UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	17 April 2007

	Subject:	Thiamethoxam.  Summary of Analytical Chemistry and Residue
Data.

		PC Code:  060109	40 CFR 180.565

		Chemical Class:  Neonicotinoid Insecticide (Group 4A)

		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).

DP Numbers:	D281702, D325447	Decision Number:	363553

MRID Nos.:	44829301, 44939801, 44939802, 45086203, 45093301,
45093705-45093707, 45093709, 45093711, 45093713-45093716, 45108001,
45140901, 45499901-45499903,  45659201-45659206, 45701201,
45880901-45880903, 46724901-46724903

		Thiamethoxam.  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).

DP Number:	D335847	Decision Number:	366608

MRID Nos.:	46801401-46801404

		Thiamethoxam.  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.

		DP Numbers:	292865, 296610, 297966, 298143, 298157, 300775

MRID Nos.:	45530901, 46114701, 46159201, 46162201, 46162501, 46162502,
46162503, 46162504, 46203601, 46203602

	To:	Dani Daniel/Venus Eagle, PM

		Insecticide/Rodenticide Branch

		Registration Division (7505P)

	From:	Michael A. Doherty, Ph.D., Chemist

		Registration Action Branch 2

		Health Effects Division (7509P)

	Through:	William T. Drew, Chemist

		Registration Action Branch 2

		Health Effects Division (7509P)

		Richard A. Loranger, Ph.D., Branch Senior Scientist

		Registration Action Branch 2

		Health Effects Division (7509P)

This document was originally prepared under contract by Dynamac
Corporation (2275 Research Blvd, Suite 300; Rockville, MD 20850;
submitted 11/06/2006).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.

Executive Summary

  SEQ CHAPTER \h \r 1 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.  It is a
broad-spectrum, systemic insecticide with activity against sucking and
chewing insects on a wide variety of crops.

Tolerances for residues of thiamethoxam are listed in 40 CFR 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 for plant commodities, under 180.565(a), range
from 0.02 ppm to 1.5 ppm; most of those tolerances are set at the
combined limit of quantitation (LOQ; 0.02 ppm) for thiamethoxam and
CGA-322704.  Tolerances have also been established, under 180.565(a) for
livestock commodities (milk, and meat and meat byproducts of cattle,
goat, hog, horse, and sheep), at 0.02 ppm each.  In addition,
time-limited tolerances for residues of thiamethoxam and CGA-322704 have
been established under 180.565(b) in connection with Section 18
emergency exemptions; these include tolerances for dried and succulent
bean at 0.02 ppm (12/31/06 expiration date) and cranberry at 0.02 ppm
(12/31/07 expiration date).

Residue chemistry data to support these tolerances were submitted by
Syngenta Crop Protection, Inc. and reviewed by HED under PP#9F5046 (DP
Number D252021, 3/30/00, G.J. Herndon); PP#9F5051 (DP Number D265079,
5/8/00, G.J. Herndon; and DERs 44647906 and 44647907); PP#0F6142 (DP
Number D285545, 11/6/02, M. Doherty); and PP#3E6524, 2E6505, 1E6349, and
2E6508 (DP Number D286726, 12/23/03, Y. Donovan).  With the exception of
the 12/23/03 memo, data deficiencies were identified by HED as
conditions of registration; additional data were required pertaining to:

directions for use (Conclusion 2 of PP#9F5046 review, Conclusions 2b-2e
of D265079 PP#9F5051 review, and Conclusions 2a and 2b of D269520
PP#9F5051 review);

plant metabolism (Conclusion 6c of PP#9F5046 review, Conclusion 6b of
D265079 PP#9F5051 review, and Conclusion 3 of D269520 PP#9F5051 review);

residue analytical methods (Conclusions 10b and 11a of PP#9F5046 review
and Conclusions 10a and 30g of D265079 PP#9F5051 review);

storage stability (Conclusion 13a of PP#9F5046 review, Conclusions 12c
and 13 of D265079 PP#9F5051 review, only residue chemistry deficiency of
PP#0F6142 review, and Conclusions 8a and 8b of D269520 PP#9F5051
review);

meat, milk, poultry, and eggs (Conclusion 30g of D265079 PP#9F5051
review);

crop field trials (Conclusion 15 of D265079 PP#9F5051 review and
Conclusions 10a and 11a of D269520 PP#9F5051 review);

processed food/feed (Conclusion 26 of PP#9F5051 review); and

field accumulation in rotational crops (Conclusions 34 and 36 of D265079
PP#9F5051 review).

As part of PP#9F5051, Syngenta had proposed the establishment of
tolerances for residues of thiamethoxam and its major metabolite,
N-(2-chloro-thiazol-5-ylmethyl)-N’-methyl-N’-nitro-guanidine
(CGA-322704), converted to parent equivalents in/on the following
commodities:

	Leafy vegetables crop group (4)	2.0 ppm

	Head and stem Brassica crop subgroup (5A)	1.0 ppm

	Leafy Brassica greens crop subgroup (5B)	2.0 ppm

In review of PP#9F5051, HED recommended against these tolerances until
submission of additional plant metabolism data and supporting crop field
trial data.

Syngenta has now submitted residue chemistry data to satisfy the data
deficiencies identified in previous reviews.  Syngenta has also
proposed, in PP#0F6142, the establishment of a tolerance for residues of
the insecticide, thiamethoxam
[3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-ox
adiazin-4-imine] (CAS Reg. No. 153719–23–4) and its metabolite
[N-(2-chloro-thiazol-5-ylmethyl)-N’-methyl -N’-nitroguanidine] in/on
the following raw agricultural commodities:

	Grapes	0.15 ppm

	Grape, juice	0.20 ppm

	Raisins	0.30 ppm

Syngenta had also proposed tolerances for peanut commodities; however,
the proposal has since been withdrawn (letter from Fred Pearson,
Syngenta to Dan Kenny, EPA/RD, 4/26/04).

In addition, Syngenta submitted a request to register a new thiamethoxam
product, Actara® 240 SC Insecticide (EPA File Symbol No. 100-RELN), a 2
lb/gal suspension concentrate (equivalent to a flowable concentrate;
FlC) formulation, for foliar uses on the bushberry subgroup, cranberry,
cotton, cucurbit vegetables, fruiting vegetables, juneberry,
lingonberry, mint, pecan, pome fruit, root vegetables subgroup, salal,
stone fruit, strawberry, tobacco, and tuberous and corm vegetables
subgroup.  Syngenta has submitted bridging crop field trial data for
selected crops to support the requested uses.

Syngenta has also submitted amended labels for three products with
food/feed uses:  Actara® Insecticide (EPA Reg. No. 100-938), a 25%
water-dispersible granule (WG) formulation; Centric® 40WG Insecticide
(EPA Reg. No. 100-1147), a 40% WG formulation; and Platinum®
Insecticide (EPA Reg. No. 100-939), a 2 lb/gal FlC formulation.  For the
25% WG formulation, the petitioner has proposed:  to add uses on globe
artichoke, barley, caneberry, brassica leafy vegetables, grapes, and
leafy vegetables; to reinstate cucurbit vegetables and fruiting
vegetables to the label; and to increase the maximum seasonal rates for
bushberry, cranberry, cucurbit vegetables, fruiting vegetables, mint,
pome fruit, stone fruit, and strawberry.  For the 40% WG formulation,
the petitioner has proposed to increase the maximum seasonal rate to
cotton.  For the 2 lb/gal FlC formulation, the petitioner has proposed:
to add uses on brassica leafy vegetables, grapes, hops, and leafy
vegetables; to increase the maximum application rate to bushberry,
cucurbit vegetables, fruiting vegetables, root vegetables subgroup 1B
(except sugarbeet), and strawberry; and to add an additional application
method for tuberous and corm vegetables.

The   SEQ CHAPTER \h \r 1 Interregional Research Project No. 4 (IR-4)
has submitted a request for an amended registration of the end-use
product Actara® Insecticide to include new uses on artichoke (globe),
barley, and caneberry.  IR-4 has also requested to amend the
registration of Platinum® Insecticide to include new use of
thiamethoxam on hops.  Concurrently, IR-4 requests the establishment of
permanent tolerances for residues of the insecticide thiamethoxam   SEQ
CHAPTER \h \r 1
[3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-ox
adiazin-4-imine] and its CGA-322704  SEQ CHAPTER \h \r 1  metabolite
[N-(2-chloro-thiazol-5-ylmethyl)-N’-methyl-N’-nitro-guanidine]  SEQ
CHAPTER \h \r 1 , in/on the following raw agricultural commodities:

	Artichoke, globe	0.40 ppm

	Barley, grain	0.30 ppm

	Barley, hay	0.40 ppm

	Barley, straw	0.40 ppm

	Caneberry subgroup 13A	0.30 ppm

	Hop, dried cones	0.10 ppm

Current thiamethoxam tolerances for barley grain, hay, and straw were
based on a seed-treatment use.  The petitioner has requested to add
foliar uses of thiamethoxam on barley to the label for the 25% WG
formulation, at a maximum seasonal rate of 0.094 lb ai/A with a 21-day
preharvest interval (PHI) and a retreatment interval (RTI) of 7 days.

In addition, IR-4 proposes to add foliar uses of thiamethoxam on
artichoke and caneberry to the label for the 25% WG formulation, at a
maximum seasonal rate of 0.188 lb ai/A with a 7-day RTI, a 4-day PHI for
artichoke, and a 3-day PHI for caneberry.  IR-4 has proposed to add use
on hops to the label for the 2-lb/gal SC formulation as a single
soil-surface band treatment at a maximum application rate of 0.125 lb
ai/A with a 65-day PHI.  Applications to artichokes, barley, and
caneberry are to be made using ground or aerial equipment; applications
to hops are to be made using ground equipment only.

  SEQ CHAPTER \h \r 1 The nature of the residues of thiamethoxam has
been adequately delineated based on metabolism studies with corn,
cucumbers, pears, rice, wheat, goats, and hens.  The metabolism of
thiamethoxam in plants and livestock generally involves: (i) opening of
the oxadiazine ring by hydrolysis; (ii) loss of the nitro group; (iii)
hydrolysis of the guanidine moiety to urea derivatives; (iv) cleavage of
the N-C bridge between the two ring systems; and (v) N-demethylation of
the oxadiazine ring or its derivatives.  Initial hydrolysis of the
oxadiazine ring of thiamethoxam yields CGA-322704.  The residues of
concern for both the tolerance expression and risk assessment purposes
are the combined residues of thiamethoxam and CGA-322704.   New
metabolism studies with lettuce, potato and tobacco have been submitted
and the new studies indicate that the metabolism of thiamethoxam in
lettuce, potato and tobacco is similar to the metabolism observed in
corn, cucumbers, pears, rice, and wheat.

  SEQ CHAPTER \h \r 1 An adequate method is available to enforce the
established and proposed tolerances, HPLC Method AG-675.  The method may
be obtained from the Analytical Chemistry Branch of the Biological and
Economic Analysis Division (ACB/BEAD).  Briefly, the method consists of
extraction with aqueous acetonitrile (ACN), liquid-liquid partitioning
and solid-phase extraction cleanup, and analysis by HPLC with UV or MS
detection.  The LOQ is 0.01 ppm for each analyte in most commodities.
The petitioner has submitted a modification of the method to add a
microwave extraction step for liver; the modification has been
adequately validated.  The petitioner should 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 fulfillment of this data requirement may be considered a
condition of registration.

Adequate field trial data have been submitted to support the requested
new uses of the 25% WG formulation (EPA Reg. No. 100-938) and the 2
lb/gal FlC formulation (EPA Reg. No. 100-939) on brassica leafy
vegetables, grapes, and leafy vegetables.  Additional information,
pertaining to residues in/on untreated samples and product formulations,
should be submitted for one of the brassica leafy vegetable studies and
two of the leafy vegetable studies; fulfillment of these requirements
may be considered a condition of registration.  The submitted crop field
trial data were collected using the existing enforcement method and are
supported by adequate storage stability data.  The data indicate that
the proposed tolerances for grapes, head and stem brassica, leafy
brassica greens, and leafy vegetables are too low; tolerances of 0.20
ppm, 4.5 ppm, 3.0 ppm, and 4.0 ppm, respectively, are needed.

Adequate crop field trial data have been submitted or are available to
support the amended use patterns of the 25% WG formulation (EPA Reg. No.
100-938) and the 2 lb/gal FlC formulation (EPA Reg. No. 100-939), with
the exception of the additional application method for tuberous and corm
vegetables proposed on the 2 lb/gal FlC formulation label.  The
submitted crop field trial data were collected using the existing
enforcement method and are supported by adequate storage stability data.
 The crop field trial data indicate that the established tolerance of
0.02 ppm for the root vegetable, except sugar beets, subgroup is too
low; an increased tolerance of 0.05 ppm is needed.  In addition, the
established tolerance for radish tops should be expanded to include the
leaves of root and tuber vegetables, except sugar beets.  The data
indicate that the established tolerance of 0.25 ppm for potato may be
reduced to 0.15 ppm.

Adequate processing data were submitted for grape, mint, and potato.
These data indicate that a tolerance for raisins is necessary; the
proposed 0.30-ppm tolerance is appropriate.  The processing data also
indicate that no tolerances are needed for grape juice or the processed
commodities of mint and potato.  Additional information is needed to
support a previously submitted apple processing study.

Adequate data have been submitted to demonstrate that there are no
significant differences in residues as a result of treatment with the
2-lb/gal flowable concentrate formulation versus the 25%
water-dispersible granule formulation of thiamethoxam.  The bridging
data support registration of the SC formulation on those crops listed as
registered for the WG formulation.

Adequate field trial data have been submitted for globe artichoke,
caneberry, and hops.  A residue decline study is required to fulfill
data requirements for barley; this requirement may be considered a
condition of registration.  The submitted crop field trial data are
supported by an adequate analytical method and adequate storage
stability data.  The residue data have been evaluated using the NAFTA
tolerance harmonization methods.  Recommended tolerance levels are
summarized below and in Table 27.  Processing study results indicate
that tolerances for barley processed commodities are not required.

The established 120-day plantback interval for crops without
thiamethoxam uses is tentatively supported by confined and field
rotational crop studies; additional information on sample storage
conditions for a potential rotational crop metabolite of concern
(CGA-265307) is required.  Fulfillment of this data requirement may be
considered a condition of registration.

There are livestock and poultry feed items associated with the proposed
and registered uses of thiamethoxam.  The calculated theoretical dietary
burdens (0.77 ppm for beef cattle and 0.98 ppm for dairy cattle)
resulting from the proposed and registered uses are supported by
previously submitted livestock feeding studies.  HED concludes that the
current tolerances for milk and the meat of cattle, goat, horse, and
sheep, and the meat byproducts of hog are adequate to cover the added
residues resulting from the proposed uses.  However, the available data
indicate that increased tolerances are needed for the meat byproducts of
cattle, goat, horse, and sheep, from 0.02 to 0.04 ppm.

