2

Flumetralin Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY................................................................... 6

CHEMICAL FACTS ...................................................................................................................... 6

USE AND USAGE INFORMATION............................................................................................ 7

RECENT ACTIONS....................................................................................................................... 8

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

TIMELINE.................................................................................................................................... 13

NEXT STEPS ............................................................................................................................... 13

Appendix – Additional Areas Considered in the Flumetralin Registration Review................. 14

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Problem Formulation for the Environmental Fate and Ecological Risk in Support of the 

Registration Review of Flumetralin. Kiernan, B.; Ibrahim, A. December 9, 2015.

2. Flumetralin. Human Health Risk Assessment for Registration Review. Bever, R.; Taylor, 

L.; Lloyd, M. December 15, 2015.

3. Flumetralin: Tier 1 (Scoping) Review of Human Incidents/Epidemiology. Recore, S; 

Evans, E. October 22, 2015.

4. BEAD Chemical Profile (BCP) for Registration Review: Flumetralin (123001). Yourman, 

L.; Paisley-Jones, C. June 17, 2015.

5. Flumetralin (123001) Screening Level Usage Analysis (SLUA). January 8, 2015.
3

6. Flumetralin (123001) EFED Table 1 Report. February 19, 2015.

7. Flumetralin (123001) HED Master Label Report. February 19, 2015.

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

in the docket EPA-HQ-OPP-2015-0076 at http://www.regulations.gov.
4

OVERVIEW

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

registration review (docket number EPA-HQ-OPP-2015-0076). Flumetralin is registered for 

conventional pesticide use as a plant growth regulator to control axillary bud growth (suckers) on

certain types of tobacco plants. This Preliminary Work Plan (PWP) document explains what 

EPA's Office of Pesticide Programs knows about flumetralin, 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 flumetralin.

This PWP also includes a summary of the draft human health risk assessment for flumetralin’s 

registration review. The last comprehensive human health risk assessment for flumetralin was 

completed in support of the 2007 Reregistration Eligibility Decision (RED). Only minor updates 

to the RED human health risk assessment were required to meet current risk assessment 

standards, so EPA developed a combined scoping document and draft human health risk 

assessment for flumetralin. The last ecological risk assessment for flumetralin was also 

completed to support the RED. The ecological risk assessment and data needs for flumetralin’s 

registration review are discussed in the Problem Formulation for the Environmental Fate and

Ecological Risk in Support of the Registration Review of Flumetralin. This document does not 

include the draft ecological risk assessment, as it cannot be conducted until the data needs are 

addressed. The draft risk human health risk assessment document and ecological problem 

formulation are posted in the docket, along with the flumetralin PWP and other supporting 

documents, for a 60-day public comment period.

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 flumetralin and what types of new data or 

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

flumetralin. 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 decisionmaking process for this chemical. In addition to general areas on which persons may wish to 

comment, there are some areas identified in the PWP and Appendix about which the Agency 

specifically seeks comments and information. Interested stakeholders could include: 

environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for flumetralin. Next, it 

discusses the statutory and regulatory authority for Registration Review. Then the document 

provides chemical facts, use and usage information, recent actions, conclusions of the draft 

human health risk assessment, an overview of the planned ecological risk assessments, and a 

projected registration review timeline for flumetralin. 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.
5

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for flumetralin. For additional discussion of 

the anticipated data needs, see the document titled Problem Formulation for the Environmental 

Fate and Ecological Risk in Support of the Registration Review of Flumetralin and the document 

titled Flumetralin. Human Health Risk Assessment for Registration Review.

Table 1: Anticipated Data Needs for the Flumetralin Registration Review

Guideline 

Number1 Study Title Test 

Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

835.2240 Aquatic photolysis TGAI 12

835.2410 Soil photolysis TGAI 12

835.4300 Aerobic aquatic metabolism TGAI 24

835.4400 Anaerobic aquatic metabolism TGAI 24

835.6100 Terrestrial field dissipation study TGAI 24

850.6100

Enforcement Analytical Method (ECM) and 

corresponding Independent Laboratory Validation 

(ILV) report for soil 

TGAI 12

850.6100

Enforcement Analytical Method (ECM) and 

corresponding Independent Laboratory Validation 

(ILV) report for water

TGAI 12

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.4500 Aquatic non-vascular plant toxicity2 TGAI 12

