UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                             WASHINGTON, DC  20460

                         OFFICE OF CHEMICAL SAFETY AND
                             POLLUTION PREVENTION

MEMORANDUM

DATE:  	16 June 2013

SUBJECT:	Methoxyfenozide.  Petition to Establish Permanent Tolerances (Associated with Section 3 Registration) for Residues Resulting from Food/Feed Uses of the Insecticide on Herbs (Subgroup 19A) Except Chives, Caneberries (Subgroup 13-07A), Dates and Sorghum; to Update the Pome Fruits and Fruiting Vegetables Crop Groups; to Extend the Tolerances in Grapes and Strawberries to Their Respective Subgroups, and in Avocadoes to Various Tropical Tree Fruits; to Remove the Tolerances in Dried Shelled Peas and Beans, and Add a Tolerance in Subgroup 6C; and to Establish Rotational Crop Tolerances in Chives, Spices (Subgroup 19B), and the Rapeseed (20A) and Sunflower (20B) Oilseed Subgroups.  Summary of Analytical Chemistry and Residue Data.

PC Code:  121027
DP Barcode:  D407758
Decision Number:  472142
Registration Number:  62719-442
Petition:  2E8118
Regulatory Action:  Section 3
Risk Assessment Type:  NA
Case Number:  7431
TXR Number:  NA
CAS Number:  161050-58-4
MRID Numbers:  48994101-04
40 CFR:  §180.544

FROM:  	 William T. Drew, Chemist
		 Risk Assessment Branch II (RAB2)
		 Health Effects Division (HED), 7509P

THROUGH:	Elizabeth Holman, Physical Scientist
		RAB2/HED, 7509P

TO:		Barbara Madden and Laura Nollen, RM Team 5
		Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)
		Registration Division (RD), 7505P

Table of Contents

1.0     Executive Summary	4
2.0     Regulatory Recommendations	7
2.1     Data Deficiencies/Data Needs	8
2.2     Tolerance Considerations	8
2.2.1      Enforcement Analytical Method/Multiresidue Methods	8
2.2.2      Recommended Tolerances	8
2.2.3      Revisions to Petitioned-For Tolerances	9
2.2.4      International Harmonization	10
2.3      Label Recommendations	11
2.4      Submittal of Analytical Reference Standards (860.1650)	11
3.0      Chemical Identity	12
3.1      Nomenclature	12
3.2      Physicochemical Characteristics	13
3.3      Pesticide Use Pattern/Directions for Use (860.1200)	13
4.0      Metabolite/Degradate Residue Profile	14
4.1      Nature of the Residue	14
4.1.1 	Summary of Plant and/or Livestock Metabolism (860.1300)	15
4.1.2	Summary of Confined Rotational Crops (860.l850)	16
4.1.3	Summary of Rat Metabolism	16
4.1.4	Summary of Environmental Degradation	17
5.0	Residue Profile	17
5.1       Residue Analytical Methods (860.1340)	17
5.1.1	Data Collection Methods	17
5.1.2	Multi-Residue Methods (860.1360)	22
5.1.3	Tolerance Enforcement Methods	22
5.2      Storage Stability (860.1380)	23
5.3      Residue Data	26
5.3.1	Crop Field Trials (860.1500)	26
5.3.2	Field Rotational Crops (860.1900)	30
5.3.3	Processed Food and Feed (860.1520)	30
5.3.4	Meat, Milk, Poultry and Eggs (860.1480)	32
5.3.5.	Food Handling (860.1460)	33
5.3.6	Water, Fish and Irrigated Crops (860.1400)	33
5.4      Food Residue Profile	33
6.0	Tolerance Derivation	33

Attachment 1:  International Residue Limit Status sheet................................................37

Attachment 2:  OECD MRL (Tolerance) Assessment Calculations...................................39

1.0	Executive Summary

Methoxyfenozide (with CAS name 3-methoxy-2-methylbenzoic acid 2-(3,5-dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide, and CAS number 161050-58-4) is a diacylhydrazine insecticide used on a wide variety of food and feed crops for the control of lepidopterous pest species.  Permanent tolerances are established for residues of methoxyfenozide in or on a wide variety of plant commodities, at levels ranging from 0.02 ppm in peanuts and tuberous/corm vegetables (subgroup 1D), to 160 ppm in soybean aspirated grain fractions (40CFR §180.544[a][1]).  Permanent tolerances are also established for residues of methoxyfenozide in the milk, meat and fat of livestock (40CFR §180.544[a][1]), and for the combined residues of the parent and its glucuronide conjugate (RH-141,518) in eggs and meat byproducts at 0.02-0.40 ppm (40CFR §180.544[a][2]).  Additionally, permanent tolerances for methoxyfenozide are established in high-moisture rotational crops (40CFR §180.544[d][1]), and for the combined residues of the parent and its metabolites RH-151,055, RH-152,072 and RH-117,236 in low-moisture rotational crops (40CFR §180.544[d][2]).  Time-limited tolerances (associated with Section 18 emergency exemptions) were established for residues of methoxyfenozide in sorghum forage, grain and stover (40CFR §180.544[b]); these tolerances expired on 31 December 2012.

The Interregional Research Project Number 4 (IR-4) has submitted a petition requesting the establishment of permanent tolerances for residues of methoxyfenozide in or on dates;
caneberries (subgroup 13-07A); grain sorghum forage, stover and grain; sweet sorghum forage, stover, grain and stalks; aspirated grain fractions (AGF), based on sorghum data; dried shelled peas and beans, except soybeans (subgroup 6C), except blackeyed peas and southern peas; fresh herbs (subgroup 19A), except chives; and dried herbs (subgroup 19A), except chives.  Tolerances were requested in the updated crop groups 8-10 and 11-10 (from groups 8 and 11, respectively), and in the updated subgroups 13-07F and 13-07G (from grapes and strawberries, respectively).  Tolerances in sugar apples, cherimoyas, atemoyas, custard apples, ilamas, soursops and biribas were also requested, based on translation of avocado residues.  Additionally, rotational crop tolerances in the rapeseed subgroup (20A) and the sunflower subgroup (20B) were requested.  The proposed new uses in dates, caneberries, sorghum and herbs are supported by magnitude-of-residue data generated by IR-4.  Other changes are supported by data previously reviewed by the Agency in 2009.  The requested rotational crop tolerances in the rapeseed and sunflower subgroups are based on 2012 recommendations by EPA.  The petition proposes the removal of the (expired) temporary tolerances in grain sorghum commodities, and their replacement with permanent tolerances in sweet and grain sorghum commodities.  The tolerance in AGF would be increased from 2.0 to 120 ppm.  The tolerance of 0.5 ppm in dried shelled peas and beans, except soybeans (subgroup 6C) was proposed at the Agency's request to better harmonize with existing Codex MRLs.  The existing tolerances in dried beans and dried peas would be removed concurrently with the establishment of tolerance in subgroup 6C.  The tolerance in okra would be removed concurrently with the update of crop group 8 to crop group 8-10.  The tolerances in grapes and strawberries would be removed concurrently with the establishment of the tolerances in crop subgroups 13-07F and 13-07G, respectively.  The primary crop tolerance in coriander leaves, along with the rotational crop tolerance in herbs and spices (group 19), except coriander leaves, would be removed concurrently with the establishment of the primary crop tolerance in subgroup 19A, except chives.  Although not proposed in the petition, rotational crop tolerances would necessarily be established in chives and in spices (subgroup 19B) upon establishment of the primary crop tolerance in subgroup 19A, except chives.  This summary document addresses the data supporting the proposed tolerances for residues of methoxyfenozide in the various commodities listed above.

Crop Field Trials:  To support the requested new uses, field trials were conducted on basil, caneberries, dates and sorghum.

Five basil field trials were conducted in the US and Canada during the 2009 growing season in North American Free Trade Agreement (NAFTA) Growing Zones 2 (NC), 3 (FL), 5A (WI), 9 (NM) and 12 (BC).  Following 4 foliar directed or broadcast applications of the flowable concentrate (FlC) formulation containing 2 pounds of active ingredient per gallon (lb ai/gal) to basil at total rates of 0.988-1.032 lb ai per acre (lb ai/A), residues (and per-trial averages) of methoxyfenozide were 9.26-47.2 (9.88-43.4) ppm in fresh basil, and 56.3-194 (60.5-188) ppm in dried basil harvested at a 1-day pre-harvest interval (PHI).  These field trial data support a tolerance of 80 ppm in fresh herbs (subgroup 19A) except chives, and a tolerance of 400 ppm in dried herbs (subgroup 19A) except chives.  However, HED has determined that it would be preferable to set a tolerance in the entire crop subgroup (herbs subgroup 19A, except chives) at 400 ppm.

Six caneberry field trials were conducted in the US during the 2010 growing season in NAFTA Growing Zones 2 (NC, blackberry), 5A (MI, blackberry), 10 (CA, blackberry) and 12 (OR, one trial on blackberry, and two trials on raspberry).  Following 3 foliar directed applications of the 2 lb ai/gal FlC formulation to caneberries at total rates of 0.744-0.778 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 0.62-2.5 (0.68-2.5) ppm in berries that were harvested at a 3-day PHI.  These field trial data support a tolerance of 6.0 ppm in caneberries (subgroup 13-07A).

Three date field trials were conducted in the US during the 2010 growing season in NAFTA Growing Zone 10 (CA).  Following 3 foliar directed applications of the 2 lb ai/gal FlC formulation at total rates of 0.501-0.933 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 1.5-3.3 (1.6-3.1)  ppm in dry fruit harvested at a 7-day PHI.  These field trial data support a tolerance of 8.0 ppm in dates.

Twelve grain sorghum field trials were conducted in the US during the 2009 growing season in NAFTA Growing Zones 2 (NC), 4 (AR), 5 (ND 3 trials; SD 1 trial), 6 (TX, 2 trials), 7 (NE), 8 (TX) and 10 (NM, 2 trials).  There was also 1 sweet sorghum field trial conducted in Growing Zone 6 (TX) during the same growing season.  Following 4 foliar broadcast or directed applications of the 2 lb ai/gal FlC formulation to grain sorghum at total rates of 0.478-0.494 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 0.70-5.6 (0.77-5.0) ppm in sorghum forage harvested at a PHI of 2-4 days, 0.15-2.6 (0.15-2.3) ppm in sorghum grain harvested at a PHI of 11-23 days, and 0.29-9.7 (0.45-7.6) ppm in sorghum stover harvested at a PHI of 21-23 days.  Following 4 foliar broadcast applications of the 2 lb ai/gal FlC formulation to sweet sorghum (only 1 trial) at a total rate of 0.481 lb ai/A, residues (and per-trial average) of methoxyfenozide were 0.045-0.18 (0.11) ppm in sorghum stalks harvested at a PHI of 3 days.  These field trial data support tolerances of 6.0 ppm in both sweet and grain sorghum grain, tolerances of 15 ppm in both sweet and grain sorghum forage (as well as sweet sorghum stalks), and tolerances of 20 ppm in both sweet and grain sorghum stover.

Processing Studies:  Because there are no processed commodities for caneberries or dates, processing studies were not required for these raw agricultural commodities (RACs).  The processed commodity for basil is dried basil, samples of which were produced at the field trial sites, and subsequently analyzed along with the fresh basil samples.

Processing data were submitted for sorghum (sweet sorghum syrup and AGF).  Residues of methoxyfenozide were 1.1 and 0.48 ppm in sorghum stalks and grain (RACs) harvested at PHIs of 3 and 21 days, respectively, following the last of 4 foliar broadcast applications of the 2 lb ai/gal FlC formulation of methoxyfenozide at a total rate of 0.481 lb ai/A.  Residues of methoxyfenozide were 1.1 and 17 ppm in sorghum syrup and sorghum AGF, respectively.   These data indicate that methoxyfenozide did not concentrate in sweet sorghum syrup (1X processing factor), but did concentrate in sorghum AGF (35X processing factor).  Ergo, a tolerance in sweet sorghum syrup is not required; the processing data support a tolerance of 120 ppm in AGF.

