Docket Number EPA -HQ-OPP-2014-0262 www.regul ations. gov



# Spirodiclofen Preliminary Work Plan

Registration Review: Initial Docket Case Number 7443

Approved by:

Date: 

# March 2015

**~col.P~/b** Richard P. Keigwin, Jr. Director Pesticide Re-evaluation Division

### Spirodiclofen Preliminary Work Plan - Table of Contents
OVERVIEW
.. . ... .. ..................................... . .. . ... . .. .. ... . ..................................... . .. . .. .. .. .. .. . ... . .. . ... . ....... 3 ANTICIPATED DATA NEEDS
........ . ... . ... .. .. . : ............ . ........................... .. .. . .. .. .. .. .. . ...................... 3 STATUTORY AND REGULATORY AUTHORITY
................. .. .. . ... . .. .. ..................................... 5 CHEMICAL FACTS
. ... . ... .. ... . ................. . ......................... . .. . ... .. .. . .. .. ................... . .................... . .... 5 USE AND USAGE INFORMATION
.............. .. ... . ... . .. .. .. .. .. . ... . .................................... . ... . .. .. ... . .. .. 6 RECENT ACTIONS
.. .. .. ... .. .. . ... .. ... . ... . ..................................... .. ... . .. . ... . .. .. .. . ... . ............................... 7 ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW
... .. ...... . .. . ... .. .. . .. .. ..... 7 TIMELINE
........... . ... ..... .. ... . .............................................. . ....... .. .. . .. .. .. .. .. . ... . ... . ............................... 9 NEXT STEPS
.. ... . ... . .... .......................................... .. . . .. . ... . ... . ... . .. .. .. . ............................................... 9 Appendix

- Additional Areas Considered in the Spirodiclofen Registration Review
............. 10

References: This Preliminary Work Plan summarizes the Environmental Protection Agency's current position based on the following documents: 1. Registration Review

- Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Spirodiclofen. Justin Housenger and Larry Liu. Ph
.D
. January 28,2015. 2. Spirodiclofen. Human Health Assessment Scoping Document in Support of Registration Review. Kelly Lowe , Thomas Bloem, and Monique M. Perron, Sc.D. January 7 , 2015. 3. Spirodiclofen: Tier I Review of Human Incidents. E lizabeth Evans and Shanna Recore. October23, 2014. 4. BEAD Chemical Profile (BCP) for Registration Review: Spirodiclofen (PC Code: 124871). Nikhil Mallampalli, Claire Paisley

- Jones , and Michelle Ranville
. November 17, 2014. 5. Spirodiclofen (124871) Screening Level usage Analysis (SLUA). June 9, 2014. These and other supporting documents for the spirodiclofen registration rev i ew case may be found in th e docket E PA

- HQ

- OPP

- 2014

- 0262 at http: //www.regulations.gov
. 2OVERVIEW The docket for spirodiclofen is now open, initiating the first public comment period for this registration review (docke t number EPA-HQ-OPP-2014-0262). Spirodiclofen is an insecticide/miticide in the tetronic and tetramic acid chemical class that acts by interfering with development in eggs, and nymphal and adult female growth stages (adult males are not affected). Products containing spirodiclofen are registered for use to control mites , leafhoppers , and San Jose scale on crops including c itrus , grapes , stone fruit , pome fruit , and tree nuts. There are no residential uses for spirodiclofen. This Preliminary Work Plan (PWP ) document explains what EPA's Office of Pesticide Programs knows about spirodiclofen, highlighting anticipated data and assessment needs , identifying the types of information that would be especia lly useful to the Agency in conducting the review, and providing an anticipated timeline for completing the registrati on review for spirodic lofen
. The registration review process was designed to include a public participation component to solicit input from interested stakehol ders. The Agency intends , by sharing this information in the docket , to inform the public of what it knows about spirod iclofen and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on spirodiclofen. The Agency encourages all interested stakeho lders 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 spirodiclofen. Next , it discusses the statutory and regulatory authority for Registration Revi ew. Then the document provides chemical facts , use and usage information , recent actions, the anticipated risk assessments, and a projected registration review timeline fo r spirodiclofen. Fina ll y, 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. ANTICIPATED DATA NEEDS Table 1 below summarizes anticipated data needs for spi rodiclofen. For additi onal discussion of the anticipated data ne eds, see the Registration Review

- Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Co nducted for Spirodiclofen and Spirodiclofen. Human Health Assessment Scoping Document in Support of Registration Review.



