Document ID: EPA-HQ-OPP-2009-0737-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-06-23T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC  20460

Office of

Chemical Safety and

Pollution Prevention

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:	3 May 2010

SUBJECT:	Thiamethoxam.  Petition to Establish a Permanent Tolerance for
Residues of the Insecticide Resulting from Food/Feed Use as a Seed
Treatment on Bulb Onions.  Response to Data Gaps from Conditional
Registration of Various Food/Feed Crops (as Specified in HED Memo
D281702; M. Doherty; 17 April 2007).  Summary of Analytical Chemistry
and Residue Data.  

PC Code:  060109	DP Barcodes:  D367065 & D369666

Decision Numbers:  415289 & 416844	Registration Numbers:  100-938 and
100-1294

Petition Number:  9F7582	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

Chemical Class:  Neonicotinoid Insecticide	Trade Name:  Actara® and
Cruiser® 70WS

FROM:	William T. Drew, Chemist  SEQ CHAPTER \h \r 1 

		Risk Assessment Branch 2 (RAB2)

		Health Effects Division (HED), 7509P

THRU:	Douglas Dotson, PhD, Chemist

		RAB2/HED, 7509P

TO:		Julie Chao and Venus Eagle, RM Team 1

		Insecticide/Rodenticide Branch (IRB) 

		Registration Division (RD), 7505P   SEQ CHAPTER \h \r 1   SEQ CHAPTER
\h \r 1 

		

  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (1901 Research Boulevard, Suite 220;
Rockville, MD 20850).  The document has been reviewed by the Health
Effects Division (HED), and revised to reflect current Office of
Pesticide Programs (OPP) policies.

 MRID #Summary Table.

MRID #Number	Study Type	Comments

47778902	860.1500 Dry Bulb Onion	New DER.  

47786101	860.1500 Barley	New DER.  

47786103	860.1340 Residue Analytical Method	No DER generated;
registrant’s response to deficiency is incorporated in this Summary
Document.  

47786102	860.1480 Poultry Feeding Study 	New DER for poultry feeding
study (MRID #47786104) includes method validation data from MRID
#47786102.

47786104

Executive Summary

	  SEQ CHAPTER \h \r 1 Thiamethoxam
(3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-ox
adiazin-4-imine) belongs to the pesticide chemical class known as the
neonicotinoids.  It is a broad-spectrum, systemic insecticide with
activity against sucking and chewing insects on a wide variety of crops.
 

	Syngenta Crop Protection submitted a petition to register a new use of
thiamethoxam on dry bulb onions.  The end-use product (EP) relevant to
this petition is Cruiser® 70WS (EPA Registration #100-1294), a wettable
powder (WP) formulation containing 70% of the active ingredient (ai),
thiamethoxam.  It is proposed for pre-plant seed treatment of dry bulb
onions at 0.05-0.20 mg ai/seed for early season protection of seedlings
and young plants against injury from aphids, leafminers, seed corn
maggots, wireworms, and onion thrips.  In conjunction with the proposed
use, Syngenta requests the establishment of a permanent tolerance for
residues of thiamethoxam and its metabolite, CGA-322704 (clothianidin),
in/on onions, as listed below.  

Onion, dry bulb	0.03 ppm

	In support of the proposed registration and tolerance, Syngenta
submitted a magnitude of the residue study on dry bulb onion (MRID
#47778902).  In addition, Syngenta submitted a final response to the
following data gaps previously identified by HED (D281702; M. Doherty;
17 April 2007) for the conditional registration of thiamethoxam on
several crops:  

1. A revision of the currently approved enforcement method, Method
AG-675, to include the full extraction steps for plant and livestock
commodities, including the microwave extraction step for liver (MRID
#47786103), 

2. a new poultry feeding study, in which liver samples are analyzed
using the modified enforcement method (MRID #47786104), along with
validation of said method (MRID #47786102), and 

3. residue decline data for barley (MRID #47786101).  

The submitted onion data are evaluated in this Summary Document.  The
Summary Document also offers conclusions regarding the adequacy of
Syngenta’s responses to the specific data gaps identified for the
conditional registration.  

	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 (milk,
meat and meat byproducts of cattle, goat, hog, horse and sheep) at 0.02
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® 70WS on dry bulb onions would result in a per
acre application rate equivalent to 0.18 lb ai/A (approximately 1X the
maximum use rate on rotatable crops).  As the submitted label for
Cruiser® 70WS does not specify PBIs, the label should be revised to
specify that only registered crops may be re-planted immediately
following harvest, or as soon as practical following the last
application.  For all other crops, a 120-day PBI should be observed.  

	Method AG-675, a method utilizing high-performance liquid
chromatography (  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 HPLC) with
ultraviolet (UV) or mass spectrometric (MS) detection, is the current
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 chicken 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.  

	The various data-collection methods, used for analysis of samples taken
from the magnitude of the residue studies discussed in this action, are
based on either Method AG-675 or Method GRM.009.04A.  Method recoveries
from concurrent analysis of samples were within the generally recognized
acceptable range of 70-120%.  

	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 studies.  There are no
storage stability issues, and no corrections for potential decline
during storage are needed for any of the residue studies.  

	The new poultry feeding study is adequate, and fulfills the requirement
for liver data analyzed by the modified enforcement method.  A dietary
burden of 0.245 ppm was recently calculated (D281702; M. Doherty; 17
April 2007) for poultry.  Given that the projected thiamethoxam ROCs at
the 1X feeding level will 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 feedstuffs are proposed
in the future.  

	As previously concluded by HED (D281702; M. Doherty; 17 April 2007),
the available data indicate that increased tolerances are needed in the
meat byproducts of cattle, goat, horse and sheep, from 0.02 to 0.04 ppm.
 The recommended increases in tolerances have not yet been established. 