Note to PM:  The tolerance expression for thiamethoxam listed in 40 CFR
180.565(a) and 180.565(b) should be revised to reflect the fact that the
enforcement method reports combined residues of thiamethxoam and
CGA-322704 in terms of parent equivalents.

The expression in 180.565(a) should be revised to:

“A tolerance is established for the combined residues of the
insecticide thiamethoxam
[3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-ox
adiazin-4-imine] (CAS Reg. No. 153719–23–4) and its metabolite
[N-(2-chloro-thiazol-5-ylmethyl)-N′-methyl-N′′-nitro-guanidine],
calculated as parent equivalents, in or on the following raw
agricultural commodities:”

The expression in 180.565(b) should be revised to:

′-methyl-N′′-nitro-guanidine], calculated as parent equivalents,
in connection with use of the pesticide under section 18 emergency
exemptions granted by EPA.”

Also, RD should ensure that the use restrictions listed on the Section
18 label that are in place to prevent transfer of residues to potable
water, fish, and irrigated crops that might otherwise result from the
use of thiamethoxam on cranberry are carried over to the Section 3
label.

  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
Directions for Use), a revised Section F (see requirements under
Proposed Tolerances), and a new certificate of analysis or new reference
standard for CGA-322704 (see requirements under Submittal of Analytical
Reference Standards), there are no residue chemistry issues that would
preclude granting a conditional registration for the requested uses of
thiamethoxam or establishment/revision of tolerances for combined
residues of thiamethoxam and CGA-322704.  In addition, there are no
residue chemistry issues that would preclude granting conditional
registration of the amended use directions for Actara® Insecticide (EPA
Reg. No. 100-938) and Platinum® Insecticide (EPA Reg. No. 100-939) as
specified on the amended labels received at EPA 8/2/06.

The proposed/amended uses and the submitted data support the following
tolerances for the combined residues of thiamethoxam and CGA-322704,
expressed as thiamethoxam equivalents:

	Artichoke, globe	0.45	ppm

	Barley, grain	0.30	ppm

	Barley, hay	0.40	ppm

	Barley, straw	0.40	ppm

	Borage, seed 	0.02 	ppm

	Brassica, head and stem, subgroup 5A	4.50	 ppm

	Brassica, leafy greens, subgroup 5B	3.0 	ppm

	Bushberry, subgroup 13B	0.20 	ppm

	Caneberry subgroup 13A	0.35	ppm

	Canola, seed	0.02 	ppm

	Cattle, meat	0.02 	ppm

	Cattle, meat byproducts	0.04 	ppm

	Cotton, gin byproducts	1.50 	ppm

	Cotton, undelinted seed	0.10 	ppm

	Crambe, seed	0.02 	ppm

	Cranberry	0.02 	ppm

	Flax, seed 	0.02 	ppm

	Fruit, pome, group 11	0.20 	ppm

	Fruit, stone, group 12	0.50 	ppm

	Goat, meat	0.02 	ppm

	Goat, meat byproducts	0.04 	ppm

	Grape	0.20 	ppm

	Grape, raisin	0.30 	ppm

	Hog, meat byproducts	0.02 	ppm

	Hop	0.10	ppm

	Horse, meat	0.02 	ppm

	Horse, meat byproducts	0.04 	ppm

	Juneberry	0.20 	ppm

	Leaves of root and tuber vegetables, except sugar beets	0.80 	ppm

	Lingonberry	0.20 	ppm

	Milk	0.02 	ppm

	Mustard, seed 	0.02 	ppm

	Peppermint	1.50 	ppm

	Potato 	0.15 	ppm

	Rapeseed, seed 	0.02 	ppm

	Safflower, seed 	0.02 	ppm

	Salal	0.20 	ppm

	Sheep, meat	0.02 	ppm

	Sheep, meat byproducts	0.04 	ppm

	Spearmint	1.50 	ppm

	Strawberry	0.30 	ppm

	Sunflower 	0.02 	ppm

	Tomato, paste	0.80 	ppm

	Vegetable, cucurbit, group 9 	0.02 	ppm

	Vegetable, fruiting, group 8	0.25 	ppm

	Vegetable, leafy, except brassica, group 4 	4.0 	ppm

	Vegetable, legume, group 6	0.02 	ppm

	Vegetable, root, except sugar beet, subgroup 1B	0.05 	ppm

	Vegetable, tuberous and corm, except potato, subgroup 1D	0.02	 ppm

There are no residue chemistry considerations that would preclude
establishment of permanent tolerances at the above levels.  There are
residue chemistry data gaps that HED believes should be filled and,
therefore, is recommending that any registrations for thiamethoxam be
made conditional upon resolution of the issues noted below.  A human
health risk assessment is forthcoming.

860.1200 Directions for Use

The following label amendments should be made for Actara® 240 SC:

The Resistance Management section should be corrected to reflect the
fact that Actara® 240 SC is applied foliarly and is not applied to the
soil.

The use directions for mint should be amended to specify a minimum
retreatment interval (RTI) of 14 days.

The proposed amended use directions for Actara® (EPA Reg. No. 100-938)
are supported by the available crop field trial, provided that the
petitioner makes the following amendments to the proposed label:

The label should clearly state that foliar applications of thiamethoxam
may not be made to any crop which was treated with thiamethoxam as a
soil application.

The proposed PHI for application to leafy vegetables should be revised
to 7 days.

The listing for “Spinach” in the crops included in the Leafy
Vegetables (except Brassica) group should be modified to state
“Spinach, including New Zealand and vine spinach” (the current
wording implies that the only types of spinach that may be treated are
New Zealand and vine spinach).

The proposed minimum RTI for strawberries should be modified from 7 days
to 10 days, the interval that is supported by the available crop field
trial data.

The proposed amended use directions for Platinum® (EPA Reg. No.
100-939) are supported by the available crop field trial, provided that
the petitioner makes the following amendments to the proposed label:

The label should clearly state that foliar applications of thiamethoxam
may not be made to any crop which was treated with thiamethoxam as a
soil application.

The proposed uses on leafy vegetables and brassica leafy vegetables
(head and stem brassica and leafy brassica greens) should be amended to
specify a PHI of 30 days.

The proposed use on tuberous and corm vegetables as a broadcast soil
application during last hilling operation should be deleted from the
label as no crop field trial data were submitted to support this use.

The proposed label for Actara® 240 SC and the current product labels
for Actara® (EPA Reg. No. 100-938) and Centric® 40WG (EPA Reg. No.
100-1147) recommend that spray adjuvants be used.  HED recommends that
statements indicating that use of a spray adjuvant may improve spray
coverage be removed from these labels.  The available crop field trial
data did not reflect use of adjuvants in the spray solutions.  HED
recommends such data be provided if the registrant desires statements on
the product labels indicating adjuvants may improve spray coverage.

The product label for EPA Reg. No. 100-941 specifies a seed treatment
rate for cotton in terms of mg ai per individual seed.  The label should
be amended to additionally include an application rate in terms of 100
lb of seed.  The available data support an application rate of 0.3 lb
ai/100 lb seed.

For products which include seed piece treatment for potatoes (EPA Reg.
Nos. 100-941 and 100-1249), a statement prohibiting the application of
thiamethoxam to potato plants grown from treated seed should be added to
the label.

For products which include seed treatment of soybeans (EPA Reg. Nos.
100-941 and 100-1247), a statement prohibiting the grazing, feeding, or
harvesting of treated soybean forage or hay for livestock should be
added to the label; no crop field trial data for soybean forage or hay
have been submitted.

Amendments to the proposed uses are required for the 25% WG formulation
(EPA Reg. No. 100-938) to reflect the parameters of field trial data for
artichoke, barley, and caneberry.

The use directions for artichoke, barley, and caneberry recommend that
spray adjuvants be used.  HED recommends that statements indicating that
use of a spray adjuvant may improve spray coverage be removed from these
labels.  The available crop field trial data did not reflect use of
adjuvants in the spray solutions.  HED recommends such data be provided
if the registrant desires statements on the product labels indicating
adjuvants may improve spray coverage.

For artichokes, the submitted label should be revised to specify a
maximum seasonal rate of 0.094 lb ai/A (6 oz product/A).  The proposed
single application rate, RTI, and PHI are supported by the submitted
crop field trial data.

For barley, the label should be revised to restrict use to barley grown
in the states of ID, ND, OR, SD, and WA.  The available data would
support an increase in the proposed application rate, to a maximum of
two applications at 0.063 lb ai/A/application (4 oz product/A) for a
maximum seasonal rate of 0.125 lb ai/A.  The proposed 7-day RTI and
21-day PHI are supported by the available data.

For caneberry, the label should be revised to specify a maximum single
application rate of 0.047 lb ai/A (3 oz product/A) and a maximum
seasonal rate of 0.094 lb ai/A (6 oz product/A).  The submitted crop
field trial data support the 7-day RTI and the 3-day PHI.

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

The analytical reference standard for thiamethoxam metabolite CGA-322704
currently available at the EPA National Pesticide Standards Repository
has expired.  The registrant should either recertify the lot in the
repository and send in an updated certificate of analysis, or submit a
new standard (different lot #) if the previous lot will not be
recertified.

860.1550 Proposed Tolerances

The proposed tolerances for grapes, head and stem brassica, leafy
brassica greens, leafy vegetables, and raisins should be revised to
reflect the recommended tolerance levels and correct commodity
definitions as specified above and in Table 27.  In addition, the
tolerance for grape juice should be removed from the petition; the
available data indicate that a tolerance is not needed for grape juice.

HED recommends that conversion of conditional registration to
unconditional registration for the requested uses may be considered upon
submission of the outstanding residue chemistry data pertaining to
residue analytical methods; meat, milk, poultry, and eggs; crop field
trials; processed food and feed; and field accumulation in rotational
crops.

860.1340 Residue Analytical Methods

The petitioner should 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.

860.1480 Meat, Milk, Poultry, Eggs

The petitioner should 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.

860.1500 Crop Field Trials

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

If the petitioner wishes to support soil applications to tuberous and
corm vegetables later than crop emergence, additional crop field trial
data are required.

The petitioner should provide an explanation for the residues observed
in/on untreated leafy vegetable samples in the crop field trial study
reported in MRID 45880901.

860.1520 Processed Food and Feed

The petitioner had previously been required to submit complete sample
history information including storage conditions for processed apple
commodities to support the apple processing study reported in MRID
44715134 (conclusion 26 of PP#9F5051 review, DP Number D265079, 5/8/00,
G.J. Herndon).  This information remains outstanding.

860.1900 Field Accumulation in Rotational Crops

The petitioner had previously been required to submit information
pertaining to sample storage conditions for rotational crop commodities
to support the field rotational crop study reported in MRID 44715106
(conclusion 34 of PP#9F5051 review, DP Number D265079, 5/8/00, G.J.
Herndon).  This information remains outstanding.

HED notes that the submitted data have resolved several previous data
deficiencies for thiamethoxam.  All data deficiencies specified in the
review for PP#9F5046 (DP Number D252021, 3/30/00, G.J. Herndon) have now
been resolved.  All data deficiencies, with the exception of those
specified in conclusions 26 and 34 (sample storage conditions only), of
the review for PP#9F5051 (DP Number D265079, 5/8/00, G.J. Herndon) have
now been resolved; and the only data deficiency specified in the review
for PP#0F6142 (DP Number D285545, 11/6/02, M. Doherty) has been
resolved.  All remaining data deficiencies have been reiterated above.

Background

Thiamethoxam is a broad-spectrum nitroguanidine insecticide which
belongs to the pesticidal class of compounds known as the neonicotinoids
(Group 4A; Insecticide Resistance Action Committee, Crop Life
International).  It has activity against sucking and chewing insects on
a wide variety of crops.  It appears to interfere with the nicotinic
acetyl choline receptors of the insect’s nervous system, but the
specific receptor site is unknown at this time.  It does not inhibit
cholinesterase or interfere with sodium channels and, therefore, has a
different mode of action than organophosphate, carbamate, and pyrethroid
insecticides.

The chemical structure and nomenclature of thiamethoxam and its
regulated metabolite CGA-322704 are presented in Table 1.  The
physicochemical properties of the technical grade of thiamethoxam are
presented in Table 2.

Table 1.		Thiamethoxam Nomenclature.

Chemical structure

Common name	Thiamethoxam

Company experimental name	  SEQ CHAPTER \h \r 1 CGA 293343

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 product (EP)	25% WG formulation (Actara® Insecticide; EPA Reg.
No. 100-938)

2 lb/gal FlC formulation (Platinum® Insecticide; EPA Reg. No. 100-939)

40% WG formulation (Centric® 40WG Insecticide; EPA Reg. No. 100-1147)

2 lb/gal FlC formulation (Actara® 240 SC Insecticide; EPA File Symbol
No. 100-RELN)

Chemical structure of CGA-322704 metabolite

N-[(2-chloro-5-thiazoyl)methyl]-N’-methyl-N”-nitroguanidine

Table 2.		Physicochemical Properties of Thiamethoxam.

Parameter	Value	Reference

Melting point/range	139.1 (C	PMRA Regulatory Note (REG2001-03) on
Thiamethoxam, 2/9/01

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 within the pH range 2–12

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

	UV/visible absorption spectrum	Not available

860.1200  Directions for Use

Syngenta has submitted a proposed label for a 2 lb/gal FlC formulation
(Actara® 240 SC Insecticide; EPA File Symbol No. 100-RELN) proposed for
foliar uses on the following crops:  bushberry subgroup; juneberry;
lingonberry; salal; cotton; cranberry; cucurbit vegetables; fruiting
vegetables; mint (peppermint and spearmint); pecan; pome fruit; root
vegetable subgroup, except sugar beets; stone fruit; strawberry;
tobacco; and tuberous and corm vegetables.  In addition, Syngenta has
submitted amended labels for three products:  Actara® Insecticide (EPA
Reg. No. 100-938), a 25% WG formulation; Centric® 40WG Insecticide (EPA
Reg. No. 100-1147), a 40% WG formulation; and Platinum® Insecticide
(EPA Reg. No. 100-939), a 2 lb/gal FlC formulation.

HED notes that the proposed label for Actara® 240 SC and amended label
for Platinum® Insecticide (EPA Reg. No. 100-939) each state on the
front page of the label that the product is a “soluble concentrate,”
containing 2 lbs of thiamethoxam per gallon.  Based on the reported
water solubility of thiamethoxam, of 4.1 g/L (0.034 lb/gal; see Table
2), it seems unlikely that the products are soluble concentrates.  The
product labels specify, under Mixing Directions:  “Vigorous agitation
is necessary for proper dispersal of the product.  Maintain maximum
agitation throughout the spraying operation.”  Based on these
considerations, we concluded that the products are flowable concentrate
(i.e., suspension concentrate) formulations.

A summary of the products for which proposed/amended labels were
submitted is presented in Table 3.  A summary of the proposed/amended
use directions on these labels is presented in Table 4.

Table 3.		Summary of Proposed/Registered End-Use Products.

