Docket Number: EPA-HQ-OPP-2011-0448 www.regulations.gov



## Fipronil Summary Document Registration Review: Initial Docket
June 20113 

### TABLE OF CONTENTS

Page

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 12

III. Summary of Data Gaps 19

______________________ __________________

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's current position base d on the following documents:

1. Registration Review– Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species and Drinking Water Assessments for Fipronil, May 4, 2011.

2. Fipronil. Human Health Assessment Scopi ng Document in Support of Registration Review, May 24, 2011.

3. Fipronil: Review of Human Incidents. March 01, 2011.

4. Screening Level Usage Analysis (SLUA) for Fipronil, August 24, 2010.

5. BEAD Chemical Profile for Regist ration Review: Fipronil. May 25, 2011.

6. Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration Review Work Planning, November 8, 2010.

Additional supporting documents for fipronil may be found in the registration review docket EPA-HQ-OPP-2011-0448 located on the internet at www.regulations.gov

.4 I. Preliminary Work Plan – Fipronil

Introduction:

The Food Quality Protection Act (FQP A) of 1996 mandated a registration review program. All pesticides sold or distributed in the United States generally must be registered by the Environmental Protection Agency (EPA), 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 intende d 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 eff ects 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 Ag ency periodically reevaluates pest icides 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 revi ew 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 th e 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 belie ves are needed to make a registration review decision. After reviewing and responding to co mments and data received in the docket during this initial comment period, the Agency will de velop and commit to a final work plan and schedule for the registration review of fipronil.

Fipronil is a non-systemic, chiral phenylpyrazole insectic ide registered for use to control ants, beetles, cockroaches, fleas, mole crickets, ticks, termites, thrips, and other insects in a variety of agricultural and residential uses . It is formulated as a te chnical chemical, formulation intermediate, dust, granular, pelletted/tablet ted, wettable powder, impregnated material, emulsifiable concentrate, flowable concentrate, soluble concentrate, solution-ready to use, or pressurized liquid, depending on the use. Fipronil degrades to form persistent and immobile degradates—fipronil sulfide (MB 45950), fipronil sulfone (MB 46136), and MB 46513.

Current outdoor fipronil re gistered uses include broadcast tr eatment, in-furrow treatment, seed treatments, soil injection, and bait treatments. Fipronil also is register ed for use by lawn care operators and pest control opera tors to treat areas such as golf courses and food handling establishments. Registered residential uses fo r fipronil include spot-on treatment for domestic animals and ant mound treatment. In addition, fipron il is registered for use on potatoes, turnips, and rutabagas. Fipronil was first registered in 1985; therefore, it was not subject to the reregistration requirements of FIFRA.5 Anticipated Risk Assessment and Data Needs:

The Agency anticipates requiring data for use in conducting a comprehensive ecological risk assessment, including an endangere d species risk assessment, for all uses of fipronil. The Agency also anticipates requiring additional data for use in conducting human exposure risk assessments. Below is a summary of the issues re levant to the registrati on review of fipronil.

Ecological Risk:

• The most recent ecological risk assessment for fipronil was completed May 2007 in support of the registration for use on turnips and rutabagas.

• The Agency has not conducted a risk asse ssment that supports a complete endangered species determination for fipronil. The ecological risk assessment planned during registration review will allow the Agency to determine whether fipronil’s use has “no effect” or “may affect” federally listed threat ened or endangered sp ecies (listed species) or their designated critical ha bitats. When an assessment c oncludes that a pesticide’s use “may affect” a listed species or its designate d critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

• The Agency completed a recent endangered species risk assessment for the delta smelt (San Francisco Bay) in June 2010, and is curren tly in consultation with the U.S. Fish and Wildlife Service (USFWS) and/or the Nationa l Marine Fisheries Service (NMFS) (the Services).

• On January 19, 2011, the Center for Biologi cal Diversity and the Pesticide Action
Network North America filed a lawsuit in th e United States District Court for the Northern District of California, against th e Environmental Protection Agency (EPA) for allegedly failing to undergo consultation with the United States Fish and Wildlife Service
and the National Marine Fisheries Service re garding the effects of over 350 pesticides, including fipronil, on over 200 endangered a nd threatened species throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.).

