Docket Number: EPA-HQ-OPP-2011-0176

www.regulations.gov

Flumioxazin Summary Document

Registration Review: Initial Docket

June 2011
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Flumioxazin Summary Document

Registration Review: Initial Docket

June 2011

Flumioxazin Case # 7244

Approved By:

___________________

Richard P. Keigwin, Jr.

Director

Pesticide Re-evaluation Division

________________________

Date
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TABLE OF CONTENTS

 Page 

I. Preliminary Work Plan 4

II. Fact Sheet 9

________________________________________

Please Note

This Preliminary Work Plan (PWP) and Fact Sheet summarize the Environmental Protection 

Agency’s current position based on the following documents:

1. Problem Formulation for the Ecological Risk, Environmental Fate and Endangered 

Species Assessment in Support of Registration Review of Flumioxazin, June 1, 2011.

2. Flumioxazin: Human Health Assessment Scoping Document in Support of Registration 

Review, June 1, 2011.

3. BEAD Chemical Profile for Registration Review: Flumioxazin, March 3, 2011.

4. Flumioxazin Screening Level Usage Analysis (SLUA), July 15, 2010.

5. Flumioxazin: Review of Human Incidents, March 1, 2011.

Additional supporting documents for Flumioxazin may be found in the docket 

EPA-HQ-OPP-2011-0176 located on the internet at www.regulations.gov.
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I. Preliminary Work Plan – Flumioxazin

Introduction:

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 U.S. 

Environmental Protection Agency (USEPA, 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 at: http://www.epa.gov/oppsrrd1/registration_review/.

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 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 and commit to a final work plan and 

schedule for the registration review of flumioxazin (Case # 7244).

Flumioxazin is a light dependent peroxidizing herbicide (LDPH) of the N-phenylphthalimide 

class that is used for weed control in the growing of a variety of crops, including soybeans, 

almonds, grapes and ornamentals, as well as in aquatic settings and in bare-ground areas,

primarily in rights-of-way zones. Its mode of action is cell membrane disruption, through its

inhibition of protoporphyrinogen oxidase (PPO). Flumioxazin is not registered for use by 

homeowners, although there are uses to control weeds in aquatic and bare ground areas in 

residential settings which may result in exposure to residents.

Flumioxazin was first registered in 2001; therefore, it was not subject to the re-registration

requirements of FIFRA.

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 flumioxazin. The Agency also 

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

relevant to the registration review of flumioxazin.

Ecological Risk:

The most recent risk assessment for flumioxazin was done in 2010 for its use in 
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controlling aquatic weeds in waters with limited or no outflow (e.g., reservoirs, canals, 

lakes).

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

species determination for flumioxazin. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether the use of flumioxazin

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.

On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit against the Environmental Protection Agency 

(EPA) in the United States District Court for the Northern District of California, for 

allegedly failing to undergo consultation with the United States Fish and Wildlife Service 

and the National Marine Fisheries Service regarding the effects of over 350 pesticides, 

including flumioxazin, on over 200 endangered and threatened species throughout the 

United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 

(N.D.Cal.).

LDPH registrants are in the process of conducting a modified freshwater fish early life stage 

study (GLN 850.1400) to quantitatively determine the increase in toxicity of this class of 

herbicides in the presence of direct sunlight. The Agency expects to receive these data in the 

summer of 2011 in response to the Data Call-in (DCI) of January 2006 for this study. These data 

will be used in the registration review ecological risk assessment for flumioxazin.

The Agency anticipates requiring the following Guideline (GLN) study data for use in 

conducting a complete ecological risk assessment for flumioxazin:

GLN 835.6100 - Terrestrial Field Dissipation (ECM/Independent Laboratory Validation (ILV)).

1) the ILV for the soil method (RM-30S-1) used in MRID 48131403 and MRID 48131404 

for the analysis of flumioxazin

2) the ILV for the modified soil method (RM-30S-1-1) used in MRID 48131402 for the 

analyses of flumioxazin, THPA, and HPA

3) two Terrestrial Field Dissipation studies conducted in Illinois and California that the 

Agency identified as data gaps in the 2005 ecological risk assessment

GLN 850.1010 - Freshwater Invertebrate Acute LC50.