Trade Name	Reg. No.	ai (% of formulation)	Formulation Type	Target Crops
Target Pests	Label Date

Actara® Insecticide	100-938	25.0	WG	Barley; Berries (caneberry
subgroup, bushberry subgroup, juneberry, lingonberry, salal); Brassica
leafy vegetables; Cranberry; Cucurbit vegetables; Fruiting vegetables;
Globe artichoke; Grapes; Leafy vegetables; Mint;  Pome fruit; Root
vegetable subgroup, (except sugar beets); Stone fruit; Strawberry;
Tobacco; and Tuberous and corm vegetables	A variety of sucking and
chewing insects	Undated

Actara® 240 SC Insecticide	100-RELN	21.6 (2 lb/gal)	FlC	Bushberry
subgroup; Juneberry; Lingonberry; Salal; Cotton; Cranberry; Cucurbit
vegetables; Fruiting vegetables; Mint; Pecan; Pome fruit; Root vegetable
subgroup, except sugar beets; Stone fruit; Strawberry; Tobacco; and
Tuberous and corm vegetables	A variety of sucking and chewing insects
12/19/05

Centric® 40WG Insecticide	100-1147	40.0	WG	Cotton; Pecan	A variety of
sucking and chewing insects	10/27/05

Platinum® Insecticide	100-939	21.6 (2 lb/gal)	FlC	Bushberry subgroup;
Juneberry; Lingonberry; Salal; Brassica leafy vegetables; Cucurbit
vegetables; Fruiting vegetables; Leafy vegetables; Grapes; Hops; Root
vegetable subgroup, except sugar beets; Strawberry; Tobacco; and
Tuberous and corm vegetables	A variety of sucking and chewing insects
Undated

Currently, several thiamethoxam products are registered for use on crops
associated with this review [canola; cotton; cranberry; mint;
strawberry; tobacco, and crop groups/subgroups 1B (root vegetables
except sugar beet), 1C (tuberous and corm vegetables), 6 (legume
vegetables), 8 (fruiting vegetables), 9 (cucurbit vegetables), 11 (pome
fruit), 12 (stone fruit), and 13B (bushberry)]:

Helix XTra™ Insecticide with Fungicides (EPA Reg. No. 100-935), a 2.23
lb/gal ready-to-use (RTU) formulation; label dated 2/3/06;

Actara® Insecticide (EPA Reg. No. 100-938), a 25% WG formulation; label
dated 12/22/04;

Platinum® Insecticide (EPA Reg. No. 100-939), a 2 lb/gal FlC
formulation; label dated 7/9/05;

Cruiser® Insecticide (EPA Reg. No. 100-941), a 5 lb/gal FlC
formulation; label dated 2/3/06;

Centric® Insecticide (EPA Reg. No. 100-968), a 25% WG formulation;
label dated 12/11/03;

Helix™ Insecticide with Fungicides (EPA Reg. No. 100-973), a 1.12
lb/gal RTU formulation; label dated 2/3/06;

Platinum Ridomil Gold™ Insecticide/Fungicide (EPA Reg. No. 100-974), a
0.406 lb/gal FlC formulation; label dated 11/24/04;

Centric® 40WG Insecticide (EPA Reg. No. 100-1147), a 40% WG
formulation, label dated 10/15/03;

CruiserMaxx™ Beans Insecticide Fungicide (EPA Reg. No. 100-1247), a
2.15 lb/gal EC formulation; label dated 5/24/06;

Adage®-Maxim® 4FS Twin Pack Insecticide-Fungicide (EPA Reg. No.
100-1249), a 5 lb/gal FlC formulation; label dated 4/14/06.

HED notes that EPA Reg. No. 100-974 (Platinum Ridomil Gold) is coded
incorrectly in PPLS as an emulsifiable concentrate formulation.

Table 4. 	Summary of Proposed/Amended Directions for Use of
Thiamethoxam.

Formulation

[EPA Reg. No.]	Application Timing	Application Rate

(lb ai/A)	Max. No. Applic. per Season	Minimum RTI1

(days)	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and other Limitations

Artichoke, Globe

25% WG

[100-938]	Foliar spray	0.047	4 (implied)	7	0.188	4	Applications are to
be made in a minimum of 10 gal/A using ground equipment or a minimum of
5 gal/A using aerial equipment.

Barley

25% WG

[100-938]	Foliar spray	0.047	2 (implied)	7	0.094	21	Applications are to
be made in a minimum of 10 gal/A using ground equipment or a minimum of
5 gal/A using aerial equipment.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

Brassica (Cole) Leafy Vegetables:  Head and Stem Brassica [Broccoli,
Chinese Broccoli, Brussels Sprouts, Cabbage, Chinese Cabbage (Napa),
Chinese Mustard Cabbage, Cauliflower, Cavalo Broccolo, Kohlrabi]

2 lb/gal FlC

[100-939]	At or post planting or transplant	0.078-0.172	1	Not applicable
(NA)	0.172	14	Application is to be made: as an in-furrow spray during
planting; as a soil drench post seeding or transplant; in trickle or
drip irrigation water; or shanked into the root zone after establishment
or transplant.  Foliar applications of thiamethoxam may not be made
following a long-residual, soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.023-0.086	Not specified (NS)	7	0.172	0
Applications are to be made in a minimum of 10 gal/A using ground
equipment or a minimum of 5 gal/A using aerial equipment.  Application
may not be made following a long-residual seed or soil application of
thiamethoxam.

Brassica (Cole) Leafy Vegetables:  Leafy Brassica Greens [Broccoli Raab,
Chinese Cabbage (Bok Choy), Collards, Kale, Mizuna, Mustard Greens,
Mustard Spinach, Rape Greens]

2 lb/gal FlC

[100-939]	At or post planting or transplant	0.078-0.172	1	Not applicable
(NA)	0.172	14	Application is to be made: as an in-furrow spray during
planting; as a soil drench post seeding or transplant; in trickle or
drip irrigation water; or shanked into the root zone after establishment
or transplant.  Foliar applications of thiamethoxam may not be made
following a long-residual, soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.023-0.086	NS	7	0.172	7	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

Bushberry Subgroup [Blueberry (high and low bush), Currant, Elderberry,
Gooseberry, Huckleberry]; Juneberry; Lingonberry; Salal

2 lb/gal FlC

[100-939]	After bud break prior to beginning of bloom	0.078-0.188	1	NA
0.188	75	Application may be made as a surface band on each side of the
row out to the plant canopy drip line or within the vegetation-free
herbicide strip, in a minimum of 10 gal/A.  On the same day as
application, sufficient irrigation is to be applied following
application to incorporate the product into the plant’s root zone.
Foliar applications of thiamethoxam may not be made following a
long-residual, soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]	Foliar spray	0.047-0.063	NS	7	0.125	3	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.047-0.063	NS	7	0.188	3

	Caneberry [Blackberry, Loganberry, Red and Black Raspberry]

25% WG

[100-938]	Foliar spray	0.031-0.063	NS	7	0.188	3	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.

Cotton

2 lb/gal FlC

[100-RELN]	Foliar spray	0.031-0.047	NS	5	0.094	21	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 3
gal/A using aerial equipment.  Application within 45 days of planting is
prohibited if seeds were treated with a neonicotinoid product.

40% WG [100-1147]	Foliar spray	0.031-0.063	NS	5	0.125	21

	Cranberry

2 lb/gal FlC

[100-RELN]	Foliar spray	0.031-0.063	NS	7	0.125	30	Applications are to be
made in a minimum of 10 gal/A using ground equipment.  Aerial
application is prohibited.  .

25% WG

[100-938]	Foliar spray	0.031-0.063	NS	7	0.188	30

	Cucurbit Vegetables [Chayote, Chinese Waxgourd, Citron Melon, Cucumber,
Edible Gourd, Gherkin, Momordica species, Muskmelon, Pumpkin, Summer And
Winter Squash, Watermelon]

2 lb/gal FlC

[100-939]	At or post planting or transplant	0.078-0.172	1	NA	0.172	30
Application is to be made: as an in-furrow spray during planting; as a
soil drench post seeding or transplant; in trickle or drip irrigation
water; or shanked into the root zone after establishment or transplant.
Foliar applications of thiamethoxam may not be made following a
long-residual, soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]	Foliar spray	0.031-0.063	NS	5	0.125	0	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.  Application may not be made following an
in-furrow or soil application of thiamethoxam.  Application may not be
made following a long-residual seed or soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.023-0.086	NS	5	0.172	0

	Fruiting Vegetables [Eggplant, Ground Cherry, Pepino, Peppers (Bell,
Chili, Cooking, Pimento, and Sweet), Tomatillo, Tomato]

2 lb/gal FlC

[100-939]	At or post planting or transplant	0.078-0.172	1	NA	0.172	30
Application is to be made: as an in-furrow spray during planting; as a
soil drench post seeding or transplant; in trickle or drip irrigation
water; or shanked into the root zone after establishment or transplant.
Foliar applications of thiamethoxam may not be made following a
long-residual, soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]	Foliar spray	0.031-0.063	NS	5	0.125	0	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.031-0.086	NS	5	0.172	0

	Grapes

2 lb/gal FlC

[100-939]	Soil surface	0.125-0.266	1	NA	0.266	60	Application may be made
as a surface band on each side of the row out to the plant canopy drip
line or within the vegetation-free herbicide strip, in a minimum of 10
gal/A.  On the same day as application, sufficient irrigation is to be
applied following application to incorporate the product into the
plant’s root zone.  Foliar applications of thiamethoxam may not be
made following a long-residual, soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.023-0.055	NS	14	0.109	5	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

Hops

2 lb/gal FlC

[100-939]	Soil surface	0.125	1	NA	0.125	65	Application may be made as a
surface band on each side of the row out to the plant canopy drip line
or within the vegetation-free herbicide strip.  On the same day as
application, apply sufficient irrigation following application to
incorporate the product into the plant’s root zone.

Leafy Vegetables (except Brassica) [Amaranth, Arugula, Cardoon, Celery,
Chinese Celery, Celtuce, Chervil, Chrysanthemum (edible-leaved and
garland), Corn salad, Cress (garden and upland), Dandelion, Dock,
Endive, Fennel, Lettuce (head and leaf), Orach, Parsley, Purslane
(garden and winter), Radicchio, Rhubarb, Spinach (New Zealand and vine),
Swiss chard]

2 lb/gal FlC

[100-939]	At or post planting or transplant	0.078-0.172	1	NA	0.172	14
Application is to be made: as an in-furrow spray during planting; as a
soil drench post seeding or transplant; in trickle or drip irrigation
water; or shanked into the root zone after establishment or transplant.
Foliar applications of thiamethoxam may not be made following a
long-residual, soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.023-0.086	NS	7	0.172	3	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

Mint [Peppermint and Spearmint]

2 lb/gal FlC

[100-RELN]	Foliar spray	0.023-0.063	NS	4	0.125	7	Applications are to be
made in a minimum of 10 gal/A using ground equipment.  Aerial
application is prohibited.

25% WG

[100-938]	Foliar spray	0.023-0.063	NS	14	0.188	7	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment.

Pecan

2 lb/gal FlC

[100-RELN]	Foliar spray	0.047-0.063	NS	7	0.125	14	Applications are to be
made in a minimum of 50 gal/A using ground equipment or a minimum of 20
gal/A using aerial equipment.

40% WG

[100-1147]	Foliar spray	0.050-0.063	NS	7	0.125	14

	Pome Fruit [Apples, Crabapples, Loquat, Mayhaw, Quince, Pear, Oriental
Pear (Pyrus pyrifolia)]

2 lb/gal FlC

[100-RELN]	Prebloom foliar spray	0.070-0.086	1	10	0.125	35 or 14
Applications are to be made in a minimum of 50 gal/A using ground
equipment.  Aerial application is prohibited.  Applications to apples
are only to be made to apples produced east of the Mississippi River.
Applications are not to be made to apples grown in NY except via SLN
NY020001.  A 35-day PHI has been proposed for applications >0.043 lb
ai/A.  A 14-day PHI has been proposed for applications ≤0.043 lb ai/A.
 Applications are not to be made to apples and pears after pre-bloom or
before post bloom.

	Postbloom foliar spray	0.031-0.086	NS

25% WG

Applications are not to be made to apples grown in NY except via SLN
NY020001.  A 35-day PHI has been proposed for applications >0.043 lb
ai/A.  A 14-day PHI has been proposed for applications ≤0.043 lb ai/A.
 Applications are not to be made to apples and pears after pre-bloom or
before post bloom.

	Postbloom foliar spray	0.031-0.086	NS

Root Vegetables Subgroup (Except Sugar beets) [Radish, Carrot, Celeriac,
Chicory, Edible Burdock, Garden Beet, Ginseng, Horseradish, Oriental
Radish, Parsnip, Rutabaga, Black Salsify, Spanish Salsify, Skirret,
Turnip, Turnip Rooted Chervil, Turnip Rooted Parsley]

2 lb/gal FlC

[100-939]	At seeding or within 24 hours of seeding	0.078-0.188	1	NA
0.102 for radish;

0.188 for all other crops	NS	Application is to be made: as an in-furrow
spray during planting; immediately after seeding using sufficient water
to incorporate into the seed zone; or in trickle or drip irrigation
water.  Foliar applications of thiamethoxam may not be made following a
long-residual, soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]

25% WG

[100-938]	Foliar spray	0.023-0.063	NS	7	0.063 for radish;

0.125 for all others	7	Applications are to be made in a minimum of 10
gal/A using ground equipment or a minimum of 5 gal/A using aerial
equipment.  Application may not be made following a long-residual seed
or soil application of thiamethoxam.

Stone Fruit [ Apricot, Chickasaw Plum, Damson Plum, Japanese Plum,
Nectarine, Peach, Plum, Plumcot, Prune (Fresh), Sweet and Tart Cherry]

2 lb/gal FlC

[100-RELN]	Foliar spray	0.031-0.086	2	7	0.125	14	Applications are to be
made as one pre-bloom and/or one post-bloom.  Applications are not to be
made after pre-bloom or before post bloom.  Applications are to be made
in a minimum of 50 gal/A using ground equipment.  Aerial application is
prohibited

25% WG

[100-938]	Foliar spray	0.031-0.086	NS	7	0.172	14	Applications are not to
be made after pre-bloom or before post bloom.  Applications are to be
made in a minimum of 50 gal/A using ground equipment.  Aerial
application is prohibited.

Strawberry

2 lb/gal FlC

[100-939]	At or post planting, or prior to or at transplant	0.078-0.188
1	NA	0.188	50	Application is to be made: as an in-furrow spray during
planting; as a post transplant drench; in trickle or drip irrigation
water; or as a plant hole treatment just prior to or at transplant.
Foliar applications of thiamethoxam may not be made following a
long-residual, soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]	Foliar spray	0.023-0.063	NS	7	0.125	3	Applications are to be
made in a minimum of 10 gal/A using ground equipment.  Aerial
application is prohibited.  Application may not be made following an
in-furrow or soil application of thiamethoxam.