• The Agency anticipates requiring the following da ta for fipronil and/or its degradates for use in conducting a complete ecological risk assessment, including an endangered species

assessment:

o Guideline 830.7840 - Water solubil ity (fipronil sulfide MB45950)

o Guideline 835.2120 – Hydrolysis (fipr onil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 835.2240 - Photodegradation in water (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 835.4100 - Aerobic soil meta bolism (fipronil sulfide MB45950 and fipronil sulfone MB46136)6 o Guideline 835.4300 - Aerobic aquatic metabolism (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 835.4400 - Anaerobic aquatic metabolism (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 835.6100 - Environmental chemistr y analytical method - soil (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 835.6200 - Environmental chem istry analytical method - water (fipronil, fipronil su lfide MB45950, fipronil su lfone MB46136, and MB46513)

o Guideline 850.1010 - Freshwater invert ebrate acute toxicity (MB46513)

o Guideline 850.1025 - Oyster acute toxici ty (fipronil sulf ide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 850.1055 - Bivalve acute toxici ty (fipronil sulf ide MB45950, fipronil sulfone MB46136, and MB46513

o Guideline 850.1075 - Freshwater fish acute toxicity (fipr onil sulfide MB45950)

o Guideline 850.1300 - Freshwater aquatic invertebrate lif e cycle (fipr onil sulfide MB45950 and fipronil sulfone MB46136)

o Guideline 850.1350 - Estuarine-marine inve rtebrate life cycle (fipronil and MB46513)

o Guideline 850.1400 - Freshwater fish ear ly life stage (fip ronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 850.1500 - Estuarine-marine fish early life stage/full life cycle (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 850.1730 - Bioaccumulation in fish (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 850.1735 - Whole sediment acute freshwater invertebrate toxicity (fipronil, fipronil su lfide MB45950, fipronil su lfone MB46136, and MB46513)

o Guideline 850.1740 - Whole sediment acute es tuarine marine inve rtebrate toxicity (fipronil, fipronil su lfide MB45950, fipronil su lfone MB46136, and MB46513)

o Guideline 850.2100 - Avian oral (fipr onil sulfide MB45950, fipronil sulfone MB46136, and MB46513) - bobwhite quail and house sparrow

o Guideline 850.2300 - Avian reproducti on (fipronil sulf ide MB45950, fipronil sulfone MB46136, and MB46513) - bobwhite quail and mallard duck

o Guideline 850.3020 - Honey bee acute c ontact (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 850.3030 - Honey bee foliage residue toxicity (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Guideline 850.3040 - Field testing for pollinators (fipronil)

o Guideline 850.4100 - Seedling emergence Tier II (fipronil)

o Guideline 850.4150 - Vegetative vigor Tier II (fipronil)

o Guideline 850.4400/5400 - Aquatic plant Tier II (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513)

o Non-guideline: Hyalella azteca 42-d Test for Measuring th e Effects of Sedimentassociated Contaminants on Survival, Growth, and Reproduction

o Non-guideline: Life-cycle Test for Measur ing the Effects of Sediment-associated
Contaminants on Chironomus dilutus (formerly known as C. tentans)7 o Non-guideline: Leptocheirus plumulosus (Chronic Toxicity of Marine and Estuarine Sediment-associated Contaminants)

• Please refer to Registration Review
– Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Spe cies, and Drinking Wate r Assessments for Fipronil , dated May 4, 2011, located in the docke t, for a detailed discussion of these anticipated risk assessment and data needs.

Human Health Risk:

• The most recent human health risk assessmen t, including a drinking water assessment, for fipronil was completed in 2007 to su pport tolerances on imported rice.

• The Agency anticipates requiring the followi ng data for fipronil for use in conducting a complete human health risk assessment:

o Guideline 860.1200 - Directions for Use

o Guideline 860.1500 - Crop Field Trials (fipronil, fipr onil sulfide MB45950, fipronil sulfone MB46136, and MB46513) – rice grain

o Guideline 870.3250 - 90-Day Dermal Study (fipronil)

o Guideline 870.3465 - 90-Day/28-Day Inhalation Study (fipronil)

o Guideline 870.7800 – Immunotoxicity (fipronil)

• After the additional toxicology studies that ar e expected to be required are submitted and reviewed, EPA will re-evaluate endpoints and safety/uncertainty factors for fipronil.

