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 Assessments for Registration Review 8

Timeline 9

Next Steps 10

Appendix – Additional Areas Considered in Buprofezin’s Registration Review 10

References:

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

based on the following documents:

1. Problem Formulation for the Environmental Fate, 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, leafhoppers, 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 what 

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 timeline 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 and 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 comments and information. Interested stakeholders could include: 

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

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

public at large.

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

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

provides buprofezin’s chemical facts, use and usage information, 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 

Registration Review 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 study1

TGAI 12

835.6200 Aquatic (sediment) field dissipation study1

TGAI 12

850.1500 Fish Life Cycle (freshwater or saltwater) TGAI 24

850.1350 Aquatic Invertebrate life cycle (saltwater) TGAI 12

Special

Study

Whole Sediment: Chronic toxicity to saltwater 

invertebrates – Examining survival, growth, and 

reproduction for Leptocheirus plumulosus (Draft 

OCSPP 850.1780)

TGAI 12

Special

Study

Whole Sediment: Chronic toxicity to freshwater 

invertebrates - Examining survival, growth, and 

reproduction for Chironomus dilutus or C. tentans. 

(Draft OCSPP 850.1760)

TGAI 12

Special

Study

Whole Sediment: Chronic toxicity to freshwater 

invertebrates - Examining survival, growth, and 

reproduction for Hyaella azteca. (Draft OCSPP 

850.1770)

TGAI 12

Special

Study Acute honey bee larvae feeding study TGAI 12

860.1340

Radiovalidation of livestock enforcement analytical 

method2 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 trials –

cucurbits2 (WP/DF formulation) TEP 24

860.1500

Magnitude of the residue crop field trials – lettuce2

(WP/DF formulation) TEP 24

860.1500

Magnitude of the residue crop field trials – stone 

fruit2 (WP/DF formulation) TEP 24

860.1500

Magnitude of the residue crop field trial – lemon2

(DF formulation) TEP 24

860.1520

Magnitude of the residue processed food/feed

Apple processing conducted at 5x2 TEP 24

860.1520

Magnitude of the residue processed food/feed grape 

processing conducted at 5x2 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 the 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 (buprofezin, 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 cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website3

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of buprofezin.

BUPROFEZIN CHEMICAL FACTS

PC code 275100

Case Number 7462

CAS Number 69327-76-0

Year first registered 2000

Pesticide Type Conventional Insecticide

Chemical class Insect Growth Regulator

Reregistration Eligibility 

Decision (RED)

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 BEAD Chemical Profile for Registration Review: Buprofezin (275100) in the 

registration review docket for more details.

Summary of Use Buprofezin is an insect growth regulator applied via foliar 

application to treat against insects in the suborder Homoptera.

Buprofezin is a chitin biosynthesis inhibitor, which disrupts 

molting, suppresses egg deposition and reduces egg viability.

Buprofezin products are sometimes co-formulated with 

flubendiamide, to control a broader spectrum of insect pests. 

Flubendiamide acts by modulating ryandine receptors when coformulated with buprofezin.

Use Sites Buprofezin is registered 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 

crops), vines, shrubs, and ground cover. Use sites also include 

nurseries, shadehouses/lath and greenhouses. Buprofezin is not

currently registered for residential uses.

Summary of Usage Buprofezin agricultural usage data from 2006 – 2010, indicates that 

approximately 100,000 pounds of buprofezin are applied annually, 

to approximately 150,000 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 buprofezin applied, California (70%) and Washington 

(15%) use more buprofezin than any other state.

Formulation Type(s) Buprofezin is formulated as a wettable 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 products4 and six Section 24c registrations

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

• Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; 

geographic limitations on use.

• Use distribution (e.g., acreage and geographical distribution of relevant use sites).

• Median and 90th 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 Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home).
8

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

and county.

• Typical application interval PHI (days).

• State or local use restrictions (if available).

• Any foreign technical registrants not listed above who supply technical buprofezin to the 

US market.

RECENT ACTIONS

New uses on brassica, head and stem, subgroup 5A; coffee, green bean; and pomegranate were

registered and tolerances established in July 2009 (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)). The most 

recent 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, the 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 assessments 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 assessments, as well as any changes to the standard operating 

procedures 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 Include? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed include 

terrestrial and aquatic 

organisms), including 

endangered species 

Y 

Human Health

Dietary
9

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 Aggregate 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 Commenters: Additional ecological information requested for this 

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

• Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency.

• Water quality monitoring data (see Appendix for further details).

TIMELINE

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

review.

Registration Review for Buprofezin – Projected Registration Review Timeline

Activities Estimated Date

Opening the Docket

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. – June
10

Registration Review for Buprofezin – Projected Registration Review Timeline

Activities Estimated Date

Registration Review Decision

Open Public Comment Period for Proposed Registration Review 

Decision

2017 – July – Sept. 

Close Public Comment Period 2017 – Oct. – Dec.

Registration Review Decision and Begin Post-Decision Follow-up 2018

Total (years) 6

NEXT STEPS

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

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of buprofezin.

Appendix – Additional Areas Considered in Buprofezin’s Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to 

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern. 

Water Quality:

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

under section 303(d) of the Clean Water Act5

. In addition, no Total Maximum Daily Loads 

(TMDL) has been developed for buprofezin6. More information on impaired water bodies and 

TMDLs can be found at the Agency’s website7

 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_

group_name=PESTICIDES 7 http://www.epa.gov/owow/tmdl/
11

Management Process8 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to buprofezin compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

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 appropriate.

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 from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision 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.htm
12

the existing hazard database. However, as required by FFDCA section 408(p), buprofezin is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

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

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

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

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

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

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

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

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

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

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

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

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

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

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 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 callins, 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 website9

.

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 such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the 

Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies supporting 

these multi-pesticide generic exposure databases, and has found no clear and convincing 

evidence that the conduct of any of them was either fundamentally unethical or significantly 

deficient relative to the ethical standards prevailing at the time the research was conducted. All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on 

these studies.

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