Document ID: EPA-HQ-OPP-2008-0270-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-05-26T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  01/26/09

SUBJECT:	Acibenzolar-S-Methyl.  Petitions for the Establishment of
Permanent Tolerances on Bulb Onions (Subgroup 3-07A) and Cucurbit
Vegetables (Crop Group 9).  Summary of Analytical Chemistry and Residue
Data.

PC Code:  061402	DP Barcode:  D352415 & D354287

Decision No.:  391032 & 393110	Registration No.:  100-922

Petition Nos.:  8E7337 & 8F7352	Regulatory Action:  Amended Section 3

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  135158-54-2

MRID No.:  See MRID Summary Table	40 CFR:  §180.561

		              									Ver.Apr.08

FROM:	Bonnie Cropp-Kohlligian, Environmental Scientist

		Risk Assessment Branch 4

		Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 		

		

THROUGH:	Susan V. Hummel, Chemist/Senior Scientist

		Risk Assessment Branch 4

		Health Effects Division (7509P)

	

TO:		Becky Daiss, Risk Assessor

		Risk Assessment Branch 4

		Health Effects Division (7509P)

		and

		Susan Stanton (RM 05)

		Risk Integration, Minor Use & Emergency Response Branch

		Registration Division (7505P)

		and

		Tony Kish (RM 22)

		Fungicide Branch

		Registration Division (7505P)

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

		

MRID Summary Table

MRID No.	Study Type	Comments

47375301	860.1500 Bulb onion	New DER; 47375301.der.doc

45105301*	860.1500 Cucurbit Vegetable Group 9	New DER; 45105301.der.doc

*  MRID 45105301 also includes residue chemistry data in support to the
use of pymetrozine 

on cucurbits which were previously reviewed by HED in a memorandum
(D250386, D.Dotson, 11/19/01).  A DER for this MRID was not previously
generated.   

  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (2275 Research Boulevard, Suite 300;
Rockville, MD).  

Dynamac Program Manager:		Date:  09/17/2008

     	Danilo Martinez

	

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 Acibenzolar-S-methyl,
[benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester], is a
systemic chemical and is in a class of chemicals known as the
benzothiadiazoles.  It is a “plant activator” that acts to protect
the plant against invading pathogens by stimulating the plant’s
natural defense mechanisms.  It is currently registered for use on leafy
vegetables, Brassica leafy vegetables, fruiting vegetables, and tobacco
for the control or suppression of downy mildew, black rot, white rust,
bacterial leaf spot and speck, and blue mold.  

  SEQ CHAPTER \h \r 1  This document summarizes the available residue
chemistry data submitted by two petitioners in support of proposed new
uses on food crops.

Under PP#8E7337, the Interregional Research Project No. 4 (IR-4), on
behalf of the Agricultural Experiment Stations of CO, NM, UT, ID, and
WA, is proposing to amend the product label for Actigard® (EPA Reg. No.
100-922), a water-dispersible granule (WG) formulation containing 50%
acibenzolar-S-methyl to add new uses on the bulb onion crop subgroup
3-07A.  Actigard® is proposed for multiple foliar applications on the
onion subgroup using ground or aerial equipment at a maximum of 0.03 lb
ai/A per application, a maximum seasonal rate of 0.125 lb ai/A, and a
7-day preharvest interval (PHI).  Concurrently, IR-4 requests the
establishment of a permanent tolerance for “the combined residues of
the fungicide acibenzolar-S-methyl,
benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester”, in/on:

Onion, bulb, subgroup 3-07A 	0.07 ppm

Under PP#8F7352, Syngenta Crop Protection, Inc. also proposes to amend
the product label for Actigard® (EPA Reg. No. 100-922) to add new uses
on the cucurbit vegetable crop group 9.  Actigard® is proposed for
multiple foliar applications on members of the cucurbit crop group using
ground or aerial equipment at a maximum of 0.06 lb ai/A per application,
a maximum seasonal rate of 0.5 lb ai/A, and a 0-day PHI.  Syngenta
requests the establishment of a permanent tolerance for “residues of
the fungicide acibenzolar-S-methyl/CGA-245704
(benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester”, in/on:

Cucurbit Vegetables Crop Group 	1.0 ppm

Tolerances have been established under 40 CFR §180.561 for residues of
acibenzolar-S-methyl.  Permanent tolerances have been established under
§180.561(a) for spinach (1.0 ppm), tomato paste (3.0 ppm), Brassica
leafy vegetables, group 5 (1.0 ppm), fruiting vegetables (1.0 ppm), and
leafy vegetables (0.25 ppm), and for bananas (0.1 ppm) as an import
tolerance.  Time-limited tolerances are established under §180.561(b)
for bulb and green onion (0.05 ppm each; to expire on 12/31/09) in
connection with use of the pesticide under section 18 emergency
exemptions.

There are no established Codex, Mexican, or Canadian maximum residue
limits for acibenzolar-S-methyl in/on any commodity.

The nature of the residues in plants has been adequately delineated
based on metabolism studies with lettuce, tomato, rice, wheat, and
tobacco.  The HED MARC has determined that the residues of concern in
plants for tolerance expression are residues convertible to
benzo(1,2,3)thiadiazole-7-carboxylic acid (CGA-210007), expressed as
acibenzolar-S-methyl.  For purposes of risk assessment, residues of the
4- and 5-hydroxy metabolites (CGA-324041 and CGA-323060) of CGA-210007
should also be considered.  For this purpose, the toxicity of CGA-324041
and CGA-323060 should be considered to be equivalent to that of the
parent compound acibenzolar-S-methyl.  These residues occur in
significant quantities in lettuce and tomato.  At this time,
acibenzolar-S-methyl does not have common metabolites with other
agrochemicals.  The residues of concern for drinking water are the same
as those listed in the tolerance expression; that is, residues
convertible to CGA-210007.

There are no livestock feedstuffs associated with the proposed uses on
bulb onions or cucurbit vegetables.  Therefore, no livestock metabolism
data, enforcement methods, storage stability data, or feeding studies
are required to support these petitions.

HPLC/UV Method AG-671A is available for tolerance enforcement.  This
method has undergone a successful tolerance method validation by the
Analytical Chemistry Branch of BEAD.  The method was forwarded to FDA
for inclusion in PAM Volume II.  Briefly, the method consists of an
initial hydrolysis with NaOH to convert acibenzolar-S-methyl to
CGA-210007 followed by methanol extraction.  Residues are then diluted
with HCl and purified by a series of solid-phase extraction steps. 
Prior to HPLC/UV analysis, residues are partitioned into ethyl acetate,
dried down, and redissolved in phosphoric acid.  This method has a limit
of quantitation (LOQ) of 0.02 ppm.  The method includes optional
detection via HPLC/MS, giving a means of residue confirmation.

Cantaloupe, cucumber, and summer squash samples from the submitted field
trial studies were analyzed for residues of acibenzolar-S-methyl using
the HPLC/UV enforcement method (AG-617A), and crop samples from the bulb
onion field trial studies were analyzed for residues of
acibenzolar-S-methyl using an LC/MS method adapted with modification
from the enforcement method.  The methods are adequate for data
collection based on acceptable method verification and/or concurrent
method recoveries.

With respect to FDA’s multiresidue methods, acibenzolar-S-methyl
yielded adequate response to GLC analysis and was completely recovered
through the Protocol D and E multiresidue methods.  Partial recovery of
CGA-210007 was achieved via Protocol B after derivatization.

The number and locations of field trials are in accordance with OPPTS
Guideline 860.1500 for bulb onion as the representative crop of the bulb
onion subgroup 3-07A, and for cantaloupe, cucumber, and summer squash as
the representative crops of the cucurbit vegetable group 9.  The trials
conducted reflect the proposed maximum seasonal rate and PHI, and there
are adequate storage stability data to validate sample storage
conditions and duration.  However an adjuvant was not used in the onion
field trials and the data do not support the use of a silicone adjuvant
as proposed on the Actigard® label.  If the petitioner desires to keep
the use of the surfactant on the label for bulb onions, then three
confirmatory trials using Actigard® with a surfactant should be tested
side-by-side with product applied without using a surfactant in the
NAFTA Growing Zones 10 (2 sites) and 11 (1 site).  Alternatively, the
petitioner may revise the product label to disallow the use of silicone
surfactant on the proposed label.

