2 

### Buprofezin Preliminary Work Plan

– Table of Contents

Overview 3

Anticipated Data Needs 4

Statutory and Regulatory Authority 6

Chemical Facts 6

Use and Usage Information 7

Recent Actions 8

Anticipated Risk Assessment s for Registration Review 8

Timeline 9

Next Steps 10

Appendix

– Additional Areas Considered in Buprofezin’s Registration Review 10

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. Problem Formulation for the Environmental Fate, Ecological Risk, and Endangered Species in Support of the Registration Review of Buprofezin

. Parker

, Ronald and Mastrota

, Nicholas

. May 21, 2012

.

2. Buprofezin: Human Health Risk Scoping Document in Support of Registration Review

. Miller, James S; Hummel, Susan; and Khasawinah, Abdallah

. April 17, 2012

.

3. BEAD Chemical Profile for Registration Review: Buprofezin (275100)

. Kaul, Monisha; Doucoure, Cynthia; and Lee, Andrew

. December 15, 2012

.

4. Buprofezin: Review of Human Incidents

. Recore, Shanna

. February 14, 2012

.

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

in the docket EPA

- HQ

- OPP

- 2012

- 0373 at http://www.regulations.gov

.3 OVERVIEW

The docket for case number 7462 is now open , initiating the first public comment period for this registration review (docket number EPA

- HQ

- OPP

- 2012

- 0373 )

. Buprofezin is an insect growth regulator registered for use against a variety of homopteran pests (e.g.

, cicadas, whiteflies, plant lice, mealy bugs, leafho ppers, and scale insects ) . There are no registered residential/homeowner

uses, and buprofezin products are used primarily in agricultural areas on various food and feed

crops, ornamentals, and trees. This Preliminary Work Plan (PWP) document explains wha t EPA's Office of Pesticide Programs knows about buprofezin , highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timel ine for completing buprofezin’s review.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about buprofezin a nd what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on buprofezin . The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional information that will help the Agency’s

decision

- making process for this chemical. In addition to general areas on which persons may wish to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comment s and information. Interested stakeholders could include:

environmental non

- profit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, residential, and other users of pesticides; or the public a t large.

The Preliminary Work Plan begins by listing the anticipated data needs for buprofezin

. Next, it discusses the statutory and regulatory authority for R egistration R eview. Then the document provides buprofezin ’s chemical facts, use and usage info rmation, recent actions, the anticipated risk assessments, and a projected registration review timeline. Finally, the Appendix to this document includes identification and discussion of some areas that are considered generally in

R egistration R eview along with some additional chemical case

- specific information.4 ANTICIPATED DATA NEEDS

1. The table below summarizes anticipated data needs for buprofezin . For additional discussion of the anticipated data needs, see the Problem Formulation for the Environmental Fate, Ecological Risk, and Endangered Species in Support of the Registration Review of Buprofezin and Buprofezin: Human Health Risk Scoping Document in Support of Registration Review

.

Anticipated Data Needs for Buprofezin ’s Registration Review

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

835.4300 Aerobic Aquatic Metabolism TGAI or

PAIRA 24

835.6100 Terrestrial field dissipation study 1 TGAI 12

835.6200 Aquatic (sediment) field dissipation study 1 TGAI 12

850.1500 Fish Life Cycle (freshwater or saltwater) TGAI 24

850.1350 Aquatic Invertebrate life cycle (saltwater) TGAI 12

Sp ecial Study Whole Sediment: Chronic toxicity to saltwater

invertebrates

– Examin ing survival

, growth

, and reproduction for Leptocheirus plumulosus ( Draft OCSPP 850.1780) TGAI 12

Sp ecial Study Whole Sediment: Chronic t oxicity to f reshwater

i nvertebrates

- Examining s urvival, g rowth, and

r eproduction for Chironomus dilutus or C. tentans

. ( Draft OCSPP 850

. 1760) TGAI 12

Sp ecial Study Whole Sediment: Chronic t oxicity to f reshwater

i nvertebrates

- Examining s urvival, g rowth, and

r eproduction for Hyaella azteca . ( Draft OCSPP

850.1770 ) TGAI 12

Sp ecial Study Acute honey bee larvae feeding study TGAI 12

860.1340 Radiovalidation of livestock enforcement analytical

method 2 TEP 24

1 See footnote 7 of 40 CFR 835.6100 and 835.6200 . EPA anticipates requiring only the environmental chemistry

analytical methods and independent laboratory (ILV) portions of this guideline for soil and water, rather than the full field dissipation study. Storage stability data are also required for 835 .6100 to upgrade the terrestrial field dissipation study (MRID 44394044, guideline 835.6100)

