Docket Number EPA-HQ-OPP-2014-0279

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## Imazapic Preliminary Work Plan Registration Review: Initial Docket Case Number 7234

September 2014

Approved by: 

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Richard P. Keigwin, Jr. Director Pesticide Re-evaluation Division

Date: 

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### Imazapic Preliminary Work Plan — Table of Contents

OVERVIEW................................................................................................................................... 4
ANTICIPATEDDATA NEEDS .................................................................................................... 5
STATUTORY AND REGULATORY AUTHORITY ................................................................... 6
CHEMICALFACTS ...................................................................................................................... 6
USE AND USAGE INFORMATION ............................................................................................ 7
RECENTACTIONS ....................................................................................................................... 8
ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 8
TIMELINE.................................................................................................................................... 11
NEXTSTEPS ............................................................................................................................... 12
Appendix — Additional Areas Considered in the Imazapic Registration Review ..................... 13

References: This Preliminary Work Plan summarizes the Environmental Protection Agency's current position based on the following documents:
1. Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Imazapic and its Ammonium Salt. Michael Wagman and Iwona L. Maher. September 12, 2014.
2. Imazapic (129041) and the Ammonium Salt of Imazapic (128943); Human Health Assessment Scoping Document in Support of Registration Review. William D. Wassell, Anwar Dunbar, and Lata Venkateshwara. September 4, 2014..
3. Imazapic and Imazapic Ammonium: Tier 1 Review of Harman Incidents. Elizabeth Evans and Shanna Recore. July 31, 2014.
4. BEAD Chemical Profile for Registration Review: Imazapic (129041) and Imazapic-ammonium (128943). Sunil Ratnayake. July 10, 2014.

P)

### 5. Imazapic (129041) and Imazapic-ammonium (128943) Case Level Screening Level U.sage

Analysis 

### (SLUA). Apri13, 2014.
6. EFED Table I Report for Imazapic Ammonium (128943). June 10, 2014.
7. EFED Table 1 Report for Imazapic (129041). June 16, 2014.
8. HED Master Label Report for hnazapic- Ammonium (128943). June 10, 2014.
9. HED Master Label Report for Imazapic (129041). June 16, 2014. These and other supporting documents for the imazapic registration review case may be found in the docket EPA-HQ-OPP-2014-0279 at http://w-w-w.regulations.gov



### .OVERVIEW

The docket for imazapic and imazapic ammonium (imazapic) is now open, initiating the first public comment period for this registration review (docket number EPA-HQ-OPP-2014-0279).This case includes the following active ingredients: imazapic (PC Code 129041) and imazapicamonium (PC Code 128943). Imazapic is a systemic herbicide belonging to the imidazolinine class of pesticide, which share a common mechanism of action that involves the inhibition of acetolactate synthase (ALS) enzyme, an enzyme found in plants. Imazapic is registered to control certain grasses and broadleaf weeds on peanuts, grass (pasture and rangeland) and a widerange of non-crop areas including utility right-of-ways, airports, turf, , and recreational (nonresidential) sites. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about imazapic, 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 imazapic. 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 imazapic and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on imazapic. The Agency encourages all interested stakeholders to review the PWP and Appendixand to provide comments and additional information that will help the Agency's decisionmaking 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 imazapic. 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 imazapic. 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 imazapic. For additional discussion of the anticipated data needs, see the 

### Problem Formulation for Ecologfcal Rfsk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Imazapic and its Ammonium Salt.

Table 1: Anticipated Data Needs for the Imazapic Registration Review
Estimated Guideline Study Title` Timeframe Number Test Material (Months from receipt of DCI)
830.6317 Storage Stability (soil) TGAI 12 835.4100 Aerobic Soil Metabolismz TGAI 24 835.4200 'Anaerobic Soil Metabolism TGAI 24 835.4300 Aerobic Aquatic Metabolism TGAI 24 850.2100 Avian Acute Oral Toxicity Test 3 TGAI 12 Non- Pollinator Acute Oral Toxicity

- Honeybee TGAI 12 guideline Adult 4 Non- Pollinator Chronic Oral Toxicity

— Honey TGAI 12 guideline Bee Adult 4 Non- Pollinator Acute and Chronic Oral Toxicity

— TGAI 12 guideline Honey Bee Larvae 4 850.3040 Field Testing for Pollinatorss TEP 24 850.4100 Seedling Emergence and Seedling Growthb TEP 12 850.4150 Vegetative vigor TEP 12

Environmental chemistry methods and associated 850.6100 independent laboratory validations for soil and TGAI 12

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

I 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.Pov/#! documentDetai 1; D=E PA-H O-OPPT-2009-0154-0028 z Need three additional soils.
3Conducted with a passerine species.
4 A protocol should be submitted to the Agency for review prior to study initiation.
5 The need for this test may be waived pending the results of the requested lower tier pollinator tests.
6 Data is requested for tomato, oats and ryegrass.

