2 

### Pymetrozine Preliminary Work Plan

– Table of Contents

Overview 3

Anticipated Data Needs 4

Statutory and Regulatory Authority 5

Chemical Facts 5

Use and Usage Information 6

Recent Actions 7

Anticipated Risk Assessment s for Registration Review 7

Timeline 9

Next Steps 10

Appendix

– Additional Areas Considered in the Pymetrozine Registra tion Review 11

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. Registration Review: Preliminary Problem Formulation for Pymetrozine

. Bohaty, Hetrick,

Stebbins

. April 29, 2013

.

2. Pymetrozine. Human Health Assessment Scoping Document in Support of Registration

Review

. Dotson, Middleton

. May 7, 2013.

3. Pymetrozine: Review of Human Incidents. Evans, Recore. February 5, 2013

4. BEAD Chemical Profile for Registration Review: Pymetrozine (PC Code 101103)

. Mallampalli, Alsadek, Smearman. May 15, 2013

.

5. Pymetrozine (101103), Screening Level Usage Analysis (SLUA)

. June 21, 2012

.

6. PRD Label Data Report: Food/Feed & Non

- Food/Non

- Feed Uses Considered in Regis tration Review Work Planning , Pymetrozine (101103)

. January 14, 2013

.

These and other supporting documents for the pymetrozine registration review case may be

found in the docket EPA

- HQ

- OPP

- 2013

- 0368 at http://www.regulations.gov

.3 OVERVIEW

The docket for pymetrozine is now open , initiating the first public comment period for this registration review (docket number EPA

- HQ

- OPP

- 2013

- 0368 )

. Pymetrozine is a pyridine azomethine insecticide that is currently registered for use on ornamental plants, non

- bearing fruit and nut trees in nurseries, Christmas trees, and a variety of agricultural crops. This group of insecticides exhibits a unique mode of action characterized as neural inhibition of feeding

behavior in its target pests ( i.e., insects in the order Homoptera , including aphids, whiteflies, and leafhoppers). Pymetrozine has residual activity in the plant and is intended to control pests that move onto the plant after spraying. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about pymetrozine

, highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review , and pr oviding an anticipated timeline for completing the registration review for pymetrozine

.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, b y sharin g this information in the docket, to inform the public of what it knows about pymetrozine and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on pymetrozine

. The Agency encourages all in terested 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 som e 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 gr oups; 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 pymetrozine

. Next, it discusses the statutory and regulatory authority for R eg istration R eview. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review timeline for pymetrozine

. Finally, the Appendix

to this document includes identi fication and discussion of some areas that are considered generally in R egistration R eview along with some additional chemical case

- specific information.4 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for pymetrozine . For additional discussion of the anticipated data needs, see the Registration Review: Preliminary Problem Formulation for Pymetrozine and Pymetrozine. Human Health Assessment Scoping Document in Support of Registration Review.

Table 1: Anticipated Data Needs for the Pymetrozine Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated D ata Needs for the Parent Pymetrozine

835.2120 Hydrolysis TGAI 12

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.6100 Terrestrial field dissipation study 2 T GAI 12

850.6100 Environmental Chemistry Methods and Associated Independent Laboratory Validation for soil and

water TGAI 12

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.4100 Terrestrial plant toxicity, seedling emergence TEP 12

850.4150 Terrestrial plant toxicity, vegetative vigor TEP 12

Non

Guideline Semi

- field Toxicity Test with Honey Bee TGAI 24

870.7800 Immunotoxicity TGAI 12

TGAI = tec hnical grade active ingredient

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 guidelin e 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 A new t errestrial field dissipation study is not needed; only storage stability data are needed for CGA

- 359009 , a degradate of concern for drinking water

.5 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 envi ronment 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

s ure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website

. 3

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicid e, 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

. T he 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 additi onal 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 F inal W ork P lan (FWP) and anticipated schedule for the registration review of pymetrozine

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for pymetrozine

.

Table 2: Chemical Facts for Pymetrozine

PC code 101103

Case Number 7474

CAS Number 123312

- 89

- 0

Year first registered 1999 Pesticide Type Insecticide

Chemical class Pyridine Azomethines

R eregistration Eligibility Decision (R E D) Pymetrozine was r egistered after November 1984, and therefore was not subject to reregistration

. Tolerance Reassessment Eligibility Decision (TRED) Not applicable

.

Cumulative group Not applicable. Pymetrozine 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/6 Table 2: Chemical Facts for Pymetrozine

40 CFR Citation Tolerances for pymetr ozine are established in 40 CFR Part 180.556

. Dual

- use Pymetrozine is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses

. Non

- pesticidal uses There are no identified non

- pesticidal uses of pymetrozine.

