2 

### Indoxacarb Preliminary Work Plan – Table of Contents

Overview 4

Anticipated Data Needs 5

Statutory and Regulatory Authority 5

Chemical Facts 6

Use and Usage Information 7

Recent Actions 9

Anticipated Risk Assessments for Registration Review 9

Timeline 12

Next Steps 12

Appendix – Additional Areas Considered in the Indoxacarb Registration Review 13

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Registration Review Problem Formulation for Indoxacarb

. Christopher M. Koper, Robin Sternberg. May 9, 2013.

2. Indoxacarb Human Health Risk Assessment Sc oping Document in Support of Registration

Review . Danette Drew. May 9, 2013.

3. Indoxacarb: Review of Human Incidents . Elizabeth Evans, Shanna Recore. March 13,

2013.

4. BEAD Chemical Profile for Registration Review: Indoxacarb (067710). Monisha Kaul. December 10, 2012.

5. Indoxacarb (067710) Screening Level Usage Analysis (SLUA) . October 12, 2012.

6. PRD Label Data Report: Food/Feed & N on-Food/Non-Feed Uses Considered in Registration Review Work Planning. Indoxacarb. November 27, 2012.3 These and other supporting documents for the in doxacarb registration re view case may be found in the docket EPA-HQ-OPP-2013-0367 at http://www.regulations.gov

.4 OVERVIEW

The docket for indoxacarb is now open, initiati ng the first public comment period for this registration review (docket number EPA-HQ-O PP-2013-0367). Indoxacarb is a broad-spectrum, oxadiazine insecticide register ed for use against caterpilla rs, beetles, leafhoppers, ants, cockroaches, and mole crickets. Indoxacarb products are registered for use in agricultural, residential, commercial, institutional, and industr ial sites. The term “indoxacarb” can refer to any of several chemical forms of the compound, differentiated by S-enantiomer to R-enantiomer ratio. See Table 3 of this document for more information. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about indoxacarb, highlighting anticipated data and assessment need s, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing the registration review for indoxacarb.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows ab out indoxacarb and what types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on indoxacarb. The Agency encourages all intere sted stakeholders to review the PWP and Appendix and to provide comments and addition al 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 iden tified in the PWP and Appendix about which the Agency specifically seeks comments and informa tion. Interested stakeholders could include: environmental non-profit or interest groups; pe sticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for indoxacarb. Next, it discusses the statutory and regul atory authority for Registration Review. Then the document provides chemical facts, use and usage info rmation, recent actions, the anticipated risk assessments, and a projected registration review timeline for indoxacarb. Finally, the Appendix

to this document includes identification and di scussion of some areas that are considered generally in Registration Review along with some additional chem ical case-specific information.5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data need s for indoxacarb. For additional discussion of the anticipated data needs, see the Registration Review Problem Formulation for Indoxacarb and

Indoxacarb Human Health Risk Assessment Sc oping Document in Support of Registration

Review

.

Table 1: Anticipated Data Needs fo r the Indoxacarb Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent Indoxacarb

835.4200 Anaerobic soil metabolism TGAI 24

835.6100 Terrestrial field dissipation study – Storage stability in soil and Analytical methods, soil and

water TGAI 12

850.1075 Acute toxicity estuarine and marine organisms –

estuarine/marine fish DPX-MP062 12

850.2100 Avian oral toxicity (passerine species) DPX-MP062 12

850.4100 Terrestrial plant toxicity, seedling emergence TEP with DPXMP062 and

TEP with DPXKN128 12

850.4150 Terrestrial plant toxicity, vegetative vigor TEP with DPXMP062 and

TEP with DPXKN128 12

Nonguideline (Special Study) Larval honey bee acute oral toxicity DPX-MP062 12

Anticipated Data Needs for Indoxacarb Degradates

850.1075 Freshwater fish toxicity, coldwater species Degradate INMP819 12

TGAI = technical grade active ingred ient; TEP = typical end-use product

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 Stat es (U.S.) generally must be registered by the

1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-00286 Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website. 2

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration 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 docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of indoxacarb.

