Document ID: EPA-HQ-OPP-2010-0041-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-08-17T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                             WASHINGTON, DC  20460
                                   OFFICE OF
                              CHEMICAL SAFETY AND
                             POLLUTION PREVENTION
                                                                               
MEMORANDUM

DATE:	2 November 2010

SUBJECT:	Thiamethoxam.  Petition to Establish Permanent Tolerances for Residues of the Insecticide Resulting from Food/Feed Use as a Seed Treatment on Peanuts and Alfalfa, and from Applications in Food-Handling Establishments.  Summary of Analytical Chemistry and Residue Data.  

PC Code:  060109
DP Barcodes:  D376367, D380653
Decision Numbers:  424517, 436785
File Symbol, Registration Numbers:  100-RGAL, 100-941, 100-1306
Petition Numbers:  9F7657, 0F7707, 0F7734
Regulatory Action:  Amended Section 3
Risk Assessment Type:  NA
Case Number:  NA
TXR Number:  NA
CAS Number:  153719-23-4
MRID #Numbers:  See MRID Summary Table
40CFR:  §180.565

FROM:	William T. Drew, Chemist
		Risk Assessment Branch 2 (RAB2)
		Health Effects Division (HED), 7509P

THRU:	Dennis McNeilly, Chemist
		Richard A. Loranger, PhD, Senior Scientist
		RAB2/HED, 7509P

TO:		Kable Davis and Venus Eagle, RM Team 1
		Insecticide/Rodenticide Branch (IRB) 
		Registration Division (RD), 7505P

MRID Summary Table.
                                 MRID #Number
                                  Study Type
                                   Comments
45093704
860.1500 Crop Field Trials/Residue Decline
New DER; peanut (nutmeat, hay).  

860.1520 Processed Food and Feed
New DER; peanut (meal, refined oil).  
48020201
860.1500 Crop Field Trials/Residue Decline
New DER; alfalfa (forage, hay).  
48110202
Food-Handling Establishments
New DER; spot, void, or crack and crevice treatment.  

Executive Summary

	Thiamethoxam (3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-imine) belongs to the pesticide chemical class known as the neonicotinoids (Group 4A).  It is a broad-spectrum, systemic insecticide with activity against sucking and chewing insects on a wide variety of crops.  It is also effective against a wide variety of interior and exterior pests, including termites, ants, beetles, and cockroaches.  
	Syngenta Crop Protection submitted a petition to register a new use of thiamethoxam on peanuts (PP#9F7657).  One end-use product (EP) relevant to this petition is Cruiser PD (EPA File Symbol 100-RGAL), a wettable powder formulation intended for dry-application seed treatment (WS), containing 70% of the active ingredient (ai), thiamethoxam.  The other EP relevant to this petition is Cruiser 5FS (EPA Registration #100-941), a flowable concentrate formulation intended for seed treatment (FS), containing 5 pounds of ai per gallon (lb ai/gal).  Both are proposed for pre-plant seed treatment of peanuts at 0.20-0.29 mg ai/seed, to provide early season protection of seedlings against injury from thrips, aphids, wireworms and white grubs, and suppression of three-cornered alfalfa hoppers, and plant bugs.  In conjunction with the proposed use, Syngenta has requested the establishment of permanent tolerances for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), in or on peanut commodities, as listed below.  

        Peanut	0.05 ppm
        Peanut, hay	0.25 ppm

In support of the proposed registration and tolerances, Syngenta submitted a magnitude of the residue study on peanut nutmeat and hay (MRID #45093704).  The submitted peanut data are evaluated in this Summary Document.  
	Syngenta also submitted a petition to register a new use of thiamethoxam on alfalfa (PP#0F7707).  The EP relevant to this petition is Cruiser 5FS (EPA Registration #100-941).  It is proposed for pre-plant seed treatment of alfalfa at 0.001 mg ai/seed, to provide early season protection of seedlings against damage caused by aphids and leafhoppers (first cut crop only).  In conjunction with the proposed use, Syngenta has requested the establishment of permanent tolerances for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), in/on alfalfa commodities, as listed below.  

        Alfalfa, forage	0.05 ppm
        Alfalfa, hay	0.12 ppm

In support of the proposed registration and tolerances, Syngenta submitted a magnitude of the residue study on alfalfa forage and hay (MRID #48020201).  The submitted alfalfa data are evaluated in this Summary Document.  
	Additionally, Syngenta submitted a petition to register a new food use of thiamethoxam in food handling establishments (PP#0F7734).  The EP relevant to this petition is Optigard Flex Liquid (EPA Registration #100-1306), a suspension concentrate (SC) formulation that contains 2 lb ai/gal.  It is proposed for indoor spot, void, and crack and crevice applications as 0.05 and 0.1% ai solutions, to control a wide variety of insect pests.  In conjunction with the proposed use, Syngenta has requested the establishment of a permanent tolerance for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), in/on food or feed commodities, as listed below.  

        Food commodities/feed
        commodities (other than
        those covered by a higher
        tolerance as a result of use
        on growing crops) in
        food/feed handling
        establishments	0.01 ppm

In support of the proposed registration and tolerance, Syngenta submitted a magnitude of the residue study on various food items following indoor applications in two different food handling establishments (MRID #48110202).  The submitted food handling establishment data are evaluated in this Summary Document.  
	Tolerances for residues of thiamethoxam are listed in 40CFR §180.565, and are expressed in terms of the combined residues of the insecticide thiamethoxam and its metabolite, CGA-322704.  The metabolite CGA-322704 is identical to the active ingredient, clothianidin (PC Code 044309).  The established tolerances in plant commodities, under 40CFR §180.565[a], range from 0.02 ppm to 4.5 ppm; about half of the tolerances are set at the combined limit of quantitation (LOQ) for thiamethoxam and CGA-322704 of 0.02 ppm.  Tolerances are also established under 40CFR §180.565[a] in livestock commodities. The tolerances in milk and meat of cattle, goat, horse and sheep, and in meat and meat byproducts of hog, are set at 0.02 ppm each.  The tolerances in meat byproducts of cattle, goat, horse and sheep are set at 0.04 ppm each.  
	The nature of the residue in plants and animals has been adequately delineated, based on metabolism studies with corn, cucumber, lettuce, pear, potato, rice, tobacco, wheat, goats and hens.  The studies on corn, potato and wheat reflected seed treatment and/or soil drench applications.  The residues of concern (ROCs), for the purposes of tolerance expression and risk assessment, are the combined residues of thiamethoxam and CGA-322704.  
	The nature of the residue in rotational crops is adequately understood.  HED has determined (RAB2 continues to support the decision) that the major residues from the confined rotational crop studies are the parent, thiamethoxam, and its CGA-322704 metabolite.  In animal feedstuffs, CGA-265307, a metabolite containing the N-nitro group, was found to be a major residue.  HED recommended that all three compounds be analyzed in field rotational crop studies.  
	Several field rotational crop studies on thiamethoxam are available.  These data indicate that at an application rate of 0.179 pounds ai per acre (lb ai/A), roughly 1X the maximum seasonal use rate of 0.188 lb ai/A on rotatable crops, quantifiable levels of thiamethoxam ROCs are not expected from a 120-day plantback interval (PBI).  The proposed seed treatment use of Cruiser PD and Cruiser 5FS on peanuts would result in a maximum per acre application rate equivalent to 0.08 lb ai/A (approximately 0.43X the maximum use rate on rotatable crops), based on 850 seeds/lb, and a seeding (planting) rate of 142 pounds of seeds per acre (lb seeds/A).  The proposed seed treatment use of Cruiser 5FS on alfalfa would result in per acre application rates equivalent to 0.0037-0.0130 lb ai/A (approximately 0.02-0.07X the maximum use rate on rotatable crops), depending on the seeding rate, in lb seeds/A.  
	Novartis Analytical Method AG-675, a method utilizing high-performance liquid chromatography (HPLC) with ultraviolet (UV) or mass spectrometric (MS) detection, is the original enforcement method, and was submitted in conjunction with previous thiamethoxam petitions.  Method AG-675 determines residues of thiamethoxam and CGA-322704 in crop and livestock commodities.  The method has undergone a successful independent laboratory validation (ILV), and Agency petition method validation (PMV).  
	Following approval of Method AG-675 as an enforcement method, Syngenta submitted a modification of the method to include a microwave extraction step for liver.  In its review of the modified Method AG-675, HED (D281702; M. Doherty; 17 April 2007) required that the method be completely rewritten to include the full residue extraction steps for both plant and livestock commodities.  Syngenta responded to this data gap by submitting Method GRM.009.04A (MRID #47786103), which supersedes Method AG-675.  Method GRM.009.04A determines residues of parent thiamethoxam and its metabolites (CGA-322704 and CGA-265307) individually using HPLC/UV for fruits, vegetables, oils, grains, and animal matrices other than liver.  The LOQ for each analyte is 0.010 ppm in all substrates except milk and fruit juices (0.005 ppm).  The method includes a step in the calculation to convert residues of CGA-322704 to thiamethoxam equivalents.  For analysis of cotton, tobacco, and the forage, fodder and straw of cereal grains, the method determines thiamethoxam ROCs using HPLC/MS, with an LOQ of 0.010 ppm in each analyte except grass (0.050 ppm).  For analysis of liver, final residue determination is made using HPLC with tandem mass spectrometric detection (HPLC/MS/MS); the LOQ is 0.010 ppm each for thiamethoxam, CGA-322704 and CGA-265307.  Syngenta also submitted method validation data for Method GRM.009.04A (MRID #47786102).  No ILV data have been submitted, nor will ILV data be required, because the method is a revised version of an existing enforcement method.  HED will forward Method GRM.009.04A (MRID #47786103) to FDA for an update of the thiamethoxam enforcement method in PAM Volume II.  
	Samples of the peanut raw agricultural commodities (RACs), nutmeat and hay, were analyzed for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), using Method AG-675 with either ultraviolet (HPLC/UV), or tandem mass spectrometric detection (HPLC/MS/MS).  This method is adequate for data collection, based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte, resulting in an LOQ for combined residues of 0.02 ppm.  
	Samples of the alfalfa RACs, forage and hay, were analyzed for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), using an HPLC/MS/MS method, Syngenta Analytical Method GRM009.02A.  This method is also known as ADPEN Method M1104, and is adequate for data collection, based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte, resulting in an LOQ for combined residues of 0.02 ppm.  
	Samples of the various food commodities utilized in the food handling establishment study were analyzed for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), via HPLC/MS/MS using Method AG-675.  This method is adequate for data collection, based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte in all matrices, resulting in an LOQ for combined residues of 0.02 ppm.  
	The FDA multiresidue methods (MRMs) of PAM Volume I are not adequate for tolerance enforcement, as thiamethoxam ROCs are not adequately recovered by any of the tested MRM protocols.  
	Adequate storage stability data are available for thiamethoxam and CGA-322704 to support the storage conditions and durations of samples collected from the magnitude of the residue and food handling establishment studies.  There are no storage stability issues, and no corrections for potential decline during storage are needed for any of the residue studies.  
	The submitted field trial data for thiamethoxam on peanuts are acceptable, and support the proposed use of Cruiser PD and Cruiser 5FS as pre-plant seed treatments.  An adequate number of trials were conducted in the appropriate geographic regions at roughly 1.5-3X the maximum proposed rate.  Based on the maximum combined thiamethoxam ROCs of 0.09 and 0.23 ppm in treated nutmeat and hay samples, respectively, HED concurs with the proposed tolerances of 0.05 ppm in peanut nutmeat, and 0.25 ppm in peanut hay.  
	The submitted field trial data for thiamethoxam on alfalfa are acceptable, and support the proposed use of Cruiser 5FS as a pre-plant seed treatment.  An adequate number of trials were conducted in the appropriate geographic regions at 1X the maximum proposed rate.  Based on the maximum combined thiamethoxam ROCs of 0.04 and 0.10 ppm in treated forage and hay samples, respectively, HED concurs with the proposed tolerances of 0.05 ppm in alfalfa forage, and 0.12 ppm in alfalfa hay.  
	The submitted data for thiamethoxam use in food handling areas are acceptable, and support the proposed use of Optigard Flex Liquid as a spot, void, and crack and crevice treatment in food handling establishments.  An adequate variety of food commodities were exposed to thiamethoxam, in two different types of food handling establishments, at 1X the maximum proposed rate.  Maximum thiamethoxam and CGA-322704 residues were each <0.01 ppm in food commodities exposed to 1X treatment in food handling areas (with the vast majority of samples containing non-detectable residues).  Based on the presence of detectable residues of thiamethoxam or CGA-322704 in various samples, HED recommends a tolerance of 0.02 ppm in food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops).  
	There are no processed commodities associated with the proposed use on alfalfa.  The processed commodities associated with the proposed use on peanuts are peanut meal and refined oil.  Two peanut field trials were conducted in the US during the 1999 growing season in which peanut seeds treated at an exaggerated (roughly 6-6.5X) rate were grown for processing into peanut meal and refined oil.  Thiamethoxam residues were not detected in the nutmeat nor processed fractions of peanuts grown from peanut seeds treated at the 6-6.5X rate.  Residues were not detected in any of the peanut oil samples upon processing.  Residues were observed in the nutmeat and meal of peanuts, grown from peanut seeds treated at roughly a 2X rate, from both field trials.  The theoretical concentration factor for peanut meal (OPPTS Residue Chemistry Test Guideline 860.1520, Table 3) is 2.2X.  The empirical concentration factors for thiamethoxam in meal (range 2.0-3.1X, average 2.6X) conform well to the theoretical value.  A tolerance is not required in peanut oil.  Based on the HAFT combined residues of 0.05 ppm (0.09 ppm at a 2X rate) in peanut nutmeat, and the theoretical concentration factor for peanut meal of 2.2X, HED recommends a tolerance of 0.15 ppm in peanut meal.  
	Analytical reference standards for thiamethoxam and its metabolite, CGA-322704, are currently available at the EPA National Pesticide Standards Repository (NPSR).  
	There are no Codex or Mexican maximum residue limits (MRLs) established for residues of thiamethoxam in crops associated with this review.  Canada has established an MRL of 0.02 mg/kg for combined residues of thiamethoxam and CGA-322704 in all food crops.  