Pesticide Re

- evaluation Division, Chemical Review Manager Steven Snyderman, snyderman.steven@epa. gov , 703

- 347

- 0249

Registration Division

, Product Manager John Hebert, hebert.john@epa.gov , 703

- 308

- 6249

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for pymetrozine

. Please see the BEAD Chemical Profile for Registration Review: Pymetrozine (PC Code 101103) in the registration

review docket for more details

.

Table 3: Pymetrozine Use and Usage Information

Summary of Use The insecticide pymetrozine acts through nerve action to block feeding behavior; mainly in insects in the order Homoptera (includes aphids, whiteflies, and leafhoppers, which are often major agricultural pests and vectors of plant diseases). These are the only target insects listed on pymetrozine labels.

Use Sites A gricultural use sites incl ude lettuce and potatoes ; specialty crops

include pecans , turmeric, melons, gourds, cucurbits, cotton, chayote, asparagus, celery, mustard , hops, turnips, fruiting vegetables, tobacco, and spinach

. Pymetrozine is also registered for

use on Christ mas tree plantations, nonbearing nut/fruit trees in nurseries, outdoor ornamentals and greenhouse crops. Summary of Usage From the years of 2000

- 2011 the use of pymetrozine has gradually

increased. An annual average of 9,000 pounds active ingredient (lbs . a.i.) is used to treat an annual average of 106,000 acres, for an overall average application rate of 0.1 lb. a.i. per acre from 2000

- 2011. Potatoes mak e up the majority of its usage. California has the highest percentage of both total pounds A.I. used and total

percent area t reated ; Maine has the maximum a.i. use intensity. Formulation Type(s) Pymetrozine is formulated only as water dispersible granules. Application Method(s) Products can be applied by tractor mounted spray (e.g. air blast )

, chemigation, aerial, and handheld equipments. Technical Registrant (s) Syngenta Crop Protection, LLC No. of Registrations 3 Section 3 products 4 and 10 Section 24c registrations

Restricted Use No

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

( http://oaspub.epa.gov/pestlabl/ppls.home ).7 Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , and of particular interest to EPA, are described below.

• C onfirmation 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

.

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

.

• M edian and 9 0 th percentile reported use rates (lbs ai/ A ) from usage data

– national, state, and county

.

• Information for non

- agricultural uses on target pests and treatment costs.

• Recent resistance reports for pymetrozine in populations of important target pests.

• Recent comparative efficacy data for pymetrozine vs. likely alternatives for major target

pests.

• Typical a pplication timing (date of first application and application intervals)

– national, state, and county

.

• Usage/use information for non

- agricultural uses

.

• Typical application interval (days)

.

• S tate or local use restrictions

.

• F oreign technical registrants not listed above who supply technical pymetrozine to the US

market

.

RECENT ACTIONS

In 2010 the Agency updated a previous risk assessment to complete the Agency’s actions required for a response to objections submitted by the Natural Resources Defense Council (NRDC) 5 . These objections concerned establishing tolerances for pymetrozine using a reduced FQPA safety factor for the protection of infants and chi ldren in the absence of a required toxicity study. The required study was subsequently received, reviewed, and incorporated into the Agency’s updated aggregate risk assessment for the chemical. Other than the aforementioned NRDC petition, there are no ad ditional recent actions for pymetrozine.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for pymetrozine was completed o n A pril 2010 as an update to the aggregate human health risk assessment

. T he most recent ecological and environmental fate risk assessment was completed in July 2006 in support of a

new use assessment on potatoes. Findings and conclusions from these risk assessments are

summarized in the Registration Review: Preli minary Problem Formulation for Pymetrozine and Pymetrozine. Human Health Assessment Scoping Document in Support of Registration Review

.

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, incl uding an endangered species assessment, for all uses of pymetrozine

. For human health, EPA anticipates the need to conduct revised dietary, residential

,

5 http://www.copyright.gov/fedreg/2010/75fr47464.pdf8 and occupational risk assessment s 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 assessment s
, as well as any changes to the standard operating p rocedures or default exposure assumptions

.

T able 4 belo w summarizes the anticipated registration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document

.

Table 4: Anticipated Risk Assessments for the Pymetrozine Registration Review

Type of Risk Assessment Conduct ? Notes

Eco logical and Environmental Fate Comprehensive ecological (species to be assessed

include terrestrial and aquatic organisms ), including endangered species Y The registration review assessment will consider the 5 major degradates estimated to exhibit approximately equal toxicity to the parent pymetrozine (CGA 359009, CGA 215525, GS 23199, CGA 249257, and CGA 300407).

