### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM

DATE: October 23

, 2013

SUBJECT: Acibenzolar-S

- methyl: Human Health Risk Scoping Document in S upport of Registration Review

PC Code : 061402 Decision No.: 481700 Petition No.: None DP Barcode: 04138 32 Registration No

. : NA Regulatory Action: Registration Review Reregistration Case No. : NA Assessment Type : Single ChemicaV Aggrega t e TXR No.: None CAS No.: 135158-54-2 MRID No.: None 40 CFR: § 180.561



### F ROM:

THROUGH:

TO:

Introduction T hur ston Morton, Chemist ·

### ~ f

### ~**:?"'~**

# ,.**__.. ?/~~**  

# . 

# wt_

James Scott Miller, Environmental

# Scient**ist** "-

# ~ 

# »-

Abdallah Khasawinah

, Toxicologist Risk Assessme nt Branch 4 " 

### Health Effects Division (7509P)

# ~v.~~ Susan V. 

### Hummel, Senior Scientist
E li ssa Reaves, PhD., Branch Chief

## C~~ Risk Assessment Branch 

### 4, HED (7509P)

Dana Fr i e dman, Risk Manager Reviewer
Risk Management and Implementation Branch Pesticide Re-Evaluation Division (7508 P )

The Health Effects Division (HED) Acibenzo lar-S-me thy l Registration Review Team has eval uated the status of the human heal th risk assessmen t for acibenzolar to determine the

scope of work necessary to suppo rt Registration Review. Acibenzolar-S

- methyl is a plant act i vator. It i s a member of th e benzothiadia zo l e class of compounds. AcibenzolarS-methyl is registered to Syngenta Crop Protection, Inc for use on a number of leafy and fruiting vegetables crops and tobacco for the control or suppression of downy mildew,
black rot

, white rust

, bacterial leaf spot and speck, and blue mold. Permanent to lerances ranging from 0.1-3.0 ppm are estab li shed under § 180 .561(a). Acibenzolar-S -meth y l is
also used in commercial seed treatment operations for p rotection against certain early



### season seed and seed-borne nematodes in cotton and on ornamenta l s, sod farms, golf

courses, collegiate athletic fields, and lawns around commercial and industrial buildings

to control turf diseases. Acibenzolar

- S-methyl acts to protect plants against invading

Page 1 of20

### pathogens by inducing a natural defense reaction that enhances the plants ability to ward off disease. Agricultural applications may be made u si ng ground or aerial equ ipmen t. Acibenzolar-S-methy l is also registered for residential application to 

### turf grass using
handheld spray equipme nt. Based on the current use profile, exposures can be expected

to occur via the dietary (food and drinking water), as well as residential and occupational (handler and post-application) routes for acibenzolar.

The most recent risk assessment for acibenzolar was completed in 2012 (T. Morton; 0396885; 04 / 25 / 2012). This assessment exam i ned the proposed Experimental Use Permi t (Section 5 Reg i stration) for use of acibenzolar-S -m ethyl on apple, pear, and grapefruit, as well as all of the other currently registered uses of acibenzolar.
For acibenzolar-s-methyl, HED does not anticipate the need for an updated Turf
Trans ferabl e Residue (TTR) or Dislodgable Foliar Residue (DFR) study for the risk

assessment during registration review, since sufficien t margins of safety were met for a variety of residential and occupational post-application exposure scenarios.



### Hazard ldentificationffoxicology

The toxicology database for acibenzolar-S-methyl is adequate for evaluating and characterizing toxicity and se l ecting endpoints for purposes of this risk assessme n t. In subchronic and chronic oral stud ie s in rats, dogs and mice, signs of mild regenerative hemolytic anemia were consistently observed in all three species. Additio nal toxic effects observed in these studies included decreases in body weight, body weight gain and/or food consumption. No other significant treatment

- related effects of toxicological

concern were observed in these subchronic and chronic oral studies. No neurotoxic effects were seen at the highes t dose tested in a subchronic neurotoxicity study in rats. In

a 28 day dermal toxicity study in rats, no systemic or dermal effects were seen at the limit
dose. In a developmental toxicity and developmental neurotoxicity studies in rat s,
treatment related effects were observed in fetuses at levels that were not toxic to the parent indicating increased sensitivity of rat fetuses compared to adults. Increased
sensi tivity was not observed in a developmental toxicity study in rabbits, nor in 1- and 2- generation reproduction studies in rats. In a 28 day dermal developm ental toxicity study
in rats, no maternal or developmental toxicity was observed at dose levels up to 500 mg/kg/day, the highest dose level tested.

Acibenzolar-S- m ethyl was classified by HED ' s Hazard Identification Assessmen t Review Committee (HIARC) as "not likely" to be a human carcinogen based on negative carci no genicity findings in male and fema l e rats and mice and negative results in an acceptable battery of genotoxicity stud i es. Acibenzo lar-S-m ethyl showed no significant

tox icity in a battery of acute toxicity tests (Toxicity Category III or IV in all tests) but showed considerable sk in-sens i tivity. The end -u se product (ActigardTM 50WG) displayed no significant acute toxicity and no dermal sensitizing potential. In an imrnunotoxicity study Acibenzolar-S -m ethyl did not produce systemic toxicity or immunotoxicity at any dose (0, 15, 75, 406 mlk/d) including the highest dose tested.
Based on the weight

- of-evidence (WOE)

, the HED Hazard and Science Policy Council (HASPOC) waived the requirement for a 28-day inhalation toxicity study (TXR0056450).