25% WG

[100-938]	Foliar spray	0.023-0.063	NS	7	0.188	3	Applications are to be
made in a minimum of 50 gal/A using ground equipment.  Aerial
application is prohibited.  Application may not be made following a
long-residual seed or soil application of thiamethoxam.

Tobacco

2 lb/gal FlC

[100-939]	At transplant	0.008-0.02 lb/ 1,000 plants	1	NA	0.125	NS
Application is to be made at transplant to transplants in trays or as a
drench during transplanting.  Foliar applications of thiamethoxam may
not be made following a long-residual, soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]

25% WG

[100-938]	Foliar spray	0.031-0.047	NS	NS	0.047	14	Applications are to be
made in a minimum of 20 gal/A using ground equipment.  Application may
not be made following a long-residual seed or soil application of
thiamethoxam.

Tuberous And Corm Vegetables [Arracacha, Arrowroot, Canna, Bitter And
Sweet Cassava, Chayote (Root), Chinese Artichoke, Chufa, Dasheen,
Ginger, Jerusalem Artichoke, Leren, Potato, Sweet Potato, Tanier,
Turmeric, Yam Bean, Yams]

2 lb/gal FlC

[100-939]	Before planting, at planting, at emergence, or during last
hilling operation	0.078-0.125	1	NA	0.125	NS	Application is to be made:
as an in-furrow spray during planting; before or during planting
impregnated on granular fertilizer; at plant emergence as a directed
spray; or as a broadcast spray during last hilling operation.  Foliar
applications of thiamethoxam may not be made following a long-residual,
soil application of thiamethoxam.

2 lb/gal FlC

[100-RELN]

25% WG

[100-938]	Foliar spray	0.023-0.047	NS	7	0.094	14	Applications are to be
made in a minimum of 10 gal/A using ground equipment or a minimum of 5
gal/A using aerial equipment. Application may not be made following a
long-residual seed or soil application of thiamethoxam.

1  RTI = Retreatment interval

Applications are to be made before pests reach damaging levels.  A
restricted-entry interval (REI) of 12 hours is proposed.  The proposed
label for Actara( 240 SC and the current labels for Actara® (EPA Reg.
No. 100-938) and Centric® 40WG (EPA Reg. No. 100-1147) state that the
use of a spray adjuvant may improve spray coverage but is not required.
Applications to cranberry may be made through sprinkler irrigation
equipment and applications to tuberous and corm vegetables may be made
using chemigation; application may not be made using irrigation
equipment physically connected to a public water system.

The following recommendations were made on the amended label for
Actara® (EPA Reg. No. 100-938) regarding resistance management:  avoid
using a block of more than three consecutive applications of Actara®
and/or other Group 4A insecticides; following a block of Group 4A
insecticides, rotate to a block of applications of effective products
with a different mode of action before using additional applications of
Group 4A insecticides; and foliar applications of Actara® or other
Group 4A insecticides may not be made following a long-residual soil
application of thiamethoxam or other seed- or soil-applied Group 4A
insecticides.

The following recommendations were made on the amended label for
Platinum® (EPA Reg. No. 100-939) regarding resistance management:  only
a single soil application of Platinum® may be made; and foliar
applications of Group 4A insecticides may not be made following a
long-residual soil application of thiamethoxam or other seed- or
soil-applied Group 4A insecticides.

The following recommendations were made on the proposed label for
Actara® 240 SC regarding resistance management:  only a single soil
application of Actara® 240 SC may be made; and foliar applications of
thiamethoxam or other Group 4A insecticides may not be made following a
long-residual soil application of Actara® 240 SC or other seed- or
soil-applied Group 4A insecticides.

With the exception of EPA Reg. Nos. 100-935, 100-973, and 100-974, the
following rotational crop restrictions are specified:  (i) treated areas
may be replanted immediately following harvest, or as soon as practical
following the last application, with any crop listed on the label and/or
 barley, brassica vegetables, canola, corn, cotton, cucurbit vegetables,
fruiting vegetables, leafy vegetables, legume vegetables, mint, oilseed
crops (rapeseed, Indian rapeseed, Indian mustard seed, field mustard
seed, black mustard seed, flax seed, safflower seed, crambe seed and
borage seed), root vegetables (except sugar beet), sorghum, strawberry,
sunflower, tobacco, tuberous and corm vegetables, and wheat; (ii) any
cover crop planted for erosion control or soil improvement may be
planted as soon as practical following last application, however, the
cover crop may not be grazed or harvested for food or feed; and (iii)
for all other crops, a 120-day plant-back interval (PBI) must be
observed.  HED notes that the amended labels for Actara® and Platinum®
(EPA Reg. Nos. 100-938 and 100-939) received for review did not contain
the rotational crop restrictions sections of the labels; rotational crop
restrictions were obtained from the current approved labels for these
products.

The product label for EPA Reg. No. 100-974 specifies more limiting
rotational crop restrictions than those listed above presumably because
the product also contains the active ingredient mefenoxam.

The following rotational crop restrictions are specified for EPA Reg.
Nos. 100-935 and 100-973:  treated areas may be replanted immediately
following harvest with canola or wheat, or as soon as practical
following the last application; all other crops may be planted 30 days
after the last application.

The proposed changes to the Actara® label (EPA Reg. No. 100-938) are
detailed below:

The resistance management section was expanded;

Uses on the following crops or crop groups were added:  artichoke
(globe); barley; caneberry; brassica leafy vegetables; grapes; and leafy
vegetables;

Uses on the following crops, which had been voluntarily deleted to
address risk issues, were re-introduced:  cucurbit vegetables and the
fruiting vegetables eggplant, groundcherry, pepino, tomatillo, and
tomato;

The maximum seasonal application rate was increased for the following
crops or crop groups:  bushberry; cranberry; cucurbit vegetables;
fruiting vegetables; mint; pome fruit; stone fruit; and strawberry;

The restriction to only make applications to mint using ground equipment
was deleted;

The restriction to only make applications to apples grown east of the
Mississippi River was deleted;

The restriction to only make one pre-bloom application to pome fruit was
deleted;

The restriction on the number of pre-bloom and post-bloom applications
to stone fruit was deleted.

The proposed changes to the Centric® 40WG label (EPA Reg. No. 100-1147)
are an increase in the maximum single and seasonal application rates to
cotton, and modification of the rotational crop restrictions to include
crops which have registered thiamethoxam uses on other Syngenta
products.

The proposed changes to the Platinum® label (EPA Reg. No. 100-939) are
detailed below:

The resistance management section was expanded;

Uses on the following crops or crop groups were added:  brassica leafy
vegetables; grapes; hops; and leafy vegetables;

The maximum single and seasonal application rates were increased for the
following crops or crop groups:  bushberry; cucurbit vegetables;
fruiting vegetables; root vegetables (except sugar beet) other than
radish; and strawberry;

An additional soil application method was added to the use direction for
tuberous and corm vegetables, to allow broadcast application to the soil
during the last hilling operation.

Conclusions.  The submitted labels are adequate to allow evaluation of
the residue data relative to the proposed/amended uses.

The use directions for the following crops on the Actara® 240 SC
proposed label are identical to the use directions on the approved
product label for the 25% WG formulation (Actara®; EPA Reg. No.
100-938; label dated 12/22/04):  bushberry subgroup; juneberry;
lingonberry; salal; cranberry; peppers; pome fruit; root vegetable
subgroup, except sugar beets; stone fruit; strawberry; tobacco; and
tuberous and corm vegetables.  For mint, the use directions are
identical except that the Actara® 25% WG formulation specifies a 14-day
minimum RTI.  The current label for the Actara® 25% WG formulation does
not include use directions for cotton, cucurbit vegetables, or pecan.

The use directions for cotton and pecan on the Actara® 240 SC proposed
label are identical to the use directions for cotton and pecan on the
approved label for the 40% WG formulation (Centric® 40WG; EPA Reg. No.
100-1147; label dated 10/15/03).

There are no registered thiamethoxam products with foliar uses on
cucurbit vegetables or on fruiting vegetables other than peppers.
However, data to support foliar use of the 25% WG formulation on these
crops have been submitted previously (see 860.1500 – Crop Field
Trials).

The petitioner intends to rely on crop field trial data reflecting
foliar applications of the WG formulation to support foliar applications
of the FlC formulation to the same crops.  To support this translation
of data, the petitioner submitted bridging data reflecting side-by-side
treatments of the 2 lb/gal FlC formulation and the 25% WG formulation.
Limited side-by-side field trial data were submitted for root vegetables
subgroup 1B (carrot and radish), leafy vegetables (head lettuce, leaf
lettuce, and spinach), brassica leafy vegetables (broccoli, cabbage, and
mustard greens), fruiting vegetables (tomatoes), and stone fruits
(plums); see 860.1500 – Crop Field Trials.  Of these crops, use of
Actara® 240 SC has only been proposed for use on fruiting vegetables,
root vegetables subgroup 1B, and stone fruits.  The side-by-side data
for leafy vegetables and root vegetables subgroup 1B indicated no
significant difference in residues between the two formulations;
however, the side-by-side data for brassica leafy vegetables and plums
indicated that residues resulting from use of the WG formulation were
slightly higher than those resulting from use of the FlC formulation.
For tomatoes, the data indicate that foliar applications of the FlC
formulation may result in slightly higher residues in tomatoes than
applications of the 25% WG formulation; however, residues were low in/on
all samples.  Based on the overall results, HED has concluded (see
860.1200) that sufficient bridging crop field trial data have been
submitted to allow translation of data for the 25% WG formulation to
support foliar uses of the 2 lb/gal FlC formulation.

The following label amendments are needed for Actara® 240 SC:

The Resistance Management section needs to be corrected to reflect the
fact that Actara® 240 SC is applied foliarly and is not applied to the
soil.

The use directions for mint should be amended to specify a minimum RTI
of 14 days.

The proposed amended use directions for Actara® (EPA Reg. No. 100-938)
are supported by the available crop field trial, provided that the
petitioner makes the following amendments to the proposed label:

The label should clearly state that foliar applications of thiamethoxam
may not be made to any crop which was treated with thiamethoxam as a
soil application.

The proposed PHI for application to leafy vegetables should be revised
to 7 days.

The listing for “Spinach” in the crops included in the Leafy
Vegetables (except Brassica) group should be modified to state
“Spinach, including New Zealand and vine spinach” [the current
wording implies that the only types of spinach that may be treated are
New Zealand and vine spinach].

The proposed minimum RTI for strawberries should be modified from 7 days
to 10 days, the interval that is supported by the available crop field
trial data.

The proposed amended use directions for Platinum® (EPA Reg. No.
100-939) are supported by the available crop field trial, provided that
the petitioner makes the following amendments to the proposed label:

The label should clearly state that foliar applications of thiamethoxam
may not be made to any crop which was treated with thiamethoxam as a
soil application.

The proposed uses on leafy vegetables and brassica leafy vegetables
(head and stem brassica and leafy brassica greens) should be amended to
specify a PHI of 30 days.

The proposed use on tuberous and corm vegetables as a broadcast soil
application during last hilling operation should be deleted from the
label as no crop field trial data were submitted to support this use.

The proposed label for Actara® 240 SC and the current product labels
for Actara® (EPA Reg. No. 100-938) and Centric® 40WG (EPA Reg. No.
100-1147) recommend that spray adjuvants be used.  HED recommends that
statements indicating that use of a spray adjuvant may improve spray
coverage be removed from these labels.  The available crop field trial
data did not reflect use of adjuvants in the spray solutions.  HED
recommends such data be provided if the registrant desires statements on
the product labels indicating adjuvants may improve spray coverage.

The product label for EPA Reg. No. 100-941 specifies a seed treatment
rate for cotton in terms of mg ai per individual seed.  The label should
be amended to additionally include an application rate in terms of 100
lb of seed.

For products which include seed piece treatment for potatoes (EPA Reg.
Nos. 100-941 and 100-1249), a statement prohibiting the application of
thiamethoxam to potato plants grown from treated seed should be added to
the label.

For products which include seed treatment of soybeans (EPA Reg. Nos.
100-941 and 100-1247), a statement prohibiting the grazing, feeding, or
harvesting of treated soybean forage or hay for livestock should be
added to the label; no crop field trial data for soybean forage or hay
have been submitted.

The submitted labels are adequate to allow evaluation of the residue
data relative to the proposed uses on globe artichoke, barley,
caneberry, and hops.  Label amendments are required for the 25% WG
formulation (EPA Reg. No. 100-938) to reflect the parameters of field
trial data for artichoke, barley, and caneberry.

The use directions for artichoke, barley, and caneberry recommend that
spray adjuvants be used.  HED recommends that statements indicating that
use of a spray adjuvant may improve spray coverage be removed from these
labels.  The available crop field trial data did not reflect use of
adjuvants in the spray solutions.  HED recommends such data be provided
if the registrant desires statements on the product labels indicating
adjuvants may improve spray coverage.

For artichokes, the submitted label should be revised to specify a
maximum seasonal rate of 0.094 lb ai/A (6 oz product/A).  The proposed
single application rate, RTI, and PHI are supported by the submitted
crop field trial data.

For barley, the label should be revised to restrict use to barley grown
in the states of ID, ND, OR, SD, and WA.  The available data would
support an increase in the proposed application rate, to a maximum of
two applications at 0.063 lb ai/A/application (4 oz product/A) for a
maximum seasonal rate of 0.125 lb ai/A.  The proposed 7-day RTI and
21-day PHI are supported by the available data.

For caneberry, the label should be revised to specify a maximum single
application rate of 0.047 lb ai/A (3 oz product/A) and a maximum
seasonal rate of 0.094 lb ai/A (6 oz product/A).  The submitted crop
field trial data support the 7-day RTI and the 3-day PHI.

The proposed use directions for hops are in agreement with the submitted
field trial parameters.

860.1300 Nature of the Residue - Plants

DER Reference:	44939802.der.doc (Cucumber)

		45093709.der.doc (Tobacco)

		45093711.der.doc (Tobacco)

		45093713.der.doc (Potato)

		45093714.der.doc (Lettuce)

MRID 44939801 (summarized below; no DER prepared)

See:    SEQ CHAPTER \h \r 1 MARC Decision Memo:  D258614, 8/31/99, G.J.
Herndon

Residue Chemistry Memo D252021, 3/30/00, G.J. Herndon (PP#9F5046)

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D265079, 5/8/00, G.J.
Herndon (PP#9F5051)

Metabolism studies with thiamethoxam have been submitted on corn,
cucumbers, pears, rice, and wheat; the studies on cucumbers, pears, and
rice reflected foliar applications, and the studies on corn and wheat
reflected seed treatment and/or soil drench applications.    SEQ CHAPTER
\h \r 1 The metabolism of thiamethoxam in crops generally involves:  (i)
opening of the oxadiazine ring by hydrolysis; (ii) loss of the nitro
group; (iii) hydrolysis of the guanidine moiety to urea derivatives;
(iv) cleavage of the N-C bridge between the two ring systems; and (v)
N-demethylation of the oxadiazine ring or its derivatives.  Initial
hydrolysis of the oxadiazine ring of thiamethoxam yields CGA-322704,
which is a major metabolite in corn, pears, rice and wheat.  CGA-322704
can then either:  (i) lose its nitro group to form NOA-421275 (a major
metabolite in corn); (ii) undergo N-demethylation to yield CGA-265307;
or (iii) be cleaved at the N-C bridge to form NOA-405217 and the
thiazole ring metabolites CGA-359683 and CGA-349208.  Alternatively,
thiamethoxam may initially lose its nitro group to form NOA-407475, and
then undergo hydrolysis of the oxadiazine ring to form NOA-421275, or
oxidation of the oxadiazine ring to form CGA-355190.  [For the chemical
names and structures of identified metabolites, see Appendix I.]