Incidents Will check for updates No incidents were reported. S ee page 24 of the

Problem Formulatio n

. Human Health Dietary

Food Y EPA anticipates needing to incorporate updated

percent crop t reated estimates in accordance with Agency policies regarding the use of anticipated residues for dietary risk assessment. The major degradate CGA 359009 is currently considered a

residue of concer n in drinking water. In the last dietary assessment, water was considered the key dietary risk driver

. As drinking water will likely be the primary risk driver in the new dietary assessment, a revised drinking water assessment is anticipated to be perform ed

. Drinking water Y

Occupational Handlers (mixers, loaders, applicators) Y The Agency anticipates the need to conduct an occupational assessment to update doses and endpoints, maximum rates for applications to ornamentals using handheld equipment, along

with chemical

- specific dislodgeable foliar residue

data (DFR) , and updated transfer coefficients and activity data. Post

- application Y

Residential

Handlers Y9 Post

- application Y A residential assessment is anticipated to be

needed due to updated doses and endpoints, revisions to the HED Residential SOPs, and the

available chemical

- specific DFR data.

Other Aggregate Y An aggregate human health risk assessment

e valuates the combined risk from dietary and residential exposures. EPA anticipates conducting

t his assessment to incorporate the potential for

short

- term residential exposures following use of pymetrozine in gardens.

Cumulative N / A Pymetrozine is not a member of a cumulative

group. Tolerances Y EPA expects to revise the tolerance expression

. Incidents Will check for updates For a discussion of reported human incidents for pymetrozine , see page 10

- 11 of the Scoping

Document and the Pymetrozine: Review of Human

Incidents

. Between 2007 and 2012, two moderate severity and t wo low

- severity incidents were reported.

Guidance for Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

• Ec ological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

.

• Water quality m onitoring data (see Appendix for further details)

.

TIMELINE

EPA has created the following estimated timeline for the completion of the pymetrozine registration review in Table 5 below

.

Table 5: Projected Pymetrozine Registration Review Timeline

Activities Estimated Dat e Opening the Docket Open Docket and 60

- day Public Comment Period 2013

– June

Close Public Comment 2013

– August

Case Development

Final Work Plan 2013

– November

Issue DCI 2014 July

- September

Data Submission 2016 July

- September10 Table 5: Projected Pymetrozine Registration Review Timeline

Activities Estimated Dat e
6 0

- day Public Comment Period for Draft Risk

Assessments 6 2018 January

– March

Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision 2018 October

- December

Registration Review Decision and Begin Post

- Decision

Follow

- up 2019

Total (years) 6

NEXT STEPS

After the 6 0

- 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 pymetrozine

.

6 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, t he Agency plans to provide a 60 calendar day public comm ent period generally for draft risk assessment s

.11 

### Appendix

– Additional Areas Considered in the Pymetrozine Registration

Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference to sou rces of additional information c ould 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 (MRL s ) 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:

Pymetrozine is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 7 In addition, n o Total Maximum Daily Load s (TMDL) has been developed for pymetrozine

. 8 More information on impaired water bodies and

TMDLs can be found at the Agency’s website

. 9 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conf orm 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 10 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 d evelopment, 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 locati on, cultural practices, or other factors, may have atypical, unusually high exposure to pymetrozine 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.

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

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

gro up_name=PESTICIDES

9 http://www.epa.gov/owow/tmdl/

10 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 ENDANGERED SPECIES :

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

conducted for pymetrozine

. The ecological risk assessment planned during registration review will allow the Agency to determ ine whether use of pymetrozine 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 i ts 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, neurotoxici ty, 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 maturati on, 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 pymetrozine, 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),

pymetr ozine 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 wi ldlife 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 ba ttery 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 wi th 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 ca used 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. P ymetrozine is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, a s part of registration review, EPA will issue future EDSP orders/data call

ins, requiring the submission of EDSP screening assays for pymetrozine. For further information13 on the status of the EDSP, the policies and procedures, the list of 67 chemicals, fu ture lists, the test guidelines and the Tier 1 screening battery, please visit our website

. 11

HUMAN STUDIES :

Occupationa l and Residentia l

Past pymetrozine 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 gen eric pesticide exposure databases such as the Pesticide Ha ndlers 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 t hese 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 resea rch was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been

satisfied , and t here is no regulatory barrier to continued reliance on these studies

.

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