	The submitted field trial data for thiamethoxam on dry bulb onions are
acceptable, and support the proposed use of Cruiser® 70WS 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 <0.026 ppm in
1X-treated samples, HED recommends a tolerance of 0.03 ppm.  

	The submitted field trial data for thiamethoxam on barley are adequate,
and fulfill the request for residue decline data.  The data confirm that
the total thiamethoxam residues do not increase in barley matrices with
later sampling intervals than the established 21-day precutting interval
for barley hay, or the 21-day pre-harvest interval (PHI) for barley
grain and straw.  The additional trials also support the Section 3
registration of Actara® (EPA Registration #100-938), a 25% ai
water-dispersable granule (WDG) formulation, on barley.  The aggregate
of residue data support the established tolerances for the combined
thiamethoxam ROCs in barley grain at 0.30 ppm, and in barley hay and
straw at 0.40 ppm each.  

	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 residues of thiamethoxam
and CGA-322704 in all food crops.  

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

	HED has examined the residue chemistry database for thiamethoxam. 
Pending submission of a revised Section B (see requirements under
860.1200 Direction for Use, below), there are no residue chemistry
issues that would preclude granting a Section 3 registration, and
establishing a permanent tolerance, for the requested use of
thiamethoxam (as Cruiser® 70WS) on dry bulb onions.  Provided that the
forthcoming human health risk assessment (D373596; D. McNeilly; 3 May
2010) does not identify any issues of concern, the submitted data
support a tolerance for thiamethoxam, including its metabolites and
degradates, in or on dry bulb onions, at the level listed below. 
Compliance with the tolerance level specified below is to be determined
by measuring only thiamethoxam and CGA-322704 (calculated as
thiamethoxam equivalents).  

Onion, bulb	0.03 ppm

	Note to RD:  The data gaps identified by HED (D281702; M. Doherty; 17
April 2007) pertaining to the revision of Method AG-675,  the submission
of a new poultry feeding study, and the submission of residue decline
data for barley, have now been resolved.  

	860.1200 Directions for Use

	The product label for Cruiser® 70WS (EPA Registration #100-1294)
should be revised to specify that only registered crops may be replanted
immediately following harvest, or as soon as practical following the
last application.  For all other crops, a 120-day PBI should be
observed.  

Additionally, the product label should be revised to specify that
Cruiser® 70WS is to be applied at the rate of 0.05 to 0.20 mg of ai per
seed.  

Background

	  SEQ CHAPTER \h \r 1 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 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 bulb onions
(PP#9F7582), Syngenta submitted field trial data reflecting the seed
treatment use of thiamethoxam (70% ai WP) on dry bulb onions.  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	  SEQ CHAPTER \h \r 1 CGA 293343

Molecular formula	C8H10ClN5O3S

Molecular weight	291.71

IUPAC name	  SEQ CHAPTER \h \r 1
3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene
(nitro)amine

CAS name	  SEQ CHAPTER \h \r 1
3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxa
diazin-4-imine

CAS registry number	  SEQ CHAPTER \h \r 1 153719-23-4

End-use products (EPs)	70% ai WP formulation (Cruiser® 70WS
Insecticide; EPA Registration #100-1294)

25% ai WDG formulation (Actara® Insecticide; EPA Registration #100-938)

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.  

860.1200  Directions for Use

	The EP proposed for use on dry bulb onions is Cruiser® 70WS (EPA
Registration #100-1294), a wettable powder formulation of thiamethoxam
containing 70% ai.  It is proposed for use as a pre-plant seed treatment
of dry bulb onions to provide early season protection of seedlings and
young plants against injury from aphids, leafminers, seed corn maggots,
wireworms, and onion thrips.  The proposed use directions on dry bulb
onions, obtained from a draft label dated 3 June 2009 for Cruiser®
70WS, are presented in Table 3 (below).  

	For the evaluation of new barley data, the most recent product label
for Actara® Insecticide (EPA Registration #100-938, approved 6 October
2009), a 25% ai WDG formulation, was examined, along with a
Syngenta-provided thiamethoxam label registered under a Special Local
Needs Registration (SLN CO090004).  HED’s review of previous barley
data submissions (D281702; M. Doherty; 17 April 2007) required the
revision of the product label to restrict use of the product to the
states of ID, ND, OR, SD and WA, based on the available data.  The
requested label revision has been made.  However, it is now Syngenta’s
intention to expand the use of thiamethoxam on all major barley growing
regions without geographic restriction; see 860.1500 Crop Field Trials,
below, for a more detailed discussion of new data.  The registered use
directions on barley are also presented in Table 3 (below).  

Table 3	Summary of Proposed Use Directions on Dry Bulb Onions, and
Registered Use Directions 	on Barley.  

Use Timing; Type; and Equipment	Product

[Registration Number]	Single Use Rate	Maximum Uses per Season	Maximum
Seasonal Use Rate	PHI

(Days)	Use Directions and Limitations

Dry Bulb Onion 

Pre-plant; seed treatment	Cruiser® 70WS

[100-1294]	0.05-0.20 mg ai/seed	1 (Implied)	0.18

lb ai/A 1	Not specified	Cruiser® 70WS may also be applied with
Trigard™ OMC (cyromazine)2 for onion maggot protection.  The label
restricts any soil or foliar application of products containing
thiamethoxam to crops grown from seed treated with Cruiser® 70WS.  

Barley

Pest pressure; foliar spray;

ground/aerial	Actara®

[100-938]

	0.0625 lb ai/A	2	0.125 lb ai/A	21	Use of Actara® Insecticide on barley
is restricted to crops grown in ID, ND, OR, SD and WA.  The SLN
registration for CO090004 is restricted to crops grown in CO.  Apply
before pests reach damaging levels using ground (minimum spray volume of
10 GPA) or aerial (5 GPA) equipment.  Minimum retreatment interval (RTI)
is 7 days.  