The Metabolism Assessment Review Committee (MARC) has determined that
the residues of concern for purposes of tolerance enforcement and risk
assessment are the combined residues of thiamethoxam and CGA-322704.
Based on the uses requested under PP#9F5046 and 9F5051, the Committee
recommended that a new plant metabolism study be conducted on a leafy
vegetable (one of the representative commodities in either Crop Group 4
or 5).  Syngenta has now submitted the requested leafy vegetable
metabolism study.  Syngenta has also submitted an amendment to the
previously submitted cucumber metabolism study (reviewed under
PP#9F5046; DP Number D252021, 3/30/00, G.J. Herndon), a potato
metabolism study, and two metabolism studies for tobacco.

In addition, Syngenta submitted (MRID 44939801) an amendment to the
previously submitted pear metabolism study (reviewed under PP#9F5046).
The amendment contained additional data generated for pear leaves, and
amended results tables for pear fruit.  The data for pear leaves will
not be addressed herein.  Amended results tables for pear fruit were
presented to clarify results for the analysis of the aqueous fraction
from fruit treated with [14C-oxadiazine]thiamethoxam at the 16x rate;
however, the amended tables do not change any of the results that were
previously reported.  Therefore, the conclusions of the previous review
regarding the nature of the residue in pears do not need revision.

Cucumber:  Syngenta submitted an amendment to a previously submitted
cucumber metabolism study.  Samples of cucumber fruit were re-extracted
and analyzed to provide further metabolite
identification/characterization information.  In the previous study,
extractable organosoluble residues were analyzed by HPLC; however
studies in other crops indicated inconsistencies in the quantitation of
metabolite NOA-407475 by HPLC as a result of retention time dependency
on pH.  In the current submission, organosoluble residues were analyzed
by two-dimensional (2-D) TLC.

In the original study, [14C]thiamethoxam, separately labeled in the
thiazole (labeled at the 2- position) and oxadiazine (labeled at the 4-
position) rings, was applied to cucumbers twice foliarly at ~50 g
ai/ha/application, at a RTI of 10 days, for a total rate of ~100 g ai/ha
(0.09 lb ai/A/season; referred to as 0.5x rate).  Samples of mature
fruit were collected at 0 and 14 days after the last treatment, and
leaves were collected 14 days after the last treatment.  In addition, an
exaggerated rate study was conducted in which each test substance was
applied as a soil drench to seedlings at the first true-leaf stage at
~1500 g ai/ha (1.34 lb ai/A) followed 42 days later by a broadcast
foliar application at ~500 g ai/ha for a total rate of ~2000 g ai/ha
(1.78 lb ai/A/season; referred to as 10x rate).  Samples of leaves and
fruits were harvested prior to the foliar application at 42 days after
the last treatment to provide samples representing the early-season soil
application alone; samples of mature fruit, leaves, and roots and stems
were also collected 14 days after the foliar application.

As reported in the previous review, following treatment with
thiazole-label and oxadiazine-label [14C]thiamethoxam, TRR were 0.035
and 0.031 ppm, respectively, in samples harvested 14 days following 0.5x
treatment, 0.280 and 0.383 ppm, respectively, in samples harvested 42
days following soil drench treatment, and 0.295 and 0.323 ppm,
respectively, in samples harvested 14 days following soil drench +
foliar treatment.

For the current submission, subsamples of cucumber fruit from all
treatments were re-extracted using the same procedures as the original
study.  The petitioner reported that because the re-extractions of
cucumber fruit yielded very similar extraction profiles to those from
the original extractions, the original extraction balance values were
used to generate the quantitative distribution.

The re-analysis data indicate that metabolite NOA-407475 is a
significant component of cucumber residues, at 11.9-19.5% TRR in
thiazole-label samples and 13.2-34.4% TRR in oxadiazine-label samples.
NOA-407475 was only identified at low levels (up to 5.1% TRR) in the
original study.  The re-analysis yielded results similar to those from
the original study for levels of thiamethoxam and metabolites
CGA-322704, and CGA-355190 in cucumber fruit:  thiamethoxam was found at
9.2-28.0% TRR (0.003-0.103 ppm) and CGA-322704 and CGA-355190 were each
found at <7% TRR.  Levels of CGA-353968 were generally found to be lower
in the re-analyzed samples than in the original report:  0.5-2.4% TRR in
the re-analyzed samples versus 1.1-9.7% TRR in the original report.
Individual unknowns were found to be ≤8.9% TRR (≤0.033 ppm) in the
re-analyzed samples.

Derivatization and HPLC analysis of two components (Peaks A and B) of
the aqueous extractable residues indicates that each peak is comprised
of multiple unknowns, each ≤6.6% TRR (≤0.02 ppm).

Based on the results of the cucumber metabolism study, including
characterization and identification of residues in leaves (not reported
herein), the petitioner concluded that thiamethoxam is metabolized in
cucumber via one of two pathways.  The first pathway involves loss of
the nitro group to form NOA-407475, which then undergoes hydrolysis to
form CGA-355190.  Opening of the oxadiazine ring results in the
formation of CGA-353968, which then conjugates with glucose or undergoes
N-demethylation.  The second pathway involves opening of the oxadiazine
ring to form CGA-322704 followed by cleavage of the nitro group to form
NOA-421275.  CGA-322704 may also undergo N-demethylation, to form
CGA-265307, or conjugate with glucose to form the hydroxylamine
glucoside.

No dates of extraction and/or analysis were provided for the current
submission.  Based on the completion date of the study in comparison
with the experimental termination date of the original study, samples
may have been stored frozen for up to an additional 17 months after the
completion of the original study.  No supporting storage stability data
were provided for the current study.  Because the petitioner used a
different method of analysis for extractable residues, the metabolite
profile of the re-extracted samples cannot be compared with the
metabolite profiles from the original samples to evaluate stability.

Lettuce:  Syngenta submitted a study investigating the metabolism of
[thiazol-2-14C]thiamethoxam and [oxadiazin-4-14C]thiamethoxam (specific
activities 2.18 MBq/mg and 2.03 MBq/mg, respectively) in lettuce.  The
radiolabeled test substances were formulated as water-dispersible
granule formulations using formulation blank, diluted with water, and
applied to lettuce plants as three sequential foliar treatments at
0.046-0.048 lb ai/A or 0.445-0.480 lb ai/A.  The total application rates
were 0.137-0.144 lb ai/A, 0.8x the proposed maximum seasonal rate, and
1.35-1.43 lb ai/A, 8x the proposed maximum seasonal rate.  Samples were
collected 0, 3, 7, and 14 days following the final application (days
after treatment; DAT) from the 0.8x treatment plots, and 14 DAT from the
8x treatment plots.

Total radioactive residues (TRR) in lettuce samples were 1.740, 1.023,
0.633, and 0.570 ppm in the 0-, 3-, 7-, and 14-DAT samples,
respectively, from the [thiazol-2-14C]thiamethoxam 0.8x treatment;
1.976, 1.501, 0.772, and 0.688 ppm in the 0-, 3-, 7-, and 14-DAT
samples, respectively, from the [oxadiazin-4-14C]thiamethoxam 0.8x
treatment; and 4.962 and 5.067 ppm in samples harvested 14 days
following the 8x treatments with [thiazol-2-14C]thiamethoxam and
[oxadiazin-4-14C]thiamethoxam, respectively.

Extraction with 80% methanol in water released the majority of the
radioactivity (83-99%) from lettuce samples.  Soxhlet extraction
released a small amount of additional radioactivity (1.0-1.2%) from
14-DAT samples.  Additional radioactivity (12-15% in total) was released
from the nonextractable residues of 14-DAT samples, 0.8x treatment rate,
using sequential extractions at reflux with methanol/water, water, 1 N
HCl, and 1 N NaOH.  Remaining nonextractable residues in lettuce samples
from the 0.8x treatment accounted for 0.6-11.6% TRR.

These procedures adequately extracted the majority of residues from
lettuce; accountabilities were 98-108%.  Lettuce extracts were profiled
by TLC; metabolites were identified and/or confirmed by LC/MS analyses
of isolated fractions from the extracts of 8x treatment rate samples.
Adequate storage stability data were submitted to support the storage
durations and conditions of samples from the study.

Approximately 74-95% TRR were identified in lettuce.  Thiamethoxam was
the major residue identified in all samples, at 78-83% TRR (1.4-1.9 ppm)
in 0-DAT samples, 66-70% TRR (0.67-1.1 ppm) in 3-DAT samples, 53-55% TRR
(0.35-0.41 ppm) in 7-DAT samples, and 38-42% TRR (0.24-0.26 ppm) in
14-DAT samples from the 0.8x treatment, and at 48-60% TRR (2.4-3.0 ppm)
in samples from the 8x treatment.  Metabolite CGA 322704 was found in
all samples, at levels ranging 2.1-5.8% TRR (0.022-0.049 ppm), with the
higher levels (in terms of % TRR) found at longer sampling durations.
All other identified metabolites were found at <8% TRR; these included
NOA 407475, CGA 353042, CGA 382191, NOA 421275, NOA 424255, CGA 204261,
NOA 405217, CGA 265307, 1-(2-chloro-thiazol-5-yl)-urea, CGA 353968, CGA
359683, and CGA 355190, as well as the S-glucose conjugate of
3-(2-mercapto-thiazol-5-ylmethyl)-5-methyl-[1,3,5]oxadiazinan-4-one,
N-glucose conjugate of CGA 353968, O-glucose-conjugate of
(2-chloro-thiazol-5-yl)-methanol (CGA 349208), and O-glucose conjugate
of 1-(2-chloro-thiazol-5-ylmethyl)-1-hydroxymethyl-3-methyl-urea; refer
to Appendix I for the chemical structures of the identified metabolites.

Based on the results of the metabolism study, the petitioner proposed
that thiamethoxam is metabolized in lettuce via opening of the
oxadiazinan ring, loss of the nitro group followed by hydrolysis of the
resulting guanidine derivative to the corresponding urea compound,
demethylation, and cleavage of the nitrogen-carbon bridge between the
two rings, leading to oxadiazin- and thiazol-label specific metabolites.
 Metabolite CGA 349208 is sugar conjugated or oxidized to CGA 359683.
Replacement of the chlorine atom by glutathione conjugation appeared to
occur as a very minor pathway, based on the identification of the
S-glucose conjugate.

Potato:  Syngenta has submitted a study investigating the metabolism of
[thiazol-2-14C]thiamethoxam and [oxadiazin-4-14C]thiamethoxam in
potatoes.  The radiolabeled test substances were formulated with
red-colored formulation blank (Cruiser WS 70), diluted with water, and
applied to potato seed pieces as a seed treatment on the day of planting
at 0.0061 and 0.0063 lb/100 lb seed pieces, respectively, for
[thiazol-2-14C]thiamethoxam and [oxadiazin-4-14C]thiamethoxam, or at
0.0264 and 0.0334 lb/100 lb seed pieces, respectively.  The petitioner
referred to the lower treatment rate as 1x and the higher treatment rate
as 5x; based on the registered potato seed treatment uses, the lower
treatment rates represent ~0.8x and the higher treatment rates represent
~3-4x the maximum seed application rate.  The specific activities of the
test substances were 60.1-60.2 μCi/mg for 1x treatments and 28.5-30.4
μCi/mg for 5x treatments. Samples of immature potato tubers (new
potatoes) and foliage were harvested 84 DAT, and mature potato tubers
and foliage were harvested 106 DAT.

For tubers, TRR in the 84- and 106-DAT samples were 0.324 and 0.220 ppm,
respectively, from the [thiazol-2-14C]thiamethoxam 1x treatment; 1.163
and 0.853 ppm, respectively, from the [thiazol-2-14C]thiamethoxam 5x
treatment; 0.215 and 0.130 ppm, respectively, from the
[oxadiazin-4-14C]thiamethoxam 1x treatment; and 1.023 and 0.857 ppm,
respectively, from the [oxadiazin-4-14C]thiamethoxam 5x treatment.  For
foliage, TRR in the 84- and 106-DAT samples were 7.436 and 7.637 ppm,
respectively, from the [thiazol-2-14C]thiamethoxam 1x treatment; 42.036
and 41.916 ppm, respectively, from the [thiazol-2-14C]thiamethoxam 5x
treatment; 7.252 and 8.946 ppm, respectively, from the
[oxadiazin-4-14C]thiamethoxam 1x treatment; and 26.430 and 37.174 ppm,
respectively, from the [oxadiazin-4-14C]thiamethoxam 5x treatment.

Extraction with ACN/water and methanol/water released the majority of
the radioactivity (64-92% TRR) from tubers and foliage.  Additional
residues were released using ACN/water at reflux (2-10% TRR) and water
at reflux (5-14% TRR); enzyme and mild or harsh chemical hydrolysis of
the remaining solids released small amounts of additional radioactivity.
 Remaining nonextractable residues accounted for 0.5-3.8% TRR.  These
procedures adequately extracted the majority of residues from potatoes;
accountabilities were 88-107%.  Metabolite identification and
quantification were conducted by 2-D TLC, with confirmation of
metabolite identification by HPLC.  Adequate storage stability data were
submitted to support the storage durations and conditions of samples
from the study.

 (≤2.5% TRR).  All other identified metabolites were found at <5% TRR;
these included CGA-353968, CGA-265307, CGA-349208, CGA-340575,
NOA-407475, CGA-353042, NOA-405217, N-desmethyl-CGA-353968, NOA-421275,
CGA-382191, and NOA-436944.  A total of 1.7-14.4% TRR was found to be
associated with polysaccharides, and 0.5-2.2% TRR was found to be
associated with lignins and cellulose in foliage.  Individual unknowns
in tubers were each <10% TRR (<0.07 ppm).

