Page 1 of 30 

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. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 2 of 30 

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 3 of 30 

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 4 of 30 

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 CGA265307) 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 CGA322704 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. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 5 of 30 

 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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 6 of 30 

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 CGA322704 (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 Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 7 of 30 

 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) 

N

O

N

N

H C3

N

S

Cl

O2N
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 8 of 30 

TABLE 1 Test Compound Nomenclature. 

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 139.1°C PMRA Regulatory Note 

(REG2001-03) on 

Thiamethoxam, 9 February 

2001 

pH 4.7 (1% solution in water) 

Density 1.57 x 103 kg/m3

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 (20°C) 

6.6 x 10-9 Pa (25°C) 

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

Octanol/water partition coefficient, 

Log(KOW) 

0.13 ± 0.0017 (25°C) 

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. 

N

H

N

H

N

H C3

N

S

Cl

O2N

NH2

NH

N N

S

Cl

NO2
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 9 of 30 

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). 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 10 of 30 

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 

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 lowpressure 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
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 11 of 30 

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 CGA322704 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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 12 of 30 

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 13 of 30 

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 CGA322704. 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 widemouth 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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 14 of 30 

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, 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 15 of 30 

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 HPLCgrade 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%. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 16 of 30 

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. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 17 of 30 

 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) 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 18 of 30 

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 19 of 30 

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.

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. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 20 of 30 

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). 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 21 of 30 

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. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 22 of 30 

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 HAFT3 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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 23 of 30 

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 HAFT3

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 24 of 30 

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 1Xtreated 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) 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 25 of 30 

 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 NC3

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 26 of 30 

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 [14C]-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 CGA322704 metabolite. In some animal feedstuffs, CGA-265307, a metabolite containing the Nnitro group, was found to be a major residue. HED recommended that all three compounds be 

analyzed in field rotational crop studies. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 27 of 30 

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 28 of 30 

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 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 29 of 30 

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® Insecticide (EPA Reg. No. 100-938), Centric® 

40WG Insecticide (EPA Reg. No. 100-1147), and Platinum® Insecticide (EPA Reg. No. 100-939) 

and to Register Actara® 240 SC Insecticide (File Symbol No. 100-RELN). PP#6E7060. IR-4 

Request to Add Uses on Artichoke, Barley, and Caneberry to Actara® Insecticide (EPA Reg. No. 

100-939) and Uses on Hops to Platinum® 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® 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. 
Thiamethoxam Summary of Analytical Chemistry and Residue Data D376367, D380653 

Page 30 of 30 

INTERNATIONAL RESIDUE LIMIT STATUS 

CAS Name: 3-[(2-chloro-5-

thiazolyl) methyl]tetrahydro-5-

methyl-N-nitro-4H-1,3,5-oxadiazin4-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-chlorothiazol-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)