Regulatory Recommendations and Residue Chemistry Deficiencies

	HED has examined the residue chemistry database for thiamethoxam.  There are no residue chemistry issues that would preclude granting Section 3 registrations, and establishing permanent tolerances, for the requested use of thiamethoxam (as Cruiser PD or Cruiser 5FS) on peanuts, for the requested use (as Cruiser 5FS) on alfalfa, and for the requested use (as Optigard Flex Liquid) in food handling establishments.  Provided that the forthcoming human health risk assessment does not identify any issues of concern, the submitted data support tolerances for thiamethoxam, including its metabolites and degradates, in or on peanut nutmeat, hay and meal, alfalfa forage and hay, and food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops), at the levels listed below.  Compliance with the tolerance levels specified below is to be determined by measuring only thiamethoxam and CGA-322704 (calculated as thiamethoxam equivalents).  

        Peanut	0.05 ppm
        Peanut, hay	0.25 ppm
        Peanut, meal	0.15 ppm
        Alfalfa, forage	0.05 ppm
        Alfalfa, hay	0.12 ppm
        Food commodities/feed
        commodities (other than
        those covered by a higher
        tolerance as a result of use
        on growing crops) in
        food/feed handling
        establishments	0.02 ppm

	A revised Section F should be submitted to reflect the additional tolerance in peanut meal, and the higher tolerance arising from the food/feed handling use.  
Background

	Thiamethoxam is a broad-spectrum nitroguanidine insecticide which belongs to the pesticidal class of compounds known as the neonicotinoids (Group 4A).  It has activity against sucking and chewing insects, such as leafhoppers and potato beetles, as well as other insect pests, on a wide variety of crops.  It also is effective against a wide variety of interior and exterior pests, including termites, ants, beetles, and cockroaches.  It appears to interfere with the nicotinic acetylcholine receptors of the insect's nervous system, but the specific receptor site is unknown at this time.  It does not inhibit cholinesterase, nor does it interfere with sodium channels, and thus has a different mode of action than the organophosphate, carbamate and pyrethroid insecticides.  
	In support of a petition for use of thiamethoxam on peanuts (PP#9F7657), Syngenta submitted field trial data reflecting the seed treatment use of thiamethoxam (70% ai WS, and 5 lb ai/gal FS) on peanuts.  In support of a petition for use of thiamethoxam on alfalfa (PP#0F7707), Syngenta submitted field trial data reflecting the seed treatment use of thiamethoxam (5 lb ai/gal FS) on alfalfa.  In support of a petition for use of thiamethoxam in food handling establishments (PP#0F7734), Syngenta submitted data reflecting spot, void, and crack and crevice applications of thiamethoxam (2 lb ai/gal SC) in food handling areas of a restaurant and a delicatessen.  The nomenclature of thiamethoxam and its metabolites, is summarized in Table 1 (below), and the physicochemical properties of the technical grade of thiamethoxam are summarized in Table 2 (below).  

TABLE 1	Test Compound Nomenclature.  
Compound
                                       
Common name
Thiamethoxam
Company experimental name
CGA 293343
Molecular formula
C8H10ClN5O3S
Molecular weight
291.71
IUPAC name
3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene(nitro)amine
CAS name
3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-imine
CAS registry number
153719-23-4
End-use products (EPs)
70% ai WS formulation (Cruiser PD Insecticide; EPA File Symbol 100-RGAL)
5 lb ai/gal FS formulation (Cruiser 5FS Insecticide; EPA Registration #100-941)
2 lb ai/gal SC formulation (Optigard Flex Liquid; EPA Registration #100-1306)
Chemical structure of CGA-322704 metabolite (clothianidin)
                                       
        N-[(2-chloro-5-thiazoyl)methyl]-N'-methyl-N"-nitroguanidine
Chemical structure of CGA-265307 metabolite
                                       
              N-(2-chloro-thiazol-5-ylmethyl)-N'-nitroguanidine

TABLE 2	Physicochemical Properties of Technical Grade Thiamethoxam.  
Parameter
Value
Reference*
Melting point/range
139.1C
PMRA Regulatory Note (REG2001-03) on Thiamethoxam, 9 February 2001
pH
4.7 (1% solution in water)

Density
1.57 x 10[3] kg/m[3]

Water solubility
4.1 g/L (25°C)

Solvent solubility
Solvent
acetone
dichloromethane
ethyl acetate
hexane
methanol
octanol
toluene
                               Solubility (g/L)
                                      48
                                      110
                                      7.0
                                  <1 mg/L
                                      13
                                     0.62
                                     0.68

Vapor pressure
2.7 x 10-9  Pa (20C)
6.6 x 10-9  Pa (25C)

Dissociation constant, pKa
No dissociation for pH range 2 - 12

Octanol/water partition coefficient, Log(KOW)
0.13 +- 0.0017 (25C)

UV/visible absorption spectrum
Molar absorbance coefficients for the absorbance maximum:
16,800 L/mol/cm at 255 nm (neutral)
17,000 L/mol/cm at 255 nm (acidic)
15,900 L/mol/cm at 255 nm (basic)
(No further adsorption maxima between 290 and 750 nm were observed.)  
MRID #47287502
* As referenced in D349272; M. Doherty; 12 August 2008.  