### 3Table 1: Anticipated Data Needs for the Spirodiclofen Registration Re vi ew



### Estimated Guideline Timeframe Study Title 1 Test Number (Months from Material receipt of DCI) Anticipated Data Needs for the Parent Spirodiclofen 835.4200 Anaerobi c Soi l Metabo li sm TGAI 24 835.4400 Anaerobic Aquatic Metaboli sm TGA I 24 850
. 6100 Environmental C hemi stry Methods a nd Associate d TGA l 12 Indepe nd ent L abo ra tory Validation s fo r Water 850.135 0 Aq uatic Inverte brate Life Cycle (Saltwater) TGAI 12 850.1735 Wh o le Se dime nt: Acute Toxicity Fr es hw ater TGA I 12 Invertebrat es with Chironomus dilutus 1 • 3 850.1735 Whole Sedim e nt: Acute Toxic ity Freshwater T GA I 12 Invertebrates with H ya lella azteca1 .4 850.1740 Who l e Sediment: Acute To xic i ty Marine In verteb rate s T GA I 12 with Leptocheirus plumulosus 5•6 850.2100 Avian Oral T o xicity (Passer ine Speciesf TGAI 12 850.3040 Field Testing for Pollinators TEP 24 Spec ial S tud y (OEC D TG 237 ) : Honey Bee Larvae Acute Oral TGA I 12 Toxicit y& S pec ial St udy Honey Bee Larvae C hr onic Oral Toxici ty TGAI 12 S pec ial S tudy Hone y B ee A dult C hronic Oral Tox ic ity TGA I 12 Spec ial Stu dy F ie ld Tr ial of Residues in P o lle n and Nectar TEP 36 Spec ia l Stu dy Semi-Fie ld testing for Pollinators (Tu nnel or Co lony TEP 24 Feeding Studies) Anticipated Data Needs for Spirodiclofen Degradates 850.6100 Environmental C hem i stry Me thods a n d Associate d Oegra d ates 9 12 Independe nt La bora tory Validati o n s fo r Water TGA I 

### = tec hmcal grad e act tv e mgredtent ; TEP 

### = typtca l end-use product 1 On June 27,201 2, E PA an n o un ce d certain revis ions in harmoni zed g uideline serie s 850

- Eco logi cal Effects T es t s

- incl uding renumbering and other des ign atio ns or chan ges for so m e g uid e lin e s tud ies. See " F inal Test Gu idelines; OCSPP 850 Series; Notice of Availability " 77 FR 38282, Jun e 27 ,20 12. http: //www.regulations.gov 1# !documentDetaii:D = EPA-IfQ-OPPT-2009-0154-0028 2 Also known as "Who le Sediment: Subchronic Freshwater Invertebrates ," as per EFED Guidance Document

Entitled "Toxicity Testin g an d Ecolog ical Risk Assessment Guidance for Benthic In verteb rates." April20 14
. 3 A I0 -d ay study is anticipated to be requested. 4 A I 0

- day study is anticipated to be request ed. s Also known as " Whole Sediment: Subchronic Marine In vertebrates," as p er EFED Guidance Document Entitled

" Toxicity Testin g and Eco l ogical Ri sk Assessment Guidance for B en thi c In verteb rates." Apri l 2014. 6 A 1 0-day study is anti cipa ted to be requested. 7 A protocol does not ne ed to be s ubmitted for Agen cy approv a l prior to s tudy initiation provided that the stud y

adheres to the parameters outlined in the guidance available at: http: //www.epa.gov / pe s ticides l science /efed/policy guidance/team authors/terrestrial biology tech team lpasserin e ocspp850 21 00 avian oral tox.pdf 8 Depending on the des ign of the " H oney Bee Larvae Chronic Oral Toxicity," study, a 72- hour L Dso value may be

derived. I f this endpoint is a bl e to be derived, then it would obviate the anticipated need for the (OECD TG 237) (T ier I) Honey Bee Larvae Acute Oral Toxicity (Tier I) study. 9 Degradates of concern spirodiclofen-enol (BAJ 2740-enol) , spi rodiclofen-dihydroxy (BAJ 2740-dihydroxy) , and s pirodiclofen-ketohydroxy (BAJ 2740-ketohydroxy). 4STATUTORY AND REGULATORY AUTHORITY The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program . All pesticides distributed or sold in the United S tates (U.S.) generally must be registered

