Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

Office of Chemical Safety and Pollution Prevention

MEMORANDUM

Date: February 23, 2012

SUBJECT: Acibenzolar-S-Methyl. Petition for the Establishment of Permanent Tolerances 

on Low Growing Berries (Subgroup 13-07G). Summary of Analytical Chemistry and Residue 

Data.

PC Code: 061402 DP Barcodes: 386364

Decision Nos.: 443561 Registration No.: 100-922

Petition Nos.: 0E7818 Regulatory Action: Amended Section 3

Risk Assessment Type: NA Case No.: NA

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

MRID Nos.: 48332801 40 CFR: §180.561

 

FROM: Thurston G. Morton, Chemist

Risk Assessment Branch 4

Health Effects Division (7509P)

THROUGH: Susan V. Hummel, Chemist/Senior Scientist

Elissa Reaves PhD, Branch Chief

Risk Assessment Branch 4

Health Effects Division (7509P)

TO: Becky Daiss, Risk Assessor

Risk Assessment Branch 4

Health Effects Division (7509P)

And

Sidney Jackson (RM 05)

Risk Integration, Minor Use & Emergency Response Branch

Registration Division (7505P)

MRID Summary Table

MRID No. Study Type Comments

48332801 860.1500 Strawberry New DER; 48332801.der.doc
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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Executive Summary

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 bulb vegetables, leafy vegetables, Brassica 

leafy vegetables, fruiting vegetables, cucurbits, and tobacco for the control or suppression of 

downy mildew, black rot, white rust, bacterial leaf spot and speck, and blue mold. 

This document summarizes the available residue chemistry data submitted by the petitioner in 

support of proposed new use on food crops.

Under PP#0E7818, 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 a new use on the low growing berry crop subgroup 13-07G. 

Actigard® is proposed for multiple foliar applications on the low growing berry subgroup using 

ground or aerial equipment at a maximum of 0.023 lb ai/A per application, a maximum seasonal 

rate of 0.188 lb ai/A, and a 0-day pre-harvest interval (PHI). Concurrently, IR-4 requests the 

establishment of a permanent tolerance for “the combined residues of the fungicide acibenzolarS-methyl, benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester”, in/on:

Low growing Berry Crop Subgroup 13-07G..............0.15 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), 

onion, bulb, subgroup 3-07A (0.1 ppm), vegetable, cucurbit, group 9 (2.0 ppm) and leafy

vegetables (0.25 ppm), and for bananas (0.1 ppm) as an import tolerance. 

There are no established Codex, Mexican, or Canadian maximum residue limits (MRLs) 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 use on the low growing berry

subgroup. Therefore, no livestock metabolism data, enforcement methods, storage stability data, 

or feeding studies are required to support this petition.
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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HPLC/UV Method AG-617A 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 CGA210007 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 re-dissolved 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.

Strawberry samples from the submitted field trial studies were analyzed for residues of 

acibenzolar-S-methyl using Method AG-671A, 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 

strawberry as the representative crop of the low growing berry subgroup 13-07G. The trials 

conducted reflect the proposed maximum seasonal rate and pre-harvest interval (PHI), and there 

are adequate storage stability data to validate sample storage conditions and duration. The 

majority of the tank mixes contained an adjuvant. 

The results for strawberry indicate that following application of the test formulation according to 

the proposed use rate and PHI (0-day), the maximum residues of acibenzolar-S-methyl (i.e., 

residues convertible to CGA-210007) were 0.087 ppm in/on strawberry. The residue data was

entered into the OECD MRL Calculator. The available strawberry field trial data are deemed 

adequate to support a tolerance of 0.15 ppm for residues of acibenzolar-S-methyl in/on the low 

growing berry subgroup 13-07G.

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.

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for acibenzolar-S-methyl. Pending 

submission of 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 13-07G, or the establishment of a tolerance for 

residues of acibenzolar-S-methyl, as follows:

Berry, low growing, subgroup 13-07G............0.15 ppm
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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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 read as follows. 