860.1200  Directions for Use

	Peanuts:  The EPs proposed for use on peanuts are Cruiser PD (EPA File Symbol 100-RGAL), a WS formulation of thiamethoxam containing 70% ai, and Cruiser 5FS (EPA Registration #100-941), an FS formulation of thiamethoxam containing 5 lb ai/gal.  They are proposed for use as pre-plant seed treatments of peanuts to provide early season protection of seedlings against injury from thrips, aphids, wireworms and white grubs, and suppression of three-cornered alfalfa hoppers, and plant bugs.  The proposed use directions on peanuts, obtained from draft labels dated 7 December 2009 for Cruiser PD and Cruiser 5FS, are presented in Table 3 (below).  
	In response to questions from HED, Syngenta clarified that the maximum use rate for peanuts should be 0.08 lb ai/A instead of 0.266 lb ai/A (electronic message of 18 October 2010, from Syngenta's Patrick McCain to RD's Kable Davis).  This rate was calculated using assumptions which HED considers reasonable (850 seeds/lb, and 142 lb seeds/A).  
	Alfalfa:  The EP proposed for use on alfalfa is Cruiser 5FS (EPA Registration #100-941).  It is proposed for use as a pre-plant seed treatment of alfalfa to provide early season protection of seedlings against damage caused by aphids and leafhoppers (first cut crop only).  The proposed use directions on alfalfa, obtained from a draft label dated 3 March 2010 for Cruiser 5FS, are presented in Table 3 (below).  
	Food handling establishments:  The EP proposed for use in food handling establishments is Optigard Flex Liquid (EPA Registration #100-1306), an SC formulation of thiamethoxam that contains 2 lb ai/gal.  It is proposed for use as spot, void, and crack and crevice applications in food handling and other areas of food handling establishments.  The proposed use directions for food handling establishments, obtained from a draft label dated 10 June 2010 for Optigard Flex Liquid, are presented in Table 3 (below).  

TABLE 3	Summary of Proposed Use Directions on Peanuts and Alflalfa, and in Food Handling 		Establishments.  
                        Use Timing; Type; and Equipment
                 Product [File Symbol or Registration Number]
                                Single Use Rate
                            Maximum Uses per Season
                           Maximum Seasonal Use Rate
                                      PHI
                                    (Days)
                        Use Directions and Limitations
                                   Peanuts 
Pre-plant; seed treatment.  
                                  Cruiser PD
                                  [100-RGAL]
                                  Cruiser 5FS
                                   [100-941]
                             0.20-0.29 mg ai/seed
                                  1 (Implied)
                                     0.08
                                    lb ai/A
                                    NS [1]
No soil or foliar application of thiamethoxam to peanuts grown from seed treated with Cruiser PD or Cruiser 5FS.  Apply Cruiser PD in dry form, using equipment intended for dry-application seed treatment only (not for use in on-farm applicators; use in commercial seed treatment facilities only).  
                                   Alflalfa
Pre-plant; seed treatment.  
                                  Cruiser 5FS
                                   [100-941]
                               0.001 mg ai/seed
                                  1 (Implied)
                                NS (0.0130) [2]
                                      NS
No soil or foliar application of thiamethoxam to alfalfa grown from seed treated with Cruiser 5FS.  
                         Food Handling Establishments
Pest pressure; coarse low-pressure spot spray, void injection, or crack and crevice spray.  
                             Optigard Flex Liquid
                                  [100-1306]
                               0.05-0.10% spray
                                      NS
                                      NS
                                    NA [3]
Prior to application, remove or cover all food items in areas to be treated.  Do not apply where food utensils or food surfaces may become contaminated.  Treatments to be made by commercial pesticide applicators only.  
1. NS = Not Specified.  
2. The alfalfa field trials utilized single (and seasonal) use rates of 0.0037-0.0130 lb ai/A, based on the respective seeding rates (8.00-27.90 lb seeds/A), and an average of 210,000 alfalfa seeds/lb.  
3. NA = Not Applicable.  

	Conclusion
	The submitted use directions for treatment of peanuts and alfalfa, and for applications in food handling establishments, are sufficient to allow for evaluation of the submitted residue data relative to the proposed use patterns.  

860.1300 Nature of the Residue - Plants
	Metabolism Decision Memo D258614; G.J. Herndon; 31August 1999
	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000
	Residue Chemistry Memo D265079; G.J. Herndon; 8 May 2000
	Residue Chemistry Memo D281702; M. Doherty; 17 April 2007

	Plant metabolism studies with thiamethoxam have been submitted on corn, cucumber, lettuce, pear, potato, rice, tobacco and wheat.  The studies on cucumber, lettuce, pear and rice reflected foliar applications, while the studies on corn, potato and wheat reflected seed treatment and/or soil drench applications.  The tobacco studies included soil and foliar treatments.  HED previously determined (and continues to support the decision) that the ROCs, for purposes of tolerance enforcement and risk assessment, are the combined residues of thiamethoxam and CGA-322704.  

860.1300 Nature of the Residue - Livestock
	Metabolism Decision Memo D258614; G.J. Herndon; 31August 1999
	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000
	Residue Chemistry Memo D265079; G.J. Herndon; 8 May 2000

	The nature of the residue in livestock is adequately understood, based on acceptable goat and hen metabolism studies.  For purposes of tolerance enforcement and risk assessment, the ROCs are the combined residues of thiamethoxam and CGA-322704.  

860.1340 Residue Analytical Methods
	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000
	Residue Chemistry Memo D265079; G.J. Herndon; 8 May 2000
	Residue Chemistry Memo D271516; M. Doherty; 29 May 2001
	Residue Chemistry Memo D281702; M. Doherty; 17 April 2007

