Document ID: EPA-HQ-OPP-2012-0420-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-12-27T05:00Z

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

MEMORANDUM

Date:	02-May-2013

Subject:	Indoxacarb.  Petition for the Establishment of Permanent Tolerances and Registration for Use on Dry Bean, Snap Bean, Small Fruit Vine Climbing Subgroup (except kiwifruit) 13-07F and Low Growing Berry Subgroup (except strawberry) 13-07H.  Summary of Analytical Chemistry and Residue Data.

PC Code:  067710 
DP Barcode:  D408982
Decision No.: 464583
Registration No.:  352-579 and 352-638
Petition No.: 2E8029 
Regulatory Action:  New Tolerance
Risk Assessment Type:  NA
Case No.:  NA
TXR No.:  NA
CAS No.:  173584-44-6
MRID No.:  48788901 and 48788902
40 CFR: §180.564

From:	Ideliz Negrón-Encarnación, Ph.D., Chemist
	   Risk Assessment Branch V
	Health Effects Division (HED; 7509P)

Through:	Danette Drew, Senior Chemist
	   Risk Assessment Branch V
	Health Effects Division (HED; 7509P)

To: 	Laura Nollen, Risk Manager Reviewer
	Risk Management Division (7505P)

                               Table of Contents

1.0	Executive Summary	3
2.0	Regulatory Recommendations	4
2.1	Data Deficiencies/Data Needs	5
2.2	Tolerance Considerations	5
2.2.1	Enforcement Analytical Method	5
2.2.2	Recommended Tolerances	5
2.2.3	Revisions to Petitioned-For Tolerances	6
2.2.4	International Harmonization	6
3.0	Introduction	7
3.1	Chemical Identity	8
3.2	Physical/Chemical Characteristics	8
3.3	Pesticide Use Pattern/Directions for Use (860.1200)	9
4.0	Metabolite/Degradate Residue Profile	11
4.1	Nature of the Residue	11
4.1.1 	Summary of Plant Metabolism (860.1300)	11
4.1.3	Summary of Confined Rotational Crops (860.l850)	12
4.3	Residues of Concern Summary and Rationale	12
5.0	Residue Profile	13
5.1	Residue Analytical Methods (860.1340)	13
5.1.1	Data Collection Methods	13
5.1.2	Multi-Residue Methods (860.1360)	14
5.1.3	Tolerance Enforcement Methods	14
5.1.4	Submittal of Analytical Reference Standards (860.1650)	16
5.2	Storage Stability (860.1380)	16
5.3	Residue Data	17
5.3.1	Crop Field Trials (860.1500)	17
5.3.2	Field Rotational Crops (860.1900)	20
5.3.3	Processed Food and Feed (860.1520)	20
5.3.4	Meat, Milk, Poultry and Eggs (860.1480)	20
5.3.5.	Food Handling (860.1460)	21
5.3.6	Water, Fish, and Irrigated Crops (860.1400)	21
6.0	Tolerance Derivation	21
Appendix A.  International Residue Limits Table	22
Appendix B.  OECD MRL Calculation Procedure Inputs/Outputs	23
Appendix C.  Highest/average residues of indoxacarb in feedstuff commodities	28

  
1.0	Executive Summary

Indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl] amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate, is an insecticide active ingredient (ai) developed by DuPont for the control of lepidopteran pests on fruit, vegetable, and field crops.  IR-4 has submitted field trial data in support of a petition proposing tolerances for the use of Avaunt(R) and Steward[(R)] EC on dried beans, and Avaunt[(R)] on snap beans.  In addition, registration (Avaunt[(R)]) and subgroup tolerances for small fruit vine climbing subgroup (except kiwifruit) 13-07F and low growing berry subgroup (except strawberry) 13-07H are proposed based on the current tolerances for grapes and cranberry, respectively.  

Permanent tolerances are established under 40 CFR 180.564(a) for the combined residues of indoxacarb and its inactive R-enantiomer on a number of plant as well as livestock commodities.  The Interregional Research Project No. 4 (IR-4) has submitted Petition No. 2E8029 requesting new crop uses of indoxacarb.  In this petition, IR-4 is proposing that permanent tolerances for residues of indoxacarb be established in/on the following raw agricultural commodities (RACs):   

      Bean, dry, seed ...................................................................... 0.07 ppm
      Bean, succulent .................................................................... 0.64 ppm
      Bean, forage ......................................................................... 37 ppm
      Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F ........ 2.0 ppm
      Low growing berry, except strawberry, subgroup 13-07H..................... 0.9 ppm

Avaunt[(R)] Insecticide (EPA Reg. No. 352-597) is a water-dispersible granular (WDG) product which contains 30% of the indoxacarb ai by weight.  The prescribed use will allow broadcast foliar treatments to be made at the maximum rate of 0.11 lb ai/A/application using ground or aerial equipment, for a combined total of 0.44 lb ai/A/season for dry beans, snap beans and low growing berry subgroup 13-07H and 0.22 lb ai/A/season for small fruit vine climbing subgroup 13-07F. A specified minimum retreatment interval (RTI) of 7days is proposed for all crops except small fruit vine climbing subgroup 13-07F which has a RTI of 21-days. The preharvest intervals (PHIs) are 3-days for snap beans, 7-days for dry beans and small fruit vine climbing subgroup 13-07F, and 30 days for low growing berry subgroup 13-07H.  In situations where it can be difficult to achieve adequate coverage, the proposed label specifies that an adjuvant may be used to improve performance.   

The dry bean and snap bean field trial studies were carried out using different analytical procedures to determine the combined residues of indoxacarb and its R-enantiomer.  However, both methods were adapted from the DuPont method (DuPont Report No. AMR 2712-93), dated Aug. 08, 1997, titled, "Analytical Enforcement Method (HPLC/Column Switching/UV) for the Determination of Residues of DPX-KN128 (S-enantiomer) and IN-KN127 (R-enantiomer) in Crops." Both methods were adequately validated in conjunction with the sample analyses.  The validated LOQs for residues of indoxacarb were 0.01 ppm for dry bean and snap bean, and 0.03 ppm for snap bean foliage.

Provided that label revisions are made, the field trial data submitted for this petition are adequate to support the proposed use of indoxacarb on dry bean, and snap bean.  A representative number of tests were conducted in the appropriate geographic regions.  Applications were made at the proposed maximum seasonal use rate following the recommended RTI and PHI specified for each crop in the corresponding label.  Samples were all analyzed using adequate analytical methods with sample holding intervals supported by storage stability data generated concurrently with each field trial study.  Tolerances were recommended based on OECD calculation procedures and harmonization considerations, see Table 2.2.2.  In addition, the existing grape and cranberry residue data are adequate to support tolerances for the small fruit vine climbing subgroup 13-07F and low growing berry subgroup 13-07H, respectively.  The residue data for grapes and cranberries were used to recommend new tolerances following OECD calculation procedures and harmonization considerations.  

Data requirements for rotational crops have already been fulfilled in earlier actions made to obtain the prior registered crop uses of indoxacarb.  In accordance, the current plant-back restrictions on the label remain adequate.

The residue data for bean, snap, forage can be used to establish a tolerance for cowpea, forage which is a dairy cattle feedstuff.  HED is recommending a tolerance be established for residues of indoxacarb on cowpea hay; a tolerance for cowpea hay was not proposed. Dietary burden calculations previously performed for dairy cattle made use of tolerance level residues and dietary contribution from feedstuff commodities that lead to conservative dietary burden estimates (S. Levy, D276516, 30-May-2002).  The current dietary burden estimate for dairy cattle covers the proposed new uses of indoxacarb and existing tolerances for ruminant commodities are not underestimated.  However, dietary burden calculations for beef cattle, dairy cattle and poultry should be revisited during registration review to re-evaluate the existing tolerances.  