CHEMICAL FACTS

Table 2 provides a summary of th e chemical facts for indoxacarb.

Table 2: Chemical Facts for Indoxacarb

PC code 067710; The term ‘indoxacarb’ generally refers to the Senantiomer, but may also refer to a mixture. For a description of the various forms of indoxacarb, see Table 3 below.

Case Number 7613

CAS Number 173584-44-6 Year first registered 2000 Pesticide Type Insecticide

Chemical class Oxadiazine class Reregistration Eligibility Decision (RED) Because it was registered afte r November 1984, indoxacarb was not subject to reregistration. Cumulative group Not applicable. Indoxacarb ha s not been identifie d as a member of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for indoxaca rb are established in 40 CFR 180.564(a).

Pesticide Re-evaluation Division, Chemical Review Manager Katie Weyrauch, weyrauch.katie@epa.gov , (703) 308-0166

2 http://www.epa.gov/oppsrrd1/registration_review/7 Table 2: Chemical Facts for Indoxacarb

Registration Division, Product Manager John Hebert, hebert.john@epa.gov , (703) 308-6249

The term “indoxacarb” generally refers to th e S-enantiomer (also called DPX-KN128 or KN128) but may also refer to a racemic mixture. Als o, there are two indoxacarb degradates that EPA plans to consider in the indoxacarb ecological ri sk assessment. See Table 3 below for more

information.

Table 3: Indoxacarb Parent Compounds and Degradates 3

Indoxacarb Parent Compound Descriptions Name Also referred to as

S-enantiomer DPX-KN128 KN128

R-enantiomer DPX-KN127 KN127

75:25 S:R ratio DPX-MP062 MP062

50:50 S:R ratio DPX-JW062 JW062 Indoxacarb Degradates to be Cons idered in the Ecological Assessment

IN-JT333

IN-MP819

USE AND USAGE INFORMATION

Table 4 summarizes the use and usage information for indoxacarb. Please see the BEAD Chemical Profile for Registra tion Review: Indoxacarb (067710) in the registration review docket

for more details.

Table 4: Indoxacarb Use and Usage Information

Summary of Use Broad-spectrum insecticid e registered for use against caterpillars, beetles, leafhoppers, ants, fire an ts, cockroaches, mole crickets,

fleas and ticks. Use Sites Indoxacarb products are registered for use in agricultural sites including bush berries, cane berrie s, grapes, nut crops, stone fruits, pome fruits, spice crops, cucurbit s, fruiting vegetables, leafy and stem vegetables (grown for greens and salads), root crop vegetables, corn, peas, forage gra sses, alfalfa, cotton, soybeans, and
peanuts. Indoxacarb products are also re gistered for use indoors and outdoors in non-agricultural, residen tial, commercial, institutional, and industrial sites, including orna mental plants, ornamental lawns and turf, ornamental woody shrubs a nd vines, ornamental trees, pets and animals in enclosures, pr ivate or commercial domestic

3 For more information about the chemical forms of indoxacarb parent and degradates, see p. 2 of the Indoxacarb Human Health Risk Assessment and Scoping Document in Support of Registration Review , and p. 40 of the Registration Review Problem Formulation for Indoxacarb

.8 Table 4: Indoxacarb Use and Usage Information

dwellings and their contents, uncul tivated non-agricultural areas, schools and buildings, commercial transportation facilities, food and feed processing plants and areas, eating establishments, food marketing/storage/distribution f acilities, hospitals and related institutions, bathrooms, refuse a nd solid waste sites, conifers, and

crack and crevice treatments. Summary of Usage From 2007-2011, indoxacarb’ s total agricultural usage averaged 39,000 pounds a.i. for 558,000 treate d acres with an overall application rate averaging 0.07 lbs a.i. per acre. The crops on which the greatest usage was reported were tomato, cotton, broccoli, soybean, and peanuts. The available non-agricultural usage data sources did not report any usage for the non-agricultural

use sites. Formulation Type(s) Formulation types incl ude granules; impregnated materials; water dispersible granules; emulsifi able, flowable, and soluble concentrates; and ready-to-use solution. Application Method(s) Products can be applied via broadcas t spray or spot treatment, mound treatment, chemigation, spot-on, and baits. Technical Registrant(s) E.I. Du Pont de Nemours and Company No. of Registrations 37 Section 3 products 4 ; 2 Section 24c registrations

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 Confirmation of the following label information: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

 Use distribution ( e.g. , acreage and geographical distri bution of relevant use sites).