- b y the Environmental Protection Agency (EPA or the Agency), based on scie ntific 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 website. 1 The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide , and Rodent icide 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 beg in 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 believ es are needed to make a re gist ration 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 spirodiclofen. CHEMICAL FACTS Tab le 2 provides a summary of the chemical facts for spirodiclofen. Table 2: Chemical Facts for Spirodiclofen PC code 124871 Case Numb er 7443 CAS Number 148477-71-8 Year first registered 2005 Pesticide Type Insecticide/mi tic ide Chemical class Tetronic and tetramic acid family Reregistration Eligibility Because it was registered after November 1984, spirodiclofen Decision (REDi was not subject to reregistration. Tolerance Reassessment Because it was registered after November 1984, spiro diclofen Eligibility Deci sion (TRED) was not subject to tolerance reassessment. Cumulative group Not applicable. Spirodiclofen has not been identified as a member of a cumulative group that s hares a common mechanism oftoxicity.

1 http :// www.epa.gov/oppsrrd 1 / registration_review / 

### 5Table 2: Chemical Facts for Spirodiclofen 40 C FR Citation Tolerances for sp irodiclofen are established at 40 CFR § 180.608. Dual-use Spirodicl ofen is reg i stered for conventional pesticidal uses only and has no registered a ntimicrobial or biopesticidal use s. Non -p esticidal u ses There are no identified non-pesticidal uses of spi rodiclofen. Pesticide Re-evaluatio n Julia Stokes Division, Chemical Re v iew Stokes. j ulia @. epa.gov Manager (7 0 3) 347 -8 966 Registration Division, Mark Suarez Product Manager Suarez.Mark@epa.gov (703) 305-0120 USE AND USAGE INFORMATI ON Tab le 3 summari zes t h e use and usage information fo r spi rodiclof en. P leas e see the 

### BE AD Chemical Profile ( B C P

) for Registration Review : Spirodiclofen ( PC Cod e: 1 2 48 71 ) in the registration review do cket for more detail s. Table 3: Spirodiclofen Use and Usage Information Summary of Us e Spirodiclof e n is an in secticide/miticide that acts by interfering with growth regul ati o n and lipid bio synthes is. Use Sites Agricultural Us e Sites: Citrus , grapes , pome fru it , stone fruit , tre e nuts , tropical fruits, berries, h op s , and Chri stmas tree plantations. No n-Agricultural Use Sites: Spirodiclofen is not registered for any no n-agr icultura l uses. Summary of Usage An average of 85 ,000 p ounds of spirodiclofen was app li ed annually to 315,000 ac re s (2008-2012). The l a rgest usage of spirodiclof en was on o ranges (30% of the tot al pounds applied) , grapefrui t (20%), g rapes ( 18 %), and almonds (15%). The majority of spirodiclofen was applied in Fl orida (45% of total pounds applied) and Cal if ornia (40%). Formulation Type(s) Soluble concentrate Application Method(s) Product app li ed once per crop season by airblast eq uipment for all registered crops and by aer ial equipment on avocado and Christmas trees only. Technical Registrant( s) Bayer CropSci e nce LP No. of Registrations Two Sect i on 3 produ c ts 2
, one technical and one end-u se Restr ic ted Use No

2 S ection 3 product label s can be obtained from the Pesticide Product Lab el System (PPL S ) we bsite

(http: / / oas pub.epa. gov / pe s tlab 1/pp ls
.home). 

### 6Guidance for Commenters: Additional areas of use and usage related informati on requested for this registration review , and of particular interest to EPA, are described below
.
• The following usage information may assist in future Agency assessments for Spirodiclofen: Recent reports of pest resistance, information on comparative product performance or other aspects that underli e the drop in total spirodi c l ofen us e since 2010, and typical application rates
. • Confirmation of the following label information: site s of application, application method s and equipment, maximum application rates, frequency of application, application intervals, maximum number of applications per season, and geograp hic limitat ions on use. • Use distribution (e.g., acreage and geographical distribution ofrelevant use sites). • Median and 90th percentile reported use rates (lbs ailA) from usage data

- national, state, and county
. • Typical application timing (date of first application and application inte rvals )

- national , state, and county. • Usage/use information for non-agricultural us es . • T ypical app li cation interval (days). • State or local u se restrictions. RECENT ACTIONS Bayer CropScience requested a tolerance amendment for residues of spirodiclofen in citrus oil that was published on June 11 ,2014 (Docket ID: EPA-HQ-OPP -2013-041 1