1. The draft label specifies a maximum seasonal use rate of 0.18 lb ai/A
(or 81.6 g ai/A), based on a maximum 	seeding rate of 406,000 seeds/A.  

ndation with Trigard™ OMC (cyromazine) is appropriate because a
cyromazine 	tolerance for bulb onion has been established under 40CFR
§180.414.  

	Rotational crop restrictions:  There are no rotational crop
restrictions listed in the submitted label for Cruiser® 70WS.  For the
Actara® Insecticide label, the following rotational crop restrictions
are established:  

Treated areas may be replanted immediately following harvest, or as soon
as practical following the last application with any crops listed on
this label or to barley, canola, cotton, cucurbit vegetables, legume
vegetables, oilseeds (rapeseed, Indian rapeseed, Indian mustard seed,
field mustard seed, black mustard seed, flax seed, safflower seed,
crambe seed and borage seed), sorghum, sunflower, and wheat.  Any cover
crop planted for erosion control or soil improvement may be planted as
soon as practical following the last application.  However, the cover
crop may not be grazed or harvested for food or feed.  For all other
crops, a 120-day PBI must be observed.  

	Conclusions:  The submitted use directions for bulb onions are
sufficient to allow for evaluation of the submitted residue data
relative to the proposed use patterns.  However, as specified in
860.1900 Field Accumulation in Rotational Crops, below, the product
label for Cruiser® 70WS (EPA Registration #100-1294) should be revised
to specify that only registered crops may be replanted immediately
following harvest, or as soon as practical following the last
application.  For all other crops, a 120-day PBI should be observed.  

	The submitted use directions for barley are also adequate to allow HED
to make a determination regarding the adequacy of Syngenta’s request
to expand the use of thiamethoxam to all major barley growing regions,
without geographic restriction.  

860.1300 Nature of the Residue - Plants

	  SEQ CHAPTER \h \r 1 Metabolism Decision Memo D258614; G.J. Herndon;
31August 1999

	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D265079; G.J. Herndon; 8
May 2000

	  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 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.    SEQ CHAPTER \h \r 1 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

	  SEQ CHAPTER \h \r 1 Metabolism Decision Memo D258614; G.J. Herndon;
31August 1999

	Residue Chemistry Memo D252021; G.J. Herndon; 30 March 2000

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D265079; G.J. Herndon; 8
May 2000

	There are no livestock feedstuffs associated with the proposed use of
thiamethoxam on dry bulb onions.  A discussion of the nature of the
residue in animals would typically not be relevant to this registration
action.  However, as this Summary Document also addresses the adequacy
of a new confirmatory poultry feeding study, submitted by Syngenta in
response to a topical data gap for conditional registration on numerous
food/feed crops reviewed in D281702; M. Doherty; 17 April 2007, it is
appropriate to summarize the status of data requirements for animal
metabolism.  The nature of the residue in livestock is adequately
understood, based on acceptable goat and hen   SEQ CHAPTER \h \r 1
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

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D265079; G.J. Herndon; 8
May 2000

	Residue Chemistry Memo D271516; M. Doherty; 29 May 2001

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D281702; M. Doherty; 17
April 2007

	Enforcement method:  An   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1
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,
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.  

	Data-collection methods:    SEQ CHAPTER \h \r 1 Samples from the
submitted onion field trials were analyzed for residues of thiamethoxam
and CGA-322704 using the current tolerance enforcement method, Method
AG-675, with modifications.  The modifications included the elimination
of two clean-up steps (partitioning and amino/alumina SPE), and the use
of HPLC/MS/MS instead of HPLC/UV.  The method LOQs are 0.010 ppm for
each analyte.  This method is adequate for data collection, based on
acceptable method recoveries.  The average concurrent recoveries (±
standard deviation) were 86 ± 11% for thiamethoxam, and 90 ± 12% for
CGA-322704, following fortification of untreated samples of bulb onion
with the analytes at 0.01-0.50 ppm.  

	Samples from the submitted barley field trials were analyzed for
residues of thiamethoxam and CGA-322704 using ADPEN Method M1104,
entitled Analytical Method for the Determination of Residues of
Thiamethoxam (CGA293343) and the Metabolite CGA322704 in Rice and Barley
by LC/MS/MS.  Briefly, commodity samples were   SEQ CHAPTER \h \r 1
extracted twice with ACN/water (4:1, v:v), filtered, and brought to
volume with additional ACN/water (4:1, v:v).  An aliquot of the extract
was concentrated, reconstituted in ACN/water (1:9, v:v), and analyzed by
HPLC/MS/MS.  The LOQ for each analyte was 0.010 ppm.  This method is
adequate for data collection, based on acceptable method recoveries. 
Method recoveries from concurrent analysis of samples, as well as from
additional method validation, were within the generally recognized
acceptable range of 70-120%, except for one barley hay sample fortified
with thiamethoxam at 0.010 ppm, which resulted in a recovery of 69%, and
one barley grain sample fortified with CGA-322704 at 0.010 ppm, which
resulted in a recovery of 128%.  

	The liver samples from the submitted poultry feeding study were
analyzed for residues of thiamethoxam and its metabolites, CGA-322704
and CGA-265307, using the revised enforcement method, Method
GRM.009.04A.  The LOQ for each analyte was 0.010 ppm.  The method was
validated prior to, and concurrently with, the analysis of liver
samples.  The average concurrent recoveries (± standard deviation) were
99 ± 12% for thiamethoxam, 91 ± 10% for CGA-322704, and 83 ± 9% for
CGA-265307, following fortification of untreated samples of liver with
the analytes at 0.01-0.10 ppm.  