Residue Analytical Methods:  Validated methods are available for the enforcement of methoxyfenozide tolerances.  Adequate methods were used for the quantitation of methoxyfenozide residues in samples from the various crop field trial and processing studies, based on acceptable method validation and concurrent recovery data.

Storage Stability:  Adequate storage stability data are available to support the storage durations and conditions of samples from the submitted field trial and processing studies.

Meat, Milk, Poultry and Eggs:  The current action for the proposed uses will not result in revisions to the existing tolerances in livestock commodities.

MRL Harmonization:  Codex has not established maximum residue limits (MRLs) in any of the proposed new uses.  As such, there are no harmonization issues associated with Codex for the proposed new uses in the current action.  Canada's Pest Management Regulatory Agency (PMRA) has established MRLs in fresh Chinese chive leaves and fresh chive leaves at 5 mg/kg.  There are no Canadian MRLs in dates, caneberries or sorghum commodities.  However, PMRA and the Agency are jointly reviewing the basil and caneberry data in the current action; EPA and PMRA will attempt to harmonize the recommended tolerances/MRLs in herbs and caneberries.

Codex has established MRLs in grapes at 1 mg/kg, in strawberries and pome fruits at 2 mg/kg, in avocadoes at 0.7 mg/kg, and in papayas at 1 mg/kg.  The recommended tolerance of 2.0 ppm in the updated pome fruits group (11-10), increased from the current tolerance of 1.5 ppm in group 11, would be harmonized with the Codex MRL.  The recommended tolerance of 1.0 ppm in small vine-climbing fruit, except fuzzy kiwifruit (subgroup 13-07F), translated from grape data, would be harmonized with the Codex MRL in grapes.  The recommended tolerance of 2.0 ppm in low-growing berries (subgroup 13-07G), translated from strawberry data, and increased from the current tolerance of 1.5 ppm in strawberries, would be harmonized with the Codex MRL in strawberries.  The recommended tolerance of 0.60 ppm in various tropical tree fruits, translated from avocado data (there is also a tolerance of 0.6 ppm in papaya), would not be harmonized with the Codex MRLs in avocadoes or papayas.  The recommended tolerance of 0.50 ppm in dried shelled peas and beans, except soybeans (subgroup 6C) was proposed at the Agency's request to better harmonize with the existing Codex MRL of 0.5 mg/kg in dried beans.  This tolerance would replace the current tolerances of 0.24 ppm in dried beans, and 2.5 ppm in dried peas, which would both be removed.

2.0	Regulatory Recommendations

HED has examined the residue chemistry database for methoxyfenozide.  Pending submission of a revised Section F (to propose tolerance levels and additional commodities in accordance with those recommended by HED, and to correct the commodity definition for the herb subgroup 19A), there are no residue chemistry issues that would preclude establishing tolerances in the requested commodities.  The recommended tolerances are listed in Table 2.2.2, below.

Note to RD:  Analytical standards for methoxyfenozide and its 4 metabolites are currently available at EPA's National Pesticide Standards Repository (NPSR).  However, the RH-152072 metabolite standard expired on 10 October 2010, and the RH-141518 metabolite standard expired on 26 July 2013; neither has been replenished by the registrant.  Additionally, the RH-117236 metabolite standard expires on 3 September 2013.  The registrant should resubmit new analytical reference standards, or updated certificates of analysis (COAs), for all 3 of these standards, most urgently for the expired RH-152072 and RH-141518, but also for RH-117236 before its expiration date.  See Section 2.4, below.

Note to RD:  Concurrent with the establishment of permanent tolerances in sweet and grain sorghum commodities (40CFR §180.544[a][1]), the paragraph referring to, and the table containing, the time-limited tolerances in grain sorghum commodities (40CFR §180.544[b]) should be removed, and replaced with "[Reserved]".

Concurrent with the establishment of the tolerance in subgroup 6C (except blackeyed and southern peas), the tolerances in dried beans and dried peas should be removed (40CFR §180.544[a][1]).

Concurrent with the establishment of the tolerance in group 8-10, the tolerances in okra and group 8 should be removed (40CFR §180.544[a][1]).

Concurrent with the establishment of the tolerance in group 11-10, the tolerance in group 11 should be removed (40CFR §180.544[a][1]).

Concurrent with the establishment of the tolerance in subgroup 13-07F, the tolerance in grapes should be removed (40CFR §180.544[a][1]).

Concurrent with the establishment of the tolerance in subgroup 13-07G, the tolerance in strawberries should be removed (40CFR §180.544[a][1]).

Concurrent with the establishment of the tolerance in subgroup 19A (except chives), the tolerance in coriander leaves should be removed (40CFR §180.544[a][1]), and tolerances in subgroup 19B and chives should be established (40CFR §180.544[d][2]).

2.1	Data Deficiencies/Data Needs

None.

2.2	Tolerance Considerations

2.2.1	Enforcement Analytical Method/Multiresidue Methods

Adequate methods using high performance liquid chromatography with ultraviolet or mass spectrometric detection (HPLC/UV or /MS) are available for enforcing the current tolerances for methoxyfenozide in primary and rotational crops, and in animal commodities.  Depending on the plant commodity, the limits of quantitation (LOQs) for methoxyfenozide in primary crop commodities are 0.01-0.05 ppm.

Data concerning the recovery of methoxyfenozide using the FDA multiresidue method protocols (PAM Volume I) were previously submitted to, and reviewed by, HED.  Methoxyfenozide was not recoverable by any of these procedures.  The data were forwarded to FDA for evaluation, and the updating of PAM Volume I.

2.2.2	Recommended Tolerances

TABLE 2.2.2	Tolerance Summary for Methoxyfenozide.
                    Commodity as Proposed by the Petitioner
                           Proposed Tolerance (ppm)
                          Recommended Tolerance (ppm)
                    Comments; Correct Commodity Definition
Herb subgroup 19A, fresh, except chives
                                      70
                                      400
Herb subgroup 19A,  except chive
Herb subgroup 19A, dried, except chives
                                      400

Caneberry subgroup 13-07A
                                      6.0
                                      6.0

Date
                                      7.0
                                      8.0
One date and all sorghum OECD calculator inputs were increased to account for field trials conducted at half (date) or (2/3) (sorghum) the proposed use rate (based on OECD's preliminary guidance on proportionality of sample residues to application rate).
Sorghum, grain, forage
                                      9.0
                                      15

Sorghum, grain, stover
                                      15
                                      20

Sorghum, grain, grain
                                      4.0
                                      6.0

Sorghum, sweet, forage
                                      9.0
                                      15

Sorghum, sweet, stover
                                      15
                                      20

Sorghum, sweet, grain
                                      4.0
                                      6.0

Sorghum, sweet, stalk
                                      9.0
                                      15

Grain, aspirated grain fractions
                                      80
                                      120

Pea and bean, dried shelled, except soybean, subgroup 6C, except pea, blackeyed, seed and pea, southern, seed
                                      0.5
                                     0.50
Revise tolerance from 0.5 ppm to 0.50 ppm.
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                      1.0
                                      1.0

Berry, low growing, subgroup 13-07G, except cranberry
                                      1.5
                                      2.0
Tolerance harmonized with Codex MRL in strawberry.
Fruit, pome, group 11-10
                                      1.5
                                      2.0
Tolerance harmonized with Codex MRL in pome fruits.
Vegetable, fruiting, group 8-10
                                      2.0
                                      2.0

Sugar apple
                                      0.6
                                     0.60
Revise tolerances from 0.6 ppm to 0.60 ppm.
Cherimoya
                                      0.6
                                     0.60

Atemoya
                                      0.6
                                     0.60

Custard apple
                                      0.6
                                     0.60

llama
                                      0.6
                                     0.60

Soursop
                                      0.6
                                     0.60

Biriba
                                      0.6
                                     0.60

Rapeseed subgroup 20A
                                      1.0
                                      1.0
Rotational crop tolerances.
Sunflower subgroup 20B
                                      1.0
                                      1.0

Spice subgroup 19B*
                                     None
                                      4.5

Chive*
                                     None
                                      4.5

* These commodities were not proposed by the petitioner, but are recommended by HED.

2.2.3	Revisions to Petitioned-For Tolerances

In fresh herbs, subgroup 19A (except chives), the petitioner proposed a tolerance of 70 ppm, based on the Organization of Economic Development and Cooperation's (OECD's) tolerance calculation procedure.  The petitioner entered all 10 individual sample residues into the MRL calculator.  When the average residues from each of the 5 basil field trials were entered, as the OECD guidance stipulates, the resulting recommended tolerance would be 80 ppm.  In dried herbs, subgroup 19A (except chives), the petitioner proposed a tolerance of 400 ppm, based on OECD's tolerance calculation procedure.  However, the Agency has determined that setting separate subgroup 19A tolerances in fresh and dried commodities is not feasible from a regulatory perspective.  Therefore, HED recommends setting the tolerance in the entire subgroup 19A (both fresh and dried commodities), except chives, at the higher level of 400 ppm.

In dates, the petitioner proposed a tolerance of 7.0 ppm, based on 4 date field trials and the OECD's tolerance calculation procedure.  However, HED determined that only 3 of the trials were truly independent.  The 4 sample residues from the 2 trials deemed to be non-independent were averaged together as one input into the MRL calculator.  Also, the total application rate at one of the other trials was only half the proposed maximum seasonal use rate, a difference of >25%.  Ergo, the residue values from this trial were doubled, per OECD's preliminary guidance on proportionality of sample residues to application rate (decision from the minutes of HED's Chemistry Science Advisory Council meeting of 28 March 2012).  When the average of these residues, along with the average residues from each of the other 2 field trials were entered into the MRL calculator, the resulting recommended tolerance was 8.0 ppm.

In sorghum commodities, the petitioner proposed tolerances of 9.0, 15 and 4.0 ppm in the forage, stover and grain, respectively, of both grain and sweet sorghum, and 9.0 ppm in sweet sorghum stalks, based on OECD's tolerance calculation procedure.  A tolerance of 80 ppm in sorghum AGF was proposed, based on the sorghum processing study.  However, the total application rate at the sorghum field trials was only two thirds the proposed maximum seasonal use rate, a difference of >25%.  Ergo, the residue values from the trials were increased by half, per OECD's preliminary guidance on proportionality (ChemSAC meeting; 28 March 2012).  When these values were entered into the MRL calculator, the resulting recommended tolerances were 15, 20 and 6.0 ppm in the forage, stover and grain, respectively, of both grain and sweet sorghum, and 15 ppm in sweet sorghum stalks.  Similarly, when the HAFT from the sorghum field trials (2.25 ppm) was increased by half, and multiplied by the AGF processing factor (35X), the resulting recommended tolerance was 120 ppm in sorghum AGF.

Instead of the proposed tolerances in the various tropical tree fruits (0.6 ppm), HED recommends establishing the tolerances at 0.60 ppm, in order to avoid the situation where a field sample containing residues significantly above the tolerance (0.64 ppm, for example) would be considered non-violative.  For the same reason, HED recommends that the proposed tolerance of 0.5 ppm in subgroup 6C (except blackeyed and southern peas) be revised to 0.50 ppm.

2.2.4	International Harmonization

Codex has not established MRLs in any of the proposed new uses.  As such, there are no harmonization issues associated with Codex for the proposed new uses in the current action.  Canada's PMRA has established MRLs in fresh Chinese chive leaves and fresh chive leaves at 5 mg/kg.  There are no Canadian MRLs in dates, caneberries or sorghum commodities.  However, PMRA and the Agency are jointly reviewing the basil and caneberry data in the current action; EPA and PMRA will attempt to harmonize the recommended tolerances/MRLs in herbs and caneberries.