- 003). ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW The most recent comprehensive human health risk assessment for sp irod iclofen was performed for pending uses on bushberries and tropical fruit; however, the app lica t i ons for amendments to add these uses were withdrawn
. The most recent human health risk assessment that covers currently registered uses for spirodiclofen was completed in October 2009. The most recent ecological and environmental fate risk assessment was completed in April 20 11. Findings and conclusions from th ese risk assessments are summarized in the Registration Review

- Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Spirodiclofen and Spirodiclofen. Human Health Assessment Scoping Document in Support ofRegistration 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 spirodiclofen. For human health, EPA anticipates the need to conduct revised dietary and occupational risk assessments during registration review. The need for spray drift and volati lizati on risk assessments will be considered during registration review. Table 4 below summarizes the anticipated registration review risk assessments based on the 

### EFED Problem Formulation and HED Scoping Document.

7

### Tab le 4: Anticipated Risk Assessments fo r the Spir odiclofen Registration Review Type of Risk Assess m ent Conduct? Notes Ecological and Environmental Fate Comprehensive eco logica l y Spirodiclofen will be considered the stressor of concern (species to be assessed for the risk asse s sment. Spirodiclofen and degradates include terrestrial and aquatic will be included in the drinking water exposure organisms) , including assessment. endangered species Incidents Will check For a discussion of the sole reported ecologica l inc ident for updates for spirodiclofen, see page 3 1 of the Problem Fo rmulat io n . Human Health D ietary Food y May be required to reflect the most recent d ietaryexposure models and revised estimated drinking water concentrations (EDWCs). Drinking water y May be revised to reflect the most recent d ietaryexposure models (specifically , use of PRZM

- GW). Occupational Handlers (mixers , loaders , y Updated inhalation assessments may be conducted to applicators) reflect maximum application rates , using current occupational exposure policies and updated inhalation toxicological points of departure. Post -application y A post-application inhalation assessment may be conducted to reflect maximum application rates, the highest exposure post-application activit ies, curre nt exposure po licies, and u pdated inhal ati on t ox icolog ical po ints of departure. Res i dent i al Handlers N There are no residential uses of spirodic lo f e n. Post-applicat ion y T h e need for spray drift and vo l atili zation ri sk assessments will be examined. Other Aggregate y Evaluates the combined risk from dietary and residential exposures and may be required to reflect potentially revised E DWCs. Cumulative N Spirodiclofen has not been identified as a member of a cumulative group that shares a common mechanism of toxicity , and spirodiclofen does not appear to produce a toxic metabo lite produced by other s ubstances. Tolerances 

### y Decisions concerning harmonization of the U.S. tolerance values with either the Canadian and/or Codex MRLs will be made as part of Regi stration Review.



### 8

### Table 4: Anticipated Risk Assessments for the Spirodiclofen Registration Review Type of Risk Assessment Conduct? Notes Incidents Will check For a discussion of the small number of reported human for updates incident s for spirodicl ofen, see page 1 0 of the Scoping Document and the Spirodiclofen: Tier I Review of Human Incid ents. 

### TIME LINE The estimated timeline for the completion of the spirodiclofen registration review appears in Table 5 below. 

### Table 5 : Projected Spirodiclofen Registration Review Timeline Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2015- March Close Public Comment 20 15- May Case Development F inal Work Plan 2015

- Au gust Issue DCI 2015- October- December Data Submission 2018- October- December 60

- day Public Comment Period for Draft Risk 2020- April- June Assessments 3 Registration Review Decision 60-day Public Comment Period for Pr oposed 2021

- January- March Regis tration Review Decision Registration Review Decision and Begin Post-Decision 2021 Follow

- up Total (years) 6 

### NEXT STEPS After the 60-day public c omment period clo ses, the Agency will re view and re spond to any co mments received in a timel y manner and then i ssue a Final Work Plan for the registration review of spirodiclofen.

3 The regulations governing Registra tion 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 conventiona l pesticides , the Agency plans to provide a 60 calendar day public comment pe riod generall y for draft ri sk assessments. 

