed in 1998. Although Method FAMS 105-01 performs adequately 

for metrafenone in grapes and raisins, it was decided that a more modern methodology was 

needed which could take advantage of current advances in sample clean-up and liquid 

chromatography with tandem mass spectrometric detection (LC/MS/MS) techniques. The 

QuEChERS method was validated on eight diverse matrices (MRID #48981303) according to 

the OECD guidance document on pesticide analytical methods (ENV/JM/MONO(2007)17). The 

method has also been subjected to an independent laboratory validation (ILV) by Sprecht 

Laboratories (MRID #48981304) in accordance with the OECD guidance document. 

Acceptable multiresidue methods testing data have previously been submitted for metrafenone in 

grapes. The data indicate that multiresidue methods may be suitable for determining residues of 

metrafenone in grapes for tolerance enforcement. 
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2.2.2 Recommended Tolerances

TABLE 2.2.2 Tolerance Summary for Metrafenone. 

Commodity as Proposed by 

Registrant

Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Apricot 0.7 0.70 Based on submitted peach data.

Cherry subgroup 12-12A 2 2.0

Fruits, pome group 11-10 1.5 1.5 Fruit, pome, group 11-10

Fruit, small, vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F

4.5 4.5* Based on data supporting the 

existing tolerance in grape.

Hop, dried cones 70 70

Peach subgroup 12-12B 0.7 0.70

Vegetable, cucurbit, group 9 0.5 0.50

Vegetables, Fruiting, group 8-10 1.0 0.90 Vegetable, fruiting, group 8-10

*Upon establishment of the tolerance in subgroup 13-07F, the existing tolerance in grapes should be removed.

2.2.3 Revisions to Petitioned-For Tolerances

Instead of the proposed tolerance in cucurbit vegetables (0.5 ppm), HED recommends 

establishing the tolerance at 0.50 ppm, in order to avoid the situation where a field sample 

containing residues significantly above the tolerance (0.54 ppm, for example) would be 

considered non-violative. For the same reason, HED recommends that the proposed tolerances

of 0.7 ppm in the peach subgroup (12-12B) and apricots be revised to 0.70 ppm. Similarly, HED 

recommends that the proposed tolerance of 2 ppm in the cherry subgroup (12-12A) be revised to 

2.0 ppm. 

Because HED determined that 2 of the 9 pepper field trials should be considered replicates, the 

OECD tolerance calculation procedure result for 8 trials was 0.9 ppm, instead of the 1 ppm result 

when 9 trial values were entered. The tolerance calculation result for tomatoes was 0.6 ppm, 

which is in accordance with the Agency’s guidelines for setting a crop group tolerance (within 

5X of the result for peppers). Since a crop group tolerance is set based on the representative 

commodity having the larger (or largest) tolerance calculation result, HED recommends that the 

tolerance in fruiting vegetables (group 8-10) be established at 0.90 ppm. 

2.2.4 International Harmonization

The proposed uses in IR-4’s petition (PP#3E8211) are also being reviewed by Canada’s PMRA. 

EPA and PMRA have agreed to harmonize (wherever possible) the recommended tolerances and 

MRLs, based on use of the OECD tolerance calculation procedure. Harmonization of EPA’s 

recommended tolerances with PMRA’s recommended MRLs has been agreed upon for all 

commodities requested in PP#3E8211 except apricot. PMRA has decided against translating the 

peach field trial data to apricot, and will therefore not be establishing an MRL in apricot. 
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2.3 Label Recommendations

None.

2.4 Submittal of Analytical Reference Standards (860.1650)

The analytical standard for metrafenone, with an expiration date of 1 August 2019, is currently

available in the EPA’s National Pesticide Standards Repository (NPSR), per Email 

communication from Theresa Cole of the Biological and Economic Analysis Division’s 

(BEAD’s) Analytical Chemistry Branch (ACB) on 7 January 2014. The metrafenone metabolite 

is also currently available, with an expiration date of 1 November 2014. The registrant is 

required to maintain reasonable amounts of the analytical reference standard for metrafenone in 

the NPSR. However, as the metabolite is not included in the tolerance expression, it is not 

required to be stocked in the NPSR. When necessary, a new reference standard, or updated 

certificate of analysis (COA), should be sent to the ACB, which is located at Fort Meade, MD. It 

should be sent to the attention of either Theresa Cole or Thuy Nguyen at the address listed 

below, along with a letter of transmittal. Please note that the full 9-digit ZIP Code is 

required, or the mail will be returned to the registrant. 

USEPA

National Pesticide Standards Repository

Analytical Chemistry Branch/BEAD/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

The letter of transmittal should include the assay of the standard, name of the analytical method 

used, a statement of principal impurities, purification procedures employed, storage 

requirements, and special precautions for safe handling. Replacement of standards may be 

required periodically if supplies are exhausted, if the standards expire, or if decomposition 

occurs during storage. Material Safety Data Sheets (MSDSs) must accompany all analytical 

standards as specified in 29CFR§1910.1200 by the Occupational Safety and Health 

Administration (OSHA). 

3.0 Chemical Identity

Metrafenone is a benzophenone fungicide with preventative properties. It is intended for the 

control of powdery mildew produced by Uncinula necator in grapes and Podosphaera in pome 

fruit. The chemical structure and nomenclature of metrafenone are presented in Table 3.1, 

below. The physicochemical properties of the technical grade of metrafenone are presented in 

Table 3.2, below. 
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3.1 Nomenclature

TABLE 3.1 Metrafenone Nomenclature

Compound

Common name Metrafenone

Company experimental names BAS 560 F; AC 375839; CL 375839

Molecular formula C19H21BrO5

Molecular weight 409.27

IUPAC name 3′-bromo-2,3,4,6′-tetramethoxy-2′,6-dimethylbenzophenone

CAS name (3-bromo-6-methoxy-2-methylphenyl)(2,3,4-trimethoxy-6-

methylphenyl)methanone

CAS registry number 220899-03-6

End-use product (EP) Vivando Fungicide (2.5 lb ai/gal; EPA Registration #7969-284)

3.2 Physicochemical Characteristics

TABLE 3.2 Physicochemical Properties of Metrafenone.

Parameter Value Reference

Melting point/range 99.2-100.8oC Petition administrative 

pH 3.45 (1% aqueous suspension) materials (MRID 49055900)

Density 1.45 g/cm3(20°C)

Water solubility

deionized

pH >5

pH 7

pH 9

mg/L

0.474

0.552

0.492

0.457

Solvent solubility

acetone

acetonitrile

dichloromethane

ethyl acetate

n-hexane

methanol

toluene

g/L

403

165

1950

261

4.8

26.1

363

Vapor pressure 1.15 x 10-6 mm Hg (20oC)

Dissociation constant, pKa No dissociation

Octanol/water partition coefficient, 

Log [KOW]

4.3 (25oC, pH 4)

UV/visible absorption spectrum Not available

O CH3

CH3

O

CH3

O O

H3C CH3 O

CH3

Br
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Metrafenone is a solid under ambient conditions, and has low volatility. The compound has a 

relatively low solubility in water, and moderate to high solubility in organic solvents. Its 

octanol/water partition coefficient suggests that accumulation of metrafenone in fatty tissues is 

possible. 

3.3 Pesticide Use Pattern/Directions for Use (860.1200)

BASF submitted an undated draft label for the BASF 2.5 lb ai/gal formulation (Vivando, EPA 

Registration #7969-284). A summary of the proposed use patterns is presented in Table 3.3, 

below.

TABLE 3.3 Summary of Proposed Directions for Use of Metrafenone. 

Application Timing; 

Type; Equipment1

Use Rate

(lb ai/A)

Maximum

Uses Per 

Season

Max. Seasonal 

Use Rate

(lb ai/A)

PHI2

(Days)

Use Directions, Application 

Timing, and Limitations

Pome Fruits Group 11-10

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 3 0.90 7 Minimum RTI3of 7 days. Apply 

in a minimum of 10 gallons of 

spray solution per acre (GPA) for 

aerial applications. 

Fruiting Vegetables Group 8-10

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 3 0.90 0 Minimum RTI of 7 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 

Peach Subgroup 12-12B

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 2 0.60 7 Minimum RTI of 7 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 

Apricot

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 2 0.60 7 Minimum RTI of 7 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 

Cherry Subgroup 12-12A

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 2 0.60 7 Minimum RTI of 7 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 

Hops

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 2 0.60 3 Minimum RTI of 7 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 

Cucurbit Vegetables Group 9

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 3 0.90 0 Minimum RTI of 7 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 
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TABLE 3.3 Summary of Proposed Directions for Use of Metrafenone. 

Application Timing; 

Type; Equipment1

Use Rate

(lb ai/A)

Maximum

Uses Per 

Season

Max. Seasonal 

Use Rate

(lb ai/A)

PHI2

(Days)

Use Directions, Application 

Timing, and Limitations

Small Vine Climbing Fruit (Except Fuzzy Kiwifruit) Subgroup 13-07F

Prior to disease 

development; foliar; 

ground/aerial equipment.

0.20-0.30 3 0.90 14 Minimum RTI of 14 days. Apply 

in a minimum of 10 GPA for 

aerial applications. 

1. The labels state that the product must be applied before visual symptoms of powdery mildew appear, as it has no 

curative properties, and will not control latent or established infections of powdery mildew. Aerial 

applications may be made where the use of ground equipment is not possible. Not to be applied via 

chemigation. No more than 2 sequential applications may be made before alternating to a labeled fungicide 

with a different mode of action. 

2. PHI = Pre-Harvest Interval. 

3. RTI = Re-Treatment Interval. 

A 12-hour re-entry interval (REI) is specified. 

Discrepancies in the stated minimum RTI (7 versus 14 days) and minimum PHI (0 versus 7 days) 

for pome fruit were noted in various proposed master and supplemental labels for Vivando. The 

registrant stated that the correct RTI and PHI are both 7 days for the use on pome fruit. RD 

should ensure that the final label lists the correct RTI and PHI. 

Conclusions: The proposed use directions are adequate to allow evaluation of the residue data 

relative to the requested uses. The proposed maximum seasonal use rates, minimum RTIs, and 

minimum PHIs are supported by the submitted crop field trial data.

4.0 Metabolite/Degradate Residue Profile

Grape: Based on the results of the grape metabolism study, the petitioner concluded that 

metrafenone is rapidly metabolized in grapes and grape vines to compounds more polar than the 

parent. There was no evidence of cleavage of the methanone bridge between the two rings of the 

compound. One metabolite that was tentatively identified in grape juice suggested a two-fold 

oxidation of the methyl group of the bromophenyl ring. Two metabolites tentatively identified in 

the acetone surface wash of mature grape leaves appeared to have been formed by oxidation of 

the methyl group of the bromophenyl or trimethoxyphenyl ring (with lactone formation), and a 

third metabolite suggested de-halogenation of the bromophenyl ring in addition to oxidation. 

The proposed metabolic profile in grapes is summarized in Figure 4.0.1, below. 

HED notes that the grape metabolism is only marginally adequate with respect to elucidation of 

all metabolites of concern, due to high percentages of unidentified residues. HED has not 

required a new grape metabolism study since the data were considered acceptable for both 
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tolerance enforcement and conducting an upper-bound dietary exposure assessment (D312307;

D. McNeilly; 24 August 2006). 

Cucumber: In the cucumber metabolism study, metrafenone accounted for 95.0% (6.076 ppm) 

of the total radioactive residues (TRR) in 0 days after treatment 1 (0-DAT1) foliage, 12.6% TRR 

(0.0021 ppm) in 14-DAT1 whole fruit, 42.4% TRR (0.0216 ppm) in 3 days after treatment 2 (3-

DAT2) whole fruit, 6.5% TRR (0.0009 ppm) in 3-DAT2 pulp, 61.0% TRR (0.1607 ppm) in 3-

DAT2 peel, and 80.4% TRR (7.084 ppm) in 3-DAT2 rest of the plant. No other components 

were identified in cucumber matrices. Remaining radioactivity consisted of multiple unknown 

components, characterized as polar, medium polar, or nonpolar. Polar unknowns (4-6/matrix) 

accounted for 13.1-36.9% TRR (0.0041-0.0067 ppm) in whole fruit (both sampling intervals) 

and pulp, and for 0.82% TRR (0.0715 ppm) in the rest of the plant, with no single component 

accounting for >18.9% TRR or >0.0299 ppm. Medium polar unknowns (4-20/matrix) accounted 

for 3.8-46.8% TRR (0.0062-1.2278 ppm) in all cucumber matrices, with no single component 

accounting for >12.2% TRR or >0.2742 ppm.

Based on the cucumber metabolism study, metrafenone is metabolized in cucumber and 

cucumber plant to more polar components. The unchanged parent was the major residue 

component in most matrices; in pulp, where metrafenone was a minor component, some polar 

components were detected at concentrations similar to those of metrafenone; see the data 

evaluation record (DER) for MRID #48981307.
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FIGURE 4.0.1 Proposed Metabolic Profile of Metrafenone in Grapes

Wheat: Based on the results of the wheat metabolism study, the petitioner proposed that 

metrafenone initially undergoes Phase I biotransformations, beginning with a single oxidative 

de-methylation of the parent to form CL 434223, CL 376991 and CL 377160, followed by a 

second oxidative de-methylation to form CL 1500835 (see Figure 4.0.2, below). The lactones

CL 3000402 and CL 1500831 are formed by oxidation at each benzylic carbon followed by 

cyclization. Oxidation of the methyl groups on either of the two phenyl rings gives rise to the 

aldehyde derivatives, CL 1500833, CL 1500834 and CL 1500837. Aromatic oxidation and 

O CH3

CH3

O

CH3

O O

H3C CH3 O

CH3

Br

O

H C3

O

O

H C3

O

CH3

O

O

CH3

Br

CH3

O O O

CH3

CH3

H C3

CHO

Br

O

CH3

O

CH3

O O O

O

Br

COOH

H C3

H C3

CH3

O

CH3

CH3

O O O

H3C O

H C3

CH3

O

CH3

CH3

CHO

Metrafenone

Surface rinse metabolite 2 Surface rinse metabolite 3

Juice metabolite Surface rinse metabolite 1
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oxidative de-methylations can produce CL 1500832. Additionally, CL 1500836 is formed by 

oxidation at the benzylic carbon of the bromophenyl-ring to an aldehyde followed by reductive 

de-bromination. The oxidations are proposed to be either enzymatic and/or chemical 

(photolysis) in nature. These Phase I processes are then followed by Phase II transformation

reactions, which are enzymatic glucoside conjugation reactions to yield the conjugates CL

1500838 and CL 1500839 from their corresponding aglycones, CL 434223 and CL 376991. 

These results show that the benzophenone backbone of metrafenone remains intact without 

cleavage at the carbonyl group. Rather, the metabolites are derived from metrafenone through 

various reactions occurring on the ring systems (see the DER for MRID #49119101).

FIGURE 4.0.2 Proposed Metabolic Profile of Metrafenone in Wheat

Goat: Following oral dosing with [bromophenyl-6-

14C]-metrafenone at 13 and 87 ppm in the 

diet for 5 consecutive days, TRR in the low and high dose groups, respectively, were <0.005 and 

0.008-0.010 ppm in milk, 0.231 and 1.278 ppm in liver, 0.060 and 0.329 ppm in kidney, <0.005 
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and 0.008 ppm in muscle, and <0.005 and 0.015 ppm in fat. Following oral dosing with 

[trimethoxyphenyl-U14C]-metrafenone at 8 and 60 ppm in the diet for 5 consecutive days, TRR 

in the low and high dose groups, respectively, were <0.005 and <0.005-0.006 ppm in milk, 0.208 

and 0.718 ppm in liver, 0.047 and 0.157 ppm in kidney, <0.005 and 0.006 ppm in muscle, and 

<0.005 and 0.022 ppm in fat. Radioactivity in milk was generally stable throughout the dosing 

period. Most of the administered dose was excreted (75.7-85.7%), with the majority (61.8-

74.1%) excreted in the feces. 

Parent was the major residue in milk (24.12% TRR), and was the major and only identified 

residue component in fat, accounting for 60.00-85.32% TRR. Metrafenone was a minor residue 

in liver (2.74-3.49% TRR) and kidney (3.25-4.35% TRR). Region of interest 13 (ROI-13) was a 

major residue component in milk (10.67% TRR) and was the major residue component in liver 

and kidney, accounting for 14.77-21.05% TRR and 26.29-28.15% TRR, respectively. ROI-9 

was also a major component in liver and kidney, accounting for 9.89-13.23% TRR and 9.51-

13.57% TRR, respectively; ROI-9 was a minor component in milk (2.83% TRR). ROI-16 was a 

minor residue component in milk (3.8% TRR), liver (6.41-7.12% TRR), and kidney (1.46-4.19% 

TRR). Remaining radioactivity was found to consist of up to 18 minor ROIs, together 

accounting for: 55.94% TRR in milk; 13.45-14.46% TRR in fat; 50.63-61.70% TRR in liver; 

and 48.81-55.08% TRR in kidney. The single largest ROI accounted for 11.7% TRR in TMPlabel liver, with the majority (10.86% TRR) found in the pepsin hydrolysate. 

Based on the submitted goat metabolism study, the registrant has proposed the following 

metabolic pathway for metrafenone in ruminants (see Figure 4.0.3, below). Metabolism of 

metrafenone in lactating goat occurred at the methyl and methoxy groups on the rings. 

Hydroxylation of the methyl groups yielded hydroxymethyl derivatives, whereas Odemethylation yielded hydroxyphenyl derivatives. These hydroxylated metabolites underwent 

Phase II glucuronidation to produce various mono-O-glucuronides. All of the prominent goat 

metabolites were identified as O-glucuronides (see the DER for MRID #49267201). 
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FIGURE 4.0.3 Proposed Metabolic Profile of Metrafenone in Goats

Rat: In the rat metabolism and pharmacokinetics study, excretion was 91-100 % after 168 hours, 

most of which was excreted in the feces within the first 48 hours. The highest concentration of 

metrafenone was found in the liver. Bile was the major excretion pathway, based on the results 

in bile duct-cannulated rats. Six urinary and biliary metabolites were identified. In urine, up to 
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21 other minor unknowns were found. In bile, up to 24 minor unknowns were found. The 

parent compound was not detected in urine or bile. Most of the fecal radioactivity consisted of 

parent metrafenone, and an additional 12 fecal metabolites were 0.03-15% of administered dose. 

There were up to 45 other fecal minor unknowns. The absorbed material was metabolized by

ortho-dealkylation, aliphatic oxidation, debromination, ring hydroxylation and conjugation 

reactions. Primary excretion was as glucuronic acid conjugates in bile and urine. Residues in 

feces were primarily as parent and aglycones of bile and urine conjugates (D354166; D. 

McNeilly; 1 March 2010). 

4.1 Nature of the Residue

Residue Chemistry Summary D312307; D. McNeilly; 24 August 2006

Metabolism DER for MRID #48981307 (Cucumber)

Metabolism DER for MRID #49119101 (Wheat)

Metabolism DER for MRID #49267201 (Goat)

Grape: The nature of the residue in grapes is adequately understood. Although the previously

submitted metabolism study reflects treatment at roughly 0.5X the proposed maximum seasonal 

rate to grapes, sufficient radioactive residues were obtained in grapes to enable characterization/

identification of residues. The ROC in grapes for risk assessment and tolerance enforcement is 

metrafenone. For risk assessment purposes, HED’s Residues of Concern Knowledge-based 

Subcommittee (ROCKS) concluded that the residues described as “acetone unknowns” and 

“juice” in the metabolism study should be included (D370903; G.F. Kramer; 18 Nov 2009).