• During registration review, the Agency anticipa tes revising the dietary risk assessment if the FQPA safety factor (SF) changes, if a new drinking water assessment reflects changes in the estimated drinking water concentrati on, or a request for a new use is received.

• There are residential uses of fipronil. The residential exposure data base is adequate to support the registration review process; however, an updated residential exposure assessment may be required under registra tion review based upon revisions to the Agency’s Residential Standard Operating Pr ocedures (SOPs) which was reviewed by the Scientific Advisory Panel (SAP) in Oct ober 2009. Furthermore, if new data are identified which impact exposure estimates, or if new points of departure, a revised FQPA SF, or revisions to exposure policies and procedures are made, a new residential assessment will be conducted. An updated assessment of fipronil pet products will be conducted under registration review based upon the updates to the SOPs for Residential Exposure Assessment.

• Residential bystander exposures might occur as a result of spray applications and off-site transport (e.g., spray drift or volatilization). Revisions to Agency policies and procedures may warrant the Agency to consider the n eed for a bystander inhalation risk assessment for fipronil during re gistration review.8 • During registration review, the Agency may n eed to revise the aggregate assessment to include changes in the toxicological endpoint s and uncertainty factors; this will be
determined once additional toxi cology studies that are required for all fipronil technical products as a condition of re gistration are submitted and reviewed by the Agency.

• An updated occupational assessment and occ upational post-application assessment may be required for any fipronil use scenario if new data are identified which impact exposure estimates, or if new points of departure, a revised FQPA SF, or revisions to exposure policies and procedures are made.

• The Agency will modify tolerances as need ed, and work to harmonize tolerance/MRLs where possible in key export mark ets during registration review.

• For more information please refer to Fipronil: Human Health Assessment Scoping Document in Support of Registration Review, dated May 24, 2011, located in the docket.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent fipronil registration decision

, EPA reviewed these data and selected the most sensitive endpoints fo r relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), fipronil is subject to the endocrine screening part of the Endoc rine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required
determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 679 chemicals, which contains 58 pest icide active ingredients and 9 inert ingredients. Fipronil 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 issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for fipron il. For further information on the status of the EDSP, the policie s and procedures, the lis t 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 fipronil registration
review.

Registration Review for Fipronil – Pr ojected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and Public Co mment Period 2011 – June Close Public Comment 2011 – August Case Development
Final Work Plan 2011 – November Issue DCI 2012 – July – September Data Submission 2014 – July – September Open Public Comment Period for Draft Risk Assessments 2015 – Jan. – March Close Public Comment Period 2016 – April – June Registration Review Decision Open Public Comment Period for Proposed Registration Review
Decision 2016 – July – September

Close Public Comment Period 2016 – October –
December Registration Review Decision and Begin Post-Decision Follow-up 2017 Total (years) 6

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 fipronil.

Trade Irritants: Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any trad e irritant issues resul ting from lack of MRLs or disparities between U.S. tolerances and MR Ls in key export markets, providing as much specificity as possible regardi ng the nature of the concern.10 Water Quality: Total Maximum Daily Loads (TMDL) have been de veloped for fipronil in six water bodies that were listed as impaired under section 303(d) of the Clean Water Act in Louisiana 1 2 . More information on impaired water bodies and TM DLs can be found at the Agency’s website 3 . 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 Im paired Water Body and Other Water Quality Data in OPP’s Registration Review Risk A ssessment and Management Process 4 in order to ensure they can be used quantitatively or qualitativel y in pesticide risk assessments.

Environmental Justice:
EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to fipronil, compared to the gene ral population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.