Codex has established MRLs in grapes at 1 mg/kg, in strawberries and pome fruits at 2 mg/kg, in avocadoes at 0.7 mg/kg, and in papayas at 1 mg/kg.  The recommended tolerance of 2.0 ppm in the updated pome fruits group (11-10), increased from the current tolerance of 1.5 ppm in group 11, would be harmonized with the Codex MRL.  The recommended tolerance of 1.0 ppm in small vine-climbing fruit, except fuzzy kiwifruit (subgroup 13-07F), translated from grape data, would be harmonized with the Codex MRL in grapes.  The recommended tolerance of 2.0 ppm in low-growing berries (subgroup 13-07G), translated from strawberry data, and increased from the current tolerance of 1.5 ppm in strawberries, would be harmonized with the Codex MRL in strawberries.  The recommended tolerance of 0.60 ppm in various tropical tree fruits, translated from avocado data (there is also a tolerance of 0.6 ppm in papaya), would not be harmonized with the Codex MRLs in avocadoes or papayas.  The recommended tolerance of 0.50 ppm in dried shelled peas and beans, except soybeans (subgroup 6C) was proposed at the Agency's request to better harmonize with the existing Codex MRL of 0.5 mg/kg in dried beans.  This tolerance would replace the current tolerances of 0.24 ppm in dried beans, and 2.5 ppm in dried peas, which would both be removed.

2.3	Label Recommendations

None.

2.4	Submittal of Analytical Reference Standards (860.1650)

	The analytical standard for methoxyfenozide (RH-112485), with an expiration date of 17 October 2014, is currently available in the EPA's NPSR, per Email communication from Theresa Cole of the Biological and Economic Analysis Division's (BEAD's) Analytical Chemistry Branch (ACB) of 9 May 2013.  However, the RH-152072 metabolite standard expired on 10 October 2010, and the RH-141518 metabolite standard expired on 26 July 2013; neither has been replenished by the registrant.  Additionally, the RH-117236 metabolite standard expires on 3 September 2013.  The registrant is required to maintain reasonable amounts of the analytical reference standards for methoxyfenozide and its 4 metabolites.  New reference standards, or updated COAs, 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 by the Occupational Safety and Health Administration (OSHA) in 29CFR§1910.1200.  In addition to the parent compound, 4 metabolites (included in risk assessment) are currently available in the NPSR, as listed below with their respective expiration dates.

Methoxyfenozide metabolite RH-117236		3 September 2013
Methoxyfenozide metabolite RH-141518		26 July 2013
Methoxyfenozide metabolite RH-151055		15 July 2014
Methoxyfenozide metabolite RH-152,072		10 October 2010

3.0	Chemical Identity

Methoxyfenozide is a diacylhydrazine insecticide used on a variety of crops for control of armyworms and other lepidopterous pest species.  It mimics the action of the molting hormone of lepidopterous larvae, causing the larvae to undergo an incomplete and premature molt, which ultimately results in their death.  Methoxyfenozide is currently registered to Dow AgroSciences.  The chemical structure and nomenclature of methoxyfenozide are listed in Table 3.1, and its physicochemical properties are presented in Table 3.2 (below).

3.1	Nomenclature

TABLE 3.1	Methoxyfenozide Nomenclature.
Chemical structure

Common name
Methoxyfenozide
Company experimental name
RH-2485
Molecular formula
C22H28N2O3
Molecular weight
368.47
IUPAC name
N-tert-butyl-N′-(3-methoxy-o-toluoyl)-3,5-xylohydrazide
CAS name
3-methoxy-2-methylbenzoic acid 2-(3,5-dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide
CAS registry number
161050-58-4
End-use product (EP)
2 lb ai/gal (240 g ai/L) flowable concentrate (FlC) formulation (Intrepid 2F; EPA Registration #62719-442).

3.2	Physicochemical Characteristics

TABLE 3.2	Physicochemical Properties of Methoxyfenozide.
                                   Parameter
                                     Value
                                   Reference
Melting point/range (ºC)
206.1-208
D231303, H. Podall, 19 May 1997
pH
7.0

Density (g/cm[3])
0.740 +- 0.0081

Water solubility (mg/L at 20ºC)
3.3

Solvent solubility (g/L at 20ºC)
N-heptane		1.87
Xylene			3.38
1,2-dichloroethane	36.72
Methanol		192.92
2-Propanol		50.22

Vapor pressure (Pa at 25ºC)
1.33 x 10[-5]

Dissociation constant, pKa
None

Octanol/water partition coefficient (Log [KOW])
3.72 +- 0.04

UV/visible absorption spectrum
No absorption expected at λ> 300 nm

Methoxyfenozide is a solid under ambient conditions, and has a somewhat low volatility.  The compound has a relatively low solubility in water, and moderate solubility in organic solvents.  Its octanol/water partition coefficient suggests that accumulation of methoxyfenozide in fatty tissues is possible.

3.3      Pesticide Use Pattern/Directions for Use (860.1200)

IR-4 has requested that new Section 3 uses of the insecticide methoxyfenozide be added to the label for Intrepid 2F (Registration #62719-442).  The proposed new uses would be on herbs (subgroup 19A) except chives, dates, sorghum and caneberries (subgroup 13-07A).  Intrepid 2F is an FlC formulation containing 22.6% ai by weight, which is equivalent to 2 lb ai/gal.  Examples of supplemental labels for Intrepid 2F were provided, and the proposed use directions therein are summarized in Table 3.3, below.

TABLE 3.3	Summary of Directions for Use of Methoxyfenozide.
                          Application Type; Equipment
                                   Use Rate
                                   (lb ai/A)
                             Max. Uses Per Season
                            Max. Seasonal Use Rate
                                 (lb ai/A)[1]
                                 PHI[1] (Days)
              Use Directions, Application Timing, and Limitations
                      Herbs (Subgroup 19A) Except Chives
                           Foliar; Ground and Aerial
                                     0.12
                                     NS[2]
                                      1.0
                                       1
Minimum RTI[3] of 10 days.  Ground application:  Apply in a minimum of 10 GPA[4] to young crop or small plants.  Apply in a minimum of 20 GPA to densely foliated or difficult-to-cover crops to ensure thorough coverage.  Aerial application:  Apply in a minimum of 10 GPA.
                                     Dates
                               Ground (Airblast)
                                     0.31
                                      NS
                                      1.0
                                       7
Begin applications before eggs hatch. Minimum RTI of 10 days.  Alternate or intersperse with other insecticides. Apply in a minimum of 100 GPA.
                                    Sorghum
                           Foliar; Ground and Aerial
                                     0.16
                                      NS
                                     0.75
                                   3, 21[5]
Apply at first sign of egg hatch or when infestations reach threshold levels.  Ground application:  Apply in a minimum of 15 GPA.  Aerial application:  Apply in a minimum of 10GPA.
                         Caneberries (Subgroup 13-07A)
                           Foliar; Ground and Aerial
                                     0.25
                                       3
                                     0.75
                                       3
Apply at initiation of egg-laying.  Make second application at 100% petal fall.  A third application may be required under high pest pressure.  Minimum RTI of 7 days.  Ground application:  Apply in a minimum of 30 GPA.  Aerial:  Apply in a minimum of 10 GPA.
1. PHI = Pre-Harvest Interval.
2. NS = Not Specified.
3. RTI = Re-Treatment Interval.
4. GPA = Gallons Per Acre.
5. Minimum PHI of 3 days for forage and sweet sorghum stalks, and 21 days for grain and stover.

Conclusions:  The use directions for application to herbs, caneberries, dates and sorghum are sufficient to allow for evaluation of the submitted residue data relative to the proposed use patterns.

4.0	Metabolite/Degradate Residue Profile

4.1	Nature of the Residue
	Metabolism Assessment Review Committee (MARC) Memo; D258034 W. Wassell; 23 July 1999
	D251225; W. Wassell; 27 July 1999
	D259989; W. Wassell; 8 August 2000

The nature of methoxyfenozide residues in primary crops is adequately understood, based on acceptable metabolism studies in cotton, apples, grapes and rice.  Methoxyfenozide does not undergo extensive metabolism in primary crops.  HED has determined that the residue of concern (ROC), for both the tolerance expression and risk assessment in primary crops (and drinking water), is parent methoxyfenozide only.

	D269986; M. J. Nelson; 7 August 2002

The nature of methoxyfenozide residues in rotational crops is adequately understood, based on acceptable metabolism studies in confined, limited field, and extensive field rotational crop studies.  For enforcement purposes, the ROC for high-moisture rotational crops is the parent compound; the metabolites RH-151,055, RH-152,072, RH-117,236, RH-152,067, RH-131,157 and RH-152,071 are also to be taken into account for risk assessment.  For enforcement purposes, the ROCs for low-moisture rotational crops are the combined residues of parent and metabolites RH-151,055, RH-152,072 and RH-117,236; metabolites RH-152,067, RH-131,157 and RH-152,071 are also to be taken into account for risk assessment.

	Metabolism Assessment Review Committee (MARC) Memo; D258034 W. Wassell; 23 July 1999

The nature of the residue in ruminants and poultry is adequately understood, based on the available metabolism studies in lactating goats, and laying hens, respectively.  HED has determined that the ROC in milk and ruminant tissues (other than liver and kidney) is parent compound; in ruminant liver and kidney it is methoxyfenozide and its RH-141,518 metabolite.  The residue of concern in poultry meat (muscle) and fat is parent methoxyfenozide.  The residue of concern in eggs, poultry liver, and poultry meat byproducts is methoxyfenozide and its metabolite RH-141,518.

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

Data have been submitted and reviewed depicting the metabolism of methoxyfenozide 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, below.

Table 4.1.1	Summary of Methoxyfenozide 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
Parent methoxyfenozide
Parent methoxyfenozide

Rotational Crops (High Moisture)
Parent methoxyfenozide and metabolites, RH-151,055, RH-152,072, and RH-117,236, RH-152,067, RH-131,157 and RH-152,071
Parent methoxyfenozide

Rotational Crops (Low Moisture)
Parent methoxyfenozide and metabolites, RH-151,055, RH-152,072, and RH-117,236, RH-152,067, RH-131,157 and RH-152,071
Parent methoxyfenozide and metabolites RH-151,055, RH-152,072, and RH-117,236
Table 4.1.1	Summary of Methoxyfenozide Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression.
                                    Matrix
                     Residues Included in Risk Assessment
                   Residues Included in Tolerance Expression
Livestock
Ruminant Milk, Meat and Fat
Parent methoxyfenozide
Parent methoxyfenozide

Ruminant Liver and Other Meat Byproducts
Parent methoxyfenozide and metabolite RH-141,518
Parent methoxyfenozide and metabolite RH-141,518

Poultry Meat and Fat
Parent methoxyfenozide
Parent methoxyfenozide

Poultry Eggs, Liver and Other Meat Byproducts
Parent  methoxyfenozide and metabolite RH-141,518
Parent  methoxyfenozide and metabolite RH-141,518
Drinking Water
Parent methoxyfenozide
Not applicable

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

4.1.2	Summary of Confined Rotational Crops (860.l850)
	Metabolism Assessment Review Committee (MARC) Memo; D258034 W. Wassell; 23 July 1999
	D251225; W. Wassell; 27 July 1999
	D269986; M. J. Nelson; 7 August 2002

The nature of methoxyfenozide residues in rotational crops is adequately understood, based on the available confined rotational crop study.  Following three soil applications of [14]C-methoxyfenozide at rates totaling 2.0 lb ai/A (1X rate), total radioactive residues accumulated at >=0.01 ppm in mustard, radishes and wheat planted 31, 91 and 364 days after the last application.  Methoxyfenozide was highly metabolized in rotational crops by oxidation, demethylation, and hydroxylation to non-conjugated metabolites, which were then conjugated with biomolecules, yielding bound residues and precursors in the sugar synthesis pathway.