Page 2 of20

### Page 3 of 20

The Points of Departures (PoDs) and endpoints of concern used for dietary and non

dietary (occupational and residential) risk assessments are presented in Table 1

. The PoDs, endpoints , UFs, a nd Food Quality Protection Action ( FQPA ) Safety Factors will be re

- evaluated during the preparation of the registration review risk assessment.

Conclusion s for Toxicology

T he toxicology database for acibenzolar

- S

- methyl is adequate for evaluating and characterizing toxicity and selecting endpoints for purposes of this risk assessment. No additional studies are required at this time.

Residue Chemistry The existing residue chemistry database for acibenzolar is adequate for risk assessment purposes. No additional data are required during the registration review process. The qualitative nature of the residue(s) of acibenzolar in plants and livestock is understood

. Nature of the residue studies in three diverse crops ha ve been submitted ( lettuce, tomato, rice, wheat, and tobacco )

. The residues of concern in plants and animals for tolerance expression are residues convertible to benzo(1,2,3)thiadiazole

- 7

- carboxylic acid (CGA

210007), expressed as acibenzolar

- S

- methyl. F or purposes of risk assessment, residues of the 4

- and 5

- hydroxy metabolites (CGA

- 324041 and CGA

- 323060) of CGA

- 210007 should also be considered.

Dietary Exposure and Risk Assessment The acibenzolar dietary exposure database is adequate to support the existing registrations

. For the 2012 risk assessment, refined acute and screening

- level chronic dietary and drinking water exposure and risk assessments were conducted for acibenzolar using DEEM

- FCID. The acute analysis assumed a distribution of residues based on field trial data and tolerance values for apple, pear, and grapefruit. Empirical and DEEM default processing factors were used to modify the field trial data. M aximum screening

level percent crop treated estimates were used for commodities for which data were available. If no percent crop treated data were available, 100% crop treated was assumed. The acute analysis incorporated the 1 in 10 year peak surface drinking water estimate f rom application of acibenzolar

- S

- methyl to cucurbit vegetable s. Tolerance level residues and 100 crop treated assumptions were used for the chronic dietary assessment. The results of aggregate dietary (food + drinking water) analysis show that the acute and chronic dietary risk for the general U.S. population and a ll population subgroups are below HED’s level of concern (<100% acute Population Adjusted Dose (aPAD) and chronic Population Adjusted Dose (c PAD ) ).

Conclusions for Dietary Exposure The acibenzolar

- S

- methyl residue chemistry database is complete and adequate to support registration review. During registration review, updated dietary exposure assessments may be conducted if there are any significant changes to the toxicolog ical PODs or FQPA and other uncerta inty factors ( UFs ) . In addition, any significant changes to the estimated drinking water concentrations ( EDWCs ) may also necessitate changes to the dietary assessment

.

### Page 4 of 20

Residential Exposure and Risk Assessment Acibenzolar

- S

- Methyl is currently registered for use on lawns, and landscape ornamentals and for weed control on non

- cropland areas by commercial applicators and homeowners. Residential handler and post

- application exposures were assessed to reflect changes to the Standard Operating Procedures (SOPs ) , body weight parameters, and toxicological information. Updated residential handler and post

- application risk estimate s for the most conservative exposure scenarios (Handler: backpack sprayer margin of exposure ( MOE ) = 165 and Post

- Application for high contact lawn activities MOE = 1,100) do not exceed HED’s level of concern (MOEs ≥ 100) and therefore not of
concern to HED. Furthermore, HED does not anticipate the need for an updated TTR or DFR study for the risk assessment during registration review, whereas sufficient margins of safety were met for a variety of residential post

- application exposure scenarios. In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a pesticide has residential or occup ational uses that could result in post

- application dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure
Assessmen t , HED analyzed a number of DFR studies and selected a new default value for the fraction of the application rate available to be dislodged after a foliar application (F AR 

### ). This default value is 25%. Of the analyzed DFR studies, the maximum F AR 

### value seen was 89% or 3.6 times higher than the defa ult residue transfer value. Therefore, a calculated MOE of approximate ly 4 times higher than the LOC, i.e. an MOE > 400 if the LOC = 100, using the default dislodged residue value would provide an adequate margin of safety for any potentially higher resid ues seen in a chemical

- specific DFR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies . 6/7/2012, Exposure Science Advisory Council ). The most conservative post

- application exposure scenario resulted in an MOE of 1,100, therefore, HED does not anticipate the need for an updated TTR or DFR study.

Residential exposures result ing from off

- site transport (i.e ., spray drift or volatilization) may occur as a result of agricultural applications of acibenzolar

- S

- methyl . The Agency is in the process of evaluating these types of exposures and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate these post

- application ex posures into the Agency's risk assessments. The need for spray drift and volatilization risk assessment for acibenzolar

- S

- methyl will be examined during Registration Review

.

Conclusions for Residential Exposure

Residential handler and post

- application e xposures were assessed for the 2012 risk assessment to reflect changes to the SOPs , body weight parameters, and toxicological information. A quantitative exposure/risk assessment for direct residential application may be necessary during registration review to update changes to the SOPs. The potential for r esidential exposures resulting from off

- site transport (e.g., spray drift or volatilization) may need to be quantitatively evaluated for acibenzolar

- S

- methyl during the registration review process. HED does not anticipate the need for an updated TTR or DFR study for the risk assessment during registration review.

