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Acibenzolar S-methyl Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY................................................................... 6

CHEMICAL FACTS ...................................................................................................................... 6

USE AND USAGE INFORMATION............................................................................................ 7

RECENT ACTIONS....................................................................................................................... 8

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW................................ 8

TIMELINE.................................................................................................................................... 10

NEXT STEPS ............................................................................................................................... 11

Appendix – Additional Areas Considered in the Acibenzolar-S-methyl Registration Review 12

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, 

and Drinking Water Exposure Assessments in Support of the Registration Review of 

Acibenzolar-S-methyl. Lowit, M. and Wente, S. December 5, 2013.

2. Acibenzolar-S-methyl: Human Health Risk Scoping Document in Support of Registration 

Review. Morton, T., Miller, J.S., and Khasawinah, A. October 23, 2013.

3. Acibenzolar: Tier I Review of Human Incidents. Recore, S. and E. Evans. August 20, 

2013.

4. BEAD Chemical Profile (BCP) for Registration Review: Acibenzolar-S-methyl (061402). 

Chen, C., Alsadek, J., and Ranville, M. August 12, 2013.

5. Acibenzolar (061402) Screening Level Usage Analysis (SLUA). December 6, 2012.
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6. Acibenzolar-S-methyl EFED Label Data Report. July 11, 2013.

7. Acibenzolar-S-methyl HED Master Label Report. July 11, 2013.

These and other supporting documents for the acibenzolar-S-methyl registration review case may 

be found in the docket EPA-HQ-OPP-2013-0755 at http://www.regulations.gov.
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OVERVIEW

The docket for acibenzolar-S-methyl (hereafter, referred to as acibenzolar) is now open, 

initiating the first public comment period for this registration review (docket number EPA-HQOPP-2013-0755). Acibenzolar is registered for use to protect plants against invading pathogens 

by inducing a natural defense reaction that enhances the plants ability to ward off disease. It is 

registered 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. Acibenzolar is also registered for use in commercial seed treatment operations for 

protection against certain early season seed and seed-borne nematodes in cotton and sunflower. 

It is also used on sod farms, golf courses, professional and collegiate athletic fields, and lawns 

around commercial and industrial buildings to control turf diseases. This Preliminary Work Plan 

(PWP) document explains what EPA's Office of Pesticide Programs knows about acibenzolar, 

highlighting anticipated data and assessment needs, identifying the types of information that 

would be especially useful to the Agency in conducting the review, and providing an anticipated 

timeline for completing the registration review for acibenzolar

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about acibenzolar and what types of new data or 

other information would be helpful for the Agency to receive as it moves toward a decision on 

acibenzolar. The Agency encourages all interested stakeholders to review the PWP and 

Appendix and to provide comments and additional information that will help the Agency’s 

decision-making process for this chemical. In addition to general areas on which persons may 

wish to comment, there are some areas identified in the PWP and Appendix about which the 

Agency specifically seeks comments and information. Interested stakeholders could include: 

environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for acibenzolar. Next, it 

discusses the statutory and regulatory authority for Registration Review. Then the document 

provides chemical facts, use and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for acibenzolar. Finally, the Appendix 

to this document includes identification and discussion of some areas that are considered 

generally in Registration Review along with some additional chemical case-specific information.
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ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for acibenzolar. For additional discussion of 

the anticipated data needs, see the Registration Review: Preliminary Problem Formulation for 

Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure 

Assessments for Acibenzolar-S-methyl and Acibenzolar-S-methyl: Human Health Risk Scoping 

Document in Support of Registration Review.

Table 1: Anticipated Data Needs for the Acibenzolar Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Acibenzolar

850.4100 Seedling emergence (Tier II); wheat and tomato TEP 12

850.4400 Aquatic plant growth toxicity (Tier II) TGAI 12

850.3020 Larval honeybee acute oral toxicity TGAI 12

850.6100 Environmental chemistry methods and associated 

independent laboratory validations for water TGAI 12

Anticipated Data Needs for the CGA-210007 Degradate

850.2300 Avian reproduction test (bobwhite quail) CGA-210007 24

850.6100 Environmental chemistry methods and associated 

independent laboratory validations for water CGA-210007 12

Outstanding Data Requirements from Conditional Registration2

850.6100 Environmental chemistry methods and associated 

independent laboratory validations for soil CGA-210007 In review

850.5400 Aquatic plant growth (freshwater diatom, saltwater 

diatom, cyanobacteria ) TGAI In review

850.2100 Avian acute oral toxicity (passerine) TGAI In review

TGAI = technical grade active ingredient; TEP = typical end-use product;

 1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test 

Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 2 The studies listed in this section were previously required as conditions of registration in April 2013 and are still 

outstanding. These studies will not be included in the anticipated Registration Review DCI because they are 

already required as conditions of registration.
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STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website.