Additional Information:

Stakeholders are also specifically asked to prov ide information and data that will assist the Agency in refining its risk assessments, incl uding any species-specific ecological effects determinations. The Agency is interested in receiving the following information:

1. confirmation on the following label information

a. sites of application
b. formulations

c. application methods and equipment
d. maximum application rates in units rela ted to mass per unit area of treatment

zone

e. frequency of application, applicati on intervals and maximum number of applications per season
f. geographic limitations on use
2. use or potential use distri bution (e.g., acreage and geogr aphical distribution of relevant crops)
3. use history
4. median and 90 th percentile reported use rates (lbs. a.i./acre) from usage data – national, state, and county
5. application timing (date of first applica tion and application intervals) by crop – national, state and county

1 http://iaspub.epa.gov/tmdl_waters10/attains _nation_cy.cause_detail_30 3d?p_cause_group_id=885

2 http://iaspub.epa.gov/tmdl_waters10/attain s_nation.tmdl_pollutant_detail ?p_pollutant_group_id=885&p_ pollutant_group_name=PESTIC IDES

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

4 http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm11 6. sub-county crop location data
7. directly acquired county-level usage da ta (not derived from state level data)

a. maximum reported use rate (lbs. a.i. /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 us ed in the county/sub-county area
f. the years in which the pesticide was applied in the county/sub-county area
8. typical interval (days)
9. state or local use restrictions
10. ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency
11. monitoring data
12. information on why use shows up on pot atoes for the first time in 2008

Next Steps:

After the 60-day comment period closes, the Ag ency will review and respond to any comments received in a timely manner, and expects to issue a Final Work Plan for fipronil during November, 2011.12 II. FACT SHEET

Background Information:

• Fipronil registration re view case number 7423

• Fipronil PC code: 129121

• The first fipronil-containing pest icide was registered in the U. S. in 1985; therefore, it was not subject to the reregistration process under FIFRA.

• There are currently 85 FIFRA Section 3 registra tions and 7 Section 24(c) registrations for fipronil.

• Technical registrants for fipronil include : Bayer Environmental Science, BASF Corporation, Irvita Plant Pr otection N.V., Argite, LLC, Fipronex Solutions, Inc., and Raymat Materials, Inc.

• Tolerances for residues of fipronil exist under 40 CFR §180.517.

• Pesticide Re-evaluation Di vision (PRD) Chemical Revi ew Manager (CRM): Susan Bartow, bartow.susan@epa.gov

• Registration Division (RD) Produc t Manager (PM): Richard Gebken, gebken.richard@epa.gov

Use & Usage Information: For additional detail s, please refer to Appendix A: Food/Feed &
Non-Food/Non-Feed Uses Considered in Registration Review Work Planning, November 8

, 2010; Screening Level Usage Analysis (SLUA), August 24, 2010; and BEAD Chemical Profile for Registration Review: Fipronil (PC Code: 129121 May 25, 2011)

.

• Fipronil is a non-systemic, chir al phenylpyrazole insecticide re gistered for use to control ants, beetles, cockroaches, fleas, mole crickets, ticks, termites, thrips, and other insects. Fipronil is registered for outdoor use, in-furrow treatment, seed treatment, soil injection, and bait treatments. In terms of non-agricultura l usage, fipronil is registered for use by lawn care operators and pest control operato rs to treat golf courses and food handling establishments. Fipronil is registered fo r use on potatoes, turnips, and rutabagas.

• There are residential uses for fipronil. It is registered for use for spot-on treatment on
domestic animals and ant mound tr eatment at residential settings.

• Fipronil is formulated as dust, granules, pe lleted/tableted, wettable powder, impregnated material, water dispersible granules, emulsifi able concentrate, flowable concentrate,
soluble concentrate or solubl e ready-to-use. End-use produc t concentrations range from 0.0001 – 80 percent active ingredient.

• Application methods include spot treatment, crack and crevice treatm ent, bait application, broadcast, mound treatment, subsurface/slit application treatment, animal treatments (rub-on and spray methods), and soil/media tr eatment. Application equipment includes low pressure ground sprayer, ready-to-use spray container, foam-making generator, airplane, and helicopter.13 Recent Actions:

• Tolerances for residues of fipronil, including its metabolites and degradates, in or on turnip and rutabaga were extended until December 31, 2013 (FR Vol. 75 No. 245, December 22, 2010). EPA has authorized under FIFRA section 18 the use of fipronil on turnip and rutabaga for control of cabbage maggot in Oregon. Th is regulation extends
time-limited tolerances for combined residues of fipronil for an additional 3-year period.