The results for bulb onion indicate that following application of the
test formulation according to the proposed use rate and PHI (7-days) but
without an adjuvant, the maximum residues of acibenzolar-S-methyl (i.e.,
residues convertible to CGA-210007) were 0.062 ppm in/on bulb onions. 
The residue data were not entered into the Agency’s tolerance
spreadsheet (Guidance for Setting Pesticide Tolerances Based in Field
Trial Data) because fourteen out of sixteen treated bulb onion samples
bore nonquantifiable (<0.05 ppm) residues.  The two treated bulb onion
samples which did have quantifiable residues (0.050 ppm and 0.062 ppm)
were harvested at 7-day PHI and allowed to dry in the field for 14-days
after harvest but before collection.  These bulb onion field trial data
and previously submitted cured tobacco leaf metabolism/field trial data
(D246673, M. Doherty, 03/15/2000) suggest that drying may tend to
concentrate residues of acibenzolar-S-methyl; therefore, in order to
ensure that the tolerance level is adequate, and pending submission of
the requested confirmatory data discussed in the paragraph above or
label revisions, the available bulb onion field trial data are deemed
adequate to support a tolerance of 0.1 ppm for residues of
acibenzolar-S-methyl in/on the bulb onion subgroup 3-07A.

The results for cucurbit vegetables indicate that following application
of the test formulation according to the proposed use rate and PHI
(0-days), with and without an adjuvant, the maximum residues of
acibenzolar-S-methyl (i.e., residues convertible to CGA-210007) were
0.868 ppm in/on cantaloupe, 0.382 ppm in/on cucumber, and 0.151 ppm
in/on summer squash.  The maximum residues for these representative
crops differ by >5x. 

The cucurbit vegetables residue data were entered into the Agency’s
tolerance spreadsheet which recommended tolerances of 1.0 ppm for
cantaloupe, 0.40 ppm for cucumber, and 0.35 ppm for summer squash.  For
the cantaloupe-dataset, visual inspection of the lognormal probability
plot and the result from the approximate Shapiro-Francia test statistic
indicated that the assumption of lognormality should be rejected.  The
recommended tolerances for these representative crops differ by <5x. 

  

The results of the cucurbit vegetables residue decline studies
demonstrate that average residues of acibenzolar-S-methyl (i.e.,
residues convertible to CGA-210007) in/on cantaloupe remained generally
constant between the 0- and 3-day PHIs and increased in/on cucumber and
summer squash by approximately 10% and 100%, respectively.  Residues
generally decreased in cantaloupe, cucumber, and summer squash by the
7-10 day PHIs and were the lowest at the 10-day PHI.  These data suggest
that residues of acibenzolar-S-methyl in/on cucurbit vegetables
resulting from the proposed use rate and 0-day PHI may not represent the
worst case as residues may increase between 0- and 7-day PHIs and
generally decrease thereafter.  This phenomenon was noted in an earlier
acibenzolar-S-methyl review (D258680, M. Doherty, 05/02/2000) where
decline trials demonstrated that average residues of
acibenzolar-S-methyl in/on broccoli increased between the 0- and 5-day
PHIs by approximately 300% and than generally decreased thereafter.  An
explanation for this phenomenon is not readily apparent.  

Given the indication of variability within and between these cucurbit
vegetable data sets and the demonstrated potential for significant
increases in acibenzolar-S-methyl residues between 0- and 7-day PHIs,
six additional field trial/decline studies are required to support the
proposed use of acibenzolar-S-methyl on cucurbit vegetables.  Two
side-by-side cantaloupe and honeydew melon decline studies demonstrating
the proposed use rate and using an adjuvant must be conducted in Zones 6
and 10 (a total of 4 trials), samples must be collected at 0, 1, 3, 5,
7, and 10 days after the last application (DALA).  Two cantaloupe
decline studies, using the same protocol, must be conducted in Zones 2
and 5 (a total of 2 trials). 

The available cucurbit vegetable field trial and decline data indicate
that a tolerance of 2.0 ppm for residues of acibenzolar-S-methyl
convertible to CGA-210007 in/on cucurbit vegetables group 9 would be
adequate to cover maximum residues resulting from the proposed use rate
and PHI.  A lower tolerance may be deemed appropriate once the required
field trial/decline data discussed in the paragraph above are submitted.

Adequate confined rotational crop data have been submitted previously. 
Based on the available field rotational crop data for wheat, turnip, and
lettuce, it has been determined that tolerances are not needed for
rotational crops provided a 30-day plant-back interval is established
for all crops not listed as target crops.  The existing rotational crop
restrictions on the Actigard® label are adequate.

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

HED has examined the residue chemistry database for
acibenzolar-S-methyl.  Pending submission of confirmatory crop field
trial data and/or a revised Section B (see requirements under Directions
for Use), the submission of a reference standard for the metabolite CGA
210007 (see requirements under Submittal of Analytical Reference
Standards), and a revised Section F (see requirements under Proposed
Tolerances), there are no residue chemistry issues that would preclude
granting a Section 3 registration for the requested use of
acibenzolar-S-methyl on crop subgroup 3-07A, or the establishment of a
tolerance for residues of acibenzolar-S-methyl, as follow:

Onion, bulb, subgroup 3-07A 	0.1 ppm

HED has examined the residue chemistry database for
acibenzolar-S-methyl.  Pending submission of a revised Section B (see
requirements under Directions for Use), the submission of a reference
standard for the metabolite CGA 210007 (see requirements under Submittal
of Analytical Reference Standards), and a revised Section F (see
requirements under Proposed Tolerances), there are no residue chemistry
issues that would preclude granting a time-limited acceptance of the
proposed use of acibenzolar-S-methyl on crop group 9, or the
establishment of a tolerance for residues of acibenzolar-S-methyl, as
follow:

Vegetable, cucurbit, group 9 	2.0 ppm

Pending receipt of required additional field trial/decline studies (see
requirements under 860.1500 Crop Field Trials - Cucurbit Vegetables,
group 9), the conversion of the time-limited acceptance of the proposed
use of acibenzolar-S-methyl on cucurbit vegetables group 9 to an
unconditional registration may be considered.  An amended tolerance
level may be deemed appropriate once the required field trial/decline
data are submitted.

Note to Registration Division:  Tolerances have been established under
40 CFR §180.561 for residues of acibenzolar-S-methyl.  HED continues to
recommend that the appropriate tolerance expression for
acibenzolar-S-methyl should be for “residues of acibenzolar-S-methyl,
benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester, convertible
to benzo(1,2,3)thiadiazole-7-carboxylic acid (CGA-210007), expressed as
acibenzolar-S-methyl.”

A human-health risk assessment is forthcoming.

860.1500 Directions for Use

For bulb onions, if the petitioner desires to keep the use of the
surfactant on the label, then three confirmatory trials using Actigard®
with a surfactant should be tested side-by-side with product applied
without using a surfactant in the NAFTA Growing Zones 10 (2 sites) and
11 (1 site).  Alternatively, the petitioner may submit a revised Section
B to disallow the use of silicone surfactant on the proposed label.

For cucurbit vegetables, a revised Section B must be submitted to remove
the statement “allow 14 days between the last application and
harvest” since the proposed PHI is 0 days.  The label should also be
revised to specify a minimum retreatment interval of 7 days based on the
submitted data.

860.1550 Proposed Tolerances

For the bulb onion petition, a revised Section F is required to remove
reference to “combined” residues in the tolerance expression.  The
tolerance level should be 0.1 ppm.  

For the cucurbit vegetable petition, a revised Section F must be
submitted to reflect the correct commodity definition, Vegetable,
cucurbit, group 9.  The tolerance level should be 2.0 ppm.