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The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of acibenzolar.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for acibenzolar.

Table 2: Chemical Facts for Acibenzolar

PC code 061402

Case Number 7031

CAS Number 135158-54-2

Year first registered 2000

Pesticide Type Host plant resistance activator

Chemical class Benzothiadiazole

Reregistration Eligibility 

Decision (RED)

Acibenzolar was not subject to reregistration since it was registered 

after 1984.

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not applicable.

Cumulative group Not applicable. Acibenzolar has not been identified as a member of 

a cumulative group that shares a common mechanism of toxicity.

 3 http://www.epa.gov/oppsrrd1/registration_review/
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Table 2: Chemical Facts for Acibenzolar

40 CFR Citation Tolerances for acibenzolar are established in §180.561(a).

Dual-use Acibenzolar is registered for conventional pesticidal uses only and 

has no registered antimicrobial or biopesticide uses.

Non-pesticidal uses There are no identified non-pesticidal uses of acibenzolar.

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Dana L. Friedman, friedman.dana@epa.gov, 703-347-8827

Registration Division, 

Product Manager

Tony Kish, kish.tony@epa.gov, 703- 308-9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for acibenzolar. Please see the BEAD 

Chemical Profile (BCP) for Registration Review: Acibenzolar-S-methyl (061402) in the registration 

review docket for more details.

Table 3: Acibenzolar Use and Usage Information

Summary of Use Acibenzolar-S-methyl belongs to the benzo-thiadiazole (BTH) 

chemical group of fungicides which controls or suppresses diseases 

by inducing the host plant's natural defense responses, and has no 

direct activity on pathogens.

It is registered for use to control or suppress plant diseases such as 

downy mildew on lettuce, spinach, cucurbits, and cole crops; 

bacterial diseases caused by Xanthomonas spp. or Pseudomonas 

syringae on tomatoes, peppers, and cucurbits; blue mold on 

tobacco; and black root rot, Fusarium wilt, and early season plantparasitic nematodes on cotton and turf.

Use Sites Agricultural Use Sites

Registered for use on brassica vegetables, cotton, cucurbits, fruiting 

vegetables, leafy vegetables, onion, peppers, chili peppers, low 

growing berry 13-07G, spinach, sunflower, tobacco and tomato.

Non-agricultural Use Sites

Registered for use on commercial/industrial lawns, golf course turf, 

ornamental lawns and turf, and ornamental sod farm (turf).

Summary of Usage Available data shows that from 2000-2011, the annual total 

agricultural usage averaged approximately 1,000 pounds a.i. to treat 

approximately 48,000 acres for an average application rate of 0.02 lbs. 

a.i. per acre. This time frame shows an increase in usage from 2000-

2005, and a decrease thereafter through 2011. For the more recent 

2007-2011 timeframe, usage averaged approximately 1,000 pounds 

active ingredient (a.i.) annually on 53,000 treated acres

with an overall application rate of 0.02 lbs. a.i. per acre.

Formulation Type(s) Formulated as water dispersible granules and flowable concentrates.
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Table 3: Acibenzolar Use and Usage Information

Application Method(s) Products may be applied as a band treatment, broadcast, chemigation, 

directed spray, foliar treatment, seed treatment, or soil/media treatment

using ground or aerial application equipment.

Technical Registrant(s) Syngenta Crop Protection LLC

No. of Registrations 4 Section 3 products4, 8 Section 24(c) products

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

• Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use.

• Use distribution (e.g., acreage and geographical distribution of relevant use sites).

• Median and 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county.

• Typical application timing (date of first application and application intervals) – national, 

state, and county.

• Usage/use information for non-agricultural uses, including pounds a.i. applied, average 

application rate, regional application, time of application, and number of applications per 

year.

• Typical application interval (days).

• State or local use restrictions.

• Foreign technical registrants not listed above who supply technical acibenzolar to the US 

market.

RECENT ACTIONS

New uses on turf and cotton were added in August 2010, the low growing berry subgroup was 

added in April 2012, and the sunflower seed treatment was added in January 2013. An 

Experimental Use Permit (EUP) was granted in June 2012 for apple, grapefruit, and pear. The 

EUP approval period and time-limited tolerances will expire in December 2015.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent human health risk assessment for acibenzolar was completed in April 2012 for a 

proposed Experimental Use Permit on apples, pears, and grapefruit, as well as for all of the other 

currently registered uses of acibenzolar. The most recent ecological and environmental fate risk 

assessment was completed June 2012 for the registration of the sunflower seed treatment use. 