2.0	Regulatory Recommendations

Pending the revision of Sections B and F, there are no residue chemistry deficiencies that preclude granting an unconditional registration of indoxacarb for use on dry bean, snap bean, small fruit vine climbing subgroup 13-07F and low growing berry subgroup 13-07H.  The proposed use-pattern and supporting data are sufficient to support permanent tolerances for the combined residues of the insecticide indoxacarb and its R-enantiomer in/on:       

      Bean, dry.............................................................................. 0.2 ppm
      Bean, succulent.................................................................... 0.9 ppm
      Cowpea, forage ..................................................................... 50 ppm
      Cowpea, hay ....................................................................... 100 ppm
      Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F ........ 2 ppm
      Low growing berry, except strawberry, subgroup 13-07H..................... 1 ppm

A human health risk assessment for indoxacarb will be prepared as a separate document.
 
860.1200 Directions for Use

The new label directions are adequate for an evaluation of the residue data to be made relative to the proposed new uses.  However, recommendations to clarify discrepancies or add specificity should be considered, see section 2.3.

860.1550 Proposed Tolerances

A revised Section F must be submitted according to Table 2.2.2. 

2.1	Data Deficiencies/Data Needs

No data deficiencies/needs associated with the current petition would preclude granting registration.  However, residue data for cowpea, hay is not available at this time.  This data is required to determine if a tolerance and dietary burden re-evaluation is needed.

860.1500 Crop Field Trials

Residue data depicting residues in/on cowpea, hay.

2.2	Tolerance Considerations

2.2.1	Enforcement Analytical Method

Two High Performance Liquid Chromatograph/Ultraviolet Detection (HPLC/UV) methods, DuPont protocols AMR 2712-93 and DuPont-11978, are available for enforcing tolerances established on crops.  The methods limits of quantitation (LOQs) are within 0.01 to 0.05 ppm for a variety of plant commodities.  A third Gas Chromatograph/Mass-Selective Detection (GC/MSD) procedure, DuPont method AMR 3493-95 Supplement No. 4, is also available for the confirmation of residues in plants.  Adequate validation and concurrent recovery data was submitted for indoxacarb in/on dry beans and snap beans using a method similar to AMR 2712-93.  In addition, method AMR 3493-95 was used for determining residues in cranberries and grapes.  Based on this, the enforcement methods available are adequate for enforcing tolerances for indoxacarb in/on snap bean, dry bean, small fruit vine climbing subgroup 13-07F, and low growing berry subgroup 13-07H.  

2.2.2	Recommended Tolerances

HED recommends that 40 CFR be amended by establishing tolerances for the plant commodities listed in the Table 2.2.2.  Tolerances for livestock commodities and rotational crops are not needed to support the proposed uses of indoxacarb.  The tolerances for plant commodities should be defined as follows:

Table 2.2.2.  Tolerance Summary for Indoxacarb.
Commodity
                     Established/Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                    Comments (correct commodity definition)
Bean, dry, seed
                                     0.07
                                      0.2

Pea, southern, seed
                                      0.1
                                    Remove

Bean, succulent
                                     0.64
                                      0.9

Bean, forage
                                      37
                                      50
Cowpea, forage
Cowpea, hay
                                      NA
                                      100

Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                      2.0
                                       2

Low growing berry, except strawberry, subgroup 13-07H
                                      0.9
                                       1

Cranberry
                                     0.90
                                    Remove

Grape
                                      2.0
                                    Remove

2.2.3	Revisions to Petitioned-For Tolerances

The proposed tolerances are different from those recommended by the HED.  The tolerances recommended by the HED were established by using the Organization for the Economical Cooperation and Development (OECD) calculation procedures while the registrant used the North America Free Trade Agreement (NAFTA) calculation procedures.  In addition, the tolerance for dry beans covers the southern pea variety (cowpea) which already has a tolerance established in the CFR.  Since the forage of cowpea are the only significant feedstuff associated with beans, the correct commodity definition would be cowpea, forage instead of bean, forage.  In order to harmonize with the Codex MRL for cowpea (see discussion below), the tolerance for dry bean obtained by the OECD calculation procedures (0.06 ppm) will be increased to 0.2 ppm.  The registrant should submit a revised Section F in which the proposed tolerances are the same as those recommended by the HED.

2.2.4	International Harmonization

U.S. tolerances are recommended for dry beans, succulent beans, small fruit vine climbing subgroup 13-07F, and low growing berry subgroup 13-07H based on residues of indoxacarb and its R-enantiomer.  Maximum residue limits (MRLs) have not been established by Canada or Mexico.  However, Codex has established MRLs for grapes (2 ppm), dry grapes (5.0 ppm), cranberries (1ppm), dry chick-pea (0.2 ppm), dry mung bean (0.2 ppm), and dry cowpea (0.1 ppm) based on measurement of indoxacarb and its R-enantiomer.  The U.S. tolerances for raisins (5.0 ppm) and cranberries (1 ppm) are harmonized with the corresponding Codex MRLs.  The U.S. tolerance for grapes (subgroup 13-07F) obtained with the OECD calculator (3 ppm) is higher than the Codex MRL for grapes (2 ppm).  Since the U.S. crop field trial data for grapes show that the highest residue is 1.74 ppm and the registrant proposed tolerance is 2.0 ppm (based on the NAFTA calculator procedures), HED understand that establishing a tolerance of 2 ppm is appropriate for this case and will allow harmonization with Codex.  The tolerance for dry bean (0.06 ppm) obtained by the OECD calculation procedures will be increased to 0.2 ppm in order to harmonize with the Codex MRL for dry check pea and dry mung bean and cover the MRL for dry cowpea.  

2.3	Label Recommendations

The new label directions are adequate in allowing for an evaluation of the residue data to be made relative to the proposed new uses.  The following are recommendations to clarify discrepancies or add specificity.  
   * Under the application instructions (page 3 of Avaunt[(R)] label) include dry bean in the sentence: "For bushberry, cranberry, dry bean, pome and stone fruit the minimum interval between treatments is 7 days."  
   * Under the tabulated instructions (page 6 of Avaunt[(R)] label and page 5 of Steward[(R)] EC label) for dry bean and/or succulent bean edit the sentence "Make a uniform application in approximately 20-100 gallons of water per acre" to specify the volume for ground and/or aerial applications.

3.0	Introduction

Indoxacarb is an oxadiazine insecticide (Group 22) used for controlling the larval stages of lepidopteran pests on a variety of fruit, vegetable, and field crops.  It is a reduced-risk insecticide registered to Dupont as the Avaunt[(R)] (EPA Reg. No. 352-597, WDG formulation) and Steward(R) EC (EPA Reg. No. 352-638, emulsifiable concentrate formulation) end-use products.  These end-use formulations contain an isometric mixture of indoxacarb (insecticidally active S-enantiomer; DPX-KN128) + its R-enantiomer (insecticidally inactive; IN-KN127); however, the percentage of ai listed on the labels and the labeled use rates for each crop are based only on the amount of indoxacarb.

As an alternative to organophosphate insecticides, indoxacarb works by blocking the sodium channels in the insect nervous system through ingestion and contact routes.  Applications are to be made at the labeled use rates when insect populations reach locally determined economic thresholds.  Follow-up treatments should be made as needed to control insect populations for the purposes of forming a comprehensive integrated pest management program.  Permanent tolerances are established under 40 CFR 180.564(a) for the combined residues of indoxacarb and its inactive R-enantiomer.  Plant commodities specified for tolerance enforcement range at levels from 0.01 ppm in/on peanuts and potatoes up to 50.0 ppm for alfalfa hay.  Tolerances are also established for several livestock commodities which range at levels from 0.03 ppm in meat byproducts up to 4.0 ppm in milk fat.  