GLN 850.1400 - Estuarine/Marine Fish Early Life-Stage.

GLN 850.1500 - Fish Full Life-Cycle.

The results of the modified light freshwater fish early life-stage study may be applied to 

the Estuarine/Marine Fish Early Life-Stage study as appropriate.

Please refer to the document “Problem Formulation for the Environmental Fate and Ecological 

Risk, Endangered Species, and Drinking Water Assessments in Support of the Registration 

Review of Flumioxazin, June 1, 2011, located in the docket, for a detailed discussion of the 
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anticipated ecological risk assessment and data needs.

Human Health Risk:

The most recent human health risk assessment for flumioxazin was completed in 2010 in

conjunction with an application for an aquatic use registration.

Aggregate assessments will be updated to include any changes that have been made in 

toxicological endpoints, or exposure estimates.

Revised occupational assessments will be conducted for all scenarios based on updated 

points of departure and procedures for dermal and inhalation risk assessment.

During registration review, an updated residential exposure assessment will likely be 

required to include updates in endpoints or use patterns. 

The Agency anticipates requiring the following data specified in 40 CFR Part 158:

- GLN 870. 3465 – 28-Day Inhalation Toxicity Study

- GLN 870.6200 - Neurotoxicity Battery (acute and subchronic studies)

- GLN 870.7800 - Immunotoxicity

- GLN 860.1360 - Multiresidue Methods Testing for flumioxazin and water 

degradates 482-HA and APF

Following the submission of the additional toxicological data, the Agency plans to update 

the human health toxicity profile as needed.

Please refer to the following document for additional detail: Flumioxazin: Human Health 

Assessment Scoping Document in Support of Registration Review, June 1, 2011.

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), flumioxazin 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 
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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. Flumioxazin 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 flumioxazin. 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 flumioxazin

registration review:

Registration Review for Flumioxazin – Projected Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and Public Comment Period 2011 – June

Close Public Comment 2011 – August

Case Development

Final Work Plan 2011 – November

Issue DCI 2012 – July – Sept.

Data Submission 2014 – July – Sept.

Open Public Comment Period for Draft Risk Assessments 2016 – Jan. – March

Close Public Comment Period 2016 – April – June

Registration Review Decision

Open Public Comment Period for Proposed Registration Review 

Decision

2016 – July – Sept.

Close Public Comment Period 2016 – Oct. – Dec.

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

Total (years) 6
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Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the flumioxazin registration review case.

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. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (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:

Flumioxazin is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act1. In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for flumioxazin2. More information on impaired water bodies and

TMDLs can be found at the Agency’s website3. 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 

Process4in 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 flumioxazin 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.

Additional Information:

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining risk assessments, including any species-specific ecological effects

determinations. The Agency is interested in obtaining the following information regarding the 

use of flumioxazin:

1. confirmation on the following label information:

a. frequency of application, application intervals, and maximum number of applications per

 season

 

1

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

2

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES

3

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

4

http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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b. geographic limitations on use

2. use or potential use distribution (e.g., acreage and geographical distribution of relevant 

crops)

3. use history

4. median and 90th percentile reported use rates (lbs ai/acre) from usage data – national, state, 

and county

5. application timing (date of first application and application intervals) by crop – national, 

state, and county

6. sub-county crop location data

7. usage/use information for non-agricultural uses (e.g., forestry)

8. directly acquired county-level usage data (not derived from state level data)

a. maximum reported use rate (lbs ai/acre) from usage data – county

b. percent crop treated – county

c. median and 90th percentile number of applications – county

d. total pounds per year – county

e. the year the pesticide was last used in the county/sub-county area

f. the years in which the pesticide was applied in the county/sub-county area

9. typical interval (days)

10. state or local use restrictions

11. ecological incidents (non-target plant damage and avian, fish, reptilian, honey bee, 

amphibian and mammalian mortalities) not already reported to the Agency

12. any species-specific effects determinations

13. monitoring data

Next Steps:

After the 60-day comment period closes, the Agency will review and respond to any comments 

received in a timely manner, and intends to issue a Final Work Plan in November 2011 for the 

registration review of flumioxazin.
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II. Fact Sheet: Flumioxazin Registration Review

Background Information:

Flumioxazin Registration Review case number: 7244.