Approximately 28-77% TRR were identified in foliage.  Thiamethoxam
comprised 8.3-13.8% TRR in 84-DAT samples and 1.5-3.3% TRR in 106-DAT
samples.  The metabolite CGA-322704 was found in all samples, at levels
ranging 0.7-3.4% TRR.  The hydroxylamine glucoside conjugate of
CGA-322704 was a major metabolite in immature foliage treated with
[oxadiazin-4-14C]thiamethoxam, at 16.6-20.0% TRR; the metabolite was
identified at 1.9-6.0% TRR in [thiazol-2-14C]thiamethoxam-treated
immature foliage and 3.4-4.5% TRR in
[oxadiazin-4-14C]thiamethoxam-treated mature foliage, and was not
identified in [thiazol-2-14C]thiamethoxam-treated mature foliage.  Other
major metabolites identified in foliage were:  NOA-407475 in all
samples, at 5.6-17.0% TRR; NOA-421275 in all samples, at 5.8-11.9% TRR;
the N-glucoside of CGA-353968 in foliage of
[oxadiazin-4-14C]thiamethoxam-treated immature tubers, at 4.8-12.6% TRR
(found at <2% TRR in other samples); and label-specific metabolites
CGA-353042 and NOA-436944 in foliage of
[oxadiazin-4-14C]thiamethoxam-treated mature tubers, at 9.4-12.1% TRR
and 13.2-14.7% TRR, respectively.  CGA-353042 and NOA-436944 were found
in the foliage of [oxadiazin-4-14C]thiamethoxam-treated immature tubers
at <1% TRR and 5.1-6.8% TRR, respectively.  All other identified
metabolites were found at <6% TRR; these included all metabolites except
CGA-282149 that were identified in tubers, as well as foliage
metabolites CGA-355190 and NOA-421276.  A total of 3.5-10.1% TRR was
found to be associated with polysaccharides, and 0.6-3.8% TRR was found
to be associated with lignins and cellulose.  Individual unknowns in
foliage were each <10% TRR (<3.9 ppm).

HED notes that because the petitioner did not confirm the identification
of significant foliage metabolites hydroxylamine glucoside of
CGA-322704, NOA-407475, NOA-421275, N-glucoside of CGA-353968,
CGA-353042, and NOA-436944, the identifications of these metabolites in
foliage should be considered to be tentative.

Based on the results of the metabolism study, the petitioner proposes
that thiamethoxam is metabolized in potatoes via cleavage of the
oxadiazine ring to form CGA-322704 with subsequent hydrolysis of the
imine to form CGA-353968.  Thiamethoxam may also undergo bridge cleavage
to form CGA-349208, CGA-282149 and CGA-340575, with the latter two
metabolites being precursors of guanidine.  Alternatively, thiamethoxam
may lose the nitro group to form NOA-407475 which undergoes hydrolysis
of the imine to form CGA-355190.  CGA-322704 may also lose the nitro
group to form CGA-421275 and/or undergo oxidation to form the
hydroxylamine analog; the hydroxylamine analog and CGA-353968 may then
conjugate with glucose.  The petitioner noted that the glucose
conjugates were found to be present in higher quantities in foliage.

Tobacco:  Syngenta submitted a study investigating the metabolism of
[oxadiazin-4-14C]thiamethoxam in tobacco and the pyrolysis products of
[oxadiazin-4-14C]thiamethoxam-treated tobacco.  The test substance was
applied to tobacco plants using three treatment patterns.  Treatment 2
consisted of an in-furrow application at the time of transplanting at
0.132 lb ai/A (~1x the maximum rate for soil application) followed by a
foliar application at 0.058 lb ai/A (1.2x the maximum rate for foliar
application), for a total application rate of 0.189 lb ai/A.  Treatment
3 consisted of an in-furrow application at the time of transplanting at
1.35 lb ai/A (11x) followed by a foliar application at 0.57 lb ai/A
(12x), for a total application rate of 1.92 lb ai/A.  Treatment 4
consisted of a single application as an in-furrow application at the
time of transplanting at 0.186 lb ai/A (1.5x).  The specific activities
of the test substances were 40.8 (Ci/mg for Treatments 2 and 4 and 8.2
(Ci/mg for Treatment 3.  For the in-furrow applications, the
radiolabeled test substance was dissolved in ACN and then diluted with
water for application.  For the foliar applications, the test substance
was formulated as a wettable powder formulation using formulation blank
and then diluted with water for application.  HED notes that the current
and proposed labels prohibit foliar applications to tobacco if a soil
application was made.

Immature tobacco samples were collected prior to foliar application for
all three treatments (126 days after in-furrow treatment).  Mature
tobacco leaf samples were collected at three priming durations:  14, 28,
and 42 days following foliar application for Treatments 2 and 3, and
140, 154, and 168 days following Treatment 4.  Subsamples of mature
green foliage were flue-cured.

TRR in tobacco matrices are presented in the table below.  The
petitioner noted that appreciable residues were observed in immature
samples, indicating significant uptake of radioactivity from the
in-furrow application.  In general, TRR in composite mature and cured
foliage from Treatment 3 were 10x greater than TRR in samples from
Treatment 2, which corresponds to the difference in the dose level.  TRR
in samples from Treatment 4 were slightly lower than TRR in samples from
Treatment 2, which further indicates that the parent compounds was
readily absorbed and distributed within the tobacco plants after
in-furrow treatment.

Matrix	Priming	ppm [oxadiazin-4-14C]thiamethoxam equivalents

Treatment 2	Treatment 3	Treatment 4

Immature foliage	--	0.875	20.611	1.757

Mature green foliage	First	3.798	27.569	1.592

	Second	0.747	8.819	0.568

	Third	1.026	11.045	0.452

	Composite sample	1.386	13.356	0.711

Cured foliage	First	18.125	176.635	12.383

	Second	17.901	166.413	9.952

	Third	12.739	119.192	10.079

	Composite sample	15.793	161.301	11.048

Extraction with ACN:water (8:2, v:v) released the majority of the
radioactivity from mature green foliage samples (78-87% TRR) and cured
foliage samples (67-73% TRR); immature foliage samples were not
subjected to extraction procedures.  Additional radioactivity (13-28%
TRR in total) was released from the nonextractable residues of Treatment
3 green foliage and Treatment 4 cured foliage using sequential
extractions/hydrolyses with 2-propanol/water, cellulase/cellobiase, 0.1N
HCl, 6 N HCl, 0.1 N NaOH, and 6 N NaOH.  Remaining nonextractable
residues in these tobacco samples were <1% TRR.

These procedures adequately extracted the majority of residues from
tobacco matrices; accountabilities were 94-100%.  Extracts were profiled
by HPLC and TLC; metabolites were identified and/or confirmed by LC/MS,
LC/MS/MS, and/or 1H-NMR analyses of isolated fractions from the extracts
of Treatment 3 green foliage.  Adequate storage stability data were
submitted to support the storage durations and conditions of samples
from the study.

Approximately 55-65% TRR were identified in green foliage.  Thiamethoxam
was the major residue identified in all green foliage samples, at 14-25%
TRR (0.20 ppm in Treatment 2 foliage).  Metabolite CGA-322704 was found
in all green foliage samples at low levels (3.1-4.2% TRR; 0.049 ppm in
Treatment 2 foliage).  All other identified metabolites were found at
≤10% TRR; these included CGA-353042, CGA-382191, NOA-405217,
NOA-421275, NOA-407475, N-desmethyl-CGA-353968, CGA-353968, CGA-265307,
CGA-355190, guanidine, and the N-glycoside of CGA-353968.

Approximately 49-58% TRR were identified in cured foliage.  Thiamethoxam
was found to account for a small proportion of the residue in cured
foliage, at 3.5-8.6% TRR (0.723 ppm in Treatment 2 cured foliage).
Metabolite CGA-322704 was found in all cured foliage samples at slightly
higher levels than were observed in green foliage samples (7.2-8.5% TRR;
1.144 ppm in Treatment 2 cured foliage).  Metabolite NOA-407475 was
identified at 13.1% TRR (1.448 ppm) in Treatment 4 cured foliage, and at
lower levels in Treatment 2 and 3 cured foliage (6.4% and 7.6% TRR,
respectively).  All other identified metabolites were found at <9% TRR;
no metabolites were identified in cured foliage that were not identified
in green foliage.

Cigarettes made from cured tobacco from each treatment were subjected to
pyrolysis.  The majority of the radioactivity was found in the extracts
and traps of side stream fractions, at 68.5-74.4% TRR, with the majority
of side stream radioactivity found in the traps designed to retain 14CO2
and [14C]methyl isocyanate (54.7-67.2% TRR).  The main stream extract
and trap fractions accounted for 10.0-17.7% TRR, with 3.0-8.3% TRR found
in the 14CO2 and [14C]methyl isocyanate traps.  Radioactivity remaining
in the filter pads, cigarette butt, and ash following extraction
accounted for a total of 5.5-8.6% TRR.  Approximately 71-77% TRR were
identified in the pyrolysis fractions of cigarettes.  Thiamethoxam and
CGA-322704 were found at low levels (0.7% TRR and 0.4-1.0% TRR,
respectively).  The majority of the radioactivity was attributed to
14CO2, at 61.4-69.2% TRR.  [14C]Methyl isocyanate was found to account
for ≤1.0% TRR.  All other identified metabolites were found at ≤2.0%
TRR, and no metabolites, other than methyl isocyanate, were identified
that had not been identified in cured tobacco foliage.

Based on the results of the metabolism study, the petitioner proposed
that thiamethoxam is metabolized in tobacco via one of two major
pathways.  The first pathway involves loss of the nitro group to form
NOA-407475, which is then cleaved to form polar metabolite CGA-353042.
CGA-353042 is then further metabolized to form N-methylguanidine and
guanidine, which are incorporated into natural products.  NOA-407475 may
also be oxidized to form urea analog CGA-355190, which undergoes ring
opening to form CGA-353968, its N-glycoside conjugate, and
N-desmethyl-CGA-353968, or may undergo ring opening to form NOA-421275.
The second pathway involves ring opening of thiamethoxam to form
CGA-322704 which is then demethylated at a nitrogen to form CGA-265307.
The petitioner noted that CGA-322704 and CGA-265307 were more abundant
in cured tobacco than uncured tobacco, indicating that they are
generated preferentially during the curing process.  NOA-421275 may also
form from CGA-322704 via loss of the nitro group, and then undergo
further metabolism to guanidine-related metabolites.

Syngenta also submitted a study investigating the metabolism of
[thiazol-2-14C]thiamethoxam in tobacco and the pyrolysis products of
[thiazol-2-14C]thiamethoxam-treated tobacco.  The test substance was
applied to tobacco plants using three treatment patterns.  Treatment 2
consisted of an in-furrow application at the time of transplanting at
0.128 lb ai/A (1x) followed by a foliar application at 0.058 lb ai/A
(1.2x), for a total application rate of 0.186 lb ai/A.  Treatment 3
consisted of an in-furrow application at the time of transplanting at
1.27 lb ai/A (10x) followed by a foliar application at 0.58 lb ai/A
(12x), for a total application rate of 1.85 lb ai/A.  Treatment 4
consisted of a single application as an in-furrow application at the
time of transplanting at 0.178 lb ai/A (1.4x).  The specific activities
of the test substances were 40.6 (Ci/mg for Treatments 2 and 4 and 8.0
(Ci/mg for Treatment 3.  For the first application, the radiolabeled
test substance was dissolved in ACN and then diluted with water for
application.  For the foliar applications, the test substance was
formulated as a wettable powder formulation using formulation blank and
then diluted with water for application.

Immature tobacco samples were collected prior to foliar application for
all three treatments (71 days after in-furrow treatment).  Mature
tobacco leaf samples were collected at three priming durations:  14, 28,
and 42 days following foliar application for Treatments 2 and 3, and 85,
99, and 113 days following Treatment 4.  Subsamples of mature green
foliage were flue-cured.

TRR in tobacco matrices are presented in the table below.  The
petitioner noted that TRR in composite foliage from Treatment 3 were
~14x greater than TRR in samples from Treatment 2.  TRR in samples from
Treatment 4 were comparable to TRR in samples from Treatment 2,
indicating that the parent compound was readily absorbed and distributed
within the tobacco plants after in-furrow treatment.

Matrix	Priming	ppm [thiazol-2-14C]thiamethoxam equivalents

Treatment 2	Treatment 3	Treatment 4

Immature foliage	--	5.757	55.230	2.777

Mature green foliage	First	2.900	28.329	2.382

	Second	1.633	33.117	1.462

	Third	1.322	21.435	0.924

	Composite sample	1.833	25.463	1.230

Cured foliage	First	16.095	228.634	12.945

	Second	16.636	156.337	12.591

	Third	11.309	122.976	8.949

	Composite sample	13.359	163.462	10.395

Extraction with ACN/water then methanol/water released the majority of
the radioactivity from mature green and cured foliage samples (65-79%
TRR); immature foliage samples were not subjected to extraction
procedures.  Additional radioactivity (16-18% TRR in total) was released
from the nonextractable residues of green foliage (all treatments) and
Treatment 2 cured foliage using extraction at reflux in ACN/water and
then water, followed by hydrolysis using 10% NaOH.  The remaining solid
residues in these tobacco samples were characterized as cellulose (≤2%
TRR).

These procedures adequately extracted the majority of residues from
tobacco matrices; accountabilities were 94-100%.  Extracts were profiled
by HPLC and TLC.  Adequate storage stability data were submitted to
support the storage durations and conditions of samples from the study.

Approximately 66-77% TRR were identified in green foliage.  Thiamethoxam
was a major residue in all green foliage samples, at 15.3-18.2% TRR
(0.28 ppm in Treatment 2 foliage).  Metabolite NOA-407475 was identified
in all samples, at 13.0-17.0% TRR (0.24 ppm in Treatment 2 foliage), and
the N-glucoside of CGA-353968 was also found to be a major residue in
all samples, at 10.2-13.2% TRR (0.24 ppm in Treatment 2 foliage).
Metabolite CGA-322704 was found in all green foliage samples at low
levels (2.6-3.7% TRR; 0.050 ppm in Treatment 2 foliage).  All other
identified metabolites were found at <9% TRR; these included
N-desmethyl-CGA-353968, CGA-353968, CGA-355190, CGA-265307, CGA-349208,
NOA-408445, and NOA-421275.

Approximately 61-64% TRR were identified in cured foliage.  Thiamethoxam
was found to account for a small proportion of the residue in cured
foliage, at 2.1-6.7% TRR (0.278 ppm in Treatment 2 cured foliage).
Metabolite CGA-322704 was found in all cured foliage samples at higher
levels than were observed in green foliage samples (8.9-11.0% TRR; 1.185
ppm in Treatment 2 cured foliage).  Metabolite NOA-407475 was identified
at 15.5-18.5%% TRR in all cured foliage samples (2.427 ppm in Treatment
2 foliage).  All other identified metabolites were found at <10% TRR; no
metabolites were identified in cured foliage that were not identified in
green foliage.

The nonextractable residues of green foliage samples (all treatments)
and Treatment 2 cured foliage were subjected to additional extraction
procedures which indicated radioactivity associated with polysaccharides
(4.5-6.9% TRR), lignin (0.2-0.3% TRR in green foliage; 3.0% TRR in cured
foliage), and cellulose (0.4-1.5% TRR).