4.1.3	Summary of Rat Metabolism
	Risk Assessment Document D388978; M. Collantes; 23 May 2012 (PP#1E7842)

In the rat, [14]C-radiolabeled methoxyfenozide was rapidly absorbed following gavage administration, with maximum peak plasma concentrations observed within 15 minutes of dosing.  Peak plasma concentrations at 10 mg/kg ranged from 0.70-1.09 ppm in males, and 0.50-0.59 ppm in females, depending on the ring location of the radiolabel.  At 1000 mg/kg, peak levels were 26.11-35.52 ppm in males, and 21.92-29.74 ppm in females.   Plasma elimination was biphasic, with an α-phase T1/2 of 0.2-0.6 hours, and a β-phase T1/2 of 15.2-35.6 hours, and showed some variation with radiolabel location.  The total plasma elimination rate was longer for the high dose compared to the low dose animals, suggesting metabolic pathway saturation, and the effect was more prominent in female rats.  Radioactivity was extensively distributed among tissues, with the highest concentrations at Cmax (0.25 hr) observed in the intestinal tract, stomach, liver and residual carcass.  Enterohepatic circulation was observed.

Methoxyfenozide did not show a potential for bioaccumulation.  By 5 days post-treatment, the highest levels were observed in the liver and carcass, but tissue radioactivity in all tissues was insignificant by that time.  Excretion of radiolabel was essentially complete by 48 hours post-dosing.  Based on the minimal level of radioactivity in tissues at 72 hours, absorption was estimated to be at least 62-70% of the administered dose (biliary plus urinary excretion).  The major route of excretion was in the feces (86-97% of the administered dose), with 5-13% of the dose excreted in the urine.  Significant dose- or sex-dependent differences in metabolic disposition were not observed.  Methoxyfenozide was extensively metabolized.  The major routes of metabolism involved o - demethylation and oxidative hydroxylation of the A-ring phenyl and/or B-ring methyl groups, followed by glucuronic acid or sulfate conjugation.

In addition to the parent compound, seven major metabolites were identified in excreta.  These included RH-131,157, RH-141,581 and RH-117,236, metabolites also identified in residues in crops and/or livestock.  Up to 25 metabolites were isolated from urine, but the majority represented <1-2% of the radioactive dose.  Up to 16 metabolites were identified in the feces, including the parent compound, with only six containing >=5% of the administered radiolabel.  The major fecal metabolites in all groups were products of Phase I O-demethylation and oxidative hydroxylation on the A-ring and, to a lesser extent, the B-ring.  Levels of excreted parent compound in the feces were greater in animals receiving 1000 mg/kg test material (30-39% of dose) when compared to the 10 mg/kg groups (14-26% of dose), consistent with saturation of absorption.  In the bile, up to 24 metabolites were detected, with the primary metabolite (13-18% of dose) being derived by glucuronide conjugation at the o-demethylated alpha ring.

4.1.4	Summary of Environmental Degradation
	EFED Memo; D388876; K. Milians; 17 August 2011

Methoxyfenozide is very persistent (T1/2 = 1 to 3 years in soil and water), and moderately mobile (Koc = 219 - 922 L/kgoc in various soils).  It is stable to photolysis and hydrolysis, is not significantly volatile, and degrades only very slowly by microbial activity.  Degradates are predominantly RH-117,236 and RH-131,154, but these are only present at low concentrations. Because of its resistance to degradation and its mobility, methoxyfenozide has the potential to accumulate and to move off the site of application by leaching and erosion/runoff, resulting in ground- and surface-water contamination.

5.0	Residue Profile

5.1	Residue Analytical Methods (860.1340)

5.1.1	Data Collection Methods
	MRIDs #48994101 to -04

Basil:  Samples of fresh and dried basil were analyzed for residues of methoxyfenozide using high performance liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) according to a slight modification of Dow AgroSciences Method GRM: 02.25, Determination of Residues of Methoxyfenozide in High Moisture Crops by Liquid Chromatography with Tandem Mass Spectrometry Detection.  This method has been assessed previously, and deemed acceptable for data gathering purposes.  The petitioner used the lowest levels of method validation (LLMVs) of 0.01 and 0.05 ppm for fresh and dried samples, respectively, as the limits for reporting residues.  The method was adequate for data collection, based on acceptable method validation and concurrent recovery data.  The fortification levels used in the concurrent recoveries were adequate to bracket expected residue levels.  With the exception of one sample (0.0592 ppm detected in one dried basil sample from Trial NM-05) residues of methoxyfenozide equal to or above the LLMVs were not detected in any of the control samples.

Modifications to the reference method included cleanup with hexane and dichloromethane (DCM) partition instead of solid phase (SPE) extraction, concentration by rotary evaporation instead of nitrogen blow down, and reconstitution of residues in water/acetonitrile (ACN) (7:3, v/v) containing 0.01% formic acid instead of water/ACN (7:3, v/v) containing 0.1% formic acid.

Briefly, residues of methoxyfenozide were extracted from the homogenized samples with methanol/0.1N HCl (9:1, v/v).  After filtration, the filtrate was brought to known volume with methanol/0.1N HCl (9:1, v/v), and an aliquot of the aqueous extract was partitioned against hexane following the addition of 10% NaCl solution.  The aqueous extract was then partitioned twice against DCM, and the DCM fraction was reduced to dryness with rotary evaporation before the sample was reconstituted in water/acetonitrile (7:3, v/v) containing 0.01% formic acid for analysis by LC/MS/MS in the positive ionization mode.  MS/MS detection of methoxyfenozide monitored the ion transition from m/z 369.2-->313.2.

The method limit of detection (LOD) and limit of quantitation (LOQ) were calculated to be 0.00307 and 0.00921 ppm, respectively, in fresh basil, and 0.0163 and 0.0489 ppm, respectively, in dried basil.  The method was adequately validated prior to, and in conjunction with, the analysis of the basil field trial samples (see Table <IP_ADDRESS>).

TABLE <IP_ADDRESS>	Summary of Method Validation and Concurrent Recoveries of Methoxyfenozide from Fresh and Dried Basil.
                                 Basil Matrix
                                  Spike Level
                                     (ppm)
                                Sample Size (n)
                                  Recoveries
                                      (%)
                           Mean +- Std. Dev. (%)[1]
                         Method Validation Recoveries
                            Fresh leaves and stems
                                     0.01
                                       6
                           84, 75, 93, 69[2], 74, 71
                                    78 +- 9

                                     0.30
                                       3
                                  88, 87, 87
                                    87 +- 1

                                     10.0
                                       3
                                  86, 86, 99
                                    90 +- 8
                            Dried leaves and stems
                                     0.05
                                       6
                          81, 105, 104, 106, 105, 101
                                   100 +- 10

                                      2.0
                                       3
                                  92, 94, 91
                                    92 +- 2

                                     50.0
                                       3
                                  94, 95, 96
                                    95 +- 1
                             Concurrent Recoveries
                            Fresh leaves and stems
                                     0.30
                                       2
                                   93[3], 89
                                      91

                                   74.9-75.0
                                       3
                                  93, 90, 91
                                    91 +- 2

                                      2.0
                                       2
                                    87, 88
                                      88

                                     300.0
                                       3
                                  96, 94, 85
                                    92 +- 6
1. The standard deviation is not calculated for sample sizes n < 3; all statistics were calculated by study reviewer, with the exception of those at 0.01 and 0.05 ppm.
2. The value outside the acceptable range of 70-120% is shown in boldface type.
3. This is the average of two recoveries.

Caneberries:  Samples of blackberries and raspberries were analyzed for residues of methoxyfenozide via LC/MS/MS using a modification of Dow AgroSciences Method GRM: 02.25.  This method has been assessed previously, and deemed acceptable for data gathering purposes.  The petitioner used the LLMV of 0.05 ppm as the limit for reporting residues.  The method was adequate for data collection, based on acceptable method validation and concurrent recovery data.  The fortification levels used in the concurrent recoveries were adequate to bracket expected residue levels.  No residues of methoxyfenozide equal to or above the LLMV were detected in any of the control samples.

The modifications made to the referenced method were minor, and included omitting use of a centrifuge to clarify sample extracts and using vacuum filtration; substituting a PFP phase for the SB-C8 phase HPLC column; and adjusting the mobile phase to use ammonium acetate instead of formic acid.

Briefly, residues of methoxyfenozide were extracted from the homogenized samples with methanol/0.1N HCl (9:1, v/v).  After filtration, the filtrate was brought to known volume with methanol, and an aliquot was diluted with water for clean up on an Evolute acidic basic neutral solid phase extraction cartridge.  After loading the extract, the cartridge was dried under high vacuum, and residues were eluted with ACN.  The eluate was diluted with ACN/10mM ammonium acetate (1:1, v/v) for analysis by LC/MS/MS in the positive ionization mode.  MS/MS detection of methoxyfenozide monitored the ion transition from m/z 369-->149.

Based on recoveries of samples fortified at the LLMV (0.05 ppm), the method LOD and LOQ were calculated to be 0.0040 and 0.012 ppm, respectively.  The method was adequately validated prior to, and in conjunction with, the analysis of caneberry field trial samples (see Table <IP_ADDRESS>).

TABLE <IP_ADDRESS>	Summary of Method Validation and Concurrent Recoveries of Methoxyfenozide from Caneberries.
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                           Mean +- Std. Dev. (%)[1]
                         Method Validation Recoveries
                                 Blackberries
                                     0.05
                                       3
                                  90, 91, 89
                                    90 +- 1

                                     0.50
                                       3
                                  93, 91, 91
                                    92 +- 1

                                      5.0
                                       3
                                  89, 88, 91
                                    89 +- 2
                             Concurrent Recoveries
                         Blackberries, raspberries[2]
                                     0.05
                                       3
                                  86, 85, 90
                                    87 +- 3
                                  Raspberries
                                      5.0
                                       1
                                      92
                                      92
1. The standard deviation is not calculated for sample sizes n < 3; all statistics were calculated by study reviewer.
2. One recovery is from a raspberry sample, and two recoveries are from blackberry samples.

Dates:  Date samples were analyzed for residues of methoxyfenozide via LC/MS/MS using a procedure derived from Dow AgroSciences Method GRM: 02.25 and Rohm and Haas Report #34-98-87 (Tolerance Enforcement Method for Parent RH-2485 in Pome Fruit).  The petitioner used the LLMV of 0.01 ppm as the limit for reporting residues.  The method was adequate for data collection, based on acceptable method validation and concurrent recovery data.  The fortification levels used in the method recoveries were adequate to bracket expected residue levels.  No residues of methoxyfenozide equal to or above the LLMVs were detected in any of the control samples.

Briefly, residues of methoxyfenozide were extracted from the homogenized samples with methanol/0.1N HCl (9:1, v:v).  After filtration, the filtrate was brought to known volume with methanol, and an aliquot was diluted with water for clean up on an Evolute acidic basic neutral solid phase extraction cartridge.  After loading the extract, the cartridge was dried under high vacuum, and residues were eluted with ACN.  The eluate was diluted with ACN/10mM ammonium acetate (1:1, v:v) for analysis by LC/MS/MS in the positive ionization mode.  MS/MS detection of methoxyfenozide monitored the ion transition from m/z 369-->149.

Based on recoveries of samples fortified at the LLMV (0.01 ppm), the method LOD and LOQ were calculated to be 0.0040 and 0.012 ppm, respectively.  The method was validated prior to, and in conjunction with, the analysis of date field trial samples (see Table <IP_ADDRESS>).

TABLE <IP_ADDRESS>	Summary of Method Validation and Concurrent Recoveries of Methoxyfenozide from Dates.
                                  Date Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                            Mean +- Std. Dev. (%)*
                         Method Validation Recoveries
                                  Dried fruit
                                     0.01
                                       3
                                  85, 84, 84
                                    84 +- 1

                                      1.0
                                       3
                                  87, 87, 89
                                    88 +- 1

                                      20
                                       3
                                  88, 86, 88
                                    87 +- 1
                             Concurrent Recoveries
                                  Dried fruit
                                     0.01
                                       2
                                    92, 91
                                      92
* The standard deviation is not calculated for sample sizes n < 3; all statistics were calculated by study reviewer.