5STATUTORY 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. 7
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 imazapic.
CHEMICAL FACTS Table 2 provides a summary of the chemical facts for imazapic.
Table 2: Chemical Facts for Imazapic PC code 129041 and 128943 imaza ic- ammonium Case Number 7234 CAS Number 104098-48-8 (imaza ic) and 10498-49-9 (imaza ic- ammonium) Year first re istered 1994 Pesticide Type Herbicide Chemical class Imidazolinone Reregistration Eligibility Decision (RED) Because it was registered after November 1984, imazapic was not sub'ect to reregistration. Tolerance Reassessment Eligibility Decision (TRED) Not applicable

Cumulative group Imazapic has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

' http://www.epa.gov/oppsrrdl/registration_review/ 

## n.Table 2: Chemical Facts for Imazapic

40 CFR Citation Tolerances for imaza ic are established in 40 CFR § 180.490. Dual-use Imazapic is registered for conventional pesticidal uses only and has no re istered antimicrobial or biopesticidal uses. Non- esticidal uses There are no identified non- esticidal uses of imazapic. Pesticide Re-evaluation Ricardo Jones Division, Chemical Jones. ricardo(Loepa. gov Review Manager 703-347-0493 Registration Division, Kable Davis Product Manager Davis.kabler,epa.gov 703-306-0415


### USE AND USAGE INFORMATION Table 3 summarizes the use and usage information for imazapic. Please see the BEAD Chemical Profrle for RegistYation Review: Imazapic (129041) and Imazapic-ammonium (128943) in the registration review docket for more details.

Table 3: Imazapic Use and Usage Information Summary of Use Systemic herbicide used for the control of certain annual and perennial grasses and broadleaf weeds in peanuts, grass (pasture and rangeland) and non-crop lands. Use Sites Used on peanuts as early post-emergence treatment for weedcontrol. Used on roadsides and utilities as a pre-emergent or postemergent treatment to control undesirable grass species. Used on commercial and recreational sites as a perimeter and spot treatment to control broadleaf weeds and undesirable grass species. Used as a residential spot treatment for weed control. Summary of Usage Imazapic used primarily on peanuts and pasture based on EPA data from the time period of 1998-2012. This data suggests that use on peanuts was variable during this time period, and use on pasture spiked in 2002, decreasing since through 2012. In 2012, peanuts constituted 98.6% of pounds applied to crops in the U.S., with approximately 42,600 total pounds applied. In addition, data provided by the Bureau of Land management shows that in 2011, the most recent year data was available, 21,194 pounds of imazapic were applied to BLM pasture and rangelands. There is no data available on non-agricultural (i.e. commercial, recreational, residential) usa e. Formulation Type(s) Granules, water-dispersible granules, soluble concentrates, and ready-to-use solutions. Application Method(s) Products can be applied by handheld sprayers, mechanical sprayers, and aerial application. Technical Registrant(s) 

# I BASF Corporation and AGAN CHEM MFG, LTD

7Table 3: Imazapic Use and Usage Information

No. of Re istrations 23 Section 3 products 8 Restricted Use 

# I 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. Labels for EPA Reg. Nos. 71995-49 and 71995-51 are unclear with respect to application parameters such as the size of the treated area or maximum annual application rates. Without further information, EPA expects to use conservative assumptions to approximate these parameters in order to conduct a quantitative risk assessment. However, the Agency will work with registrants to clarify information onimazapic product labels, especially the maximum annual application rates for nonagricultural perimeter or spot-treatment uses. • 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 90`" 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. • Typical application interval (days). • State or local use restrictions. • Foreign technical registrants not listed above who supply technical imazapic to the US market.
RECENT ACTIONS On August 16, 2014 an import tolerance (a tolerance without U.S. registrations) was established for imazapic on sugarcane (78 FR 49927), and on Apri14, 2014 an import tolerance was established for imazapic on soybean, seed (79 FR 18815).
ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW The most recent comprehensive human health risk assessment for imazapic was completed onMay 16, 2013 in response to a petition for import tolerances on sugarcane and geneticallymodified soybean. The most recent ecological and environmental fate risk assessment conducted by the EPA was completed in 2001 for new use on pasture and rangeland. Findings and conclusions from these risk assessments are summarized in the Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments
$ Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website (http://oaspub.epa.gov/pestlabl/ppls.home).
8

### for Imazapic and its Ammonium Salt and 

### Imazapic (129041) and the Ammonium Salt of Imazapic

(128943); Human Health Assessment 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 imazapic. For human health, EPA anticipates the need to conduct revised dietary, residential, and occupational, and aggregate 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.