IR-4 has submitted field trial data in support of a petition proposing tolerances for the use of Avaunt(R) and Steward[(R)] EC on dried beans and Avaunt[(R)] on snap beans.  In addition, subgroup tolerances for small fruit vine climbing subgroup (except kiwifruit) 13-07F and low growing berry subgroup (except strawberry) 13-07H are proposed based on the current tolerances for grapes and cranberry.  The nomenclature and physicochemical properties of indoxacarb are presented below in Tables 3.1 and 3.2 for review.

3.1	Chemical Identity

Table 3.1	Indoxacarb Nomenclature.
Compound
                                       
Common name
Indoxacarb
Company experimental name
DPX-KN128
IUPAC name
(S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate
CAS name
methyl (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-
(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate
CAS registry number
173584-44-6
End-use product (EP)
30% WDG (DuPont Avaunt[(R)] Insecticide; EPA Reg. No. 352-597) and 16% Emusifiable Concentrate (Steward[(R)] EC Insecticide; EPA Reg. No. 352-638)
Compound
                                       
Common name
IN-KN127 (inactive R-enantiomer)

3.2	Physical/Chemical Characteristics

Indoxacarb has a very low vapor pressure of 1.9x10[-10] mmHg at 25 ºC; therefore, is not a volatile pesticide.  The octanol water partition coefficient (Kow = 44000) suggests that it is lipophilic.  Indoxacarb is soluble in water (15.4 ug/L) and does not dissociate under environmental relevant conditions.  

Table 3.2	Physicochemical Properties of Indoxacarb
Parameter
Value
Reference
Melting point/range
140-141ºC
DP# D244253, S. Levy, 1/19/2000
pH
5.32 at 25ºC

Density
1.34 at 20ºC

Water solubility
15.4 +- 2.3 ppb in pH 5 buffer

Solvent solubility
1.72 g/L in n-heptane; 14.5 g/L in 1-octanol; 103 g/L in methanol; 117 g/L in o-xylene; 139 g/L in acetonitrile; 160 g/L in ethyl acetate; and >250 g/kg in methylene chloride, acetone, and dimethyl-formamide

Vapor pressure
2.5 x 10[-8] Pa (1.9x10[-10] mmHg)

Dissociation constant, pKa
Does not dissociate at pHs of 2.42-11.36

Octanol/water partition coefficient, Log(KOW)
4.65 at pH 5

UV/visible absorption spectrum
Molar absorptivities at three maxima were affected by pH, but not over wavelengths of environmental significance.

 

3.3	Pesticide Use Pattern/Directions for Use (860.1200)

IR-4 has submitted field trial data in support of a petition proposing tolerances for the use of Avaunt(R) and Steward[(R)] EC on dried beans and Avaunt[(R)] on succulent beans.  In addition, crop subgroup tolerances and registration of Avaunt[(R)] WDG for use on small fruit vine climbing subgroup (except kiwifruit) 13-07F, and low growing berry subgroup (except strawberry) 13-07H are proposed based on established tolerances for grapes and cranberry.  The proposed new uses are summarized below in Table 3.3.
Table 3.3	Summary of Directions for Use of Indoxacarb.
Applic. Timing, Type, and Equip. [1]
                                  Formulation
                                [EPA Reg. No.]
                                 Applic. Rate 
                                   (lb ai/A)
                          Max. No. Applic. per Season
                          Max. Seasonal Applic. Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                              Use Directions and 
                                Limitations [2]
                                Bean, succulent
Broadcast foliar applications when insects reach economic thresholds; ground or air equipment
                                    30% WDG
                                   [352-597]
                                     0.11
                                      NS
                                     0.44
                                       3
A minimum 7-day RTI is specified.  Make a uniform application of approximately 20-100 gal/A.
                                   Bean, dry
Broadcast foliar applications when insects reach economic thresholds; ground or air equipment
                                    30% WDG
                                   [352-597]
                                     and 
                                    16% EC
                                   [352-638]
                                     0.11
                                      NS
                                     0.44
                                       7
A minimum 7-day RTI is specified.  Make a uniform application of approximately 20-100 gal/A.
      Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F
Broadcast foliar applications when insects reach economic thresholds; ground or air equipment
                                    30% WDG
                                   [352-597]
                                     0.11
                                      NS
                                     0.22
                                       7
A minimum 21-day RTI is specified.  Apply in a minimum of 10 gal/A and 50 gal/A for aerial and ground applications, respectively.
             Low growing berry, except strawberry, subgroup 13-07H
Broadcast foliar applications when insects reach economic thresholds; ground or air equipment
                                    30% WDG
                                   [352-597]
                                     0.11
                                      NS
                                     0.44
                                      30
A minimum 7-day RTI is specified.  Apply in a minimum of 5 gal/A and 10 gal/A for aerial and ground applications, respectively.
[1]	Do not apply through any type of irrigation system, expect for application to cranberry, mint, potato, and sweet corn, and as allowed on supplemental labels.
[2]	Applications may include the use of an adjuvant.  Rotational crop restrictions: (1) 30%WDG: Crops with labeled uses and alfalfa, cotton, peanuts and soybeans may be planted immediately following harvest of a treated crop.  Do not plant any food or feed crops not registered for use with indoxacarb for 30 days after last use. (2) 16% EC:  Crops that are on this label and all brassica leafy vegetables, cucurbit vegetables, fruiting vegetables, leafy green vegetables, leafy petiole vegetables, pome fruit and stone fruit, plus sweet corn, cranberry, grape, mint, southern pea and the tuberous and corm vegetables found in crop subgroup 1C (arracacha, arrowroot, Chinese artichoke, edible canna (Queensland arrowroot), bitter and sweet cassava, chayote(root), chufa, dasheen (taro), ginger, leren, potato, sweet potato, tanier (cocoyam), tumeric, yam bean (jicama, manoic pea) and true yam) may be planted immediately following harvest. Do not plant for food or feed any other crops not registered for use with indoxacarb for 30 days after last use.

Conclusions.  The proposed use pattern is supported by the crop field trials in all commodities.  For the low growing berry subgroup 13-07H, the residue data may support either a 14 or 30-day PHI; however, in accordance with the proposed use pattern the tolerance was calculated with the residue data obtained for a 30-day PHI.  The following are label recommendations to clarify discrepancies or add specificity.  Under the application instructions (page 3 of Avaunt[(R)] label) include dry bean in the sentence: "For bushberry, cranberry, dry bean, pome and stone fruit the minimum interval between treatments is 7 days."  Under the tabulated instructions (page 6 of Avaunt[(R)] label and page 5 of Steward[(R)] EC label) for dry bean and/or succulent bean edit the sentence "Make a uniform application in approximately 20-100 gallons of water per acre" to specify the volume for ground and/or aerial applications.

4.0	Metabolite/Degradate Residue Profile

4.1	Nature of the Residue

4.1.1 	Summary of Plant Metabolism (860.1300)

Adequate metabolism studies on cotton, lettuce, and tomatoes were previously reviewed in conjunction with an earlier indoxacarb petition (D244253, S. J. Levy, 01/19/2000).  Based upon these studies, the MARC determined that indoxacarb and its R-enantiomer were the relevant residues of concern to be established for the tolerance enforcement and risk assessment of crops (D263986, S. J. Levy, 07/10/2000). 

Conclusions.  For the purposes of this petition, the available plant metabolism data will also support the new uses of indoxacarb proposed for dry beans and snap beans.  

4.1.2	Summary of Livestock Metabolism (860.1300)

Adequate ruminant and poultry metabolism studies were previously reviewed in conjunction with an earlier indoxacarb petition (D244253, S. J. Levy, 01/19/2000).  Based on these studies, the MARC has determined that the tolerance expression for milk and ruminant commodities will include indoxacarb and its R-enantiomer (D263986, S. J. Levy, 07/10/2000).  For the purposes of risk assessment, the MARC at this time determined that indoxacarb and its R-enantiomer are likewise the residues of concern for ruminants.  In conjunction, the MARC went on to determine that the residues of concern in milk for risk assessment will be indoxacarb and its R-enantiomer along with the metabolite IN-MP819. 