### Page 5 of 20

Aggregate Exposure and Risk Assessment The acute aggregate risk estimates associated with exposure to acibenzolar are equivalent to the acute dietary risk estimates. The acute dietary risk estimates from the 2012 risk

assessment do not exceed HED’s level of concern. Acute dietary risk estimates are not of concern for general population or other population subgroups. The subgroup with th e highest risk estimate was children 3

- 5 years old with a 99.9 th 

### percentile acute exposure estimate of 37% of the acute Population Adjusted Dose (aPAD). The 99.9 th 

### percentile aPAD for the general U.S. population was 18%.

A short

- term aggregate risk ass essment was conducted for acibenzolar. The short

- term aggregate ( the highest residential exposure was combined with background food and water exposure) risk estimates from the 2012 risk assessment does not exceed HED’s level of concern (MOEs ≥ 100 ). The MOE for short

- term aggregate risk for residential handlers was 700. MOEs for short

- term aggregate risk for residential post

- application

exposure were 700

- 1600. MOEs are protective for all exposure scenarios.

Chronic exposure is not expected for the re sidential exposure pathway. Therefore, the chronic aggregate risk would be equivalent to the chronic dietary exposure estimate. The chronic d ietary risk estimates from the 2012 risk assessment do not exceed HED’s level of concern.

Conclusions for Aggreg ate Exposure and Risk

In the 2012 risk assessment, there were no aggregate (food and water) risk estimates of concern for acibenzolar

- S

- methyl. During registration review, updated aggregate assessments may be conducted as required to include any significant change that might

o ccur for toxicological PODs, FQPA and uncertainty factors, dietary exposure estimates, or EDWCs. Emerging policies related to pesticide drift and volatilization assessments may dictate further changes to the existing aggregate risk assessment.

Occupati onal Exposure and Risk Assessment There is a potential for short

- and intermediate

- term occupational exposure to acibenzolar

- S

- m ethyl during mixing, loading, application, and post

- application activities, however chronic exposure is not expected

. Acibenzola r

- S

- methyl is registered for use on a number of crops including leafy and fruiting v egetables , low growing berries, pome fruit, citrus, and tobacco. Acibenzolar

- S

- methyl is also used in commercial seed treatment operations on cotton, and on turf for sod farms, golf courses, collegiate athletic fields, and lawns around commercial and industrial buildings to control turf diseases. Agricultural a pplications may be made using ground (including handheld) or aerial equipment. Formulations for acibenzolar

- s

- methyl include a water dispersible granule and a flowable concentrate.

HED updated the previous occupational handler exposures and the 2012 Experimental Use Permit (EUP) r equest for apples, pears, and grapefruit to reflect current use information and po licies. The results of the most conservative occupational handler exposures assessed (Backpack: mixing/loading/applying to turf; MOE = 320 and Aerial mixing /loading MOE = 730) indicate that risks do not exceed HED’s level of concern (MOEs ≥ 100).

### Page 6 of 20

S hort

- and intermediate

- term exposure to acibenzolar

- S

- methyl during post

- application activities is expected for individuals involved in hand weeding, thinning, harvesting

, s couting, transplanting, raking, and irrigation activities. Also, for turf; specific act ivities include general maintenance around golf course greens, fairways and tee boxes; collegiate athletic fields, and lawns around commercial and industrial buildings . Sod farm post

- application activities include slab and roll harvesting. The results of t he occupational post

- application exposure assessment for the most conservative exposure scenarios (leafy vegetables; scouting/hand harvesting and weeding with full density MOE = 620 and pome fruit; thinning fruit with full density MOE = 730) indicate that risks do not exceed HED’s level of concern (MOEs ≥ 100).

HED does not anticipate the need for an updated TTR or DFR study for the risk assessment during registration review, since sufficient margins of safety were met for a variety of occupational post

- application exposure scenarios. This approach is documented in an HED HASPOC document entitled Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies (dated 6/7/12).

Conclusions for Occupational Exposure

An updated occupational handler assessment was conducted for the 2012 risk assessment. The occupational handler assessment may need to be updated under registration review if

w arranted to reflect the most recent occupational handler surrogate exposure data 1 

### and by any significant change in exposure assessment methodology, toxicological PODs, or UFs

. Furthermore, HED does not anticipate the need for an updated TTR or DFR study f or the risk assessment during registration review.

P ublic Health and Pesticide Epidemiology Data OPP’s Incident Data System ( IDS ) includes reports of alleged human health incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports from registrants, other federal and state health and environmental agencies, an d individual consumers. Since 1992, OPP has compiled these reports in IDS. IDS contains reports from across the U.S. and most incidents have all relevant product information recorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in the report. It should be noted there are three incidents reported as lawsuits to IDS that are not considered in this report.

IDS records incidents in one of two modules: Main IDS and Aggregate IDS:

o Main IDS contains incidents resulting in higher severity outcomes and provides more detail with regard to case specifics. This system stores incident data for death, major and moderate incidents, and it includes information about the location, date and na ture of the incident. Main IDS

1 O utlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ” available at http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

### Page 7 of 20 incidents involving only one active ingredient (as opposed to pesticide products with multiple active ingredients) are considered to provide more certain information about the potential effects of exposure from the pesticide

.

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, or no effects outcomes). These are reported by registrants only as counts in what are aggregate summaries.

For the M ain IDS, from January 1, 200 8 to June 11, 2 013, there were no incidents reported in the database involving acibenzolar

.

In A ggregate IDS , from January 1, 200 8 to June 11, 2013, there was one reported incident involving acibenzolar

.

The SENSOR

- Pesticides database covers 11 states from 1998

- 2009, although reporting varies from state to state. Cases of pesticide

- related illnesses are ascertained from a variety of sources, including: reports from local Poison Control Centers, state Department of Labor workers’ compensation claims when reported by ph ysicians, reports from State Departments of Agriculture, and physician reports to state Departments of Health. Although both occupational and non

- occupational incidents are included in the database, SENSOR

- Pesticides focuses on occupational pesticide incid ents, and is of particular value in providing that information. The state coordinator at each of the 11 respective state Departments of Health conducts case follow

- up activities such as obtaining medical records to verify symptoms and severity. Using sta ndardized protocol and case definitions derived from poison center reporting, the state SENSOR

- Pesticide coordinator enters the incident information into the state

- based system which is sent to NIOSH annually to be aggregated.