Sorghum:  Samples of sorghum commodities, from both the field trial and processing studies, were analyzed for residues of methoxyfenozide via LC/MS/MS using a slight modification of Dow AgroSciences Method GRM 02.25.  For all matrices (forage and stalks, grain and stover), the petitioner used the LLMV of 0.01 ppm as the limit for reporting residues.  The method was adequate for data collection, based on acceptable method validation and concurrent recovery data.  The fortification levels used in the concurrent recoveries were adequate to bracket expected residue levels.  No residues of methoxyfenozide equal to or above the LLMV were detected in any control samples.

Briefly, residues of methoxyfenozide were extracted from the homogenized samples with methanol/0.1N HCl (9:1, v:v).  After filtration, the filtrate was brought to known volume with methanol, and an aliquot was diluted with water for clean up on an Evolute acidic basic neutral solid phase extraction cartridge; after loading the extract, the cartridge was dried under high vacuum, and residues were eluted with ACN.  The eluate was diluted with ACN/10mM ammonium acetate (1:1, v:v) for analysis by LC/MS/MS in the positive ionization mode.  MS/MS detection of methoxyfenozide monitored the ion transition from m/z 369-->149.

The method LOD and LOQ, respectively, were calculated to be 0.00711 and 0.02134 ppm in sorghum forage/stalks, 0.00125 and 0.00374 ppm in sorghum grain, 0.00263 and 0.00790 in sorghum stover, 0.00064 and 0.00191 in AGF, and 0.00028 and 0.00083 in syrup.  The LLMV for all sorghum matrices was 0.01 ppm.  The method was validated prior to, and in conjunction with, the analysis of sorghum field trial and processing study samples (see Table <IP_ADDRESS>).

TABLE <IP_ADDRESS>	Summary of Method Validation and Concurrent Recoveries of Methoxyfenozide from Sorghum Commodities.
                                Sorghum Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                           Mean +- Std. Dev. (%)[1]
                         Method Validation Recoveries
                                    Forage
                                     0.01
                                       3
                                88, 85, 131[2]
                                    101  26

                                     0.10
                                       3
                                  85, 86, 83
                                     85  2

                                      1.0
                                       3
                                  86, 85, 85
                                     85  1

                                      10
                                       3
                                  85, 86, 79
                                     83  4
                                     Grain
                                     0.01
                                       3
                                  88, 85, 83
                                     85  3

                                     0.10
                                       3
                                  84, 85, 85
                                     85  1

                                      1.0
                                       3
                                  87, 86, 86
                                     86  1
                                    Stover
                                     0.01
                                       3
                                  75, 72, 75
                                     74  2

                                     0.10
                                       3
                                  80, 77, 78
                                     78  2

                                      1.0
                                       3
                                  80, 82, 82
                                     81  1
                             Concurrent Recoveries
                                    Forage
                                     0.01
                                       3
                                  75, 77, 78
                                     77  2

                                     0.10
                                       3
                                    83, 83
                                      83

                                      10
                                       3
                                  87, 88, 89
                                     88  1
                                    Stalks
                                     0.10
                                       1
                                      86
                                      86
                                     Grain
                                     0.01
                                       2
                                    88, 78
                                      83

                                     0.10
                                       1
                                      87
                                      87

                                      1.0
                                       1
                                      89
                                      89

                                      5.0
                                       3
                                  89, 88, 89
                                     89  1
                                    Stover
                                     0.01
                                       2
                                 60[2], 57[2]
                                      59

                                      1.0
                                       1
                                      90
                                      90

                                      20
                                       4
                                86, 86, 87, 90
                                     87  2
1. The standard deviation is not calculated for sample sizes n < 3; all statistics were calculated by the study reviewer.
2. Values outside the range of 70-120% are shown in boldface type.

Conclusions:  Adequate method validation data have been submitted for the LC/MS/MS method used for the determination of methoxyfenozide residues in the various commodities.  No additional data are required in support of this data collection method.

5.1.2	Multi-Residue Methods (860.1360)
	D249438, D249458, D251218 & D251225; W. Wassell; 27 July 1999

Data concerning the recovery of methoxyfenozide using the FDA multiresidue method protocols (PAM Volume I) were previously submitted to, and reviewed by, HED.  Methoxyfenozide was not recoverable by any of these procedures.  The data were forwarded to FDA for evaluation, and the updating of PAM Volume I.

5.1.3	Tolerance Enforcement Methods
	D358341; D. Rate; 10 June 2009

Several HPLC/UV and HPLC/MS methods are available for enforcing tolerances of methoxyfenozide in primary crops, Method TR 34-96-88, Method TR 34-98-87, Method TR 34 - 00-38, Method TR 34-00-107, Method TR 34-00-109, and Method TR 34-99-74.  Adequate method validation, radio-validation, and independent laboratory validation (ILV) data have been provided for these methods.  Successful petition method validation (PMV) trials were conducted on Methods TR 34-96-88 and TR 34-98-87, and the Biological and Economic Analysis Division's (BEAD's) Analytical Chemistry Branch (ACB) concluded that PMV trials were not required for the other methods, since they are similar to the validated methods.

For each of these methods, residues of methoxyfenozide are extracted with acidic aqueous methanol, filtered, and diluted with 10% sodium chloride.  Extracts are then purified by sequential liquid-liquid partitioning with hexane and dichloromethane (DCM).  Residues in the DCM fraction are further purified by elution through one or more of the following column types:  basic alumina, silica gel, carbon, Florisil, or C18.  Residues in the final eluate are concentrated, re-dissolved in ACN/water, and analyzed by reverse-phase HPLC using UV (240 nm) or MS (m/z 367) with external standards.  The LOQ for methoxyfenozide is 0.01-0.05 ppm, depending on the plant commodity.

An adequate enforcement method is also available for determining the ROCs in rotated crops.  Method TR 34-00-41 includes an HPLC/UV method that determines methoxyfenozide residues in high-moisture rotational crops, and an HPLC/MS method that determines residues of methoxyfenozide and its metabolites RH-117,236, RH-151,055 and RH-152,072 (determined as RH-151,055) in low-moisture rotational crops.  Adequate method validation, radio-validation, and ILV data have been submitted for this method, and ACB concluded that a PMV trial was not needed for this method owing to its similarity to Method TR 34-98-87.

5.2	Storage Stability (860.1380)
	MRIDs #48994101 to -04

Basil:  Sample storage conditions and durations are reported in Table 5.2.1, below.  Samples of basil leaves and stems (both fresh and dried) were stored frozen (-37 to -0.6°C), from sampling to extraction, for 735-806 days (24.1-26.5 months) and 735-805 days (24.1-26.4 months), respectively.  Samples were analyzed within 0-4 days of extraction.  To support the sample storage durations, a concurrent storage stability study was conducted with the field trial study; the results are presented in Table 5.2.2, below.  Stability during frozen storage was evaluated after intervals of 760 and 758 days in fresh basil and dried basil, respectively.  The data demonstrate that residues of methoxyfenozide were stable in the fresh and dried basil samples for intervals of up to 760 and 758 days (25.0 and 24.9 months) of frozen storage, respectively.  Zero-day data were not provided; IR-4 is reminded that storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage (see OCSPP 860.1380[d][6][i]).  Although the storage interval tested in the concurrent storage stability study is less than the maximum storage duration of the field trial samples, it is 94% as long as the longest actual storage duration.  These data are adequate to support the storage conditions and durations of the basil samples from the submitted field trials.

TABLE 5.2.1	Summary of Storage Conditions.
                                 Basil Matrix
                           Storage Temperature (°C)
                          Actual Storage Duration[1]
                                (Days [Months])
         Interval of Demonstrated Storage Stability[2] (Days [Months])
                            Fresh leaves and stems
                                  -37 to -0.6
                              735-806 [24.1-26.5]
                                  760 [25.0]
                            Dried leaves and stems

                              735-805 [24.1-26.4]
                                  758 [24.9]
1. Duration from sampling to extraction.  Samples were analyzed within 0-4 days of extraction.
2. Based on concurrent storage stability study.  See Table C.2.2 (below).

TABLE 5.2.2	Stability of Methoxyfenozide in Basil Matrices.
                                 Basil Matrix
                                  Spike Level
                                     (ppm)
                              Storage Interval[1]
                                    (Days)
                      Fresh Fortification Recoveries (%)
                            Recovered Residues (%)
                               Mean Recovery (%)
                           Corrected Recovery (%)[2]
                            Fresh leaves and stems
                                      1.0
                                      760
                                     85.9
                               92.5, 91.6, 92.0
                                     92.0
                                     107.1
                            Dried leaves and stems
                                      1.0
                                      758
                                     87.6
                               83.0, 83.1, 83.7
                                     83.3
                                     95.1
1. Interval from fortification to extraction.  Samples were analyzed on the day of extraction.
2. Corrected for the recovery in a freshly fortified sample; calculated by the study reviewer.

Caneberries:  Sample storage conditions and durations are reported in Table 5.2.3, below.  Berry samples were stored frozen (-20°C), from sampling to extraction for analysis, for 130-189 days (4.3-6.2 months).  Samples were analyzed within 0-1 days of extraction.  No storage stability data were provided.  Samples for a concurrent storage stability study were prepared; however, they were not analyzed because the protocol stated that analysis of these samples would be required only in the event of a freezer failure.  Existing storage stability data indicate that methoxyfenozide is stable at <=-20°C for intervals of up 629 days in citrus fruits (D396397; W.T. Drew; 2 March 2012).  In addition, freezer storage stability has been demonstrated for a period of at least 12 months in 5 diverse crops, including cottonseed (PMRA #586719), field corn grain (PMRA #586721), head lettuce (PMRA #586722), sugar beet roots (PMRA #1843187), and tomatoes (PMRA #586720).  These data are adequate to support the storage conditions and durations of the caneberry samples from the submitted field trials.

TABLE 5.2.3	Summary of Storage Conditions.
                                    Matrix
                           Storage Temperature (°C)
                  Actual Storage Duration[1] (Days [Months])
         Interval of Demonstrated Storage Stability[2] (Days [Months])
                                  Caneberries
                                      -20
                               130-189 [4.3-6.2]
                                  629 [20.6]
1. Duration from sampling to extraction.  Samples were analyzed within 0-1 days of extraction.
2. In citrus fruit (refer to D396397; W.T. Drew; 2 March 2012).

Dates:  Sample storage conditions and durations are reported in Table 5.2.4, below.  Samples of dates were stored frozen (-20°C), from sampling to extraction for analysis, for 104-131 days (3.4-4.3 months).  Samples were analyzed on the day of extraction.  To support the sample storage durations, a concurrent storage stability study was conducted with the field trial study; the results are presented in Table 5.2.5, below.  Stability during frozen storage was evaluated after an interval of 118 days.  The data demonstrate that residues of methoxyfenozide were stable in date samples for intervals of up to 118 days (3.9 months) of frozen storage.  Zero-day data were not provided; IR-4 is reminded that storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage (see OCSPP Residue Chemistry Test Guideline 860.1380[d][6][i]).  Although the storage interval tested in the concurrent storage stability study is less than the maximum storage duration of field trial samples, it is 90% as long as the longest actual storage duration.  These data are adequate to support the storage conditions and durations of date samples from the submitted field trials.

TABLE 5.2.4	Summary of Storage Conditions.
                                  Date Matrix
                              Storage Temperature
                                     (°C)
                          Actual Storage Duration[1]
                                (Days [Months])
         Interval of Demonstrated Storage Stability[2] (Days [Months])
                                  Dried fruit
                                      -20
                             104-131[3] [3.4-4.3]
                                   118 [3.9]
1. Duraton from sampling to extraction.  Samples were analyzed on the day of extraction.
2. Based on concurrent storage stability study.  See Table 5.2.5, below.
3. One of the control samples was not extracted until after 157 days of storage; all other control samples were extracted after 104-111 days of storage.

