Docket Number EPA-HQ-OPP- 2014-0778 www.regulations.gov



# Oxyfluorfen Preliminary Work Plan

Registration Review: Initial Docket Case Number 2490

Approved by:

Date: 

# December 2014

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# ;:p Richard P
. Keigwin, Jr. Director Pesticide Re

-evaluation Division
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## '-1Oxyfluorfen Preliminary Work Plan- Table of Contents OVERV IE W . .. ... ........................ .. ..... .. ........ . .. . .. .. ...... . ........... . .................. . ............................. ....... .. 4 ANTICIPATED DATA NEEDS .................................. . .............. . ................ . ................................. 5

STATUTORY AND REGULATORY AUTHORITY ................. . ...... . .... . ................ . .. . ... . ... . ......... 6

CHEMICAL FACTS .. .. . ... .. .. .. .. .. .. . .. .. .. .. .. .. .. .. .. . ... . .. .. .. .. ... . .. .. .. ... .. . .. .. ... . ... . .. ... .. .. .. .. .. .. .. ... .. . ... .. ... . ... . 6 USE AND USAGE INFORMATION . .. .. .. .. . .. ... . .. .. .. .. .. .. .. .. ... . .. .. .. .. .. .. ... . .. .. ... . ... . ... .. .. ... .. .. .. ....... . .... 7 RECENT ACTIONS ................................... . ...................................... . ............................................ 8 ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 8 TIMELINE .............................................................................. . ....... . ... .. .. . ... .. .. .. .. .. ... . ... . ....... ... . ... .. 12 NEXT STEPS ......................................... ... ...... .................................................................. .. .. ....... 12 Appendix- Additional Areas Considered in the Oxyfluorfen Registra t ion Review ................ 13

References: Th i s Preliminary Work Plan summarizes the Environmenta l Protection Agency's current position based on the fo ll owing documents: 1 . Registration Review Problem Formulation for Oxyfluorfen. Rob i n Sternberg and He Zhong . 11103/20 14. 2. Human Health Assessment Seeping Document in Support of Registration Revie w. I van Nieves, Ayaad Assaad, Marquea King, Bonnie Cropp-Kohlligan, and Susan Hummel. 10 /9/1 4. 3. Oxyfluorfen: Tier 1 Review of Human Incidents. Elizabe th Evans and S h anna Recore. 07 / 17/2014. 4. BEAD Chem i cal Profi l e (BCP) for Registration Review: Oxyfluorfen (11160l).Sunil Ra tnayake, Rafael A. Prieto, Stephen Smearman, and Amet Jone s. 1114 /2014 . 5. Screening Level Usage Analysis (SLUA) . 04/30/2014. 26. HED Master Label Report (Oxyfluorfen 111601). 06/30 /2014. 7. EFED Table 1 Report (Oxyfluorfen 111601). 06/3 0/2014. These and other supporting documents for the oxyfluorfen registration review case may be found in the docket EPA-HQ-OPP

-20 14-0778 at http://www.regulations.gov.

3OVERVIEW The docket for oxytluorfen is now open, initiating the first public comment period for this registration review (docket number EPA-HQ-OPP-2014-0778). The oxyfluorfen registration review case is catalogued by the pesticide chemical (PC) code 111601. Oxyfluorfen is a light dependent pe r oxidizing herbicide (LDPH) in the diphenyl-ether chemical class. It is registered for use for pre- and post-emergence control of monocotyledonous and broad leaf weeds in agricultural and non-agricultural crops (including fallow fields prior to p l anting), ornamentals, and residential settings. LDPHs target a specific enzyme , protoporphyrinogen oxidase, in the heme and ch l orophy ll biosynthetic pathway. Inhibiting protoporphyrinogen oxidase in plants leads to an accumulation of photo toxic heme and chlorophyll precursors that, in the presence of light , produce activated oxygen species which rapidly disrupt cell membrane integrity. This Preliminary Work Plan (PWP) document exp lain s what EPA's Office of Pesticide Programs knows about oxyfluorfe n , highlighting anticipated data and assessme n t 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 the registration review for oxyfluorfen. The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends , by s haring t hi s information in the docket , to inform the public of what it knows about oxyfluorfen and what types of new data or

other information would be helpful for the Agency to receive as it moves toward a decision on oxyfluorfen. 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 stakeholde r s 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 l arge. The Preliminary Work Plan beg in s by listing the anticipated data needs for oxyfluorfen. Next, it discusses the statutory and regulatory authority for Registration Review. Then the document provides chemical facts, use and usage inf ormation , recent act i ons , t he anticipated risk assessments, and a projected registration review timeline for oxyfluorfen. Finall 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 -spe cific information. 4ANTICIPATED DATA NEEDS Table 1 below summarizes anticipated data needs for oxyfluorfen. For additional discussion of the anticipated data needs, see the Registration Review Problem Formulation for Oxyjluorfen and Oxyjluorfen: Human HealthAssessmentScoping Document available in the public docket EPA-HP-OPP-2014-0778, accessible at http://www.regulations

