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Introduction

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan

(FWP) for the registration review of flufenacet. The Final Work Plan includes the expected 

registration review timeline. The FWP also addresses public comments received concerning the 

Preliminary Work Plan (PWP) in the Summary Document which was posted in the flufenacet 

registration review docket (EPA-HQ-OPP-2010-0863) and any other comments concerning the 

initial docket postings. The Summary Document provided information on what EPA knows 

about the pesticide and what additional risk analyses and data or information the Agency 

believes are needed to make a registration review decision. 

The Agency is implementing the registration review program and will review each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices occur over time. 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 that statutory standard. The public 

phase of registration review begins when the initial docket is opened for each case. Information 

on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/. 

Flufenacet (case number 7245) is an oxyacetamide herbicide registered for use on wheat 

(including triticale), perennial grasses grown for seed, corn (field and sweet), soybeans, and fir 

trees (FIFRA 24(c) Special Local Need (SLN) in Washington and Oregon only). Flufenacet is 

not registered for homeowner use, and there are currently no uses expected to result in residential 

exposure. Flufenacet was first registered in 1993 and therefore was not subject to the 

reregistration process under FIFRA. 

This document makes final the work plan for the flufenacet registration review processes. 

Comments Received on Preliminary Work Plan 

 On March 30, 2011 EPA opened a 60-day public comment period for the registration 

review of flufenacet. The comment period ended on May 31, 2011. The Preliminary Work Plan 

document can be located in the flufenacet registration review docket (EPA-HQ-OPP-2010-0863) 

at www.regulations.gov. 

During the public comment period, the Agency received comments from Bayer 

CropScience (Bayer) and the FIFRA Endangered Species Task Force (FESTF). A detailed 

description of the Bayer comments as well as the Agency’s response to these comments is 

available in separate response memoranda from the Agency’s Environmental Fate and Effects 

Division (EFED) and Human Health Effects Division (HED), which are located in the flufenacet 

registration review docket (EPA-HQ-OPP-2010-0863) at www.regulations.gov. The Agency’s 

response to FESTF’s comment is below. The comments received do not change the anticipated 

data and risk assessment needs that were described in the PWP and the timeline remains 

unchanged. The anticipated data and risk assessment needs are detailed below. 
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 In the PWP, EPA solicited comments on three specific topics: environmental justice, 

water body impairment and trade irritants. No comments or information were received during 

the public comment period concerning these issues. 

Comment from FESTF

In June of 2004, March of 2005, and October 19, 2007, the FIFRA Endangered Species 

Task Force (FESTF) submitted its Information Management System (FESTF Information 

Management System (IMS): Documentation of Structure and Function of IMS 1.1, MRID 

#46325901) and documentation of the beta-tested IMS, NatureServe data (FESTF Task Force 

Information Management System (IMS): Beta-Tested IMS 2.0 and Access to NatureServe Data -

Final Report, MRID #46486301) and NatureServe Data Evaluation and Review (MRID 

#47260101). These data fulfill the data requirements spelled out in Pesticide Registration Notice 

2000-2 and provide the best available data necessary for the proximity analysis of Flufenacet use 

and listed species locations. The leading registrant, as identified on the fact sheet included in the 

Registration Review Summary, is Bayer CropScience (Bayer), a FESTF member. Bayer is 

entitled to rely on FESTF data. 

Agency Response

The Agency thanks FESTF for its comment, and will consider this information as it 

conducts the registration review and makes its registration review decision. 

Anticipated Risk Assessment and Data Needs

The Agency anticipates conducting a comprehensive ecological risk assessment, 

including an endangered species assessment, for all pesticide uses of flufenacet. The Agency 

also anticipates conducting a human health risk assessment. Below is a summary of the issues 

relevant to the registration review of flufenacet. 

Ecological Risk 

A summary of the anticipated risk assessment and data needs for the ecological and 

endangered species assessments follows: 

 The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for flufenacet. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether flufenacet’s use has 

“no effect” or “may affect” federally listed threatened or endangered species (listed 

species) or their designated critical habitants. 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 (the Services), as appropriate.

 The Agency anticipates requiring the following data in order to conduct a complete 

ecological risk assessment for flufenacet.
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o GLN 835.6100 (footnote 7) Environmental Chemistry Methods (ECM) for 

Soil with Independent Laboratory Validation (ILV)

o GLN 835.6200 (footnote 7) Environmental Chemistry Methods (ECM) for 

Water and Sediment with Independent Laboratory Validation (ILV)

o GLN 850.1035 Estuarine/marine Invertebrate Acute Toxicity Test

o GLN 850.1350 Mysid Chronic Toxicity Test

o GLN 850.1400 Estuarine/Marine Fish Early Life Stage Test 

o GLN 850.2100 Acute Oral Avian Toxicity Test (Passerines) 

o GLN 850.4100 Seedling Emergence, Tier II (Axiom DF end-use product)

o GLN 850.4150 Vegetative Vigor, Tier II (Axiom DF end-use product) 

o GLN 850.4400 Aquatic vascular plant toxicity, Tier II (Thiadone, degradate 

of flufenacet)

 Please refer to the document, Revised: Registration Review – Preliminary Problem 

Formulation for Ecological Risk and Environmental Fate; Endangered Species, and 

Drinking Water Assessments for Flufenacet (February 3, 2011), located in the docket, 

for a detailed discussion of the anticipated ecological risk assessment and data needs. 