860.1650 Submittal of Analytical Reference Standards

The standard for the metabolite CGA 210007 (used for quantitation) has
expired (4/30/2008).  The registrant must either recertify the lot in
the repository and send in an updated certificate of analysis (COA), or
submit new standards (different lot #) if the previous lots will not be
recertified.  If new COAs are being submitted, they should be faxed to
the repository at 410-305-2999.  If new standards are being submitted,
they should be sent to the Analytical Chemistry Lab, which is located at
Fort Meade, to the attention of either Theresa Cole or William Chism at
the following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD  20755-5350

HED recommends that conversion of time-limited acceptance of use to an
unconditional registration for the proposed use of acibenzolar-S-methyl
on cucurbit vegetables may be considered upon submission of the
following outstanding residue chemistry data.

860.1500 Crop Field Trials - Cucurbit Vegetables, group 9

Six additional field trial/decline studies are required to support the
proposed use of acibenzolar-S-methyl on cucurbit vegetables.  Two
side-by-side cantaloupe and honeydew melon decline studies reflecting
the proposed maximum use rate and employing an adjuvant must be
conducted in Zones 6 and 10 (total of 4 trials), samples must be
collected at 0, 1, 3, 5, 7, and 10 days after the last application
(DALA).  Two cantaloupe decline studies, using the same protocol, must
be conducted in Zones 2 and 5 (total of 2 trials). 

Background

Acibenzolar-S-methyl has been classified as a reduced-risk compound with
a mode of action that mimics the natural systemic activated resistance
response found in most plant species.  The chemical structures and
nomenclature of acibenzolar-S-methyl and its metabolites CGA-210007 are
presented in Table 1.  The physicochemical properties of technical grade
acibenzolar-S-methyl are listed in Table 2.

Table 1.	Acibenzolar-S-Methyl Nomenclature.

Chemical structure	

mol wt 210

Common name	acibenzolar-S-methyl

Company experimental name	CGA-245704

IUPAC name	benzo[1,2,3]thiadiazole-7-carbothioic acid-S-methyl ester

CAS name	S-methyl, 1,2,3-bensothiadiazole-7-carbothioate

CAS registry number	135158-54-2

End-use product (EP)	Actigard® 50 WG (EPA Reg. No. 100-922)

Structure of metabolite 

CGA-210007  SEQ CHAPTER \h \r 1 	

1,2,3-benzothiadiazole-7-carboxylic acid 

mol wt 180

Table 2.	Physicochemical Properties of Acibenzolar-S-Methyl.

Parameter	Value	Reference

Melting point/range	133 ºC	DP# 250963, 2/10/99, H. Podall

pH	  SEQ CHAPTER \h \r 1 7.9 (1% solution in water) at 25 ºC

	Density	  SEQ CHAPTER \h \r 1 1.54 g/cc at 22 ºC (bulk density)

	Water solubility	0.0077 g/L

	Solvent solubility	Methanol	  4.2 g/L

Acetone		  28 g/L

Toluene		  36 g/L

n-Octanol	  5.4 g/L

n-Hexane	  1.3 g/L

Ethyl acetate	   25 g/L

Dichloromethane   160 g/L 	European Commission, 6506/VI/99-final,
5/21/02

Vapor pressure	3.6 x 10-6 Torr at 25 ºC	DP# 250963, 2/10/99, H. Podall

Dissociation constant, pKa	No dissociation constant in an

accessible pH range (1.0 - 9.0)	European Commission, 6506/VI/99-final,
5/21/02

Octanol/water partition coefficient, Log(KOW)	Log (POW) 3.1 at 25 ºC
DP# 250963, 2/10/99, H. Podall

UV/visible absorption spectrum	253 nm ε : 14.7 103 l mol-1 cm-1

288 nm ε : 5.4 103

324 nm ε : 7.2 103	European Commission, 6506/VI/99-final, 5/21/02

860.1200  Directions for Use

The proposed end-use product relevant to this registration action is
Actigard® (EPA Reg. No. 100-922), a 50% WG formulation.  The proposed
new uses are summarized in Table 3.

Table 3.	Summary of Directions for Use of Acibenzolar-S-methyl.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Onions, bulb dry (including all cultivars, varieties, and/or hybrids of
bulb daylily, bulb fritillaria, bulb garlic, great-headed bulb garlic,
Serpent bulb garlic, bulb lily, Chinese bulb onion, pearl onion, potato
bulb onion, and shallot bulb)

Postemergence

Foliar or banded

Ground or aerial	50% WG

[100-922]	0.023-0.031	4 (Implied)	0.125	7	Apply preventatively on a 7-10
day schedule.  Begin applications after thinning or after the 3-4 leaf
stage.

For best results for IYSV, begin at 4 to 6 weeks pre-bulb initiation and
continue on a 7-10 day interval.  A thrips control program in
conjunction with Actigard® is recommended.

For Xanthomonas leaf blight, begin 2-4 weeks pre-bulb initiation and
continue on a 7-10 day interval.  After the final Actigard®
application, use a recommended copper-based bactericide program to
finish the season.

Cucurbits (cantaloupe, cucumber, watermelon, squash, zucchini, and
hybrids or cultivars of these and chavote, Chinese waxgourd, gourds,
honeydew, Mormordica SDD (Bitter melon, Balsam apple), muskmelon and
pumpkin)

Postemergence

Foliar 

Ground or aerial	50% WG

[100-922]	0.02-0.06	Not specified	0.4	0	Apply in sufficient water to
ensure adequate coverage using a minimum of 20 GPA of water.  May be
tank-mixed with other fungicides and bactericides such as copper
products; use of an adjuvant is recommended.

The proposed use states to “allow 14 days between the last application
and harvest”, but also states “may be applied the day of harvest
(0-day PHI).”

The following additional use directions were specified for bulb onions: 
“Apply in sufficient water (minimums of 10 and 20 GPA for aerial and
ground equipment, respectively) to ensure thorough coverage.  It is
recommended to use a silicone adjuvant at the recommended rate.  Banded
applications can be made early when plants are small (7” proportional
band) as long as coverage is adequate.  Actigard® should be applied to
healthy, actively growing plants.  Do not apply prior to thinning or
within 5 days of transplanting.  Do not apply Actigard® to plants that
are stressed due to drought, excessive moisture, cold weather, or
herbicide injury, etc.  Avoid spray overlap as injury may occur. 
Planting of any crop other than tobacco, leafy vegetables including cole
(Brassica) crops and fruiting vegetable is prohibited within 30 days
after application, and a restricted-entry interval of 12 hours is
specified.”

Conclusions.  The submitted labels are adequate to allow evaluation of
the residue data relative to the proposed use rate and PHI on bulb
onions.  However, since the product label for Actigard® (EPA Reg. No.
100-922) allows for the use of a silicone surfactant, residue trials
should also reflect a surfactant during application of the test
formulation.

The submitted labels are adequate to allow evaluation of the residue
data relative to the proposed use rate and PHI on cucurbit vegetables. 
However, the product label must be revised to remove the statement
“allow 14 days between the last application and harvest” since the
proposed PHI is 0 days.  In addition the label should be revised to
specify a minimum retreatment interval of 7 days.

860.1300 Nature of the Residue - Plants

DP# 246673, 3/15/00, M. Doherty (PP#8F4974)

DP# 258680, 5/2/00, M. Doherty (PP#9F6004)

No new plant metabolism studies were submitted.  Adequate metabolism
studies with [phenyl-U-14C]acibenzolar-S-methyl on lettuce, tomato,
rice, wheat, and tobacco have previously been submitted and reviewed. 
The metabolic pathway for acibenzolar-S-methyl was similar in all tested
crops and involves the hydrolysis of the S-methyl ester to form the
carboxylic acid metabolite (CGA-210007).  Further hydroxylation of
CGA-210007 at the C-4 and C-5 positions results in the formation of the
minor metabolites CGA-324041 (all crops tested) and CGA-323060 (lettuce
and tomato), which may also form acyl sugar conjugates.

The HED MARC (11/9/99) determined that the residues of concern for
tolerance expression are residues convertible to
benzo(1,2,3)thiadiazole-7-carboxylic acid (CGA-210007), expressed as
acibenzolar-S-methyl.  For purposes of risk assessment, residues of the
3- and 5-hydroxy (CGA-324041 and CGA-323060) metabolites of CGA-210007
should also be included and considered as toxic as parent
acibenzolar-S-methyl. 