850.4550 Aquatic non-vascular plant toxicity2 TGAI 12

Non-GDLN 

(OECD 213) Tier I honeybee adult acute oral toxicity TGAI 12

Non-GDLN Tier I honeybee adult chronic oral toxicity TGAI 12

Non-GDLN

(OECD 237) Tier I honeybee larval acute oral toxicity TGAI 12

Non-GDLN Tier I honeybee larval chronic oral toxicity TGAI 12

Non-GDLN Tier II field trial of residues in pollen and nectar3 TEP 24

Non-GDLN

(OECD 75)

Tier II semi-field testing for honeybee toxicity 

(tunnel/enclosure or colony feeding)3 TEP 24

 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 While data on green algae are used provisionally in the EFED Problem Formulation, the underlying study has not 

been reviewed by EPA. Further, studies using three other taxa of aquatic nonvascular species are necessary to 

complete a risk assessment.

3 The need for theses anticipated data requirements is contingent on results of the tier 1 bee studies (including acute 

oral toxicity to adult honey bees, acute oral toxicity to larval honey bees, chronic oral toxicity to adult honey bees, 

and chronic oral toxicity to larval honey bees).
6

Table 1: Anticipated Data Needs for the Flumetralin Registration Review

Guideline 

Number1 Study Title Test 

Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

850.3040 Tier III field testing for pollinator toxicity3 TEP 24

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

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 flumetralin.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Flumetralin

PC code 123001

Case Number 4119

CAS Number 62924-70-3

Year first registered 1983

Pesticide Type Plant growth regulator

 4 http://www2.epa.gov/pesticide-reevaluation
7

Table 2: Chemical Facts for Flumetralin

Chemical class 2,6-Dinitroaniline

Reregistration Eligibility 

Decision (RED)

2007

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not applicable

Cumulative group Not applicable; flumetralin has not been identified as a member of 

a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Not applicable; no tolerances are required to support the use of 

flumetralin on tobacco.

Dual-use Not applicable; flumetralin is registered for conventional 

pesticidal uses only.

Non-pesticidal uses There are no identified non-pesticidal uses of flumetralin.

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Katherine St. Clair, stclair.katherine@epa.gov, 703-347-8778

Registration Division, 

Product Manager

Tony Kish, kish.tony@epa.gov, 703-308-9443

USE AND USAGE INFORMATION

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

Chemical Profile (BCP) for Registration Review: Flumetralin (123001) in the registration review 

docket for more details.

Table 3: Flumetralin Use and Usage Information

Summary of Use Flumetralin is registered for conventional pesticide use as a plant 

growth regulator to control axillary bud growth (suckers) on

certain types of tobacco plants.

Flumetralin is applied only once or twice per growing season. As 

a sucker control chemical, flumetralin is applied after the floral 

portions of tobacco plants have topped, usually within two days

of topping. Flumetralin is absorbed by the plant within a few 

hours of application and provides residual control throughout the

remainder of the growing season.

There are no registered residential uses.

Use Sites Agricultural Use Sites

Flumetralin is registered for use on tobacco only. It is not 

registered for use on any other agricultural crops.

Non-Agricultural Use Sites

Flumetralin is not registered for any non-agricultural uses.
8

Table 3: Flumetralin Use and Usage Information

Summary of Usage In the period from 2009 to 2013, approximately 103,000 pounds 

of flumetralin were applied over 170,000 acres annually, treating 

an average of 50 percent of tobacco crops. 

Formulation Type(s) Flumetralin end use products are formulated as emulsifiable 

concentrates.

Application Method(s) Flumetralin products can be applied by hand or by ground sprayer 

equipment.

Technical Registrant(s) Flumetralin technical registrants include Drexel Chemical 

Company, MacDermid Agricultural Solutions, and Syngenta.

No. of Registrations As of December 2015, there are seven Section 3 registrations,5

including three technical products and four end-use products.

Restricted Use Flumetralin is not classified as a restricted use pesticide.

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.

• Percent of applied flumetralin that is absorbed by tobacco plants.

• Typical application timing (date of first application and application intervals) – national, 

state, and county.

• Typical application interval (days).

• Foreign technical registrants not listed above who supply technical flumetralin to the US 

market.

RECENT ACTIONS

There are no recent or pending actions. The RED for flumetralin was signed in September 2007, 

and the product reregistration process has been completed.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health and ecological risk assessments for flumetralin

were completed in support of the 2007 Reregistration Eligibility Decision (RED), and an updated 

human health risk assessment was completed in December 2015 for the flumetralin registration 

review docket opening. Findings and conclusions from these risk assessments are summarized in 

the document titled Problem Formulation for the Environmental Fate and Ecological Risk in 

Support of the Registration Review of Flumetralin and the document titled Flumetralin. Human 

Health Risk Assessment for Registration Review.