Flumioxazin Pesticide Chemical (PC) Code: 129034.

Flumioxazin CAS number: 103361-09-7.

Flumioxazin was first registered in the United States in 2001, and was, therefore, not 

subject to the re-registration requirements of FIFRA.

There are currently one technical and 13 product registrations for flumioxazin under 

FIFRA Section 3.

There are currently 22 Special Local Need (SLN) registrations for flumioxazin under 

FIFRA Section 24.

Technical Registrant: Valent USA Corp. (EPA Company # 59639).

Tolerances for flumioxazin are established under 40 CFR Part 180.568

Pesticide Re-evaluation Division (PRD), Chemical Review Manager (CRM)

Anne Overstreet: email to: overstreet.anne@epa.gov.

Registration Division (RD), Product Manager (PM) Kay Montague, email to: 

montague.kathryn@epa.gov.

Use & Usage Information:

Please refer to the documents BEAD Chemical Profile for Registration Review: Flumioxazin,

March 3, 2011 and Flumioxazin Screening Level Usage Analysis (SLUA), July 15, 2010, located 

in the docket, for further detailed information.

Flumioxazin is currently registered for use as a pre- and post-emergent herbicide to 

control susceptible weeds in a variety of fruit, vegetable and other agricultural crops, 

ornamentals, forestry, aquatic settings, and non-crop and bare-ground use in commercial 

and industrial areas. Flumioxazin is also registered for use in fall and spring pre-plant 

burndown programs and may be tank-mixed with other herbicides to broaden the 

spectrum of weed control. 

Flumioxazin products are formulated as water dispersible granules, wettable powder, dry 

granules and an emulsifiable concentrate

The percentage of active ingredient in the end-use formulations ranges from 0.17% (in 

dry granules) to 51% in both the water dispersible granules and wettable powders.

Flumioxazin is registered for ground and aerial application methods. Equipment includes 

boom sprayers, aerial sprayers, rotary spreaders and drop spreaders

Based on private market usage data from 2006-2008, the annual total agricultural usage 

averaged approximately 400,000 pounds active ingredient for 4.5 million acres treated.
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Recent Actions:

Flumioxazin was registered for aquatic use in November, 2010.

Ecological Risk Assessment Status:

Please refer to the document Problem Formulation for the Ecological Risk, Environmental Fate 

and Endangered Species Assessment in Support of Registration Review of Flumioxazin, June 1, 

2011, for the key findings of the most recent ecological assessment.

The most recent ecological risk assessment was done in 2010. These assessments 

identified risks to terrestrial and aquatic plants, chronic risk to small herbivorous

mammals, and chronic concerns for freshwater fish and estuarine/marine invertebrates.

In the presence of sunlight flumioxazin blocks the creation of chlorophyll in plants and 

heme in animals. In order to assess its toxicity in an aquatic environment appropriately 

the Agency issued a DCI in January 2006 for a modified light 850.1400 Fish Early Life 

Stage study to a group of registrants of LDPH pesticides. The studies will be completed 

during summer 2011, and the results will be incorporated into the ecological risk 

assessment process.

Human Health Risk Assessment Status:

The following were key findings of the most recent human health risk assessment for 

Flumioxazin. Please refer to the document Flumioxazin: Human Health Risk Scoping Document 

in Support of Registration Review, June 1, 2011 for a detailed discussion of the human health 

risk assessment.

Past flumioxazin 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.

Hazard Characterization

Flumioxazin had mild or low acute toxicity (Categories III or IV) when administered 

orally, dermally, or by inhalation. It was not an eye or skin irritant or a dermal sensitizer. 

Subchronic and chronic toxicity studies demonstrated that toxicity associated with 

flumioxazin included anemia, as well as effects on the liver and the cardiovascular 

system.
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Flumioxazin was classified as “not likely” to be a human carcinogen, based on the 

absence of tumors in mouse and rat carcinogenicity studies.