For poultry commodities, the MARC has determined that for risk assessment purposes the residues of concern are indoxacarb, its R-enantiomer, and the metabolites IN-JT333, IN-JU873, IN-KB687, IN-KG433, IN-KT319, 5-HO-IN-JT333, and Metabolite F (D277922, S. J. Levy, 04/10/2001).  However, the MARC concluded at this time that additional data were still needed to determine if finite indoxacarb residues are incurred in poultry through feed items so that tolerances could be established. Through the submission of a subsequent feeding study (MRID No. 46114302), adequate data were appropriately provided which established the relevant residues of concern needed for tolerance enforcement in poultry.  In accordance, the tolerance expression for poultry commodities will include indoxacarb, its R-enantiomer, and the metabolites IN-JT333, IN-JU873, IN-KB687, IN-KG433, and IN-KT319 (D297936, S. J. Levy, 09/22/2004).   

Conclusions.  As previously noted, the only significant feedstuff associated with the proposed new indoxacarb uses is cowpea, forage which is fed to dairy cattle.  The ruminant metabolism study available is appropriate to cover residues of concern in dairy cattle.

4.1.3	Summary of Confined Rotational Crops (860.l850)

An adequate confined rotational crop study was reviewed in conjunction with an earlier indoxacarb petition (D244253, S. J. Levy, 01/19/2000).  The submitted confined rotational crop study were considered marginally adequate because the test substance was applied at 0.268 lb ai/A of the active isomer S-indoxacarb which was 0.6x the maximum seasonal rate for cotton.  However, a confined rotational study was not required because the nature of the residue was adequately delineated.  From this data the MARC has concluded that the residues of concern in rotated crops should include only the parent expression of indoxacarb and its R-enantiomer (D263986, S. J. Levy, 07/10/2000).  Although some commodities showed total radioactive residues (TRR) above 0.01 ppm 36 days after the last application, the parent compound was not detected (LOD of 0.002 ppm) in any rotational crop commodity at any plantback intervals.  The LOQs of the enforcement methods are within 0.01 to 0.05 ppm for a variety of plant commodities.  Therefore, field rotational studies were not requested.  Subsequently, it was determined that the available data are adequate in supporting a 30-day plant-back interval for all non-labeled crops (D256351, S. J. Levy, 09/07/2000).  

Conclusions.  The application rate of the confined rotational crop study corresponds to 0.6x the maximum seasonal rate proposed for dry beans and succulent beans as well.  However, based on the rationale discussed above no additional rotational crop data are required to support the current petition.

4.3	Residues of Concern Summary and Rationale

Table 4.3  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression[1]
Matrix
Residues included in Risk Assessment
Residues included in Tolerance Expression
Plants
Primary Crop
Indoxacarb and its R enantiomer
Indoxacarb and its R enantiomer

Rotational Crop
Indoxacarb and its R enantiomer 
Indoxacarb and its R enantiomer 
Livestock
Ruminant
Indoxacarb and its R enantiomer (for all)
Metabolite IN-MP819 (for milk only)
Indoxacarb and its R enantiomer 

Poultry
Indoxacarb, its R-enantiomer, and the metabolites IN-JT333, IN-JU873, IN-KB687, IN-KG433, IN-KT319, 5-HO-IN-JT333, and Metabolite F
Indoxacarb, its R-enantiomer, and the metabolites IN-JT333, IN-JU873, IN-KB687, IN-KG433, and IN-KT319
Drinking Water

Indoxacarb, and the degradation products IN-JT333, IN-KG4333, IN- KT413, and IN-ML437-0H
[1] Adapted from: S. Levy, D325479, 03/09/2007; and D402100, Christopher M. Koper, 11/06/2012.

5.0	Residue Profile

5.1	Residue Analytical Methods (860.1340) 

5.1.1	Data Collection Methods

The method used for analysis of snap bean samples (pods/seeds and foliage) was working outline 9.97, versions 1, 2 and 3.  Samples of bean (dry) seeds were analyzed using the Cornell Analytical Laboratory Method titled "Residue Analysis of Indoxacarb on Bean (dry) by HPLC/UV Detection, Version #2".  Both methods were adapted from the DuPont method (DuPont Report No. AMR 2712-93), dated Aug. 08, 1997, titled, "Analytical Enforcement Method (HPLC/Column Switching/UV) for the Determination of Residues of DPX-KN128 (S-enantiomer) and IN-KN127 (R-enantiomer) in Crops."  Modifications made to the reference method were considered minor and did not adversely affect the study. 

For snap bean, the sample was extracted using hexane-saturated acetonitrile and acetonitrile-saturated hexane via homogenization of the mixture in tissuemizer.  The mixture was filtered under vacuum over a Whatman GF/A filter paper and the filtrate was collected.  The filtrate was transferred to a separatory funnel and phases were allowed to separate.  The bottom layer containing product was charged to a TurboVap flask.  The top hexane layer was discarded.  The filter cake was re-extracted 2-5 times, as described above and the combined acetonitrile layers were concentrated using a TurboVap flask.  The extract diluted with acetonitrile in three portions was transferred to a preconditioned disposable 5g/20 cc Silica Mega Bond Elut[R] column and purified. The column was further washed with additional acetonitrile and the combined eluent was evaporated to dryness resulting in a residue.  The residue was dissolved in acetonitrile and buffer (0.03M, pH 2.6, 5:50 v/v) analyzed.  

For dry bean, indoxacarb was extracted from bean (dry) seeds (10 grams) with hexane/acetonitrile (ACN).  The ACN fraction was then concentrated under vacuum and cleaned up by solid phase extraction (SPE) with a combination of silica and a strong anion exchange (SAX) cartridge. After evaporation of the ACN eluent solvent, the purified sample was reconstituted in a mixture of 60% ACN and 40% 0.03M phosphate buffer, and analyzed.  

Samples were analyzed by HPLC equipped with an ultraviolet (UV) detector operating at 310 nm. The residue results are expressed as the sum of the residues of the two enantiomers, KN128 (indoxacarb) and KN127, as the analytical method does not distinguish between the two enantiomers.  The instrument LOQ was set at the LLMV for indoxacarb in/on bean (snap) pods/seeds samples at 0.01 ppm and for bean (snap) and bean (dry), and at 0.03 ppm for foliage.  Based on recoveries at the LLMV, the calculated LOD (std. dev. x one-tailed t-statistic) and LOQ (LOD x 3) for indoxacarb residues were 0.002 and 0.006 ppm in/on pods/seeds, 0.007 and 0.02 ppm in/on foliage, and 0.003 and 0.01 ppm in/on bean (dry) seed samples, respectively. 

Method validation with snap bean commodities was performed both prior to and concurrent with sample analysis.  For method validation, untreated control samples were fortified with indoxacarb/IN-KN127 at 0.01 ppm, 0.03 ppm, 0.10 ppm, and 1.0 ppm for pods/seeds and at 0.03 ppm, 0.5 ppm, 10.0 ppm, and 32.0 ppm for foliage.  Since residues in some treated trials were found to be greater than the highest method validation levels, additional sets of method validation were performed with pods/seeds fortified at 1 ppm and foliage fortified at 32 ppm to bracket the residue ranges.  Method validation recoveries ranged from 69%-111% (93% +- 11%, n = 15) for pods with seeds and 70%-108% (91% +- 12%, n = 15) for plants.  A single recovery for bean (snap) pods with seeds fell below 70%.  Concurrent recovery samples were analyzed for combined residues of indoxacarb and IN-KN127 together with field treated samples.  Recoveries ranged from 91%-109% (101% +- 6%, n = 11) for bean (snap) pods/seeds, with samples fortified at levels of 0.03 ppm and 0.1 ppm.  Recoveries ranged from 82%-95% (90% +- 4%, n = 11) for foliage with samples fortified at levels of 0.52 ppm and 10.5 ppm.  