	Enforcement Method
	An HPLC method with UV or MS detection, Method AG-675, submitted in conjunction with previous thiamethoxam petitions, is adequate for collecting residue data, and enforcing tolerances for residues of thiamethoxam and CGA-322704 in crop and livestock commodities.  The validated LOQ for each analyte is 0.010 ppm in all plant matrices, with the exception of fruit juices (0.005 ppm), grass (0.05 ppm) and cured tobacco (0.10 ppm).  In livestock, the validated LOQs for residues of thiamethoxam and CGA-322704 are 0.010 ppm for each analyte in meat, poultry and eggs, and 0.005 ppm each in milk.  
	Briefly, samples are extracted with acetonitrile (ACN)/water (4:1, volume to volume, or v/v), and the extract is subjected to partitioning with toluene and hexane (livestock commodity and oil samples only), and then cleaned up by solid-phase extraction (SPE).  Residues of thiamethoxam and CGA-322704 are determined in fruits, vegetables, oils, grains, and livestock commodities using HPLC/UV.  HPLC/MS is used to determine residues in cotton commodities, tobacco commodities, and the forage, fodder and straw of cereal grains and grasses to achieve the desired LOQs.  The method includes a step in the calculation to convert residues of CGA-322704 to thiamethoxam equivalents.  
	Adequate method validation data have been submitted, and the method has undergone a successful ILV and PMV.  In addition, the method has been adequately radiovalidated in crop and livestock commodities.  
	Syngenta has submitted a re-written version of Method AG-675, and renamed it as Method GRM.009.04A (MRID #47786103), which supersedes Method AG-675.  The full extraction steps for plant and livestock commodities, including the microwave extraction step for liver, have been incorporated, as previously requested by HED as a condition of registration.  The LOQs of Method GRM.009.04A have been established at 0.010 ppm each for residues of thiamethoxam, CGA-322704 and CGA-265307.  Syngenta has submitted method validation data for Method GRM.009.04A (MRID #47786102).  No ILV data have been submitted, nor will ILV data be required, because the method is a revised version of an existing enforcement method.  Although the addition of a microwave extraction step is a significant change to the method, residues of thiamethoxam, CGA-322704 and CGA-265307 are likely to be low in livestock commodities (the dosing levels used in the metabolism studies were 100X for goats, and 400X for poultry).  In addition, the extensive cleanup procedures after the microwave extraction step are very similar to the cleanup procedures used for the Polytron extract of livestock commodity samples in Method AG-675, which has been adequately validated by the Biological and Economic Analysis Division's Analytical Chemistry Branch (BEAD/ACB).  HED will forward MRID #47786103 to FDA for an update of the current method in PAM Volume II.  
	Data-collection methods
	Peanuts:   Novartis Analytical Method AG-675 was used to determine residues of thiamethoxam and its metabolite, CGA-322704, in peanut nutmeat, hay, meal and oil, with HPLC/UV, HPLC/MS and HPLC/MS/MS systems successfully utilized to analyze the samples.  The limits of detection (LODs), defined as the lowest mass injected that could be reliably detected, were 1.25 ng for the HPLC/UV system, 0.125 ng for the HPLC/MS system, and 4 pg for the HPLC/MS/MS system.  The LOQ, defined as the lowest recovery level analyzed in peanut samples, was 0.01 ppm for each analyte in all matrices, resulting in an LOQ for combined residues of 0.02 ppm.  The analytical procedures that were used are summarized below.  
	The majority of the peanut nutmeat samples were analyzed using HPLC/UV.  Samples (10 grams) were extracted twice by polytron homogenization in ACN/water (4:1 v/v).  The extraction volume was 200 mL, and a 50-mL aliquot was analyzed.  The aliquot was evaporated to aqueous, and initially purified using reverse-phase (phenyl) SPE.  After elution from the phenyl SPE column with methanol/water (1:1, v/v), the sample was evaporated to aqueous, and partitioned with ethyl acetate.  The ethyl acetate fraction was evaporated, and further purified by normal-phase SPE, using a combination of amino and alumina cartridge columns (the amino column was omitted in a few analytical sets without affecting the results).  The eluted sample was evaporated, and reconstituted in 1 mL of mobile phase (increased volumes were used as needed for larger compound concentrations).  Analysis was performed using a normal-phase Spherisorb Amino HPLC column (250 mm length x 4.6 mm ID), with a mobile phase of hexane/ethyl acetate/methanol/ isopropanol (11:3:1:1, v/v).  The analytes were detected using a wavelength of 255 nm.  
	Peanut hay, and a few peanut nutmeat samples, were analyzed using HPLC/MS/MS.  Samples (10 grams) were extracted twice by polytron homogenization in ACN/water (4:1, v/v).  The extraction volume was 200 mL, and a 50-mL aliquot was analyzed.  Samples were first purified using a combination of anion-exchange (SAX) and reverse-phase (phenyl) SPE.  After elution from the phenyl SPE column with methanol/water (1:1, v/v), the sample was evaporated to aqueous, and partitioned with ethyl acetate (although some of the nutmeat samples were analyzed after elution from the phenyl SPE by evaporating to aqueous, and diluting to final volume as described below).  The ethyl acetate fraction was evaporated, and further purified by normal phase SPE using an alumina cartridge column.  The eluted sample was evaporated, and reconstituted in 30 mL of ACN/water (1:9, v/v); increased volumes were used as needed
for larger compound concentrations.  Analysis was performed using a Phenomenex Luna 311 C18 HPLC column (250 mm length x 2.0 mm ID).  The mobile phase was a gradient of ACN and water, each mixed with 0.1% acetic acid.  Thiamethoxam was detected by collision-induced dissociation (CID) of the parent ion (M+H[+] ion, m/z of 292), to form the daughter ion with m/z of 211.2.  The m/z 211.2 daughter ion was used to detect and quantify thiamethoxam.  The metabolite, CGA-322704, was detected by CID of the parent ion (M+H[+] ion, m/z of 250), to form a daughter ion with m/z of 169.  The m/z 169 daughter ion was used to detect and quantify CGA-322704.  
	Peanut meal samples were analyzed by HPLC/MS.  Samples (10 grams) were extracted twice by polytron homogenization in ACN/water (4:1, v/v).  The extraction volume was 200 mL, and a 50 mL aliquot was analyzed.  The aliquot was evaporated to aqueous, and initially purified using reverse-phase (phenyl) SPE.  After elution from the phenyl SPE column with methanol/water (1:1, v/v), the sample was evaporated to aqueous, and partitioned with ethyl acetate.  The ethyl acetate fraction was evaporated, and further purified by normal phase SPE using a combination of amino and alumina cartridge columns.  The eluted sample was evaporated, and reconstituted in 1 mL ACN/water (1:9, v/v).  Analysis was performed using a Phenomenex Luna 311 C18 HPLC column (250 mm length x 2.0 mm ID).  The mobile phase was a gradient of ACN and water, each mixed with 0.1% acetic acid.  Thiamethoxam was detected using the parent ion (M+H[+] ion, m/z of 292). The metabolite, CGA-322704, was detected using the parent ion (M+H[+] ion, m/z of 250).  
	Peanut oil samples were analyzed by HPLC/UV.  Samples (5 grams) were extracted by shaking in hexane, salt and toluene to form a 3-layer partition (aqueous in the bottom layer, ACN and toluene in the middle layer, and hexane in the top layer).  The middle layer was isolated, evaporated, and initially purified using reverse-phase (phenyl) SPE.  After elution from the phenyl SPE column with methanol/water (1:1, v/v), the sample was evaporated to aqueous, and partitioned with ethyl acetate.  The ethyl acetate fraction was evaporated, and further purified by normal phase SPE, using a combination of amino and alumina cartridge columns.  Oil samples were analyzed using the HPLC/UV system described above.  
	The validity of the method for the analysis of thiamethoxam and CGA-322704 in peanuts, peanut hay, peanut meal, and peanut oil was demonstrated by including control (untreated) samples, and fortified control samples along with each analytical sample set.  The fortification levels used for the concurrent recoveries were sufficient in magnitude to bracket the measured residue levels.  The overall (all matrices, all fortification levels) average concurrent recoveries ( -  - +- standard deviation) were 91 +- 13% for thiamethoxam, and 89  -  - +- 13% for CGA-322704.  Adequate sample calculations and example chromatograms were provided.  Where detected in control (untreated) samples, total thiamethoxam residues were below the LOQ.  
	Alfalfa:  Syngenta Analytical Method GRM009.02A was used to determine residues of thiamethoxam and its metabolite, CGA-322704, in alfalfa commodities.  
	For forage analysis, approximately 10.0 grams of sample were weighed into a wide-mouth bottle.  The control samples used for procedural recoveries were fortified at the LOQ and higher to bracket the residues found in the treated samples.  ACN/water (4:1 v/v) was added (135 mL) to each sample, and then homogenized (using a Polytron homogenizer) for two minutes at 8,000-12,000 rpm.  Subsequently, 20 mL of ACN/water (4:1 v/v) was used to rinse the rotating shaft of the Polytron, and then added to the sample bottle.  The sample was allowed to settle for 3-5 minutes.  A Whatman #5 filter was placed onto a Buchner funnel, and the funnel was positioned on top of a 250 mL side-arm flask.  The solvent and any suspended material were decanted into a funnel, leaving the precipitate on the bottom of the bottle.  A total of 35 mL of ACN/water (4:1 v/v) was used to rinse the sample bottle, Buchner funnel, side-arm flask, and filter paper (20 mL to rinse out the sample bottle, and 15 mL to rinse out the side-arm flask).  The sample was transferred to a 200 mL volumetric flask, and diluted to 200 mL with ACN/water (4:1 v/v).  An aliquot of 5 mL was placed into a 25 mL concentration tube, and concentrated in a nitrogen evaporator (at 35°C) to a volume of less than 2 mL.  The sample was brought to a volume of 5 mL using ACN/water (1:9 v/v).  The necessary dilutions were performed, and the samples were vialed for HPLC/MS/MS analysis.  
	For hay analysis, approximately 5.0 grams of sample were weighed into a wide-mouth bottle.  Control samples used for procedural recoveries were fortified at the LOQ and higher to bracket the residues found in the treated samples.  ACN/water (4:1 v/v) was added (75 mL) to each sample, and then homogenized (using a Polytron homogenizer) for two minutes at 8,000-1,2000 rpm.  Subsequently, 10 mL of ACN/water (4:1 v/v) was used to rinse the rotating shaft of the Polytron, and then added to the sample bottle.  The sample was allowed to settle for 3-5 minutes.  A Whatman #5 filter was placed onto a Buchner funnel, and the funnel was positioned on top of a 250mL side-arm flask.  The solvent and any suspended material were decanted into a funnel, leaving the precipitate on the bottom of the bottle.  A total of 15 mL of ACN/water (4:1 v/v) was used to rinse the sample bottle, Buchner funnel, side-arm flask, and filter paper (10 mL to rinse out the sample bottle, and 5 mL to rinse out the side-arm flask).  The sample was transferred to a 100 mL volumetric flask, and diluted to 100 mL with ACN/water (4:1 v/v).  An aliquot of 5 mL was placed into a 25 mL concentration tube, and concentrated in a nitrogen evaporator (at 35°C) to a volume of less than 2 mL.  The sample was brought to a volume of 5 mL using ACN/water (1:9 v/v).  The necessary dilutions were performed, and the samples were vialed for HPLC/MS/MS analysis.  
	Method validation was completed at three fortification levels for thiamethoxam and CGA-322704 prior to analysis of the field trial samples.  The average recoveries of thiamethoxam from alfalfa forage at the LOQ (0.01 ppm), 2X LOQ and 10X LOQ were 77, 70 and 66%, respectively, whereas the average recoveries from alfalfa hay were 84, 117 and 95%, respectively.  The average recoveries of CGA-322704 from alfalfa forage at the LOQ (0.01 ppm), 2X LOQ and 10X LOQ were 79, 70 and 76%, respectively, whereas the average recoveries from alfalfa hay were 93, 96 and 89%, respectively.  Adequate sample calculations and example chromatograms were provided.  
	In addition, the performance of the method was demonstrated by fortifying untreated control samples with thiamethoxam and CGA-322704 prior to extraction.  These fortified samples were analyzed along with each analytical sample set.  The overall (all fortification levels) average concurrent thiamethoxam recoveries ( -  - +- standard deviation) were 95 +- 9% and 91 +- 15% from forage and hay, respectively.  The overall average concurrent CGA-322704 recoveries were 85 +- 17% and 85 +- 17% from forage and hay, respectively.  Recovery values were corrected for control residues, if any.  The fortification levels used for the concurrent recoveries were sufficient in magnitude to bracket the measured residue levels.  
	Food handling establishments:  Samples of the various food commodities were analyzed using Novartis Analytical Method AG-675.  Method modifications were issued 28 July 2008 to:  

                  1. document apparatus that was removed from analysis, 
                  2. document modifications to the method, 
                  3. describe preparation of the calibration standard solutions, 
                  4. identify the HPLC/MS/MS detector used and provide the instrument conditions employed, and 
                  5. describe the calculations used for residue determination.  

	To summarize the method, 10.0-gram samples were extracted twice by homogenization in ACN/water (4:1, v/v).  The extracts were combined, and brought to a final volume of 200 mL.  A 20.0-mL aliquot was processed through a saltwater/toluene/hexane/ACN liquid-liquid partition cleanup step, resulting in three layers:  

                  1. a hexane layer (containing fats and oils), which was discarded, 
                  2. an ACN/toluene layer, which was transferred to an evaporation flask, and 
                  3. an aqueous layer, which was back-extracted with 2% toluene in ACN, and transferred to the same evaporation flask containing the ACN/toluene layer. 

The remaining organic layers were combined, and concentrated to an aqueous remainder.  Additional water, saturated with NaCl, was added to the concentrate.  The analytes were then partitioned (two times) into ethyl acetate.  The combined ethyl acetate extracts were evaporated to dryness, reconstituted in ethyl acetate/hexane (1:4, v/v), and subjected to amino SPE cleanup.  The resulting eluate was evaporated to dryness.  The sample was re-dissolved in 1 mL of HPLC-grade ACN, followed by 9 mL of HPLC-grade water, and then subjected to HPLC analysis.  Final determination was by HPLC/MS/MS.  The LOQ was 0.01 ppm for both analytes.  
	The analytical method was validated using control samples of white bread, whole milk, butter, raw hamburger, and processed chicken prior to the analysis of food samples in this study.  Triplicate samples were fortified with thiamethoxam and CGA322704 at the LOQ (0.010 ppm), and 10X LOQ (0.10 ppm).  The analytical method was not validated in lettuce and apples as part of this study because these were matrices for which the method had been used previously.  The performance of the method for determination of thiamethoxam and CGA322704 residues was also demonstrated by fortifying at least one untreated control sample of each matrix with thiamethoxam and CGA322704 prior to extraction.  These fortified samples were analyzed concurrently with each analytical sample set.  All method recoveries, from both the method validation study, and the concurrent analysis of fortified samples, were within the generally recognized acceptable range of 70-120%.  

	Conclusions
	The various data-collection methods, used for analysis of samples taken from the magnitude of the residue studies discussed in this summary document, are based on either Method AG-675 or Method GRM009.02A.  The methods were deemed acceptable for use with all matrices analyzed in these studies.  HED will forward Method GRM.009.04A (MRID #47786103) to FDA for an update of the thiamethoxam enforcement method in PAM Volume II.  

