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 

Support of Registration Review 

PC Code : 061402 

Decision No.: 481700 

Petition No.: None 

DP Barcode: 0413832 

Registration No.: NA 

Regulatory Action: Registration Review 

Assessment Type: Single ChemicaV Aggregate Reregistration Case No.: NA 

TXR No.: None CAS No.: 135158-54-2 

MRID No.: None 40 CFR: § 180.561 

FROM: 

THROUGH: 

TO: 

Introduction 

Thurston Morton, Chemist · ~ f ~ :?"'~ ,. __..?/~~ . wt_ 

James Scott Miller, Environmental Scientist "-~ »-

Abdallah Khasawinah, Toxicologist 

Risk Assessment Branch 4 " 

Health Effects Division (7509P) 

Susan V. Hummel, Senior Scientist ~v.~~ 

E

Risk 

lissa 

Assessment 

Reaves, PhD., 

Branch 

Branch 

4, HED 

Chief 

(7509P) 

C~~ 

Dana Friedman, Risk Manager Reviewer 

Risk Management and Implementation Branch 

Pesticide Re-Evaluation Division (7508P) 

The Health Effects Division (HED) Acibenzolar-S-methyl Registration Review Team has 

evaluated the status of the human health risk assessment for acibenzolar to determine the 

scope of work necessary to support Registration Review. Acibenzolar-S-methyl is a 

plant activator. It is a member of the benzothiadiazole 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 tolerances 

ranging from 0.1-3.0 ppm are established under §180.561(a). Acibenzolar-S-methyl is 

also used in commercial seed treatment operations for protection against certain early 

season seed and seed-borne nematodes in cotton and on ornamentals, 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 using ground or aerial equipment. 

Acibenzolar-S-methyl is also registered for residential application to turf grass using 

handheld spray equipment. 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 examined the proposed Experimental Use 

Permit (Section 5 Registration) for use of acibenzolar-S-methyl 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 

Transferable Residue (TTR) or Dislodgable Foliar Residue (DFR) study for the risk 

assessment during registration review, since sufficient 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 selecting endpoints for purposes of this risk assessment. In 

subchronic and chronic oral studies in rats, dogs and mice, signs of mild regenerative 

hemolytic anemia were consistently observed in all three species. Additional 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 highest 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 rats, 

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 

sensitivity 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 developmental 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-methyl was classified by HED's Hazard Identification Assessment 

Review Committee (HIARC) as "not likely" to be a human carcinogen based on negative 

carcinogenicity findings in male and female rats and mice and negative results in an 

acceptable battery of genotoxicity studies. Acibenzolar-S-methyl showed no significant 

toxicity in a battery of acute toxicity tests (Toxicity Category III or IV in all tests) but 

showed considerable skin-sensitivity. The end-use product (ActigardTM 50WG) 

displayed no significant acute toxicity and no dermal sensitizing potential. In an 

imrnunotoxicity study Acibenzolar-S-methyl 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 nondietary (occupational and residential) risk assessments are presented in Table 1. The 

PoDs, endpoints, UFs, and Food Quality Protection Action (FQPA) Safety Factors will 

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

Conclusions for Toxicology

The 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 have 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 (CGA210007), 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.

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. Maximum screeninglevel 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 from application of acibenzolar-S-methyl to cucurbit vegetables. 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 all population subgroups are 

below HED’s level of concern (<100% acute Population Adjusted Dose (aPAD) and 

chronic Population Adjusted Dose (cPAD)).

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 toxicological 

PODs or FQPA and other uncertainty 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 

estimates 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 occupational 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 

Assessment, 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 

(FAR). This default value is 25%. Of the analyzed DFR studies, the maximum FAR value 

seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, a 

calculated MOE of approximately 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 residues 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 resulting 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 exposures 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 exposures 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 residential 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 the 

highest risk estimate was children 3-5 years old with a 99.9th percentile acute exposure 

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

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

A short-term aggregate risk assessment 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 residential exposure pathway. Therefore, the 

chronic aggregate risk would be equivalent to the chronic dietary exposure estimate. The 

chronic dietary risk estimates from the 2012 risk assessment do not exceed HED’s level 

of concern.