Human Health Risk: 

A summary of the anticipated risk assessment and data needs for the human health 

assessment follows: 

 The Agency anticipates conducting a new dietary assessment for the purpose of 

registration review to incorporate a revised drinking water assessment, which will 

include the thiadone degradate. 

 The Agency will consider the existing toxicity database as well as all additional 

toxicity studies received during registration review and will re-evaluate the sensitivity 

determination, as well as the points of departure and safety factors, used for risk 

assessment purposes. 

 Flufenacet is not currently registered for use in residential settings. Therefore, 

residential exposure to flufenacet is not expected. However, if exposure data and 

methodologies for estimating exposure have changed for issues such as volatilization, 

spray drift and track-in from field applications to residential settings at the time of the 

draft registration review assessment, then the Agency would anticipate requiring a 

residential exposure assessment. 

 The Agency anticipates conducting a revised occupational assessment during 

registration review. The following scenarios have not been assessed under current 

occupational residential exposure (ORE) policies and will be added to the revised 

occupational assessment: 
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o New mixer/loader, applicator, and flagger assessments will be needed for the 

aerial application of flufenacet on fir trees. 

o New mixer/loader occupational risk assessments will be needed to incorporate 

the liquid formulation of flufenacet for corn (field and sweet), soybeans, 

wheat (and triticale). 

 The Agency is currently evaluating the March 2, 2010 Scientific Advisory Panel 

(SAP) final report on issues related to volatilization of pesticides and may, as 

appropriate, develop policies and procedures to identify whether to incorporate postapplication inhalation exposure into the Agency’s risk assessment, and methods to 

assess post-application inhalation exposure. If new policies or procedures are 

implemented, the Agency would anticipate revisiting the need for a quantitative 

occupational post-application inhalation exposure assessment for flufenacet. 

 The tolerance expression in 40 CFR §180.527 will be reviewed during registration 

review to ensure that it appropriately covers flufenacet and its metabolites containing 

the 4-fluoro-N-methylethyl benzenamine moiety and that it specifies the residues to 

be measured for each commodity. 

 The Agency anticipates requiring the following data in order to conduct a complete 

human health risk assessment for flufenacet:

o GLN 870.7800 Immunotoxicity Study

o Special Study -- Comparative Thyroid Assay (CTA) is anticipated to be required 

because available data support the possibility of decreases in thyroid hormones at 

dose levels similar to those used in the submitted developmental neurotoxicity 

(DNT) study, as well as increases in neurobehavioral and neuropathological 

findings in multiple species. 

 Please refer to the document, Flufenacet. Human Health Assessment Scoping Document 

in Support of Registration Review (January 21, 2011), located in the docket, for a 

detailed discussion of the anticipated risk assessment and needs for human health. 

Changes to Data Needs: 

The Agency has received a third bridging study to support GLN 830.1500 Bridging Study 

Supporting Postemergence Application Uses of Soluble Concentrate (SC) Formulation. The 

study is currently in review. 

Recently, the Agency decided to no longer require GLN 830.7050, UV/Visible light 

absorption during registration review. These data were helpful during product reregistration, as 

they pertain to the structural analysis of the active ingredient. However, the data are not 

necessary for the registration review process because they do not concern human health or 

environmental effects.
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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, 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), flufenacet 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. Flufenacet 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 flufenacet. For further information 

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: 

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

Timeline:

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

registration review. 

 
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Registration Review for Flufenacet – Projected Registration Review Timeline

Activities Estimated Date 

Opening the docket 

Open Docket and Public Comment Period 2011 – March 

Close Public Comment 2011 – May 

Case Development 

Final Work Plan 2011 – August 

Issue DCI 2012 – April – June 

Data Submission 2014 – April – June 

Open Public Comment Period for Preliminary Risk Assessments 2015 – Oct. – Dec. 

Close Public Comment Period 2016 – Jan. - March 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review Decision 2016 – April - June 

Close Public Comment Period 2016 – July – Sept. 

Registration Review Decision and Begin Post-Decision Follow-up 2017 

Total (years) 6 

Next Steps

The Agency plans to issue a Data Call-In (DCI) for flufenacet in 2012. The new data will 

be used to conduct the risk assessments outlined in this FWP for all flufenacet uses.