2

Topramezone 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....................................................................................................................... 8

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

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

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

Appendix – Additional Areas Considered in the Topramezone 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 Ecological Risk and Drinking Water Exposure Assessments to 

be Conducted for the Registration Review for Topramezone. August 26, 2015

2. Topramezone. Human-Health Assessment Scoping Document in Support of Registration 

Review. July 10, 2015

3. Topramezone: Tier I Review of Human Incidents. July 30, 2015

4. BEAD Chemical Profile for Registration Review: Topramezone. March 9, 2015

5. Topramezone Screening Level Usage Analysis. December 4, 2014

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

found in the docket EPA-HQ-OPP-2015-0127 at http://www.regulations.gov.
3

OVERVIEW

The docket for topramezone is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP-2015-0127). This case includes the following 

active ingredient: topramezone. Topramezone is a broad-spectrum systemic herbicide registered 

for use to control broadleaf and certain grass weeds. The mode of action in plants is inhibition of 

the 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme. Topramezone is currently 

registered for use on corn, non-cropped areas, residential and non-residential turf grass, and 

aquatic use sites. This Preliminary Work Plan (PWP) document explains what EPA's Office of 

Pesticide Programs knows about topramezone, 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 topramezone.

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 topramezone and what types of new data or 

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

topramezone. 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 topramezone. 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 topramezone. 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 topramezone. For additional discussion of 

the anticipated data needs, see the Problem Formulation for the Ecological Risk and Drinking 

Water Exposure Assessments to be Conducted for the Registration Review for Topramezone,

August 26, 2015 and Topramezone. Human-Health Assessment Scoping Document in Support of 

Registration Review, July 10, 2015

Table 1: Anticipated Data Needs for the Topramezone Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Topramezone

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.2300 Avian reproduction study (mallard) TGAI 24

850.3040 Field testing for pollinators (Tier 3)2 TEP 24

850.4500 Algal toxicity study TEP 12

850.6100 Environmental chemistry methods/independent 

laboratory validations in soil, water3 TGAI 12

Nonguideline 

(OECD 

TG237)

Acute oral toxicity to larval honey bees (Tier 1) TGAI 12

Nonguideline Chronic oral toxicity to adult honey bees (Tier 1) TGAI 12

Nonguideline Chronic oral toxicity to larval honey bees (Tier 1) TGAI 12

NonguidelineSemi-field testing for pollinators (tunnel or 

colony feeding studies) (Tier 2)2 TEP 12

NonguidelineField trial of residues in pollen and nectar (Tier 

2)2 TEP 12

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 Study may be waived depending on results of Tier 1 pollinator studies.

3 ECM/ILV needed for soil. Only the ILV is needed for 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.

4

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 topramezone.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Topramezone

PC code 123009

Case Number 7268

CAS Number 210631-68-8

Year first registered 2005

Pesticide Type Herbicide

Chemical class n/a

Reregistration Eligibility 

Decision (RED)

Because it was registered after November 1984, topramezone was 

not subject to reregistration.

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Because it was registered after 1996, topramezone was not 

subject to tolerance reassessment.

Cumulative group Topramezone belongs to a group of chemicals that inhibit the 

HPPD enzyme.

 

4 http://www.epa.gov/oppsrrd1/registration_review/
6

Table 2: Chemical Facts for Topramezone

40 CFR Citation Tolerances for topramezone are established in 40 CFR §180.612.

Dual-use Topramezone is registered for conventional pesticidal uses only 

and has no registered antimicrobial or biopesticidal uses.

Non-pesticidal uses HPPD inhibitors are used to treat genetic diseases of tyrosine 

catabolism.

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Jose Gayoso, gayoso.jose@epa.gov, (703) 347-8652

Registration Division, 

Product Manager

Kathryn Montague, montague.kathryn@epa.gov, (703) 305-1243

USE AND USAGE INFORMATION

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

Chemical Profile for Registration Review: Topramezone. March 9, 2015 in the registration 

review docket for more details.

