Document ID: EPA-HQ-OPP-2011-0086-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-04-11T04:00Z

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)  SEQ CHAPTER \h \r 1 	

  SEQ CHAPTER \h \r 1 

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

	

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 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.  

  SEQ CHAPTER \h \r 1 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 acibenzolar-S-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.

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 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

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

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

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.  

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 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:    SEQ CHAPTER \h \r 1 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 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-S-methyl 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.  

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 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-S-methyl 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:

	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.

 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 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.  

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):

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

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

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
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,

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.

Appendix II.  Tolerance Assessment Calculations.

Berry, low growing, subgroup   13-07G

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4 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

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

 	 

 

 

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

	Page   PAGE  16  of   NUMPAGES  17