 Median and 90 th percentile reported use rates (lbs a i/A) from usage data – national, state, and county.

 Typical application timing (date of first applic ation and application in tervals) – national, state, and county.

 Usage/use information for non-agricultural uses.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrants not listed above who supply tech nical indoxacarb to the US

market.

4 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).9 RECENT ACTIONS

New use requests are pending for dry bean, snap bean, small fruit vine climbing (subgroup 13- 07F), low-growing berry (subgroup 13-07H). The PRIA due date for these requests is August

2013.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for indoxacarb was completed on May 2, 2013 in preparation for a new use request. The most recent ecological and environmental fate risk assessment was completed January 3, 2013 for the same purpose. Findings and

conclusions from these risk assessments are summarized in the Registration Review Problem Formulation for Indoxacarb and Indoxacarb Human Health Risk Assessment Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of indoxacarb. For human health, EP A anticipates that there will be no need for revised dietary, residential, or occupational risk assessments dur ing registration review, be cause the toxicological database in respect to human health is complete, and all human health assessments have been recently updated for the pending new uses. If t oxicological endpoints or points of departure are revised, they will be considered in future asse ssments, as well as any changes to the standard operating procedures or defa ult exposure assumptions.

Table 5 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.

Table 5: Anticipated Risk Assessments for the Indoxacarb Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms), including endangered species Y In addition to parent indoxacarb, the aquatic ecological risk assessment will consider indoxacarb degradates IN-JT333 and IN-MP819 using a toxic equivalency (TEQ) approach.

Incidents Will check for updates For a discussion of reporte d ecological incidents for indoxacarb, see page 17 of the Problem Formulation.

Human Health Dietary Food N In the most recent dietary assessment, there were no dietary risk estimates of concern. No new data are needed to assess potential dietary exposure and risk and there are no dietary risks of concern for indoxacarb. A new dietary risk assessment is not anticipated for the registra tion review of indoxacarb. Drinking water N10 Occupational Handlers (mixers, loaders, applicators) N In the most recent occupational exposure assessment,there were no occupational handler or postapplication risk estimates of concern. No new data are anticipated to be required to assess potential occupational exposure and risk. A new occupational exposure assessment is not anticipated for the registration review of indoxacarb. Post-application N

Residential Handlers N In the most recent residential handler exposure assessment, there were no handler risks estimates of concern. No new data are anticipated to be required to assess potential residen tial exposure and risk. A new residential exposure assessment is not anticipated for the registrati on review of indoxacarb. Post-application N In the most recen t residential risk assessment for indoxacarb, there are no reside ntial risk estimates of concern for the current uses, except for indoor surface directed sprays when a s pot-directed treatment isassumed. In that case, non-dietary oral (hand-tomouth) exposures for children (1 to <2 years)

exceeded the level of con cern. When a crack and crevice only treatment is assumed for the spray, there

are no risks estimates of concern. The crack and crevice treatment scenario uses a lower exposure estimate than the spot-directed treatment scenario.

The current label does not restrict the indoor spray use to crack and crevice only, and EPA is working with registrants to address this concern. No new data are needed to assess po tential residential postapplication risk. A new residential risk assessment is not anticipated for the registration review of

indoxacarb.