Table 3: Topramezone Use and Usage Information

Summary of Use Broad spectrum, systemic pre- and post-emergence herbicide used 

to control broadleaf weeds and grasses by inhibition of the HPPD

enzyme and blockage of the pathway of phenylquinone 

biosynthesis in plants.

Use Sites Residential turf grass, golf courses, sod farms, non-crop 

ornamentals, rights-of-way, tree plantations, aquatic vegetation, 

and other non-crop areas, as well as for application to corn (field, 

pop, seed, and sweet).

Summary of Usage From 2006-2013, an annual average of approximately 19,000 lbs 

of active ingredient (a.i.) were applied. 

In the same timeframe, approximately 1.3 million acres of field 

and sweet corn were treated with topramezone.

The average application rate was 0.01 lbs a.i. per acre. 

Approximately 93% of the total pounds of topramezone applied

was to field corn but the percent crop treated (the ratio of base 

acres treated to crop acres grown) for field corn was <2.5%, 

whereas the percent crop treated for sweet corn was 15%.

No national level topramezone usage data were found on 

nonagricultural sites.

Formulation Type(s) Suspension (flowable) and emulsifiable concentrates.

Application Method(s) Products can be applied by ground, aerial, and hand held spray 

equipment.

Technical Registrant(s) Amvac, BASF
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Table 3: Topramezone Use and Usage Information

No. of Registrations 7 Section 3 products5

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.

 For some terrestrial uses, the number of applications of topramezone that can be applied 

per calendar year or the maximum annual application rate for a given use is not explicitly 

stated on many of the current labels.

 The following uncertainties exist regarding aquatic uses of topramezone:

o There is no defined maximum duration of maintaining some concentration of 

topramezone in the water body. The current label language is vague and states to 

‘retreat the water to maintain a sufficient concentration for a minimum of 60 days 

or until satisfactory weed control is achieved.

o No maximum depth is stated on the label. It is possible the water bodies may 

become stratified; therefore, the concentration of topramezone based on total 

volume may result in a much higher concentration in a given layer if thorough 

mixing is not observed. 

o The label indicates a maximum rate of 62 fl oz/acre-ft (1.35 lb a.i./acre-ft). This 

would suggest a potential for periods of time where concentrations may 

temporarily exceed the target concentration during an application (i.e., > 0.05 mg 

a.i./L) upon initial and subsequent applications of topramezone until dilution (i.e., 

achieving the desired concentration).

o The treatment of flowing water is dependent on flow rate and length of time that 

the application occurs. The label doesn’t provide information on minimum or 

maximum flow rates that can be treated. Potential Concentration Spikes: The 

maximum concentration permitted for the direct in-water uses (single or multiple 

applications) per year, per season, or per treatment period should also be clarified 

in the current label (Oasis® aquatic herbicide, EPA Reg. No. 7969-339).

 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.

 Typical application interval (days).

 State or local use restrictions.

 

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
8

 Foreign technical registrants not listed above who supply technical topramezone to the 

US market.

RECENT ACTIONS

On September 10, 2013, a new use of topramezone was registered for direct applications to 

various aquatic sites.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for topramezone was completed in 

2013 for a new use on non-crop aquatic sites. The most recent ecological and environmental fate 

risk assessment was completed in 2013 for the same purpose. Findings and conclusions from 

these risk assessments are summarized in the Problem Formulation for the Ecological Risk and 

Drinking Water Exposure Assessments to be Conducted for the Registration Review for 

Topramezone, August 26, 2015 and Topramezone. Human-Health Assessment Scoping Document 

in Support of Registration Review, July 10, 2015.

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

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

topramezone. For human health, EPA anticipates the need to conduct revised occupational 

handler and post-application 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.
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Table 4: Anticipated Risk Assessments for the Topramezone 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 Both topramezone and environmental transformation 

products are considered the stressors of concern. 