The metabolite profile was very similar for both radiolabels. Metrafenone was the only 

component of the residue that was conclusively identified in grapes and leaves. Metrafenone 

accounted for 41-53% TRR in grapes harvested immediately following the last of five foliar 

applications of radiolabeled metrafenone, and it accounted for 23-25% TRR in grapes harvested 

35 days after the final application. 

Based on the results of the study, metrafenone is rapidly metabolized in grapes and grape vines 

to more polar compounds. There was no evidence of cleavage of the methanone bridge between 

the two rings of the compound. One metabolite that was tentatively identified in grape juice 

suggested a two-fold oxidation of the methyl group of the bromophenyl ring. Two metabolites 

tentatively identified in the acetone surface wash of mature grape leaves appeared to have been 

formed by oxidation of the methyl group of the bromophenyl or trimethoxyphenyl ring (with 

lactone formation), and the third metabolite suggested de-halogenation of the bromophenyl ring 

in addition to oxidation. (See Tables C.2.2.1, C.2.2.2, C.2.3.1, C.2.3.2 and C.2.3.3 in the DER 

for MRID #46415749.) 

Cucumber: BASF Corporation has submitted a study investigating the metabolism of uniformly

ring-labeled [trimethoxyphenyl-U14C]metrafenone (specific activity 6 MBq/mg) in cucumber. 

The radiolabeled test substance was formulated as an SC, and applied to greenhouse-grown 

cucumber plants as two broadcast foliar applications at 0.18 lb ai/A/application (200 g 
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ai/ha/application), for a total application of 0.36 lb ai/A (400 g ai/ha). The applications were 

made at a 14-day RTI. Samples of foliage were harvested immediately after the first application 

(0-DAT1), and samples of whole fruit were harvested 14 days after the first application (14-

DAT1), immediately before the second application. Samples of mature whole fruit, pulp, peel, 

and rest of plant were harvested 3 days after the second application (3-DAT2).

The TRR, determined by summing extractable and nonextractable radioactivity, were 6.397 and 

0.016 ppm in 0-DAT1 foliage, and 14-DAT1 in whole fruit harvested following the first

application at 0.18 lb ai/A; TRR were 0.051, 0.013, 0.263 and 8.807 ppm, respectively, in 3-

DAT2 whole fruit, pulp, peel, and rest of plant harvested following two applications at 0.36 lb 

ai/A. 

Extraction with methanol released the majority of the radioactivity from cucumber matrices: 

~99% TRR for 0-DAT1 foliage, ~88% for 14-DAT1 whole fruit, ~93% for 3-DAT2 whole fruit, 

~91% for 3-DAT2 pulp and peel, and ~93% for 3-DAT2 rest of plant. Extraction with water 

released an additional 0.3-3.2% TRR from all matrices. Remaining nonextractable residues

were, respectively, 0.9% TRR (0.058 ppm), 11.0% TRR (0.0018 ppm), 5.7% TRR (0.0029 ppm), 

7.8% TRR (0.0010 ppm), 7.8% TRR (0.0205 ppm), and 4.2% TRR (0.374 ppm). The extraction 

procedures adequately extracted the majority of residues from cucumber matrices. Results were 

normalized; therefore, accountabilities were 100%.

Residues were identified and quantitated in cucumber matrices by high performance liquid 

chromatography with UV detection (HPLC/UV). Identification of metrafenone was achieved by

HPLC co-chromatography with an unlabeled reference standard in 0-DAT1 cucumber foliage,

and 14-DAT1 whole fruit. No other reference standards were included in the study. 

Identification of metrafenone in the other samples was achieved by comparison of the retention 

times and the HPLC elution profiles with those of the extracts investigated by cochromatography. Confirmatory HPLC/UV analysis was conducted on all samples. Samples 

were stored frozen (approximately -18°C) after collection, and were processed, extracted and 

subjected to initial analysis by HPLC for quantitation purposes within 67-86 days (2.2-2.8 

months) of harvest. Final analyses were completed within 80-203 days (2.6-6.7 months) of 

harvest. Because samples were analyzed within roughly 4-6 months of harvest, no storage 

stability data are required to support the study.

Metrafenone accounted for 95.0% TRR (6.076 ppm) in 0-DAT1 foliage, 12.6% TRR (0.0021 

ppm) in 14-DAT1 whole fruit, 42.4% TRR (0.0216 ppm) in 3-DAT2 whole fruit, 6.5% TRR 

(0.0009 ppm) in 3-DAT2 pulp, 61.0% TRR (0.1607 ppm) in 3-DAT2 peel, and 80.4% TRR 

(7.084 ppm) in 3-DAT2 rest of plant. No other components were identified in cucumber 

matrices. Remaining radioactivity consisted of multiple unknown components, characterized as 

polar, medium polar, or nonpolar. Polar unknowns (4-6/matrix) accounted for 13.1-36.9% TRR 

(0.0041-0.0067 ppm) in whole fruit (both sampling intervals) and pulp, and for 0.82% TRR 

(0.0715 ppm) in the rest of the plant, with no single component accounting for >18.9% TRR or 
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>0.0299 ppm. Medium polar unknowns (4-20/matrix) accounted for 3.8-46.8% TRR (0.006-

1.228 ppm) in all cucumber matrices, with no single component accounting for >12.2% TRR or 

>0.2742 ppm. A single nonpolar component was detected in 3-DAT2 rest of plant at 0.02% 

TRR (0.0016 ppm). (See Tables C.2.1, C.2.2.1, C.2.2.2, C.2.3.1 and C.2.3.2 in the DER for 

MRID #48981307.) 

Wheat: BASF Corporation has submitted a study investigating the metabolism of [bromophenyl6-

14C]metrafenone (BP label; specific activity 20.30 μCi/mg) and uniformly ring-labeled 

[trimethoxyphenyl-U14C]metrafenone (TP label; specific activity 18.16 μCi/mg) in wheat. The 

radiolabeled test substances were formulated as emulsifiable concentrates (ECs), and applied to 

field-grown wheat plants as three broadcast foliar applications, the first two at nominal 

application rates of 0.268 lb ai/A (300 g ai/ha), and the third at 0.179 lb ai/A (200 g ai/ha). The 

actual total application rates were 0.674 lb ai/A (756.0 g ai/ha) for the BP label, and 0.642 lb 

ai/A (719.3 g ai/ha) for the TP label. Applications were made at 13- to 14-day RTIs. Samples of 

immature whole plants were collected within roughly 3 hours of each application; forage (whole 

plant) was collected 3 days after the first application; hay was collected 14 days after the second 

application; and mature straw, chaff and grain were collected at maturity, 35 days after the third 

application. The in-life phase of the study was conducted by Excel Research Services (Fresno, 

CA) and Qualls Agricultural Laboratory (Ephrata, WA), while the analytical phase of the study 

was conducted by BASF (Princeton, NJ). 

Following three broadcast foliar applications of [bromophenyl-6-

14C]metrafenone or 

[trimethoxyphenyl-U14C]metrafenone at total application rates of 0.674 lb ai/A (756 g ai/ha) for 

the BP label, and 0.642 lb ai/A (719.3 g ai/ha) for the TP label, TRR in immature wheat plants 

sampled immediately following applications 1, 2 and 3, respectively, were 7.275, 5.959 and 

6.997 ppm in BP-label samples, and 9.890, 8.416 and 5.382 ppm in TP-label samples. Although 

immature plants were subjected to further extraction and analysis procedures, results were not 

included in the submission, and these matrices are not discussed further herein. TRR in 

remaining BP- and TP-label samples, respectively, were 8.167 and 5.265 ppm in forage, 7.784 

and 8.498 ppm in hay, 8.914 and 8.248 ppm in straw, and 0.209 and 0.399 ppm in grain. The 

higher TRR in hay and straw were attributed by the petitioner to dehydration of the samples.

Results were similar for both labels, although residues of parent were consistently higher in BPlabel samples. Metrafenone was the major identified residue in wheat forage, hay and straw, 

accounting for 58.9-64.4% TRR in forage, 12.7-26.0% TRR in hay, and 7.7-13.6% TRR in 

straw. Metrafenone was the only identified residue in wheat grain, accounting for 3.1-7.7% 

TRR. All remaining metabolites were identified in all samples of forage, hay and straw. 

Metabolites CL 3000402, which was ROI 4, CL 1500838 (ROI 5), and CL 434223 (ROI 8) each 

accounted for 0.8-6.6% TRR. Combined residues of the following metabolite pairs or groups 

each accounted for 1.5-6.5% TRR: CL 1500837 + CL 1500836 (ROI 3), CL 1500839 + CL

1500832 (ROI 6), and CL 1500833 + CL 1500834 + CL 1500835 + CL 377160 + Unknown ROI 
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7C (ROI 7). Two remaining metabolites, CL 376991 (ROI 9) and CL 1500831 (ROI 10), each 

accounted for ≤1.8% TRR. 

No other components were identified in wheat matrices. Polar unknowns ROI 1 and ROI 2, 

comprised of multiple minor components, each accounted for 3.1-4.3% TRR in forage, 11.5-

17.4% TRR in hay, and 8.3-10.6% TRR in straw; one additional multicomponent unknown, ROI 

11, accounted for ≤1.7% TRR in forage, hay and straw. Polar unknown ROI 1 accounted for 

21.3-26.2% TRR in grain, while remaining unknowns together accounted for <2.0% TRR. 

Although quantitative results were not reported for α-amylase hydrolysis of grain, ROI 1 

comprised ~59% and 74%, respectively, of the recovered radioactivity following hydrolysis. 

(See Tables C.2.1, C.2.2.1, C.2.2.2, C.2.2.3, C.2.3.1, C.2.3.2 and C.2.3.3 in the DER for MRID 

#49119101.) 

Goat: BASF Corporation has submitted a study investigating the metabolism of [bromophenyl6-

14C]-metrafenone (BP label; specific activity 8.03 μCi/mg) or uniformly ring-labeled 

[trimethoxyphenyl-U14C]-metrafenone (TMP label; specific activity 8.02 μCi/mg) in the 

lactating goat. The test substances were administered orally via gelatin capsule to two lactating 

goats per label, once daily for 5 consecutive days, at 13 and 87 ppm in the feed for the BP label,

and at 8 and 60 ppm in the feed for the TMP label. A control goat received capsules containing 

carrier only. Milk was collected twice daily, in the morning and afternoon, prior to dosing. 

Goats were sacrificed approximately 21-23 hours after administration of the final dose, and the 

following tissues were collected: Liver (entire), kidney (both), muscle (composite of loin and 

leg), and fat (omental). The in-life phase of the study was conducted by Fort Dodge Animal 

Health, Division of American Home Products Corporation, Agricultural Research Center 

(Princeton, NJ), and the analytical phase of the study was conducted by BASF Agro Research 

(Princeton, NJ). 

TRR in BP-label milk and tissues from the low and high dose goats, respectively, were <0.005 

and 0.008-0.010 ppm in milk, 0.231 and 1.278 ppm in liver, 0.060 and 0.329 ppm in kidney, 

<0.005 and 0.008 ppm in muscle, and <0.005 and 0.015 ppm in fat. TRR in TMP-label samples 

from low and high dose goats, respectively, were <0.005 and <0.005-0.006 ppm in milk, 0.208 

and 0.718 ppm in liver, 0.047 and 0.157 ppm in kidney, <0.005 and 0.006 ppm in muscle, and 

<0.005 and 0.022 ppm in fat. In general TRR were higher in BP-label samples than in TMPlabel samples. Radioactivity in milk was generally stable throughout the dosing period. Most of 

the administered dose was excreted (75.7-85.7%), with the majority (61.8-74.1%) excreted in the 

feces. 

The following samples from high dose goats were subjected to further extraction and analysis: 

Day 5 BP-label milk, and BP- and TMP-label liver, kidney, and fat; samples of TMP-label Day 5 

milk and muscle (both labels) were not were not analyzed further because TRR were <0.01 ppm. 

The majority of the radioactivity in milk (98.9% TRR) was extracted with acetone. Sequential 

extraction with acetonitrile (ACN), ACN/water, methanol/acetone/water/triethylamine (TEA), 
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and methanol/water/trifluoroacetic acid (TFA) released the majority of the radioactivity in liver 

(59.2-68.9% TRR) and kidney (87.1-93.1% TRR). The majority of the radioactivity in fat 

(~100% TRR) was extracted with methanol. The nonextractable residues of liver and kidney

were subjected to hydrolysis with pepsin, followed by extraction with acidic methanol, which 

together released an additional 25.9-37.6% TRR in liver, and 7.5-10.6% TRR in kidney. 

Remaining nonextractable residues following extraction and hydrolysis procedures were 14.3% 

TRR (0.001 ppm) in milk, 5.3-7.5% TRR (0.054-0.068 ppm) in liver, 4.6-7.7% TRR (0.012-

0.015 ppm) in kidney, and 6.0% TRR (0.0013 ppm) in TMP-label fat (nonextractable residues in 

BP-label fat were not reported). The extraction procedures adequately extracted the majority of 

residues from goat milk and tissues. Accountabilities were roughly 100-122%. 

Residues were quantitated in milk and tissues by HPLC/UV. Metrafenone was identified in 

milk, liver and fat by co-chromatography. Three ROIs, ROI-9, -13 and -16, were major residue 

components in milk, liver and/or kidney. Individual components of these ROIs were identified 

primarily in liver by LC/MS, in conjunction with hydrolysis via beta-glucuronidase. The three 

ROIs were found to include O-glucuronide conjugates of metabolites. ROI-9 was comprised of 

metabolites CL 1023361, CL 1023362 and CL 1500702; ROI-13 was comprised of metabolites 

CL 1500698, CL 1023363 and a minor unknown; and ROI-16 was comprised of metabolites CL 

1500701, CL 1500699 and a minor unknown. The metabolite profiles were similar for both 

labels, and the metabolite profiles in liver and kidney were similar. 

Parent was the major residue in milk (24.12% TRR, 0.0024 ppm), and was the major and only 

identified residue component in fat, accounting for 60.00-85.32% TRR (0.0090-0.0188 ppm). 

Metrafenone was a minor residue in liver (2.74-3.49% TRR; 0.025-0.035 ppm) and kidney (3.25-

4.35% TRR; 0.005-0.014 ppm). ROI-13 was a major residue component in milk (10.67% TRR, 

0.001 ppm), and was the major residue component in liver and kidney, accounting for 14.77-

21.05% TRR (0.106-0.269 ppm) and 26.29-28.15% TRR (0.044-0.086 ppm), respectively. ROI9 was also a major component in liver and kidney, accounting for 9.89-13.23% TRR (0.071-

0.169 ppm) and 9.51-13.57% TRR (0.021-0.031 ppm), respectively; ROI-9 was a minor 

component in milk (2.83% TRR). ROI-16 was a minor residue component in milk (3.8% TRR), 

liver (6.41-7.12% TRR), and kidney (1.46-4.19% TRR). Remaining radioactivity was found to 

consist of up to 18 minor ROIs, together accounting for 55.94% TRR (0.0056 ppm) in milk,

13.45-14.46% TRR (0.0022-0.0030 ppm) in fat, 50.63-61.70% TRR (0.443-0.647 ppm) in liver,

and 48.81-55.08% TRR (0.077-0.181 ppm) in kidney. The single largest ROI accounted for 

11.7% TRR (0.084 ppm) in TMP-label liver, with the majority (10.86% TRR) found in the 

pepsin hydrolysate. 

Based on the submitted goat metabolism study, the registrant has proposed the following 

metabolic pathway for metrafenone in ruminants. Metabolism of metrafenone in lactating goat 

occurred at the methyl and methoxy groups on the rings. Hydroxylation of the methyl groups 

yielded hydroxymethyl derivatives, whereas O-demethylation yielded hydroxyphenyl

derivatives. These hydroxylated metabolites underwent Phase II glucuronidation to produce 
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various mono-O-glucuronides. All of the prominent goat metabolites were identified as Oglucuronides. (See Tables 8a, 8b, 8c, 8d, 8e, 8f and 8g in the DER for MRID #49267201.) 

Conclusions: Based on the wheat, cucumber and grape metabolism studies, metrafenone is 

metabolized in plants to more polar components. The unchanged parent was the major residue 

component in most matrices; in cucumber pulp, where metrafenone was a minor component, 

some polar components were detected at low concentrations similar to those of metrafenone. All 

of the prominent goat metabolites were identified as O-glucuronides.

4.1.1 Summary of Plant and/or Livestock Metabolism (860.1300)

ROCKS Memo D370903; G.F. Kramer; 18 Nov 2009

Residue Chemistry Summary D312307; D. McNeilly; 24 August 2006

Metabolism DER for MRID #48981307 (Cucumber)

Metabolism DER for MRID #49119101 (Wheat)

Data have been submitted and reviewed depicting the metabolism/degradation of metrafenone in 

numerous crops and the environment. HED has determined the plant and livestock ROCs for 

purposes of tolerance enforcement and risk assessment (see Table 4.1.1.1, below). 

TABLE 4.1.1.1 Summary of Metrafenone 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 crops Metrafenone + acetone unknowns + juice (correction 

factor derived from grape metabolism study)

Metrafenone

Rotational crops Not Applicable Not applicable

Livestock Ruminants Not Applicable Not applicable

Poultry Not Applicable Not applicable

Drinking water Metrafenone + total extractable residues Not applicable

For primary crops, metrafenone parent serves as an adequate measure of misuse based on its 

percentage of the TRR in the metabolism studies, and the significant residues seen in crop field 

trials. For dietary risk assessment purposes, HED concludes that some of the significant amounts 

of tentatively identified and unidentified material in the grape metabolism study need to be 

included. The tentatively identified metabolites in the “acetone unknowns” and “juice” fractions 

retain the dual ring structure of the parent compound. Such residues may be of comparable 

toxicity to the parent, metrafenone. At this time, the residues described as “acetone unknowns” 

and “juice” should be included along with the parent for assessing dietary risk. This approach 

would account for 93% and 77% of the TRR in grapes harvested after the fifth application of the 

BP-labeled metrafenone ([bromophenyl-6-

14C]metrafenone) and TMP labeled metrafenone 

([trimethoxyphenyl-U14C]metrafenone), respectively.

Data from the metrafenone grape and cucumber metabolism studies were used to derive a dietary

exposure adjustment factor by dividing residues (as a percent of the TRR) of the parent plus the 
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“acetone unknowns” and “juice” fractions by the residue of parent only in the grape metabolism 

study. Conducting this evaluation for both radiolabels, and both harvesting intervals resulted in a 

maximum ratio of 2.1, and an average ratio of 1.9. HED decided to use a dietary exposure ratio 

factor of 2.0. This adjustment factor was then used to convert tolerance levels for the parent to 

residues of parent plus the “acetone unknowns” and “juice” fractions (see ROCKS Memo, 

D370903; G. Kramer; 19 November 2009). 