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
9

During registration review, EPA anticipates the need to conduct a comprehensive ecological risk 

assessment, including a pollinator risk assessment and an endangered species assessment, for the 

use of flumetralin as a plant grown regulator on tobacco crops.

EPA anticipates requiring data to support the planned risk assessments. 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 anticipated ecological risk assessment or in 

a revised human health risk assessment, as will any changes to the standard operating procedures 

or default exposure assumptions.

Table 4 summarizes the recently completed registration review human health draft risk 

assessment and the planned ecological risk assessments as detailed in the document titled 

Problem Formulation for the Environmental Fate and Ecological Risk in Support of the 

Registration Review of Flumetralin and the document titled Flumetralin. Human Health Risk 

Assessment for Registration Review.

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Flumetralin Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Yes – to be 

conducted

EPA anticipates conducting an updated 

comprehensive ecological risk assessment during 

registration review. The new assessment will 

incorporate the most up-to-date modeling 

methodologies, updated toxicological endpoints, and 

data submitted under the anticipated registration 

review data call-in.

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

flumetralin, see Section 4.3 of the document titled

Problem Formulation for the Environmental Fate and

Ecological Risk in Support of the Registration Review 

of Flumetralin.

Human Health

Dietary

Dietary Yes -

completed

The registration review human health risk assessment 

did not identify any dietary (drinking water) risks of 

concern. For the highest exposed population 

subgroup, females 13-49 years old, acute exposure to 

flumetralin in drinking water resulted in a dietary risk 

of < 1.0% of the acute reference dose (aRfD), which

is well below the Agency’s level of concern. In 

addition, intermediate-term exposure to flumetralin in 

drinking water resulted in no risks of concern.
10

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Flumetralin Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Food No Flumetralin is a non-food use pesticide active 

ingredient since it is only used on tobacco to control 

axillary bud (sucker) growth. Dietary exposure to 

flumetralin through food is not expected. There is 

potential for flumetralin to reach drinking water 

sources through its application to tobacco. The 

registration review dietary assessment considered 

dietary exposure to flumetralin in drinking water only.

Drinking water Yes -

completed EPA conducted an updated assessment for flumetralin

to incorporate updated drinking water concentrations.

Occupational

Handlers (mixers, loaders, 

applicators)

Yes -

completed

The registration review human health risk assessment 

did not identify any risks of concern for occupational 

handlers of flumetralin. 

In the absence of an endpoint for dermal toxicity, 

dermal handler exposure assessments were not 

conducted. Occupational risk from inhalation 

exposure to flumetralin was assessed. All 

occupational handler scenarios for the registered uses 

resulted in inhalation MOEs greater than 100 at 

baseline (i.e., without respiratory protection). MOEs 

ranged from 3,300 to 44,000. HED determined that 

no additional personal protective equipment (PPE) 

recommendations (beyond the current 

recommendations on registered labels) are needed for 

flumetralin. 

Post-application No In the absence of an endpoint for dermal toxicity and 

in the absence of relevant systemic toxicity, 

occupational post-application dermal exposure 

assessments were not conducted for the registration 

review of flumetralin. 

Based on the Agency's current practices, a 

quantitative occupational post-application inhalation 

exposure assessment was not performed for 

flumetralin. If new policies or procedures are put into 

place, the Agency may revisit the need for a 

quantitative occupational post-application inhalation 

exposure assessment for flumetralin.
11

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Flumetralin Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Re-Entry Interval (REI) Yes -

completed

In the registration review human health risk 

assessment, the Agency reviewed the REI on 

flumetralin labels. HED is recommending that the 

REI be revised to 48 hours on all labels.

Residential

Smoking Yes -

completed

It is HED policy to assess only acute exposure to 

pesticide residues in tobacco products as the chronic 

health effects from tobacco use are well documented. 

The Agency conducted an assessment of acute 

inhalation exposure to flumetralin residues in tobacco 

(via smoking cigarettes). No risks of concern were 

identified.

Handlers No A residential handler assessment was not completed 

for registration review because flumetralin is not 

registered for residential use.

Post-application

Non-occupational Spray Drift 

Exposure and Risk Estimates

Yes –

completed

There are currently no registered or proposed 

residential uses for flumetralin.