Tolerances are established for residues of acibenzolar-S-methyl, benzo(1,2,3)thiadiazole-7-

carbothioic acid-S-methyl ester, including its metabolites and degradates, in or on the 

commodities in the table below. Compliance with the tolerance levels specified below is to be 

determined by measuring only those acibenzolar-S-methyl residues convertible to 

benzo(1,2,3)thiadiazole-7-carboxylic acid (CGA-210007), expressed as the stoichiometric 

equivalent of acibenzolar-S-methyl, in or on the commodity.

A human health risk assessment is forthcoming.

860.1550 Proposed Tolerances

For the low growing berry subgroup petition, a revised Section F is required to remove reference 

to “combined” residues in the tolerance expression. 

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 Theresa Cole, ACB, 6/21/11). 

acibenzolar metabolite (CGA210007), expiration date 1/31/2012

acibenzolar S-methyl (CGA245704), expiration date 3/1/2013

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 Thuy Nguyen at the 

following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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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-Smethyl are listed in Table 2.

Table 1. Acibenzolar-S-Methyl Nomenclature.

Chemical structure

N

N

S

O S

CH3

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

N

N

S

COOH

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

mol wt 180
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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

Parameter Value Reference

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

pH 7.9 (1% solution in water) at 25 oC

Density 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 103l mol-1cm-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

Low growing berries

Postemergence

Foliar or 

banded

Ground /Aerial

50% WG

[100-922]

0.016-

0.023 8 (Implied) 0.188 0

Scout fields regularly for 

angular leaf spot after 

plant establishment. 

Begin applications when 

disease appears, and 

continue on a 7- to 14-day

interval.

The following additional use directions were specified for low growing berries: “Apply in 

sufficient water to ensure adequate coverage. 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. 

Conclusions. The submitted label is adequate to allow evaluation of the residue data relative to 

the proposed use rate and PHI on low growing berries. 
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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-U14C]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 CGA323060 (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 (CGA324041 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 low 

growing berries. 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 low growing berry

subgroup 13-07G. 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: An adequate method, HPLC/UV Method AG-617A, 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 re-dissolved 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 strawberry 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 homogenized strawberry
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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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 of 8-10 mL, and an equal amount of 1 M HCl was added for 

cleanup through a Chem Elute column; residues were eluted with dichloromethane:ethyl acetate 

(9:1, v:v). The sample was then evaporated to dryness at 35 C, taken up in 80:20 0.5% formic 

acid:acetonitrile, sonicated, and filtered prior to analysis of CGA-210007 by LC/MS. The 

column used was Agilent, Zorbax SB-C18. The mobile phase was 0.5% formic acid (mobile 

phase A) and acetonitrile (mobile phase B). The method was validated at 0.02 ppm. The LC/MS 

method used to determine residues of acibenzolar-S-methyl in/on strawberry was adequately 

validated in conjunction with field sample analyses. Concurrent method recoveries from 

strawberry fortified with acibenzolar-S-methyl at 0.02-2.0 ppm were generally within the 

acceptable range of 70-120% (see Table C.1); one slightly high recovery (130%) was obtained at 

the 0.02 ppm fortification level. Adequate sample calculations and chromatograms were 

provided. The fortification levels used in the concurrent method recoveries were adequate to 

bracket expected residue levels in/on strawberry.

Conclusions. The LC/MS methods are adequate for collecting data on residues of acibenzolar-Smethyl in/on strawberry. The existing enforcement method (HPLC/UV Method AG-617A) will 

be adequate for tolerance enforcement purposes for low growing berry subgroup.

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 strawberry field trials. 

Samples of untreated strawberry 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 stable in/on strawberries

stored frozen for up to 317 days. 
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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

Matrix Storage Temperature

(°C)

Actual 

Maximum 

Storage

Duration

Interval of Demonstrated Storage Stability

Strawberry ≤-21 314 days

(10.3 months)

Concurrent storage stability data indicate that residues of 

acibenzolar-S-methyl are stable for up to 317 days in/on frozen 

strawberries.

Conclusions. The concurrent storage stability data are adequate to support the storage durations

and conditions of samples of strawberry from the submitted crop field trial studies. 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)].

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 strawberry. Therefore, 

data requirements pertaining to meat, milk, poultry, and eggs are not relevant to this tolerance 

petition.