Other11 Aggregate N Evaluates the combined risk from dietary and residential exposures. In the most recent aggregate risk assessment for indoxacarb, there were no aggregate risks estimates of concern for indoxacarbwhen the aggregate assessment uses the crack-andcrevice exposure estimates for indoor surface spray. Note: the aggregate asse ssment for indoor surface directed sprays assumed only crack and crevicetreatment. The residential post-application (hand-tomouth) exposure to spot-directed sprays , for which EPA uses a higher exposure estimate, resulted in a risk estimate of concern for children. The Agency is working with registrants to address this concern. No

new data are needed to address potentia l aggregate risk. A new aggregate risk assessment is not anticipated for the registra tion review of indoxacarb. Cumulative N The Food Quality Prot ection Act (FQPA) requires the Agency to consider the cu mulative risks of chemicals sharing a common mechanism of toxicity. EPA does not have, at this time, available data to determine

whether indoxacarb has a common mechanism of toxicity with other subs tances. Therefore, a cumulative risk assessment has not been performed for indoxacarb, and is not anticipated for the registration review of indoxacarb. Tolerances N During registration review, the Agency will evaluate the tolerance levels to determine if they can be

harmonized with Codex maximum residue limits (MRLs).

Incidents Will check for updates For a discussion of reported human incidents for indoxacarb, see page 9 of the Scoping Document and

the Indoxacarb: Review of Human Incidents

.

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 alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).12 TIMELINE

EPA has created the following estimated ti meline for the completion of the indoxacarb registration review in Table 6 below.

Table 6: Projected Indoxacarb Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2013 – June Close Public Comment 2013 – August Case Development

Final Work Plan 2013 – November Issue DCI 2014 July – September Data Submission 2016 July – September 60-day Public Comment Period for Draft Risk

Assessments 5 2018 January – March

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision 2018 October – December

Registration Review Decisi on and Begin Post-Decision Follow-up 2019

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 i ssue a Final Work Plan for the registration

review of indoxacarb.

5 The regulations governing Registration Review generally require the Agency to provide a public comment period

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.13 

### Appendix – Additional Areas Considere d in the Indoxacarb Registration

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

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. 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, provi ding as much specificity as possible regarding

the nature of the concern.

Water Quality:

Indoxacarb is not identified as a cause of impa irment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 6 In addition, no Tota l Maximum Daily Loads (TMDL) have been developed for indoxacarb. 7 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 8 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 Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process 9 in order to ensure they can be us ed quantitatively or qualitatively 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 indox acarb compared to th e general population. Please comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to the general population.

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

7 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

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

9 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm14 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for indoxacarb. The ecological risk assessment planned durin g registration review will allow the Agency to determine whether us e of indoxacarb has “no effect” or “may affect” federally listed threatened or endangered specie s (listed species) or their designated critical habitats. When an assessment concludes that a pe sticide’s use “may affect” a listed species or its designated critical habitat, the Agency will c onsult with the U.S. Fish and Wildlife Service

and/or National Marine Fisheries Service (the Se rvices), 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 Protecti on Agency (EPA) for allegedly failing to undergo

consultation with the United States Fish and W ildlife Service and the National Marine Fisheries Service regarding the effect s of over 350 pesticides, incl uding indoxacarb, on over 200 endangered and threatened species throughout the United States (C enter 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 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 e ndpoints 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 re cent registration decision for indoxacarb, EPA reviewed these data and selected the most sensitive endpoint s for relevant risk assessment scenarios from the existing hazard database. However, as re quired by FFDCA section 408(p), indoxacarb is subject to the endocrine screeni ng part of the Endocrine Disrup tor 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 screening 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. Between15 October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingr edients and 9 inert ingredients. Indoxacarb is not among the group of 58 pesticide active ingredient s 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 indoxacarb. For further information on the status of the EDSP, the policies and procedur es, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 scr eening battery, please visit our website. 10

HUMAN STUDIES:

Occupational and Residential

Past indoxacarb risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to de termine their dermal and inhalation exposure. Many such studies, involving exposur e to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handl ers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Database, and th e Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, and has found no clear and c onvincing evidence that the conduct of any of them was either fundamentally unethical or si gnificantly deficient relative to the ethical standards prevailing at the time the research wa s conducted. All applicab le requirements of EPA’s Rule for the Protection of Human Subject s of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barri er to continued reliance on these studies.

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