Method validation with dry beans was performed prior to and concurrent with sample analysis.  Method validation recoveries at 0.01, 0.30 and 3.0 ppm ranged from 87%-103% (95% +- 5%, n = 9).  Concurrent recoveries of indoxacarb on bean (dry) seed control samples fortified at 0.01, 0.30 and 1.0 ppm ranged from 69%-120% (92% +- 13%, n = 23).  The results are presented in Tables C.1.

Conclusions.  Adequate methods were used to determine residue levels in the crop field trials for snap bean and dry bean commodities.  In general, the residue levels are adequately bracketed within the spike levels used in the recovery studies.  In all, both data collection procedures used for testing were adequately validated prior to and in conjunction with the analysis of field samples.

5.1.2	Multi-Residue Methods (860.1360)

Acceptable data are available depicting the recovery of indoxacarb and its R-enantiomer using FDA multiresidue method Protocols C, D, and E found in PAM, Volume 1.  The indoxacarb residues of concern were not evaluated through FDA multiresidue method Protocol A since neither compound possesses an N-methylcarbamate structure.  They were also not tested through Protocol B given that neither compound possesses carboxylic acid or phenolic moiety, and Protocol F because they are not recoverable from Florisil at a level >=30%.  However, indoxacarb and its R-enantiomer were found to be completely recovered through Protocol D but it was noted that matrix enhancement effects were observed in certain samples.  In accordance, the indoxacarb multiresidue testing results obtained were appropriately forwarded to FDA for their review and concurrence D260953, S. J. Levy, 11/03/1999).

5.1.3	Tolerance Enforcement Methods

A number of adequate methods are available for enforcing indoxacarb tolerances on both plant and livestock commodities.  These protocols are all common moiety methods which work to provide a total measure of concentration by determining both indoxacarb and its R-enantiomer as a single component. 

Plants

The primary protocol for the tolerance enforcement of plant commodities is DuPont method AMR 2712-93 which is an HPLC/UV procedure.  It has been validated by the Agency and forwarded to the FDA for inclusion in PAM Vol. II (D267339, S. J. Levy, 10/12/2000).  For this method, residues are extracted with acetonitrile (ACN):hexane and centrifuged.  Residues in the ACN phase are purified by solid-phase extraction (SPE) using silica gel and strong anion exchange (SAX) cartridges.  Residues are then determined by column switching HPLC/UV (310 nm) using C18 and cyano columns, with an external standard.  The method LOQs are 0.01-0.05 ppm for a variety of plant commodities, and the LOD is 0.0025 ppm.

For the confirmation of residues in plant commodities, DuPont method AMR 3493-95 Supplement No. 4 is a GC/MSD procedure which is also available for use.  This method has also been validated by the Agency and forwarded to the FDA accordingly (D282821, S. J. Levy, 05/09/2002).  For this method, residues are extracted with ethyl acetate:water and filtered, and residues in the ethyl acetate fraction are concentrated and purified using silica gel and carbon SPE cartridges.  Residues are then determined by GC/MSD using an external standard.  Residues are quantified using the m/z 527 ion, and confirmatory analyses utilize the 218, 321 and 527 ions.  The method LOQ ranges from 0.2 to 1.0 ppm depending on the matrix, and the LODs are 0.0008-0.21 ppm.
    
Another HPLC/UV procedure developed by the registrant, DuPont-11978, is also available for use to perform tolerance enforcement analyses on crops (D313518, S. J. Levy, 02/18/2005).  This protocol works by uniquely combining the extraction procedure of method AMR-3493-95 with the cleanup and determination techniques developed in method AMR 2712-93.  For this procedure, residues are extracted with ethyl acetate:water, and residues in the ethyl acetate fraction are purified by SAX SPE and determined by column switching HPLC/UV (310 nm) using cyano and C18 columns, with an external standard.  For grape matrices, the method LOQ is 0.01 ppm and the LOD is 0.006 ppm.

Livestock

To enforce the current tolerances established for livestock commodities, DuPont method AMR 3337-95 is a HPLC/UV developed by the registrant which is available for use.  It is capable of determining residues of the parent compound as well as the metabolite IN-JT333 in livestock commodities.  This method has also been validated by the Agency and forwarded to the FDA for inclusion in PAM Vol. II (DP No. 267339, S. J. Levy, 10/12/2000).  The method LOQ is 0.01 ppm and the LOD is 0.002-0.003 ppm.  Residues can be confirmed by GC/MSD using the m/z 527 and 469 ions.

For poultry commodity analyses, DuPont method AMR 12739 is a Liquid Chromatograph/Mass Spectrometer/Mass Spectrometer (LC/MS/MS) procedure developed by the registrant for use.  This method has been successfully validated using hen muscle, liver, skin, and fat as well as, whole egg, egg yolk, and egg white samples proving it to be adequate for data collection (MRID No. 46116302).   Subsequently, an amended version of this protocol, DuPont method AMR 12739 Revision No. 1, was forwarded to ACL/BEAD for petition method validation (P. Savoia, D356925, 28-Nov-2008).

Conclusions.  In the field trials submitted with the current petition, combined indoxacarb residues were determined using a modification of an enforcement method.  The data collection method was adequately validated in conjunction with the samples analyses, using control samples fortified at an appropriate range of concentrations.  Acceptable recoveries were obtained for all commodities.  The recommended tolerance level for succulent bean foliage (50 ppm) is above the highest spike level tested; however, good recoveries were consistently observed at all spike levels (0.03 to 32 ppm) being within 82-103% at spike levels of 10 and 32 ppm.  Based on this the enforcement methods are adequate to support the tolerances recommended for the proposed new uses.  In addition, appropriate enforcement methods for residues in livestock are available.

5.1.4	Submittal of Analytical Reference Standards (860.1650)

An analytical standard for the insecticide indoxacarb is currently available in the EPA National Pesticide Standards Repository.  However, the indoxacarb standard has an expiration date of 4/2013.  A reference standard should be sent to the Analytical Chemistry Laboratory located in Fort Meade to the attention of either Theresa Cole or Thuy Nguyen at the following address:

      USEPA
      National Pesticide Standards Repository/Analytical Chemistry Branch/OPP
      701 Mapes Road
      Fort George G. Meade, MD  20755-5350

Please note that mail will be returned if the entire extended zip code is not used when addressing correspondence to the Repository. 

5.2	Storage Stability (860.1380)

Storage stability data have been reviewed for a number of commodities in conjunction with earlier indoxacarb petitions.  Indoxacarb residues are relatively stable in frozen storage on a wide variety of plant commodities such as broccoli, wet apple pomace, wet grape pomace, wine, tomatoes, peppers, cotton (hulls, meal and refined oil) for 12 months; apple juice for 6 months; pears, cabbage, lettuce, cottonseed, and cotton gin byproducts for 13-15 months; apples and grapes for 18 months; and corn forage, stover and ears for 19-23 months. In furthering the above mentioned data, concurrent storage stability studies were carried out along with the snap bean and dry bean crop field trials.  

Maximum storage intervals for field-treated samples were 203 days for snap beans (pods with seeds), and 205 days for plant/foliage samples.  Storage stability samples (both matrices) fortified with a racemic mixture of KN128 and KN127 (50:50) at 0.03 ppm and held in frozen storage under similar conditions to the field generated samples had recoveries of 90%-101% for snap bean (pods with seeds) and 90%-106% for plant/foliage after 209 days.  The data indicated that indoxacarb was stable under the conditions that the samples were stored between harvest and analysis.