.gov. Table 1: Anticipated Data Needs for the Oxyfluorfen Registration Review I Estimated Guideline Study Title 1 Timeframe Number1 Test Material (Months from receipt ofDCI) Anticipated Data Needs for the Parent Oxytluorfen 835.2240 Aqueous Photolysis TGAI 12 835.4300 Aerobic Aquatic Metabolism TGAI 24 835.4400 Anaerobic aquatic metabolism TGAI 24 850.1400 Saltwater fish early life stage J 12 850.2100 Avian oral toxicity TGAI 12 850.1075 Fish acute toxicity test , estuarine/marine fish or TGAI, TEP 12-18 fathead minnow 850

.3040 Field testing forpollinators2 TEP 24 850

. 6100 Environmental Chemistry Method/Independent Laboratory Validation (ECM\IL V) forsoil and TGAI 12 water 870

.3200 21128-Day dermal toxicity TGAI 24 875

.2100 Dislodgeable foliar residue (bulb vegetable) TEP 12-24

Non
- Pollinator Chronic Oral Toxicity- honeybee TGAI 12 Guideline larvae

Non- Pollinator Chronic Oral Toxicity- honeybee adult TGAI 18 Guideline

Non- PollinatorAcute Oral Toxicity- honeybee adult TGAI 12 Guideline

Non
- PollinatorAcute Oral Toxicity- honeybee larvae TGAI 12 Guideline

Non- Residue analysis ofnectar andpollen in flowering TEP 12 Guideline

**crop~**

1 On June 27,201 2, 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 ofAvailability" 77 FR 3 8282, June 27 ,201 2. http:// www.regulations.gov/# !d ocumentDetaii;D=EPA-HO-OPPT-2009-0 154

-0028 2 Anticipated requirement for field test for pollinators, including semi-field data or full field data, is contingent on results oftier I studies including the Pollinator Acute Oral Toxicity

- honeybee larvae study; the Pollinator Chronic Oral Toxicity

- honeybee adult study; and the Pollinator Acute Oral Toxicity

- honeybee adult study

. 3 Anticipated requirement is contingent on results oftier I studies including the Pollinator Acute Oral Toxicity

- honeybee larvae study; the Pollinator Chronic Oral Toxicity- honeybee adult study; and the Pollinator Acute Oral Toxicity

- honeybee adult study. 

### 5STATUTORY AND REGULATORY AUTHORITY The Food Quality Protection Act (FQPA) of 1996 mandated a regis t ration review program. All pesticides distributed or sold in the Uni ted States (U.S.) generally must be registered by the Env i ronmental Protection Agency (EPA or the Agency), based on scient ific data showing that they will not cause unreasonable r i sks to human heal th 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 pract ices change, all regis t ered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, pub li c policy, and pesticide use pract i ces will occur over time. Through the reg i strat i on review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketp l ace can be used safely. Information on this program i s provided on EPA's website. 4 The Agency is implementing the registration review program pursuant to Section 3(g) of the Federa l Insect i c i de, Fung icide, and Rodenticide Act (FIFRA), and will review each registered pesticide every 15 years to determine whether i t cont i nues to meet th e FIFRA standard for registration. The regulations governing regis trat ion review begin at 40 CFR 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of reg i st ra t i on rev i ew 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 i t believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during thi s initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of oxyfluorfen. CHEMICAL FACTS Tab l e 2 provides a summary of the chemical facts for oxy fluorf en. Table 2 : Chemical Facts for Oxyfluorfen PC code 111601 I Case Number 2490 CAS Number 4 287 4-0 3 - 3 Year first registered 1 979 I Pesticide Type Herbicide Chemical class Diphenyl Ether Reregistration Eligibility October 2002 Decision (RED)Tolerance Reassessment To l erance reassessment was included in the RED . E ligibili ty Decision I (TRED) 4 http :// www . epa.gov / oppsrrd 1/registrat i on _review / 6