	Syngenta’s Response (MRID #47786103) to Residue Analytical Method
Data Gaps:  

Syngenta previously submitted a modification of Method AG-675 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.  In response,
Syngenta has submitted MRID #47786103 which provided the requested
method revisions.  The specific deficiency is re-stated below, followed
by Syngenta’s response, and HED’s comments regarding the adequacy of
the response.  

	Deficiency

	“Syngenta must submit a revised version of Method AG-675 which
includes the full extraction steps for plant and livestock commodities,
including the microwave extraction step for liver.  The revised method
will then be forwarded to FDA for inclusion in PAM Vol. II.”  

	Syngenta’s response

	“MRID 47786103 was submitted which contains descriptions for Method
GRM.009.04A which will supersede Method AG-675 following incorporation
of the revisions requested by HED.  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 0.01 ppm for all substrates except milk and fruit juices (0.005 ppm).
 For analysis of cotton, tobacco, and the forage, fodder, and straw of
cereal grains and grasses, the method determines thiamethoxam ROCs using
a reverse phase HPLC/MS with an LOQ of 0.01 ppm except in grass (0.05
ppm).  For analysis of chicken liver, final residue determination is
made using a reverse phase HPLC/MS/MS; the LOQ is 0.01 ppm each for
thiamethoxam, CGA-322704, and CGA-265307.   The salient features of
Method GRM.009.04A are described below.  

	For crop and livestock matrices excluding liver, eggs, milk, juices and
oils, samples are extracted twice using ACN:water (80:20, v:v), vacuum
filtered through Celite leaving the settled solid portion in the
extraction bottle, and brought to volume if necessary with ACN:water
(80:20, v:v).  For liquid substrates such as eggs, milk, or juice,
samples are extracted twice using ACN:water (80:20, v:v), filtered
through Celite, and brought to volume with ACN:water (80:20, v:v).  For
oils and/or oily matrices, samples are extracted with ACN:water (80:20,
v:v), and the sample is mixed.  For chicken liver, samples are extracted
with ACN:water (80:20, v:v) followed by a microwave digestion step using
a predetermined set of temperature gradient; the sample is then
centrifuged to remove solids.  

	The cleanup procedures vary by matrix and are presented below.  

	For fruits, vegetables, and grain samples analyzed by HPLC/UV, the
ACN/water extract is evaporated to an aqueous residue without a
partition step.  The aqueous residue is cleaned up using a phenyl solid
phase extraction (SPE) column, eluted with methanol:water (50:50, v:v),
evaporated to remove the methanol, partitioned twice into ethyl acetate,
evaporated to dryness, and reconstituted in ethyl acetate:hexane (20:80,
v:v).  This solution is cleaned up using an amino SPE column, eluted
with methanol:ethyl acetate (3:97, v:v), and further purified using an
alumina SPE column, eluted with methanol:ethyl acetate (10:90, v:v);
sonication at each column clean-up step is essential.  The final eluate
is evaporated to dryness and reconstituted in the appropriate volume of
hexane:ethyl acetate:isopropanol:methanol (11:3:1:1, v:v:v:v) for
HPLC/UV analysis.  

	For cotton, tobacco, and the forage, fodder, and straw of cereal grains
and grasses, the extract is evaporated to an aqueous residue, buffered
to pH 7.0, cleaned up using an SAX SPE column, eluted with 10-mM sodium
phosphate buffer, and further purified using a phenyl SPE column, eluted
with methanol:water (1:1, v:v).  The eluate is evaporated to remove the
methanol, and residues are partitioned twice into ethyl acetate.  The
sample is evaporated and reconstituted in ethyl acetate:hexane (20:80,
v:v), and cleaned up using an alumina SPE column, eluted with
methanol:ethyl acetate (10:90, v:v); sonication at each column clean-up
step is essential.  The eluate is evaporated to dryness and
reconstituted in ACN:water (10:90, v:v) for HPLC/MS analysis.  

	For oil and animal matrices other than liver, water saturated with
sodium chloride and toluene are added, and the sample is partitioned
against hexane.  This partition forms three layers:  a bottom, aqueous
layer (which will contain residual amounts of thiamethoxam, CGA-322704
and CGA-265307), a middle layer comprised primarily of ACN and toluene
(which will contain the majority of thiamethoxam, CGA-322704, and
CGA-265307 as well as some residual water), and a top, hexane layer. 
The two bottom phases are combined, partitioned into 2% toluene in ACN,
and rotary evaporated to an aqueous residue.  The aqueous residue
cleanup procedures are identical to those described above for fruits,
vegetables, and grain samples.  The final eluate is evaporated to
dryness and reconstituted in the appropriate volume of hexane:ethyl
acetate:isopropanol:methanol (11:3:1:1, v:v:v:v) for HPLC/UV analysis.  

	For chicken liver, water saturated with sodium chloride and toluene are
added, and the sample is partitioned against hexane.  This partition
forms three layers:  a bottom, aqueous layer (which will contain
residual amounts of thiamethoxam, CGA-322704 and CGA-265307), a middle
layer comprised primarily of ACN and toluene (which will contain the
majority of thiamethoxam, CGA-322704, and CGA-265307 as well as some
residual water), and a top, hexane layer.  A phosphate buffer solution
(10 mM) is added, and the sample is cleaned up using an SAX SPE column,
eluted with 10-mM sodium phosphate buffer, and further purified using a
phenyl SPE column, eluted with methanol:water (1:1, v:v).  The eluate is
evaporated to remove the methanol, and residues are partitioned twice
into ethyl acetate.  The sample is evaporated to dryness and
reconstituted in ethyl acetate:hexane (20:80, v:v) and further purified
using an amino SPE column, eluted with methanol:ethyl acetate (3:97,
v:v) followed by an alumina column, eluted with methanol:ethyl acetate
(10:90, v:v); sonication at each column clean-up step is essential.  The
eluate is evaporated to dryness and reconstituted in acetonitrile:0.1%
formic acid (10:90, v:v) for HPLC/MS/MS analysis.  