The metabolism studies on dissimilar crops are adequate to support the
requested uses on bulb onions and cucurbit vegetables.  For the purposes
of these petitions, the residue of concern for tolerance setting and
risk assessment purposes is considered to be residues of the parent
acibenzolar-S-methyl and CGA-210007, expressed as acibenzolar-S-methyl.

860.1300 Nature of the Residue - Livestock

There are no livestock feedstuffs associated with the proposed use on
the bulb onion subgroup 3-07A or the cucurbit vegetable group 9. 
Therefore, data requirements for livestock metabolism are not relevant
to these tolerance petitions.

860.1340 Residue Analytical Methods

DP# 246673, 3/15/00, M. Doherty (PP#8F4974)

DP# 258680, 5/2/00, M. Doherty (PP#9F6004)

Enforcement method:    SEQ CHAPTER \h \r 1 An adequate method, HPLC/UV
Method AG-671A, is available for tolerance enforcement.  This method has
undergone a successful tolerance method validation by the Analytical
Chemistry Branch of BEAD.  The method was forwarded to FDA for inclusion
in PAM Volume II.  Briefly, the method consists of an initial hydrolysis
with NaOH to convert acibenzolar-S-methyl to CGA-210007 followed by
methanol extraction.  Residues are then diluted with HCl and purified by
a series of solid-phase extraction steps.  Prior to HPLC/UV analysis,
residues are partitioned into ethyl acetate, dried down, and redissolved
in phosphoric acid.  This method has an LOQ of 0.02 ppm.  The method
includes optional detection via HPLC/MS, giving a means of residue
confirmation.  

Data collection methods:  Crop samples from the submitted bulb onion
field trial studies were analyzed for residues of acibenzolar-S-methyl
using a LC/MS method adapted with modification from the enforcement
method AG-617A.  Modifications from Method AG-671A included using MS
detection (confirmatory method) and, therefore, the alkaline
partitioning, C18 SPE and acidic partitioning cleanup steps were not
needed.  Briefly, samples of onion were extracted with water:1 N NaOH
(9:1, v:v) at 65-70 ºC for 30 minutes.  After cooling, methanol was
added with shaking for 30 minutes.  Following vacuum filtering, the
solvent was evaporated to a known volume and 1 M HCl was added for
cleanup through a Chem Elute column; residues were eluted with methylene
chloride:ethyl acetate (9:1, v:v).  The eluate was evaporated to
dryness, redissolved in 0.5% formic acid:acetonitrile (80:20, v:v), and
filtered for LC/MS analysis.  Hydrolyzed residues of
acibenzolar-S-methyl are quantitated as CGA-210007 and reported in terms
of acibenzolar-S-methyl equivalents.  The lowest level of method
validation (LLMV) for this method was 0.05 ppm for acibenzolar-S-methyl
in bulb onion.  Based on the recoveries from samples fortified at the
LLMV, the calculated LOQ and LOD for acibenzolar-S-methyl in onion were
0.04 and 0.013 ppm, respectively.  The method was adequately validated
prior to and concurrent with analysis of the field samples; untreated
bulb onion samples were fortified with acibenzolar-S-methyl at 0.05-2.0
ppm.  The fortification levels used in method verification and
concurrent method recovery were adequate to bracket expected residue
levels in/on bulb onion.

Cantaloupe, cucumber and summer squash samples from the submitted
cucurbit field trial studies were analyzed for residues of
acibenzolar-S-methyl using the HPLC/UV enforcement method.  Briefly,
homogenized samples were extracted with water:1 N NaOH (9:1, v:v) at
60-70 ºC for 30 minutes.  After cooling, methanol was added with
shaking for 30 minutes.  Following vacuum filtering, the solvent was
evaporated to a known volume and 1 M HCl was added for cleanup through a
Chem Elute column; residues were eluted with dichloromethane:ethyl
acetate (9:1, v:v).  The eluate was partitioned with 1 N NaOH and the
aqueous phase passed through a C18 Mega Bond Elut column.  The eluate,
mixed with the saturated sodium chloride rinse and phosphoric acid, was
partitioned with ethyl acetate.  The aqueous phase was partitioned again
with additional ethyl acetate, and the organic phases were combined,
evaporated to dryness, and redissolved in 0.02 M phosphoric acid for
HPLC/UV analysis.  The LOQ was set at the LLMV of 0.02 ppm; the limit of
detection was not reported.  The method was adequately validated
concurrent with analysis of the field samples; untreated cantaloupe,
cucumber and summer squash samples were fortified with
acibenzolar-S-methyl at 0.02-5.0 ppm.  The fortification levels used in
concurrent method validation were adequate to bracket expected residue
levels in/on cucurbit vegetables.

Conclusions.  The HPLC/UV and LC/MS methods are adequate for collecting
data on residues of acibenzolar-S-methyl in/on cucurbit vegetables and
bulb onions, respectively.  The existing enforcement method (HPLC/UV
Method AG-617A) will be adequate for tolerance enforcement purposes for
bulb onion and cucurbit vegetables.

860.1360 Multiresidue Methods

DP# 246673, 3/15/00, M. Doherty (PP#8F4974)

Data depicting the recovery of acibenzolar-S-methyl and its metabolite,
CGA-210007, using FDA Multiresidue Methods, were previously submitted. 
Acibenzolar-S-methyl yielded adequate response to GLC analysis and was
completely recovered through Protocols D and E.  Partial recovery of
CGA-210007 was achieved via Protocol B after derivatization.

860.1380 Storage Stability

DP# 246673, 3/15/00, M. Doherty (PP#8F4974)

47375301.der.doc

Previously submitted storage stability data indicate that residues of
acibenzolar-S-methyl and CGA-210007 are relatively stable in a variety
of crops.  Acibenzolar-S-methyl and CGA-210007 were stable in/on
fortified samples of cabbage, green and cured tobacco, leaf lettuce,
squash, tomato, turnip roots, wheat grain, and wheat straw stored frozen
for up to ~21-23 months.  The storage durations and conditions of
samples from the crop field trials submitted to support the subject
petitions are presented in Table 4.

IR-4 provided supporting storage stability data in conjunction with the
bulb onion field trials.  Samples of untreated bulb onion were fortified
with acibenzolar-S-methyl at 0.20 ppm and stored frozen with the field
trial samples.  No zero-day data were provided.  The concurrent storage
stability data indicate that fortified residues of acibenzolar-S-methyl
are reasonably stable in/on bulb onions stored frozen for up to 443
days.  

Table 4.	Summary of Storage Conditions and Durations of Samples from
Crop Field Trial Studies.

Matrix 	Storage Temperature

 (°C)	Actual Storage

Duration	Interval of Demonstrated Storage Stability

Onion, bulb	≤-21	104-463 days

(3.4-15.2 months)	Concurrent storage stability data indicate that
residues of acibenzolar-S-methyl are stable for up to 443 days in/on
frozen dry bulb onion.

Cantaloupe, cucumber and summer squash 	≤-20

	25-317 days

(0.8-10.4 months)	Acibenzolar-S-methyl  and CGA-210007 are stable in/on
a variety of fortified crops, including squash, stored frozen for up to
~21 months

Conclusions.  The concurrent storage stability data are adequate to
support the storage durations and conditions of samples of bulb onion
from the submitted crop field trial studies.  Although these data do not
completely encompass all sample durations from the onion trials,
acibenzolar-S-methyl has been demonstrated as stable in various crops
and decline over an additional month is not expected.  Zero-day data
were not provided with the concurrent storage stability studies.  IR-4
is reminded that storage stability studies should always include a
zero-day sampling interval to establish the residue levels present at
the time samples are placed into storage [see OPPTS 860.1380(d)(6)(i)].

The available storage stability on a variety of crops, including squash,
will support the storage durations and conditions of cantaloupe,
cucumber and summer squash samples from the submitted cucurbit field
trials.  No corrections for potential decline during storage are needed
for any of the residue studies.