The wheat metabolism study was classified as marginally scientifically acceptable. Insufficient 

attempts were made to characterize/identify radioactivity in the nonextractable residues of wheat 

hay and straw, which accounted for 20.8-23.0% TRR (1.615-1.952 ppm) in hay and at least 27.7-

38.1% TRR (2.465-3.139 ppm) in straw. In addition, insufficient quantitative data were 

provided concerning the characterization of radioactivity in the nonextractable residues of grain 

for HED to ascertain whether these residues were sufficiently characterized. 

In addition, the study was missing much of the data supporting the limited characterization 

attempts that were described. However, the finding that metrafenone is the major residue of 

concern in wheat is consistent with the previous plant metabolism studies, and the European 

Food Safety Authority (EFSA) has accepted the results of this study in conjunction with the 

other metabolism studies in establishing MRLs. Also, the progression of residue distribution 

from forage to hay and straw in terms of the relative amounts of extractable and nonextractable 

residues, and the consistency of the metabolite profile across these matrices are mitigating 

factors. It is likely that the nonextractable residues of hay and straw are comprised of further 

breakdown products incorporated into natural components (conjugates), which are not 

considered toxic. Furthermore, previous metabolism studies (in grape, cucumber and rat) have 

demonstrated that metrafenone tends to be broken down into a multitude of metabolites, many of 

which were ultimately unidentified. 

Because there are no current or proposed uses on cereal grains at this time, data from the wheat 

metabolism study were not included in calculation of the dietary exposure adjustment factor. 

Should the registrant submit any future petition requesting the use of metrafenone on cereal 

grain(s), the derivation and calculation of this adjustment factor will need to be revisited. 

Ideally, a new metabolism study in a cereal grain would be conducted, with a more thorough 

attempt to identify many of the resulting metabolites. Otherwise, an adjustment factor of 6 (as

calculated in Table 4.1.1.2, below) would need to be included for cereal grain commodities in the 

column for adjustment factor 2 in the dietary exposure assessment. 

TABLE 4.1.1.2 Metrafenone Metabolism Adjustment Factor.

BP Label TMP Label Maximum/Average 

Ratio1

Grape

Residue %TRR2

0 DALT335 DALT 0 DALT 35 DALT

Metrafenone 53.3% 24.7% 40.7% 22.8%
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TABLE 4.1.1.2 Metrafenone Metabolism Adjustment Factor.

BP Label TMP Label Maximum/Average 

Ratio1

“Acetone 

Unknown”

32.6% -- 23.5% --

“TRR in Juice 

fraction”

7.1% 18% 12.5% 25.3%

Ratio 1.74 1.73 1.88 2.11 2.1/1.9

Cucumber (Whole fruit)

Residue %TRR (Note: Only one ring was labeled in the cucumber metabolism study.)

14 DAT15 3 DAT2

Metrafenone 12.6% 42.4%

Polar unknowns 24.0% 13.1%

Medium polar 

unknowns

41.3% 23.4%

Ratio 6.042.0 2.0

Wheat (Grain), 35 DAT3

Residue %TRR ppm %TRR ppm

Metrafenone 7.7% 0.016 3.1% 0.013

Unknown ROI 15.1% 0.032 20.2% 0.081

Unknowns ROI 2-

11

<2% <0.004 <2% <0.004

Ratio 3.22 8.16 8.16/5.69

Wheat (Forage), 3 DAT1

Residue %TRR ppm %TRR ppm

Metrafenone 64.4% 5.261 58.9% 3.101

All metabolites and 

unknowns in extract

27.3% 2.228 27.6% 1.444

Ratio 1.42 1.47 1.47/1.45

Wheat (Hay), 14 DAT2

Residue %TRR ppm %TRR ppm

Metrafenone 26.0% 2.021 12.7% 1.078

All metabolites and 

unknowns in extract

50.0% 3.905 59.8% 5.095

Ratio 2.92 5.71 5.71/4.32

Wheat (Straw), 35 DAT3

Residue %TRR ppm %TRR ppm

Metrafenone 13.6% 1.215 7.7% 0.635

All metabolites and 

unknowns in extract

39.1% 3.511 44.9% 3.702

Ratio 3.88 6.83 6.83/5.36

1. Ratio = [parent + other ROC]/parent.

2. TRR= Total Radioactive Residues

3. DALT = Days After Last Treatment. 

4. While the percentages of these fractions are high, the actual TRR is less than 0.005 ppm and therefore, were not 

used in the calculation of the correction factor. 

5. (#) DAT(#) = (number of) Days After Treatment (treatment number). 
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To obtain dietary exposure residue values for all commodities, a factor of 2.0 was entered into 

the column for adjustment factor 2 in the dietary exposure assessment (D371367; D. McNeilly; 

18 February 2010). 

Conclusions: The nature of the residue in plants and animals has been adequately delineated. 

4.1.2 Summary of Confined Rotational Crops (860.l850)

Confined Accumulation in Rotational Crops DER for MRID #49119105

BASF Corporation has submitted a confined rotational crop study with [bromophenyl-6-

14C]metrafenone (BP label; specific activity 10.15 μCi/mg) and [trimethoxyphenyl-U14C]metrafeneone (TP label; specific activity 8.97 μCi/mg). The radiolabeled test substances

were formulated as ECs, and applied to bare sandy loam soil in outdoor plots at a rate equivalent 

to 0.558 lb ai/A (625 g ai/ha). Rotational crops (lettuce, radish and canola) were planted at plantback intervals (PBIs) of 30, 60, 90 and 365 days after soil treatment. Immature and mature 

lettuce, mature radish roots and tops, and canola straw, seed and whole plant were harvested. 

The in-life phase of the study was conducted by Excel Research Services at the Qualls 

Agricultural Laboratory (Ephrata, WA), and the analytical phase of the study was conducted by

BASF Corporation (Princeton, NJ).

Following a single foliar broadcast application of [bromophenyl-6-

14C]metrafenone or 

[trimethoxyphenyl-U14C]metrafenone at 0.558 lb ai/A, TRR, determined by combustion/LSC, 

accumulated at ≥0.01 ppm in immature lettuce at the 90-day PBI (both labels), radish tops at the 

30-, 60- (TP label only) and 90-day PBIs, radish root at the 30-, 60- and 90-day PBIs (BP label 

only), canola seed at the 90-day PBI (BP label only), and canola straw at the 30-, 60-, 90- and 

365-day PBIs (both labels). The petitioner also analyzed samples where TRR were <0.01 ppm,

but greater than the reported LOQ (0.004 ppm), which included mature lettuce at the 30-day PBI 

(both labels), radish tops at the 60-day PBI (BP label only), radish roots at the 90-day PBI (TP 

label only), and canola (whole plant) at the 60-day PBI (both labels). TRR were below the LOQ 

in mature lettuce at the 60- and 365-day PBI (both labels). TRR in 365-day samples were 

≤0.008 ppm in all matrices, and were not further analyzed with the exception of 365-day canola 

straw (0.023-0.029 ppm). TRR were generally highest in 30-day PBI matrices, ranging from 

0.005 ppm in mature lettuce to 0.048 ppm in canola straw. For lettuce, higher residues of 0.030-

0.034 ppm were detected at the 90-day PBI; however, the petitioner attributed the increase in 

residues to harvesting the crop at an immature stage due to late planting. TRR generally

decreased at the 60-day PBI, ranging from <0.004 ppm in mature lettuce to 0.027 ppm in canola 

straw, but residues increased slightly at the 60-day PBI in radish tops (0.018 ppm). TRR 

increased at the 90-day PBI in radish tops, and canola straw and seed, ranging from 0.010 ppm in 

canola seed to 0.033 ppm in canola straw, and decreased slightly in 90-day radish root (0.009-

0.010 ppm).
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Extraction with MeOH/water released the majority of the radioactivity, 62.1-85.2% TRR, in 30-

and 90-day lettuce, 30-, 60- and 90-day radish tops and roots, 30-, 60-, 90- and 365-day canola 

straw, and 60-day canola whole plant (BP label only). Extraction with hexane released the 

majority of radioactivity, 51.6-86.2% TRR, in 30- and 90-day canola seed (BP label only) and 

60-day canola seed (TP label only); extraction with hexane released 41.9% TRR in 60-day

canola seed samples (BP label), and 45.6-47.9% TRR in 30- and 90-day canola seed samples (TP 

label). Samples of 90-day immature lettuce, 30-day radish tops, 60-day radish roots, and 30-, 

60-, 90- and 365-day canola straw were subjected to additional extraction procedures to release 

bound residues. Extraction with MeOH/2% HCl released 5.9-19.9% TRR from immature 

lettuce, radish tops and roots, and canola straw. 

Remaining nonextractable residues in the matrices that were subjected to additional extraction 

procedures to release bound residues were 18.7-19.6% TRR (0.006 ppm) in immature lettuce,

17.6-20.8% TRR (0.003-0.005 ppm) in radish tops, 25.0-31.8% TRR (0.005 ppm) in radish 

roots, and 11.8-29.4% TRR (0.004-0.008 ppm) in canola straw. For the remaining matrices,

nonextractable residues were 17.7% TRR (0.001 ppm) in 30-day mature lettuce, 14.8-36.0% 

TRR (0.002-0.006 ppm) in 60- and 90-day radish tops, 19.8-31.2% TRR (0.003-0.005 ppm) in 

30- and 90-day radish roots, 13.8-58.1% TRR (0.001-0.005 ppm) in 30-, 60- and 90-day canola 

seed, and 23.9-100% TRR (0.001-0.006 ppm) in 60-day canola whole plant. Initial extraction 

results were normalized; therefore, accountabilities were approximately 100%.

Select sample extracts were analyzed by HPLC/UV. All samples of rotational crop commodities 

were analyzed within 205-740 days (6.7-24.3 months) of harvest. No storage stability data were 

submitted. However, a 2012 storage stability study (MRID #48981308) reviewed in conjunction 

with the recent pome fruit petition (PP#3F8163) supports the sample storage conditions and 

durations of samples in this rotational crop study.

Metrafenone was identified by HPLC co-chromatography with reference standards. Additional 

ROIs were characterized on the basis of HPLC fractionation profiles. HPLC analysis of the 

MeOH/water extracts showed multiple unknown peaks in each sample. Metrafenone was 

identified at 6.2-11.1% TRR (<0.001-0.004 ppm) in 30-day and 90-day (BP label only) lettuce 

samples, and 3.9-27.7% TRR (<0.001-0.004 ppm) in 30-, 60- and 90-day radish roots. The most 

abundant residue in the majority of samples was the polar ROI 1, which accounted for 8.1-17.3% 

TRR (0.001-0.003 ppm) in 30- and 90-day lettuce, 15.3-43.7% TRR (0.001-0.01 ppm) in 60- and 

90- radish tops (BP label), 10.3-17.9% TRR (0.002-0.003 ppm) in 30-, 60- and 90-day radish 

tops (TP label), 16.6-26.5% TRR (0.002-0.004 ppm) in 30-, 60- and 90-day radish roots, and 

25.1-42.4% TRR (0.007-0.015 ppm) in canola straw, all PBIs. A second ROI, ROI 2, was 

present at 11.9% TRR (0.004 ppm) in 90-day immature lettuce (TP label only), 8.8-20.0% TRR 

(<0.001-0.005 ppm) in 60- and 90-day radish tops (BP label only), 12.8% TRR (0.002 ppm) in 

60-day radish roots (TP label only), 9.6-12.4% TRR (0.003-0.005 ppm) in 30- and 90-day (BP 

label only) canola straw. These peaks were not further investigated in any matrix. 
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Because only parent was identified in the submitted confined rotational crop study, a metabolic 

profile was not provided. 

Conclusions: The results from the confined rotational crop study indicated that there is no 

expected accumulation of metrafenone or its degradation products in the parts of plants used for 

human food or animal feed consumption. The levels of individual metabolites were below 0.01 

ppm. Owing to the low concentrations of metrafenone and related residues in subsequent rotated

crops, no field rotational crop trials are required. Plant-back restrictions are not necessary for 

metrafenone. 

4.1.3 Summary of Rat Metabolism

Risk Assessment D354166; D. McNeilly; 1 March 2010

In a rat metabolism and pharmacokinetics study, excretion was 91-100% after 168 hours. Most 

radioactivity was excreted within the first 48 hours (84-99% in feces, 0.5-4.8% in urine). The 

highest concentration was in the liver. Bile was the major excretion pathway. In bile ductcannulated rats, total recovery was 97-100% at 72 hours. At the low dose, bile recovery was 85-

90%; at the high dose, feces had 80-82%, with bile having 15-17% (indicating absorption was 

saturated). Six urinary and biliary metabolites were found. In urine, up to 21 other minor 

unknowns were found. In bile, up to 24 minor unknowns were found (21-24% for the low dose,

and 3-4% for the high dose). The parent compound was not detected in urine or bile. Twelve 

fecal metabolites along with the parent were found. Most of the fecal radioactivity was 

contained in parent metrafenone. Fecal metabolites were 0.03-15% of the administered dose. 

There were up to 45 other fecal minor unknowns. In feces of bile duct-cannulated animals, 

metabolites plus parent were identified. The parent accounted for most of the activity; however, 

there were up to 17 minor unknowns. The absorbed material was metabolized by orthodealkylation, aliphatic oxidation, debromination, ring hydroxylation, and conjugation. Primary

excretion was as glucuronic acid conjugates in bile and urine. Residues in feces were primarily 

as parent and aglycones of bile and urine conjugates. 

4.1.4 Summary of Environmental Degradation

EFED Drinking Water Memo D411540, D414403, D416312; J.A. Hetrick; 25 November 2013

The only positively identified major degradate of metrafenone in the environmental fate studies 

was CL 377160 (3-bromo-6-methoxy-2-methylphenyl)(3-hydroxy-2,4-dimethoxy-6-

methylphenyl)-methanone). CL 377160 was formed through soil photolysis at up to 18.9% of 

the applied radioactivity (AR), and through anaerobic aquatic metabolism at up to 10.8% AR in 

the total system. It was also formed as a minor degradate through aquatic photolysis, and aerobic 

aquatic metabolism. 

In one anaerobic aquatic metabolism study, another six degradates were formed at >9%, but 

these were either unidentified or only tentatively identified. These included TN (tentatively 
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identified as a lactone compound at maximums of 3.3%, 26.9% and 28.0% in the water layer, 

sediment and total system, respectively), MB (tentatively identified as a hydroxylation product of 

TN at maximums of 1.1%, 11.6% and 11.7% in the water layer, sediment and total system, 

respectively), and four unidentified degradates formed in the total system at 9.3% to 13% AR. 

Carbon dioxide was also a major degradate, formed through aquatic photolysis at up to 25% AR,

and through all other measured processes as a minor degradate. 

Most processes also resulted in formation of a substantial amount of minor degradates, some 

individually measured and identified, but most not. Although all of these degradates were 

present at less than 10%, and some at very low levels, they still may be of exposure concern 

because of the large overall amounts. In some cases, minor degradates, mostly unidentified, 

made up more than 50% of the AR in a single sampling event. In addition, based on the 

structure of the parent compound, and the proposed degradation pathways, many of the minor 

degradates may have a high degree of structural similarity to each other and/or the parent, and so 

may have toxic properties similar to those of the parent. 

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1.1 Data Collection Methods

QuEChERS: The hops (NAFTA trials), pome fruit, fruiting vegetable, cucurbit, cherry and 

peach RAC samples, and apple processed commodities were analyzed for residues of 

metrafenone using an LC/MS/MS method which is described in Metrafenone (BAS 560 F): 

Validation of the Multi-Residue Enforcement Method QuEChERS for the Determination of 

Residues in Plant Matrices using LC/MS/MS (BASF Study #398340). A QuEChERS method 

uses dispersive solid phase extraction (dSPE) to prepare the sample for analysis. The method 

detects parent metrafenone, which has been determined to be the ROC for tolerance enforcement 

purposes in primary crops, based on plant metabolism studies. A summary of the methodology

used to analyze the samples follows.

Briefly, metrafenone residues in RAC samples are extracted by shaking with a buffered solution 

of water and ACN in the presence of salts (Supelco 55227-u mixture, containing sodium 

chloride, magnesium sulfate, and citrate buffering agents) and centrifuged. An aliquot of the 

supernatant is further purified on a dSPE clean-up tube (Restek 26215, containing magnesium 

sulfate to remove residual water, and primary secondary amine sorbent to remove sugars and 

fatty acids) and centrifuged. An aliquot of the extract is diluted with an acidified solution of 

ACN and water (0.1% formic acid in 1:1 ACN/water) prior to analysis by LC/MS/MS. 

Metrafenone is quantitated via MS/MS detection using the positive ionization mode monitoring
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ion transitions from m/z 409→209 for quantitation, and m/z 409→227 for confirmation. 

Quantitation was obtained using an external calibration curve of metrafenone standards. 

The method was validated before the analysis of any treated pome fruit samples by fortifying 

untreated control apple fruit samples at 0.010 and 0.10 ppm. Concurrently with the analysis of 

field trial samples, the method was also validated using samples of untreated pome fruits 

fortified with metrafenone at 0.01, 0.10 and 1.0 ppm. Additionally, the method was validated, 

before the analysis of any treated apple processed commodities, by fortifying untreated control 

dried apple samples at 0.01 and 0.10 ppm. Concurrently with the analysis of processed 

commodities, the method was also validated using samples of untreated apple RAC and 

processed commodities fortified with metrafenone at 0.01 to 10 ppm. 

The method was validated before the analysis of any treated tomato samples by fortifying 

untreated control tomato fruit samples at 0.01, 0.10 and 1.0 ppm. Concurrently with the analysis 

of field trial samples, the method was also validated using samples of untreated tomatoes

fortified with metrafenone at 0.01 and 0.10 ppm. 

The method was validated before the analysis of any treated pepper samples by fortifying 

untreated control pepper fruit samples at 0.01, 0.10, and 3.0 ppm. Concurrently with the analysis 

of field trial samples, the method was also validated using samples of untreated peppers fortified 

with metrafenone at 0.01 and 0.10 ppm. 

The method was validated before the analysis of any treated cucurbit samples by fortifying 

untreated control samples of cantaloupe and summer squash at 0.01, 0.10 and 1.0 ppm, and 

untreated cucumber samples 0.01 and 0.10 ppm. Concurrently with the analysis of field trial 

samples, the method was also validated using samples of untreated cantaloupes, cucumbers and 

summer squash fortified with metrafenone at 0.01 and 1.0 ppm. 

The method was validated before the analysis of any treated cherry samples by fortifying 

untreated control cherry fruit samples at 0.01, 0.10 and 1.0 ppm. Concurrently with the analysis 

of field trial samples, the method was also validated using samples of untreated cherries fortified 

with metrafenone at 0.01, 0.10 and 1.0 ppm. 

The method was validated before the analysis of any treated peach samples by fortifying 

untreated control peach fruit samples at 0.01, 0.10, 1.0 and 2.0 ppm. Concurrently with the 

analysis of field trial samples, the method was also validated using samples of untreated peaches

fortified with metrafenone at 0.01, 0.10 and 1.0 ppm. 

The method was validated before the analysis of any treated hops cone samples (reported in 

MRID #49145403) by fortifying untreated control samples of dried and fresh hops cones at 0.01-

200 and 0.01-1.00 ppm, respectively. Concurrently with the analysis of field trial samples, the 
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method was also validated using samples of untreated dried and fresh hops cones fortified with 

metrafenone at 0.01-200 and 0.01-50 ppm, respectively. 

