Docket Number : EPA

- HQ

- OPP

- 20 11

- 017 6

www.regulations.gov



# Flumioxazin Summary Document Registration Review: Initial Docket

June 20 1 1Page 2 of 13



# Flumioxazin Summary Document

Registration Review: Initial Docket

June 20 1 1

Flumioxazin Case # 7 2 4 4

Approved By:

___________________ Richard P. Keigwin , Jr.

Director

Pesticide Re

- evaluation Division

________________________ DatePage 3 of 13 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 , 201 1

.

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

- 017 6 located on the internet at www.regulations.gov.Page 4 of 13 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 t he 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 mee t 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 reevalua tes 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 implement ing the r egistration r eview program pu rsuant 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. T he 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 w ork plan and schedule for the registration review of f lumioxazin (Case # 7 2 4 4 )

.

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 zone s

. Its mode of action is cell membra n e disrupt i o n , through its

inhibit ion of protoporphyrinogen oxidase (PPO )

. Flumioxazin is not registered for use by

homeowners

, al though there are use s to control weeds i n 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 flum ioxazin. The Agency also anticipate s conducting a human health risk assessment . Below is a summary of the issues relevant to the registration review of f lumioxazin.

Ecological Risk:

The most recent risk assessment for f lumioxazin was done in 2010 for its use inPage 5 of 13

controlling aquatic weeds in waters with limited or no outflow (e.g., reservoirs, canals, lakes)

. The Agency has not conducted a r i sk assessment that supports a complete endangered species determination for f lumioxazin

. The ecological risk asse ssment planned during registration review will allow the Agency to determine whether the use of f lumioxazin has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical habitats

. When an a ssessment 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 Janu ary 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 fa iling 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

Unite d 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 r eceive 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 Gui deline (GLN) study data f o r use in

conduct ing a complete ecological risk assessment for f lumioxazin :

GLN 835.6100

- Terrestrial Field Dissipation (ECM/I ndependent L aboratory V alidation (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 T errestrial F ield D issipation 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 LC 50

.
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, E ndangered Species, and Drinking Water Assessments in Support of the Registration Review of Flumioxazin, June 1 , 20 11, located in the docket, for a detailed discussion of thePage 6 of 13

antic i pated ecological risk assessment and data needs

.

Human Health Risk :

The most recent human health risk assessment for f lumioxazin wa s completed in 20 10 in conjunction with an application for a n a quatic use registration

.

A ggregate assessments will be updated to include any changes that have been made in toxicological endpoints, or exposure estimates

.

R evised 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, a n updated residential exposure assessment will likely be required to include updates in endpoints or use pattern s

.

T he Agency anticipates requir in g 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 , 201 1.

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 pa rt 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 t o the endocrine screening part of the Endocrine Dis ruptor 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 AdministratorPage 7 of 13

may designate.” The EDSP employs a two

- tiered approach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screenin g 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 hormon al 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 substan ce, and

establish a dose

- response relationship between the dose and the E, A, or T e ffect.

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 ingred ients. 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 call

ins, 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/

.

T imeline:

EPA has created the following estimated timeline for the completion of the f lumioxazin registration review :

Registration Review for Flumioxazin

– Projected Registration Review Timeline

Activities Estimated Date Opening the D ocket 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

D ecision 2016

– July

– Sept.

Close Public C omment P eriod 2016

– Oct.

– Dec. Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2017 Total ( years ) 6Page 8 of 13

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 is suing a final work plan for the f lumioxazin 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 irritan t 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 Act 1

. In addition, n o Total Maximum Daily Load s (TMDL) have been developed for f lumioxazin 2 . More information on impaired water bodies and

TMDLs can be found at the Agency’s website 3

. The Agency invites submission of water quality

data for th is 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

Process 4 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 hel p 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 f lumioxazin c ompared 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 info r mation and data that will assist the Agency in refining risk assessment s , including any species

- specific ecological effects

determinations

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

use of f lumioxazin :

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_gr oup_name=PESTICIDES

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

4 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htmPage 9 of 13

b. geographic limitations on use

2. use or potential use distribution (e.g., acreage and geographical distribution of releva nt crops)

3. use history

4. median and 90 th 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 l ocation 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 90 th 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 S teps:

After the 6 0

- 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.Page 10 of 13 II

. F act S heet : Flumioxazin Registration Review

Background Information:

Flumioxazin R egist ration R eview case number: 7 24 4

.