EFED will use a total toxic residue (TTR) approach, 

which is based on the assumption that the 

transformation products are of equal toxicity to the 

assessed organisms tested with the parent compound. 

The TTRs are defined as topramezone, M670H05, 

M670H01, and M670H10 for all taxa except plants. 

For plants, M670H05 is excluded. 

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

topramezone, see page 24 of the Problem 

Formulation.

Human Health

Dietary

Food N A new dietary exposure assessment is not anticipated 

to be needed during Registration Review unless there 

are significant increases to the drinking water 

exposure estimates and/or there are updates to the 

toxicity endpoints or safety factors.

Drinking water N A new dietary exposure assessment is not anticipated 

to be needed during Registration Review unless there 

are significant increases to the drinking water 

exposure estimates and/or there are updates to the 

toxicity endpoints or safety factors.

Occupational

Handlers (mixers, loaders, 

applicators)

Y Updated occupational handler exposure assessments 

will be conducted during Registration Review for 

topramezone use on corn; all other exposure scenarios

will be re-evaluated if there are changes in the 

toxicity endpoints or safety factors. 

Post-application Y Updated occupational post-application exposure 

assessments will be conducted during Registration 

Review for topramezone use on corn; all other 

exposure scenarios will be re-evaluated if there are 

changes in the toxicity endpoints or safety factors. 

Residential

Handlers N New residential handler exposure and risk 

assessments are not anticipated to be needed during 

Registration Review unless there are updates to the 

toxicity endpoints or safety factors. 
10

Post-application N New post-application residential exposure and risk

assessments are not anticipated to be needed during 

Registration Review unless there are updates to the 

toxicity endpoints or safety factors. Further, the 

Agency will examine the need for a volatilization 

assessment, as well as evaluate the potential 

topramezone exposure from spray drift during 

Registration Review.

Other

Aggregate N New aggregate assessments are not anticipated to be 

needed during Registration Review, unless there are 

changes in uses, procedures, drinking water exposure 

estimates, toxicity endpoints, and/or safety factors.

Cumulative N? The Agency has sought additional information from 

registrants regarding the mode of action/adverse 

outcome pathway (MOA/AOP) for HPPD inhibiting 

chemicals. Submitted data are currently under review

and will be used to evaluate the need for a cumulative 

assessment as part of Registration Review.

Tolerances N

Incidents Will check for 

updates

For a discussion of reported human incidents for 

topramezone see page 9 of the Scoping Document and 

the Topramezone: Tier I Review of Human Incidents. 

July 30, 2015

TIMELINE

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

registration review in Table 5 below.

Table 5: Projected Topramezone Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period September 2015

Close Public Comment November 2015

Case Development

Final Work Plan February 2016

Issue DCI April – June 2016

Data Submission April – June 2018

60-day Public Comment Period for Draft Risk 

Assessments6

Oct. – Dec. 2019

 

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

Table 5: Projected Topramezone Registration Review Timeline

Activities Estimated Date

Registration Review Decision

60-day Public Comment Period for Proposed 

Registration Review Decision

July - Sept. 2020

Registration Review Decision and Begin Post-Decision 

Follow-up

2021

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 topramezone.
12

Appendix – Additional Areas Considered in the Topramezone 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:

Topramezone 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) have been developed for torpramezone.

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.

Aquatic benchmarks have been established for topramezone and are available online.11 Any data 

submitted or otherwise located as part of the registration review process may be used to update 

aquatic life benchmarks if applicable.

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 

 

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

8http://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

11 http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm
13

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

atypical, unusually high exposure to topramezone 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:

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

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

will allow the Agency to determine whether use of topramezone 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 topramezone 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), 

topramezone 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 
14

of chemicals identified for EDSP screening was published on June 14, 201312 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. 

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.13

HUMAN STUDIES:

Occupational and Residential

Past topramezone 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.

 

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

chemicals.

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