860.1360 Multiresidue Methods
	Residue Chemistry Memos D259838 and D259839; G.J. Herndon; 28 September 1999
	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000
	FDA Pestrak Database; June 2005

	The Agency has reviewed data concerning the recovery of residues of thiamethoxam using FDA MRM protocols of PAM Volume I.  Thiamethoxam was partially recovered (50-60%) using MRM Section 302 (Protocol D), but was not recovered using Sections 303 or 304 (Protocols E or F).  Metabolites CGA-322704 and CGA-265307 were tested using Protocol C, but did not yield adequate responses; no further testing was conducted for the metabolites.  The results of the multiresidue testing were forwarded to FDA and ACB/BEAD.  

860.1380 Storage Stability
	Residue Chemistry Memo D285545; M. Doherty; 6 November 2002
	Residue Chemistry Memo D281702; M. Doherty; 17 April 2007

	Samples in the peanut field trial and processing studies were stored frozen from sampling to extraction for a maximum duration of 5.1 months.  Samples in the alfalfa field trial study were stored frozen from sampling to extraction for a maximum duration of 15.9 months.  Samples in the food handling establishment study were stored frozen from sampling to extraction for a maximum duration of 2.6 months.  
	Concurrent storage stability data were not submitted with these studies.  However, the storage durations and conditions for samples from the current field trial, processing, and food handling establishment studies are supported by previously conducted storage stability studies on diverse crops, and animal commodities.  
	For plant commodities, adequate storage stability data are available on five diverse crops.  These data indicate that residues of thiamethoxam and its metabolite, CGA-322704, are stable for up to approximately 24 months of frozen storage (-18°C) in apple, tomato, potato, rapeseed, and corn grain (D281702; M. Doherty; 17 April 2007).  In addition, residues of thiamethoxam and CGA-322704 have been demonstrated to be relatively stable in canola oil, corn meal, leaf lettuce, safflower seed, and tomato puree for up to roughly 40-42 months at -20°C.  These data represent sufficiently diverse crops (a root crop, a leafy vegetable, a grain, an oilseed, a fruit, and a fruiting vegetable) to allow the determination that residues of thiamethoxam and CGA-322704 are stable in all crops for at least 24 months, and in associated processed commodities for at least 40 months.  
	For animal commodities, HED has reviewed data indicating that residues of thiamethoxam, CGA-322704 and CGA-265307 are reasonably stable in eggs, milk, beef muscle, and beef liver for 15-17 months.  In addition, residues of CGA-322704 have been demonstrated to be stable in beef liver stored frozen for up to 47.7 months.  
	Samples collected from the magnitude of the residue studies were stored frozen prior to residue analysis.  The storage durations and conditions of samples are presented in Table 4 (below).  

TABLE 4	Summary of Storage Conditions and Durations of Samples from the Peanut, Alfalfa, and 			Food Handling Establishment Studies.  
                                    Matrix
                           Storage Temperature (°C)
                      Maximum Storage Duration (Months) 1
             Interval of Demonstrated Storage Stability (Months) 2
Peanut nutmeat
                                      -20
                                      5.1
                                      24
Peanut hay
                                       
                                       
                                       
Peanut meal
                                       
                                       
                                      40
Peanut refined oil
                                       
                                       
                                       
Alfalfa forage
                                      -10
                                     15.9
                                      24
Alfalfa hay
                                       
                                       
                                       
Butter
                                    <-10
                                      2.6
                                       
Whole milk
                                       
                                       
                                       
Raw hamburger
                                       
                                       
                                       
Apple
                                       
                                       
                                       
Head lettuce
                                       
                                       
                                       
Processed chicken
                                       
                                      2.6
                                      40
White bread
                                       
                                       
                                       
1. Actual storage duration from harvest to extraction for analysis.  
2. Thiamethoxam and CGA-322704 residues are relatively stable for up to 24 months in frozen RAC samples of apple, tomato, potato, rapeseed, leaf lettuce, and corn grain, and for up to 40 months in frozen processed commodity samples of corn meal, tomato puree, and canola oil (D281702; M. Doherty; 17 April 2007).  

	Conclusions
	The available storage stability data for thiamethoxam ROCs in plants are adequate to support the storage durations and conditions of samples of peanut and alfalfa commodities from the submitted field trial and processing studies.  The submitted food handling establishment study is supported by the available storage stability data in plant and animal commodities.  There are no storage stability issues, and no corrections for potential decline during storage are needed for any of the residue studies.  

860.1400 Water, Fish, and Irrigated Crops

	There are no proposed uses that are relevant to this guideline topic.  
860.1460 Food Handling
	DER for MRID #48110202 (Food handling establishment study with various food items)

TABLE 8	Summary of (1X) Residue Data from Uncovered Foods Exposed to Thiamethoxam in the 		Food Handling Establishment Study.  
Commodity
                                Total Use Rate 
                                  (%ai, w/v)
                             Sample Event (Hours)
                           Thiamethoxam Levels (ppm)

                                       n
                                     Min.
                                     Max.
                                     HA 1
                                    Median
                                     Mean
                                   Std. Dev.
Butter
                                      0.1
                                       1
                                       2
                                    ND [2]
                                      ND
                                      ND
                                      ND
                                      ND
                                    NA [3]

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
White bread
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA
Whole milk
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Raw hamburger
                                      0.1
                                       1
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Processed chicken
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Apple
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA

                                       
                                       8
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA
Head lettuce
                                      0.1
                                       1
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
1. HA = Highest Average.  
2. ND = Not Detected.  
3. NA = Not Applicable (standard deviation is only applicable for sample sets of n >= 3 samples).  

TABLE 9	Summary of (1X) Residue Data from Uncovered Foods Exposed to Thiamethoxam in the 		Food Handling Establishment Study.  
Commodity
                                Total Use Rate 
                                  (%ai, w/v)
                             Sample Event (Hours)
                            CGA-322704 Levels (ppm)

                                       n
                                     Min.
                                     Max.
                                     HA 1
                                    Median
                                     Mean
                                   Std. Dev.
Butter
                                      0.1
                                       1
                                       2
                                    ND [2]
                                      ND
                                      ND
                                      ND
                                      ND
                                    NA [3]

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
White bread
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Whole milk
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA
Raw hamburger
                                      0.1
                                       1
                                       2
                                      ND
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Processed chicken
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Apple
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
Head lettuce
                                      0.1
                                       1
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       4
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA

                                       
                                       8
                                       2
                                      ND
                                      ND
                                      ND
                                      ND
                                      ND
                                      NA
1. HA = Highest Average.  
2. ND = Not Detected.  
3. NA = Not Applicable (standard deviation is only applicable for sample sets of n >= 3 samples).  

	A summary of the reviewed data from the food handling establishment study is presented in Tables 8 and 9 (above).  The study was conducted to determine the amount of thiamethoxam residues in food following indoor spot, and crack and crevice treatments in a food handling establishment, using the 2 lb ai/gal SC formulation at the maximum proposed label rate.  The study also provided information on the residues in food resulting from treatment at an exaggerated rate, in order to gauge the potential for misuse of the product.  The study report summarized residue data for thiamethoxam and its major metabolite, CGA322704 (clothianidin), in samples of foods typically used in 2 types of food handling establishments, including an oily food (butter), baked cereal product (bread), beverage (milk), raw meat (hamburger), processed meat (chicken), fresh fruit (apple), and fresh vegetable (lettuce).  
	Two types of food handling establishments (in which the principal business involved the preparation and sale of food directly to the consuming public) were used in the study.  The establishments selected, a restaurant and a delicatessen, were typical of the expected product use areas.  Each establishment received an initial application of Optigard Flex Liquid at a dilution rate of 0.1% ai, weight to volume (ai, w/v), equal to 16 mL (3.9 g ai) per gallon of finished solution, and a second application at 0.2% ai, w/v, equal to 32 mL (7.8 g ai) per gallon of finished solution.  Two days elapsed between applications at each establishment.  Crack and crevice, and spot treatments were made to the kitchen, storage and eating areas of each facility by a commercial licensed pest control operator.  Crack and crevice treatment included the lower portion of the walls, cabinets and areas where pests may hide or enter a building.  Spot treatment included baseboard areas of the floor and walls that did not exceed 2 square feet per spot (sq ft/spot).  
	Foods that were used in the study represented the wide range of food items that are expected to be prepared and served in food service establishments.  A single control sample of each of the seven food types was collected at each establishment prior to the 1X rate application.  Six replicates of each food type without any packaging (uncovered), and six replicates of each food type that were covered, were placed on tables in the food preparation and serving areas (three replicates of each food type/coverage type in each area).  Duplicate samples of each food type/coverage type (one replicate from each of the two areas) were collected at 1, 4 and 8 hours following each application at each establishment.  All samples were stored frozen after collection, and shipped frozen to Morse Laboratories in Sacramento, CA.  
	Samples were analyzed by Morse Laboratories using Method AG-675.  Final determination was by HPLC/MS/MS.  The LOQ was 0.01 ppm for both analytes in all matrices, resulting in an LOQ for combined residues of 0.02 ppm.  
	The first stage of sample analysis was focused on the uncovered food samples exposed for eight hours following the application of the exaggerated (2X) use rate, which would be considered the worst-case scenario for residues.  The results of these analyses (all residues were either non-detectable or <LOQ) led to the second stage, which was analysis of uncovered food samples only from each of the exposure intervals (1, 4 or 8 hours) following each application rate (1X or 2X).  These data showed that residues were not present at levels at or above the LOQ from any sampling event following either application rate.  
	Conclusions
	The submitted data on thiamethoxam residues in food commodities following indoor spot, and crack and crevice treatments in food handling establishments are adequate.  The data reflect the use of the 2 lb ai/gal SC formulation of thiamethoxam at 0.1% ai (w/v) and 0.2% ai (w/v).  An acceptable method was used for the quantitation of thiamethoxam residues in the various food commodities, and adequate storage stability data are available to support the sample storage durations and conditions.  In addition, there were no thiamethoxam residues detected at quantifiable levels in any of the wide variety of uncovered food types which were exposed for up to 8 hours to an exaggerated use pattern (1X rate, followed by 2X rate within 48 hours).  
	Based on the presence of detectable residues of thiamethoxam or CGA-322704 in various samples, HED recommends a tolerance of 0.02 ppm in food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops).  