Flumioxazin Pesticide Chemical (PC) Code: 129034

.

Flumioxazin CAS number: 103361

- 09

- 7

.

Flumioxazin was first registered in the United States in 200 1 , and wa s
, therefore

, not subject to the re

- registration requirements of FIFRA

.

There are currently one technical and 1 3 product regist rations for f lumioxazin under

FIFRA Section 3

.

There are currently 22 Special Local Need (SLN) regist rations for f lum ioxazin under

FIFRA Section 24

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

.

Tolerances for f

lumioxazin are established under 40 CFR Part 180.568

Pesticide Re

- evaluation Division ( PR D), Chemical Review Manager (CRM)

Anne Overstreet : e mail to: overstreet.anne@epa.gov

. Registration Division (RD) , Product Manager (PM) Kay Montague

, e mail to: montague.kathryn @epa.gov

.

Use & Usage Information :

Please refer to the document s BEAD Chemical Profile for Registration Review: Flumioxazin

, March 3 , 201 1 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 varie ty 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.

Flum ioxazin p roducts ar e f ormulated as wa t e r d i s p ers ibl e g ranules

, wettable powder, dry granules an d a n e mul s ifiabl e c oncentrate

The percent a ge of ac ti ve ingredient in t h e e n d

- u se for mul ations ranges from 0.17% (in dry granul es ) to 5 1% i n both t h e water dis persible granules and wettable powders.

Flumioxazin is registered for ground and aerial application methods

. E quipment includes boom sprayers, aerial sprayers, rotary spre aders 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 mill i on acres treated.Page 11 of 13

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 Flu mioxazin

, 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 risk s 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 block s the creation of chlorophyll in plants and

hem e in animals

. In order to assess its toxicity in an aquatic environment appr opriately 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 ecolo gical risk

assessment process.

Human Health Risk Assessment Status :

The following we re 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 Revie w, 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 the ir 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) Dat abase 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 th e 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 relianc e on these studies.

Hazard Characterization

Flumioxazin ha d mild or low acute toxicity ( C ategories III or IV) when administered orally, dermally, or by inhalation. It wa s not an eye or skin irritant or a dermal sensitizer.

Subchronic and chronic toxicity studies demonstrated that toxicity associated with

flumioxazin include d anemia, as well as effects on the liver and the cardiovascular

system

.Page 12 of 13

F lumioxazin wa s classified as “not likely” to be a human carcinogen

, based on the

absence of tumors in m ouse and rat carcinogenicity studies

.

Dietary Exposure

Flumioxazin wa s registered for use on various crops including fruits, vegetables, tree nuts, legumes, and field corn. In addition there wa s a tolerance for residues in freshwater fish resulting from aquatic application

. T he acute and chronic dietary risk estimates we re not of concern to EPA.

Residential Exposure

Flumioxazin wa s not registered for use by homeowners , but such a scenario was assessed because the label does not contain a restriction p rohibiting it. The registered

uses that could result in residential exposure include d 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 result ed in exposure to children and adults . N one of the scenarios were found to

be of concern

.

Aggregate Exposure

A ll aggregate risk estimates for all duration s and all population subgroups were not of

concern.

Occupational Exposure

All of the occupational exposure scenarios identi fied for the registered uses of

flumioxazin were addressed, and none of the scenarios we re of concern with baseline Personal Protective Equipment ( PPE ) and chemical

- resista nt 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 A gency 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 O ffice of P esticide P rograms Incident Data System (IDS) was used to determine the number and severity of incidents that resulted from flumioxazin exposu re. 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

wa s not a concern that would warrant further investigation a s of th e time of the report

.Page 13 of 13

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 we re 151 incident reports involving exposure of terrestrial organisms to flumioxazin that have been reported since 2001 . All incidents involve d plant damage. Flumioxazin was applied to agricultural crops (soybeans, peanuts and cotton) and non

agricultural crops (railroad right s

- of

- way). Only four incidents show ed 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 treat ed 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 we re established for residues of flumioxazin in or on food and feed

c ommodities under 40 CFR 180.568. These tolerances we re 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 pro posed 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 M RLs when th e 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

pro cess 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

.