• A Federal Register notice for fipronil was issued on February 3, 2010 (FR Vol. 75 No. 22) which announced the expiration of certa in corn-in-furrow and turfgrass end-use fipronil products registered under section 3 of FIFRA. The notice also announced the amendment to terminate uses of all corn-in-furrow end use fipronil products registered under section 3 of FIFRA, and included a cance llation order to provide for existing stocks of affected products.

• In 2009, conditional registrations of outdoor gr anular turf products were converted to unconditional registrations and the use status was changed to Rest ricted Use Pesticide (RUP). All non-RUP granular products labele d for turf and reside ntial landscapes, and that would be applied over wide areas were cancelled. All remaining corn uses were also cancelled except for corn seed treatme nts on seed intended for export only.

Ecological Risk Assessment Status :

The following are key findings of the most recent eco logical risk assessments for fipronil. Please
refer to Registration Review– Preliminary Problem Formulation for the Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Fipronil May 4,
2011

, located in the docket, for a detailed disc ussion of the ecological risk assessments.

• The most recent ecological risk assessment of fipronil was completed in May 2007 in support of the registration for use to cont rol Cabbage Maggot on tu rnips and rutabagas.

• The Agency has conducted more than 20 ecological risk assessments for fipronil. These

assessments have identified the following risk concerns:

o Acute and chronic risks to freshwater, estuarine, and marine invertebrates

o Acute risk to endangered freshwater invertebrates

o Direct chronic risks to both fresh- and saltwater fish species

o Indirect effects to endangered fish species

o Acute lethal and reprodu ction risks to birds

o Reproductive effects in insectivorous mammals

o Acute and chronic terres trial vertebrate risk14 • To mitigate ecological risks, the major remaining outdoor use products were converted to
restricted use classification, to avoid indi scriminate use by homeowners. Additionally, the Agency recommended setbacks for applicat ions near bodies of water (buffer zones), and prohibition of applications near outdoor drainage areas, storm drains, french drains, etc. Additional mitigation included cancellati on of the corn-in furrow use, and corn seed treatment use (except for corn seed tr eatments on seed intended for export only).

Human Health Risk Assessment Status:

The following are key findings of the most recent human health risk assessments for fipronil.
Please refer to Fipronil: Human Health Assessme nt Scoping Document in Support of Registration Review, dated May 24, 2011, located in the docket, for a detailed discussion of the
human health risk assessment.

The most recent human health risk assessment for fipronil was completed in 2007 to support the tolerance on imported rice.

Hazard Characterization:

• Fipronil has moderate acute toxicity (Categor y II) by the oral and inhalation routes in rats. By the dermal route, it is of moderate toxicity in rabbits, and low toxicity (Category III) in rats. Fipronil technical is relatively non-irritating to the skin (Category IV) and eye (Category III) of rabbits and is not a dermal sensitizer.

• The Agency reduced the 10x FQPA Safety Factor to 1x because of the overall quality of the database, the low degree of concern for su sceptibility, and the lack of evidence of neurotoxicity.

• The carcinogenic potential of fipronil has b een classified as a Group C, possible human carcinogen, based on increases in thyroid follicular cell tumors in both sexes of the rat, which were statistically signi ficant by both pair-wise and trend analyses. There is no apparent concern for mutagenicity (no mu tagenic activity). In 1998, the Agency’s
Hazard Identification Assessment Review Co mmittee (HIARC) determined that dietary risk concerns from the long-term consumpti on of fipronil residues could be adequately addressed in chronic dietary exposure analyses using the RfD. Therefore, a separate assessment of cancer risk was deemed unnecessary. A cancer aggregate risk assessment was not performed because HIARC determined that cancer dietary risk concerns due to long-term consumption of fipronil residues are adequately addressed by the chronic exposure assessment.15 Dietary:

• Acute and refined chronic dietary risk anal yses were conducted using the DEEM-FCIDTM model to estimate the exposure to fipronil. The acute and refined chronic risk estimates were below the level of concern for each population subgroup.

Residential:

• An assessment in 2000 evalua ted homeowner exposure from the registered fipronil products used to control fire ants. Margin s of exposure (MOE) for dermal contact and inhalation resulting from assessment of granul ar formulations were not of concern.

• Assessments of the application of fipron il pet shampoo, spot-on and spray-on products did not identify any risks of concern.