Findings and conclusions from these risk assessments are summarized in the Problem 

 4 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home).
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Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking 

Water Exposure Assessments in Support of the Registration Review of Acibenzolar-S-methyl. and 

Acibenzolar-S-methyl: Human Health Risk Scoping Document in Support of Registration Review.

During registration review, the Agency anticipates the need to conduct a comprehensive

ecological risk assessment, including an endangered species assessment, for all uses of

acibenzolar. For human health, EPA does not anticipate the need to conduct revised dietary, 

residential, and occupational risk assessments during registration review. If toxicological 

endpoints or points of departure are revised based on the data that are anticipated to be required 

for registration review, they will be considered in the new assessments, as well as any changes to 

the standard operating procedures or default exposure assumptions.

Table 4 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document.

Table 4: Anticipated Risk Assessments for the Acibenzolar Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Y Acibenzolar-S-methyl and the major degradate of 

concern, CGA-210007, will be considered the 

stressors of concern in the ecological risk assessment. 

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

acibenzolar, see page 15 of the Problem Formulation.

Human Health

Dietary

Food N Updated dietary exposure assessments may be 

conducted if there are any significant changes to the 

toxicological points-of-departure (PODs) or Food 

Quality Protection Act (FQPA) and other uncertainty 

factors (UFs). 

Drinking water N If any significant changes to the estimated drinking 

water concentrations (EDWCs) may also necessitate 

changes to the dietary assessment.

Occupational

Handlers (mixers, loaders, 

applicators)

N The occupational handler assessment may need to be 

updated to reflect the most recent occupational 

handler surrogate exposure data or any significant 

change in exposure assessment methodology, 

toxicological PODs, or UFs.

Post-application N

Residential

Handlers N
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Post-application Y A quantitative exposure/risk assessment for direct 

residential application may be necessary during 

registration review to incorporate any changes to the 

Agency’s policies regarding off-site transport.

Other

Aggregate Y Emerging policies related to pesticide drift and 

volatilization assessments may warrant changes to the 

existing aggregate risk assessment.

Cumulative N Acibenzolar is not a member of a cumulative group, 

so no cumulative risk assessment is planned.

Tolerances N The current tolerance expression as listed in the 40 

CFR§180.561 (a) has been updated to reflect current 

policy.

Incidents Will check for 

updates

For a discussion of reported human incidents for 

acibenzolar, see page 6 of the Scoping Document and 

the Acibenzolar: Tier I Review of Human Incidents.

Guidance for Commenters: Additional ecological information requested for this 

registration review, and of particular interest to EPA, is described below.

• Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency.

• Water quality monitoring data (see Appendix for further details).

TIMELINE

EPA has created the following estimated timeline for the completion of the acibenzolar

registration review in Table 5 below.

Table 5: Projected Acibenzolar Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2013 – December

Close Public Comment 2014 – February

Case Development

Final Work Plan 2014 – May

Issue DCI 2014 July – Sept.

Data Submission 2016 July – Sept.

60-day Public Comment Period for Draft Risk 

Assessments5

2018 Jan. - March

 5 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.
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Registration Review Decision

60-day Public Comment Period for Proposed 

Registration Review Decision

2018 July – Sept.

Registration Review Decision and Begin Post-Decision 

Follow-up

2019

Total (years) 6

NEXT STEPS

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of acibenzolar.
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Appendix – Additional Areas Considered in the Acibenzolar Registration 

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to 

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern. 

Water Quality:

Acibenzolar is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act.

6

 In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for acibenzolar.

7

 More information on impaired water bodies and 

TMDLs can be found at the Agency’s website.

8 The Agency invites submission of water 

quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process9 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to acibenzolar compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

 6 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

7

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES 8 http://www.epa.gov/owow/tmdl/

9 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been 

conducted for acibenzolar. The ecological risk assessment planned during registration review 

will allow the Agency to determine whether use of acibenzolar has “no effect” or “may affect” 

federally listed threatened or endangered species (listed species) or their designated critical 

habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its 

designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service 

and/or National Marine Fisheries Service (the Services), as appropriate.

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, 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 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, 201310 and includes some 

pesticides scheduled for registration review and chemicals found in water. For further 

 10 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.
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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.11

HUMAN STUDIES:

Occupational and Residential

Past acibenzolar risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural 

Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force 

(ORETF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic 

exposure databases, and has found no clear and convincing evidence that the conduct of any of 

them was either fundamentally unethical or significantly deficient relative to the ethical 

standards prevailing at the time the research was conducted. All applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.

.

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