.5 Anticipated Data Needs for Buprofezin ’s Registration Review

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

860.1500 Magnitude of the residue crop field tr i a l s

– cucurbits 2 (WP/DF formulation) TEP 24

860.1500 Magnitude of the residue crop field tr i a l s

– lettuce 2
(WP/DF formulation) TEP 24

860.1500 Magnitude of the residue crop field tr i a l s

– stone

fruit 2 (WP/DF formulation) TEP 24

860.1500 Magnitude of the residue crop field trial

– lemon 2
(DF formulation) TEP 24

860.1520 Magnitude of the residue processed food/feed
Apple processing conducted at 5x 2 TEP 24

860.1520 Magnitude of the residue processed food/feed grape processing conducted at 5x 2 TEP 24

870.3465 Sub

- chronic (28/90

- day) inhalation

– rat TGAI 12

The study listed below was previously required as a condition of registration by the Registration Division in connection with the approval of new buprofezin uses on brassica, coffee, green bean and pomegranate. This data requirement will be included in th e buprofezin registration review generic data

call

- in.
Special Study Developmental Thyroid study TGAI 24

TGAI = technical grade active ingredient; TEP = typical end

- use product; PAIRA = pure active ingredient, and

radiolabeled ; WP = Wettable Powder; DF = Dry Flowable

__________________________ 2 Analyses required for BF

- 4 conjugate, and all residues for risk assessment (b uprofezin, BF

- 9, BF

- 12, and BF

- 26 )6 STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program

. All pesticides distributed or sold in the United States (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cau se 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 p esticides 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 Age ncy periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website 3

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

, and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40

. 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

comme nt period, the Agency will develop a F inal W ork P lan (FWP) and anticipated schedule for

the registration review of buprofezin

.

BUPROFEZIN CHEMICAL FACTS

PC code 275100

Case Number 74 6 2

CAS Number 69327

- 76

- 0

Year first registered 2000 Pesticide Type Conventional Insecticide

Chemical class Insect Growth Regulator

R eregistration Eligibility Decision (R E D) Not Applicable

Cumulative group Not Applicable

40 CFR Citation Tolerances for buprofezin are established in 40 CFR 180.511

. Dual

- use No

Non

- pesticidal uses None

Pesticide Re

- evaluation Division, Chemical Review Manager James Parker

, parker.james@epa.gov

, ( 703 ) 306

- 0469

Registration Division

, Product Manager Mark Suarez

, suarez.mark @epa.gov

, (703) 305

- 0120

______________________ 3 http://www.epa.gov/oppsrrd1/registration_review/7 USE AND USAGE INFORMATION

Please see the B EAD Chemical Profile for Registration Review: Buprofezin (275100) in the registration review docket for more details

.

Summary of Use Buprofezin is an i nsect growth regulator applied via foliar application to treat against insects in the suborder Homoptera

. Buprofezin is a chitin biosynthesis inhibitor, which disrupts

mo lting, suppresses egg deposition and reduces egg viability.

Buprofezin p roducts are sometimes co

- formulated with

flubendiamide

, to control a broader spectrum of insect pests

. Flubendiamide acts by modulating ryandine receptors when co

formulated with buprofezin

. Use Sites Buprofezin is r egistered for use on various agricultural food/feed

crops (e.g.

, vegetable, fruit and nut crops)

, coffee, beans, ornamentals, trees, cotton (fiber crop), sapodilla (specialized field

crop s ), vines, shrubs, and ground cover . U se sites also include nurseries, shadehouses/lath and greenhouses

. Buprofezin is n o t currently registered for residential uses

. Summary of Usage Buprofezin agricultural usage data from 2006

– 2010, indicates that approximately 10 0

, 000 pounds of buprofezin are applied annually,

to approximately 15 0

, 000 acres. Buprofezin is primarily applied to

pears (20%)

, wine grapes (19%) , oranges (18%) , raisin grapes (11%), cotton (7%), table grapes (6%), and other ( 9%) . In terms of pounds of buprof ezin applied, California (70%) and Washington (15%) use more buprofezin than any other state. Formulation Type(s) Buprofezin is f ormulated as a w ettable powder, soluble concentrate

and emulsifiable concentrate

. Application Method(s) Buprofezin is applied using foliar spray applications including: broadcast applications via ground and aerial equipment or ground/airblast sprayers

. Technical Registrant (s) Nichino America, Inc. No. of Registrations There are five Section 3 products **4** and six Section 24c registrations

Restricted Use No

Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , and of particular interest to EPA, are described below.

**•** C onfirmation of the following label information : sites of application ; formulations ; application methods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum number of applications per season ; geographic limitations on u se

.

**•** U se distribution ( e.g. , acreage and geographical distribution of relevant use sites )

.

**•** M edian and 90 th percentile reported use rates (lbs ai/1000 sq ft) from usage data

– national, state, and county

.

**4** Section 3 product labels can be obtained from the Pesticide Produ ct Label System (PPLS) website ( http://o aspub.epa.gov/pestlabl/ppls.home ).8 **•** A pplication timing (date of first application and app lication intervals)

– national, state, and county

.

**•** Typical application interval PHI (days)

.

**•** S tate or local use restrictions (if available)

.

**•** Any f oreign technical registrants not listed above who supply technical buprofezin to the

US market

.