• Adult dermal and child (3 to < 6 years old) dermal and incidental oral post-application exposure (combined) were previously assess ed and these were not of concern to the Agency.

Aggregate:

• Based on fipronil’s existing uses, the wors t case aggregate exposure for adults is represented by their combined estimated handler dermal and inhalation exposures resulting from applying a fipronil product to co ntrol fire ants. The worst case aggregate exposure for children younger than 6 years old is represented by their combined estimated post-applicatio n dermal and incidental oral e xposures resulting from contact with fipronil-treated pets. These combined exposures/risks along with average food and drinking water exposure estimates were used to determine short- and intermediate aggregate risks. These aggregate risk estimat es were below the Agency's level of concern
for children and adults.

Occupational :

• Results from assessments of occupational hand ler scenarios previously evaluated indicate that short- and intermediate-term exposure/ri sks were not of concern to the Agency at either baseline or minimum level of personal protection.

• Occupational post-application e xposure to fipronil is anti cipated to occur based on the following use patterns of the chemical—in-fu rrow, seed treatment, pet treatment, and broadcast on turf. Dermal post-application occupational exposure ba sed on the in-furrow uses of fipronil are expected to be negligible as the soil is norma lly not contacted after incorporation. The seed trea tment use is for field corn seed to be exported only, and secondary handlers are not i nvolved; therefore post-applic ation exposure to fipronil treated seeds is not expected to occur. Do mestic pets are expected to be treated and immediately returned to their owners such that post-applica tion contact will be negligible16 and an occupational pos t-application dermal exposure assessment was not performed for this use. For the broadcast turf use, post- application exposure also is expected to be negligible.

Human Studies:

• Past fipronil 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, invo lving exposure to many different pesticides, comprise generic pesticide exposure database s such as PHED, the Outdoor Residential Exposure Task Force (ORETF) Database, a nd 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 fundament ally 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 th e 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.

Cumulative:

• The Agency has not determined whether fipr onil shares a common me chanism of toxicity with other chemical substances. If, in th e future, the Agency determines that new information on fipronil is available that c ould potentially impact a cumulative risk assessment, the Agency will revisit the need for one.

Incidents:

• The Office of Pesticide Programs (OPP) Incident Data System (IDS) was consulted for reports of fipronil incidents. From 2002 to 2010, 4,243 incide nts involving fipronil were reported. Although the frequency of incidents ap pears to be decreasing over time and the majority of incidents were low to moderate se verity, there were eight incidents classified as having major severity and one incident result ed in a death due to an allergic reaction. Based on the number of incidents reported invol ving fipronil, and the effects noted in the incidents, the evaluation warrants further an alysis in the preliminary risk assessment phase of registration review. This further analysis will include reviewing other incident data from other sources (such as, Sentinel Event Notification System for Occupational Risks (SENSOR) and Poison Control Center (PCC )) as well as the National Institute for Occupational Safety and Health (NIOSH) article Acute illnesses associated with exposure to fipronil—surveillance data from 11 states in the United States, 2001–2007 (Lee, et al. 2010. Clin Toxicol 2010; 48:737-44).

• There are 49 incidents in the Agency da tabase for effects on non-target organisms associated with the labeled use of fipronil in the United States. The reported incidents involved crawfish and corn crops. The likeli hood of fipronil as the cause of the incidents17 was classified as highly proba ble for one incident, probable for one incident, and possible for one incident. Two additional incidents were reported outside the United States—one incident involved bird species and termites, but did not contain confirmatory analytical data, and the other incident involved honeybee hive mortality, but the findings are uncertain because another pesticide besides fipronil was also implicated in the honeybee
hive incident.

• Several pet incidents have been reported to the Agency. The Agency is developing mitigation measures to address these inci dents. Please see the Agency’s website ( http://www.epa.gov/pesticides /health/spot-on-meetings.html ) for more information.

Tolerances and International Harmonization:

• Tolerances are established for re sidues of fipronil under 40 CFR §180.517. Currently, the 40 CFR § 180.517 has permanent tolerances for fipronil (which include its 2 metabolites and 1 photodegradate) in/on: field co rn grain, stover and forage; the fat, liver, meat and meat byproducts (except liver) of cat tle, goat, hog, horse and sheep; eggs; milk fat; potato and potato wet peel; poultry fat, meat and meat byproducts; and rice grain and straw. Time-limited tolerances for turnip and rutabaga are in effect until December 31, 2013. Finally, tolerances for indi rect or inadvertent residues are established in/on wheat, grain, forage, hay, and straw.