A query of SENSOR

- Pesticide s 1998

- 2009 finds no cases involving acibenzolar.

The Agricultural Health Survey ( AHS ) is a high quality

, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. The AHS includes private and c ommercial pesticide applicators and their spouses . If there are AHS findings relevant to a particular pesticide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase of the process and, if ap propriate, fully reviewed in the risk assessment phase of the process

. The AHS includes information on use of 50 different pesticide active ingredients commonly used in agriculture. Acibenzolar is not included in the AHS, and therefore this study does not provide information for this report.

Based on the low frequency and severity of incident cases reported for acibenzolar in both IDS and SENSOR

- Pesticides

, there does not appear to be a concern at this time that would warrant further investigation

. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk

assessment.

### Page 8 of 20

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180. 561 for residues of acibenzolar

- S

- methyl

, including its metabolites and degradates, in or on a variety of commodities

. The Codex Alimentarius Commission and Mexico have not established maximum residue limits (MRLs) for acibenzolar

. Included in Table 6 are the M RLs harmonized with Canada. Any acibenzolar tolerances reassessed during the registration review process will be considered for possible harmonization with international MRLs should they be established. (see Table 6 )

The current tolerance expression as listed in the 40 CFR§180. 5 61 (a ) has been updated to reflect current HED policies and thus will not need to be revised during the reg istration review process.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possib le, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

Income Populations," http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf

. 

### The Office of Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use of a pesticide when conducting h uman health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these high exposures indicate potential risks of concern, OPP will further refine the risk assessments to ensure that the risk estimates are based on the best available information.

Cumulative Risk Assessment

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to acibenzolar and any other substances and acibenzolar does not appear to

pro duce a toxic metabolite produced by other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by E PA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http ://www.epa.gov/pesticides/cumulative/

.

Human Studies

The 2012 acibenzolar r isk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. Studies such as the Pesticide Handle rs Exposure Data base and the Agricultural Handler Exposure Task Force, have been reviewed by the Agency and found on the basis of available evidence to have been neither fundamentally unethical nor significantly deficient relative to standards

### Page 9 of 20

of ethical r esearch conduct prevailing when they were conducted. There is no barrier in EPA's "Protection of Human Subjects" Regulation to reliance on these studies.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxic ity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturat ion, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for acibenzolar

- S

- methyl

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408( p), acibenzolar

S

- methyl is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estr ogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which , if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T ef fect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 iner t ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 2 

### and includes some pesticides scheduled for Registration Review and chemicals found in

water

. For further information on the status of the EDSP, the pol icies and procedures, the list s of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 3



### In the interim, EPA is making no human health or environmental safety findings associated with the EDSP screening of acibenzolar

- S

- methyl . Before completing this

2 See http://www.regul ations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

3 http://www.epa.gov/endo/

### Page 10 of 20

Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.

Data R equirements

HED does not anticipate that additional residue chemistry , exposure, or toxicology data will be required for the acibenzolar

- S

- methyl registration review process

.
Barring submission of any data that would impact the outcome of the 2012 risk assessment, HED does not anticipate the need for any updates to the acibenzolar

- S

methyl risk assessment during registration review.

### Page 11 of 20

Table 1. Toxicological Doses and Endpoints for Past Acibenzolar

- s - Methyl Human Health Risk Assessment ( D 396885; 04/25/2012 ).

Exposure/ Scenario Point of

Departure Uncertainty/F

QPA Safety Factors RfD, PAD,

LOC for Risk Assessment Study and Toxicological Effects

Acute Dietary (General Population) NOAEL =

8.2 mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x Acute RfD =

0.082 mg/kg/day aPAD = 0.082 mg/kg/day Developmental Neurotoxicity Toxicity

-

Rat Developmental LOAEL = 82 mg/kg/day based on changes in brain morphometrics in the cerebellum in offspring.

Maternal LOAEL = was not observed NOAEL = 326.2 mg/kg/day HDT

Chronic Dietary (Females 13

- 49 years & Young Children) NOAEL =

8.2 mg/kg/day UF A = 10x.

UF H =10x FQPA SF= 1x Acute RfD =

0.082 mg/kg/day aPAD = 0.082 mg/kg/day Developmental Neurotoxicity Toxicity

-

Rat Developmental LOAEL = 82 mg/kg/day based on changes in brain morphometrics in the cerebellum in offspring.

Maternal LOAEL = was not observed NOAEL = 326.2 mg/kg/day HDT

Chronic Dietary (Adult Males and Females 50+ yrs) NOAEL =

25 mg/kg/day UFA= 10x

UFH=10x FQPA SF= 1x Chronic RfD =

0.25 mg/kg/day cPAD = 0.25 mg/kg/day Chronic Toxicity

- Dog; Co

- critical;

Chronic/Cancer

- Rat & Mouse, Reproduction Toxicity

- Rat LOAEL = 105 mg/kg/day based on hemolytic anemia with compensatory

response.

Incidental Oral NOAEL=

8.2 mg/kg/day UF A = 10x

UF H =10x Occupational

LOC for MOE = 100 Developmental Neurotoxicity Toxicity

-

Rat Developmental LOAEL = 82 mg/kg/day based on changes in brain morphometrics in the cerebellum in offspring.