TABLE 5.2.5	Stability of Methoxyfenozide in Dates (Dried Fruit).
                                  Date Matrix
                               Spike Level (ppm)
                      Storage Interval[1] (Days [Months])
                      Procedural Recoveries [Mean] (%)[2]
                            Recovered Residues (%)
                             Mean Recovery (%)[2]
                                   Corrected
                                Recovery (%)[3]
                                  Dried fruit
                                      1.0
                                      118
                                87, 88, 81 [85]
                              0.843, 0.807, 0.884
                                      84
                                      99
1. Interval from fortification to extraction.  Samples were analyzed on the day of extraction.
2. Calculated by study reviewer.
3. Corrected for mean recovery in freshly fortified samples; calculated by the study reviewer.

Sorghum:  Sample storage conditions and durations are reported in Table 5.2.6, below.  Samples of sorghum forage, stalks, grain and stover were stored frozen (-20°C), from collection to extraction, for 573-640 days (18.8-21.0 months), 564-609 days (18.5-20.0 months), and 557-596 days (18.3-19.6 months), respectively.  Samples were analyzed within 0-3 days of extraction.  To support the sample storage durations, a concurrent storage stability study was conducted with the field trial study; the results are presented in Table 5.2.7, below.  Stability during frozen storage was evaluated after intervals of 607, 598 and 599 days in forage, grain and stover, respectively.  The data demonstrated that residues of methoxyfenozide were stable in the forage, grain and stover samples for intervals of up to 607, 598 and 599 days (19.9, 19.6 and 19.7 months), respectively.  Zero-day data were not provided; IR-4 is reminded that storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage (see OCSPP 860.1380[d][6][i]).  Although the storage intervals tested in the concurrent storage stability study are less than the maximum storage durations of field trial samples for forage/stalks and grain, they are >=95% as long as the longest actual storage duration.  These data are adequate to support the storage conditions and durations of samples from the submitted sorghum field trials.

TABLE 5.2.6	Summary of Storage Conditions.
                                Sorghum Matrix
                           Storage Temperature (°C)
                  Actual Storage Duration[1] (Days [Months])
         Interval of Demonstrated Storage Stability[2] (Days [Months])
                                 Forage/stalks
                                      -20
                              573-640 [18.8-21.0]
                                  607 [19.9]
                                     Grain

                              564-609 [18.5-20.0]
                                  598 [19.6]
                                    Stover

                              557-596 18.3-19.6]
                                  599 [19.7]
1. Duration from sampling to extraction.  Samples were analyzed within 0-3 days of extraction.
2. Based on concurrent storage stability study.  See Table 5.2.7, below.

TABLE 5.2.7	Stability of Methoxyfenozide in Sorghum Matrices.
                                Sorghum Matrix
                                  Spike Level
                                     (ppm)
                              Storage Interval[1]
                                    (Days)
                Fresh Fortification Recoveries [Average[2]] (%)
                            Recovered Residues (%)
                             Mean Recovery[2] (%)
                           Corrected Recovery[3] (%)
                                    Forage
                                      1.0
                                      607
                            89.7, 89.2, 86.1 [88.3]
                               85.7, 86.8, 86.0
                                     86.2
                                     97.5
                                     Grain
                                      1.0
                                      598
                            85.5, 85.0, 85.6 [85.4]
                               79.3, 80.7, 79.4
                                     79.8
                                     93.5
                                    Stover
                                      1.0
                                      599
                            84.1, 81.5, 83.9 [83.2]
                               83.7, 82.2, 85.2
                                     83.7
                                     100.6
1. Interval from fortification to extraction.  Samples were analyzed on the day of extraction.
2. Calculated by the study reviewer.
3. Corrected for mean recovery in freshly fortified samples; calculated by the study reviewer.

Conclusions:  There are no storage stability issues, and no corrections for potential decline during storage are needed in reviewing the residue studies submitted for the various commodities.

5.3	Residue Data

5.3.1	Crop Field Trials (860.1500)
	MRIDs #48994101 to -04

Basil:  IR-4 submitted field trial data for methoxyfenozide on basil.  A total of 5 crop field trials were conducted in the US and Canada during the 2009 growing season in NAFTA Growing Zones 2 (NC), 3 (FL), 5A (WI), 9 (NM) and 12 (BC).

Each trial consisted of one untreated (control) plot, and one plot treated with an FlC formulation of methoxyfenozide (Intrepid 2F) containing 2 lb ai/gal.  The treated plots received 4 foliar directed or broadcast applications of the FlC formulation at rates of 0.242-0.261 lb ai/A per application, with RTIs of 9-11 days, for total application rates of 0.988-1.032 lb ai/A.  Applications were made using backpack sprayers, in spray volumes of 21-43 GPA of water, using a non-ionic surfactant (NIS) as an adjuvant (0.25-0.50% v/v).  Samples of mature fresh basil (stems and leaves) were harvested at a PHI of 1 day at all trial sites.  At each trial site, additional samples were collected at a 1-day PHI, and dried (in a drying oven or forced-air dryer) for 1-7 days to generate dried basil (stems and leaves).  At one field trial, fresh basil was harvested at PHIs of 1, 3, 6 and 12 days to assess residue decline.

Following 4 foliar directed or broadcast applications of methoxyfenozide to basil at total rates of 0.988-1.032 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 9.26-47.2 (9.88-43.4) ppm in fresh basil, and 56.3-194 (60.5-188) ppm in dried basil harvested at a 1-day PHI (see Table <IP_ADDRESS>, below).  As noted previously in Section 5.1.1, one control sample at Trial NM-05 had a residue of 0.0592 ppm, which exceeded the LLMV.  However, the residues observed in the trial far exceeded this residue; therefore, this control sample had minimal to no impact on the final residue values summarized below.  In the residue decline trial, the per-trial average residues at PHIs of 1, 3, 6 and 12 days were 43.4, 14.3, 11.5 and 0.823 ppm, respectively, which demonstrated that residues decreased with longer PHIs.

TABLE <IP_ADDRESS>	Summary of Residue Data from Basil Field Trials with Methoxyfenozide.
                                Basil Commodity
                           Total Use Rate (lb ai/A)
                                   [g ai/ha]
                                  PHI (Days)
                            Residue Levels (ppm)[1]

                                       n
                                     Min.
                                     Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
                            Fresh leaves and stems
                                  0.988-1.032
                                  [1107-1157]
                                       1
                                      10
                                     9.26
                                     47.2
                                      --
                                      --
                                     19.2
                                     21.7
                                     12.3

                                       5
                                      --
                                      --
                                     9.88
                                     43.4
                                     19.2
                                     21.7
                                     12.8
                            Dried leaves and stems

                                      10
                                     56.3
                                      194
                                      --
                                      --
                                      100
                                      110
                                     44.8

                                       5
                                      --
                                      --
                                     60.5
                                      188
                                      102
                                      110
                                     47.0
1. For n = 5, values reflect per-trial averages; for n = 10, values reflect statistics for individual samples.
2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

Caneberries:  IR-4 submitted field trial data for methoxyfenozide on caneberry.  A total of 6 crop field trials on caneberry were conducted in the US during the 2010 growing season in NAFTA Growing Zones 2 (NC, blackberry), 5A (MI, blackberry), 10 (CA, blackberry) and 12 (OR, one trial on blackberry, and two trials on raspberry).  Examination of the field trial records indicates that one Field Research Director (FRD) supervised all 3 field trials at one city in OR.  Nonetheless, each trial in OR constitutes a separate trial for purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data requirements because of sufficient differences in their residue levels.  In addition, these trials differed with regard to spray volumes and crops (2 raspberry, 1 blackberry).

Each trial consisted of one untreated (control) plot, and one plot treated with Intrepid 2F.  The treated plots received 3 foliar directed applications of Intrepid 2F at rates of 0.244-0.261 lb ai/A per application, with RTIs of 6-8 days, for total application rates of 0.744-0.778 lb ai/A.  Applications were made using backpack sprayers, in spray volumes of 30.85-86.26 GPA of water, using an NIS as an adjuvant (0.01-0.13% v/v).  Samples of berries were harvested at a PHI of 3 days at all trial sites.  At one field trial, berries were harvested at PHIs of 1, 3, 6 and 13 days to assess residue decline.

Following 3 foliar directed applications of methoxyfenozide to caneberries at total rates of 0.744-0.778 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 0.62-2.5 (0.68-2.5) ppm in berries that were harvested at a 3-day PHI (see Table <IP_ADDRESS>, below).  At the residue decline trial, the per-trial average residues at PHIs of 1, 3, 6 and 13 days were 2.3, 2.2, 1.8 and 1.6 ppm, respectively, which demonstrated that residues decrease with longer PHIs.

TABLE <IP_ADDRESS>	Summary of Residue Data from Caneberry Field Trials with Methoxyfenozide.
                                   Commodity
                           Total Use Rate (lb ai/A)
                                   [g ai/ha]
                                  PHI (Days)
                            Residue Levels (ppm)[1]

                                       n
                                     Min.
                                     Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
                                  Caneberries
                                  0.744-0.778
                                   [834-872]
                                       3
                                     12[1]
                                     0.62
                                      2.5
                                      --
                                      --
                                     1.90
                                     1.70
                                     0.65

                                     6[1]
                                      --
                                      --
                                     0.68
                                      2.5
                                     1.90
                                     1.73
                                     0.67
1. For n = 6, values reflect per-trial averages; for n = 12, values reflect statistics for individual samples.  Statistics were calculated by the study reviewer.
2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

Dates:  IR-4 submitted field trial data for methoxyfenozide on dates.  A total of 3 crop field trials on dates were conducted in the US during the 2010 growing season in NAFTA Growing Zone 10 (CA).  Examination of the field trial records indicates that one Field Research Director (FRD) supervised 4 trials (all trials in the study), which were within approximately 10 miles of each other.  For purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data requirements, the Trials 10-CA22 and 10-CA23 are considered replicates of the same trial.  The other two trials are considered sufficiently different from this replicate pair, and from each other, to be considered separate trials.  The 3 trials (including one replicate pair) are considered separate trials because of sufficient differences in locations, crop varieties, and/or spray concentrations.

Each trial consisted of one untreated (control) plot, and one plot treated with Intrepid 2F.  Each plot consisted of 6 trees.  The treated plots received 3 foliar directed applications of Intrepid 2F at rates of 0.096-0.313 lb ai/A per application, with RTIs of 9-11 days, for total application rates of 0.501-0.933 lb ai/A.  Applications were made using skid pump sprayers, in spray volumes of 64.65-291 GPA of water, using an NIS, or a combined vegetable oil concentrate and silicone surfactant, as an adjuvant.  The first 2 applications at one trial, and the first application at another trial, used substantially lower application rates, reflecting application of the test substance at a rate proportional to 0.31 lb ai/A, directed to the fruit bunches to runoff.  An amendment to the protocol was made to specify an application rate of 0.31 lb ai/A as a spray directed to the tree canopy, wetting the fruit bunches to runoff.  All remaining applications in all trials were made according to this amendment.  The amendment was necessitated by the determination that the number of date bunches in the plots was lower than normal, which resulted in much less spray being applied than the target rate.  Mature date fruit was harvested at a PHI of 7 days at all trials.

Following 3 foliar directed applications of methoxyfenozide at total rates of 0.501-0.933 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 1.5-3.3 (1.6-3.1) ppm in dry fruit harvested at a 7-day PHI (see Table <IP_ADDRESS>, below).  There was no residue decline study; however, none is needed for crops such as this that require fewer than 5 total field trials.