Cigarettes made from cured tobacco from each treatment were subjected to
pyrolysis.  For the Treatment 2 and 4 cigarettes, the majority of the
radioactivity was found in the extracts and traps of side stream
fractions, at 41.9% and 55.1% TRR, respectively; the extracts and traps
of main stream fractions accounted for 31.4% TRR (Treatment 2) and 28.0%
TRR (Treatment 4).  For Treatment 3 cigarettes, approximately equal
amounts of radioactivity were found in the extracts/traps of main stream
and side stream fractions, at 38.4% and 35.9% TRR, respectively.  For
main stream fractions, the cigarette butt and the 40% KOH traps (which
would retain 14CO2) accounted for the largest portion of the
radioactivity, at 11.1-15.3% TRR and 13.6-17.5% TRR, respectively.  The
KOH traps accounted for the largest portion of the radioactivity in the
side stream fractions, at 29.6-47.5% TRR.  The 1,3-diaminopropane traps,
which would retain carbonyl sulfide (14COS), accounted for a minor
amount of radioactivity (<1.5% TRR).  Radioactivity remaining in the
filter pads, cigarette butt, and ash following extraction accounted for
a total of 10.9-15.1% TRR.  Approximately 61-77% TRR were identified in
the pyrolysis fractions of cigarettes.  Thiamethoxam and CGA-322704 were
found at low levels (0.2-1.1% TRR and 1.1-1.9% TRR, respectively).  The
majority of the radioactivity was attributed to 14CO2, at 47.1-61.1%
TRR.  All other identified metabolites were found at ≤6.8% TRR, and no
metabolites were identified that had not been identified in cured
tobacco foliage.

Based on the results of the metabolism study, the petitioner proposed
that thiamethoxam is metabolized in tobacco via one of two pathways.
The first pathway involves loss of the nitro group to form NOA-407475,
which then undergoes hydrolysis to form CGA-355190.  Opening of the
oxadiazine rings results in the formation of CGA-353968, which then
conjugates with glucose or undergoes N-demethylation.  The second
pathway involves opening of the oxadiazine ring to form CGA-322704
followed by cleavage of the nitro group to form NOA-421275.  NOA-421275
may then undergo bridge cleavage to form CGA-349208 and CGA-359683,
which conjugates with glycine to form NOA-408445.  CGA-322704 may also
undergo N-demethylation to form CGA-265307.

Conclusions.  The submitted metabolism data for lettuce, potato and
tobacco are adequate to satisfy data requirements.  The available data
indicate that the metabolism of thiamethoxam in lettuce, potato and
tobacco is similar to that observed in other crops.  The nature of the
residue in thiamethoxam is now adequately understood.  The residues of
concern in plant commodities are thiamethoxam and CGA-322704.

The submitted additional metabolism data for cucumber may not be used to
fulfill data requirements because no supporting storage stability data
were provided.  However, sufficient plant metabolism data are available
from other crops (corn, pears, rice, wheat, lettuce, potato and tobacco)
to fulfill data requirements for 860.1300 – Nature of the Residue for
thiamethoxam.

The submitted leafy vegetable metabolism study satisfies the data
requirements of the previous reviews pertaining to plant metabolism
(Conclusion 6c of PP#9F5046 review, Conclusion 6b of D265079 PP#9F5051
review, and Conclusion 3 of D269520 PP#9F5051 review).

Because combined residues of thiamethoxam and CGA-322704 exceeded 0.1
ppm in green tobacco, crop field trial data for tobacco are needed.
Crop field trial data for tobacco have been submitted and reviewed by
HED (D265079 PP#9F5051 review); the data are discussed under 860.1500
– Crop Field Trials.  The crop field trial data indicate that combined
residues of thiamethoxam and CGA-322704 exceeded 0.1 ppm in cured
tobacco.  The petitioner has conducted the required pyrolysis studies
with thiamethoxam-treated tobacco.  In general, the pyrolysis of tobacco
treated with thiamethoxam labeled in the thiazolyl ring yielded similar
results to that for thiamethoxam labeled in the oxadiazine ring, with
14CO2 accounting for the majority of the radioactivity (~50-70% TRR).
However, in the oxadiazine-ring label study, the majority of the
radioactivity was found in the side stream smoke fractions (70-75% TRR)
but the radioactivity was more evenly split between the main stream and
side stream fractions in the thiazole-ring study.

860.1300 Nature of the Residue - Livestock

DER Reference:	None

See:    SEQ CHAPTER \h \r 1 MARC Decision Memo:  D258614, 8/31/99, G.J.
Herndon

Residue Chemistry Memo D252021, 3/30/00, G.J. Herndon (PP#9F5046)

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D265079, 5/8/00, G.J.
Herndon (PP#9F5051)

The nature of the residue in livestock is adequately understood based on
acceptable goat and hen   SEQ CHAPTER \h \r 1 metabolism studies.  The
metabolism of thiamethoxam in ruminants and poultry is similar.  The
major metabolic pathway involves hydrolysis of the oxadiazine ring to
form CGA-322704 and subsequent demethylation to produce CGA-265307; loss
of the nitro group from these two metabolites also yields NOA-421275 and
NOA-421276.  Several major metabolites (MU3, L14, and MU12) in both
ruminants and poultry also result from the reduction of the nitro group
in thiamethoxam or CGA-265307 to a hydrazine, and subsequent conjugation
with acetic or 2-oxo-propionic acids.  Separation of the thiazole and
oxadiazine rings was only a minor pathway in ruminants and poultry.
[For the chemical names and structures of identified metabolites, see
Appendix I and Residue Chemistry Memo D257676, 7/21/99, G.J. Herndon and
P. Hurley.]

The MARC has determined that the residues of concern for purposes of
tolerance enforcement and risk assessment are the combined residues of
thiamethoxam and CGA-322704, expressed as thiamethoxam.  The Committee
determined that ruminant metabolites MU12 and N-5 and poultry metabolite
MU3, which contain the chloro-thiazole ring but not the nitro group,
would not need to be included in the tolerance expression or
quantitatively used in a human health risk assessment.

The MARC additionally concluded that in a laying hen feeding study for
thiamethoxam, the petitioner would need to analyze for the additional
metabolite CGA-265307 (in addition to the parent thiamethoxam and
CGA-322704 metabolites) based on it containing the N-nitro group and
being the major residue in eggs and fat.

860.1340 Residue Analytical Methods

DER Reference:	45140901.der.doc (also includes review of MRIDs 45499901
and 45499903)

		45659202.der.doc (also includes review of MRID 45659203)

See:  Residue Chemistry Memo D252021, 3/30/00, G.J. Herndon (PP#9F5046)

  SEQ CHAPTER \h \r 1 Residue Chemistry Memo D265079, 5/8/00, G.J.
Herndon (PP#9F5051)

Residue Chemistry Memo D271516, 5/29/01, M. Doherty

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 petitions (PP#9F5046 and PP#9F5051) is adequate for
collecting residue data and enforcing tolerances for residues of
thiamethoxam and CGA-322704 in/on crop and livestock commodities.  The
validated LOQ for each analyte is 0.01 ppm for all plant matrices with
the exception of fruit juices (0.005 ppm), grass (0.05 ppm), and cured
tobacco (0.1 ppm).  In livestock, the validated LOQ for residues of
thiamethoxam and CGA-322704 is 0.01 ppm each in meat, poultry, and eggs,
and 0.005 ppm each in milk.

Briefly, samples are extracted with ACN:water (80:20, 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.

Adequate method validation data have been submitted, and the method has
undergone a successful independent laboratory validation (ILV) and
Agency tolerance method validation (TMV).  The method includes a step in
the calculation to convert residues of CGA-322704 to thiamethoxam
equivalents.

This method has been adequately radiovalidated in crop and livestock
commodities, with the exception of liver.  As a condition of
registration under PP#9F5051, the petitioner was required to modify
Method AG-675 to add a microwave extraction step for liver, or propose a
new enforcement method for liver.  Radiovalidation data for the
revised/new method were also required.

Syngenta has now submitted (MRID 45659202) a modification of Method
AG-675 to include a microwave extraction step for liver.  Liver samples
are first subjected to Polytron extraction using the procedures
described in Method AG-675, yielding the Polytron extract.  The
remaining solids are then subjected to microwave extraction in ACN:water
(8:2, v:v) using a temperature gradient of ambient temperature to 150 (C
over 60 minutes.  The extract is then cleaned up by liquid-liquid
partitioning with toluene and hexane, followed by SPE using strong anion
exchange and phenyl columns, additional partitioning with ethyl acetate,
and sequential SPE using amino and alumina columns.  Residues in the
Polytron extract and microwave extract are then separately determined by
HPLC/MS, and results are summed to determine total residues.  The
reported LOQ is 0.01 ppm.

The Polytron and microwave extraction procedures of the modified method
were adequately validated using fortified samples of goat and chicken
liver; samples were fortified prior to Polytron extraction, and the
solids remaining after Polytron extraction were fortified and subjected
to microwave extraction.  For Polytron extraction, recoveries of
thiamethoxam and CGA-322704 respectively averaged 84% with a standard
deviation of 6.0%, and 93% with a standard deviation of 6.8%, from
samples of goat and chicken liver fortified at 0.01 and 1.0 ppm.  For
microwave extraction, recoveries of thiamethoxam and CGA-322704
respectively averaged 81% with a standard deviation of 8.5%, and 100%
with a standard deviation of 12%, from samples of goat and chicken liver
fortified at 0.01 and 1.0 ppm.

  SEQ CHAPTER \h \r 1 The fortification levels used in method validation
are adequate to bracket expected residue levels.  The microwave
extraction step is to be used only for analysis of liver samples.  No
confirmatory analysis procedures were included in the description of the
modified method; however, confirmatory analysis procedures, using
HPLC/MS/MS, are specified in the original Method AG-675.

Adequate radiovalidation data were submitted (MRID 45659203).  The
radiovalidation data indicate that the Polytron and microwave extraction
steps adequately extract aged residues of thiamethoxam and CGA-322704
from samples of chicken liver.  Aged residues of thiamethoxam were
adequately extracted from samples of goat liver; however, the extraction
efficiency for CGA-322704 averaged ~40% from goat liver.  The low
extraction efficiency will be considered when risk assessments are
conducted for thiamethoxam.

No ILV data were submitted; however, ILV data will not be required
because adequate ILV data were submitted for the original method.

Data-collection method:  Samples of plant commodities from the storage
stability, crop field trial, and processing studies included in this
review were analyzed for residues of   SEQ CHAPTER \h \r 1 thiamethoxam
and its metabolite CGA-322704 using the current tolerance enforcement
method, Method AG-675 (with the exception of one storage stability study
discussed below).  For certain commodities (blueberry, canola,
cranberry, grape, and mint), the method was modified to use MS/MS
detection; additional minor modifications were made to remove or modify
sample cleanup steps.  Adequate method validation and concurrent method
recovery data were submitted with the crop field trial and processing
studies.  The LOQ or lowest level of method validation (LLMV) was 0.01
ppm for each analyte in each commodity, with the exception of mint tops
and oil, for which the LOQ was 0.05 ppm for each analyte, and
commodities included in the storage stability studies with plant and
animal commodities, for which the LOQ was reported to be 0.05 ppm for
each analyte.

Samples of apple, tomato, potato, rapeseed, and corn grain from the
storage stability study with CGA-322704 (see 860.1380 – Storage
Stability) were analyzed for residues of CGA-322704 using HPLV/UV Method
REM 179.03.  This method was also used for the analysis of samples in
coffee crop field trial submissions (see DP Number D286726, 12/23/03, Y.
Donovan).  A description of this method was required in a previous
review (PP#9F5046 review; see conclusion 13a).  Syngenta has submitted
(MRIDs 45140901 and 45499903) a description and radiovalidation data for
Method REM 179.03 for the determination of residues of thiamethoxam and
CGA-322704 in plant commodities.

Homogenized non-fatty plant samples are extracted with water/methanol,
and homogenized fatty crop samples are extracted with ACN; the extract
from fatty crop samples is partitioned with hexane, and the hexane phase
is discarded.  The extract is cleaned up by sequential SPE on phenyl and
ENVI-Carb columns prior to HPLC/UV analysis using column-switching.  The
reported LOQs are 0.02 ppm for each analyte in food commodities (edible
plant parts) and 0.05 ppm for each analyte in feedstuffs (non-edible
plant parts).  Residues of thiamethoxam and CGA-322704 may be confirmed
by LC/MS/MS, using electrospray ionization in the positive ion mode with
selected reaction monitoring.

Although MRID 45140901 did not include full validation data for the
method, the representative chromatograms included in the submission
included recovery information; the source of these recovery data was not
specified.  Based on samples of melon fruit, sweet pepper fruit, maize
grain, tomato fruit, and rice grain fortified with each analyte at 0.02
and 0.2 ppm and samples of rice straw fortified with each analyte at
0.05 and 0.5 ppm, thiamethoxam recovery averaged 89% with a standard
deviation of 9% and CGA-322704 recovery averaged 84% with a standard
deviation of 10%.  Adequate method validation data for Method REM 179.03
were also included with studies in which the method was used for
analysis of samples.

Adequate radiovalidation data have been submitted for pear fruit which
indicate that the method adequately extracts aged residues of
thiamethoxam and CGA-322704.  No ILV data have been submitted.  The
method has not been proposed for enforcement purposes; therefore, no ILV
data are needed.

Conclusions.  The existing HPLC/UV (or MS) enforcement method, Method
AG-675, is adequate for collecting data on residues of thiamethoxam and
its metabolite CGA-322704 in/on plant commodities.  The method is
adequate for tolerance enforcement purposes for plant commodities.

The modified version of Method AG-675, which includes a microwave
extraction step for liver, is adequate for data collection and tolerance
enforcement purposes for livestock commodities.  The petitioner should
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 method submitted in MRID
45659202 only includes directions for the microwave extraction of liver
samples).  The revised method will then be forwarded to FDA for
inclusion in PAM Vol. II.

The submission of the modified version of Method AG-675 satisfies the
data requirements of the previous reviews pertaining to residue
analytical methods for livestock commodities (Conclusion 11a of
PP#9F5046 review and Conclusions 10a and 30g of D265079 PP#9F5051
review).

In the PP#9F5046 review, HED had made the following conclusion regarding
Method AG-675:

  SEQ CHAPTER \h \r 1 Based on achieving adequate recoveries on canola
using the LC/MS method (MRID# 447035-27), the petitioner has not
adequately explained why the majority of the canola field trial data
were analyzed by a LC/MS/MS method.  It appears that there may have been
some interference problems and, rather than modify or add clean-up steps
to eliminate the interference, the petitioner chose to eliminate 2
clean-up steps and use a more selective detection system (LC/MS/MS using
single ion monitoring).  The LC/MS/MS is the proposed enforcement method
for canola.  HED has reservations about proposing an enforcement method
which uses equipment most enforcement laboratories do not yet have
access to in lieu of better clean-up procedures.  In addition, no ILV
was submitted for the LC/MS/MS method.  However, HED will defer to the
Analytical Chemistry Branch (ACB) of BEAD for their recommendations
concerning this issue.