	The instrument conditions are as follows.  

	For HPLC/UV:  normal phase HPLC/UV using an amino column, a mobile
phase of hexane:ethyl acetate:isopropanol:methanol (11:3:1:1, v:v:v:v),
and a UV detector at 255 nm.  Retention times are ~20 min for
thiamethoxam, ~12 min for CGA-322704, and ~21 minutes for CGA-265307.  

tabolites.  The ion transitions monitored are m/z 292.0→211.22 for
thiamethoxam, m/z 247.0→166.0 for CGA-322704, and m/z 234.0→151.8
for CGA-265307.  The retention times are 1.25 minutes for thiamethoxam,
5.26 minutes for CGA-322704, and 5.19 minutes for CGA-265307.  

	An additional set of conditions for reverse phase HPLC/MS are also
provided; these use an SB-C18 column, a gradient mobile phase of 0.1%
acetic acid in water and 0.1% acetic acid in ACN, and MS detection in
the positive ion mode.  Retention times of 9.5-11 minutes for
thiamethoxam and 10.5-13 minutes for CGA-322704 are reported, depending
on the exact instrumentation used; retention times for CGA-265307 are
not reported.  

	Residues are reported individually in ppm; a molecular weight
conversion factor must be used to determine each metabolite in
thiamethoxam equivalents for combined residues.  The LOQ in this method
has been set at 0.01 ppm for each analyte in chicken liver. 
Additionally, the petitioner states that the LOQ for HPLC/UV analysis of
milk has been reduced to 0.005 ppm, and that the LOQ for HPLC/MS
analysis of plant matrices is 0.01 ppm (0.05 ppm for grasses).”  

	HED’s comments/conclusions

	“Syngenta has submitted a re-written version of Method AG-675 which
has been renamed as Method GRM.009.04A to supersede the previous
approved method.  The full extraction steps for plant and livestock
commodities, including the microwave extraction step for liver, were
incorporated in the revised method.  HED will forward MRID 47786103 to
FDA for inclusion in PAM Vol. II.”  

	Conclusions:  An   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 HPLC
method (Method AG-675) with UV or MS detection has been previously
submitted in conjunction with previous thiamethoxam petitions.  Method
AG-675 has been determined to be adequate for enforcing tolerances for
residues of thiamethoxam and CGA-322704 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).  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 Analytical Chemistry Branch (ACB). 
HED will forward MRID #47786103 to FDA for an update of the current
method in PAM Volume II.  

	The various data-collection methods, used for analysis of samples taken
from the magnitude of the residue studies discussed in this action, are
based on either Methods AG-675 or GRM.009.04A.  Method recoveries from
concurrent analysis of samples were within the generally recognized
acceptable range of 70-120%.  

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

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D281702; M. Doherty; 17
April 2007

	Concurrent storage stability data were not submitted with the onion or
barley field trials, nor were they submitted with the poultry feeding
study.  However, the storage durations and conditions for samples from
the current field trial and feeding studies are supported by previously
conducted storage stability studies on diverse crops (including barley),
and animal commodities.  

	For plant commodities, adequate storage stability data are available on
five diverse crops.  These data indicate that residues of   SEQ CHAPTER
\h \r 1 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   SEQ CHAPTER \h \r 1 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   SEQ CHAPTER \h \r 1 thiamethoxam and CGA-322704 are stable
in all crops for at least 24 months, and in most associated processed
commodities for at least 40 months.  

	Also, concurrent storage stability data (refer to the DER for MRID
#46801401), previously submitted in conjunction with earlier barley
field trials, indicate that residues of thiamethoxam and CGA-322704 are
stable for intervals of up to 592 days in barley grain, 594 days in
barley hay, and 599 days in barley straw stored frozen (D281702; M.
Doherty; 17 April 2007).  

	For animal commodities, HED has reviewed data indicating that residues
of   SEQ CHAPTER \h \r 1 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   SEQ CHAPTER \h \r 1 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
Barley and Onion 			Field Trials, and the Poultry Feeding Study.  

Matrix	Storage Temperature (°C)	Actual Storage

Duration	Interval of Demonstrated Storage Stability

Barley hay, grain, and straw	-30 to -3.5	3.5-6.2 months	24 months

Onion	-20 ± 5	2.5-15 months

	Poultry liver	Frozen (temperature unspecified)	42-56 days	15-17 months
in beef liver

	Conclusions:  The available storage stability data for thiamethoxam
ROCs in plants are adequate to support the storage durations and
conditions of samples of barley and onion commodities from the submitted
crop field trial studies.  The submitted poultry feeding study is
supported by the available storage stability data in 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

	There are no proposed uses that are relevant to this guideline topic.  

860.1480 Meat, Milk, Poultry, and Eggs

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D281702; M. Doherty; 17
April 2007

	  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D346216; M. Doherty; 13
November 2002

	There are no livestock feedstuffs associated with the proposed seed
treatment use of Cruiser® 70WS on dry bulb onions.  Secondary transfer
of thiamethoxam ROCs in meat, milk, poultry and eggs is not expected
from the proposed use on onions.  