860.1480 Meat, Milk, Poultry, and Eggs

	The livestock feedstuffs associated with the proposed seed treatment uses of thiamethoxam on peanuts and alfalfa are peanut meal and hay, and alfalfa forage, hay, meal and silage.  These uses have the potential for exposing livestock to thiamethoxam residues in their diet.  Secondary transfer of thiamethoxam ROCs to meat, milk, poultry and eggs is therefore possible from the proposed uses on peanuts and alfalfa.  Ergo, reasonably balanced dietary burdens (RBDBs) were recalculated for the currently requested uses, and are presented in Table 5 (below).  

TABLE 5	Calculation of Reasonably Balanced Dietary Burdens of Thiamethoxam Residues to 			Livestock.  
Feedstuff
                                    Type 1
                                % Dry Matter 2
                                   % Diet 2
                                Tolerance (ppm)
                         Dietary Contribution (ppm) 3
                      Beef Cattle - R 15%, CC 80%, PC 5%
Soybean hulls
                                       R
                                      90
                                      15
                                      2.0
                                     0.34
Potato processed waste
                                      CC
                                      20
                                      30
                                    0.25 4
                                     0.38
Barley grain
                                      CC
                                      88
                                      50
                                      0.3
                                     0.17
Soybean meal
                                      PC
                                      88
                                       5
                                    0.02 5
                                    0.0012
TOTAL BURDEN
                                       
                                       
                                      100
                                       
                                     0.90
                     Dairy Cattle - R 45%, CC 45%, PC 10%
Almond hulls
                                       R
                                      90
                                      10
                                      1.2
                                     0.14
Wheat forage
                                       R
                                      25
                                      20
                                      0.5
                                      0.4
Barley hay
                                       R
                                      88
                                      15
                                      0.4
                                     0.07
Barley grain
                                      CC
                                      88
                                      45
                                      0.3
                                     0.16
Undelinted cottonseed
                                      PC
                                      88
                                      10
                                      0.1
                                     0.012
TOTAL BURDEN
                                       
                                       
                                      100
                                       
                                     0.78
                           Poultry - CC 75%, PC 25%
Barley grain
                                      CC
                                      88
                                      75
                                      0.3
                                     0.26
Alfalfa meal
                                      PC
                                      89
                                       5
                                     0.12
                                     0.007
Cottonseed meal
                                      PC
                                      88
                                      20
                                     0.1 6
                                     0.023
TOTAL BURDEN
                                       
                                       
                                      100
                                       
                                     0.29
                            Swine - CC 85%, PC 15%
Barley grain
                                      CC
                                      88
                                      20
                                      0.3
                                     0.068
Field corn grain
                                      CC
                                      88
                                      65
                                     0.02
                                     0.015
Cottonseed meal
                                      PC
                                      88
                                      15
                                     0.1 6
                                     0.017
TOTAL BURDEN
                                       
                                       
                                      100
                                       
                                     0.10
1. R = Roughage, CC = Carbohydrate Concentrate, PC = Protein Concentrate.  
2. OPPTS 860.1000 Table 1 Feedstuffs (June 2008).  
3. Contribution = ([Tolerance / %DM] x %Diet) for beef and dairy cattle.  Contribution = (Tolerance x %Diet) for poultry and swine.  
4. Based on the 0.25 ppm potato tolerance.  
5. Based on the 0.02 ppm soybean seed tolerance.  
6. Based on the 0.1 ppm undelinted cottonseed tolerance.  

	Conclusions
	Because the projected thiamethoxam ROCs in poultry at the 1X feeding level would still be <LOQ, HED concludes that residues in eggs and poultry meat, fat, and meat byproducts remain a 40CFR §180.6[a][3] situation (there is no expectation of finite residues in these commodities).  As a result, tolerances are not required.  This conclusion will be reevaluated when new poultry feed items are proposed in the future.  The RBDBs to cattle and swine have not increased significantly from those previously calculated.  Therefore, the current tolerances in livestock commodities remain appropriate, and do not need to be increased.  

860.1500 Crop Field Trials
	DER for MRID #45093704 (Crop field trials with peanuts)
	DER for MRID #48020201 (Crop field trials with alfalfa)

TABLE 6	Summary of Residue Data from Peanut Field Trials with Thiamethoxam.  
                                 Peanut Matrix
                         Use Rate (g ai/100 kg Seeds)
                                      EP
           Combined Residue Levels (ppm Thiamethoxam Equivalents) 1
                                       
                                       
                                       
                                       n
                                     Min.
                                   Max. [2]
                                    HAFT 3
                                     Mean
                                   Std. Dev.
Hay
                                      200
                                      5FS
                                      18
                                   <0.02
                                     0.06
                                     0.05
                                     0.026
                                     0.011

                                       
                                     70WS
                                      36
                                   <0.02
                                     0.23
                                     0.20
                                     0.032
                                     0.043
Nutmeat
                                       
                                      5FS
                                      18
                                   <0.02
                                     0.05
                                     0.05
                                     0.026
                                     0.011

                                       
                                     70WS
                                      36
                                   <0.02
                                     0.04
                                     0.03
                                     0.021
                                     0.004
Hay
                                      600
                                     70WS
                                       4
                                   <0.02
                                     0.79
                                     0.64
                                     0.33
                                     0.38
Nutmeat
                                       
                                       
                                       4
                                   <0.02
                                     0.02
                                     0.02
                                     0.02
                                       0
1. For calculation of the mean, HAFT, and standard deviation, the LOQ was used for residues reported as below the LOQ.  
2. The table does not include the residue level in nutmeat used for the processing study.  As noted in Section 860.1520, a RAC residue of 0.09 ppm was found in nutmeat following application at 200g ai/100 kg seeds (equivalent to 0.16 lb ai/A).  
3. HAFT = Highest Average Field Trial.  

	Peanuts:  A summary of the reviewed data from the peanut field trials is presented in Table 6 (above).  Twelve peanut field trials were conducted in the US during the 1999 growing season.  Each site consisted of one untreated plot, and at least one treated plot.  At all trial sites, one treated plot was planted with peanut seeds that had been treated with an aqueous slurry of the 70% ai WS formulation.  At 3 sites, side-by-side trials were conducted, comparing the 70% ai WS product with the 5 lb ai/gal FS formulation.  For both formulations, peanut seeds were treated at the rate of 200 grams ai per 100 kg of seeds.  Based on the amounts of seeds planted per acre, the rates were 0.126-0.24 lb ai/A (1.5-3X the proposed maximum per-acre rate).  The peanut crops were allowed to grow to commercial maturity according to good agricultural practices.  Samples of nutmeat and hay were harvested 101-153 days after planting (DAP).  At 2 of the trial sites (in GA and TX), peanut seeds treated at an exaggerated rate (0.48-0.522 lb ai/A) were also grown, for processing into peanut meal and refined oil.  Additionally, at 2 trial sites (in GA and TX) samples were harvested at 4 time intervals, in order to assess residue decline.  
	Samples of the peanut RACs were analyzed for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), using Method AG-675.  This method is adequate for data collection, based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte matrices, resulting in an LOQ for combined residues of 0.02 ppm.  
	In nutmeat, the highest individual residue was 0.04 ppm for thiamethoxam, and 0.01 ppm for CGA-322704, excluding the samples generated for processing.  The nutmeat for processing, from an application rate of 0.16 lb ai/A, had total residues of 0.09 ppm.  In hay, the highest individual residue was 0.19 ppm for thiamethoxam, and 0.03 ppm for CGA-322704.  A rate response was observed where exaggerated rates were included.  Residues following application of the 70% ai WS and 5 lb ai/gal FS formulations were similar in the side-by-side comparison trials. The magnitude of the residue is therefore unaffected by the choice of either formulation.  Total residues in hay were observed to decline with time at one decline field trial, dropping from a highest average residue of 0.04 ppm on day 111 (after planting of the treated seed) to 0.02 ppm on day 132.  Total nutmeat residues from this field trial increased from day 111 (highest average residue of 0.01 ppm) to day 118 (0.04 ppm), and subsequently declined to 0.01 ppm by day 132.  No decline was detected in the other decline field trial due to the low residues observed.  
	Conclusions
	The submitted peanut field trial data are adequate, and reflect the planting of peanut seeds treated with either the 70% ai WS formulation, or the 5 lb ai/gal FS formulation of thiamethoxam at 200 g ai/100 kg seeds (0.126-0.24 lb ai/A, 1.5-3X the maximum proposed use rate).  The study satisfied OPPTS Residue Chemistry Test Guideline 860.1500 (Tables 1 and 5) for number and geographic distribution of the twelve field trial locations to determine the magnitude of the residues of thiamethoxam and its major metabolite, CGA-322704 (clothianidin), in peanut RACs.  An acceptable method was used for the quantitation of thiamethoxam residues in peanut nutmeat and hay, and adequate storage stability data are available to support sample storage durations and conditions.  
	Because a large percentage of the residue values were below the combined LOQ of 0.02 ppm, the tolerance harmonization spreadsheet was not used to determine an appropriate tolerance.  Based on the maximum combined thiamethoxam ROCs of 0.09 and 0.23 ppm in 1.5X- to 3X-treated nutmeat and hay samples, respectively, HED recommends a tolerance of 0.05 ppm in peanut nutmeat, and a tolerance of 0.25 ppm in peanut hay.  