Treated dry bean seed samples in this study were stored frozen for 190-225 days.  Storage stability samples fortified with a racemic mixture of KN128 and KN127 (50:50) at 0.3 ppm and held in frozen storage under similar conditions to the field generated samples had recoveries of 103% (3 samples) after 210 days.  The data indicated that indoxacarb was stable under the conditions that the samples were stored between harvest and analysis.

TABLE 5.2	Summary of Storage Conditions For Indoxacarb on Bean (Snap) 
Matrix 
(RAC or extract)
                              Storage Temperature
                                     (°C)
                       Storage Stability Recoveries (%)
                        Actual Storage Duration (days)
                  Interval of Demonstrated Storage Stability
                                    (days)
Bean (snap) pods with seeds
                                  -29 to -16
                                  101, 91, 90
                                    68-203 
                                      209
Bean (snap) plants
                                       
                                  93, 99, 106
                                    70-205
                                      209
Bean (dry) seed
                                   -21 +- 7
                                 103, 103, 103
                                    190-225
                                      210

Conclusions.  The concurrent storage stability studies are inadequate due to a lack of 0-day data for the fortified samples stored for testing.  However, given the fact that recoveries averaged 90-106%, the data obtained will support the storage intervals incurred in the field trials for purposes of this petition.  

5.3	Residue Data

5.3.1	Crop Field Trials (860.1500)

Crop field trials were conducted for dry beans and snap beans following application of Avaunt(R) 30 WG Insecticide.  In addition, three side-by-side crop field trials with the Steward[(R)] EC Insecticide were conducted to support the use of on dry beans.  No additional crop field trials were conducted to support tolerances on the proposed new subgroups, small fruit vine climbing subgroup (except kiwifruit) 13-07F and low growing berry subgroup (except strawberry) 13-07H, since the proposal is based on the established tolerances for grapes and cranberries, respectively.

Snap Bean (48788901.der.doc)

The Interregional Research Project No. 4 (IR-4) has submitted field trial data for indoxacarb on bean (snap).  Nine field trials were conducted in the United States during the 2005 growing season, one each in NJ and NC (EPA Region 2), two in FL (EPA Region 3), one each in MI, WI and OH (EPA Region 5), one in CA (EPA Region 10) and one in ID (EPA Region 11).  The number and geographical distribution of the supervised field trials on bean (snap) are adequate.  Each field trial site comprised one untreated control plot and one treated plot.  At all the trials, Avaunt(R) 30 WG was applied as four foliar applications 6-8 days apart with a pre-harvest interval (PHI) of 2-3 days.  The application rates ranged from 0.108-0.119 lb ai/A per application for a total of 0.438-0.457 (0.542 at OH12) lb ai/A per season.  No adjuvants were used at any of the trials.

Snap bean (pods with seeds) and foliage (snap bean plants) samples were harvested.  At the CA trial, additional samples were taken at 0, 7, and 13 days after the last application.  No residues of indoxacarb were found in control samples above the LLMV (0.01 ppm) during the field trials.  For pods with seeds samples at 2-3 days PHI, residues in treated field samples were found between 0.04 ppm (OH12) and 0.59 ppm (CA107).  For plant/foliage samples at 2-3 days PHI, residues in treated field samples were found between 1.3 ppm (OH12) and 32.1 ppm (MI21).  Representative chromatograms for control samples were free from interference.

At the CA107 decline trial, in pods with seeds and plant/foliage samples, residues at 13-day PHI declined to approximately 63% and 86%, respectively, of the residues in the 2-day PHI samples.  In pods with seeds and plant/foliage samples, residues at 13-day PHI declined to 46% and 56%, respectively, of the residues in the 0-day PHI samples.  There was a slight increase in residues in the foliage/plant samples from the 2-day PHI samples (15.4 ppm) to the 7-day PHI samples (17.39 ppm), which were within normal variability.

TABLE 5.3.1.1.	Summary of Residue Data from Bean (Snap) Field Trials with Indoxacarb
Commodity
                              Total Applic. Rate
                                   (lb ai/A)
                                  PHI (days)
                                Residue Levels
                                     (ppm)

                                       n
                                     Min.
                                     Max.
                                    HAFT[1]
                                    Median
                                     Mean
                                   Std. Dev.
Bean (Snap) Pods with seed
0.438-0.542 
                                      2-3
                                      18
                                     0.04
                                     0.59
                                     0.585
                                     0.15
                                     0.18
                                     0.15
Bean (Snap) Plant/Foliage
0.438-0.542
                                      2-3
                                      18
                                      1.3
                                     32.1
                                     31.7
                                     10.2
                                     12.6
                                      8.2
[1]HAFT = Highest Average Field Trial

Dry Beans (48788902.der.doc)

The Interregional Research Project No. 4 (IR-4) has submitted field trial data for indoxacarb on a variety of dry beans (Phaseolusspp).  Thirteen field trials were conducted in the United States in EPA region 2: NJ (1 trial); region 5: MI (2 trials), ND, OH, WI (1 trial each); region 7: ND (2 trials); region 8: CO (1 trial); region 9: CO (1 trial); region 10: CA (1 trial); region 11: ID and WA (1 trial each) during the 2006 growing season.  The number and geographical distribution of the supervised field trials on bean (dry) are adequate. Each crop field trial consisted of one untreated control plot and one treated plot with the exception of three field trials where an additional treated plot was included. At all the trials, four foliar applications (5 at CA86) of Steward[(R)] EC were performed with a pre-harvest interval (PHI) of 6-8 days.  Avaunt[(R)] 30 WG was used for a second treated plot at tree field trials.

Dry bean seed samples were either hand or mechanically harvested.  At the CA and ND trials, additional samples were taken at 0, 13, and 20-22 days after the last application.  No residues of Indoxacarb were found in control samples above the LLMV (0.01 ppm) during the field trials.  For the samples harvested 6-8 days after the last application, the total combined residues of indoxacarb (DPX  -  KN128) and IN  -  KN127 in/on bean (dry ) seeds treated with Steward[(R)] ranged from <0.01 ppm to 0.093 ppm.  Residues in/on bean (dry) seeds treated with Avaunt[(R)] ranged from <0.01 ppm to 0.032 ppm.  The side-by-side trials for dry beans with the Avaunt[(R)] and Steward[(R)] EC formulations show similar/slightly higher residues with the former.

At the CA86 decline trial, samples had residues of 0.038 ppm and 0.048 ppm in/on bean (dry) seeds samples at 0-day PHI.  In the ND06 trial, the 0-day PHI samples had residues of <0.01 and 0.01 ppm.  No detectable residues (>0.01 ppm) were observed in the samples from the other sampling intervals.  The decline data indicated that residues of indoxacarb decayed fairly rapidly after the application.

TABLE 5.3.1.2.	Summary of Residue Data from Bean (dry) Field Trials with Indoxacarb
Commodity
                              Total Applic. Rate
                                   (lb ai/A)
                                 PHI[1] (days)
                                Residue Levels
                                   (ppm)[2]

                                       n
                                     Min.
                                     Max.
                                    HAFT[1]
                                    Median
                                     Mean
                                   Std. Dev.
Bean (dry)
                                Steward[(R)] EC

0.438-0.551
                                      6-8
                                      26
                                   <0.01
                                     0.093
                                    0.0695
                                     0.005
                                     0.01
                                     0.02

                               Avaunt[(R)] 30 WG

0.439-0.454
                                      6-7
                                       6
                                   <0.01
                                     0.032
                                     0.03
                                     0.02
                                     0.02
                                     0.01
[1]HAFT = Highest Average Field Trial
[2]For samples with no detectable residues (<0.01 ppm), a value of (1/2) LLMV (0.005 ppm) was used in calculating the median, mean and standard deviation

Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F 

Adequate crop field trials (13) were conducted during the year 2002 to support registration and tolerances for indoxacarb (Avaunt[(R)] 30% WDG) on grapes (S. Levy, D290126, 18-Feb-2005).  The crop field trials consisted of four broadcast foliar applications at 0.109-0.158 lb ai/A, and an interval of 5-days between applications for a total of 0.438-0.507 lb ai/A/season.  All applications were made using ground equipment.  Samples of grapes were collected at 7 days after the last application.  A tolerance of 0.9 ppm was recommended based on NAFTA calculation procedures.