	Syngenta’s Response (MRID #47786104, includes method validation data
from MRID 	#47786102) to a Poultry Feeding Study Data Gap:  

	Syngenta previously submitted a poultry feeding study (MRID #45093715)
with thiamethoxam.  Five treatment groups of fifteen laying hens each
were dosed with thiamethoxam at 0, 0.2, 0.6, 2 and 10 ppm in the feed
for 28 consecutive days.  Samples collected from the feeding study were
analyzed for residues of thiamethoxam, CGA-322704, and CGA-265307 using
an HPLC/UV method, Method AG-675.  Following dosing at 10 ppm, residues
of CGA-265307 were <0.01-0.028 ppm in eggs; residues of thiamethoxam and
CGA-322704 were below the LOQ (<0.010 ppm each) in these samples. 
Residues of thiamethoxam, CGA-322704, and CGA-265307 were below the LOQ
(<0.010 ppm each) in egg samples from the 2-ppm dosing level.  Residues
of thiamethoxam, CGA-322704, and CGA-265307 were below the LOQ (<0.010
ppm each) in all tissue samples (skin with attached fat, peritoneal fat,
liver, and muscle) from the 10-ppm dosing group.  Based on these
results, the petitioner did not analyze egg samples from the 0.2- and
0.6-ppm dosing groups, or tissue samples from the 0.2-, 0.6- or 2-ppm
dosing groups.  

	In its review of the poultry feeding study, HED (D281702; M. Doherty;
17 April 2007) concluded that the submitted data for poultry commodities
other than liver are adequate.  HED had reservations regarding the liver
data, because of concern with bound and/or conjugated residues in
consideration of the availability of an improved Method AG-675 which
incorporates microwave digestion to release bound/conjugated residues. 
Because it would be impractical for the petitioner to re-analyze liver
samples from this study, and generate supporting storage stability data
(the study was conducted in 1997), HED required a new poultry feeding
study.  In response, Syngenta has submitted a new poultry feeding study
(MRID #47786104), along with method validation data (MRID #47786102). 
The specific deficiency is re-stated below, followed by Syngenta’s
response.  

	Deficiency

	“Syngenta must conduct a new poultry feeding study in which liver
samples are analyzed using the modified enforcement method, which
includes a microwave extraction step.  Liver samples should be analyzed
for residues of CGA-322704 and CGA-265307 as these metabolites were
found in significant quantities in the microwave hydrolysate in the
metabolism study.”  

	Syngenta’s response

	“A new poultry feeding study with thiamethoxam was conducted.  Four
treatment groups of fifteen laying hens each were dosed with
thiamethoxam at 0, 0.2, 0.6, and 2 ppm in the feed for 28 consecutive
days.  Hens were sacrificed 20-24 hours after the treated feed was
replaced with untreated feed, and composite samples of skin (with
attached fat), peritoneal fat, liver and muscle were collected and only
the liver samples were analyzed.  

	Liver samples were analyzed for residues of thiamethoxam and its
metabolites CGA-322704 and CGA-265307 using HPLC/MS/MS Method
GRM.009.04A which is a modification of the current tolerance enforcement
method and includes microwave extraction.  This method is adequate for
data collection based on acceptable method recoveries.  The validated
LOQ is 0.01 ppm for each analyte in poultry liver.  

	The maximum storage duration from collection to analysis was 56 days
for poultry liver.  The available storage stability data for eggs and
beef tissues are adequate to support the storage durations and
conditions of the poultry feeding study samples.  

	Average dose levels (low, mid, and high dose groups) of thiamethoxam in
the prepared feed were 97-104% of nominal.  

	Residues of thiamethoxam, CGA-322704, and CGA-265307 were each below
the LOQ (<0.01 ppm) in all liver samples from the 0.2- and 0.6-ppm dose
groups.  For the 2.0-ppm dose group, thiamethoxam residues were all
below the method LOQ (<0.01 ppm), CGA-322704 residues were <0.01-0.01
ppm (two samples measured 0.01 ppm), and CGA-265307 residues were 0.01
ppm.”  

	Conclusions:  The new poultry feeding study is adequate, and fulfills
the requirement for liver data analyzed by the modified enforcement
method.  A dietary burden of 0.245 ppm was recently calculated (D281702;
M. Doherty; 17 April 2007) for poultry.   Given that the projected
thiamethoxam ROC at the 1X feeding level will 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.  

860.1500 Crop Field Trials

	DER for MRID #47778902 (CFTs with Dry Bulb Onions)

	DER for MRID #47786101 (CFTs with Barley)

	A summary of the reviewed data for crop field trials with dry bulb
onion and barley is presented in Table 5 (below).  

Table 5	Summary of Residue Data From Crop Field Trials with
Thiamethoxam.  

Crop Matrix	Total Use Rate	PHI

(Days)	

Analyte	Residue Levels (ppm Thiamethoxam Equivalents)

n	Min.	Max.	HAFT*	Median	Mean	Std. Dev.

Dry Bulb Onion

Onion,

bulb	0.2 mg ai/seed	--	Thiamethoxam	14	<0.010	0.014	0.014	0.010	0.011
0.001

	CGA-322704	14	<0.012	<0.012	0.012	0.012	0.012	0

	Combined 	14	<0.022	<0.026	0.025	0.022	0.022	0.001

Barley

Barley

hay	0.125-0.127 lb ai/A	20-21	Thiamethoxam	4	<0.010	<0.010	0.010	0.010
0.010	0

	CGA-322704	4	<0.012	<0.012	0.012	0.012	0.012	0

	Combined	4	<0.022	<0.022	0.022	0.022	0.022	0

Barley grain	0.125-0.127 lb ai/A	22-24	Thiamethoxam	4	<0.010	0.087	0.081
0.042	0.045	0.041

	CGA-322704	4	<0.012	0.026	0.023	0.016	0.018	0.007

	Combined	4	<0.022	0.113	0.104	0.058	0.063	0.048

Barley straw	0.125-0.127 lb ai/A	22-24	Thiamethoxam	4	0.019	0.202	0.191
0.100	0.105	0.099

	CGA-322704	4	0.025	0.039	0.034	0.032	0.032	0.006

	Combined	4	0.046	0.232	0.225	0.135	0.137	0.102

* HAFT = Highest Average Field Trial.  