TABLE 7	Summary of Residue Data from Alfalfa Field Trials with Thiamethoxam.  
                                    Alfalfa
                                   Commodity
                                    Maximum
                            Use Rate [1] (lb ai/A)
                                     EP 2
                             Residue Levels (ppm)
                                       
                                       
                                       
                                    Minimum
                                    Maximum
                                    HAFT 3
                                 Thiamethoxam
Forage 1st cutting 
                                    0.0130
                                  Cruiser 5FS
                                   <0.01
                                     0.03
                                     0.03
Forage 2nd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
Forage 3rd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
Hay 1st cutting 
                                       
                                       
                                   <0.01
                                     0.09
                                     0.08
Hay 2nd cutting 
                                       
                                       
                                   <0.01
                                     0.01
                                     0.01
Hay 3rd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
                                  CGA-322704
Forage 1st cutting 
                                    0.0130
                                  Cruiser 5FS
                                   <0.01
                                   <0.01
                                   <0.01
Forage 2nd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
Forage 3rd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
Hay 1st cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
Hay 2nd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
Hay 3rd cutting 
                                       
                                       
                                   <0.01
                                   <0.01
                                   <0.01
1. The alfalfa field trials utilized single (and seasonal) use rates of 0.0037-0.0130 lb ai/A, based on the respective seeding rates (8.00-27.90 lb seeds/A), and an average of 210,000 alfalfa seeds/lb.  
2. EP = End-use Product.  
3. HAFT = Highest Average Field Trial (average of duplicate measurements).  

	Alfalfa:  A summary of the reviewed data from the alfalfa field trials is presented in Table 7 (above).  Twelve alfalfa field trials were conducted in the US during the 2008 and 2009 growing seasons.  Each site consisted of one untreated plot, and one treated plot.  The treated plots were planted with alfalfa seeds that had been treated with an aqueous slurry of the 5 lb ai/gal FS formulation, at the rate of 0.001 milligrams of ai per seed (mg ai/seed).  Based on seeding rates of 8.0 to 27.9 lb seeds/A, the application rate is equivalent to 0.0037 to 0.0130 lb ai/A.  The alfalfa crop was allowed to grow to commercial maturity according to good agricultural practices.  Samples of forage and hay were harvested at roughly 45 DAP (first cutting), 45 days after first cutting (second cutting), and 45 days after second cutting (third cutting) at all trial sites except one (in IA), where the third cutting was not harvested.  At one trial site (in CA), additional samples were harvested at 24, 31, 38, and 52 DAP, in order to assess residue decline.  
	Samples of the RACs, alfalfa forage and hay, were analyzed for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), using Method GRM009.02A.  This method is also known as ADPEN Method M1104, and is adequate for data collection, based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte, resulting in an LOQ for combined residues of 0.02 ppm.  
	The maximum residues of thiamethoxam and CGA-322704 were, respectively, 0.03 and <0.01 ppm in alfalfa forage grown from treated seed.  The maximum residues of thiamethoxam and CGA-322704 were, respectively, 0.09 and <0.01 ppm in alfalfa hay grown from treated seed.  The maximum combined residues of thiamethoxam and CGA-322704 were 0.04 and 0.10 ppm in alfalfa forage and hay, respectively.  In addition, residue decline data indicated that thiamethoxam residues in alfalfa forage decreased from 0.16 ppm at 24 DAP to below the method LOQ (<0.01 ppm) at 52 DAP.  The CGA-322704 residues in alfalfa forage were <LOQ at all time points.  Residue decline data indicated that thiamethoxam residues in alfalfa hay decreased from 0.44 ppm at 24 DAP to below the method LOQ (<0.01 ppm) at 90 DAP (second cutting).  The CGA-322704 residues in alfalfa hay were 0.02 ppm at 24 DAP, and <LOQ at all time points thereafter.  
	Conclusions
	The submitted alfalfa field trial data are adequate, and reflect the planting of alfalfa seeds treated with the 5 lb ai/gal FS formulation of thiamethoxam at 0.001 mg ai/seed, with harvest occurring at 45 DAP.  The study satisfied OPPTS Residue Chemistry Test Guideline 860.1500 (Tables 1 and 5) for number and geographic distribution of the twelve field trial locations to determine the magnitude of the residues of thiamethoxam and its major metabolite, CGA-322704 (clothianidin), in alfalfa RACs.  An acceptable method was used for the quantitation of thiamethoxam residues in alfalfa forage and hay, and adequate storage stability data are available to support sample storage durations and conditions.  
	Because a large percentage of the residue values were below the combined LOQ of 0.02 ppm, the tolerance harmonization spreadsheet was not used to determine an appropriate tolerance.  Based on the maximum combined thiamethoxam ROCs of 0.04 and 0.10 ppm in 1X-treated forage and hay samples, respectively, HED recommends a tolerance of 0.05 ppm in alfalfa forage, and a tolerance of 0.12 ppm in alfalfa hay.  
860.1520 Processed Food and Feed
	DER for MRID #45093704 (Processed food/feed from peanuts)

	There are no processed commodities associated with the proposed use on alfalfa.  
	Two peanut field trials were conducted in the US during the 1999 growing season in which peanut seeds treated at exaggerated rates were grown for processing into peanut meal and refined oil.  
	Samples of the peanut RACs and processed fractions were analyzed for residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin), using Method AG-675 via HPLC/UV, HPLC/MS or HPLC/MS/MS.  This method is adequate for data collection, based on acceptable concurrent method recoveries.  The LOQ was 0.01 ppm for each analyte in all matrices, resulting in an LOQ for combined residues of 0.02 ppm.  
	Thiamethoxam residues were not detected in the nutmeat nor processed fractions of peanuts grown from peanut seeds treated at 0.48-0.522 lb ai/A (roughly 6-6.5X the proposed maximum use rate).  Residues were not detected in any of the peanut oil samples upon processing.  Reduction of thiamethoxam residues in peanut oil after processing was at least 0.22-0.40X.  Residues were observed in the nutmeat and meal of peanuts, grown from peanut seeds treated at 0.16-0.174 lb ai/A (roughly 2X the proposed rate), from both field trials.  The theoretical concentration factor for peanut meal, presented in OPPTS Residue Chemistry Test Guideline 860.1520, Table 3 (Theoretical Concentration Factors Based upon Separation into Components), is 2.2X.  The empirical concentration factors for thiamethoxam in meal (range 2.0-3.1X, average 2.6X) conform well to the theoretical value.  
	A summary of the data from the peanut processing study is presented in Table 10 (below).  

TABLE 10	Residue Data from Peanut Processing Study with Thiamethoxam.  
                                      RAC
                        Trial ID (Number County/State)
                              Processed Commodity
                                  Total Rate
                                   (lb ai/A)
                                      PHI
                                    (Days)
                                Residues (ppm)
                               Processing Factor
Peanut Nutmeat
0S-SR-837-99
Turner/GA
RAC
                                  0.170-0.174
                                      126
                                     0.05
                                    NA [1]

Meal
                                       
                                       
                                     0.10
                                      2.0

Refined Oil
                                       
                                       
                                   <0.02
                                   0.40 [2]

RAC
                                  0.510-0.522
                                       
                                   <0.02
                                      NA

Meal
                                       
                                       
                                   <0.02
                                    NC [3]

Refined Oil
                                       
                                       
                                   <0.02
                                      NC

0S-SR-309-99
Lavaca/TX
RAC
                                     0.160
                                      132
                                     0.09
                                      NA
                                       
                                       
Meal
                                       
                                       
                                     0.28
                                      3.1
                                       
                                       
Refined Oil
                                       
                                       
                                   <0.02
                                   0.22 [2]
                                       
                                       
RAC
                                     0.480
                                       
                                   <0.02
                                      NA
                                       
                                       
Meal
                                       
                                       
                                   <0.02
                                      NC
                                       
                                       
Refined Oil
                                       
                                       
                                   <0.02
                                      NC
1. NA = Not Applicable.  
2. Residues in oil were undetected; 0.02 ppm was used as the oil residue to calculate the processing factor.  
3. NC = Not Calculable.  Residues were undetected in RAC and processed fraction samples.  

	Conclusions
	A tolerance is not required in peanut oil.  With HAFT combined residues of 0.05 ppm in peanut nutmeat (based on residues of 0.09 ppm at a 2X rate), and the theoretical concentration factor for peanut meal of 2.2X, HED recommends a tolerance of 0.15 ppm in peanut meal.  

860.1650 Submittal of Analytical Reference Standards

	Analytical reference standards for thiamethoxam (expiration date 30 August 2012) and its metabolite, CGA-322704 (expiration date 31 August 2010, new standard on order) are currently available at the EPA's NPSR, via personal communication with Dallas Wright, of ACB, on 23 August 2010.  Analytical reference standards should be replenished as requested by the Repository.  The reference standards should be sent to the ACB, which is located at Fort Meade, to the attention of Theresa Cole 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 the mail will be returned if the extended zip code is not used.)

860.1850 Confined Accumulation in Rotational Crops
	Metabolism Decision Memo D258614; G.J. Herndon; 31August 1999
	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000 (PP#9F5046)
	Residue Chemistry Memo D281702; M. Doherty; 17 April 2007

	Confined rotational crop studies were previously reviewed in conjunction with the petition for thiamethoxam use on canola (PP#9F5046).  These studies indicated that limited field rotational crop studies are necessary to support the proposed 120-day PBI for rotational crops, and that the metabolism of [[14]C]-thiamethoxam in rotational crops is similar to the metabolism observed in primary crops.  In a meeting held on 28 July 1999, HED determined that the major residues from the confined rotational crop studies were the parent thiamethoxam, and its CGA-322704 metabolite.  In some animal feedstuffs, CGA-265307, a metabolite containing the N-nitro group, was found to be a major residue.  HED recommended that all three compounds be analyzed in field rotational crop studies.  

860.1900 Field Accumulation in Rotational Crops
	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000 (PP#9F5046)
	Residue Chemistry Memo D281702; M. Doherty; 17 April 2007

	Several field rotational crop studies on thiamethoxam have been submitted and reviewed.  These data indicate that at an application rate of 0.179 lb ai/A (roughly 1X the maximum seasonal use rate of 0.188 lb ai/A on rotatable crops), quantifiable residues of thiamethoxam ROCs are not expected from a 120-day PBI.  The proposed maximum use rate of 0.08 lb ai/A in the petitions under review is well below the rate used in these studies.  