TABLE <IP_ADDRESS>	Summary of Residue Data from Date Field Trials with Methoxyfenozide.
                                Date Commodity
                           Total Use Rate (lb ai/A)
                                  PHI (Days)
                            Residue Levels (ppm)[1]

                                       n
                                     Min.
                                     Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
                                  Dried fruit
                                  0.501-0.933
                                       7
                                       8
                                      1.5
                                      3.3
                                      1.6
                                      2.3
                                      2.0
                                      2.0
                                     0.70
1. Except for the minimum and maximum, values reflect per-trial averages; n = number of field trials; statistics were calculated by the study reviewer.
2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.
3. The number of trials equals 3 instead of 4 because trial pair 10-CA22/10-CA23 constitutes a single trial with replicate samples (for purposes of OCSPP 860.1500 data requirements).

Sorghum:  IR-4 submitted field trial data for methoxyfenozide on sorghum.  A total of 12 crop field trials on grain sorghum were conducted in the US during the 2009 growing season in NAFTA Growing Zones 2 (NC), 4 (AR), 5 (ND 3 trials; SD 1 trial), 6 (TX, 2 trials), 7 (NE), 8 (TX) and 10 (NM, 2 trials).  There was also 1 crop field trial on sweet sorghum conducted in Growing Zone 6 (TX) during the same growing season.  Examination of the field trial records indicates that one Field Research Director (FRD) supervised three trials in ND, another supervised 4 trials in TX, and another supervised 2 trials in NM, with the trials in all three sets being close to each other, with the exception of one trial in TX.  For purposes of OCSPP Residue Chemistry Test Guideline 860.1500 data requirements, the trials in all three sets are considered to be separate because of sufficient differences in their residue levels for at least one of the sorghum commodities.  In addition there were differences between trials in some of the sets regarding crop variety, adjuvant class, application spray volume, and irrigation type.

Each trial consisted of one untreated (control) plot, and one plot treated with Intrepid 2F.  The treated plots received 4 foliar broadcast (11 trials) or foliar directed (2 trials) applications of Intrepid 2F at rates of 0.117-0.127 lb ai/A per application, with RTIs of 9-14 days, for total application rates of 0.478-0.494 lb ai/A.  Applications were made using ground equipment with CO2 or compressed air as the propellant, in spray volumes of 8-49 GPA of water, using an NIS or a crop oil concentrate (COC) as an adjuvant.  In the grain sorghum trials, forage was harvested at PHIs of 2-4 days; grain was harvested at PHIs of 11 days (one trial only) or 21-23 days, and was allowed to dry for 0-5 days prior to collection; and stover was harvested at PHIs of 21-23 days, and was allowed to dry for 1-9 days prior to collection.  In one field trial, additional samples of forage were harvested at PHIs of 0, 7, 11 and 14 days to assess residue decline.  In the sweet sorghum trial, stalks were harvested at a PHI of 3 days.

Following 4 foliar broadcast or directed applications of methoxyfenozide to grain sorghum at total rates of 0.478-0.494 lb ai/A, residues (and per-trial averages) of methoxyfenozide were 0.70-5.6 (0.77-5.0) ppm in sorghum forage harvested at a PHI of 2-4 days, 0.15-2.6 (0.15-2.3) ppm in sorghum grain harvested at a PHI of 11-23 days, and 0.29-9.7 (0.45-7.6) ppm in sorghum stover harvested at a PHI of 21-23 days (see Table <IP_ADDRESS>, below).  Following 4 foliar broadcast applications of methoxyfenozide to sweet sorghum (only 1 trial) at a total rate of 0.481 lb ai/A, residues (and per-trial average) of methoxyfenozide were 0.045-0.18 (0.11) ppm in sorghum stalks harvested at a PHI of 3 days.  In the residue decline trial, the per-trial average residues in grain sorghum forage harvested at PHIs of 0, 4, 7, 11 and 14 days were 6.2, 4.5, 2.6, 3.6 and 2.6 ppm, which demonstrated a residue decline during the first 7 days, with no further decline.

TABLE <IP_ADDRESS>	Summary of Residue Data from Sorghum Field Trials with Methoxyfenozide.
                                Sorghum Matrix
                                   Total Use
                                Rate (lb ai/A)
                                  PHI (Days)
                            Residue Levels (ppm)[1]

                                       n
                                     Min.
                                     Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                 Std. Dev.[3]
                                 Grain Sorghum
                                    Forage
                                  0.478-0.494
                                      2-4
                                      12
                                     0.70
                                      5.6
                                     0.77
                                      5.0
                                     2.15
                                     2.76
                                     1.45
                                     Grain

                                   11; 21-23
                                      12
                                     0.15
                                      2.6
                                     0.15
                                      2.3
                                     0.40
                                     0.72
                                     0.72
                                    Stover

                                     21-23
                                      12
                                     0.29
                                      9.7
                                     0.45
                                      7.6
                                     2.95
                                     3.18
                                     2.39
                                 Sweet Sorghum
                                    Stalks
                                     0.481
                                       3
                                       1
                                     0.045
                                     0.18
                                     0.11
                                     0.11
                                     0.11
                                     0.11
                                      NA
1. Except for the minimum and maximum, values reflect per-trial averages; n = number of field trials.
2. LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.
3. NA = Not Applicable (the standard deviation is not calculated for sample sizes n < 3).

Conclusions:  The submitted crop field trial data are adequate, and support the establishment of permanent tolerances in the various basil, caneberry, date and sorghum commodities, as listed in Table 6.0 (see Section 6.0).

5.3.2	Field Rotational Crops (860.1900)

Label directions for methoxyfenozide (Intrepid 2F) currently specify that crops with registered uses may be replanted at any time, and all other food or feed crops may be replanted 7 days after the last application.  Adequate limited and extensive rotational crop field trials are available that support these rotational crop restrictions.

Because the maximum seasonal use rate being proposed for dates and herbs (1.0 lb ai/A) is the same as for other registered field and vegetable crops, no changes are required in the current rotational crop restrictions.

The petitioner has proposed inadvertent tolerances in oilseed crops (the rapeseed subgroup 20A, and the sunflower subgroup 20B), based upon HED's review of existing rotational crop data, and subsequent Agency recommendations.

5.3.3	Processed Food and Feed (860.1520)
	MRIDs #48994102

IR-4 submitted a processing study for methoxyfenozide on grain sorghum and sweet sorghum.  Two sorghum field trials were conducted in NAFTA Growing Zones 6 (TX; sweet sorghum) and 7 (NE; grain sorghum) during the 2009 growing season.  At these trials, Intrepid 2F was applied to sorghum as 4 foliar broadcast applications at rates of 0.119-0.121 lb ai/A per application, with RTIs of 9-11 days, for a total application rate of 0.481 lb ai/A.  Applications were made using ground equipment (boom sprayers), in a spray volume of 15-21 GPA of water, containing an NIS as an adjuvant.

Bulk samples of the RACs, sweet sorghum stalks, and sorghum grain, were collected at PHIs of 3 and 21 days, respectively.  The RACs were processed within 56-80 days of harvest into sorghum AGF, and sweet sorghum syrup, using simulated commercial procedures.

Samples of sorghum stalks and grain, and the processed sorghum commodities, were analyzed for residues of methoxyfenozide via LC/MS/MS using a slight modification of Dow AgroSciences Method GRM 02.25.  The petitioner used the LLMV of 0.01 ppm as the limit for reporting residues of methoxyfenozide in sorghum commodities.  The method was adequate for data collection, based on acceptable method validation and concurrent recovery data.  No residues of methoxyfenozide equal to or above the LLMV were detected in any control samples.

Samples of sorghum stalks and grain were stored frozen, from harvest to extraction, for 21.0 and 19.4 months, respectively.  Samples of sorghum AGF and syrup were stored frozen from collection until extraction, for 16.7 and 18.4 months, respectively.  Samples were analyzed on the day of extraction.  Storage stability data generated concurrently with the study demonstrated that residues of methoxyfenozide were stable in sorghum forage, grain, AGF and syrup for up to 19.9, 19.6, 17.3 and 18.4 months), respectively.  Although the storage interval for forage tested in the concurrent storage stability study is shorter than the storage duration for stalks in the processing study, it is 95% as long as the actual storage duration. These data are adequate to support the storage conditions and durations of samples from the submitted sorghum processing study.

Residues of methoxyfenozide were 1.1 and 0.48 ppm in sorghum stalks and grain (RACs) harvested at PHIs of 3 and 21 days, respectively, following the last of 4 foliar broadcast applications of Intrepid 2F at a total rate of 0.481 lb ai/A.  Residues of methoxyfenozide were 1.1 and 17 ppm in sorghum syrup and sorghum AGF, respectively (see Table 5.3.3, below).   These data indicate that methoxyfenozide did not concentrate in sweet sorghum syrup (1X processing factor), but did concentrate in sorghum AGF (35X processing factor).

A maximum theoretical concentration factor for sorghum is not provided in OCSPP Residue Chemistry Test Guideline 860.1520.

TABLE 5.3.3	Residue Data from Sorghum Processing Study with Methoxyfenozide.
                               Sorghum Commodity
                             Total Rate (lb ai/A)
                                  PHI* (Days)
                                Residues (ppm)
                               Processing Factor
                                  Stalk (RAC)
                                     0.481
                                       3
                                      1.1
                                      --
                                     Syrup

                                      1.1
                                      1X
                                  Grain (RAC)
                                     0.481
                                      21
                                     0.48
                                      --
                                      AGF

                                      17
                                      35X
* PHI = Pre-Harvest Interval.

Conclusions:  The submitted sorghum processing study data are adequate, and support a tolerance of 120 ppm in (sorghum) AGF.  This will be reflected in an increase of the currently established tolerance in AGF, from 2.0 to 120 ppm.  A tolerance in sweet sorghum syrup is not required.

5.3.4	Meat, Milk, Poultry and Eggs (860.1480)

No livestock feeding studies were submitted with this petition.  Previously, the maximum reasonably balanced dietary (MRBD) burdens of methoxyfenozide to livestock were estimated by HED to be 35 ppm for beef cattle, 54 ppm for dairy cattle, 7.7 ppm for poultry, and 0.2 ppm for swine.  Because the proposed tolerances for this action include an increase of the tolerance in sorghum grain, the projected MRBD burdens have been reassessed.  The revised values were determined to be 38 ppm for beef cattle, 55 ppm for dairy cattle, 12 ppm for poultry, and 5 ppm for swine.  The revised dietary burdens are presented in Table 5.3.4 (below).

These estimated dietary burdens result in anticipated residues that do not exceed the tolerances that are currently established in livestock commodities.

TABLE 5.3.4	Calculation of Maximum Reasonably Balanced Dietary Burdens of Methoxyfenozide Residues to Livestock.
                                   Feedstuff
                                    Type[1]
                                % Dry Matter[2]
                                   % Diet[2]
                          Established Tolerance (ppm)
                         Dietary Contribution (ppm)[3]
                                  Beef Cattle
Alfalfa hay
                                       R
                                      89
                                      15
                                      150
                                     25.28
Field corn grain
                                      CC
                                      88
                                      35
                                     0.05
                                     0.020
Soybean AGF
                                      CC
                                      85
                                       5
                                      160
                                     9.412
Sorghum grain
                                      CC
                                      86
                                      40
                                      6.0
                                     2.790
Soybean seed
                                      PC
                                      89
                                       5
                                     1.00
                                     0.056
                                 TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     37.6
                                 Dairy Cattle
Grass forage
                                       R
                                      25
                                      25
                                      18
                                     18.00
Alfalfa hay
                                       R
                                      35
                                      20
                                      150
                                     33.71
Sorghum grain
                                      CC
                                      86
                                      45
                                      6.0
                                     3.135
Undelinted cotton seed
                                      PC
                                      88
                                      10
                                     2.00
                                     0.227
                                 TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     55.1
                                    Poultry
Sorghum grain
                                      CC
                                      86
                                      75
                                      6.0
                                     4.500
Alfalfa meal[4]
                                      PC
                                      89
                                       5
                                      150
                                     7.500
Soybean meal[4]
                                      PC
                                      92
                                      20
                                     1.00
                                     0.200
                                 TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     12.2
                                     Swine
Sorghum grain
                                      CC
                                      86
                                      80
                                      6.0
                                     4.800
Field corn grain
                                      CC
                                      88
                                       5
                                     0.05
                                     0.043
Soybean meal [4]
                                      PC
                                      92
                                      15
                                     1.00
                                     0.150
                                 TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     4.99
1. R = Roughage; CC = Carbohydrate Concentrate; PC = Protein 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; contribution = ([tolerance] X % diet) for poultry and swine.
4. Residues in alfalfa meal are based on the tolerance in alfalfa hay, and residues in soybean meal are based on the tolerance in soybean seeds.