	Dry bulb onion:  Seven bulb onion field trials were conducted in US
Zones 1 (NY), 5 (IL), 6 (TX), 10 (CA, 2 trials), 11 (ID) and 12 (WA)
during the 2006 and 2007 growing seasons.  Each site consisted of one
untreated plot, and one treated plot.  The treated plots were planted
with bulb onion seeds treated with an aqueous slurry of a 70% ai WP
formulation of thiamethoxam, at a rate of 0.2 mg ai/seed (1X the
proposed seasonal rate).  Based on a maximum seeding rate of 406,000
seeds/A, the seed treatment rate is equivalent to 0.18 lb ai/A.  The
onion crop was allowed to grow according to good agricultural practices.
 Samples of mature dry bulb onion were harvested 119-170 days after
planting (DAP).  At one trial site, additional samples were harvested at
61, 90, 120, and 130 DAP to assess residue decline.  

	The maximum storage duration of dry bulb onion samples, from harvest to
analysis, was 15 months.  The storage conditions and durations for bulb
onion are supported by previously submitted storage stability data for
diverse crops.  

	Samples of bulb onion were analyzed for residues of thiamethoxam and
its metabolite, CGA-322704, using the current tolerance enforcement
method, Method AG-675, with modifications.  This method is adequate for
data collection, based on acceptable concurrent method recoveries.  The
LOQ was 0.010 ppm for each analyte.  

	The maximum residues of thiamethoxam and CGA-322704 were, respectively,
0.014 and <0.010 ppm in dry bulb onions grown from treated seed.  The
maximum combined residues of thiamethoxam and CGA-322704 were <0.026 ppm
in dry bulb onions.  In addition, residue decline data indicate
thiamethoxam residues decrease from 0.082-0.124 ppm on day 61, to below
the method LOQ (<0.010 ppm) on day 90.  The CGA-322704 residues were
<LOQ at all time points.  

	Conclusions:  The submitted field trial data for thiamethoxam on dry
bulb onions are acceptable, and support the proposed use of Cruiser®
70WS for pre-plant seed treatment.  An adequate number of trials were
initiated in the appropriate geographic regions, at 1X the maximum
proposed use rate; however, one trial in Zone 8 was terminated due to
poor germination.  Since the majority of residues were nonquantifiable,
geographic representation is considered adequate.  Because a large
percentage (86%) of the residue values for onions were below the
combined LOQ of 0.022 ppm, the tolerance harmonization spreadsheet was
not used to determine an appropriate tolerance.  Based on the maximum
combined thiamethoxam ROCs of <0.026 ppm in 1X-treated samples, HED
recommends a tolerance of 0.03 ppm.  

	Barley:  Syngenta has submitted additional barley field trial data
(MRID #47786101) in response to a data gap identified by HED (D281702;
M. Doherty; 17 April 2007) during its review of initial data to support
the registration of Actara® Insecticide on barley.  The specific
deficiency is re-stated below, followed by Syngenta’s response.  

	Deficiency

	“A residue decline study is required to fulfill data requirements for
barley.”  

	Syngenta’s response

	“Two residue field trials for thiamethoxam on barley were conducted
in the U.S. during the 2008 growing season in Zones 7 (ND) and 9 (CO). 
Each field test consisted of one untreated plot (Plot 1) and two
treatment plots (Treatment Plots 2 and 3).  At each treatment plot, two
foliar broadcast applications of a 25% water-dispersible granular
formulation of thiamethoxam were made at 0.063-0.065 lb ai/A/application
with a 6- to 8-day retreatment interval for a total rate of 0.125-0.128
lb ai/A (~1X the maximum proposed seasonal rate).  Applications were
made using ground equipment in spray volumes of ~15-30 gal/A, without an
adjuvant.  Applications to Treatment Plot 2 were made prior to milk to
soft dough stage and applications to Treatment Plot 3 were made prior to
maturity.  

	Samples of barley hay, grain, and straw were harvested 20-24 days after
treatment (DAT) for each trial.  Barley hay samples from Treatment Plot
2 were cut at milk to soft dough stage and allowed to dry for 3-9 days. 
Barley grain and straw samples from Treatment Plot 3 were harvested at
maturity.  At the ND test site, additional samples of barley hay, grain,
and straw were harvested at 0, 7, 14-15, 21-22, and 28-29 DAT to assess
residue decline.  

	The maximum storage durations of samples from harvest to analysis were
189 days (6.2 months) for barley hay and 134 days (4.4 months) for
barley grain and straw.  The storage conditions and durations for barley
are supported by previously submitted storage stability data for diverse
crops and barley commodities.  

	Samples of barley matrices were analyzed for residues of   SEQ CHAPTER
\h \r 1 thiamethoxam and its metabolite CGA-322704 using an HPLC/MS/MS
method (ADPEN Method M1104).  This method is adequate for data
collection based on acceptable method recoveries.  The limits of
quantitation (LOQs) were 0.010 ppm for each analyte in each commodity;
the petitioner used the LOQ as the quantitation limit for reporting
residue results.  