860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with the proposed uses on
bulb onion and cucurbit vegetables.  Therefore, data requirements
pertaining to meat, milk, poultry, and eggs are not relevant to these
tolerance petitions.

860.1500 Crop Field Trials

47375301.der.doc (bulb onion)

45195301.der.doc (cucurbit vegetables)

Bulb Onion

The Interregional Research Project No. 4 has submitted field trial data
for acibenzolar-S-methyl on bulb onions.  Eight onion field trials were
conducted in Zones 1 (NY), 5 (MI), 6 (TX), 8 (CO), 10 (CA; 2 trials), 11
(ID) and 12 (OR) during the 2005 and 2006 growing seasons.  At each
trial, four foliar broadcast applications of a 50% WG formulation of
acibenzolar-S-methyl were made at a target rate of 0.03125 lb ai/A per
application, with 6- to 8-day retreatment intervals, for a total rate of
0.125 lb ai/A (1x the proposed maximum seasonal rate).  Applications
were made using ground equipment, in 20-51 gal/A spray volumes, without
an adjuvant.  Samples of onions were harvested 6-8 days after the last
application (DALA).  At four of the trial sites, samples were dried for
3-14 days before collection, as is the practice in those locations for
field-dry onions.  Additional samples were collected from one trial, 3,
10 and 14 DALA, to investigate residue decline.

Samples of onion were analyzed for residues of acibenzolar-S-methyl
using an LC/MS method, derived from the enforcement HPLC/UV method
(AG-671A).  The methods hydrolyzed residues of acibenzolar-S-methyl to
CGA-210007; residues are quantitated as CGA-210007 and reported in terms
of acibenzolar-S-methyl equivalents.  This method is adequate for data
collection based on acceptable method verification and concurrent method
recoveries.  The LLMV was 0.05 ppm for acibenzolar-S-methyl in/on bulb
onion.

Onion samples were stored frozen from harvest to analysis for up to 463
days (15.2 months).  Sample storage conditions and durations are
supported by storage stability data generated concurrently with the
field trials.

The results of the field trials are provided in Table 5 below.  Bulb
onion samples harvested 6-8-days following four foliar broadcast
applications of the 50% WG formulation for a total rate of 0.125-0.129
lb ai/A had nonquantifiable (<0.05 ppm) residues of acibenzolar-S-methyl
in seven  out of the eight field trials (fourteen out of sixteen treated
bulb onion samples).  Residues of acibenzolar-S-methyl were also
nonquantifiable (<0.05 ppm) in/on bulb onion samples from all sampling
intervals (3-14 days PHI) from the residue decline trial (Trial ID
#05-CA20).  Only the two bulb onion samples from the Zone 5 trial site
(Trial ID #05-MI02) harvested 7-days following four foliar broadcast
applications of the 50% WG formulation for a total rate of 0.124 lb ai/A
had quantifiable residues of acibenzolar-S-methyl measuring 0.05 ppm and
0.062 ppm.  [Note:  These samples were also dried in the field for 14
days after harvest but before collection, the longest field drying time
represented by the submitted field trial data.]

TABLE 5.	Summary of Residue Data from Bulb Onion Field Trials with
Acibenzolar-S-methyl.

Crop Matrix	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels (ppm)

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

Proposed use pattern = Maximum of 0.03 lb ai/A per application, for a
maximum seasonal rate of 0.125 lb ai/A, and a 7-day PHI.

Onion, bulb	0.124-0.129	6-8	16	<0.05	0.062	0.056	0.05	0.05	0.003

Conclusions.  The number and locations of the field trials are in
accordance with OPPTS Guideline 860.1500 for bulb onion as the
representative crop of the bulb onion subgroup 3-07A.  The trials
conducted reflect the proposed maximum seasonal rate and PHI, and there
are adequate storage stability data to validate sample storage
conditions and duration; however an adjuvant was not used in the field
trials and the data do not support the use of a silicone adjuvant as
recommended on the Actigard® label.  If the petitioner desires to keep
the use of the surfactant on the label, then three confirmatory trials
using Actigard® with a surfactant should be tested side-by-side with
product applied without using a surfactant in the NAFTA Growing Zones 10
(2 sites) and Region 11 (1 site).  Alternatively, the petitioner may
revise the product label to disallow the use of silicone surfactant on
the proposed label.

The results for bulb onion indicate that following application of the
test formulation according to the proposed use rate and PHI but without
an adjuvant, the maximum residues of acibenzolar-S-methyl were 0.062 ppm
in/on bulb onions.  The residue data were not entered into the
Agency’s tolerance spreadsheet (Guidance for Setting Pesticide
Tolerances Based in Field Trial Data) because fourteen out of sixteen
treated bulb onion samples bore nonquantifiable (<0.05 ppm) residues. 
The two treated bulb onion samples which did have quantifiable residues
(0.050 ppm and 0.062 ppm) were harvested at 7-day PHI and allowed to dry
in the field for 14-days after harvest but before collection.  These
bulb onion field trial data and previously submitted cured tobacco leaf
metabolism/field trial data (D246673, M. Doherty, 03/15/2000) suggest
that drying may tend to concentrate residues of acibenzolar-S-methyl;
therefore, in order to ensure that the tolerance level is adequate, and
pending submission of the requested confirmatory data discussed in the
paragraph above or label revisions, the available bulb onion field trial
data are deemed adequate to support a tolerance of 0.1 ppm for residues
of acibenzolar-S-methyl in/on the bulb onion subgroup 3-07A.

Cucurbit Vegetable Group 9

Syngenta Crop Protection, Inc has submitted field trial data for
acibenzolar-S-methyl on cantaloupe, cucumber, and summer squash, the
representative crops of the cucurbit vegetable group 9.  Nineteen
cucurbit field trials were conducted during the 1998-1999 growing
seasons; six cantaloupe trials in Zones 2 (GA; 1 trial), 5 (IN; 1
trial), 6 (TX; 1 trial), and 10 (AZ, CA; 3 trials); eight cucumber
trials in Zones 2 (NC, SC; 2 trials), 3 (FL; 1 trial), 5 (MI, WI; 2
trials), 6 (TX; 1 trial), and 10 (CA; 2 trials); and five summer squash
trials in Zones 1 (NY; 1 trial), 2 (GA; 1 trial), 3 (FL; 1 trial), 5
(MI; 1 trial), and 10 (CA; 1 trial).

At each trial, eight foliar broadcast applications of a 50% WG
formulation of acibenzolar-S-methyl were made at a target rate of 0.06
lb ai/A per application (1x the maximum proposed single application
rate), with 5- to 9-day retreatment intervals, for a total rate of 0.50
lb ai/A (1.25x the maximum proposed seasonal rate).  Applications were
made using ground equipment, in 10-35 gal/A spray volumes, except in
three trials where concentrated applications were made in 1-4 gal/A
spray volumes to simulate aerial applications.  A 50% WG formulation of
pymetrozine (CGA-215944) was co-applied with the last two applications
of acibenzolar-S-methyl; residue data for pymetrozine have been reviewed
separately by the Agency (PP#s 8F4984, 8F5031 and 0F6141; DP#s 250386,
267406, 267436, 267440, 270148, 273129 and 276737, 11/19/01, D. Dotson).
 The protocol required that no adjuvant be used for the
acibenzolar-S-methyl only applications (applications #1-6), but was to
be used with the pymetrozine formulation which was co-applied with the
last two acibenzolar-S-methyl applications (applications #7 and 8);
however, in 5 trials (1 cantaloupe, 3 cucumber and 1 summer squash) the
adjuvant was added to all applications.  Samples of mature cantaloupe,
cucumber, and summer squash were harvested on the day of the last
application (0-DALA).  Additional samples were collected from three
sites (one each cantaloupe, cucumber and summer squash) at 1, 3, 7 and
10 DALA, to investigate residue decline.

Samples of cantaloupe, cucumber and summer squash were analyzed for
residues of acibenzolar-S-methyl using the HPLC/UV enforcement method
(Method AG-671A).  The method hydrolyzes residues of
acibenzolar-S-methyl to CGA-210007; residues are quantitated as
CGA-210007 and reported in terms of acibenzolar-S-methyl equivalents. 
This method is adequate for data collection based on acceptable
concurrent method recoveries.  The LLMV was 0.02 ppm for
acibenzolar-S-methyl in/on cucurbit vegetables.