Conclusions:  Reassessment of the currently established livestock tolerances is not required for this petition.

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 methoxyfenozide are expected to occur at moderate (up to 6.0 ppm in caneberries and sorghum grain) to high levels (up to 400 ppm in dried herbs) from the new uses proposed in the current action.

6.0	  Tolerance Derivation
In fresh herbs, subgroup 19A (except chives), the petitioner proposed a tolerance of 70 ppm, based on OECD's tolerance calculation procedure.  The petitioner entered all 10 individual sample residues into the MRL calculator.  When the average residues from each of the 5 basil field trials were entered, as the OECD guidance stipulates, the resulting recommended tolerance would be 80 ppm.  In dried herbs, subgroup 19A (except chives), the petitioner proposed a tolerance of 400 ppm, based on OECD's tolerance calculation procedure.  However, the Agency has determined that setting separate subgroup 19A tolerances in fresh and dried commodities is not feasible from a regulatory perspective.  Therefore, HED recommends setting the tolerance in the entire subgroup 19A (both fresh and dried commodities), except chives, at the higher level of 400 ppm.

In caneberries, subgroup 13-07A, the petitioner proposed a tolerance of 6.0 ppm, based on the OECD's tolerance calculation procedure.  HED concurs with the proposed tolerance.

In dates, the petitioner proposed a tolerance of 7.0 ppm, based on 4 date field trials and the OECD's tolerance calculation procedure.  However, HED determined that only 3 of the trials were truly independent.  The 4 sample residues from the 2 trials deemed to be non-independent were averaged together as one input into the MRL calculator.  Also, the total application rate at one of the other trials was only half the proposed maximum seasonal use rate, a difference of >25%.  Ergo, the residue values from this trial were doubled, per OECD's preliminary guidance on proportionality of sample residues to application rate (ChemSAC meeting; 28 March 2012).  When the average of these residues, along with the average residues from each of the other 2 field trials were entered into the MRL calculator, the resulting recommended tolerance was 8.0 ppm.

In sorghum commodities, the petitioner proposed tolerances of 9.0, 15 and 4.0 ppm in the forage, stover and grain, respectively, of both grain and sweet sorghum, and 9.0 ppm in sweet sorghum stalks, based on OECD's tolerance calculation procedure.  A tolerance of 80 ppm in sorghum AGF was proposed, based on the sorghum processing study.  However, the total application rate at the sorghum field trials was only two thirds the proposed maximum seasonal use rate, a difference of >25%.  Ergo, the residue values from the trials were increased by half, per OECD's preliminary guidance on proportionality (ChemSAC meeting; 28 March 2012).  When these values were entered into the MRL calculator, the resulting recommended tolerances were 15, 20 and 6.0 ppm in the forage, stover and grain, respectively, of both grain and sweet sorghum, and 15 ppm in sweet sorghum stalks.  Similarly, when the HAFT from the sorghum field trials (2.25 ppm) was increased by half, and multiplied by the AGF processing factor (35X), the resulting recommended tolerance was 120 ppm in sorghum AGF.

Instead of the proposed tolerances in the various tropical tree fruits (0.6 ppm), HED recommends establishing the tolerances at 0.60 ppm, in order to avoid the situation where a field sample containing residues significantly above the tolerance (0.64 ppm, for example) would be considered non-violative.  For the same reason, HED recommends that the proposed tolerance of 0.5 ppm in subgroup 6C (except blackeyed and southern peas) be revised to 0.50 ppm.

The rationales for the establishment and deletion of other tolerances associated with the current action are listed in Table 6.0, 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.

TABLE 6.0	Tolerance Derivation for Methoxyfenozide.
                                   Commodity
                           Existing Tolerance (ppm)
                          Recommended Tolerance (ppm)
                   Correct Commodity Definition.  Rationale
                                 180.544[a][1]
Herb subgroup 19A, fresh, except chives
                                     None
                                      400
Herb subgroup 19A, except chive.  Based on submitted dried basil field trial data.
Herb subgroup 19A, dried, except chives
                                     None

Date
                                     None
                                      8.0
Based on submitted crop field trial data.
Caneberry subgroup 13-07A
                                     None
                                      6.0

Sorghum, grain, forage
                                     None
                                      15

Sorghum, grain, stover
                                     None
                                      20

Sorghum, grain, grain
                                     None
                                      6.0

Sorghum, sweet, forage
                                     None
                                      15

Sorghum, sweet, stover
                                     None
                                      20

Sorghum, sweet, grain
                                     None
                                      6.0

Sorghum, sweet, stalk
                                     None
                                      15

Grain, aspirated grain fractions
                                      2.0
                                      120
Based on sorghum field trial and processing study data.
Pea and bean, dried shelled, except soybean, subgroup 6C, except pea, blackeyed, seed and pea, southern, seed
                                     None
                                     0.50
To harmonize with Codex MRLs.
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                     None
                                      1.0
Translated from grape data.
Berry, low growing, subgroup 13-07G, except cranberry
                                     None
                                      2.0
Translated from strawberry data, and raised to harmonize with Codex MRL in strawberries.
Fruit, pome, group 11-10
                                     None
                                      2.0
Update of group 11, and raised to harmonize with Codex MRL in apples.
Vegetable, fruiting, group 8-10
                                     None
                                      2.0
Update of group 8.
Sugar apple
                                     None
                                     0.60
Translated from avocado data.
Cherimoya
                                     None
                                     0.60

Atemoya
                                     None
                                     0.60

Custard apple
                                     None
                                     0.60

llama
                                     None
                                     0.60

Soursop
                                     None
                                     0.60

Biriba
                                     None
                                     0.60

Pea, blackeyed, seed
                                      4.0
                                      4.0
Keep as exceptions to subgroup 6C.
Pea, southern, seed
                                      4.0
                                      4.0

Coriander, leaves
                                      30
                                    Remove
Covered under subgroup 19A tolerance.
Grape
                                      1.0
                                    Remove
Covered under subgroup 13-07F tolerance.
Strawberry
                                      1.5
                                    Remove
Covered under subgroup 13-07G tolerance.
Okra
                                      2.0
                                    Remove
Covered under group 8-10 tolerance.
Pea, dry seed
                                      2.5
                                    Remove
Covered under subgroup 6C tolerance.
Bean, dry, seed
                                     0.24
                                    Remove

                                  180.544[b]
Sorghum, grain, forage
                                      30
                                    Remove
Expired time-limited tolerances.
Sorghum, grain, stover
                                      60
                                    Remove

Sorghum, grain, grain
                                     0.05
                                    Remove

                                 180.544[d][2]
Herb and spice, group 19, except coriander, leaves
                                      4.5
                                    Remove
Replaced by the primary crop tolerance in subgroup 19A, except chive, and rotational crop tolerances in chive and subgroup 19B.
Spice subgroup 19B
                                     None
                                      4.5
These replace the rotational crop tolerance in group 19, except coriander leaves.
Chive
                                     None
                                      4.5

Rapeseed subgroup 20A
                                     None
                                      1.0
Based on existing rotational crop data, and HED's previous recommendation.
Sunflower subgroup 20B
                                     None
                                      1.0

Attachments

Attachment 1:  International Residue Limit Status sheet.
Attachment 2:  OECD MRL (Tolerance) Assessment Calculations.

Attachment 1:  International Residue Limit Status.

                       Methoxyfenozide (PC Code 121027)
      Summary of US Tolerances, and International Maximum Residue Limits.
                              Residue Definitions
                             US (40CFR §180.544)

                                    Canada
                                     Codex
Plants:  Methoxyfenozide (3-methoxy-2-methylbenzoic acid 2-(3,5-dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide).

Livestock:  Combined residues of methoxyfenozide and its glucuronide metabolite, RH-141,518 (3-[2-(1,1-dimethylethyl)-2-(3,5-dimethylbenzoyl)-hydrazino]carbonyl-2-methylphenyl- β-D-glucopyranuronic acid).
Plants/Livestock:  Methoxyfenozide (3-methoxy-2-methylbenzoic acid 2-(3,5-dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide).

Livestock kidney/liver: Methoxyfenozide, and its metabolite, 3-{[2-(1,1-dimethylethyl)-2-(3,5-dimethylbenzoyl)-
hydrazino]carbonyl}-2-methylphenyl- β-D-glucopyranuronic acid.
Methoxyfenozide (the residue is fat-soluble, but is not classified as fat-soluble with respect to its distribution in milk).

                                 Commodity[2]
                              Tolerance (ppm)[3]
                                   Commodity
                                  MRL (mg/kg)
                                   Commodity
                                  MRL (mg/kg)
Herb subgroup 19A, except chive
                                      400
Fresh Chinese chive
                                       5

Fresh chive

Date
                                      8.0

Caneberry subgroup 13-07A
                                      6.0

Sorghum, grain, forage
                                      15

Sorghum, grain, stover
                                      20

Sorghum, grain, grain
                                      6.0

Sorghum, sweet, forage
                                      15

Sorghum, sweet, stover
                                      20

Sorghum, sweet, grain
                                      6.0

Sorghum, sweet, stalk
                                      15

Grain, aspirated grain fractions
                                      120

Pea and bean, dried shelled, except soybean, subgroup 6C, except pea, blackeyed, seed and pea, southern, seed
                                     0.50

Bean, dry, seed
                                      0.5
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                      1.0

Grape
                                       1
Berry, low growing, subgroup 13-07G, except cranberry
                                      2.0

Strawberry
                                       2
Fruit, pome, group 11-10
                                      2.0
Apples, crabapples, loquats, mayhaws, oriental pears, pears, quinces
                                      1.5
Pome fruits
                                       2
Vegetable, fruiting, group 8-10
                                      2.0

Peppers, tomato
                                       2
Sugar apple
                                     0.60

Cherimoya
                                     0.60

Atemoya
                                     0.60

Custard apple
                                     0.60

llama
                                     0.60

Soursop
                                     0.60

Biriba
                                     0.60

Pea, blackeyed, seed
                                      4.0

Pea, southern, seed
                                      4.0

Rapeseed subgroup 20A
                                      1.0

Sunflower subgroup 20B
                                      1.0

Completed:  M. Negussie, 7 May 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.

Attachment 2:  OECD MRL (Tolerance) Assessment Calculations.

Basil (Dried)

Residues (ppm)
                                    92.000
                                    102.000
                                    188.000
                                    60.500
                                    109.000

                                Methoxyfenozide

                                  Dried basil

                                      USA

                             1 lb ai/A, 1-day PHI

Total number of data (n)
                                       5

Percentage of censored data
                                      0%

Number of non-censored data
                                       5

Lowest residue
                                    60.500

Highest residue
                                    188.000

Median residue
                                    102.000

Mean
                                    110.300

Standard deviation (SD)
                                    47.230

Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                    188.000

- Mean + 4 SD
                                    299.221

- CF x 3 Mean
                                    330.900

Unrounded MRL
                                    330.900

Rounded MRL
                                      400

 High uncertainty of MRL estimate.

[Small dataset]