QuEChERS Conclusions: The metrafenone residues in hops (NAFTA trials), pome fruit, fruiting 

vegetable, cucurbit, cherry and peach RAC samples, and apple processed commodities were 

quantitated using an LC/MS/MS multi-residue QuEChERS method (BASF Study #398340). The 

method was successfully validated for all these commodities in conjunction with the studies prior 

to analysis of the field trial samples. Acceptable concurrent method recovery data in all matrices 

were also obtained for metrafenone. The validated LOQ for residues of metrafenone in pome 

fruits RAC and processed commodity samples was 0.01 ppm; the method limit of detection 

(LOD) was 0.003 ppm. The validated LOQ for residues of metrafenone in fruiting vegetable 

samples was 0.01 ppm; the estimated method LOD was reported as 0.001 ppm, or approximately

10% of the LOQ. The validated LOQ was 0.01 ppm for metrafenone in dried and fresh hops 

cones; the calculated LODs were 0.0034 and 0.0035 ppm in dried and fresh hops cones, 

respectively. The validated LOQ was 0.01 ppm for metrafenone in all cucurbit matrices; the 

reported LOD in cucumber was 0.001 ppm (10% LOQ). The LOQ was 0.01 ppm for 

metrafenone in cherries. The LOQ was 0.01 ppm for metrafenone in peaches; the calculated 

LOD was 0.0041 ppm. No additional data are required in support of this data collection method.

BASF Methods #535/1 and #535/3: The hops (German trials) RAC samples were analyzed for 

residues of metrafenone using BASF Methods #535/1 (L0076/01) and #535/3 (L0076/03). The 

tomato processed commodities were analyzed for residues of metrafenone using BASF Method 

#535/1 (L0076/01). 

The two methods are essentially identical. Briefly, samples were extracted with 

methanol/water/2N HCl (14:5:1, v/v/v), and centrifuged. The supernatant was partitioned with 

cyclohexane/0.2N NaOH (5:1, v/v), and the organic phase was evaporated to dryness, then

reconstituted in methanol/water (1:1, v/v) for LC/MS/MS analysis. The method monitors two 

ion transitions for determination of metrafenone, m/z 411→209 for quantitation, and m/z

411→229 for confirmation. 

BASF Methods #535/1 and #535/3 were validated before the analysis of any treated hops cone 

samples (reported in MRIDs #49145407 and 49145408) by fortifying untreated control samples 

of dried and fresh hops cones at 0.01-200 and 0.01-1.00 ppm, respectively. Concurrently with 

the analysis of field trial samples, the methods were also validated using samples of untreated 

dried and fresh hops cones fortified with metrafenone at 0.01-200 and 0.01-50 ppm, respectively. 

Concurrently with the analysis of tomato RAC and processed commodity samples, BASF 

Method #535/1 was validated using samples of untreated control tomato RAC and processed 

commodity samples (washed fruit, vegetable stock, paste, wet pomace, and peel) fortified with 

metrafenone at 0.01, 0.10, 1.0 and 5.0 ppm. 
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BASF Methods #535/1 and #535/3 Conclusions: The hops (German trials) RAC samples were 

analyzed for residues of metrafenone using BASF Methods #535/1 and #535/3. The tomato 

processed commodities were analyzed for residues of metrafenone using BASF Method #535/1. 

The methods were successfully validated for these commodities in conjunction with the studies

prior to analysis of the field trial samples. Acceptable concurrent method recovery data in all 

matrices were also obtained for metrafenone. The validated LOQ was 0.01 ppm for metrafenone 

in tomato RAC and processed commodity samples; the method LOD was not specified. The 

validated LOQ was 0.01 ppm for metrafenone in fresh hops cones, dried hops cones, and the 

hops processed commodities; the method LOD was not specified. No additional data are 

required in support of these data collection methods.

5.1.2 Multi-Residue Methods (860.1360)

Multi-Residue Methods DER for MRID #46857701

BASF Corporation previously submitted multiresidue method testing data for metrafenone with

PP#4E6884. Multiresidue method testing data were submitted for metrafenone and its 

metabolites CL 376991, CL 434223, and CL 3000402. Metabolite CL 3000402 corresponds to a 

metabolite identified in the grape metabolism study as surface rinse metabolite 2; the other two 

metabolites appear to have been identified in cereal grains (data not submitted to EPA). The test 

substances were analyzed according to the Food and Drug Administration (FDA) Multiresidue 

Method Test guidelines in PAM Vol. I. Metrafenone and its metabolites were tested through 

Protocols A, B, C, D, E and F; the compounds were not tested under Protocol G because they are 

not substituted ureas. The study was conducted by Maxim Technologies (Middleport, NY).

The test substances do not have N-methylcarbamate structures and were not found to be naturally 

fluorescent in testing under Protocol A. In Protocol B testing, metrafenone, CL 376991, and CL 

434223 were completely recovered from grapes fortified at 0.05 and 0.50 ppm, and metrafenone 

and CL 376991 were partially recovered from peanuts fortified at 0.05 and 0.50 ppm; low 

recoveries were obtained for CL 434223. CL 3000402 was not recovered in Protocol B testing 

due to matrix interferences in both grapes and peanuts. 

Protocol C testing of the compounds indicated that further testing using Protocols D, E and F 

was required for all test substances. The Protocol C results indicated that all analytes were 

detected using an electron capture detector (ECD). 

Metrafenone was recovered from grapes fortified at 0.05 and 0.50 ppm using Protocols D and E 

(mixed ether and methylene chloride elution systems), and from peanuts fortified at 0.05 and 

0.50 ppm using Protocol F. CL 376991, CL 434223, and CL 3000402 were also recovered using 

Protocol D (without Florisil cleanup). CL 376991, CL 434223, and CL 3000402 were not 

recovered from the Florisil column in Protocol E and F testing. 
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These data indicate that FDA multiresidue methods Protocols D, E and F may be suitable for 

determining residues of metrafenone in grapes and peanuts.

 

Conclusions: The submitted multiresidue methods test data are adequate. The data indicate that 

multiresidue methods are probably suitable for determining residues of metrafenone in grapes for 

tolerance enforcement. These results were previously submitted to FDA. 

5.1.3 Tolerance Enforcement Methods

Residue Analytical Method DER for MRIDs #48981303 and 48981304

Residue Analytical Method DER for MRIDs #49267202 and 49267203

QuEChERS: BASF has submitted the QuEChERS method as the new enforcement method for 

metrafenone residues in plant commodities. The data previously requested regarding 

fortification at tolerance levels for the previous tolerance enforcement method (FAMS 105-01 

for grape, and FAMS 106-01 for wine) are no longer relevant. This conditional data issue is 

considered resolved, and the new enforcement method and supporting ILV are discussed and 

reviewed below, and in the supporting DER for MRIDs #48981303 and 48981304. 

Briefly, homogenized samples are extracted with ACN. A mixture of magnesium sulfate, 

sodium chloride, and citrate salts is added to buffer the solution to pH 5-5.5, and after shaking, 

the mixture is centrifuged to separate the phases. An aliquot of the ACN phase is cleaned-up by

dSPE on primary secondary amine sorbent for analysis using LC/MS/MS. Two parent-daughter 

ion transitions are monitored, one for quantitation (m/z 409→209), and the other for 

confirmation (m/z 411→209 for dried hop cones, m/z 409→227 for all other matrices). Based 

on the lowest level of method validation (LLMV), the validated LOQ is 0.01 ppm for 

metrafenone.

The method was adequately validated using samples of dry bean seed, cucumber, dried hops 

cones, lemon, rapeseed, and wheat forage, grain and straw. Samples were fortified with 

metrafenone at the LOQ (0.01 ppm) and 10X the LOQ (0.1 ppm) for dry bean seed and rapeseed; 

at 0.01, 0.10 and 0.50 ppm for wheat grain; at 0.01, 0.10, and 5.0 ppm for cucumber, lemon, 

wheat forage, and wheat straw; and at 0.01, 0.10, and 20 ppm for dried hop cones. For samples 

fortified at the LOQ, recoveries ranged from 79-91% (average of 86% and standard deviation of 

4.9%) for dry bean seed; 102-105% (average of 104% and standard deviation of 1.2%) for 

cucumber; 97-101% (average of 99% and standard deviation of 1.8%) for dried hop cones; 96-

108% (average of 104% and standard deviation of 4.6%) for lemon; 94-99% (average of 97% 

and standard deviation of 2.0%) for rapeseed; 96-102% (average of 100% and standard deviation 

of 2.5%) for wheat forage; 102-105% (average of 104% and standard deviation of 1.1%) for 

wheat grain; and 96-105% (average of 100% and standard deviation of 3.4%) for wheat straw. 

Individual recoveries at each fortification level were within the acceptable range of 70-120% and 

coefficients of variance ranged from 0.9-6.6%. 
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The QuEChERS method is proposed as an enforcement method for metrafenone residues in plant 

commodities. Because the method includes monitoring of two parent-daughter ion transitions, a 

separate confirmatory method is not required. An adequate ILV study was submitted for the 

method (with dry bean seed, cucumber, dried hop cones, lemon, rapeseed, and wheat forage, 

grain and straw) at fortification levels including the LOQ and 10X the LOQ. 

No radiovalidation data were submitted. However, the cucumber metabolism study conducted 

with metrafenone included data demonstrating the ability of ACN to extract incurred residues 

from treated crop matrices. Ergo, no radiovalidation data are required. 

Because the QuEChERS method is a German multi-residue method, Agency method validation 

is not required. 

DFG Method S19: BASF has submitted DFG Method S19 (extended revision) as the new 

enforcement method for metrafenone residues in livestock commodities. The new enforcement 

method and supporting ILV are discussed and reviewed below, and in the supporting DER for 

MRIDs #49267202 and 49267203. 

Briefly, the samples are extracted with acetone/water (2:1, v:v), and the extracts are partitioned 

with ethyl acetate/cyclohexane (1:1, v:v). An aliquot of the organic phase is evaporated to near 

dryness, and the residue is re-dissolved in ethyl acetate. A salt mixture and cyclohexane are 

added to the residue and mixed. The samples are cleaned up through gel permeation 

chromatography (GPC), and residues are eluted with ethyl acetate/cyclohexane (1:1, v:v). The 

eluate is concentrated, and dissolved in ethyl acetate for analysis. The LOQ is 0.01 ppm in milk, 

and 0.05 ppm in meat and eggs. The LOD is 0.002 ppm in milk, and 0.01 ppm in meat and eggs. 

The method was adequately validated using samples of milk fortified with metrafenone at 0.010 

and 0.10 ppm, and samples of meat and eggs fortified with metrafenone at 0.05 and 0.50 ppm. 

Overall mean recoveries were 69-97%, with relative standard deviations of less than 20%, from

each matrix tested. 

An ILV study was also conducted using samples of milk fortified with metrafenone at 0.010 and 

0.1 ppm, and samples of meat and eggs fortified with metrafenone at 0.05 and 0.50 ppm. 

Acceptable mean recoveries ranging from 76% to 101%, with relative standard deviations of less 

than 20%, were found from each matrix tested. 

No confirmatory procedures, or radiovalidation data were included in the submission. Because 

this method monitors multiple ions for the determination of metrafenone, no confirmatory

procedures are needed. No radiovalidation data are required for the method because the solvent 

systems utilized in method DFG S 19 should efficiently extract metrafenone residues in meat, 

milk and eggs based on similar polarity of the solvents used in the goat metabolism study with

metrafenone (refer to the DER for MRID #49267201). 
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Conditional Data - Method Validation/Radiovalidation: Additional method validation data were 

requested in the previous HED Risk assessment (D354166; D. McNeilly; 1 March 2010) for the 

analytical Method FAMS 105-01, reflecting fortifications at 4.5 ppm for grapes, and at both the 

LOQ (0.05 ppm) and 17 ppm for raisins. In addition, radiovalidation data were also required to 

demonstrate that Method FAMS 105-01 adequately recovers weathered residues of metrafenone 

from grapes. Since a new enforcement analytical method has been submitted these two issues 

related to the previous enforcement method are no longer relevant. It should be noted that the 

registrant did provide data showing adequate extractability using the 4:1 n-heptane/acetone 

extraction approach. HED notes that the cucumber data demonstrate adequate extractability

using 4:1 n-heptane/acetone. 

Conditional Data - Data Collection Method Radiovalidation: The extraction solvent used in the 

data collection method for grapes was different from that used in the proposed enforcement 

method, and radiovalidation data were required to support the data collection method, BASF 

Method 535/0. Samples from the grape field trial and processing studies submitted with 

PP#8F7371 were analyzed for residues of metrafenone using an LC/MS/MS method, BASF 

method 535/0. Briefly, samples of grape commodities were extracted with methanol/water/2N

HCl (14:5:1, v/v/v), and centrifuged. The supernatant was partitioned against cyclohexane under 

alkaline conditions, evaporated to dryness, and reconstituted in methanol/water (1:1, v/v) for 

LC/MS/MS determination of residues of metrafenone. 

This conditional data issue is considered resolved by the data extraction efficiency data discussed 

below, and summarized in Tables 5.1.3.1 and 5.1.3.2, below. These data compare the extraction 

efficiency for the Method 535/0 together with the extraction efficiency for the extraction system 

used in the cucumber and grape metabolism studies. The data demonstrate a high extraction 

efficiency for the methanol/water/HCl system. All the cucumber fruit samples had extraction 

efficiencies equal to or greater than 88%. 

Conditional Data – Extraction Efficiencies Using Different Solvent Systems: Cucumber plants 

were treated with two applications of radio-labeled metrafenone (labeled in the trimethoxyphenyl

ring) at a rate of 200 g ai/ha (total seasonal application rate of 400 g ai/ha). There was a 14-day

interval between treatments. Leaf samples were collected directly after the first application, and 

three days after the second application. Whole fruit samples were harvested 14 days after the 

first application, and three days after the second application. 

The whole fruit was divided into pulp and peel samples. The samples were homogenized and 

then extracted with the solvent systems listed in the table below. Radioactivity was determined 

by liquid scintillation counting. 
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TABLE 5.1.3.1 Extractability of 14C-Metrafenone in Cucumber Matrices (%TRR1).

Sample Matrix (Timing2) Metabolism Extraction Method 535 Method 105-01 S19 Method

3X 

Methanol

Followed by 

2X Water

Methanol/Water/

HCl (70/25/5)

n-Heptane/ 

Acetone (80/20)

Acetone/

Water (2/1)

Cucumber Fruit (14-DAT1) 87.5 1.6 87.6 71.0 86.2

Cucumber Fruit (3-DAT2) 92.9 1.4 95.3 85.4 93.4

Cucumber Pulp (2-DAT2) 91.1 1.1 93.5 56.2 91.0

Cucumber Fruit (3-DAT2) 91.2 1.1 94.0 84.0 93.6

Cucumber Fruit (0-DAT1) 98.8 0.3 94.2 95.8 96.8

Cucumber Fruit (3-DAT2) 92.6 3.2 91.9 85.3 90.3

1. DAT = Days After first Treatment. 

2. TRR = Total Radioactive Residues. 

The recoveries for metrafenone using the extraction profile in the cucumber metabolism study

are similar to the other three extraction profiles tested, except for one cucumber pulp sample 

which did have low recovery. The extractability of radioactive residues from cucumber peel in 

the metabolism study was very high, 92.2% of the TRR from pulp, and 99.1% of the TRR from

cucumber leaves. Most of the radioactive residue was extracted with methanol. The additional 

extraction with water released very low amounts of the TRR (1.1%). 

The extractability with solvents was tested for all cucumber matrices (leaf, fruit, pulp, peel and 

the rest of the plant). Three one-step extraction methods were investigated: methanol/water/2N

HCl (14:5:1, v/v/v/), n-heptane/acetone (4:1, v/v), and acetone/water (2:1, v/v). The results of 

the extractability tests are summarized in the table below. 

TABLE 5.1.3.2 Extractability of Cucumber Whole Fruit Samples with Different Solvent Systems.

Sample

Matrix

DAT1Solvent ERR2

Mg/Kg %TRR

RRR3

Mg/Kg %TRR

Whole Fruit 14 3X Methanol, 2X water

(metabolism extraction)

0.015 89.0 0.002 11.0

Methanol/Water/2N HCl

(Method 535/1)

0.011 87.6 0.002 12.4

n-Heptane/Acetone

(Method 105-01)

0.004 71.0 0.002 29.0

Acetone/Water (S-19 

Method)

0.012 86.2 0.002 13.8

Whole Fruit 17 3X Methanol, 2X water 0.048 94.3 0.003 5.7

Methanol/Water/2N HCl 0.042 95.3 0.002 4.7

n-Heptane/Acetone 0.038 85.4 0.007 14.6

Acetone/Water 0.045 93.4 0.003 6.6

1. DAT = Days After first Treatment. 

2. ERR = Extracted Radioactive Residues. 

3. RRR = Remaining or bound Radioactive Residues. 
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Conclusions: Radiovalidation data are no longer required to demonstrate that Method FAMS 

105-01 and BASF Method 535 adequately recover weathered residues of metrafenone from 

grapes. HED agrees that the cucumber data, and other extraction efficiency data conducted as a

part of the cucumber metabolism study, adequately demonstrate the extractability of metrafenone 

residues using 4:1 n-heptane/acetone solvent and methanol/water/2N HCl (70:25:5, v/v/v) 

solvent systems. No additional data are required to satisfy the conditional data requirements that 

were previously identified by HED. 

Method validation and ILV data submitted for the QuEChERS method (MRIDs #48981303 and 

48981304) demonstrate that it is adequate as the new tolerance enforcement method for 

metrafenone. 

Method validation and ILV data submitted for the QuEChERS method (MRIDs #48981303 and 

48981304) demonstrate that it is adequate as the new tolerance enforcement method for 

metrafenone. 

5.2 Storage Stability (860.1380)

Residue Chemistry Summary D312307; D. McNeilly; 24 August 2006

Storage Stability DER for MRID #48981308

BASF submitted the results of a storage stability study with metrafenone in wheat (whole plant, 

grain, and straw), grape, tomato, dried pea, and soybean seed (MRID #48981308). These crops 

meet the OECD requirement for stability in five diverse crops, including high-water, high-oil, 

high-protein, high-starch and high-acid. Untreated samples were fortified with metrafenone at 

0.10 ppm, and stored frozen at roughly -20°C, followed by analysis at intervals of 0, 28-31, 55, 

84, 85, 174-178, 358-360, 455, and/or 726-739 days. 

Samples were analyzed for residues of metrafenone using an LC/MS/MS method, BASF Method 

#535/1 (L0076/01). This method was adequate for data collection, based on acceptable 

concurrent recovery data. The LOQ, determined as the LLMV, was 0.01 ppm in each sample 

matrix. It was not reported whether concurrent recoveries and recoveries in stored samples were 

corrected for apparent residues in controls. 

The study results indicate that residues of metrafenone are stable in wheat (whole plant, grain, 

and straw), grape, tomato, dried pea, and soybean seed stored frozen (roughly -20°C) for

intervals of up to 726-739 days (approximately 2 years).
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TABLE 5.2 Storage Stability of Metrafenone in Wheat, Grape, Tomato, Dried Pea, and Soybean.