860.1550 Proposed Tolerances

	The submitted field trial data for thiamethoxam on peanuts are acceptable, and support the proposed use of Cruiser PD and Cruiser 5FS as pre-plant seed treatments.  An adequate number of trials were conducted in the appropriate geographic regions at roughly 1.5-3X the maximum proposed rate.  Based on the maximum combined thiamethoxam ROCs of 0.09 and 0.23 ppm in treated nutmeat and hay samples, respectively, HED recommends a tolerance of 0.05 ppm in peanut nutmeat, and a tolerance of 0.25 ppm in peanut hay.  
	The submitted field trial data for thiamethoxam on alfalfa are acceptable, and support the proposed use of Cruiser 5FS as a pre-plant seed treatment.  An adequate number of trials were conducted in the appropriate geographic regions at 1X the maximum proposed rate.  Based on the maximum combined thiamethoxam ROCs of 0.04 and 0.10 ppm in 1X-treated forage and hay samples, respectively, HED recommends a tolerance of 0.05 ppm in alfalfa forage, and a tolerance of 0.12 ppm in alfalfa hay.  
	The submitted data for thiamethoxam use in food handling areas are acceptable, and support the proposed use of Optigard Flex Liquid as a spot, void, and crack and crevice treatment in food handling establishments.  An adequate variety of food commodities were exposed to thiamethoxam, in two different types of food handling establishments, at 1X the maximum proposed rate.  Based on the presence of detectable residues of thiamethoxam or CGA-322704 in various samples, HED recommends a tolerance of 0.02 ppm in food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops).  
	There are no processed commodities associated with the proposed use on alfalfa.  The processed commodities associated with the proposed use on peanuts are peanut meal and refined oil.  Two peanut field trials were conducted in the US during the 1999 growing season in which peanut seeds treated at exaggerated (roughly 6-6.5X) rates were grown for processing into peanut meal and refined oil.  Thiamethoxam residues were not detected in the nutmeat nor processed fractions of peanuts grown from peanut seeds treated at 6-6.5X rates.  Residues were not detected in any of the peanut oil samples upon processing.  Residues were observed in the nutmeat and meal of peanuts, grown from peanut seeds treated at the 2X rate, from both field trials.  The theoretical concentration factor for peanut meal (OPPTS Residue Chemistry Test Guideline 860.1520, Table 3) is 2.2X.  The empirical concentration factors for thiamethoxam in meal (range 2.0-3.1X, average 2.6X) conform well to the theoretical value.  A tolerance is not required in peanut oil.  Based on the HAFT combined residues of 0.05 ppm in peanut nutmeat (based on residues of 0.09 ppm at a 2X rate), and the theoretical concentration factor for peanut meal of 2.2X, HED recommends a tolerance of 0.15 ppm in peanut meal.  
	There are no Codex or Mexican MRLs established for residues of thiamethoxam in crops associated with this review.  Canada has established an MRL of 0.02 mg/kg for residues of thiamethoxam and CGA-322704 in all food crops, and is transitioning to specific commodity MRLs (all at 0.02 mg/kg) on a variety of crops including various cereal grains, peas and beans, soybeans, sweet corn, and sunflower.  

TABLE 11	Tolerance Summary for Thiamethoxam.  
                                   Commodity
                     Proposed/Established Tolerance (ppm)
                          Recommended Tolerance (ppm)
                    Comments; Correct Commodity Definition
Peanut
                                     0.05
                                     0.05

Peanut, hay
                                     0.25
                                     0.25

Peanut, meal
                                     None
                                     0.15

Alfalfa, forage
                                     0.05
                                     0.05

Alfalfa, hay
                                     0.12
                                     0.12

Food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops)
                                     0.01
                                     0.02

References

	Thiamethoxam.  Results of the HED Metabolism Assessment Review Committee Meeting Held on 7/28/99.; D258614; G.J. Herndon; 31 August 1999.  

	Multi-Residue Method Testing of Thiamethoxam (CGA-293343) and Its Metabolite; D259838; G.J. Herndon; 28 September 1999.  

	Multiresidue Test information for the updating of PAM I; D259839; G.J. Herndon; 28 September 1999.  

	PP#9F5046.  Thiamethoxam on Canola.  Section 3 Registration and Permanent Tolerance Request for Use of Thiamethoxam (Helix Formulation) for Use as a Seed Treatment on Canola Seed Prior to Planting.  First Food Use.  Residue Chemistry Review:  Evaluation of Analytical Method and Residue Data.; D252021; G.J. Herndon; 30 March 2000.  

	PP#9F5051.  Thiamethoxam on Various Crops.  Section 3 Registration and Permanent Tolerance Request for Use of Thiamethoxam as a Seed Treatment, Soil Treatment, or Foliar Use on Barley, Brassica (Cole) Leafy Vegetables, Cotton, Cucurbit Vegetables, Fruiting (except Cucurbit) Vegetables, Leafy (except Brassica) Vegetables, Pome Fruit, Tuberous and Corm Vegetables, Sorghum, and Wheat.  Section 3 Registration for Tobacco.  Residue Chemistry Review:  Evaluation of Analytical Method and Residue Data.; D265079; G.J. Herndon; 8 May 2000.  

	PP#95046/95051.  Thiamethoxam on Canola, Barley, Sorghum, Wheat, Cotton, Tuberous and Corm Vegetables, Leafy Vegetables, Brassica Vegetables, Fruiting Vegetables, Cucurbit Vegetables, Pome Fruits, and Tobacco.  Results of Petition Method Validation.; D271516; M. Doherty; 29 May 2001.  

	PP#0F06142.  Thiamethoxam.  Section 3 Registration for Use as a Corn Seed Treatment.  Summary of Analytical Chemistry and Residue Data.; D285545; M. Doherty; 6 November 2002.

	PP#3E6524, 2E6505, 1E6349, 2E6508.  Thiamethoxam.  Section 3 Registration for Use on Stone Fruit, Coffee, Pecan, and as a Seed Treatment on Sunflower and Succulent Beans.  Summary of Analytical Chemistry and Residue Data.; D286726; Y. Donovan; 23 December 2003.  

	Thiamethoxam.  Summary of Analytical Chemistry and Residue Data.  PP#0F6142.  Request for Amended Use Patterns for Actara(R) Insecticide (EPA Reg. No. 100-938), Centric(R) 40WG Insecticide (EPA Reg. No. 100-1147), and Platinum(R) Insecticide (EPA Reg. No. 100-939) and to Register Actara(R) 240 SC Insecticide (File Symbol No. 100-RELN).  PP#6E7060.  IR-4 Request to Add Uses on Artichoke, Barley, and Caneberry to Actara(R) Insecticide (EPA Reg. No. 100-939) and Uses on Hops to Platinum(R) Insecticide (EPA Reg. No. 100-939).  PP#s3E6805, 9F5051, 3E6806, 3E6781, 2E6363, 3E6800, 3E6807, 4E6819, and 04CA0015.  Section 3 Registration for Seed Treatment Uses on Legume Vegetables, Potato Seed Pieces, Oilseed Crops; and Foliar Uses on Cranberry, Mint, Strawberry, Bushberry, and Root Vegetables (Except Sugarbeet); and the Section 18 Emergency Exemption on Artichoke.; D281702, D325447, D335847, D292865, D296610, D297966, D298143, D298157 & D300775; M. Doherty; 17 April 2007.  

	PP# 0F6142.  Thiamethoxam.  Request to Add Foliar Treatment of Soybeans to the Label for Centric(R) WG Insecticide.  Summary of Analytical Chemistry and Residue Data.; D346216; M. Doherty; 13 November 2007. 

	Thiamethoxam.  Application for Amended Section 3 Registration to Add Uses on Citrus Fruit Group 10 and Tree Nut Group 14.  Summary of Analytical Chemistry and Residue Data.; D349272; M. Doherty; 8/12 August 2008.  

Attachment:  International Residue Limit Status sheet.

                      INTERNATIONAL RESIDUE LIMIT STATUS
CAS Name:  3-[(2-chloro-5-thiazolyl) methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-imine.  
Common Name:  Thiamethoxam.  
X   Recommended tolerance
⁮   Reevaluated tolerance
⁮   Other
Date:  
2 August 2010
                     Codex Status (Maximum Residue Limits)
                                 US Tolerances
X No Codex proposal step 6 or above
□ No Codex proposal step 6 or above for the crops requested
Petition Numbers:  9F7657, 0F7707, 0F7734
DP Barcodes:  D376367, D380653
Other Identifier:  PC Code 060109
Residue definition (step 8/CXL):  Not applicable.  
Reviewer/Branch:   William T. Drew/RAB2

Residue definition:  Combined residues of the insecticide thiamethoxam [3-[(2-chloro-5-thiazolyl) methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-imine] and its metabolite [N-(2-chloro-thiazol-5-ylmethyl)-N'-methyl-N'-nitro-guanidine].  
                                    Crop(s)
                                  MRL (mg/kg)
                                     Crop
                                Tolerance (ppm)
                                       
                                       
Peanut
                                     0.10
                                       
                                       
Peanut, hay
                                     0.25
                                       
                                       
Peanut, meal
                                     0.15
                                       
                                       
Alfalfa, forage
                                     0.05
                                       
                                       
Alfalfa, hay
                                     0.12
                                       
                                       
Food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops)
                                     0.01
                              Limits for Canada 1
                              Limits for Mexico 2
⁮  No Limits
⁮  No Limits for the crops requested
⁮  No Limits
X  No Limits for the crops requested
Residue definition:  3-[(2-chloro-5-thiazolyl)
methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-
oxadiazin-4-imine,including the metabolite
(E)-N-[(2-chloro-5-thiazolyl)methyl]-N'-
methyl-N"-nitro-guanidine.  
Residue definition:  Thiamethoxam.  
                                    Crop(s)
                                  MRL (mg/kg)
                                    Crop(s)
                                  MRL (mg/kg)
                                    Alfalfa
                                     0.02
                                       
                                       
                                    Peanut
                                     0.02
                                       
                                       
                                       
                                       
                                       
                                       
Notes and/or special instructions:  
1. Includes only commodities of interest for this action.  
2. Mexico adopts US tolerances and/or Codex MRLs for its export purposes.  
(Steve Funk/Meheret Negussie)