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 Assessments for Registration Review 7

Timeline 9

Next Steps 10

Appendix – Additional Areas Considered in the Pymetrozine Registration Review 11

References:

This Preliminary Work Plan summarizes 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 

Registration 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 providing 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, by sharing 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 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 pymetrozine. 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 pymetrozine. 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.
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 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Pymetrozine

835.2120 Hydrolysis TGAI 12

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.6100 Terrestrial field dissipation study2 TGAI 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

NonGuideline Semi-field Toxicity Test with Honey Bee TGAI 24

870.7800 Immunotoxicity TGAI 12

TGAI = technical 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 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 A new terrestrial 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 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.

3

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 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

Reregistration Eligibility 

Decision (RED)

Pymetrozine was registered 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 pymetrozine 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 Agricultural use sites include 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 Christmas 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 make up the majority of its usage. California has

the highest percentage of both total pounds A.I. used and total 

percent area treated; 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 products4 and 10 Section 24c registrations

Restricted Use No

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
7

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.

• 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 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 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 children 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 additional recent actions for pymetrozine.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for pymetrozine was completed on

April 2010 as an update to the aggregate human health risk assessment. The 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: Preliminary Problem Formulation for Pymetrozine and 

Pymetrozine. 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

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

 5 http://www.copyright.gov/fedreg/2010/75fr47464.pdf
8

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 Pymetrozine 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 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. See page 24 of the 

Problem Formulation.

Human Health

Dietary

Food Y EPA anticipates needing to incorporate updated 

percent crop treated 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 concern 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 performed.

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 Y
9

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 

evaluates the combined risk from dietary and 

residential exposures. EPA anticipates conducting 

this 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 two low-severity incidents were 

reported.

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 pymetrozine

registration review in Table 5 below.

Table 5: Projected Pymetrozine Registration Review Timeline

Activities Estimated Date

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 - September
10

Table 5: Projected Pymetrozine Registration Review Timeline

Activities Estimated Date

60-day Public Comment Period for Draft Risk 

Assessments6

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 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 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, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.
11

Appendix – Additional Areas Considered in the Pymetrozine 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:

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, no Total Maximum Daily Loads 

(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 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 Process10 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 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_

group_name=PESTICIDES 9 http://www.epa.gov/owow/tmdl/

10 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
12

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 determine 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 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 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), 

pymetrozine 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. Pymetrozine is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for pymetrozine. For further information 
13

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website.

11

HUMAN STUDIES:

Occupational and Residential

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 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/