The issues raised in the conclusion have been addressed.  The petitioner
submitted data reflecting re-analysis of canola seed samples using
Method AG-675 with LC/MS/MS detection and with no elimination of cleanup
steps (see 860.1500 Crop Field Trials).  Adequate ILV data have been
submitted for the method and the method has undergone adequate
validation at ACB.  In addition, LC/MS/MS equipment is now available at
most enforcement laboratories.  HED concludes that this data requirement
has been satisfied.

860.1360 Multiresidue Methods

  SEQ CHAPTER \h \r 1 DER Reference:	None

See:  Residue Chemistry Memos D259838 and D259839, 9/28/99, G.J. Herndon

Residue Chemistry Memo D252021, 3/30/00, G.J. Herndon

FDA Pestrak Database, dated 6/05

The Agency has reviewed data concerning the recovery of residues of
thiamethoxam using FDA multiresidue method protocols of PAM Vol. I.
Thiamethoxam was partially recovered (50-60%) using multiresidue method
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

Plant commodities

DER Reference:	45086203.der.doc (includes review of MRID 45108001)

		45659205.der.doc

Adequate storage stability data have been submitted previously for   SEQ
CHAPTER \h \r 1 thiamethoxam and CGA-322704 in/on apples, tomato,
potato, rape seed, and corn grain (PP#0F6142; DP Number   SEQ CHAPTER \h
\r 1 D285545, 11/6/02, M. Doherty).  The data indicate that when stored
at -18 (C, residues of thiamethoxam are stable in/on these commodities
for up to ca. 740 days, and residues of CGA-322704 are stable in/on
these commodities for up to 364 days; the reported results for
CGA-322704 were interim results.

  SEQ CHAPTER \h \r 1 Syngenta has now submitted (MRID 45108001) the
final results of the storage stability study with CGA-322704 in apple,
tomato, potato, rapeseed, and corn grain stored frozen for up to 2
years.  Samples of apple, tomato, potato, rapeseed, and corn grain were
homogenized and fortified with CGA-322704 in water at 0.5 ppm and stored
at -18 ºC for a period up to 729 days (751 days for tomato).  Under
these conditions, residues of CGA-322704 appear to be stable in apple,
tomato, potato, rapeseed, and corn grain for up to 2 years.  Corrections
to residue data to account for in-storage dissipation during those time
periods will not be necessary.

  SEQ CHAPTER \h \r 1 The HPLC/UV method, REM 179.03, used to determine
residues of CGA-322704 in/on apple, tomato, potato, rapeseed, and corn
grain was adequately validated in conjunction with the sample analyses.
The reported LOQ for this study was 0.05 ppm for all matrices.

Syngenta has also submitted (MRID 45659205) the final results of a
storage stability study with thiamethoxam and its metabolite CGA-322704
in leaf lettuce, safflower seed, canola oil, corn meal, and tomato puree
stored frozen for 40-42 months.  The interim results of this study were
previously reported (MRID 44715113) and reviewed in conjunction with
PP#9F5046.    SEQ CHAPTER \h \r 1

Samples of untreated leaf lettuce, safflower seed, canola oil, corn
meal, and tomato puree were fortified with thiamethoxam and CGA-322704
at 0.5 ppm each, and stored frozen at -20 ºC for up to approximately 40
months.  Under these conditions, r  SEQ CHAPTER \h \r 1 esidues of
thiamethoxam and CGA-322704 appear to be relatively stable in canola
oil, corn meal, leaf lettuce, safflower seed, and tomato puree for up to
approximately 40-42 months.  Corrections to residue values from the
residue trials to account for dissipation during storage are not
necessary.

The HPLC method, Method AG-675, used to determine residues of CGA-322704
in/on leaf lettuce, safflower seed, canola oil, corn meal, and tomato
puree was adequately validated in conjunction with the sample analyses.
The reported LOQ was 0.05 ppm for each analyte in all matrices.

The petitioner conducted concurrent storage stability studies in
conjunction with the submitted crop field trial data for blueberry,
cranberry, and mint and the processing study with mint.  These data
indicate that residues of thiamethoxam and CGA-322704 are stable in
fortified samples of blueberry stored frozen up to 430 days, in
fortified samples of cranberry stored frozen for up to 110 days, in
fortified samples of mint tops stored frozen for up to 452 days, and in
fortified samples of mint oil stored frozen for up to 465 days.

The storage durations and conditions of samples from the crop field
trial and processing studies submitted to support this petition are
presented in Table 5.

Table 5.		Summary of Storage Conditions and Durations of Samples from
Crop Field Trial and Processing Studies.

Matrix

[MRID]	Storage Temperature

 (°C)	Actual Storage Duration (Days)	Interval of Demonstrated Storage
Stability

Artichoke buds [46801402]	-20	224-231	Residues of thiamethoxam are
stable for up to 740 days, and residues of the metabolite CGA-322704 are
stable for up to 364 days in/on apples, tomato, potato, rape seed, and
corn grain stored frozen.

Barley bran [46801401]	-26 to -4 	91-93	Concurrent storage stability
data indicate that residues of thiamethoxam and CGA-322704 are stable
for up to 592 days in/on barley grain, 182 days in pearled barley, 170
days in barley bran, and 172 days in barley flour stored frozen.

Barley flour [46801401]	-26 to -4 	94-96	Concurrent storage stability
data indicate that residues of thiamethoxam and CGA-322704 are stable
for up to 592 days in/on barley grain, 182 days in pearled barley, 170
days in barley bran, and 172 days in barley flour stored frozen.

Barley grain [46801401]	-26 to -4 	196	Concurrent storage stability data
indicate that residues of thiamethoxam and CGA-322704 are stable for up
to 592 days in/on barley grain, 182 days in pearled barley, 170 days in
barley bran, and 172 days in barley flour stored frozen.

Barley grain [46801401]	-26 to -4 	201-611	Concurrent storage stability
data indicate that residues of thiamethoxam and CGA-322704 are stable
for up to 592 days in/on barley grain, 594 days in/on barley hay, and
599 days in/on barley straw stored frozen.

Barley hay [46801401]	-26 to -4 	203-616	Concurrent storage stability
data indicate that residues of thiamethoxam and CGA-322704 are stable
for up to 592 days in/on barley grain, 594 days in/on barley hay, and
599 days in/on barley straw stored frozen.

Barley straw [46801401]	-26 to -4 	205-618	Concurrent storage stability
data indicate that residues of thiamethoxam and CGA-322704 are stable
for up to 592 days in/on barley grain, 594 days in/on barley hay, and
599 days in/on barley straw stored frozen.

Bean, dry seed [46162502]	Frozen (unspecified temperature)	384-414	24
months

Blueberry [46162201]	<-4	430	Concurrent storage stability data indicate
that residues of thiamethoxam and CGA-322704 are stable for up to 430
days in/on blueberry.

Blueberry [46162201]	<-4	430	430 days for residues of thiamethoxam and
CGA-322704 in/on blueberry stored frozen

Broccoli, flower [45880902]	-29 to 1	21-114	24 months

Broccoli, head & stem [46724902]	-20	101-318	24 months

Cabbage head [45880902]	-29 to 1	43-47	24 months

Cabbage, with and without wrapper leaves [46724902]	-20	253-272	24
months

Caneberry [46801403]	-25 to -16	75-118	Residues of thiamethoxam are
stable for up to 740 days, and residues of the metabolite CGA-322704 are
stable for up to 364 days in/on apples, tomato, potato, rape seed, and
corn grain stored frozen.

Canola seed [44829301]	Frozen (unspecified temperature)	111-206	24
months

Carrot [46203602]	<0	28-455	Residues of thiamethoxam are stable for up
to 740 days, and residues of the metabolite CGA-322704 are stable for up
to 364 days in/on apples, tomato, potato, rape seed, and corn grain
stored frozen.

Carrot, roots [46203602]	<0	28-455	24 months

Celery stalks [45880901]	-29 to 1	72	24 months

Cotton, gin byproducts [45093707]	-20	855-963	40-42 months for
thiamethoxam and CGA-322704 in/on canola oil, leaf lettuce, safflower
seed, and tomato puree stored frozen.

Cotton, undelinted seed [45093707]	-20	863-954	40-42 months for
thiamethoxam and CGA-322704 in/on canola oil, leaf lettuce, safflower
seed, and tomato puree stored frozen.

Cranberry [46114701]	<0	120	110 days for residues of thiamethoxam and
CGA-322704 in/on cranberry stored frozen

Cranberry [46114701]	<0	120	Concurrent storage stability data indicate
that residues of thiamethoxam and CGA-322704 are stable for up to 110
days in/on cranberry.

Dry beans, dry and succulent beans [46162501-46162503] 	Frozen
(temperature unspecified)	197-517	Residues of thiamethoxam are stable
for up to 740 days, and residues of the metabolite CGA-322704 are stable
for up to 364 days in/on apples, tomato, potato, rape seed, and corn
grain stored frozen.

Grape [45093705]	-20	45-231	24 months

Grape, juice [45093705]	-20	75-136	40-42 months for thiamethoxam and
CGA-322704 in/on canola oil, corn meal, and tomato puree stored frozen.

Grape, raisin [45093705]	-20	84-117	40-42 months for thiamethoxam and
CGA-322704 in/on canola oil, corn meal, and tomato puree stored frozen.

Hops, dry cones [46801404]	<-20	treated:  56-68; control:  54-117
Concurrent storage stability data submitted in conjunction with the hops
field trials study indicate that residues of thiamethoxam and CGA-322704
are stable in/on dry hop cones stored frozen for up to 73 days.

Lettuce, head [45880901]	-29 to 1	76	24 months

Lettuce, head [46724901]	-20	46-54	24 months

Lettuce, leaf [45880901]	-29 to 1	105	24 months

Lettuce, leaf [46724901]	-20	359-366	24 months

Mint [45530901]	<0	443-502	Concurrent storage stability data indicate
that residues of thiamethoxam and CGA-322704 are stable for up to
approximately 465 days in/on mint tops and oil.

Mint, oil [45530901]	<0	463-502	465 days for residues of thiamethoxam
and CGA-322704 in mint oil stored frozen

Mint, tops [45530901]	<0	443-482	452 days for residues of thiamethoxam
and CGA-322704 in/on mint tops stored frozen

Mustard greens leaves [46724902]	-20	175-176	24 months

Pea, dry seed [46162501]	Frozen (unspecified temperature)	430-455	24
months

Pea, succulent pods [46162503]	Frozen (unspecified temperature)	197-517
24 months

Pea, succulent seed [46162503]	Frozen (unspecified temperature)	217-315
24 months

Pearled barley [46801401]	-26 to -4 	98	Concurrent storage stability
data indicate that residues of thiamethoxam and CGA-322704 are stable
for up to 592 days in/on barley grain, 182 days in pearled barley, 170
days in barley bran, and 172 days in barley flour stored frozen.

Potato, processed commodities (culls, wet peel and trimmings, flakes,
and chips) [45093706]	-20	3-43	40-42 months for thiamethoxam and
CGA-322704 in/on canola oil, corn meal, and tomato puree stored frozen.

Potato, processed commodities (wet peel and trimmings, flakes, and
chips) [45093301]	-20	245-448	40-42 months for thiamethoxam and
CGA-322704 in/on canola oil, corn meal, and tomato puree stored frozen.

Potato, seed pieces [45093301]	-20	111-670	24 months

Potato, seed pieces [45093706]	-20	82-184	24 months

Potato, tuber [45093301]	-20	18-557	24 months

Potato, tuber [45093706]	-20	3-79	24 months

Radish [46203601]	<-2	393-740	Residues of thiamethoxam are stable for up
to 740 days, and residues of the metabolite CGA-322704 are stable for up
to 364 days in/on apples, tomato, potato, rape seed, and corn grain
stored frozen.

Radish, roots [46203601]	<-2	393-740	24 months

Radish, tops [46203601]	<-2	563-748	24 months

Soybean [46162504	Frozen (temperature unspecified)	61-134	Residues of
thiamethoxam are stable for up to 740 days, and residues of the
metabolite CGA-322704 are stable for up to 364 days in/on apples,
tomato, potato, rape seed, and corn grain stored frozen.

Soybean, seed [46162504]	Frozen (unspecified temperature)	61-134 	24
months

Spinach [45880901]	-29 to 1	29-93	24 months

Spinach [46724901]	-20	424-473	24 months

Strawberry [46159201]	<-1	28	Concurrent storage stability data indicate
that residues of thiamethoxam and CGA-322704 are stable for up to 24
days in/on strawberry.

Strawberry [46159201]	<-1	850	40-42 months for thiamethoxam and
CGA-322704 in/on canola oil, leaf lettuce, safflower seed, and tomato
puree stored frozen.

Tomato, fruit [45880903]	-29 to 1	8-79	24 months

Tomato, fruit [46724903]	-20	135-201	24 months

Conclusions.  The submitted storage stability data are adequate to
fulfill data requirements. Adequate storage stability data are now
available on five crops indicating that residues of thiamethoxam and it
metabolite CGA-322704 are stable during up to ~24 months of frozen
storage in/on apples, tomato, potato, rapeseed, and corn grain.  In
addition, adequate storage stability data have been submitted indicating
that r  SEQ CHAPTER \h \r 1 esidues of thiamethoxam and CGA-322704 are
relatively stable in canola oil, corn meal, leaf lettuce, safflower
seed, and tomato puree for up to approximately 40-42 months at -20 ºC.
These data together represent sufficient diverse crops (a root crop, a
leafy vegetable, a grain, an oilseed, a fruit, and a fruiting vegetable)
to allow determination that residues of thiamethoxam and CGA-322704 are
stable in/on all crops for at least 24 months.

 ≤24 months prior to analysis.  Adequate data are available to support
these storage durations and conditions.

The available data for canola oil, leaf lettuce, safflower seed, and
tomato puree may be translated to support the storage durations and
conditions of samples of cotton seed, cotton gin byproducts, and
strawberry from the crop field trials reported herein.  In addition, the
storage stability data for processed commodities canola oil, corn meal,
and tomato puree may be translated to support the storage durations and
conditions of the samples of processed commodities from the grape and
potato processing studies associated with this review.

The data requirements from previous reviews pertaining to storage
stability in plant commodities have now been satisfied.  In the
PP#9F5046 review, HED had required the petitioner to submit a detailed
description of Method REM 179.03, the method used to determine residues
of each analyte in some study samples (Conclusion 13a); this requirement
has been satisfied (see 860.1340 – Residue Analytical Method).

In the D265079 PP#9F5051 review, HED had required that the storage
stability study be continued to cover the interval that the plant
commodity samples were stored frozen (Conclusion 12c).  In that review,
raw agricultural commodity (RAC) samples of potato, fruiting vegetables,
cucurbits, pome fruits, wheat and cotton were stored frozen for 14-27
months; samples of grain sorghum RACs were stored for up to 30 months,
although the majority of the samples were analyzed within ~24 months;
and processed commodity samples from the potato, tomato, apple, grain
sorghum, wheat, and cotton processing studies were stored frozen for
12-26 months from collection to analysis.  The available storage
stability data are adequate to support these sample storage durations
and conditions.

In the D269520 PP#9F5051 review, HED required the submission of the