• Compliance with the tolerance levels specified below is to be determined by measuring fipronil (5-amino-1-[2,6-dichl oro-4-(trifluoromet hyl)phenyl]-4-[(1R,S) (trifluoromethyl) sulfinyl]-1H-pyrazole-3-carboni trile) and its metabolites 5-amino-1-[2,6-dichloro-4- (trifluoromethyl) phenyl]-4-[(trifluoromet hyl) sulfonyl]-1H-pyrazo le-3-carbonitrile and 5-amino-1-[2,6-dichloro-4-(trifluoromet hyl) phenyl]-4-[(trifluoromethyl)thio]-1Hpyrazole-3-carbonitrile and its photode gradate 5-amino-1-(2,6-dichloro-4- (trifluoromethyl)phenyl]-4-[( 1R,S)-(trifluoromethyl)]-1 H-pyrazole-3-carbonitrile.

• A Codex MRL has been established for fipr onil residues in several raw agricultural commodities. The proposed import toleran ce is not harmonized with the established MRL, a fact attributable to the difference in tolerance expression between Codex and the U.S. There are currently no established Canadian and Mexican MRLs for fipronil

.

• The Agency plans to revoke the tolerance for rice straw and potato wet peel in 40 CFR § 180.517. A tolerance of 0.10 ppm for processe d potato waste should be included. The Agency also plans to modify the tolerance expression in the 40 CFR § 180.517 according to the new Interim Guidance on Tolerance Expressions.

• The Agency has required data from Japan a nd crop field trials from Brazil to support a previous petition for imported rice uses and several fipronil label amendments. For the Japanese trials, information concerning the field portion of the st udy and the analytical portion of the study must be submitted. To support the proposed foliar use in Brazil, data are required which depict magnitude of the re sidues of fipronil and its metabolites MB18 45950, MB 46136, and MB 46513 in/on rice grai n harvested 30 days following postemergence foliar treatment of the propos ed formulated product at 12 g ai/ha.

• The Agency has required additional information pertaining to typical application patterns
in the countries of use. The submitted use directions information for Australia does not include information on formulation type and a.i. percentages/product density so that applications rates could be converted from product to active ingredient. The submitted use information for Brazil (spray applicat ion) does not include maximum number of applications per season and/or maximum s easonal rate. In addition, the Agency has required that the petitioner provide assuran ce that the only countries in which their fipronil products will be used on rice destined for import into the U.S. are Australia, Brazil, and Japan.

Data Call-In Status

• No data call-ins have been issued for fipronil.

Labels :

• Fipronil Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.hom

.19 III. Summary of Data Gaps – Fipronil

The table below summarizes all anticipated data needs for fipronil in Section I, of this document (Preliminary Work Plan), the Registration Review– Preliminary Problem Formulation for the Ecological Risk and En vironmental Fate, Endangered Species, and Drinking Water Assessments for Fipronil, dated May 4, 2011, and the Fipronil: Human Health Assessment Scoping Document in Support of Registration Review , dated May 24,
2011.

Guideline
Number Anticipated Data Requirement Test
Material Study
Duration
(months)