Commodity Spike 

Level

(ppm)

Storage 

Interval

(Days)

Recovered 

Residues (ppm)

Mean Recovered 

Residues1(ppm)

Mean 

Recovery (%)

Corrected 

Recovery (%)2

Wheat, 

Whole Plant

0.10 0 0.085, 0.087 0.086 86 --

31 0.074, 0.072 0.073 73 94

178 0.083, 0.083 0.083 83 96

360 0.081, 0.079 0.080 80 100

732 0.081, 0.089 0.085 85 86

Wheat, 

Grain

0.10 0 0.105, 0.109 0.107 107 --

31 0.079, 0.078 0.079 79 87

178 0.083, 0.083 0.083 83 85

360 0.085, 0.084 0.085 85 83

726 0.077, 0.077 0.077 77 86

Wheat, 

Straw

0.10 0 0.091, 0.091 0.091 91 --

29 0.090, 0.091 0.091 91 100

176 0.083, 0.086 0.085 85 95

358 0.089, 0.093 0.091 91 96

732 0.077, 0.079 0.078 78 100

Grape 0.10 0 0.088, 0.090 0.089 89 --

30 0.075, 0.079 0.077 77 95

176 0.095, 0.099 0.097 97 98

358 0.107, 0.105 0.106 106 110

730 0.078, 0.088 0.083 83 99

Tomato 0.10 0 0.088, 0.089 0.089 89 --

29 0.088, 0.087 0.088 88 97

174 0.101, 0.101 0.101 101 100

358 0.074, 0.076 0.075 75 77

455 0.076, 0.076 0.076 76 98

726 0.092, 0.100 0.096 96 106

Dried Pea 0.10 0 0.104, 0.104 0.104 104 --

29 0.087, 0.093 0.090 90 94

176 0.095, 0.097 0.096 96 92

358 0.089, 0.091 0.090 90 90

730 0.077, 0.090 0.084 84 87
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TABLE 5.2 Storage Stability of Metrafenone in Wheat, Grape, Tomato, Dried Pea, and Soybean.

Commodity Spike 

Level

(ppm)

Storage 

Interval

(Days)

Recovered 

Residues (ppm)

Mean Recovered 

Residues1(ppm)

Mean 

Recovery (%)

Corrected 

Recovery (%)2

Soybean, 

Seed

0.10 0 0.098, 0.098 0.098 98 --

28 0.071, 0.072 0.072 72 75

55 0.078, 0.079 0.079 79 84

84 0.089, 0.090 0.090 90 84

85 0.085, 0.079 0.082 82 81

176 0.057, 0.062 0.060 60 60

358 0.070, 0.073 0.072 72 72

739 0.096, 0.100 0.098 98 95

1. Mean recovered residues were determined by the study reviewer.

2. Corrected for mean concurrent recovery.

Storage stability data for grapes and wine were previously submitted and reviewed with

PP#4E6884. Those data indicate that residues of metrafenone are stable under frozen storage 

conditions for intervals of up to 18 months in grapes and wine (D312307; D. McNeilly; 24 

August 2006). 

Conclusions: The storage stability data are adequate and demonstrate that residues of 

metrafenone are stable in wheat (whole plant, grain, and straw), grape, tomato, dried pea, and 

soybean seed stored frozen (at approximately -20°C) for up to 726-739 days (roughly 2 years). 

The submitted and available storage stability data are adequate to support the storage conditions 

and durations of samples from the submitted crop field trial and processing studies. 

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)

Pome Fruit (MRID #49055901): BASF has submitted field trial data for metrafenone on 

representative crops (apple and pear) of the pome fruits crop group 11-10. A total of 18 field 

trials were conducted on pome fruits during the 2010 growing season in North American Free 

Trade Agreement (NAFTA) Growing Zones: twelve trials on apple in Zones 1 (NY, two trials; 

PA, one trial), 2 (VA, one trial), 5 (MI, WI, one trial each), 9 (UT, one trial), 10 (CA, one trial), 

and 11 (ID, WA, two trials each), and six trials on pear in Zones 1 (NY, one trial), 10 (CA, two 

trials), and 11 (ID, two trials; WA, one trial).

At 14 of the test sites (nine apple/five pear), one untreated control and one treated plot 

(Treatment 2) were established, with the treated plot receiving applications consisting of either 

concentrated or dilute spray volumes of 50-100 or 100-400 gallons per acre (GPA), respectively. 

At the four remaining test sites (three apple and one pear), which were located in zones where 
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only one trial per crop was to be conducted, one untreated control and side-by-side treated plots 

were established, with the treated plots receiving either the concentrate (Treatment 2) or dilute 

(Treatment 3) spray volume regime, described above.

At each site, the treated plots received three foliar airblast applications of metrafenone (2.5 lb 

ai/gal SC, BASF formulation code BAS 560 03 F) targeting roughly 0.3 lb ai/A/application 

(0.336 kg ai/ha/application), with a nominal 7-day RTI, resulting in a total rate of roughly 0.9 lb 

ai/A (1.0 kg ai/ha/season). The actual application rate ranged from 0.29-0.31 lb ai/A/application, 

with 5- to 9-day RTIs, for a total rate of 0.89-0.92 lb ai/A (1.00-1.03 kg ai/ha/season). The 

applications were made in approximately 59-86 GPA of water (552-804 L/ha) for concentrate 

spray volumes and approximately 101-257 GPA of water (945-2404 L/ha) for dilute spray

volumes using ground (airblast) equipment. An adjuvant (non-ionic surfactant) was included in 

the spray mixture for each application. Single control and duplicate treated apple and pear RAC 

samples (fruit) were harvested at normal crop maturity 6- to 7- and 13- to 16-day PHIs at all test 

sites. At one pear and two apple test sites, additional treated samples were collected at PHIs of 

0, 3-4, and 21 days to examine residue decline. 

TABLE 5.3.1.1 Summary of Residue Data from Pome Fruit Field Trials with Metrafenone.

Matrix Total Use 

Rate ± 5%

kg ai/ha (lb 

ai/A)

Spray 

Volume

(GPA)

PHI 

(Days)

Residue Levels (ppm)1

n Min. Max. LAFT2 HAFT2 Median Mean Std.

Dev.

Apple

(Fruit)

1.0

(0.9)

(50-100)36-7 7 0.07 0.85 0.08 0.76 0.23 0.31 0.23

13-16 7 0.04 0.57 0.05 0.54 0.20 0.22 0.16

1.0

(0.9)

(100-

400)4

6-7 8 0.13 0.60 0.14 0.54 0.29 0.31 0.15

13-15 8 0.09 0.49 0.10 0.45 0.25 0.27 0.13

1.0

(0.9)

Both

(50-400)

6-7 15 0.07 0.85 0.08 0.76 0.23 0.31 0.19

13-16 15 0.04 0.57 0.05 0.54 0.20 0.25 0.14

Pear

(Fruit)

1.0

(0.9)

(50-100)36-7 4 0.13 0.43 0.16 0.41 0.29 0.29 0.13

13-14 4 0.08 0.36 0.10 0.33 0.22 0.22 0.12

1.0

(0.9)

(100-

400)4

7 3 0.12 0.52 0.14 0.48 0.41 0.34 0.18

14 3 0.09 0.43 0.09 0.37 0.28 0.25 0.14

1.0

(0.9)

Both

(50-400)

6-7 7 0.12 0.52 0.14 0.48 0.39 0.31 0.14

13-14 7 0.08 0.43 0.09 0.37 0.28 0.23 0.12

All 

Pome 

Fruits

1.0

(0.9)

Both

(50-400)

6-7 22 0.07 0.85 0.08 0.76 0.27 0.31 0.17

13-16 22 0.04 0.57 0.05 0.54 0.21 0.24 0.13

1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 

2. LAFT = Lowest Average Field Trial value; HAFT = Highest Average Field Trial value. 

3. Concentrate spray. 

4. Dilute spray. 

The residues of parent metrafenone in apple and pear RAC samples were quantitated using an 

LC/MS/MS multi-residue QuEChERS method (BASF Study #398340). The method was 

successfully validated on apples in conjunction with this study prior to analysis of the field 
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samples. Acceptable concurrent method recovery data for pome fruit RAC samples were also 

obtained for metrafenone. The validated LOQ for residues of metrafenone in pome fruits RAC 

samples was 0.01 ppm. The LOD was 0.003 ppm.

The pome fruits RAC samples were stored frozen for a maximum of 734 days (24 months) from 

collection to extraction for analysis. The interval between extraction and analysis was 0-1 day. 

Adequate storage stability data for metrafenone are available to support the storage conditions 

and intervals incurred by the pome fruit residue samples in this study.

The results from these trials are summarized in Table 5.3.1.1, above, and show that following the 

last of three foliar airblast applications of metrafenone at roughly 0.3 lb ai/A/application, with 5-

to 9-day RTIs, residues of metrafenone (and per trial averages) were 0.07-0.85 (0.08-0.76) ppm 

(concentrate spray) and 0.13-0.60 (0.14-0.54) ppm (dilute spray) in 30 treated apple samples 

harvested at a 6- or 7-day PHI. At the same treatment rate and RTIs, metrafenone residues (and 

per trial averages) were 0.04-0.57 (0.05-0.54) ppm (concentrate spray) and 0.09-0.49 (0.10-0.45) 

ppm (dilute spray) in 30 treated apple samples collected at a 13- to 16-day PHI.

After three foliar airblast applications of metrafenone at roughly 0.3 lb ai/A/application, with 7-

to 8-day RTIs, residues of metrafenone (and per trial averages) were 0.13-0.43 (0.16-0.41) ppm 

(concentrate spray) and 0.12-0.52 (0.14-0.48) ppm (dilute spray) in 14 treated pear samples 

harvested at a 6- or 7-day PHI. At the same treatment rate and RTIs, metrafenone residues (and 

per trial averages) were 0.08-0.36 (0.10-0.33) ppm (concentrate spray) and 0.09-0.43 (0.09-0.37) 

ppm (dilute spray) in 14 treated pear samples collected at a 13- or 14-day PHI.

No substantial differences in metrafenone residues were observed between the concentrate and 

dilute spray applications. Data from the residue decline sites indicate that metrafenone residues 

in pome fruits declined with increasing PHIs (results not shown here; see the DER for MRID 

#49055901 for further details).

Pome Fruit Conclusions: The results have shown that the maximum residues of metrafenone in

pome fruits (apple and pear fruit RAC samples) following three foliar airblast applications of the 

2.5 lb ai/gal SC formulation using dilute or concentrate spray volumes and totaling roughly 0.9 

lb ai/A/season were 0.85 ppm at a 6- to 7-day PHI and 0.57 ppm at a 13- to 16-day PHI. There 

were no substantial differences in the residues of metrafenone between the application spray

volume treatments. Data from the residue decline tests indicated that metrafenone residues in 

pome fruits declined with increasing PHIs. The maximum metrafenone residues in pome fruits 

are within a factor of 5 of each other (0.85 and 0.52 ppm for apple and pear, respectively, at the 

targeted 7±1 day PHI); therefore, the residues are within the EPA guidelines for the 

establishment of a group tolerance in crop group 11-10 (pome fruits).

An acceptable method was used for residue quantitation, and adequate storage stability data are 

available to support the sample storage conditions and durations. 
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Fruiting Vegetables, Tomato (MRID #49119108): BASF has submitted field trial data for 

metrafenone (BAS 560 F) on tomato from a total of 18 trials conducted during the 2010-2011

growing seasons in NAFTA Growing Zones 1 (NY, one trial), 2 (GA, NC, one trial each), 3 (FL, 

two trials), 5 (OH, MI, one trial each), and 10 (NM and AZ, one trial each; CA, nine trials). 

HED has determined that one trial pair (-CA123 and –CA127) should be considered replicates; 

the above field trial distribution incorporates this conclusion. 

Each test location included one treated and one untreated plot. At each site, the treated plot 

received three broadcast or directed foliar applications (except as noted below for the trial 

located in AZ) of metrafenone (2.5 lb ai/gal SC, BASF formulation code BAS 560 03 F) 

targeting 0.30 lb ai/A/application (0.336 kg ai/ha/application), with a nominal 7-day RTI, 

resulting in a total rate of 0.90 lb ai/A (1.0 kg ai/ha/season). The actual application rate was 

0.29-0.33 lb ai/A/application, with a 6- to 8-day RTI, for a total rate of 0.89-0.95 lb ai/A (0.999-

1.066 kg ai/ha/season). At the trial in AZ, in order to allow the fruit to develop further and 

provide adequate samples for residue analysis, four foliar sprays of metrafenone at 0.30-0.32 lb 

ai/A/application were made, with a 7- or 8-day RTI, totalling 1.23 lb ai/A (1.38 kg ai/ha/season). 

All applications were made in approximately 31-90 GPA of water (286-841 L/ha) using ground 

equipment. An adjuvant was included in the spray mixture for each application. At all test sites 

tomato RAC samples (fruit) were harvested at normal crop maturity, at a 0 day PHI, after the 

spray had dried on the fruit, and again at a 6-8 day PHI. At two test sites (Trial CA124 and 

FL38), additional treated samples were collected 1, 3, 9-10 and 12-14 day PHI to examine residue 

decline. 

The residues of parent metrafenone in tomato RAC samples were quantitated using an 

LC/MS/MS multi-residue QuEChERS method (BASF Study #398340). Sample analysis was 

conducted by Pyxant Labs (Colorado Springs, CO). The method was successfully validated on 

tomato in conjunction with this study prior to analysis of the field samples. Acceptable 

concurrent method recovery data for tomato RAC samples were also obtained for metrafenone. 

The validated LOQ for residues of metrafenone in tomato RAC samples was 0.01 ppm. The 

estimated method LOD was reported as 0.001 ppm, or approximately 10% of the LOQ. The 

calculated LOD and LOQ for metrafenone in tomato fruit were 0.001 and 0.004 ppm, 

respectively.

The tomato RAC samples were stored frozen for 303-730 days (approximately 10-24 months) 

from collection to extraction for analysis. Adequate storage stability data for metrafenone are 

available to support the storage conditions and durations incurred by the tomato residue samples 

in this study.

As summarized in Table 5.3.1.2, below, the results from these trials show that following the last 

of three or four foliar applications of metrafenone at roughly 0.3 lb ai/A/application, with 6- to 8-

day RTIs, residues of metrafenone (and per trial averages) were 0.041-0.452 (0.069-0.427) ppm 
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in 38 treated tomato samples harvested at a 0-day PHI and <0.01-0.188 (<0.011-0.163) ppm in

38 treated tomato samples harvested at a 6-8 day PHI. Data from the residue decline sites 

indicate that metrafenone residues in tomato generally declined with increasing PHIs. 

TABLE 5.3.1.2 Summary of Residue Data from Tomato Field Trials with Metrafenone

Commodity Total Use Rate

lb ai/A (g ai/ha)

PHI 

(Days)2

Residue Levels (ppm)1

n

3 Min. Max. LAFT4 HAFT4 Median Mean Std. 

Dev.

Tomato

(Fruit)

0.891-1.234

(999-1383)

0 18 0.0409 0.452 0.0694 0.427 0.110 0.164 0.094

0.910-0.922

(1020-1033)5

1 2 0.0427 0.0865 0.0541 0.0721 0.0631 0.0631 NA6

3 2 0.0512 0.0830 0.0572 0.0748 0.0660 0.0660 NA

0.891-1.234

(999-1383)

6-8 18 <0.01 0.188 <0.0107 0.163 0.0860 0.0770 0.0446

0.910-0.922

(1020-1033)5

9, 10 2 0.0149 0.0719 0.0187 0.0536 0.0362 0.0362 NA

12, 14 2 0.0138 0.0327 0.0166 0.0247 0.0207 0.0207 NA

1. Except for sample min/max, values reflect per trial averages.

2. The first harvest was on the day of the last application (0-day PHI) at all trials. The second harvest was 6 to 8 

days after the last application (6- to 8-day PHI) at all trials, except field trials –CA124 and –FL38. At field 

trial –CA124, a decline study was conducted with the last application 0, 1, 3, 6, 10 and 12 days before 

harvest (0- to 12-day PHI). At field trial –FL38, a decline study was conducted with the last application 0, 

1, 3, 7, 9 and 14 days before harvest (0- to 14-day PHI).

3. n = number of field trials.

4. LAFT = Lowest Average Field Trial value; HAFT = Highest Average Field Trial value.

5. Data from the two residue decline trials.

6. NA = Not Applicable.

Fruiting Vegetables, Pepper (MRID #49119107): BASF has submitted field trial data for 

metrafenone (BAS 560 F) on pepper from a total of eight trials conducted during the 2010 

growing season: five on bell pepper varieties in NAFTA Growing Zones 2 (GA, one trial), 3 

(FL, one trial), 5 (IL, one trial), 6 (OK, one trial) and 10 (CA, one trial) and three on non-bell 

pepper varieties in NAFTA Growing Zones 2 (GA, one trial), 8 (KS, one trial) and 10 (CA, one 

trial). HED has determined that one trial pair (R100014 and R100019) should be considered 

replicates; the above field trial distribution incorporates this conclusion. 

Each test location included one treated and one untreated plot. At each site, the treated plot 

received three broadcast foliar applications of metrafenone as an SC formulation, targeting 0.30 

lb ai/A/application (0.336 kg ai/ha/application), with a nominal 7-day RTI, resulting in a total 

rate of 0.90 lb ai/A (1.0 kg ai/ha/season). The actual application rate was 0.29-0.31 lb 

ai/A/application, with a 7-day RTI, for a total rate of 0.88-0.91 lb ai/A (0.991-1.017 kg 

ai/ha/season). The applications were made in approximately 21-31 GPA of water (200-286 L/ha) 

using ground equipment. A nonionic surfactant (NIS) adjuvant was included in the spray

mixture for each application. 
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Pepper RAC samples (fruit) were harvested at normal crop maturity, at a 0-day PHI at all test 

sites, after the spray had dried on the fruit, and again at a 7 day PHI. At one test site (Trial 

R100014, CA), additional treated samples were collected at 3, 10 and 14 day PHIs to examine 

residue decline. 

The residues of parent metrafenone in pepper RAC samples were quantitated using an 

LC/MS/MS multi-residue QuEChERS method (BASF Study #398340, reported as Method 

#R00033). Sample analysis was conducted by Pyxant Labs (Colorado Springs, CO). The 

method was successfully validated on pepper in conjunction with this study prior to analysis of 

the field samples. Acceptable concurrent method recovery data for pepper RAC samples were 

also obtained for metrafenone. The validated LOQ for residues of metrafenone in pepper RAC 

samples was 0.01 ppm. The method LOD was reported as 0.001 ppm, or 10% of the LOQ. 

The pepper RAC samples were stored frozen for 671-764 days (approximately 22-25 months) 

from collection to extraction for analysis, and were analyzed within 16 days of extraction. 

Adequate storage stability data for metrafenone are available to support the storage conditions 

and durations incurred by the pepper residue samples in this study.