Although flumetralin is not registered for residential 

use, there is potential for indirect residential exposure

via agricultural spray drift. EPA conducted a

quantitative residential (non-occupational) postapplication spray drift assessment for the registered 

use on tobacco crops. No risks of concern were 

identified at the field’s edge.

Other

Aggregate Yes -

completed

An aggregate risk assessment evaluates the combined 

risk from dietary and residential exposures. EPA 

conducted an updated aggregate assessment. There 

are no food or residential uses of flumetralin; 

therefore, the aggregate risk assessment considered 

exposure from drinking water only. Since drinking 

water exposure resulted in no risks of concern, no 

aggregate risks were identified for flumetralin.
12

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Flumetralin Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Non-occupational Bystander 

Post-application Inhalation 

Exposure and Risk Estimates

Will revisit if 

necessary

Volatilization of pesticides may be a source of postapplication inhalation exposure to individuals nearby 

pesticide applications. A tool is being developed for 

this. Since it is not available for use yet, EPA did not 

analyze volatilization in the residential postapplication assessment. During registration review, 

EPA will determine if further analysis is required for 

flumetralin.

Cumulative No Not applicable; flumetralin has not been identified as 

a member of a cumulative group that shares a 

common mechanism of toxicity.

Tolerances No Not applicable; no tolerances are required to support 

the use of flumetralin on tobacco.

Incidents Will check for 

updates

Based on the low frequency and low severity of 

incident cases reported for flumetralin, there does not 

appear to be a concern at this time that would warrant 

further investigation. However, the Agency will 

continue to monitor the incident information and if a 

concern is triggered, additional analysis will be 

included in the risk assessment. 

For a discussion of reported human incidents for 

flumetralin, see Section 10 of the document titled

Flumetralin. Human Health Risk Assessment for 

Registration Review and see the document titled

Flumetralin: Tier 1 (Scoping) Review of Human 

Incidents/Epidemiology.

Guidance for Commenters: Additional ecological information requested for this 

registration review, and of particular interest to EPA, is described below.

• Submission of existing data on green algae for EPA review; submission of existing 

invertebrate data for EPA review; submission of 40 CFR 158 compliant passerine data; 

submission of 40 CFR 158 compliant aquatic nonvascular plant data; submission of any 

existing toxicity data not previously submitted to the Agency. This would help give the 

Agency a more complete understanding of the effects of flumetralin.

• Information on the likelihood of foraging in tobacco fields by birds and mammals given 

the nicotine in tobacco; information on the magnitude of residues on forage items; 

information on the percent of applied flumetralin that is absorbed by tobacco plants. This 

could help reduce uncertainty and refine conservative assumptions in the Agency’s 

ecological models.

• Maximum annual application rates per acre (maximum lb ai/A/year), maximum number 

of applications per season and/or year, and minimum application intervals on all labels.
13

• 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 flumetralin

registration review in Table 5 below.

Table 5: Projected Flumetralin Registration Review Timeline

Activity Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period December 2015

Close Public Comment Period February 2016

Case Development

Issue Final Work Plan May 2016

Issue DCI July – Sept. 2016

Data Submission July – Sept. 2018

Open 60-day Public Comment Period for Draft Risk 

Assessments6

Jan. – March 2020

Registration Review Decision

Open 60-day Public Comment Period for Proposed 

Registration Review Decision

Oct. – Dec. 2020

Issue Registration Review Decision and Begin PostDecision Follow-up2021

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 flumetralin.

 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.
14

Appendix – Additional Areas Considered in the Flumetralin 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:

Flumetralin is not identified as a cause of impairment, as defined under section 303(d) of the 

Clean Water Act, based on information provided at EPA’s website.7 In addition, no Total 

Maximum Daily Loads (TMDL) have been developed for flumetralin.

8 More information on 

impaired water bodies and TMDLs can be found at EPA’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 flumetralin 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://www2.epa.gov/pesticide-reevaluation/opp-guidance-submission-state-and-tribal-water-quality-monitoringdata
15

ENDANGERED SPECIES:

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

conducted for flumetralin. The ecological risk assessment planned during registration review will 

allow the Agency to determine whether use of flumetralin 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 and reregistration decisions for 

flumetralin, 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), flumetralin is subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 201311 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. 

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

chemicals.
16

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.12

HUMAN STUDIES:

Occupational

The current flumetralin human health risk assessment in support of registration review, as well as 

past flumetralin 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) and the 

Agricultural Reentry Task Force (ARTF) 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 http://www2.epa.gov/endocrine-disruption