RECENT ACTIONS

N ew use s on brassica, head and stem, subgroup 5A; coffee, green bean; and pomegranate were registered and tolerances established in July 20 09 ( 74 FR 33158 7/10/09 ( FRL

- 8421

- 3) ).

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

1. The most recent comprehensive human health risk assessment for buprofezin was completed in June 2009 to support a new use amendment request (for use of buprofezin on

coffee , green bean , pomegranate, brassica head and stem crops (subgroup 5A) )

. T he most

re cent ecological and environmental fate risk assessment was completed in February 2009 for the same purpose . Findings and conclusions from these risk assessments are

summarized in the Problem Formulation for the Environmental Fate, Ecological Risk, and Endangered Species in Support of the Registration Review of Buprofezin and Buprofezin: Human Health Risk Scoping Document in Support of Registration Review

.

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of buprofezin

. For human health, EPA anticipates the need to conduct revised dietary and occupational risk assessment s during registration review

. If toxicological endpoints or points of departure are revised based on the data that are anticipated to be required for registration review

, they will be considered in the new assessment s
, as well as any changes to the standard operating

p rocedures or default exposure assumptions

.

The table below summarizes the anticipated registration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document

.

Anticipated Risk Assessments for Buprofezin’s Registration Review

Type of Risk Assessment Incl ude? Notes

Eco logical and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms ), including endangered species Y

Human Health Dietary9 Food Y A new assessment maybe required to incorporate any

new residue chemistry data submitted prior to assessment development. Drinking water Y Occupational Handlers (mixers, loaders, applicators) Y Occupational assessments may be updated to incorporate any new standard operating procedures and any new toxicity data submitted prior to assessment development. Post

- application Y

Residential

Handlers N No residential use and no expectation of residential

exposure.
Post

- application N

Incidental oral N Companion animal N

Recreational N

Other Aggregate Y A ggregate exposure is equal to dietary (food and water) exposure as there are no residential exposures

. Cumulative N A common mechanism of toxicity with other substances has not been identified for buprofezin.

Tolerances Y

Guidance for Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

**•** Ec ological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already r eported to the Agency

.

**•** Water quality m onitoring data (see Appendix for further details)

.

TIMELINE

EPA has created the following estimated timeline for the completion of buprofezin ’s registration

review

.

Registration Review for Buprofezin

– Projected Registration Review Timeline

Activities Estimated Date Opening the D ocket Open Docket and Public Comment Period 2012

– June

Close Public Comment 2012

– August Case Development

Final Work Plan 2012

– November

Issue DCI 2013

– July

– Sept.

Data Submission 2015

– July

– Sept. Open Public Comment Period for Draft Risk Assessments 2017

– Jan.

– March

Close Public Comment Period 2017

– Apr.

– June10 Registration Review for Buprofezin

– Projected Registration Review Timeline

Activities Estimated Date Registration Review Decision Open Public Comment Period for Proposed Registration Review

D ecision 2017

– July

– Sept.

Close Public C omment P eriod 2017

– Oct.

– Dec

. Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2018 Total ( years ) 6

NEXT STEPS

After the 6 0

- day public comment period closes, the Agency will review and respond to any comments received in a timely manner and then issue a Final Work Plan for the registration

review of buprofe z in

.



### Appendix

– Additional Areas Considered in Buprofezin ’s Registration Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference to sou rces of additional information c ould be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency

will work to harmonize tolerances and international maximum r esidue limits (MRL s ) and may modify tolerance levels to do so, when possible

. Growers and other stakeholders are asked to

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export market s, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

Buprofezin is not identified as a cause of impairment for any water bodies listed as impaired
under section 303(d) of the Clean Water Act **5**

. In addition, n o Total Maximum Daily Load s (TMDL) has been developed for buprofezin **6** . More information on impaired water bodies and

TMDLs can be found at the Agency’s website **7**

**5** . 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

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

**6** http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

gr oup_name=PESTICIDES

**7** http://www.epa.gov/owow/tmdl/11 Management Process **8** in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the popula tion who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to buprofezin compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unus ually high exposure compared to the general population.

ENDANGERED SPECIES :

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

conducted for buprofezin

. The ecological risk assessment planned during registration review will allow the Agency to determine whether buprofezin ’s use 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 app ropriate.

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

North America filed a lawsuit in the United States District Court for the Northern District of California, against the Environmental Protection Agency (EPA) 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 buprofezin , 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.)

.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse

outcomes fr om 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 w hich 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 haza rd 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 for buprofezin

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from

**8** http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 the existing hazard database. However, as required by FFDCA section 408(p), buprofezin is subject to the endocrine screening part of the Endocrin e 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 e strogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chem ical 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 relationshi p 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. Buprofezin 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 buprofezin

. 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 **9**

.

HUMAN STUDIES :

Occupational

Past buprofezin 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 s uch studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Ha ndlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database

. EPA has reviewed all the studies s upporting

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 tim e the research was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied , and t here is no regulatory barrier to continued reliance on

these studies

.

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