Cantaloupe, cucumber and summer squash samples were stored frozen from
harvest to analysis for up to 10.4 months.  Sample storage conditions
and durations are supported by available storage stability data on
diverse crops, including squash.

The results of the field trials (see Table 6) indicate that the maximum
residues of acibenzolar-S-methyl were 0.868 ppm in/on cantaloupe, 0.382
ppm in/on cucumber, and 0.151 ppm in/on summer squash harvested 0 days
after foliar broadcast applications of the 50% WG formulation for a
total rate of 0.5 lb ai/A.  Based on overall average residues, residues
appear slightly lower in samples treated with concentrated spray volumes
versus dilute spray volumes.

The results of the residue decline studies demonstrate that average
residues of acibenzolar-S-methyl (i.e., residues convertible to
CGA-210007) between the 0-day and 3-day PHIs in/on cantaloupe remained
generally constant and increased in/on cucumber and summer squash by
approximately 10% and 100%, respectively.  Average residues of
acibenzolar-S-methyl generally decreased in cantaloupe, cucumber, and
summer squash after 7-10 day PHIs and were the lowest at the 10-day PHI.
 

TABLE 6.	Residue Data from Cucurbit Field Trials with
Acibenzolar-S-methyl. , 

Trial:  County, State; Year

(Trial ID #)	Zone	Cucurbit Variety	Commodity or Matrix	Total Rate

(lb ai/A)	PHI

 (days)	Acibenzolar-S-methyl

Residues (ppm)1

Cantaloupe

Hamilton, IN; 1998

(NE-IR-101-98)	5	Burpee Hybrid	fruit	0.50	0	0.261	0.209

Tift, GA; 1999

(0S-IR-830-99)	2	Edisto 47	fruit	0.50	0	0.649	0.868

Hidalgo, TX; 1998

(0S-IR-305-98)	6	Mission Hybrid	fruit	0.50	0	0.263	0.217

Yuma, AZ; 1998

(0W-IR-507-98)	10	Mission	fruit	0.50	0	0.282	0.275

Tulare, CA; 1998

(0W-IR-104-98)	10	Hales Best Jumbo	fruit	0.50	0	0.280	0.275

Imperial, CA 1999

(0W-IR-561-99)	10	Im-Pac	fruit	0.50	0	0.132	0.135

	1	0.097	0.145

	3	0.111	0.110

	7	0.094	0.091

	10	0.103	0.097

Cucumber

Madera, CA; 1998

(0W-IR-425-98)	10	Dasher II	fruit	0.50	0	0.064	0.061

Indian River, FL; 1998

(07-IR-001-98)	3	Straight Eight	fruit	0.50	0	0.104	0.158

Hidalgo, TX; 1998

(0S-IR-304-98)	6	Poinsett	fruit	0.50	0	0.089	0.104

Sampson, NC; 1998

(0S-IR-604-98)	2	Poinsett 76	fruit	0.50	0	0.116	0.098

Barnwell, SC; 1998

(0S-IR-605-98)	2	Poinsett 76	fruit	0.50	0	0.137	0.118

Ottawa, MI; 1998

(NE-IR-703-98)	5	Marketmore	fruit	0.50	0	0.294	0.382

	1	0.241	0.235

	3	0.408	0.334

	7	0.347	0.362

	10	0.131	0.125

Walworth, WI; 1998

(MW-IR-701-98)	5	Marketmore 86	fruit	0.50	0	0.141	0.168

Tulare, CA; 1998

(0W-IR-103-98)	10	Dasher II	fruit	0.50	0	0.112	0.152

Summer Squash

Tift, GA; 1998

(0S-IR-831-98)	2	Dixie Hybrid	fruit	0.50	0	0.117	0.102

Ottawa, MI; 1998

(NE-IR-704-98)	5	Yellow Straight Neck	fruit	0.50	0	0.151 2

Tulare, CA; 1998

(0W-IR-105-98)	10	Ambassador	fruit	0.50	0	0.059	0.051

	1	0.123	0.101

	3	0.116	0.100

	7	0.045	0.017

	10	0.023	0.040

Columbia, NY; 1998

(05-IR-002-98)	1	Yellow Crookneck	fruit	0.50	0	0.117	0.119

Indian River, FL; 1998

(07-IR-002-98)	3	Zucchini; Black Beauty	fruit	0.50	0	0.026	0.043

  SEQ CHAPTER \h \r 1 1  The petitioner reported residue values that had
been corrected for concurrent method recovery.  The uncorrected values
were obtained from the raw data by the study reviewer and are reported
herein.  

2  The duplicate sample was lost during analysis.

Conclusions.  The number and locations of the field trials are in
accordance with OPPTS Guideline 860.1500 for cantaloupe, cucumber and
summer squash as the representative crops of the cucurbit vegetable
group 9.  The trials conducted reflect the proposed maximum single
application rate and 0-day PHI, and adequate storage stability data are
available to validate sample storage conditions and duration.

Although side-by-side trials were not conducted comparing applications
with and without an adjuvant, the last two applications at each field
trial study were made with an adjuvant, and all applications at five of
the field trials were inadvertently made with an adjuvant.  These data
indicate that residues are not expected to be higher with the use of an
adjuvant and will support the label specification allowing use of an
adjuvant with Actigard® (EPA Reg. No. 100-922) on cucurbit vegetables.

The results indicate that following application of the test formulation
according to the proposed single use rate and 0-day PHI, the maximum
residues of acibenzolar-S-methyl were 0.868 ppm in/on cantaloupe, 0.382
ppm in/on cucumber, and 0.151 ppm in/on summer squash.  The maximum
residues for these representative crops differ by >5x. 

The residue data were entered into the Agency’s tolerance spreadsheet
which recommended tolerances of 1.0 ppm for cantaloupe, 0.40 ppm for
cucumber, and 0.35 ppm for summer squash.  For the cantaloupe-dataset,
visual inspection of the lognormal probability plot (Figure I-1) and the
result from the approximate Shapiro-Francia test statistic (Figure I-2)
indicated that the assumption of lognormality should be rejected.  The
recommended tolerances for these representative crops differ by <5x. 

The results of the residue decline studies demonstrate that average
residues of acibenzolar-S-methyl (i.e., residues convertible to
CGA-210007) in/on cantaloupe remained generally constant between the 0-
and 3-day PHIs and increased in/on cucumber and summer squash by
approximately 10% and 100%, respectively.  Residues generally decreased
in cantaloupe, cucumber, and summer squash by the 7-10 day PHIs and were
the lowest at the 10-day PHI.  These data suggest that residues of
acibenzolar-S-methyl in/on cucurbit vegetables resulting from the
proposed single use rate and 0-day PHI may not represent the worst case
as residues may increase between 0- and 7-day PHIs and generally
decrease thereafter.  This phenomenon was noted in an earlier review of
Brassica Leafy Vegetables (D258680, M. Doherty, 05/02/2000) where
decline trials demonstrated that average residues of
acibenzolar-S-methyl in/on broccoli increased between the 0- and 5-day
PHIs by approximately 300% and than generally decreased thereafter.  An
explanation for this phenomenon is not readily apparent.  

Given the indication of variability within and between these cucurbit
vegetable data sets and the demonstrated potential for significant
increases in acibenzolar-S-methyl residues between 0- and 7-day PHIs,
six additional field trial/decline studies are required to support the
proposed use of acibenzolar-S-methyl on cucurbit vegetables.  Two
side-by-side cantaloupe and honeydew melon decline studies demonstrating
the proposed use rate and using an adjuvant must be conducted in Zones 6
and 10 (a total of 4 trials), samples must be collected at 0, 1, 3, 5,
7, and 10 days after the last application (DALA).  Two cantaloupe
decline studies, using the same protocol, must be conducted in Zones 2
and 5 (a total of 2 trials). 