Conclusions for Aggregate 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 

occur 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. 

Occupational Exposure and Risk Assessment

There is a potential for short- and intermediate-term occupational exposure to 

acibenzolar-S-methyl during mixing, loading, application, and post-application activities, 

however chronic exposure is not expected. Acibenzolar-S-methyl is registered for use on 

a number of crops including leafy and fruiting vegetables, 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 applications 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) request for apples, pears, and grapefruit to reflect current use 

information and policies. 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

Short- and intermediate-term exposure to acibenzolar-S-methyl during post-application 

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

scouting, transplanting, raking, and irrigation activities. Also, for turf; specific activities 

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 the 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 

warranted to reflect the most recent occupational handler surrogate exposure data1and 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 for the 

risk assessment during registration review.

Public 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, and 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 nature of the incident. Main IDS 

 

1 Outlined 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 Main IDS, from January 1, 2008 to June 11, 2013, there were no incidents 

reported in the database involving acibenzolar. 

In Aggregate IDS, from January 1, 2008 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 physicians, 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 incidents, 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 standardized 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-Pesticides 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 commercial 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 appropriate, 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 MRLs 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§180.561 (a) has been updated to 

reflect current HED policies and thus will not need to be revised during the registration 

review process. 

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, 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 LowIncome 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 human 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 

produce 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 EPA’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 risk 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 Handlers Exposure Database 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 research 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, neurotoxicity, 

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 maturation, 

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), acibenzolarS-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 estrogen, 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 effect. 

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 inert ingredients. A 

second list of chemicals identified for EDSP screening was published on June 14, 20132

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

water. For further information on the status of the EDSP, the policies and procedures, the 

lists 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.regulations.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 Requirements

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-Smethyl risk assessment during registration review.
Page 11 of 20

Table 1. Toxicological Doses and Endpoints for Past Acibenzolar-s-Methyl Human Health Risk 

Assessment (D396885; 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

UFA= 10x

UFH=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

UFA= 10x.

UFH=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

UFA= 10x

UFH=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. UFA = extrapolation from 

animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). UFL

= use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the 

absence of 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 applicable.
Page 12 of 20

Table 2. Toxicological Doses and Endpoints for Past Acibenzolar-s-Methyl Human Health Risk 

Assessment (D396885; 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 = 44%

NOAEL= 

8.2 

mg/kg/day

UFA= 10x

UFH=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

UFA= 10x

UFH=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

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 nonrodents (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 mg/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

Maternal NOAEL = 50 mg/kg/day

LOAEL = 300 mg/kg/day based on mortality, clinical signs of 

toxicity, decreased maternal body weight and food consumption.

Developmental 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 

morphometrics 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 lactation.

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.

870.4300

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 increased 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-Smethyl)

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 277.8 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-Smethyl)

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 (1997)

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 60 g/ml (-S-9 and +S9)

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 S9. Evidence of cell cycle arresting activity at G2.

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 the 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 based 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 parameters 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 not 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)

Acceptable/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 = 728 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

870.5395

870.5550

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, 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
Page 19 of 20

Table 6. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 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 Mexico2 Codex

Banana 10.1 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 Mexico2 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 leaves, 

garden cress, garden 

purslane , garland 

chrysanthemum, head 

lettuce, leaf lettuce, orach , 

radicchio, rhubarb, swiss 

chard, upland cress, winter 

purslane

1 malabar spinach, New 

Zealand spinach, spinach

US [40 CFR §180.561 (a)(2)] Canada Mexico2 Codex3

(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 Mexico2 Codex

Apple 0.053

Grapefruit 0.053

Pear 0.053

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 Expiration/Revocation Date 12/31/15

Table 7: HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

T. Morton D396885 04/25/2012 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 D413833 08/20/2013 Acibenzolar: Tier I Review of Human 

Incidents