860.1500 Crop Field Trials

IR-4 has submitted field trials supporting a new use of acibenzolar-s-methyl on strawberries. 

The results from these studies are summarized and discussed below.

Strawberry

DER Reference: 48332801.der.doc (Strawberry)

IR-4 has submitted field trial data for acibenzolar-s-methyl on strawberries. A total of ten field 

trials were conducted in the United States in EPA Regions 1 (NY, 1 trial), 2 (NC, 1 trial), 3 (FL, 

1 trial), 5 (WI and Ontario, 2 trials), 5B (Quebec, 1 trial), 10 (CA, 3 trials), and 12 (OR, 1 trial) 

during the 2008 growing season. Geographic representation was adequate.

At each test location, the treated plots received eight to nine foliar broadcast applications of a 

water dispersible granule (WG) formulation of acibenzolar-s-methyl (100-922, 50%WG) at 

0.023 lb ai/A with a 6 to 9-day retreatment interval (RTI) and a spray volume that ranged from 

27-59 gal/A (GPA). Samples of strawberries were harvested at maturity on the day of the last 

application (0-day preharvest interval (PHI)). One site also collected decline samples at 0, 3, 7, 

10, and 14 days after the last application (DALA). An adjuvant was included in the majority of 
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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tank mixes.

Strawberry samples from the submitted field trial studies were analyzed for residues of 

acibenzolar-S-methyl using Method AG-671A, an LC/MS method adapted with modification 

from the enforcement method. The limit of quantitation (LOQ) was 0.02 ppm. 

IR-4 provided supporting storage stability data in conjunction with the strawberry field trials. 

Samples of untreated strawberry were fortified with acibenzolar-S-methyl at 0.20 ppm and stored 

frozen with the field trial samples. No zero-day data were provided. Samples were stored frozen 

for up to 314 days. The concurrent storage stability data indicate that fortified residues of 

acibenzolar-S-methyl are stable in/on strawberries stored frozen for up to 317 days. 

The results from these trials show that residues ranged from 0.020-0.087 ppm after eight to nine 

applications of approximately 0.023 lb ai/A per application of Actigard 50WG for a total 

seasonal application rate of 0.183 -0.214 lb ai/A. Residue decline data show that acibenzolar-Smethyl residues decrease in/on strawberries with increasing PHIs.

TABLE 6. Summary of Residue Data from Strawberry Field Trials with Acibenzolar-S-methyl.

Commodity Total Applic. 

Rate

(lb ai/A)

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 Median

(STMdR)

Mean

(STMR)

Std. Dev.

Strawberry ~0.188 0 20 0.020 0.087 0.085 0.040 0.046 0.022

1

 HAFT = Highest Average Field Trial.

Conclusions. The petitioner has provided adequate residue data reflecting the maximum 

proposed use pattern of acibenzolar-S-methyl on strawberries. The residue data is supported by

adequate storage stability data and an acceptable analytical method was used for quantitation. 

The residues of acibenzolar-S-methyl did not exceed the proposed tolerance level of 0.15 ppm in 

strawberries. The residues ranged from 0.020-0.087 ppm.

860.1520 Processed Food and Feed

There are no processed food/feed commodities associated with the proposed uses on low 

growing berries. Therefore, data requirements pertaining to processed food and feed are not 

relevant to these tolerance petitions.

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 Theresa Cole, ACB, 6/21/11). 

acibenzolar metabolite (CGA210007), expiration date 1/31/2012

acibenzolar S-methyl (CGA245704), expiration date 3/1/2013

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 Thuy Nguyen at the 

following address:
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

Page 11 of 17

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 plant-back 

intervals (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.

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 CGA323060, 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 CGA210007 also occurs as an acyl sugar conjugate in rotational crops. Following hydrolysis, CGA210007 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.

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). HED has determined that acibenzolar-S-methyl + its metabolites convertible to 

GCA-210007 + CGA-324041 + CGA-323060 comprise the total toxic residue for acibenzolar-Smethyl 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 cerealgrain 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)
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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An adequate limited rotational crop study with wheat, turnips, and lettuce was previously 

submitted. The primary crops (leaf lettuce, pepper, squash, or turnips) received four foliar 

applications of the 50% DF formulation of acibenzolar-S-methyl, with a 7-day retreatment 

interval, at 0.094 lb ai/A per application for a total applied rate of 0.376 lb ai/A (3x the 

maximum proposed seasonal use rate for bulb onion; ~1x the maximum proposed seasonal use 

rate for cucurbit vegetables). Following harvest of the primary crops, rotational crops of winter 

or spring wheat, leaf lettuce, and turnips were planted 30, 60, and 180 days after the final 

treatment.