The available cucurbit vegetable field trial and decline data indicate
that a tolerance of 2.0 ppm for residues of acibenzolar-S-methyl
convertible to CGA-210007 in/on cucurbit vegetables group 9 would be
adequate to cover maximum residues resulting from the proposed single
application rate and PHI.  A lower tolerance may be deemed appropriate
once the required field trial/decline data discussed in the paragraph
above are submitted.

860.1520 Processed Food and Feed

There are no processed food/feed commodities associated with the
proposed uses on bulb onions and cucurbit vegetables.  Therefore, data
requirements pertaining to processed food and feed are not relevant to
these tolerance petitions.

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

Analytical standards for acibenzolar-S-methyl (CGA 245704) and its
metabolite CGA 210007 are currently available in the EPA National
Pesticide Standards Repository (personal communication with Dallas
Wright, ACB, 6/17/08).  However, the standard for the metabolite CGA
210007 (used for quantitation) has expired (4/30/2008).  The registrant
must either recertify the lot in the repository and send in an updated
certificate of analysis (COA), or submit new standards (different lot #)
if the previous lots will not be recertified.  If new COAs are being
submitted, they should be faxed to the repository at 410-305-2999.

If new standards are being submitted, they should be sent to the
Analytical Chemistry Lab, which is located at Fort Meade, to the
attention of either Theresa Cole or William Chism at the following
address:

	USEPA

	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

	701 Mapes Road

	Fort George G. Meade, MD  20755-5350

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

860.1850 Confined Accumulation in Rotational Crops

DP# 246673, 3/15/00, M. Doherty (PP#8F4974)

Adequate confined rotational crop studies with acibenzolar-S-methyl have
been submitted previously and reviewed by HED.  Following treatment of
soil with [14C]acibenzolar-S-methyl at ~0.375 lb ai/A (~1x the maximum
seasonal rate to annual crops), total radioactive residues (TRR)
accumulated at >0.01 ppm in/on all crop samples from the 30- and 60-day
PBIs.  The relative TRR levels among the various RACs were the same at
both PBIs, although TRR values were slightly higher at the 61-day PBI
for each RAC, except radish root.  At both PBIs, levels of radioactivity
were lowest in radish roots (0.013 ppm) and highest in wheat forage
(0.107 and 0.157 ppm):  TRR in the remaining RACs ranged from
0.021-0.083 ppm.  From the 210-day PBI samples, TRR ranged from 0.004
ppm in radish roots to 0.026 ppm in 25% mature wheat forage.

  SEQ CHAPTER \h \r 1 In the 30- and 61-day PBI samples, the principal
metabolite identified in rotational crops was free CGA-210007,
accounting for 1.3-10.5% of the TRR.  Other metabolites that were
tentatively identified included the hydroxylated acid metabolites,
CGA-324041 and CGA-323060, which together accounted for <0.8-15.9% of
the TRR.  Trace levels of parent (0.1-0.7% TRR) were also detected along
with minor unknown metabolites generally accounting for <9% of the TRR. 
Cellulase and base hydrolyses of extracted residues indicated that
metabolite CGA-210007 also occurs as an acyl sugar conjugate in
rotational crops.  Following hydrolysis, CGA-210007 accounted for 17.3%
TRR and 30.4% TRR in wheat forage from the 30- and 61-day PBIs,
respectively.  In the 210-day PBI samples, residues of
acibenzolar-S-methyl (< 0.002 ppm) and CGA-210007 ( 0.001 ppm) were
identified in all samples.  Residues of CGA-324041 and CGA-323060 were
not identified in any extracts.

  SEQ CHAPTER \h \r 1 The confined rotational crop data indicate that
the metabolism of [14C]acibenzolar-S-methyl in rotational crops is
similar to the metabolism observed in the primary crops (lettuce,
tomato, wheat, and rice).    SEQ CHAPTER \h \r 1 HED has determined that
acibenzolar-S-methyl + its metabolites convertible to GCA-210007 +
CGA-324041 + CGA-323060 comprise the total toxic residue for
acibenzolar-S-methyl in rotational crops.  As combined levels of these
residues exceeded 0.01 ppm in rotational wheat forage from both the 30
and 61-day PBIs, a limited field rotational crop study for cereal-grain
crops was required.

860.1900 Field Accumulation in Rotational Crops

DP# 246673, 3/15/00, M. Doherty (PP#8F4974)

DP# 258680, 5/2/00, M. Doherty (PP#9F6004)

30, 60, and 180 days after the final treatment.

  SEQ CHAPTER \h \r 1 Residues of acibenzolar-S-methyl and its
metabolites containing the CGA-210007 moiety were nondetectable (<0.02
ppm) in all rotational crop matrices (wheat forage, hay, straw and
grain; turnip tops and roots; and leaf lettuce) from the 30-day PBI.   
SEQ CHAPTER \h \r 1 While tolerances are not needed for the rotational
crops, a plant-back restriction of not less than 30 days is required
based on the results from the confined rotational crop study.  A 30-day
plant-back interval for all crops not listed as target crops on the
acibenzolar-S-methyl label was required.  The recommended rotational
crop restrictions agree with the established rotational crop
restrictions for the 50% WG formulation (see 860.1200 Directions for
Use).

860.1550 Proposed Tolerances

Tolerances are currently listed in 40 CFR §180.561 for residues of
acibenzolar-S-methyl, (benzo(1,2,3)thiadiazole-7-carbothioic
acid-S-methyl ester). 

The HED MARC has determined that the residues of concern in plants for
tolerance expression are residues convertible to
benzo(1,2,3)thiadiazole-7-carboxylic acid (CGA-210007), expressed as
acibenzolar-S-methyl.  

The tolerance expression proposed by IR-4 (PP#8E7337) is in terms of
“the combined residues of the fungicide acibenzolar-S-methyl,
benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester”.  The
proposed tolerance expression must be revised to remove reference to
“combined” residues.  The tolerance proposed by Syngenta (PP#8F7352)
agrees with the current tolerance expression in 40 CFR §180.561.

The bulb onion residue data were not entered into the Agency’s
tolerance spreadsheet (Guidance for Setting Pesticide Tolerances Based
in Field Trial Data) because fourteen out of sixteen treated bulb onion
samples bore nonquantifiable (<0.05 ppm) residues.  The two treated bulb
onion samples which did have quantifiable residues (0.050 ppm and 0.062
ppm) were harvested at 7-day PHI and allowed to dry in the field for
14-days after harvest but before collection.  These bulb onion field
trial data and previously submitted cured tobacco leaf metabolism/field
trial data (D246673, M. Doherty, 03/15/2000) suggest that drying may
tend to concentrate residues of acibenzolar-S-methyl; therefore, in
order to ensure that the tolerance level is adequate, and pending
submission of the requested confirmatory data or label revisions, the
available bulb onion field trial data are deemed adequate to support a
tolerance of 0.1 ppm for residues of acibenzolar-S-methyl in/on the bulb
onion subgroup 3-07A.

The cucurbit vegetable residue data were entered into the Agency’s
tolerance spreadsheet (see Appendix I) which recommended tolerances of
1.0 ppm for cantaloupe, 0.40 ppm for cucumber, and 0.35 ppm for summer
squash.  The results of the cucurbit vegetables residue decline studies
demonstrate that average residues of acibenzolar-S-methyl (i.e.,
residues convertible to CGA-210007) in/on cucurbit vegetables may
increase by as much as 100% between 0-day PHI (proposed PHI) and 7-day
PHI; hence, a tolerance of 2.0 ppm for residues of acibenzolar-S-methyl
convertible to CGA-210007 in/on cucurbit vegetables group 9 would be
adequate to cover maximum residues resulting from the proposed use rate
and 0-day PHI.  Additional field trial/decline studies are required to
support the proposed use of acibenzolar-S-methyl on cucurbit vegetables
and a lower tolerance may be deemed appropriate once the required field
trial/decline data are submitted.