Low growing berry, except strawberry, subgroup 13-07H 

Adequate crop field trials (6) were conducted during 2002-2003 to support registration and tolerances for indoxacarb (Avaunt[(R)] 30% WDG) on cranberries (S. Levy, D325479, 09-Mar-2007).  The field trials consisted of four broadcast foliar applications during fruit development at 0.108-0.115 lb ai/A, at retreatment intervals (RTIs) of 6-8 days, for a total application rate of 0.436-0.451 lb ai/A.  All applications were made using ground equipment at 28-46 gallons per acre (GPA), without the use of any adjuvants.  Samples of cranberries were harvested twice from each trial, at 13-15 and 28-30 days after the last treatment (DALA).  The residue data may support either a 14 or 30-day PHI; however, in accordance with the proposed use pattern the tolerance was calculated with the residue data obtained for a 30-day PHI.  A tolerance of 2.0 ppm was recommended based on NAFTA calculation procedures.

Conclusions.  The dry bean and snap bean field trials are adequate to support the proposed new uses on bean, dry and bean, succulent crops.  A sufficient number of trials were conducted on each crop at 1x the maximum proposed rate in the appropriate geographic regions with the proper representative RACs being collected for analysis.  Samples were analyzed using adequate analytical methods, and the sample storage intervals are supported by the available storage stability data.  Adequate residue decline data was generated with snap beans and dry beans indicating that residues of indoxacarb decline at longer days after treatment.  The residue data is adequate to recommend registration of the proposed new use and tolerances for the corresponding commodities.  It is noted that although the tolerance for cowpea forage was recommended based on data from snap bean forage, data for hay was not submitted.  However, HED is recommending establishment of a tolerance for indoxacarb on cowpea hay of 100 ppm based on the product of the highest forage residue (32 ppm) and ratio of percent dry matter for hay and forage (86/30).  

Residue data for cranberries and grapes was previously evaluated and considered acceptable.  The data for cranberries is adequate to support the tolerance for low growing berry subgroup 13-07H.  The use pattern of the grape field trial correspond to the same single application rate and PHI of the proposed use pattern for small fruit vine climbing subgroup 13-07F but the grape field trials used a higher maximum seasonal application rate (0.44 lb ai/A instead of 0.22 lb ai/A) and shorter RTI (5-days instead of 21-days) than what is proposed for the small fruit vine climbing subgroup.  Since the single application rate and PHI are similar, and higher residues than the proposed tolerance would not be expected it is recommended to use available residue data without applying a scaling factor to adjust the residue level.  The residue data will be considered adequate to recommend tolerances for the corresponding crop subgroups.

5.3.2	Field Rotational Crops (860.1900)

No additional rotational crop data are required for the current petition.

5.3.3	Processed Food and Feed (860.1520)

HED does not require residue data for any processed commodities associated with dry beans, snap beans or cranberries.  Moreover, a grape processing study was previously submitted in support of the petition for tolerances on grapes.  A tolerance for grape raisins at 5.0 ppm is established.  Processing food/feed studies are not needed to support the current petition.

5.3.4	Meat, Milk, Poultry and Eggs (860.1480)

The residue data for bean, snap, forage can be used to establish a tolerance for cowpea, forage which is a dairy cattle feedstuff.  Dietary burden calculations previously performed for dairy cattle made use of tolerance level residues and dietary contribution from feedstuff commodities that lead to conservative dietary burden estimates (S. Levy, D276516, 30-May-2002).  The revised version of Table 1 (OPPTS Guideline 860.1000), the new guidelines that make use of the highest or average residue level in the feedstuff, and a livestock dietary burden calculator developed by HED were used to estimate the dietary burden for dairy cattle, see Table 5.3.4.  The new dietary burden (33.0 ppm) is lower than that used (46.1 ppm for dairy cattle and 50.0 ppm for beef cattle) to establish the current tolerances (D276516; 30-May-2002).  As a result, existing tolerances established for ruminant commodities are conservative.  Dietary burden calculations for beef cattle, dairy cattle and poultry should be revisited during registration review in order to re-evaluate the existing tolerances for meat, milk, poultry and eggs commodities.  

Table 5.3.4.  Dietary Burden for Dairy Cattle Based on Indoxacarb Proposed Uses.  
                                   Feedstuff
                                      %DM
                               Classification[1]
Highest/ Average Residue[2]
                                   % In Diet
                                Dietary Burden
Apples, wet pomace
                                                                             40
CC
                                                                           1.9 
                                                                             10
                                                                           0.48

CC
                                                                              0
                                                                             35
                                                                           0.00
Cotton, undelinted seed
                                                                             88
PC
                                                                           1.3 
                                                                             10
                                                                           0.15
Cowpea, forage
                                                                             30
R
                                                                          32.1 
                                                                             20
                                                                          21.40
Alfalfa, hay
                                                                             89
R
                                                                            39 
                                                                             25
                                                                          10.96
Total
                                       
                                      100
                                                                           33.0
[1] CC = carbohydrate concentrate; PC = protein concentrate; R = roughage
[2] The highest/average residue values were obtained from D244253, S. Levy, 01/19/2000 and D408982; I. Negron-Encarnacion.  Values used for all feedstuff commodities are in Appendix C.

5.3.5.	Food Handling (860.1460)

This guideline requirement is not relevant to the current petition as no food handling uses are being proposed. 

5.3.6	Water, Fish, and Irrigated Crops (860.1400)

This guideline requirement is not relevant to the current petition as no aquatic uses are being proposed. 

6.0	Tolerance Derivation

 The OECD MRL calculation procedures were used to determine the tolerances for all commodities.  The procedures generate tolerances based on mean field trial values.  The spreadsheets for the various commodities can be found in Appendix B.

Appendix A.  International Residue Limits Table

                          Indoxacarb (PC Code 067710)
Summary of US and International Tolerances and Maximum Residue Limits 
Residue Definition:
US
Canada
Mexico[2]
Codex[3]
40 CFR 180.564:  
Plants:  indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2- e ][1,3,4][oxadiazine-4a(3 H )-carboxylate, and its R-enantiomer, (R)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2- e ][1,3,4][oxadiazine-4a(3 H )-carboxylate.	
None

Plant/Livestock commodities: sum of indoxacarb and its R enantiomer. 
The residue is fat-soluble.

Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US
Canada
Mexico[2]
Codex[3]
Bean, dry, seed
0.2

0.2 chick-pea (dry), 0.2 mung bean (dry)
0.1 cowpea (dry)
Bean, succulent
0.9

Cowpea, forage
50

Cowpea, hay
100

Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F
2

2 (Grape)

Grape, raisin
5.0

5 Dried grapes (=currants, raisins and sultanas)
Low growing berry, except strawberry, subgroup 13-07H
1

1 (Cranberry)

                                       
                                       
                                       
                                       

                                       
                                       
                                       
                                       

                                       
                                       
                                       
                                       

                                       

Completed:  M. Negussie; 01/02/2013
[1] Includes only commodities of interest for this action.  Tolerance values in bold are based on HED recommendations, not those proposed by the applicant.
2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains.  PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

Appendix B.  OECD MRL Calculation Procedure Inputs/Outputs

Bean (Snap)

                                Residues(mg/kg)
Pods with Seeds
Plant without pods
                                     0.590
                                    16.200
                                     0.120
                                     6.800
                                     0.200
                                    10.100
                                     0.170
                                    31.700
                                     0.110
                                     9.000
                                     0.170
                                    12.300
                                     0.130
                                    10.200
                                     0.150
                                    16.500
                                     0.050
                                     1.300

 
 
 
 
 
                                  Indoxacarb
                                       
 
                         Beans (Snap); Pods with Seeds
                                       
 
                                      USA
                                       
 
                            0.45 lb ai/A, 3-day PHI
                                       
 
 
 
 
 
Total number of data (n)
                                       9
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                       9
                                       
 
Lowest residue
                                     0.050
                                       
 
Highest residue
                                     0.590
                                       
 
Median residue
                                     0.150
                                       
 
Mean
                                     0.188
                                       
 
Standard deviation (SD)
                                     0.157
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.590
 
 
- Mean + 4 SD
                                     0.815
 
 
- CF x 3 Mean
                                     0.563
 
 
Unrounded MRL
                                     0.815
                                       
 
 
                                       
 
 
Rounded MRL
                                      0.9
                                       
 
 
                                       
                                       
 
 
                                       
 
 
 
 
 
 
 

 
 
 
 
 
                                  Indoxacarb
                                       
 
                       Beans (Snap); Plant without pods
                                       
 
                                      USA
                                       
 
                            0.45 lb ai/A, 3-day PHI
                                       
 
 
 
 
 
Total number of data (n)
                                       9
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                       9
                                       
 
Lowest residue
                                     1.300
                                       
 
Highest residue
                                    31.700
                                       
 
Median residue
                                    10.200
                                       
 
Mean
                                    12.678
                                       
 
Standard deviation (SD)
                                     8.510
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                    31.700
 
 
- Mean + 4 SD
                                    46.716
 
 
- CF x 3 Mean
                                    38.033
 
 
Unrounded MRL
                                    46.716
                                       
 
 
                                       
 
 
Rounded MRL
                                      50
                                       
 
 
                                       
                                       
 
 
                                       
 
 
 
 
 
 
 

Bean (Dry)

Note:  The tolerance for dry bean (0.06 ppm) obtained by the OECD calculation procedures will be increased to 1 ppm in order to harmonize with the Codex MRL for cowpea.  

Residues(mg/kg)
                                     0.010
                                     0.010
                                     0.010
                                     0.052
                                     0.010
                                     0.010
                                     0.010
                                     0.010
                                     0.010
                                     0.010
                                     0.010
                                     0.010
                                     0.014
                                     0.011
                                     0.022
                                     0.030

 
                                  Indoxacarb
                                       
 
                               Beans (Dry); seed
                                       
 
                                      USA
                                       
 
                            0.45 lb ai/A, 7-day PHI
                                       
 
 
 
 
 
Total number of data (n)
                                      16
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                      16
                                       
 
Lowest residue
                                     0.010
                                       
 
Highest residue
                                     0.052
                                       
 
Median residue
                                     0.010
                                       
 
Mean
                                     0.015
                                       
 
Standard deviation (SD)
                                     0.011
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.052
 
 
- Mean + 4 SD
                                     0.060
 
 
- CF x 3 Mean
                                     0.045
 
 
Unrounded MRL
                                     0.060
                                       
 
 
                                       
 
 
Rounded MRL
                                     0.06
                                       
Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F 

Residues(mg/kg)
                                     0.242
                                     0.180
                                     1.520
                                     0.166
                                     0.086
                                     0.798
                                     0.317
                                     0.436
                                     0.190
                                     0.418
                                     1.330
                                     0.388
                                     0.270

 
 
 
 
 
                                  Indoxacarb
                                       
 
                                    Grapes
                                       
 
                                      USA
                                       
 
                            0.45 lb ai/A, 7-day PHI
                                       
 
 
 
 
 
Total number of data (n)
                                      13
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                      13
                                       
 
Lowest residue
                                     0.086
                                       
 
Highest residue
                                     1.520
                                       
 
Median residue
                                     0.317
                                       
 
Mean
                                     0.488
                                       
 
Standard deviation (SD)
                                     0.454
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     1.520
 
 
- Mean + 4 SD
                                     2.304
 
 
- CF x 3 Mean
                                     1.463
 
 
Unrounded MRL
                                     2.304
                                       
 
 
                                       
 
 
Rounded MRL
                                       3
                                       
 
 
                                       
                                       
 
 
 
 

Low growing berry, except strawberry, subgroup 13-07H

Residues(mg/kg)
                                     0.116
                                     0.150
                                     0.105
                                     0.180
                                     0.120
                                     0.630

 
 
 
 
 
                                  Indoxacarb
                                       
 
                                  Cranberries
                                       
 
                                      USA
                                       
 
                           0.45 lb ai/A, 30-day PHI
                                       
 
 
 
 
 
Total number of data (n)
                                       6
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                       6
                                       
 
Lowest residue
                                     0.105
                                       
 
Highest residue
                                     0.630
                                       
 
Median residue
                                     0.135
                                       
 
Mean
                                     0.217
                                       
 
Standard deviation (SD)
                                     0.204
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.630
 
 
- Mean + 4 SD
                                     1.034
 
 
- CF x 3 Mean
                                     0.651
 
 
Unrounded MRL
                                     1.034
                                       
 
 
                                       
 
 
Rounded MRL
                                       1
                                       
 
 
                                       
                                       
 
 High uncertainty of MRL estimate.
                                       
 
[Small dataset]
 
 
 
 
 

Appendix C.  Highest/average residues of indoxacarb in feedstuff commodities[6]

1.  Wet apple pomace (CC)[1]
Processing factor = 2.6x; Highest field trial residue adjusted for application rate = 0.74 ppm
Average residue in wet apple pomace = 1.9 ppm	

2.  Cotton undelinted seed (PC)[1]
Highest field trial residue adjusted for application rate = 1.3 ppm

3.  Cotton gin byproducts (R)[1] 
Highest field trial residue adjusted for application rate = 6.7 ppm
* a bridging study showed higher residues than these but were not considered because the plants were not allowed to dry before ginning; therefore, they had more leaves than normally and resulted in higher residues.

4.  Sweet Corn stover (R)[1]
Highest field trial residue adjusted for application rate = 13.4 ppm

5. Sweet Corn forage (R)[1]
Highest field trial residue adjusted for application rate = 8.7 ppm

6.  Peanut Hay (R)[2]
Highest / Average field trial residue = 18 ppm / 7.8 ppm

7.  Alfalfa forage (R)[3]
Highest / Average field trial residue = 9.0 ppm / 4.8 ppm

8.  Alfalfa hay (R)[3]
Highest / Average field trial residue = 39 ppm / 15 ppm

9.  Soybean seed (PC)[3]
Average field trial = 0.088 ppm 

10.  Soybean hulls (R)[3,4] 
Processing Factor[4] = 8.2x; Average field trial of soybean seed[3] = 0.088 ppm
Average residue in soybean hulls = 0.72 ppm 

11.  Cowpea, foliage (R)[5]
Highest / Average field trial residue = 32.1 ppm / 12.6 ppm
________________________________________________________
[1]  Sarah J. Levy; 19-JAN-2000;  DP Barcodes: D244253.  
[2] Sarah J. Levy; 7-JAN -2005; DP Barcode 301655.
[3] Sarah J. Levy; 30-MAY-2002; DP Barcode:  D276516.  
4 MRID 45384305; Devine, T.; 2000.
5 Ideliz Negron-Encarnacion; DP Barcode: D408982. 
[6] Residue values in bold were used to determine the dietary burden for dairy cattle.  These may be highest or average values, depending on the level of blending of the feedstuff commodity.  Average values, when available, were used for dietary burden calculations to support the chronic dietary assessment.