	Maximum combined residues of thiamethoxam and its metabolite CGA-322704
were below the combined LOQ (<0.022 ppm) in barley hay, 0.113 ppm in
barley grain, and 0.232 ppm in barley straw.  Maximum individual
residues of thiamethoxam were below the LOQ (<0.010 ppm) in treated
barley hay, 0.087 ppm in treated barley grain, and 0.202 ppm in treated
barley straw.  Maximum individual residues of CGA-322704 converted to
thiamethoxam equivalents were below the LOQ (<0.012 ppm) in treated
barley hay, 0.026 ppm in treated barley grain, and 0.039 ppm in treated
barley straw.  

	The residue decline data indicate that combined residues declined
steadily from 2.94 ppm at 0 DAT to <0.022 ppm by 28 DAT for barley hay,
from 0.411 ppm at 0 DAT to 0.09 ppm by 29 DAT for barley grain, and from
2.12 ppm at 0 DAT to 0.158 ppm by 29 DAT for barley straw.  The residue
decline data for barley fulfills a condition of registration for
thiamethoxam.”  

	Conclusions:  The submitted field trial data for thiamethoxam on barley
are adequate, and fulfill the requested residue decline data.  They
confirm that the total thiamethoxam residues do not increase in barley
matrices with later sampling intervals than the established 21-day
precutting interval for barley hay, or the 21-day PHI for barley grain
and straw.  The additional trials also support the Section 3
registration of Actara® Insecticide on barley.  The aggregate of
residue data support the established tolerances for the combined
thiamethoxam ROCs in barley grain at 0.30 ppm, and in barley hay and
straw at 0.40 ppm each.  

	

860.1520 Processed Food and Feed

	There are no processing commodities associated with the proposed use on
dry bulb onions.  

	For barley, HED (D281702; M. Doherty; 17 April 2007) concluded that the
previously submitted barley processing study is acceptable to satisfy
data requirements.  The data indicate that combined residues of
thiamethoxam and CGA-332704 do not concentrate in pearled barley, barley
bran, or barley flour.  No tolerances are needed in barley processed
commodities.  

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

	Analytical reference standards for thiamethoxam (expiration date 1 June
2010) and its metabolite, CGA-322704 (expiration date 31 August 2010)
are currently available at the EPA’s NPSR, via personal communication
with Dallas Wright, of the Biological and Economic Analysis Division’s
Analytical Chemistry Branch (BEAD/ACB), on 23 January 2009.  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

(Note that the mail will be returned if the extended zip code is not
used.)

860.1850 Confined Accumulation in Rotational Crops

	  SEQ CHAPTER \h \r 1 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

	  SEQ CHAPTER \h \r 1 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
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 to rotatable crops), quantifiable residues of thiamethoxam ROCs are
not expected from a 120-day PBI.  

	The proposed seed treatment use of Cruiser® 70WS on dry bulb onions
would result in a per acre application equivalent to 0.18 lb ai/A
(approximately 1X the maximum rate to rotatable crops); see Table 3,
above.  As the submitted label for Cruiser® 70WS does not specify PBIs,
the label should be revised to specify that only registered crops may be
re-planted immediately following harvest, or as soon as practical
following the last application.  For all other crops, a 120-day PBI
should be observed.  

860.1550 Proposed Tolerances

	The submitted residue data for dry bulb onions are adequate.  Because a
large percentage (86%) of the residue values for onions were below the
combined LOQ of 0.022 ppm, the tolerance harmonization spreadsheet was
not used to determine an appropriate tolerance.  Instead, the maximum
residue value (0.026 ppm) from the crop field trials was used to
determine a tolerance.  The recommended tolerance in dry bulb onion is
0.03 ppm (see Table 6, below).  

	The established tolerances for barley commodities were reassessed
following submission of additional crop field trial data (including
residue decline data).  The aggregate of residue data support the
Section 3 registration of Actara® Insecticide on barley.  They also
confirm that the established tolerances for the combined thiamethoxam
ROCs in/on barley grain at 0.30 ppm, and barley hay and straw at 0.40
ppm each are adequate.  

	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 6	Tolerance Summary for Thiamethoxam.  

Commodity	Proposed/Established Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments; Correct Commodity Definition

Onion, bulb	0.03	0.03	Adequate dry bulb onion residue data are
available. 

Barley, grain	0.30	0.30	The established barley commodity tolerances
remain adequate following evaluation of new data.  

Barley, hay	0.40	0.40

	Barley, straw	0.40	0.40

	

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®
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.  

  SEQ CHAPTER \h \r 1 Attachment:  International Residue Limit Status
sheet.



INTERNATIONAL RESIDUE LIMIT STATUS

CAS Name:  3-[(2-chloro-5-thiazolyl)
methyl]tetrahydro-5-methy⵬ⵎ楮牴ⵯ䠴ㄭ㌬㔬漭慸楤穡湩㐭
椭業敮‮ܠ潃浭湯丠浡㩥†桔慩敭桴硯浡‮ܠ⁘†牐灯
獯摥琠汯牥湡散

⁮   Reevaluated tolerance

⁮   Other	Date:  

8 December 2009

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
Number:  9F7582

DP Barcodes:  D367065 & D369666

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⁮  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)

All food crops*	0.02

Notes and/or special instructions:  * Canada is transitioning to
specific commodity MRLs, all at 0.02 ppm:  succulent shelled lima beans,
succulent shelled peas, succulent shelled pigeon peas, succulent shelled
southern peas, succulent shelled soybeans, sunflower seeds, sweet corn
kernels plus cob with husks removed, teosinte, triticale, wheat, wild
succulent shelled lima beans, succulent shelled peas, succulent shelled
pigeon peas, succulent shelled southern peas, succulent shelled
soybeans, sunflower seeds, sweet corn kernels plus cob with husks
removed, teosinte, triticale, wheat, wild rice.  

Page   PAGE  1  of   NUMPAGES  25 

Thiamethoxam	Summary of Analytical Chemistry and Residue Data	D367065 &
D369666