Pending submission of the requested confirmatory data and/or label
revisions, the available field trial data will support the proposed
tolerances of 0.1 ppm for residues of acibenzolar-S-methyl in/on the
bulb onion subgroup 3-07A, and 2.0 ppm for residues of
acibenzolar-S-methyl in/on the cucurbit vegetable group 9.  The
temporary tolerance for bulb onion at 0.05 ppm listed under 40 CFR
§180.561(b) should be removed concomitant with the establishment of a
permanent tolerance for subgroup 3-07A.  The proposed tolerances are
listed in Table 7, along with the tolerance level recommended by HED.  

There are no established Codex, Mexican, or Canadian maximum residue
limits for acibenzolar-S-methyl in/on any commodity.

Table 7.	Tolerance Summary for Acibenzolar-S-methyl.

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

Tolerances to be listed under 40 CFR §180.561(a):

Onion, bulb, 

subgroup 3-07A	--	0.07	0.1

	Cucurbit Vegetables Crop Group	--	1.0	2.0	Additional field
trial/decline studies are required to support the proposed use of
acibenzolar-S-methyl on cucurbit vegetables and a lower tolerance may be
deemed appropriate once the required field trial/decline data are
submitted.

Vegetable, cucurbit, group 9

Temporary tolerance listed under 40 CFR §180.561(b):

Bulb onion	0.05	--	Remove	Permanent tolerance to be established under
180.561(a)

References

DP#:		250963

Subject:	TGAI Product Chemistry Review/Action:  100

EPA Reg./File Symbol No.:  100-OER

Chemical:  CGA-245704  Technical; 1,2,3-benzothiadiazole-7-carbothioic
acid-S-methyl ester

Company:  Novartis Crop Protection Inc.

From:		H. Podall

To:		C. Giles-Parker/M. Rodriguez 

Dated:		02/10/99

MRIDs:	44537001-03

DP#:		259930

Subject:	Acibenzolar-S-methyl:  Briefing Memorandum for the HED
Metabolism Assessment Review Committee.

From:		M. Doherty

To:		G. Kramer and HED Metabolism Assessment Review Committee

Dated:		11/3/99

MRIDs:	None

DP#:		246673

Subject:	PP8F4974:  Request for Use of Acibenzolar-S-methyl on Leafy
Vegetables and Fruiting Vegetables.  Evaluation of Analytical Methods
and Residue Chemistry Data.

From:		M. Doherty

To:		C. Giles-Parker/M. Rodriguez

Dated:		3/15/00

MRIDs:	44014255, 44537051-63, 44828008, 44828025, 44993301-02

DP#:		258680

Subject:	PP9F06004:  Request for Use of Acibenzolar-S-methyl on Brassica
Leafy Vegetables and Bananas (imported).  Evaluation of Analytical
Methods and Residue Chemistry Data.

From:		M. Doherty

To:		C. Giles-Parker/M. Rodriguez

Dated:		5/2/00

MRIDs:	44828004-07, 44828009-24

DP#:		250386

Subject:	PP#s 8F4984, 8F5031, and 0F6141.  Tolerance Petitions for the
Use of Pymetrozine on Cotton, Hops, Pecans, Leafy Vegetables (Except
Brassica Vegetables), Head and Stem Brassica, Leafy Brassica Greens,
Turnip Greens, Cucurbits, and Fruiting Vegetables.  Evaluation of
Residue Chemistry and Analytical Methodology.

From:		D. Dotson

To:		Daniel Peacock/Deborah McCall

Dated:		11/19/01

MRIDs:	44572208, 44647906-08, 44753301, 44753302, 44830401, 45091001-04,
45105301, 45301301

  SEQ CHAPTER \h \r 1 Attachments:  

International Residue Limit Status sheet

Appendix 1:  Tolerance Assessment Calculations

Template Version September 2005



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:   benzo[1,2,3]thiadiazole-7-carbothioic acid-S-methyl
ester	Common Name:

Acibenzolar-S-Methyl	Proposed tolerance	Date:  01/2009

Codex Status (Maximum Residue Limits)	U. S. Tolerances

No Codex proposal step 6 or above	Petition Number:  PP#8E7337 &
PP#8F7352

DP#:  352415 & 354287

Other Identifier:    

Residue definition (step 8/CXL): N/A	Reviewer/Branch:  B.
Cropp-Kohlligian/RAB4 

	Residue definition:   acibenzolar-S-methyl,
benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Onion, bulb, subgroup 3-07A	0.1

Cucurbit Vegetables Crop Group 9	2.0

	Limits for Canada	Limits for Mexico

	Residue definition:  N/A

	Residue definition: 

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

	Notes/Special Instructions:  S. Funk, 06/16/2008.

Appendix I.  Tolerance Assessment Calculations.

d reasonably lognormal.  For datasets that were small (≤15 samples)
and reasonably lognormal, the upper bound estimate of the 95th
percentile based on the median residue value was compared to the minimum
of the 95% UCL on the 95th percentile and the point estimate of the 99th
percentile, and the minimum value was selected as the tolerance value. 
For datasets that were not lognormal, the upper bound on the 89th
percentile was selected as the tolerance value (distribution-free
method).  The rounding procedures specified in the SOP were also used.

Vegetable, cucurbit, group 9

The dataset used to establish a tolerance for acibenzolar-S-methyl on
the vegetable, cucurbit, group 9 consisted of field trial data for
cantaloupe, cucumber and summer squash (the representative crops of
vegetable, cucurbit group 9), representing application rates of 0.50 lb
ai/A (8 applications at 0.06 lb ai/A/application) with a 0-day PHI.  As
specified by the SOP, the field trial application rates and PHIs are
within 25% of the maximum label application rate and minimum label PHI,
respectively.  The residues values used to calculate the tolerance are
provided in Table I-1.

All field trial sample results were above the LOQ (LOQ = 0.02 ppm).  The
cantaloupe and summer squash datasets were small (12 cantaloupe samples;
9 squash samples) and the cucumber dataset was large (16 cucumber
samples).  The dataset for each crop was entered into the tolerance
spreadsheet.  

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lity plots (Figures I-3 and I-5) and the results from the approximate
Shapiro-Francia test statistics (Figures I-4 and I-6) indicated that the
datasets were reasonably lognormal.    

Using the tolerance spreadsheet, the recommended tolerances are 1.0 ppm
for cantaloupe, 0.40 ppm for cucumber, and 0.35 ppm for summer squash. 

Table I-1.	Residue data used to calculate tolerance for
acibenzolar-S-methyl on cucurbit vegetables.

Regulator:	EPA	EPA	EPA

Chemical:	Acibenzolar-S-methyl	Acibenzolar-S-methyl	Acibenzolar-S-methyl

Crop:	Cantaloupe	Cucumber	Summer Squash

PHI:	0 Days	0 Days	0 Days

App. Rate:	0.5 lb ai/A	0.5 lb ai/A	0.5 lb ai/A

Submitter:	Syngenta Crop Protection	Syngenta Crop Protection	Syngenta
Crop Protection

MRID Citation:	MRID 45105301	MRID 45105301	MRID 45105301

	Residues

	0.261	0.064	0.117

	0.209	0.061	0.102

	0.649	0.104	0.151

	0.868	0.158	0.059

	0.263	0.089	0.051

	0.217	0.104	0.117

	0.282	0.116	0.119

	0.275	0.098	0.026

	0.280	0.137	0.043

	0.275	0.118

0.132	0.294

0.135	0.382

	0.141

	0.168

	0.112

	0.152

	

Figure I-1.  Lognormal probability plot of acibenzolar-S-methyl field
trial data for cantaloupe.

Figure I-2.   Tolerance spreadsheet summary of acibenzolar-S-methyl
field trial data for cantaloupe.

Figure I-3.  Lognormal probability plot of acibenzolar-S-methyl field
trial data for cucumber.

Figure I-4.   Tolerance spreadsheet summary of acibenzolar-S-methyl
field trial data for cucumber.

Figure I-5.  Lognormal probability plot of acibenzolar-S-methyl field
trial data for summer squash.

Figure I-6.   Tolerance spreadsheet summary of acibenzolar-S-methyl
field trial data for summer squash.

Page   PAGE  2  of   NUMPAGES  30 

Acibenzolar-S-Methyl	Summary of Analytical Chemistry and Residue Data
DP#:  352415