As summarized in Table 5.3.1.3, below, the results from these trials show that following the last 

of three foliar applications of metrafenone at roughly 0.3 lb ai/A/application, with 7-day RTIs, 

residues of metrafenone (and per trial averages) were 0.067-0.667 (0.081-0.498) ppm in 18 

treated pepper samples harvested at a 0-day PHI and were 0.062-0.296 (0.065-0.295) ppm in 18 

treated pepper samples harvested at a 7-day PHI. 

The maximum residues were observed in the non-bell pepper cultivars, but were at relatively 

similar levels to those observed in the bell-pepper cultivars: Maximum metrafenone residues 

(and maximum per trial averages) for bell pepper varieties were 0.508 (0.417) ppm at the 0-day

PHI and 0.271 (0.221) ppm at the 7-day PHI, and for non-bell pepper varieties, 0.667 (0.498) 

ppm at the 0-day PHI and 0.296 (0.295) ppm at the 7-day PHI. Data from the residue decline 

site indicate that metrafenone residues in pepper declined with increasing pre-harvest intervals

(results not shown here; see the DER for MRID #49119107 for further details). 

TABLE 5.3.1.3 Summary of Residue Data from Pepper Field Trials with Metrafenone

Commodity Total Appl. Rate

lb ai/A (g ai/ha)

PHI 

(days)

Residue Levels (ppm)1

n Min. Max. LAFT2 HAFT2 Median Mean Std. Dev.

Bell Pepper

(Fruit)

0.884-0.907

(991-1017)

0 5 0.112 0.508 0.148 0.417 0.270 0.297 0.113

7 5 0.0828 0.271 0.0991 0.221 0.163 0.158 0.0506

Non-bell 

Pepper (Fruit)

0 3 0.0665 0.667 0.0813 0.498 0.353 0.311 0.212

7 3 0.0622 0.296 0.0649 0.295 0.144 0.168 0.117

Combined

Pepper (Fruit)

0 8 0.0665 0.667 0.0813 0.498 0.312 0.302 0.142

7 8 0.0622 0.296 0.0649 0.295 0.154 0.162 0.0734

1. Except for sample min/max, values reflect per trial averages; n = number of field trials

2. LAFT = Lowest Average Field Trial Value; HAFT = Highest Average Field Trial value.
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Fruiting Vegetables Conclusions: The results have shown that the maximum residues of 

metrafenone in fruiting vegetables (tomato and pepper RAC samples) following three foliar 

broadcast applications of the 2.5 lb ai/gal SC formulation totaling roughly 0.9 lb ai/A/season 

were 0.667 ppm at a 0-day PHI. Data from the residue decline tests indicated that metrafenone 

residues in fruiting vegetables declined with increasing PHIs. The maximum metrafenone 

residues in fruiting vegetables are within a factor of 5 of each other (0.452 and 0.667 ppm for 

tomato and pepper, respectively, at the targeted 0-day PHI); therefore, the residues are within the 

EPA guidelines for the establishment of a group tolerance in crop group 8-10 (fruiting 

vegetables).

An acceptable method was used for residue quantitation, and adequate storage stability data are 

available to support the sample storage conditions and durations. 

Cherry (MRID #49145402): IR-4 submitted field trial residue data for metrafenone on cherry. 

Fourteen cherry field trials (9 sweet cherry trials, and 5 tart cherry trials) were conducted in the 

United States and Canada during the 2010 growing season in NAFTA Growing Zones 1 (NY; 1 

trial), 5A (MI; 2 trials), 5 (ON; 3 trials), 9 (CO; 1 trial), 10 (CA; 2 trials) and 11 (ID, WA, and 

BC; 5 trials). HED has concluded that three trials conducted in Zone 5 should be considered 

replicates for purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data 

requirements. The above field trial distribution incorporates this conclusion. 

Each trial consisted of one untreated and one treated plot. At each trial location, the treated plot 

received two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone

(BAS560 03 F SC) at 0.286-0.314 lb ai/A/application (321-352 g ai/ha/application) for a total 

seasonal rate of 0.575-0.626 lb ai/A (645-702 g ai/ha). Applications were made at 6- to 9-day

RTIs using ground equipment (airblast sprayer) in spray volumes of 105-189 GPA (984-1767

L/ha), except at the NY trial, where higher than normal temperatures accelerated maturation, and 

required that applications be initiated earlier than anticipated; the first application at this trial was 

made in a spray volume of 60.7 GPA (568 L/ha). An NIS, methylated seed oil (MSO), crop oil 

concentrate (COC), or organo-silicone surfactant (OSS) was added to the spray mixtures for all 

applications. Samples of cherries were harvested from all trial sites at PHIs of 6-8 and 13-15

days. Additional cherry samples were collected from two trials at PHIs of 0, 3, 17 and 21 days to 

generate residue decline data. 

Samples of cherries were analyzed for residues of metrafenone using an LC/MS/MS method 

derived from QuEChERS Method #R00033. The LOQ, determined as the LLMV, was 0.01

ppm. The method was adequate for data collection, based on acceptable method validation and 

concurrent recovery data. The fortification levels used in concurrent method recovery were 

adequate to bracket expected residue levels. Concurrent recoveries were corrected for apparent 

residues in controls; residues in treated samples were not corrected for residues in controls.
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Samples of cherries were transferred to a sample preparation facility for homogenization prior to 

shipment to the analytical laboratory. Samples were stored frozen (-31 to -3°C at the field sites, 

≤-5°C at the sample preparation facility, and temperature unspecified at the analytical laboratory) 

from collection to analysis for 676-784 days (22.2-25.8 months). Samples were analyzed within 

2-9 days of extraction. Adequate storage stability data are available to support the sample 

storage conditions and durations.

The results from these trials are summarized in Table 5.3.1.4, below. Following two foliar 

directed applications of a 2.5 lb ai/gal SC formulation of metrafenone at a total rate of 0.575-

0.626 lb ai/A (645-702 g ai/ha), residues (and per trial averages) of metrafenone in cherries 

harvested at PHIs of 6-8 days and 13-15 days, respectively, were 0.280-1.17 (0.317-1.16) and 

0.117-0.704 (0.144-0.608) ppm. It was noted that the highest residues in cherries harvested at 

the 6- to 8-day PHI were observed in samples from the NY trial, where the first application was 

made in a lower than targeted spray volume, and the highest residues in cherries harvested at the 

13- to 15-day PHI were observed in samples from one of the replicate MI trials, where adjuvant 

rates were lower than expected. At the residue decline trials, residues of metrafenone generally 

declined with increasing PHI in cherries (results not shown here; see the DER for MRID 

#49145402 for further details). 

TABLE 5.3.1.4 Summary of Residue Data from Cherry Field Trials with Metrafenone.

Commodity Total Rate

lb ai/A

(g ai/ha)

PHI 

(days)

Residue Levels (ppm)

1

n Min. Max. LAFT2 HAFT2 Median Mean Std. 

Dev.

Cherry 0.575-0.626

(645-702)

6-8 14 0.280 1.17 0.317 1.16 0.493 0.547 0.221

13-15 14 0.117 0.704 0.144 0.608 0.340 0.370 0.146

1. Except for sample min/max, values reflect per trial averages; n = number of distinct field trials. 

2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

Cherry Conclusions: The submitted cherry field trial data are scientifically acceptable. 

Following two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone at a 

total rate of 0.575-0.626 lb ai/A (645-702 g ai/ha), residues (and per trial averages) of 

metrafenone in cherries harvested at PHIs of 6-8 days and 13-15 days, respectively, were 0.280-

1.17 (0.317-1.16) and 0.117-0.704 (0.144-0.608) ppm. At the residue decline trials, residues of 

metrafenone generally decreased with increasing PHIs in cherries. 

An acceptable method was used for residue quantitation, and adequate storage stability data are 

available to support the sample storage conditions and durations. 

Hops (MRID #49145403): IR-4 submitted field trial data for metrafenone on hops. Five hops 

field trials were conducted in the United States and Canada during the 2010 growing season in

NAFTA Growing Zones 5 (ON 1 trial), 5B (QC; 1 trial), 11 (ID and WA; 2 trials) and 12 (OR; 1 

trial). Examination of the field trial records indicates that there were sufficient differences 
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between the trials that each trial constitutes a separate trial for purposes of OCSPP Residue 

Chemistry Test Guideline 860.1500 data requirements. 

Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated 

plot received two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone 

(BAS560 03 F SC) at 0.304-0.319 lb ai/A/application (341-358 g ai/ha/application) for a total 

seasonal rate of 0.609-0.635 lb ai/A (683-712 g ai/ha). Applications were made at 6- to 8-day

RTIs, except at the ON trial, where the second application was delayed due to a hurricane (10-

day RTI). Applications were made using ground equipment in spray volumes of 84.6-173.8

GPA (791-1626 L/ha). An NIS, MSO, COC or OSS was added to the spray mixtures for all 

applications. Samples of fresh hops cones were harvested by hand at maturity from all trials at a

PHI of 1-4 days. Samples designated for dried hops cones were dried per normal cultural 

practices at or near the field sites. To assess residue decline in dried hops cones, additional 

samples were collected at PHIs of 0, 4, 7 and 14 days from the WA trial. Additional samples 

were also collected at the ON trial at 0- and 1-day PHIs for a residue decline study that was 

terminated due to low yields. 

Samples were analyzed for residues of metrafenone using an LC/MS/MS method derived from 

QuEChERS Method #R00033. The LOQ, determined as the LLMV, was 0.01 ppm in dried and 

fresh hops cones. The analytical method was adequate for data collection, based on acceptable 

method validation and concurrent recovery data. The fortification levels used in method 

validation and concurrent method recovery were adequate to bracket expected residue levels. 

Concurrent recoveries were corrected for apparent residues in controls; residues in treated 

samples were not corrected for residues in controls. 

Samples were transferred to a sample preparation facility for homogenization prior to shipment 

to the analytical laboratory. Samples were stored frozen (-42 to 4.2°F at the field sites, ≤5°C at 

the preparation facility, and -29 to - 17°C at the analytical laboratory) from harvest to analysis 

for 754-819 days (24.8-26.9 months) for dried hops cones, and 752-778 days (24.7-25.6 months) 

for fresh hops cones. Samples were analyzed within 1-7 days of extraction. Adequate storage 

stability data are available to support the sample storage conditions and durations for residues of 

metrafenone.

The results from these trials are summarized in Table 5.3.1.5, below. Following two foliar 

directed applications of the 2.5 lb ai/gal SC formulation of metrafenone at 0.609-0.635 lb ai/A 

(683-712 g ai/ha), residues (and per trial averages) of metrafenone in dried hops cones and fresh 

hops cones, respectively, harvested at 1- to 4-day PHIs were 15.72-158.8 (16.87-131.9) and 5.51-

31.36 ppm. It was noted that the highest residues in dried hops cones were observed in samples 

from the ON trial where the second application was delayed due to a hurricane and where, 

according to the petitioner, half of the crop was destroyed by insects between applications. 

Excluding results for the ON trial (because the hops cones were not of commercial quality), the 

highest average residues observed were 23.52 ppm. At the WA residue decline trial, residues of 
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metrafenone in dried hops cones decreased with increasing PHI. At the ON decline trial, 

residues decreased from the 0- to 1-day PHI, but the highest residues were observed in samples 

from the 2-day PHI (results not shown here; see the DER for MRID #49145403 for further 

details). 

It was noted that the highest residues in dried hops cones were observed in samples from the ON 

trial, where the second application was delayed due to a hurricane and where, according to the 

petitioner, half of the crop was destroyed by insects between applications. There were several 

communications with the petitioner (IR-4) regarding the ON trial, and an outlier analysis 

(Grubbs test) was submitted by IR-4. The outlier analysis was evaluated by HED (D421923; 

Bayazid Sarkar; 21 August 2014). HED used a different approach for analyzing the data (the

Grubbs test was conducted on transformed data because there was sufficient evidence to reject 

the assumption of normality), and ultimately concurred that the residue value obtained from the 

ON field trial constituted an outlier. The results of the HED analysis were shared with the 

PMRA reviewers, who then agreed to exclude that residue value from the dataset input to the 

OECD tolerance calculation procedure. Excluding results for the ON trial (the outlier), the 

highest average residue observed was 23.52 ppm. On a final note regarding hops, HED’s 

recommended tolerance includes the results from European field trials, even though the North 

American field trial data were adequate. Using the combined data sets results in a greater 

likelihood that any future European and Canadian MRLs, and US tolerances will all be 

harmonized.

TABLE 5.3.1.5 Summary of Residue Data from Hops Field Trials with Metrafenone (MRID #49145403).

Commodity Total Rate

lb ai/A (g ai/ha)

PHI 

(days)

Metrafenone Residue Levels (ppm)

1

n Min. Max. LAFT2 HAFT2 Median Mean Std. Dev.

Hops cones, 

dried

0.609-0.635

(683-712)

1-2 5 15.72 158.8 16.87 131.9 21.50 43.07 48.59

Hops cones, 

fresh

0.609-0.635

(683-712)

2-4 5 5.51331.3635.51331.3636.17311.76311.083

1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 

2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

3. Only one sample per trial was analyzed; therefore sample min = LAFT, and sample max = HAFT. Statistical data 

are therefore reflective of individual sample residues rather than per trial mean residue values.

Hops (MRID #49145403) Conclusions: The submitted hops field trial data are scientifically 

acceptable. Following two foliar directed applications of the 2.5 lb ai/gal SC formulation of 

metrafenone at 0.609-0.635 lb ai/A (683-712 g ai/ha), residues (and per trial averages) of 

metrafenone in dried hops cones and fresh hops cones, respectively, harvested at 1- to 4-day

PHIs were 15.72-158.8 (16.87-131.9) and 5.51-31.36 ppm. It was noted that the highest residues 

in dried hops cones were observed in samples from the ON trial, where the second application 

was delayed due to a hurricane and where, according to the petitioner, half of the crop was 

destroyed by insects between applications. Excluding results for the ON trial (because the hops 

cones were not of commercial quality, and the average residue from the trial was deemed an 
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outlier via the Grubbs test), the highest average residues observed were 23.52 ppm. At the WA 

residue decline trial, residues of metrafenone in dried hops cones decreased with increasing PHI. 

At the ON decline trial, residues decreased from the 0- to 1-day PHI, but the highest residues 

were observed in samples from the 2-day PHI.

An acceptable method was used for residue quantitation, and the study is supported by adequate 

storage stability data. 

Hops (MRIDs #49145407 & -08): IR-4 submitted crop field trial and processing study data for 

metrafenone on hops. Six field trials were conducted in Germany during the 2009 (four trials; 

MRID #49145407) and 2010 (two trials; MRID #49145408) growing seasons. Both studies 

reflected collection of fresh (green) and dried hops cones. In the 2009 study dried hops cones 

from three trials were processed to yield the following processed commodities: beer, brewer’s 

yeast, extracted hops, and hops draff. Because the processed commodities of hops are not 

considered significant food/feed commodities in the US, the results of the processing study are 

presented herein but are not discussed in detail. 

Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated 

plot received two foliar directed applications of a 4 lb ai/gal (500 g ai/L) SC formulation of 

metrafenone (BAS 560 02 F) at 0.279-0.321 lb ai/A/application (313-360 g ai/ha/application) for 

a total seasonal rate of 0.580-0.633 lb ai/A (650-710 g ai/ha). Applications were made at 6- to 8-

day RTIs using ground equipment in spray volumes of 335-388 GPA (3133-3625 L/ha) without 

an adjuvant. Samples of fresh (green) hops cones were harvested at PHIs of 0, 1, 2-4, and 7-8 

days. Additional samples of green hops cones designated for dried hops cones were collected 

from the 2- to 4-day PHIs at each site and were dried in hops kilns. 

Samples were analyzed for residues of metrafenone using LC/MS/MS via BASF methods #535/1 

(L0076/01) and #535/3 (L0076/03). The methods are essentially identical. The LOQ,

determined as the LLMV, was 0.01 ppm in all sample matrices. The analytical methods were

adequate for data collection, based on acceptable method validation and concurrent recovery

data. The fortification levels used in method validation and concurrent method recovery were 

adequate to bracket expected residue levels. Recoveries were corrected for apparent residues in 

controls; residues in treated samples were not corrected for residues in controls. 

Samples were stored frozen (≤-18°C at the field sites, preparation facility, and analytical 

laboratories) from harvest to analysis for 147-242 days (4.8-8.0 months) for green hops cones 

and 151-236 days (5.0-7.8 months) for dried hops cones. Samples were analyzed within 1-2 

days of extraction. Adequate storage stability data are available to support the sample storage 

durations and conditions for residues of metrafenone.

The results from these trials are summarized in Table 5.3.1.6, below. Following two foliar 

directed applications of the 4 lb ai/gal (500 g ai/L) SC formulation of metrafenone at 0.580-0.633 
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lb ai/A (650-710 g ai/ha), residues (and per trial averages) of metrafenone in green hops cones 

and dried hops cones, respectively, harvested at a 2- to 4-day PHI were 1.78-8.50 (1.78-8.50) and 

13.3-34.4 (13.3-34.4) ppm. At the residue decline trials, residues of metrafenone in green hops 

cones generally declined with increasing PHI in four of the six trials, but remained relatively 

stable in two trials from the 0-day PHI to 7-day PHI (results not shown here; see the DER for 

MRIDs #49145407 and -08 for further details). 

TABLE 5.3.1.6 Summary of Residue Data from Hops Field Trials with Metrafenone (MRIDs #49145407 & 

49145408).

Commodity Total Rate

lb ai/A

(g ai/ha)

PHI 

(days)

Metrafenone Residue Levels (ppm)

1

n Min. Max. LAFT2 HAFT2 Median Mean Std. 

Dev.

Hops cones, 

green

0.580-

0.633

(650-710)

2-4 6 1.78 8.50 1.78 8.50 3.57 4.16 2.31

Hops cones, 

dried

2-4 6 13.3 34.4 13.3 34.4 22.8 24.7 8.98

1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 

2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

Hops (MRID #49145407 & -08) Conclusions: Following two foliar directed applications of the 

4 lb ai/gal (500 g ai/L) SC formulation of metrafenone at 0.580-0.633 lb ai/A (650-710 g ai/ha), 

residues (and per trial averages) of metrafenone in green hops cones and dried hops cones, 

respectively, harvested at a 2- to 4-day PHI were 1.78-8.50 (1.78-8.50) and 13.3-34.4 (13.3-34.4) 

ppm. In the residue decline trials, residues of metrafenone in green hops cones generally

declined with increasing PHI in four of the six trials, but remained relatively stable in two trials 

from the 0-day PHI to 7-day PHI.

Acceptable methods were used for quantitation of residues, and the study is supported by

adequate storage stability data. 

Peach (MRID #49145401): IR-4 submitted field trial residue data for metrafenone on peach.

Fourteen peach field trials were conducted in the United States and Canada during the 2011

growing season in NAFTA Growing Zones 1 (NY; 1 trial), 2 (NJ and NC; 4 trials), 4 (AR; 1 

trial), 5A (MI; 1 trial), 5 (ON; 2 trials), 6 (TX; 1 trial), 10 (CA; 3 trials) and 11 (BC; 1 trial). 

HED has determined that two Zone 10 and two Zone 5 peach trials should be considered 

replicates for purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data 

requirements. The above field trial distribution incorporates this conclusion.

Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated 

plot received two foliar directed applications of a 2.5 lb ai/gal SC formulation of metrafenone 

(BAS560 03 F SC) at 0.291-0.307 lb ai/A/application (326.2-344.2 g ai/ha/application) for a total 

seasonal rate of 0.583-0.610 lb ai/A (653.6-683.9 g ai/ha). Applications were made at 6- to 8-

day RTIs using ground equipment in spray volumes of 104-182 GPA (973-1701 L/ha). An NIS, 
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COC or OSS was added to the spray mixtures for all applications. Samples of peaches were 

harvested at PHIs of 6-8 days and 13-15 days at all trial sites. Additional samples of peaches 

were collected from two trials at PHIs of 0, 3, 15/17 and 17/21 days to generate residue decline 

data.

Samples of peaches were analyzed for residues of metrafenone using an LC/MS/MS method

derived from a QuEChERS Method #R00033. The LOQ, determined as the LLMV, was 0.01 

ppm. The method was adequate for data collection, based on acceptable method validation and 

concurrent recovery data. The fortification levels used in method validation and concurrent 

method recovery were adequate to bracket expected residue levels. Concurrent recoveries and 

residues in the treated samples were not corrected for residues in controls. 

Samples were transferred to a sample preparation facility for homogenization prior to shipment 

to the analytical laboratory. Samples were stored frozen (frozen at the field sites, ≤-5°C at the 

sample preparation facility, and temperature unspecified at the analytical laboratory) from 

collection to analysis for 297-397 days (9.8-13.1 months). Samples were analyzed within 0-15 

days of extraction. Adequate storage stability data are available to support the sample storage 

conditions and durations.

The results from these trials are summarized in Table 5.3.1.7, below. Following two foliar 

directed applications of the 2.5 lb ai/gal SC formulation of metrafenone at 0.583-0.610 lb ai/A 

(653.6-683.9 g ai/ha), residues (and per trial averages) of metrafenone in peaches harvested at 

PHIs of 6-8 days and 13-15 days, respectively, were 0.041-0.520 (0.051-0.489) and 0.029-0.394

(0.035-0.355) ppm. At the residue decline trials, residues of metrafenone in peaches declined 

with increasing PHI in peaches (results not shown here; see the DER for MRID #49145401 for 

further details). 

TABLE 5.3.1.7 Summary of Residue Data from Peach Field Trials with Metrafenone.

Commodity Total Rate

lb ai/A (g ai/ha)

PHI 

(days)

Residue Levels (ppm)1

n Min. Max. LAFT2 HAFT2 Median Mean Std. Dev.

Peach 0.583-0.610

(653.6-683.9)

6-8 14 0.041 0.520 0.051 0.489 0.208 0.211 0.098

13-15 14 0.029 0.394 0.035 0.355 0.142 0.143 0.075

1. Except for sample min/max, values reflect per trial averages; n = number of distinct field trials. 

2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

Peach Conclusions: Following two foliar directed applications of the 2.5 lb ai/gal SC 

formulation of metrafenone at 0.583-0.610 lb ai/A (653.6-683.9 g ai/ha), residues (and per trial 

averages) of metrafenone in peaches harvested at PHIs of 6-8 days and 13-15 days, respectively, 

were 0.041-0.520 (0.051-0.489) and 0.029-0.394 (0.035-0.355) ppm. At the residue decline 

trials, residues of metrafenone in peaches declined with increasing PHI in peaches.

An acceptable method was used for residue quantitation, and adequate storage stability data are 

available to support the sample storage conditions and durations. 
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Cucurbits (MRIDs #49145404, -05 & -06): IR-4 has submitted field trial residue data for 

metrafenone on cantaloupe, cucumber and summer squash, the representative commodities of the 

cucurbit vegetable group 9, from 32 crop field trials conducted in the United States and Canada 

during the 2010 growing season. Twelve cantaloupe trials were conducted in NAFTA Growing 

Zones 2 (GA and MD; 2 trials), 5 (OH and ON; 2 trials); 5B (QC; 1 trial), 6 (TX; 2 trials) and 10 

(AZ, CA, and NM; 5 trials); six cucumber trials were conducted in Zones 2 (GA; 2 trials), 3 (FL, 

1 trial), 5 (IA and MN; 2 trials) and 6 (OK; 1 trial); and fourteen squash trials were conducted in 

Zones 1 (NY; 1 trial), 2 (MD, NC, and SC; 3 trials), 3 (FL; 1 trial), 5 (ON; 2 trials), 5B (QC; 1 

trial), 6 (TX; 2 trials), 10 (AZ and CA; 2 trials), 11 (WA; 1 trial) and 12 (BC; 1 trial). 

Examination of the field trial records indicates that there were sufficient differences between the 

trials that each trial constitutes a separate trial for purposes of OCSPP Residue Chemistry Test 

Guideline 860.1500 data requirements.

Each trial consisted of one untreated and one treated plot. At each trial location, the treated plot 

received three foliar broadcast or directed applications of a 2.5 lb ai/gal SC formulation of 

metrafenone (BAS560 03 F SC) at 0.286-0.316 lb ai/A/application (0.321-0.354 kg 

ai/ha/application) for a total seasonal rate of 0.884-0.936 lb ai/A (0.993-1.049 kg ai/ha). 

Applications were made at 6-to 9-day RTIs using ground equipment in spray volumes of 29.2-

74.2 GPA (273-693 L/ha). At one ON squash trial, the first application was made in error at half 

the target application rate (0.124 lb ai/A; 0.139 kg ai/ha); therefore, the test substance was reapplied 3 days later at 0.312 lb ai/A (0.350 kg ai/ha), and the remaining two applications were 

made according to the study protocol. This trial received a total of four applications for a total 

rate of 1.042 lb ai/A (1.168 kg ai/ha). An NIS, MSO, COC or OSS was added to the spray

mixtures for all applications. Samples of cantaloupe, cucumber and summer squash were 

harvested at a PHI of 0 days. Additional samples were collected from two trials for cantaloupe at 

PHIs of 1, 3, 7, 10/11 and 13/15 days, one trial for cucumber at PHIs of 1, 3, 7 and 10 days, and 

one trial for summer squash at PHIs of 1, 4, 6, 9 and 13 days to generate residue decline data.

Samples were analyzed for residues of metrafenone using an LC/MS/MS method derived from 

QuEChERS Method #R00033. The LOQ, determined as the LLMV, was 0.01 ppm for 

metrafenone in all crop matrices. The method was adequate for data collection, based on 

acceptable method validation and concurrent recovery data. The fortification levels used in 

method validation and concurrent method recovery were adequate to bracket expected residue 

levels. Concurrent recoveries were corrected for apparent residues in controls for cantaloupe and 

summer squash, but recoveries were not corrected for apparent residues in controls for 

cucumber. Residues in treated samples were not corrected for residues in controls.

Samples of cucurbit vegetables were transferred to a sample preparation facility for 

homogenization prior to shipment to the analytical laboratory. Samples of cucurbit vegetables 

were stored frozen (frozen at the field sites, <-10 or -5°C at the sample preparation facility, and -

29 to -10°C at the analytical laboratories) from collection to analysis for 450-842 days (14.8-27.7 
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months). Samples were analyzed within 0-2 days of extraction. Adequate storage stability data 

are available to support the sample storage conditions and durations.

The results from these trials are summarized in Table 5.3.1.8, below. Following three (or four) 

foliar broadcast or directed applications of a 2.5 lb ai/gal SC formulation of metrafenone 

(BAS560 03 F SC) at a total seasonal rate of 0.884-1.042 lb ai/A (0.993-1.168 kg ai/ha), residues 

(and per trial averages) of metrafenone in cantaloupe, cucumber and summer squash harvested at 

a 0-day PHI, were 0.038-0.332 (0.038-0.282), 0.046-0.168 (0.053-0.157), and 0.067-0.357 

(0.072-0.305) ppm, respectively. It was noted that at the one summer squash trial in which four 

applications were made for a total seasonal rate of 1.042 lb ai/A, residues were consistent with 

those observed at other trials, and are included in the values reported above. At the residue 

decline studies, residues of metrafenone generally declined with increasing PHI in cantaloupe, 

cucumbers and summer squash (results not shown here; see the DER for MRIDs #4914540, -05 

and -06 for further details). 

TABLE 5.3.1.8 Summary of Residue Data from Cuburbit Field Trials with Metrafenone.

Commodity Total Rate,

lb ai/A

(kg ai/ha)

PHI 

(days)

Residues (ppm)

1

n Min. Max. LAFT2 HAFT2 Median Mean Std. 

Dev.

Cantaloupe 0.886-0.936

(0.993-1.049)

0 12 0.038 0.332 0.038 0.282 0.143 0.152 0.068

Cucumber 0.894-0.920

(1.002-1.035)

6 0.046 0.168 0.053 0.157 0.099 0.105 0.038

Summer 

squash

0.884-1.042

(0.993-1.168)

14 0.067 0.357 0.072 0.305 0.127 0.162 0.079

1. Except for sample min/max, values reflect per trial averages; n = number of field trials. 

2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

Cucurbits Conclusions: The submitted cucurbit vegetable field trial data are scientifically 

acceptable. Following three (or four) foliar broadcast or directed applications of a 2.5 lb ai/gal 

SC formulation of metrafenone (BAS560 03 F SC) at a total seasonal rate of 0.884-1.042 lb ai/A 

(0.993-1.168 kg ai/ha), residues (and per trial averages) of metrafenone in cantaloupe, cucumber 

and summer squash harvested at a 0-day PHI, were 0.038-0.332 (0.038-0.282), 0.046-0.168 

(0.053-0.157), and 0.067-0.357 (0.072-0.305) ppm, respectively. It was noted that residues at the 

one summer squash trial in which four applications were made for a total seasonal rate of 1.042 

lb ai/A, residues were consistent with those observed at other trials, and are included in the 

values reported above. In the residue decline studies, residues of metrafenone generally declined 

with increasing PHI in cantaloupe, cucumbers and summer squash.

An acceptable method was used for residue quantitation, and the study is supported by adequate 

storage stability data.
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5.3.2 Field Rotational Crops (860.1900)

A study investigating field accumulation in rotational crops has not been conducted with 

metrafenone, and is not required. 

5.3.3 Processed Food and Feed (860.1520)

Apple (MRID #49055902): An apple processing study was conducted to determine the potential 

for concentration of residues of metrafenone in apple processed fractions. Two trials were 

conducted to generate samples for processing in NAFTA Growing Zones 1 (NY, one trial) and 

11 (ID, one trial) during the 2010 growing season.

At each test location, one untreated control and one treated plot were established. The treated 

plots received three foliar airblast applications of metrafenone (2.5 lb ai/gal SC) applying at 

roughly 1.68 kg ai/ha/application (1.5 lb ai/A/application), with a nominal 7-day RTI, resulting 

in a total exaggerated rate of roughly 5.0 kg ai/ha (4.5 lb ai/A/season). The actual application 

rates were 1.67-1.71 kg ai/ha/application (1.49-1.53 lb ai/A/application), with 6- or 7-day RTIs, 

for a total rate of 5.1 kg ai/ha/season (4.52-4.53 lb ai/A/season). The applications were made in 

80-102 GPA of water (748-954 L/ha) using ground equipment (airblast sprayers). An NIS 

adjuvant was added to the spray mixture for all applications. 

At each site, one untreated control and one treated bulk apple RAC sample were harvested at 

normal crop maturity, at a 6- or 7-day PHI. The samples were shipped to the processing facility,

ACDS Research (North Rose, NY), where they were processed, according to simulated 

commercial procedures, into processed apple commodities (juice, wet pomace, apple sauce, 

canned apples, and dried apples). Adequate descriptions of the processing procedures were 

provided, including material balance summaries.

The residues of parent metrafenone in apple RAC and processed commodity samples were 

quantitated using an LC/MS/MS multi-residue QuEChERS method (BASF Study #398340). The 

method was successfully validated on dried apples in conjunction with this study prior to 

analysis of the field samples. Acceptable concurrent method recovery data for each apple matrix 

were also obtained for metrafenone. The validated LOQ for metrafenone residues in apple RAC 

and processed commodity samples was 0.01 ppm. The method LOD was 0.003 ppm.

The processing residue results are summarized in Table 5.3.3.1, below. After three exaggerated 

rate applications of metrafenone (2.5 lb ai/gal SC) to apples at a rate of 1.68 kg ai/ha/application 

(roughly 5.0 kg ai/ha/season), metrafenone residues were 1.46 ppm (New York) and 2.17 ppm 

(Idaho) in two treated apple RAC samples (whole fruit) harvested at a 6- or 7-day PHI. The 

apple RAC samples were separately processed, using simulated commercial processing 

procedures, into the currently EPA-regulated commodities of apple, wet pomace and juice. 

Apple sauce, canned apples, and dried apples were also generated and collected for analysis.
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Metrafenone residues were 0.28 ppm in juice, 1.88 ppm in wet pomace, 7.01 ppm in apple sauce, 

0.20 ppm in canned apples, and 1.05 ppm in dried apples collected from New York. 

Metrafenone residues were 0.49 ppm in juice, 2.37 ppm in wet pomace, 8.94 ppm in apple sauce, 

0.23 ppm in canned apples, and 0.85 ppm in dried apples collected from Idaho.

A comparison of the residues in the RAC samples with those in each processed fraction indicated 

that metrafenone residues do not concentrate (processing factors <1X to 1.2X, average of two 

trials) in any apple processed commodities, with the exception of apple sauce, in which the 

processing factor was 4.5X on average, with individual results of 4.8X and 4.1X calculated from 

the samples collected at the sites in New York and Idaho, respectively. 

The processing factors calculated in this study were less than the maximum theoretical 

concentration factor of >14X for apples (based on the maximum theoretical/experimental 

concentration factor; OCSPP 860.1520, Table 1), and 14X for apple pomace (based on the 

maximum observed experimental concentration factor; OCSPP 860.1520, Table 4).

The apple RAC and processed commodity samples were stored frozen for a maximum of 

683 days (roughly 22 months) from collection to extraction for analysis. Samples were analyzed 

on the day of extraction. Processing was completed within 4 days of harvest.

Table 5.3.3.1 Metrafenone Residues in Apple Processed Fractions.

Trial ID

(City, 

State/Year)

Total Use

Rate

lb ai/A

(kg ai/ha)

PHI

(days)

Processed

Commodity

Metrafenone

Residues (ppm)

Processing

Factor1

Average

Processing 

Factor

R080753

(Alton, 

NY/2010)

4.52

(5.06)

7 Whole Fresh Fruit 1.46 NA2

Juice (raw) 0.276 0.189 <1 (0.2)

Wet Pomace 1.88 1.29 1.2

Apple Sauce 7.01 4.80 4.5

Canned Apples 0.204 0.140 <1 (0.1)

Dried Apples 1.05 0.719 <1 (0.6)

R080754

(Weiser, 

ID/2010)

4.53

(5.07)

6 Whole Fresh Fruit 2.17 NA

Juice (raw) 0.489 0.225

Wet Pomace 2.37 1.09

Apple Sauce 8.94 4.12

Canned Apples 0.226 0.104

Dried Apples 0.851 0.392

1. The processing factor was calculated by dividing the residue in the apple processed commodity by the residue in 

the apple RAC sample (LOQ = 0.01 ppm). 

2. NA = Not Applicable (whole fresh fruit, the representative apple RAC sample). 

Apple Conclusions: A comparison of the residues in the RAC with those in each processed 

fraction indicated that metrafenone residues do not concentrate appreciably (<1X to 1.2X on 
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average) in any apple processed commodities, with the exception of apple sauce, in which the 

processing factor was 4.5X on average. The observed concentration factors were less than the 

theoretical concentration factors.

An acceptable method was used for residue quantitation, and the study is supported by adequate 

storage stability data. 

Tomato (MRID #49119109): Tomato processing studies were conducted to determine the 

potential for concentration of residues of metrafenone (BAS 560 F) in the processed fractions of 

tomato.

During the 2010 growing season, four tomato field trials were conducted in Germany at 04668 

Motterwitz, Saxony; 04827 Gerichshain, Saxony; 19348 Düpow, Brandenburg; and 16248 

Oderberg, Brandenburg. At each location a treated plot was established; two of the trials also 

included an untreated control plot. 

The treated plots received two foliar applications of metrafenone (4.2 lb ai/gal SC, formulation 

code BAS 560 02 F) targeting 0.60 lb ai/A/application (0.675 kg ai/ha/application) with a 

nominal 7-day RTI, resulting in a total rate of 1.2 lb ai/A (1.35 kg ai/ha/season). The actual 

application rates were 0.54-0.65 lb ai/A/application (0.61-0.73 kg ai/ha/application), with 6-8 

day RTIs, resulting in a total rate of 1.18-1.28 lb ai/A/season (1.32-1.44 kg ai/ha/season). The 

applications were made in 48-58 GPA of water (450-544 L/ha) using ground equipment, and no

adjuvant was added to the spray mixtures.

At each location, tomato RAC samples (fruit) were harvested at PHIs of 0 and 3 or 4 days. The 

bulk tomato samples collected at 3- or 4-day PHIs at each site were promptly processed, 

according to simulated commercial procedures, into tomato processed fractions. 

The tomato RAC and processed commodity samples were analyzed for residues of metrafenone 

by SGS Institut Fresenius GmbH, Taunusstein, Germany, using BASF Method Number 535/1 

(L0076/01). Acceptable concurrent method recovery data for tomato RAC and processed 

commodity samples were obtained for metrafenone. The validated LOQ for residues of 

metrafenone in tomato RAC and processed commodity samples was 0.01 ppm. 

As summarized below in Table 5.3.3.2, the results from the processing study show that after two 

applications of metrafenone targeting 0.60 lb ai/A/application (0.675 kg ai/ha/application), 

metrafenone in treated tomato RAC samples (unwashed whole fruit) collected at 0- and 3- to 4-

day PHIs were 0.675-1.189 ppm and 0.40-0.78 ppm, respectively (n=4 for each sampling 

interval). 

A total of four separate treated bulk samples were processed for a total of four processing tests. 

The treated bulk tomato RAC samples harvested at 3- or 4-day PHIs and bearing quantifiable 
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metrafenone residues (levels discussed above) were separately processed using simulated 

commercial processing procedures into paste and puree, the currently EPA-regulated 

commodities of tomato. In addition, blanched tomatoes, blanching water, canned tomatoes, 

peeled tomatoes, wash water, tomato peel, wet pomace, washed tomatoes, raw juice, ketchup 

after pasteurization, and vegetable stock were collected for analysis. A comparison of the 

residues in the RAC with those in each processed fraction indicates that residues of metrafenone

do not concentrate in tomato processed commodities with the exception of peel and wet pomace, 

in which residues concentrate, on average, by factors of 6.3X (range, 3.51-7.86X, n=4) and 5.1X

(range, 3.31-6.16X, n=4), respectively.

The processing factors calculated in this study were greater than the maximum theoretical 

concentration factors of 1.4X for tomato puree and 5.5X for tomato paste (based on loss of

water; OCSPP 860.1520, Table 2) and 1.4X for tomato juice (based on separation into 

components; OCSPP 860.1520, Table 3).

The tomato RAC and processed commodity samples were stored frozen for a maximum of 

165 days (5.4 months) from collection to analysis for residues of metrafenone. 