830.7840 Water Solubility (fipronil sulfide MB45950) TGAI 12

835.2120 Hydrolysis(fipronil sulfide MB45950, fipronil sulfone MB46136,and MB46513) TGAI 12

835.2240 Photodegradation in water (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TGAI 12

835.4100 Aerobic soil metabolism (fipronil sulfide MB45950 and fipronil sulfone MB46136) TGAI 24

835.4300 Aerobic Aquatic Metabolism (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TGAI 24

835.4400 Anaerobic Aquatic Metabolism (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TGAI 24

835.6100 Environmental chemistry analytical method - soil (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TEP 24

835.6200 Environmental chemistry analytical method - water (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TEP 24

850.1010 Freshwater invertebrate acute toxicity (MB46513) TGAI 24

850.1025 Oyster acute toxicity (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 1 TGAI 12

850.1055 Bivalve acute toxicity (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 1 TGAI 12

850.1075 Freshwater fish acute toxicity (fipronil sulfide MB45950) TGAI 18

850.1300 Freshwater aquatic invertebrate life cycle (fipronil sulfide MB45950 and fipronil sulfone MB46136) TGAI 12

850.1350 Estuarine-marine invertebrate life cycle (fipronil and MB46513) TGAI 12

850.1400 Freshwater fish early lif e stage (fipronil sulfide MB45950, fipronil sulfone MB46136, and TGAI 1220 Guideline
Number Anticipated Data Requirement Test
Material Study
Duration
(months)

MB46513)

850.1500 Estuarine-marine fish earl y life stage/full life cycle (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TGAI 24

850.1730 Bioaccumulation in Fish (f ipronil sulfid e MB45950, fipronil sulfone MB46136, and MB46513) TGAI 12

850.1735 Whole sediment acute fr eshwater invertebrate toxicity (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TGAI 24

850.1740 Whole sediment acute estuar ine marine invertebrate toxicity (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TGAI 12

850.2100 Avian oral (fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) - bobwhite quail and house sparrow TGAI 12

850.2300 Avian reproduction (fipronil sulfide MB45950 and fipronil sulfone MB46136, and MB46513) - bobwhite quail and mallard duck TGAI 24

850.3020 Honey bee acute contact (fi pronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TEP 12

850.3030 Honey bee foliage residue toxicity (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) TEP 12

850.3040 Field testing for pollinators (fipronil) TEP 24 850.4100 Seedling emergence Tier II (fipronil) 2 TEP 12 850.4150 Vegetative vigor Tier II (fipronil) 2 TEP 12

850.4400 Aquatic plant tier II (f ipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 2 TEP 12

850.5400 Aquatic plant tier II (f ipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) 2 TEP 12

860.1200 Directions for Use TEP 12

860.1500 Crop Field Trials (fipronil, fipronil sulfide MB45950, fipronil sulfone MB46136, and MB46513) – rice grain TEP 24

870.3200 90-Day Dermal Study (fipronil) TGAI 24 870.3465 90-Day Inhalation Toxicity 3 (fipronil) TGAI 24 870.7800 Immunotoxicity (fipronil) TGAI 12

Non-guideline Hyalella azteca 42-d Test for Measuring the Effects
of Sediment-associated C ontaminants on Survival, Growth, and Reproduction 4 TGAI 24

Non-guideline Life-cycle Test for Measuring the Effects of
Sediment-associated Contaminants on Chironomus
dilutus (formerly known as C. tentans) 5 TGAI 2421 Guideline
Number Anticipated Data Requirement Test
Material Study
Duration
(months)

Non-guideline Leptocheirus plumulosus (Chronic Toxicity of
Marine and Estuarine Sediment-associated Contaminants) 6 TGAI 24

1 The anticipated DCI is expected to provide that registrants may conduct either Guideline 850.1025 (Oyster acute toxicity) or Guideline 850.1055 (Bivalve acute toxicity) although they should be the same across all chemicals and should match for parent ( Crassostrea virginianus was tested using fipronil).

2 A Tier II study is required. A Tier I plant study may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I study would necessitate conduct and submission of a Tier II study as well.

3 Based on expected duration of exposure, the anticip ated DCI is expected to provide that registrants may conduct a 28-Day inhalation toxicity study in lieu of a 90-day study.

4 Registrants must use the test method: Hyalella azteca 42-day Test for Measuring the Effects of Sediment-associated Contaminants on Survival, Growth, and Reproduction. In USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with
Freshwater Invertebrates. EPA 600/R-99/064.

5 Registrants must use the test method: Life-cycle Test for Measuring the Effects of Sedimentassociated Contaminants on Chironomus dilutus (formerly known as C. tentans). In USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with
Freshwater Invertebrates. EPA 600/R-99/064.

6 Registrants must use the test method: Leptocheirus plumulosus. In USEPA 2001. Method for Assessing the Chronic Toxicity of Marine and Estuarine Sediment-associated Contaminants with the Amphipod Leptocheirus plumulosus

. EPA 600/R-0l/020.