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. While tolerances are not needed for 

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. 

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 read as follows. 

Tolerances are established for residues of acibenzolar-S-methyl, benzo(1,2,3)thiadiazole-7-

carbothioic acid-S-methyl ester, including its metabolites and degradates, in or on the 

commodities in the table below. Compliance with the tolerance levels specified below is to be 

determined by measuring only those acibenzolar-S-methyl residues convertible to 

benzo(1,2,3)thiadiazole-7-carboxylic acid (CGA-210007), expressed as the stoichiometric 

equivalent of acibenzolar-S-methyl, in or on the commodity.

The results for strawberry indicate that following application of the test formulation according to 

the proposed use rate and PHI (0-day), the maximum residues of acibenzolar-S-methyl (i.e., 

residues convertible to CGA-210007) were 0.087 ppm in/on strawberry. The residue data was

entered into the OECD MRL Calculator. The available strawberry field trial data are deemed 

adequate to support a tolerance of 0.15 ppm for residues of acibenzolar-S-methyl in/on the low 

growing berry subgroup 13-07G.

The proposed tolerances are listed in Table 7, along with the tolerance level recommended by

HED. 
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

Page 13 of 17

There are no established Codex, Mexican, or Canadian maximum residue limits for acibenzolarS-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):

Berry, low growing

subgroup 13-07G

-- 0.15 0.15

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
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

Page 14 of 17

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

Attachments: 

International Residue Limit Status sheet

Appendix 1: Tolerance Assessment Calculations
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

Page 15 of 17

Appendix I. International Residue Limits.

Acibenzolar-s-methyl (061402; 03/29/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.561:

Plants: acibenzolar-S-methyl, 

benzo(1,2,3)thiadiazole-7-carbothioic acidS-methyl ester, including its metabolites 

and degradates, in or on the commodities in 

the table below. Compliance with the 

tolerance levels specified below is to be 

determined by measuring only those 

acibenzolar-S-methyl residues convertible 

to benzo(1,2,3)thiadiazole-7-carboxylic 

acid (CGA-210007), expressed as the 

stoichiometric equivalent of acibenzolar-Smethyl,

Livestock: Not established

1,2,3-benzothiadiazole-7-

carbothioic acid S -methyl 

ester, including the 

metabolite 1,2,3-

benzothiadiazole-7-

carboxylic acid

None

Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Berry, low growing, subgroup 

13-07G 0.15

Completed: M. Negussie; 03/31/2011

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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Appendix II. Tolerance Assessment Calculations.

Berry, low growing, subgroup 13-07G

The dataset used to establish a tolerance for acibenzolar-S-methyl on the Berry, low growing, 

subgroup 13-07G consisted of field trial data for strawberry (the representative crop of Berry, 

low growing, subgroup 13-07G), representing application rates of 0.188 lb ai/A (8 applications at 

0.0235 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 below.

Using the OECD MRL Calculator, the recommended tolerance is 0.15 ppm for Berry, low 

growing, subgroup 13-07G. 

Residues (mg/kg) n

0.021 1

0.024 1

0.026 1

0.029 1

0.039 1

0.045 1

0.0625 1

0.063 1

0.065 1

0.085 1
Acibenzolar-s-Methyl Summary of Analytical Chemistry and Residue Data DP#: 386364

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Acibenzolar s methyl

Berry, low growing, subgroup 13-07G

US

0-day

Total number of data (n) 10

Percentage of censored data 0%

Number of non-censored data 10

Lowest residue 0.021

Highest residue 0.085

Median residue 0.042

Mean 0.046

Standard deviation (SD) 0.022

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.085

- Mean + 4 SD 0.133

- CF x 3 Mean 0.138

Unrounded MRL 0.138

Rounded MRL 0.15