0Table 4: Anticipated Risk Assessments for the Imazapic Registration Review

Type of Risk Assessment Conduct? Notes Ecolo ical and Environmental Fate Comprehensive ecological Y EFED will conservatively characterize this risk by (species to be assessed utilizing a TTR approach. In this approach, a single include terrestrial and aquatic exposure concentration is estimated for total residues organisms), including (i. 

### e. parent imazapic 

### + the five degradates identified endangered species in the aqueous photolysis study) and compared to a representative toxicity endpoint for the parent (i. 

### e. assumes equal toxicity of each degradate to parent imaza ic Incidents Will check for For a discussion of reported ecological incidents for updates imazapic, see page 22 of the EFED Problem

Formulation. Human Health Dietary Food Y In the most recent risk assessment done in 2013, chronic dietary exposures were not of concern to HED. Drinking water Y A revised dietary exposure analysis may be required to reflect the most recent dietary exposure models and potential revised estiniated drinking water concentrations. Occu ational Handlers (mixers, loaders, Y Occupational handler inhalation exposure assessments applicators) need to be performed for the scenarios that have not been previously assessed. Post-application Y The need for a quantitative occupational postapplication inhalation exposure assessment will be considered during registration review. Residential Handlers Y The residential handler assessment may need to be revised based on new residential handler SOP's and policy changes for body weights and toxicological endpoints. Post-application N Residential post-application assessments do not need to be performed if label directions indicate the turf use is a specific spot treatment as in the case of imaza ic. Other Aggregate Y A new aggregate risk assessment may be required during Registration Review to incorporate any revised dietary exposure analyses and/or residential exposure assessments.

10Cumulative N EPA has not made a common mechanism of toxicity finding for imaza ic and any other substances. Tolerances N The qualitative nature of imazapic residues in plants and livestock is adequately understood. Incidents Will check for For a discussion of reported human incidents for updates imazapic, see page 10 of the Scoping Document and

the Imazapic and Imazapic Ammonium: 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. • Information on a typical percentage of an area that is spot treated for non-agricultural uncultivated areas/soils. • 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 imazapic registration review in Table 5 below.

Table 5: Projected Imazapic Registration Review Timeline Activities Estimated Date O ening the Docket O en Docket and 60-day Public Comment Period 2014 September Close Public Comment 2014 November Case Develo ment Final Work Plan 2015 February Issue DCI 2015 A ril

- June Data Submission 2017 April

- June 60-day Public Comment Period for Draft Risk Assessments 9 2018 October

- December
Re istration Review Decision 60-day Public Comment Period for Proposed Re istration Review Decision 2019 April

- June Registration Review Decision and Begin Post-Decision Follow-u 2019 Total (years) 5

9 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.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 imazapic.

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### Appendix — Additional Areas Considered in the Imazapic 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: Imazapic is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 10 In addition, no Total Maximum Daily Loads (TMDL) have been developed for imazapic. 11 More information on impaired water bodies and TMDLs can be found at the Agency's website. 12 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 Process 13 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 imazapic 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.


### ENDANGERED SPECIES:

10 http://iaspub.epa .!-

, rov/tmdl watersl0/attains nation cy.cause detail 303d?p cause group id=885
ll http://iaspub.epa.5 , ~ ov/tmdl watersl0/attains nation.tmdl pollutant detail?p pollutant group id=885&p pollutant group naine=PESTICIDES

~Z http://www.epa.aov/owow/tmdl/
13 http://www.epa.gov/oppsrrdl/registration review/water qualitX sop.htm


### 13A risk assessment that supports a complete endangered species determination has not been

conducted for imazapic. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of imazapic 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 imazapic, 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), imazapic 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, 2013 14 and includes some pesticides scheduled for registration review and chemicals found in water. Neither- of these lists should be construed as a list of known or likely endocrine disruptors.

14 See http://www.reQulations.aov/#!docutnentDetail;D=EPA-HO-OPPT-2009-0477-0074 for the final second list of chemicals.
14

### 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.
~ 5 

### HUMAN STUDIES: Occupational and Resfdential Past imazapic 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.

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


### 15