Maternal LOAEL = was not observed NOAEL = 326.2 mg/kg/day HDT Cancer (all routes) A “not likely” human carcinogen

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (i nterspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence o f key date (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c =
chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applic 

### able.

### Page 12 of 20

Table 2 . Toxicological Doses and Endpoints for Past Acibenzolar

- s - Methyl Human Health Risk Assessment ( D 396885; 04/25/2012 ). Exposure/ Scenario Point of

Departure Uncertainty

Factors LOC for Risk

Assessment Study and Toxicological Effects

Dermal Short (1

- 30 days) and Intermediate (1

- 6 months)
Term DAF = 4 4 % NOAEL=

8.2 mg/kg/day UF A = 10x

UF H =10x Occupational

LOC for MOE = 100 Developmental Neurotoxicity Toxicity

-

Rat Developmental LOAEL = 82 mg/kg/day based on changes in brain morphometrics in the cerebellum in offspring.

Maternal LOAEL = was not observed NOAEL = 326.2 mg/kg/day HDT

Inhalation Short (1

- 30 days) and Intermediate (1

- 6 months)
Term NOAEL=

8.2 mg/kg/day UF A = 10x

UF H =10x Occupational

LOC for MOE = 100 Developmental Neurotoxicity Toxicity

-

Rat Developmental LOAEL = 82 mg/kg/day based on changes in brain morphometrics in the cerebellum in offspring.

Maternal LOAEL = was not observed NOAEL = 326.2 mg/kg/day HDT Cancer (all routes) A “not likely” hum an carcinogen

DAF = Dermal Absorption Factor

. Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure (100% absorption factor).

### Page 13 of 20

Table 3 Subchronic, Chronic and Other Toxicity Profile for Acibenzolar

- S

- methyl from last assessment

Guideline No. Study Type MRID No. (year) Classification Dose Levels Results

870.3100 90

- day oral toxicity rodents (rat) 44014230 (1993) Acceptable/Guideline M : 0, 2.42, 24.6, 126, 516 mg/kg/day; F: 0, 2.64, 26.3, 131, 554 mg/kg/day NOAEL :126 mg/kg/day Males or M); 131 mg/kg/day (Females or F) LOAEL :516 mg/kg/day (M); 554 mg/kg/day females based decreased body weight, reduced food intake and efficiency and increased liver and spleen weights

870.3150
90

- day oral toxicity non

rodents (dog) 44014232 (1994) Acceptable/Guideline M & F: 0, 10, 50, 200 mg/kg/day (capsules) NOAEL :50 mg/kg/day (M & F)
LOAEL :200 mg/kg/day (F) based on regenerative hemolytic anemia evidenced by decreased erythroid parameters, pigmentation in the liver and spleen, splenic congestion, and by activation of medullary (bone marrow) and extramedullary (splenic) erythropoiesis.

870.3100
90

- day oral toxicity rodents (mice) 44014228 (1993) Acceptable/Guideline 0, 30.6, 152, and 624 mg/kg/day for males, and 0, 47.4, 220, and 803 mg/kg/day for females, respectively. NOAEL : 30.6 mg/kg/day (M); 47.4 mg/kg/day (F)
LOAEL :152 mg/kg/day (M); 220 m g/kg/day females based decreased body weight and body weight gain, increased spleen weight and microscopic changes in the spleen

870.3200 21/28

- day dermal toxicity (rat) 44014233 (1994) Acceptable/guideline M & F: 0, 10, 100, 1000 mg/kg/day NOAEL = 1000 mg/kg/day LOAEL = not identified

870.3700a Developmental Toxicity in rodents (rat) 44014236 (1994) Acceptable/guideline F: 0,10, 50, 200, 400 mg/kg/day Maternal NOAEL 200 mg/kg/day Developmental NOAEL 50 mg/kg/day Maternal LOAEL 400 mg/kg/day based on clinical signs of hemorrhagic perineal discharge Developmental LOAEL 200 mg/kg/day based on developmental malformations, anomalies, and skeletal variations

870.3700a Developmental Toxicity in rodents (rat) 45089701 (1998) Acceptable/guideline
of 0, 10, 75, 150, or 350 mg/kg/day Maternal NOAEL 350 mg/kg/day Developmental NOAEL 200 mg/kg/day Maternal LOAEL

– not established (>350) Developmental LOAEL 350 mg/kg/day based on increased incidences of rudimentary and long lumbar ribs

870.3700b Developmental Toxicity in

non

- rodents (rabbit) 44014237 (1994) Acceptable/guideline F: 0, 10, 50, 300, 600 mg/kg/day Materna l NOAEL = 50 mg/kg/day LOAEL = 300 mg/kg/day based on mortality, clinical signs of toxicity, decreased maternal body weight and food consumption. Developmenta l NOAEL = 300 mg/kg/day LOAEL = 600 mg/kg/day based on a marginal increase in vertebral anomalies.

870.6300 Developmental Neurotoxicity Toxicity in rodents (rat) 46046401 (2002) Acceptable/non

- guideline
0/0, 8.2/15.5, 82.0/153.6, and 326.2/607.8 mg/kg/day [gestation/lactation]. Maternal NOAEL 326.2 mg/kg/day Developmental NOAEL 8.2 mg/kg/day Maternal LOAEL Not Observed Developmental LOAEL 82 based on changes in brain morphometri cs in the cerebellum

### Page 14 of 20

Table 3 Subchronic, Chronic and Other Toxicity Profile for Acibenzolar

- S

- methyl from last assessment

Guideline No. Study Type MRID No. (year) Classification Dose Levels Results

870.3800 Reproduction and fertility effects in rats 4014241 (1995) Acceptable/guideline M & F: 0, 1

- 3, 11

- 31, 105

- 288, 223

- 604 mg/kg/day Parental/Systemic NOAEL = 11

- 31 mg/kg/day LOAEL = 105

- 288 mg/kg/day based on increased weights and hemosiderosis of the spleen. Reproductive NOAEL = 223

- 604 mg/kg/day LOAEL > 223

- 604 mg/kg/day based on no effects. Offspring NOAEL = 11

- 31 mg/kg/day LOAEL = 105

- 288 mg/kg/day based on reduced pup body weight gains and lower pup body weights during lac tation.