### 9

### Appendix - Additional Areas Considered in the Spirodiclofen Registration Review PU BLIC COMMENTS AND FEEDBACK: Guidance for Commenters: The areas below highli ght top ics 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 proces s, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facil itatin g irritant resolution. The Agency will work to harmonize tolerances and internationa l maximum residue limits (M RLs) and may modify tolerance le vels to do so, whenpossible. Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack ofMRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as po ssible regarding th e nature of the concern. Water Quality: Spirodiclofen is not identified as a cause of impairment for any water bodies listed as impaired under sec tion 303(d) ofthe Clean Water Act. 4 In addition, no Total Maximum Daily Loads (TMDL) have been developed for spirodiclofen. 5 More information on impaired water bodies and TMDLs can be found at the Agency's we b site. 6 The Agency invites submission of water quality data for this pesticide . To the extent pos sible, data should conform to the quality standards in Appe ndix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP ' s Registration Review Risk Assessment and Management Process 7 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 env ironmental laws, regulations, and policies. To help address potential environmental justice issues, the Agenc y seeks informa tion on any groups or segments ofthe population who, as a result of their location, cultural practices, or other factors , may have atypical, unusually hiigh exposure to sp irodiclofen 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.

4 http: //iaspub.epa.gov/ tmdl waters I0/attains nation cy.cause detail 303d?p cause group id = 885
. 5 http: // iaspub.epa
. gov/ tmdl waters I0/attains nation.tmdl pollutant detail?p pollutant group id = 885&p pollutant

group name= PESTICIDES 6 http: //www.epa.gov/owow/tmdll 7 http: //www.epa.gov/ oppsrrd ! /registration review / water quality sop.htm 10ENDANGERED SPECIES: A ri sk assessment that supports a complete endangered species determination has not been conducted for spirodiclofen. The ecological risk assessment planned during registration review will all ow the Agency to determine whether use of spirodiclofen has " no effect" or " may affect " federa ll y listed threatened or endangere d 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. ENDOCRINE DISRUPTOR SCREENING PROGRAM: As requ ired by FIFRA and FFDCA, EPA reviews numerou s st udi es to assess potential adverse outcomes from exposure to chemicals. Co ll ectively, th ese 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 susceptib le 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 offs pring. For ecological hazard assessments, EPA evaluates acute tests and chron ic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for spirodiclofen , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 4 08(p ), spirodiclofen is subject to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP). EPA has developed the EDSP to determine whether certain s ub stances (i ncluding pesticide active and other ingredients) may have an effect in human s or wildlife similar to an effect produced by a "nat urally 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 screen in g assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals t hat go t hrough Tier 1 screening and are found to have the potential to interact withE, A , or T hormonal systems will proceed to the next stage ofthe EDS P where EPA will determine which , if any, of th e Tier 2 tests are necessary based on the available data. T ier 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 , o r T effect. Under FFDCA section 408(p) , the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test order s / data call-ins for the first group of67 chemicals , which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14 , 2013 8 and includes some pesticides scheduled for registration review and chemicals found in water. Neither of these lists

8 See http: //www .reg.ulations.gov/# !documentDetaii;D=EPA- HO-OPPT-2009-0477-0074 for the final second list of

chemicals. 1 1should be construed as a list ofknown or likely endoc rine disrupters. Spirodiclofen doesn 't appear on either li st. For further information on th e status of the EDSP , th e policies and pro ced ures , the lists of chemicals, future list s, t h e te s t guidelines and th e Tier 1 screening battery , pl ease visit our website. 9 HUMAN STUDIES: Past sp irodiclo fen risk assessments rely in p art on d ata fro m stu die s in w hi c h adult human subject s were intentionally expose d to a pe sticide to determine their dermal and inhalation expos ure. Many such studies, involving expos ure to many different pesticides, comprise generic pesticide exposure databases such as the Pe sticide Ha ndl er s Exposure Database (PHED), the Ag ricultural Handler Expos ure Tas k Force (AHETF) Database, and the Ag ri cultural Reentry Task Force (ARTF) Database. EPA has re viewed a ll the studies supportin g these multi

-pes ticide gener ic exposure databases, and has found no clear and co nvincing evidence that the conduct of any of them was either fundamentally un ethical or s ignificantly deficient relative to the ethical stand ards prevailin g at the time the re search was conducted. All applicable requ iremen t s of E

P A ' s Ru le for the Prot ectio n of Human Subjects of Research (40 CFR P art 26) have be en satisfied, and there is no regulatory barrier to continued reliance on these studi es.

9 http :// www.e pa. go v /en d o/ 12