TABLE 5.3.3.2 Metrafenone Residues in Tomato Processed Fractions

Trial Location

(City, Country/ 

Year)

Total Rate

lbs ai/A

(kg ai/ha)

Processed

Commodity

PHI

(Days)1

Metrafenone Processing 

Factor2

04668 Motterwitz, 

Saxony,

Germany/2010 

(L100261)

1.26 (1.41) Fruit, 0 PHI30 0.675 ---

Fruit, 3 PHI33 0.401 ---

Fruit, RAC40.423 1.0

Blanched tomatoes 0.353 0.83

Blanching water < 0.01 0.02

Canned tomatoes < 0.01 0.02

Peeled tomatoes < 0.01 0.02

Wash water 0.066 0.16

Tomato peel 3.184 7.53

Wet pomace 2.034 4.81

Washed tomatoes 0.382 0.90

Raw juice 0.168 0.40

Ketchup after pasteurization 0.177 0.42

Paste 0.225 0.53

Puree 0.335 0.79

Vegetable stock < 0.01 0.02
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TABLE 5.3.3.2 Metrafenone Residues in Tomato Processed Fractions

Trial Location

(City, Country/ 

Year)

Total Rate

lbs ai/A

(kg ai/ha)

Processed

Commodity

PHI

(Days)1

Metrafenone Processing 

Factor2

04827 Gerichshain, 

Saxony, 

Germany/2010 

(L100262)

1.28 (1.44) Fruit, 0 PHI30 0.962 ---

Fruit, 3 PHI33 0.778 ---

Fruit, RAC40.775 1.0

Blanched tomatoes 0.352 0.45

Blanching water 0.013 0.02

Canned tomatoes 0.015 0.02

Peeled tomatoes < 0.01 0.01

Wash water 0.507 0.65

Tomato peel 4.807 6.20

Wet pomace 2.567 3.31

Washed tomatoes 0.477 0.62

Raw juice 0.198 0.26

Ketchup after pasteurization 0.327 0.42

Paste 0.207 0.27

Puree 0.501 0.65

Vegetable stock < 0.01 0.01

19348 Düpow, 

Brandenburg, 

Germany/2010 

(L100263)

1.18 (1.32) Fruit, 0 PHI30 1.189 ---

Fruit, 4 PHI34 0.782 ---

Fruit, RAC40.583 1.0

Blanched tomatoes 0.528 0.91

Blanching water 0.017 0.03

Canned tomatoes < 0.01 0.02

Peeled tomatoes 0.013 0.02

Wash water 0.218 0.37

Tomato peel 4.585 7.86

Wet pomace 3.592 6.16

Washed tomatoes 0.488 0.84

Raw juice 0.194 0.33

Ketchup after pasteurization 0.219 0.38

Paste 0.174 0.30

Puree 0.487 0.84

Vegetable stock < 0.01 0.02
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TABLE 5.3.3.2 Metrafenone Residues in Tomato Processed Fractions

Trial Location

(City, Country/ 

Year)

Total Rate

lbs ai/A

(kg ai/ha)

Processed

Commodity

PHI

(Days)1

Metrafenone Processing 

Factor2

16248 Oderberg, 

Brandenburg, 

Germany/2010 

(L100264)

1.18 (1.32) Fruit, 0 PHI30 0.925 ---

Fruit, 3 PHI33 0.435 ---

Fruit, RAC40.452 1.0

Blanched tomatoes 0.398 0.88

Blanching water 0.012 0.03

Canned tomatoes < 0.01 0.02

Peeled tomatoes 0.01 0.02

Wash water 0.152 0.34

Tomato peel 1.588 3.51

Wet pomace 2.679 5.93

Washed tomatoes 0.242 0.54

Raw juice 0.149 0.33

Ketchup after pasteurization 0.211 0.47

Paste 0.201 0.44

Puree 0.478 1.06

Vegetable stock < 0.01 0.02

1. The pre-harvest interval (PHI) for the bulk tomato RAC sample. 

2. The processing factor is calculated by dividing the residue in the processed fraction by the mean residue in the 

tomato RAC sample. Processing factor is equivalent to “transfer factor”. 

3. Result from the analysis of the smaller tomato fruit RAC sample. 

4. Result from the representative “fresh fruit” sample collected at the processing facility. 

Tomato Conclusions: A comparison of the residues in the RAC with those in each processed 

fraction indicated that residues of metrafenone do not concentrate in tomato processed 

commodities with the exception of peel and wet pomace, in which residues concentrate, on 

average, by factors of 6.3X and 5.1X, respectively. The mean transfer factor of tomato peel and 

wet pomace (>1) indicates that the metrafenone residues are mainly located in the peel of the 

tomatoes. 

An acceptable method was used for residue quantitation, and the study is supported by adequate 

storage stability data. 

5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

Metabolism DER for MRID #49267201 (Goat)

The only livestock feed item associated with the proposed metrafenone new uses is apple wet 

pomace, and it is fed only to dairy cattle, at a mazimum of 10% of the diet. Twelve apple field 

trials were conducted, with a HAFT value of 0.760 ppm. An average processing factor of 1.2 

was determined for apple wet pomace in the apple processing study (MRID #49055902). 

Therefore, the adjusted metrafenone residues in apple pomace are 0.760 ppm x 1.2 PF = 0.912 

ppm. 
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When goats in the metabolism study were dosed at 87 ppm in the feed, the highest metrafenone 

residue in tissues was in liver at 0.269 ppm. Scaling down to the anticipated dietary burden to 

dairy cattle of 0.228 mg/kg in feed, anticipated metrafenone residues are not expected to exceed 

0.000705 ppm in liver, well below the LOD. Residues would occur at lower levels in muscle, fat 

and milk. Ergo, there is no reasonable expectation of residues above the LOQ of 0.01 ppm in the 

milk or tissues of ruminant animals. 

TABLE 5.3.4 Dietary Burden to Dairy Cattle from Metrafenone.

Feedstuff Feedstuff 

Type1

% Dry 

Matter 2

% Diet2 Feeding Level

(ppm)

Dietary Contribution 

(ppm)3

Dairy Cattle

Apple wet pomace CC 40 10 0.912 0.228

TOTAL BURDEN -- -- 1040.912 0.228

1. CC = Carbohydrate Concentrate. 

2. OCSPP Residue Chemistry Test Guideline 860.1000, Table 1 Feedstuffs (30 June 2008). 

3. Contribution = (tolerance ÷ % DM x % diet) for beef and dairy cattle. 

4. The remainder of the diet will be composed of feedstuffs (roughage and protein concentrate sources) derived from 

crops that do not have registered metrafenone uses or tolerances.

Conclusions: Based on the dietary burden to dairy cattle of metrafenone residues in apple wet 

pomace, and the results of the goat metabolism study, it is not expected that detectable residues 

would be found in cattle commodities. Therefore, tolerances in livestock commodities are not 

required, nor is a livestock feeding study required. 

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

Residues of metrafenone from the new uses proposed in the current action are expected to vary

from low (up to 0.70 ppm in apricot and peaches) to high levels (up to 70 ppm in dried hops 

cones). 
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6.0 Tolerance Derivation

Adequate pome fruit field trial data were submitted in support of the proposed use. The 

submitted data support the proposed tolerance of 1.5 ppm in pome fruits (group 11-10). 

Adequate fruiting vegetable field trial data were submitted in support of the proposed use. The 

submitted data support a recommended tolerance of 0.90 ppm, rather than the proposed tolerance 

of 1.0 ppm, in fruiting vegetables (group 8-10). 

Adequate cucurbit vegetable field trial data were submitted in support of the proposed use. The 

submitted data support the proposed tolerance of 0.5 ppm in cucurbit vegetables (group 9); HED 

recommends that the tolerance be established at 0.50 ppm. 

Adequate cherry field trial data were submitted in support of the proposed use. The submitted 

data support the proposed tolerance of 2 ppm in the cherry subgroup (12-12A); HED 

recommends that the tolerance be established at 2.0 ppm. 

Adequate peach field trial data were submitted in support of the proposed use. The submitted 

data support the proposed tolerance of 0.7 ppm in the peach subgroup (12-12B); HED 

recommends that the tolerance be established at 0.70 ppm. 

Adequate hops field trial data were submitted in support of the proposed use. The submitted data 

support the proposed tolerance of 70 ppm in hops. 

The proposed tolerance of 4.5 ppm in small vine climbing fruits except fuzzy kiwifruit (subgroup 

13-07F) is based upon existing data for grapes (the representative commodity for the subgroup). 

Upon establishment of the tolerance in subgroup 13-07F, the existing tolerance in grapes should 

be removed. 

The proposed tolerance of 0.7 ppm in apricots is based upon the submitted data for peaches. 

HED recommends that the tolerance be established at 0.70 ppm. 

The rationales for the establishment and concurrent removal of tolerances associated with the 

current action are listed in Table 6, below. 

An International Residue Limit Status sheet is appended as Attachment 1. Data sets and results 

from the OECD tolerance calculation procedure for the various commodities are appended as 

Attachment 2. 
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TABLE 6 Tolerance Summary for Metrafenone (40CFR §624[a]). 

Commodity Existing 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Rationale

Apricot None 0.70 Based on submitted peach data. 

Cherry subgroup 12-12A None 2.0 Based on submitted cherry data. 

Fruit, pome, group 11-10 None 1.5 Based on submitted pome fruits 

data. 

Fruit, small, vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F

None 4.5 Based on data supporting the 

existing tolerance in grape. 

Grape 4.5 Remove Covered by the subgroup 13-07F 

tolerance to be established. 

Hop, dried cones None 70 Based on submitted hops data. 

Peach subgroup 12-12B None 0.70 Based on submitted peach data. 

Vegetable, cucurbit, group 9 None 0.50 Based on submitted cucurbit data. 

Vegetable, fruiting, group 8-10 None 0.90 Based on submitted fruiting 

vegetable data. 

References

Metrafenone. Petition for the Establishment of Tolerances on Imported Grapes. Summary of 

Analytical Chemistry and Residue Data. PP#4E6884.; D312307; D. McNeilly. 24 August 2006. 

Metrafenone: Human Health Risk Assessment for Foliar Use on Grapes.; D354166; D. 

McNeilly; 1 March 2010. 

Metrafenone. Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS).; 

D370903; G.F. Kramer; 18 Nov 2009. 

Metrafenone: Chronic Aggregate Dietary Exposure (Food and Drinking Water) and Risk 

Assessment for the Section 3 Registration on Grapes.; D371367; D. McNeilly; 18 February 2010. 

Metrafenone. Application for Section 3 Registration for Use on Grape. Summary of Analytical 

Chemistry and Residue Data.; D331685; D. McNeilly; 18 February 2010. 

PP#4E6884. New Chemical, Food Use of Metrafenone on Table and Wine Grapes. Request for 

Petition Method Validation (PMV) of the Proposed Tolerance Enforcement Methods.; D331185; 

D. McNeilly; 3 August 2006. 

Review of Proposed Tolerance Enforcement Method for Metrafenone.; ACB Project #B06-38. D. 

Wright, D. McNeilly; 29 September 2008. 

Drinking Water Assessment for the Proposed Uses of Metrafenone [(3-bromo-6-methyoxy-2-

methylphenyl) (2,3,4-trimethoxy-6-methylphenyl) methanone] on Pome Fruits, Fruiting 
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Vegetables, Peach Subgroup 12-12B, Apricot, Cherry Subgroup 12-12A, Cucurbit Vegetables 

(Group 9), and Fruit, Small, Vine Climbing (except Fuzzy Kiwifruit) Subgroup 13-07F; 

D411540, D414403, D416312; J.A. Hetrick; 25 November 2013. 

Metrafenone. Review of Residue Data from Hops Field Trials – Statistical Test for Outlier.; 

D421923; Bayazid Sarkar; 21 August 2014. 

Attachments

Attachment 1: International Residue Limit Status sheet. 

Attachment 2: OECD MRL (Tolerance) Assessment Calculations.
Metrafenone Summary of Analytical Chemistry and Residue Data DP Barcode D411389

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Attachment 1: International Residue Limit Status

Metrafenone (PC Code 000325)

Summary of US Tolerances and International Maximum Residue Limits.

Residue Definitions

US (40CFR §180.624) Canada Codex

Plants: Metrafenone (3-bromo-6-

methoxy-2-methylphenyl)(2,3,4-

trimethoxy-6-methylphenyl)methanone. 

Metrafenone (3-bromo-6-

methoxy-2-methylphenyl)(2,3,4-

trimethoxy-6-

methylphenyl)methanone. 

Commodity2 Tolerance 

(ppm)3

Commodity MRL 

(mg/kg)

Commodity MRL 

(mg/kg)

Apricot 0.70

Cherry subgroup 12-12A 2.0

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

4.5 Grapes

Raisins

4.5

17

Fruits, pome, group 11-10 1.5

Hop, cones, dried 70

Peach subgroup 12-12B 0.70

Vegetable, cucurbit, group 9 0.50

Vegetables, fruiting, group 8-

10

0.90

Completed: M. Negussie, 12 November 2013. 

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

2. Includes only commodities of interest for this action. 

3. Tolerance values are those recommended by HED, not those proposed by the petitioner. 
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Attachment 2: OECD MRL (Tolerance) Assessment Calculations. 

Apple

Residues (mg/kg)

0.218

0.158

0.492

0.446

0.360

0.230

0.214

0.314

0.141

0.155

0.165

0.078

0.536

0.760

0.392
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Metrafenone

Apple

USA

0.90 lb ai/A, 7-day PHI

Total number of data (n) 15

Percentage of censored data 0%

Number of non-censored data 15

Lowest residue 0.078

Highest residue 0.760

Median residue 0.230

Mean 0.311

Standard deviation (SD) 0.187

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.760

- Mean + 4 SD 1.058

- CF x 3 Mean 0.932

Unrounded MRL 1.058

Rounded MRL 1.5
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Pear

Residues (mg/kg)

0.405

0.409

0.189

0.141

0.160

0.477

0.392

Metrafenone

Pear

USA

0.90 lb ai/A, 7-day PHI

Total number of data (n) 7

Percentage of censored data 0%

Number of non-censored data 7

Lowest residue 0.141

Highest residue 0.477

Median residue 0.392

Mean 0.310

Standard deviation (SD) 0.141

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.477

- Mean + 4 SD 0.874

- CF x 3 Mean 0.931

Unrounded MRL 0.931

Rounded MRL 1

High uncertainty of MRL estimate.

[Small dataset]
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Tomato

Residues (mg/kg)

0.101

0.228

0.079

0.110

0.170

0.105

0.176

0.246

0.088

0.285

0.109

0.095

0.103

0.234

0.427

0.099

0.041

0.222
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Metrafenone

Tomatoes

USA

0.90 lb ai/A, 0-day PHI

Total number of data (n) 18

Percentage of censored data 0%

Number of non-censored data 18

Lowest residue 0.041

Highest residue 0.427

Median residue 0.110

Mean 0.162

Standard deviation (SD) 0.096

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.427

- Mean + 4 SD 0.547

- CF x 3 Mean 0.486

Unrounded MRL 0.547

Rounded MRL 0.6
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Pepper

Residues (mg/kg)

0.417

0.402

0.148

0.248

0.270

0.353

0.081

0.498

Metrafenone

Bell/non-bell peppers

USA

0.90 lb ai/A, 0-day PHI

Total number of data (n) 8

Percentage of censored data 0%

Number of non-censored data 8

Lowest residue 0.081

Highest residue 0.498

Median residue 0.312

Mean 0.302

Standard deviation (SD) 0.142

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.498

- Mean + 4 SD 0.869

- CF x 3 Mean 0.906

Unrounded MRL 0.906

Rounded MRL 0.9
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Cherry

Residues (mg/kg)

0.699

0.393

0.429

0.494

0.317

0.738

0.368

0.438

1.160

0.492

0.334

0.596

0.647

0.547

Metrafenone

Cherry

USA

0.60 lb ai/A, 7-day PHI

Total number of data (n) 14

Percentage of censored data 0%

Number of non-censored data 14

Lowest residue 0.317

Highest residue 1.160

Median residue 0.493

Mean 0.547

Standard deviation (SD) 0.221

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 1.160

- Mean + 4 SD 1.430

- CF x 3 Mean 1.640

Unrounded MRL 1.640

Rounded MRL 2
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Hops

Residues (mg/kg)

16.870

21.890

21.120

23.520

21.300

22.800

13.300

19.700

34.400

33.100

Metrafenone

Hops

USA

0.60 lb ai/A, 3-day PHI

Total number of data (n) 10

Percentage of censored data 0%

Number of non-censored data 10

Lowest residue 13.300

Highest residue 34.400

Median residue 21.595

Mean 22.800

Standard deviation (SD) 6.516

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 34.400

- Mean + 4 SD 48.863

- CF x 3 Mean 68.400

Unrounded MRL 68.400

Rounded MRL 70
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Peach

Residues (mg/kg)

0.211

0.247

0.227

0.185

0.166

0.489

0.208

0.139

0.208

0.136

0.051

0.289

0.222

0.186
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Metrafenone

Peach

USA

0.60 lb ai/A, 7-day PHI

Total number of data (n) 14

Percentage of censored data 0%

Number of non-censored data 14

Lowest residue 0.051

Highest residue 0.489

Median residue 0.208

Mean 0.212

Standard deviation (SD) 0.098

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.489

- Mean + 4 SD 0.604

- CF x 3 Mean 0.635

Unrounded MRL 0.635

Rounded MRL 0.7
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Cantaloupe

Residues (mg/kg)

0.154

0.226

0.133

0.088

0.282

0.177

0.132

0.038

0.132

0.209

0.178

0.080

Metrafenone

Cantaloupe

USA

0.90 lb ai/A, 0-day PHI

Total number of data (n) 12

Percentage of censored data 0%

Number of non-censored data 12

Lowest residue 0.038

Highest residue 0.282

Median residue 0.144

Mean 0.152

Standard deviation (SD) 0.068

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.282

- Mean + 4 SD 0.423

- CF x 3 Mean 0.457

Unrounded MRL 0.457

Rounded MRL 0.5
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Cucumber

Residues (mg/kg)

0.100

0.142

0.084

0.157

0.053

0.097

Metrafenone

Cucumber

USA

0.90 lb ai/A, 0-day PHI

Total number of data (n) 6

Percentage of censored data 0%

Number of non-censored data 6

Lowest residue 0.053

Highest residue 0.157

Median residue 0.099

Mean 0.106

Standard deviation (SD) 0.038

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.157

- Mean + 4 SD 0.258

- CF x 3 Mean 0.317

Unrounded MRL 0.317

Rounded MRL 0.4

High uncertainty of MRL estimate.

[Small dataset]
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Summer Squash

Residues (mg/kg)

0.305

0.294

0.125

0.129

0.101

0.174

0.072

0.137

0.216

0.105

0.100

0.113

0.277

0.124

Metrafenone

Summer squash

USA

0.90 lb ai/A, 0-day PHI

Total number of data (n) 14

Percentage of censored data 0%

Number of non-censored data 14

Lowest residue 0.072

Highest residue 0.305

Median residue 0.127

Mean 0.162

Standard deviation (SD) 0.079

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.305

- Mean + 4 SD 0.476

- CF x 3 Mean 0.487

Unrounded MRL 0.487

Rounded MRL 0.5