870.6200b Subchronic Neurotoxicity 45713601 (1997) acceptable/nonguideline pending submission of positive control data for neuropathological and FOB

assessments 0/0, 24/26, 126/143, and 575/628 mg/kg/day [M/F], respectively The study may be upgraded pending submission of acceptable positive control data. NOAEL 126/143 mg/kg/day, M/F
LOAEL 575/628 mg/kg/day, M/F based on decreased body weights, body weight gains, and food consumption

.

870.4100 Chronic toxicity in dogs 44014234 (1996) Acceptable/guideline
M & F: 0, 5, 25, 200 mg/kg/day (capsules) NOAEL 25 mg/kg/day LOAEL 200 mg/kg/day based on hematological effects, hemosiderosis of the liver and spleen, extraniedullary hematopoiesis in the spleen, and increases in liver weight.

870.43 00 Chronic toxicity/ carcinogenicity in rodents (mice) 44014325 (1996) Acceptable/guideline
M: 0, 1.14, 11.1, 237, 698 mg/kg/day F: 0, 1.14, 10.8, 234, 696 mg/kg/day NOAEL 11.1/10.8 mg/kg/day, M/F LOAEL 237/234 mg/kg/day based on mild hemolytic anemia and related microscopic changes (hemosiderosis) in the spleen, liver, and bone marrow and extramedullary hematopoiesis in the spleen.

870.4200 Carcinogenicity study in rat 44014243 (1996) Acceptable/guideline
M: 0, 0.77, 7.77, 96.9, 312 mg/kg/day F: 0, 0.90, 9.08, 111, 388 mg/kg/day NOAEL 96.9/111 (M/F) LOAEL 312/388 / 191.0 mg/kg/d (M/F) based on decreased body weights, body weight gain and food efficiency, mild hemolytic anemia, and incre ased incidence of alveolar foam cells (females only).

870.5100 Bacterial reverse mutation assay (Ames test) 44014247 (1993) Acceptable/guideline 312.5, 625, 1250, 2500, 5000 g/plate Negative with and without S

- 9 activation at 5000 g/plate and less.

870.5100 Bacterial reverse mutation assay (Ames test) Test Material: CGA

- 362020 (isomer of acibenzolar

- S

methyl) 44537025 (1998) Acceptable/guideline
61.73 to 5000 g/plate (+S

- 9)
30

- 86 to 2500 g/plate (

- S

- 9) Positive in S. typhimurium strain TA1537 at 2 77.8 g/plate and higher in the absence of S

- 9. Negative with S

- 9 activation at 5000 g/plate and less.

### Page 15 of 20

Table 3 Subchronic, Chronic and Other Toxicity Profile for Acibenzolar

- S

- methyl from last assessment

Guideline No. Study Type MRID No. (year) Classification Dose Levels Results

870.5100 Bacterial reverse mutation assay (Ames test) Test Material: NOA

- 419191 (by

- product of acibenzolar

- S

methyl) 44537024 (1998) Acceptable/guideline
312.5 to 5000 g/plate (± S

- 9) Negative with or without S

- 9 activation at 5000 g/plate and less

870.5100 Bacterial reverse mutation assay (Ames test) Test Material: CGA

- 323060 (plant metabolite of acibenzolar

- S

- methyl) 44537026 (199 7) Acceptable/guideline
312.5 to 5000 g/plate (± S

- 9) Negative with or without S

- 9 activation at 5000 g/plate and less

870.5300
In vitro mammalian gene mutation assay 44014246 (1993) Acceptable/guideline
3.70 to 100 g/ml (

- S

- 9),
37.04 to 1000 g/ml (+S

- 9) Negative with S

- 9 activation up to 1000 g/ml. Negative without
S

- 9 activation up to 100 g/ml. Compound tested to cytotoxic concentrations.

870.5375
In vitro mammalian chromosome aberration (CHO cells) 44014245 (1993) Acceptable/guideline
7.5 to 6 0 g/ml (

- S

- 9 and +S

9) Suggestive of clastogenicity in the absence of S

- 9 activation at 30
and 60 g/mL at the 18

- hour cell harvest time; effect observed only in the presence of cytotoxicity. Increase in polyploid cells at 30
and 60 g/mL at the 42 hour harvest time both with and without S

9. Evidence of cell cycle arresting activity at G 2 . 870.5395 Mammalian erythrocyte micronucleus test 44014244 (1993) Acceptable/guideline 1000, 2000, 4000 mg/kg (oral gavage) Negative at 16, 24, and 48, hour sacrifices.

870.5550 UDS in primary rat hepatocytes 44014248 (1993) Acceptable/guideline
9.77 to 500 g/ml Negative at 500 g/ml and less.