Dietary Exposure

Flumioxazin was registered for use on various crops including fruits, vegetables, tree 

nuts, legumes, and field corn. In addition there was a tolerance for residues in freshwater 

fish resulting from aquatic application. The acute and chronic dietary risk estimates were 

not of concern to EPA. 

Residential Exposure

Flumioxazin was not registered for use by homeowners, but such a scenario was 

assessed because the label does not contain a restriction prohibiting it. The registered 

uses that could result in residential exposure included aquatic and bare-ground weed 

control. The aquatic use could result in post-application exposure to children and adult 

swimmers, and the bare-ground application of flumioxazin granules might subsequently 

have resulted in exposure to children and adults. None of the scenarios were found to 

be of concern. 

Aggregate Exposure

All aggregate risk estimates for all durations and all population subgroups were not of 

concern. 

Occupational Exposure

All of the occupational exposure scenarios identified for the registered uses of 

flumioxazin were addressed, and none of the scenarios were of concern with baseline 

Personal Protective Equipment (PPE) and chemical-resistant gloves. For non-crop 

applications, dermal and inhalation risks to commercial applicators were also not of 

concern, provided applicators wear baseline PPE.

Cumulative

The Agency does not have, at this time, available data to determine whether flumioxazin 

has a common mechanism of toxicity with other substances. If, in the future, the Agency 

determines that new information on flumioxazin is available that could potentially impact 

a cumulative risk assessment and result in a risk of concern, the Agency will revisit the 

need for a cumulative risk assessment.

Incident Reports

Human Incidents:

The Office of Pesticide Programs Incident Data System (IDS) was used to determine the 

number and severity of incidents that resulted from flumioxazin exposure. Three 

incidents attributable to flumioxazin were reported between January 1, 2002 and 

November 30, 2010. Based upon the low frequency and severity of these cases, there 

was not a concern that would warrant further investigation as of the time of the report. 
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The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in the risk assessment.

Ecological Incidents:

There were 151 incident reports involving exposure of terrestrial organisms to 

flumioxazin that have been reported since 2001. All incidents involved plant damage. 

Flumioxazin was applied to agricultural crops (soybeans, peanuts and cotton) and nonagricultural crops (railroad rights-of-way). Only four incidents showed that flumioxazin 

may have damaged crops via spray drift, though each of these incidents involved a 

mixture of herbicides. The magnitude of damages ranged from a small area (5 acres) to 

the entire treated crop of 380 acres. The Agency will continue to monitor the incident 

information and, if a concern is triggered, additional analysis will be included in the risk 

assessment.

Tolerances and International Harmonization:

U.S. tolerances were established for residues of flumioxazin in or on food and feed 

commodities under 40 CFR 180.568. These tolerances were established in terms of 

parent flumioxazin and its metabolites and degradates, determined by measuring only 

flumioxazin. 

No maximum residue limits (MRLs) for flumioxazin have been established or proposed 

by the FAO/WHO Codex Alimentarius Commission (Codex) for any agricultural 

commodity. During registration review, if Codex has established tolerances for 

flumioxazin, the Agency will reconsider the U.S. tolerances and will harmonize them 

with Codex MRLs when the data warrant harmonization.

Data Call-In Status:

In January 2006, a data call-in (DCI) was issued to a group of registrants who hold 

technical registrations for the light-dependent peroxidizing herbicides (LDPH), requiring 

submission of a modified fish early life-stage toxicity test (Guideline number 850.1400) 

to quantitatively determine the increase in toxicity of this class of herbicides in the 

presence of direct sunlight. A task force of LDPH registrants, including Valent, is in the 

process of conducting this study, and the Agency expects to receive these data in the 

summer of 2011. These data will be used in the registration review ecological risk 

assessment for flumioxazin.

Labels:

Flumioxazin labels can be accessed from the Pesticide Product Label System (PPLS) 

website: http://oaspub.epa.gov/pestlab1/ppls.home.