870.7485 Metabolism and pharmacokinetics

rats 44014250 (1995) Acceptable/guideline 0.5, 100 mg/kg Following oral treatment of rats, acibenzolar

- S

- methyl was rapidly and nearly completely (>90% of administered dose) absorbed from the gastrointestinal tract into the general circulation. The majority (88

- 95%) of the administered dose was excreted in t he urine within the first 48 hours. The major metabolite (79

- 92%) in the urine was the carboxylic acid derivative of the parent.
870.7600 Dermal penetration 47430503 (1995) Acceptable/guideline 10 μg/cm2 and 100μg/cm2 An estimate of dermal absorption ba sed on the results from the low dose group (10 μg/cm2), was derived. Mean dermal absorption for this group of animals where the skin was washed after 8 hours of exposure was 43.55%. Special studies :

28

- Day dietary

rats 44014227 (1992) Acceptable/ nonguideline M: 0, 45.9, 403, 1070 mg/kg/day; F: 0, 44.8, 376, 1000 mg/kg/day NOAEL = M: 403 mg/kg/day; F: 376 mg/kg/day LOAEL = M: 1070 mg/kg/day; F: 1000 mg/kg/day based on decreased mean body weights, decreased liver weights, altered hematology param eters accompanied by increased spleen weights.

28

- Day oral gavage

rats 44014229 (1993) Acceptable/nonguideline 0, 10, 100, 800 mg/kg/day NOAEL = 100 mg/kg/day LOAEL = 800 mg/kg/day based on decreased body weights, and decreased hemoglobin

- related parameters accompanied by hemosiderosis of the spleen, increased liver and spleen weights, and decreased thymus weights.

### Page 16 of 20

Table 3 Subchronic, Chronic and Other Toxicity Profile for Acibenzolar

- S

- methyl from last assessment

Guideline No. Study Type MRID No. (year) Classification Dose Levels Results

28

- Day oral capsule dogs 44014231 (1994) Acceptable/nonguideline 0, 50, 250, 500 mg/kg/day NOAEL = 50 mg/kg/day LOAEL = 250 mg/kg/day based on decreased body weight, decreased hemoglobin

- related parameters, hepatic and splenic hemosiderosis.
90

- Day Dietary mice 44014228 (1993) Acceptable/nonguideline M: 0, 30.6, 152, 624 mg/kg/day; F: 0, 47.4, 220, 803 mg/kg/day NOAEL = M: 30.6 mg/kg/day; F: 47.4 mg/kg/day LOAEL = M: 152 mg/kg/day; F: 220 mg/kg/day based on decreased mean body weights and body weight gain in males, increased spleen weights and splenic histopathology in both sexes.

90

- Day Dietary dog 44014232 (1994) Acceptable/ nonguideline 0, 10, 50, or 200 mg/kg/day NOAEL = 50 mg/kg/day LOAEL = 200 mg/kg/day in male and female dogs, based on regenerative hemolytic anemia evidenced by decreased erythroid parameters, pigmentation in the liver and spleen, splenic congestion, and by activation of medullary (bone marrow) and extramedullary (splenic) erythropoiesis.
90

- Day Dietary

rat 44014230 (1993) Acceptable/nonguideline males: 0,2.42, 24.6, 126, or 516 mg/kg/day; females: 0,2.64,26.3, 131, or 554 mg/kg/day) NOAEL = 126 mg/kg/day in males and 131 mg/kg/day in females LOAEL = 516 mg/kg/day males and 554 mg/kg/day females based on decreased mean body weights, reduced food intake, reduced food efficiency, and increased liver and spleen weights with correlates for the liver and spleen of glycogen deposition and hemosiderosis, respectively. Special Developmental toxicity

rats 44014238 (1994) Acceptable/nonguideline 300 mg/kg/day, GD 6

- 15, 6

- 7, 8

- 9, 10

- 11, 12

- 13, or 14

- 15 Maternal and developmental NOAELS and LOAELS could no t be identified by this protocol. The most pronounced maternal and developmental toxicity occurred when dams were treated on GD 6

- 15. Special Developmental toxicity

rats 44014239 (1994) Acceptable/nonguideline 400 mg/kg/day, GD 6

- 7, 8

- 9, 10

- 11, 12

- 13, or 14

- 15 Maternal and developmental NOAELS and LOAELS could not be identified by this protocol. The most pronounced maternal and developmental toxicity occurred when dams were treated on GD 6

- 7 and 8

- 9. Dermal developmental toxicity

rats 44014240 (1994) Ac ceptable/nonguideline 0, 10, 100, 500 mg/kg/day, GD 6

- 15 Maternal NOAEL 500 mg/kg/day LOAEL >500 mg/kg/day based on no effects. Developmental NOAEL 500 mg/kg/day LOAEL >500 mg/kg/day based on no effects. Range

- finding
1

- generation reproduction

rats 44681301 (1993) Acceptable/nonguideline 0, 199

- 209, 382

- 410, 700

- 728 mg/kg/day Parental/Systemic NOAEL = 209 mg/kg/day LOAEL = 410 mg/kg/day based on decreased body weight gain and food consumption in females. Reproductive NOAEL = 410 mg/kg/day LOAEL = 72 8 mg/kg/day based on total resorptions in all dams. Offspring NOAEL = 209 mg/kg/day LOAEL = 410 mg/kg/day based on reduced pup body weight gains and lower pup body weights during lactation.

### Page 17 of 20 Table 4. Guideline Data Requirements
Guideline No. Study Type Technical MRID No. Required Submitted
870.1100 870.1200 870.1300 870.2400 870.2500 870.2500 Acute Oral Toxicity

................................ ................................ ..........

Acute Dermal Toxicity

................................ ................................ ..... Acute Inhalation Toxicity

................................ ................................ . Primary Eye Irritation

................................ ................................ ....... Primary Dermal Irritation

................................ ................................ . 870.2600 Dermal Sensitization yes yes yes yes yes yes yes

yes yes yes yes yes 44014214

44014216 44014219 44014220 44014220 44014225

870.3100

870.3150 870.3200

870.3250 870.3465 Subchronic (Oral) Toxicity

- Rodent

................................ ...............................

Subchronic (Oral) Toxicity

- Non

- Rodent

................................ ....................... 21/28

- Day Dermal Toxicity

................................ ................................ ............

90

- Day Dermal Toxicity 90

- Day Inhalation Toxicity

................................ ................................ ............ Y

Y
N

N
N * Y

Y
Y

N
N 44014230

44014228 44014232 42090013 46950310

---

---

870.3700a

870.3700b 870.3800 Prenatal Developmental Toxicity

- Rodent

................................ .....................

Prenatal Developmental Toxicity

- Non

- Rodent

................................ ............. Reproduction and Fertility Effects

................................ ................................ .. Y

Y
Y Y

Y
Y 44014236

45089701 44014237 44014241
870.4100a 870.4100b 870.4200a 870.4200b 870.4300 Chronic (Oral) Toxicity

- Rodent

................................ ................................ ....

Chronic (Oral) Toxicity

- Non

- Rodent (Dog)

................................ ................. Carcinogenicity

- Rat..................

................................ ............................... Carcinogenicity

- Mouse Combined Chronic Toxicity /Carcinogenicity Y
Y
Y
Y
Y Y

Y
Y
Y
Y 44014325

44014234 44014243 44014325 44014325
870.5100

870.5300

870.5375

870.53 95

870.555 0 Mutagenicity

— Gene Mutation

- bacterial

................................ .......................

Mutagenicity

— Gene Mutation

- mammalian

................................ .................. Mutagenicity

— Structural Chromosomal Aberrations

................................ ................................ ....................... Mammalian erythrocyte micronucleus test

.......

Mutagenicity

— UDS rat primary hepatocytes

................................ ................. Y
Y
Y

Y

Y Y

Y
Y

Y

Y 44014247

44014246

44014245

44014244

44014248

870.6100a 870.6100b 870.6200a 870.6200b 870.6300 870.7800 Neurotoxicity

- Acute Delayed Neurotox.

- Hen

................................ ..............

Neurotoxicity

- Subchronic

- Hen

................................ ................................ .. Neurotoxicity

- Acute

- Rat

................................ ................................ ............. Neurotoxicity

- Subchronic

- Rat

................................ ................................ ..... Developmental Neurotoxicity.................. Immunotoxicity.............................

................................ ......................... N
N
Y
Y
N
Y N

N
Y
Y
Y
Y ---

---

--- 45713601 46046401 48688301
*The 28

- day inhalation study was waived by HASPOC ( TXR No.: 0056450).

### Page 18 of 20

Table 5 . 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, pK
a No dissociation constant in an accessible pH ran ge (1.0

- 9.0) European Commission, 6506/VI/99

- final, 5/21/02 Octanol/water partition coefficient, Log(K OW ) Log (P OW ) 3.1 at 25 oC DP# 250963, 2/10/99, H. Podall

UV/visible absorption spectrum 253 nm ε : 14.7 10 3 l mol - 1 cm - 1

288 nm ε : 5.4 10 3
324 nm ε : 7.2 10 3 European Commission, 6506/VI/99

- final, 5/21/02

### Page 19 of 20

Table 6 . Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 

### 40 CFR 180.561:

Plants: (a) General. (1)

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

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 2 Codex

Banana 1 0.1 0.1 Berry, low growing, subgroup 13

- 07G 0.15

Onion, bulb, subgroup 3

- 07A 0.1 Spinach 1.0 1 Tomato, paste 3.0 3

Vegetable, brassica, leafy, group 5 1.0 1 bok choy Chinese cabbages, broccoli, broccoli raab , Brussels sprouts, cabbages, cauliflower, Chinese broccoli, chinese mustard cabbages, collards, kale, kohlrabi, mustard greens, mustard spinach, napa Chinese cabbages,

rape leaves Vegetable, cucurbit, group 9 2.0

Vegetable, fruiting, group 8 1.0 1 bell peppers, eggplants, ground cherries, nonbell peppers, pepinos, pepper hybrids, tomatillos,

tomatoes

3 tomato paste

### Page 20 of 20

Table 6 . Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex

Vegetable, leafy, group 4 0.25 0.25 Amaranth, arugula, cardoon, celery, celtuce, Chinese celery, corn salad, dandelion leaves, dock, edible leaved chrysanthemum, endives, fresh Florence fennel leaves and stalks, fresh chervil leaves, fresh parsley le aves, garden cress, garden pursl ane , garland chrysanthemum, head lettuce, leaf lettu ce, orach

, radicchio, rhubarb, swiss chard, upl and cress, winter purslane

1 m alabar spinach

, N ew Zealand spinach, spinach

US [40 CFR § 

### 180.561 (a)(2)] Canada Mexico 2 Codex 3
(2) 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 Same as above None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 2 Codex Apple 0.05 3 Grapefruit 0.05 3

Pear 0.05 3

Completed: : M. Negussie; 08/11/2013

1 There are no United States registrations for banana

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

3 E x piration/Revocation Date 12/31/15

Table 7 : HED Memoranda Relevant to Registration Review
Author Barcode/TXR # Date Title
T. Morton D 39 6885 0 4 / 25 / 2012 Acibenzolar

- S

- methyl Human Health Risk Assessment for Petition for the Establishment of Temporary Tolerances on Apple, Pear, and Grapefruit

– Experimental Use Permit Request.
S. Recore D 4 13833 0 8 / 2 0 /201 3 Acibenzolar : Tier I Review of Human Incidents