### Table 2: Chemical Facts for Oxyfluorfen Cumulative group Not applicable. Oxyfluorfen has not been identified as a member ofa cumulative group that shares a common mechanism of toxicit y

_. Tolerance under 40 CFR Tolerances for oxyfluorfen are established in 40 CFR 180.381. Dual-use Oxyfluorfen is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses. Non-pesticidal uses There are no identified non-pesticidal uses ofoxyfluorfen. Pesticide Re

-evaluation Benjamin Askin, askin.benjamin@epa.gov, 703-347-0503 Division, Chemica l Review Manager Registration Division, Erik Kraft, kraft.erik@epa.gov. 703-308-9358 Product Manager I 

### USE AND USAGE INFORMATION Table 3 summarizes the use and usage information for oxyfluorfen. Please see the 

### BEAD Chemical Profile ( BCP )for Registration Review: Ox y jluorfen (1 11601) in the registration review available in the public docket EPA-HP-OPP-2014-0778, accessible at http:/ /www.regulations

.gov. 

### Table 3: Oxyfluorfen Use and Usage Information Summary ofUse

Use Sites

Summary ofUsage Diphenyl-ether herbicide applied pre- and post-emergence to control broadleafand grassy weeds.
The registered agricultural uses ofoxyfluorfen include a wide range offruits, including pome, stone, tropical, and subtropical, as well as nut trees, vegetables and field crops, fallow land and conservation reserve, Christmas tree plantations, shelterbelt, deciduous trees, forest trees (softwoods, conifers), and grasses grown for seed. Oxyfluorfen is also registered for non-agricultural use sites including household/domestic dwellings, outdoor premises, industrial construction areas (outdoor), mulch, outdoor buildings/structures, rights-of way/fence rows, hedgerows, uncultivated areas/soils, paths/patios, paved areas (private roads/sidewalks), nursery stock, ornamentals, and recreational areas. For the years from 1998 to 2012, oxyfluorfen annual agricultural usage averaged 1.2 million pounds ofactive ingredient (a.i.) treating an average of2

.5 million acres.

7Table 3 : Oxyfluorfen Use and Usage Information F rom 1998 to 2012, the total acres treated (TAT) has trende d upwards as the number of pounds applied h as shown a downward tr end especially since the 2002 RED. Formulation Type(s) Emulsifiable concentrate, granular, ready to u se sol u tion, solub l e concentrate, and flowable concentrate. Application Me th od(s) Applied as band treatment, broadcast , and by chemigation . Application eq ui pment includes handheld sprayers and tracto r mounted conventional g round sp r ayers . Technical Registrant(s) Dow AgroSciences, ADAMA, Albaugh, United Phosphorous ) and Willowood. No . ofRegistrations 41 FIFRA Section 3 and 57 FIFRA Sect i on 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 . • National po u ndage of oxyfluorfen applied in a yearly basis on the rights-of-way and other nonagricultural use sites wou ld be useful. • Other usage / use inf ormation for non - agricultural uses. • Any efficacy information, product performance information and niche uses of oxyfluorfen. • Use distribution (e . g., acreage and geograp hi cal d i stribution of relevant use sites). • Median and 90 1 h percentile reported use rates (lbs ai / A) from usage data - national, state, and county . • T yp ic al application timing (date of fi rst app li cat i on and app li cation intervals) -n ational, state, and county for oxyfluorfen uses. • T yp i cal application i ntervals (days) . • State or local use restrictions. • Foreign techn i ca l registrants not listed abo ve who supply technical oxyfluorfen to the US market. RECENT AC TI ONS • There are no recent actions for oxyf)uorfen. ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW The most re cent comprehensive human health ri sk assessment for o xy fluorfen was completed 2002 in preparation fo r the Reregistration Elig ibi lity Decision. The most recent ecological and environmental fate risk assessment was completed for a 2008 5 li t ig at i on assessment for the California red- l egged frog and before that an ecological risk assessmen t was conducted for the Reregistration Eligibili ty Decision on May 2, 2002. 5 http: // epa.gov / espp / litstatus /ef fects / redleg-frog/index . html 8Findings and conclusions from these risk assessments are summarized in the Registration Review Problem Formulation for Oxyfluorfen and Oxyfluorfen: Human Health Assessment Scoping Document in Support of Registration Review. During r egistration review, the Agency anticipates the need to conduct a comprehensive ecological risk assessment, for all uses ofoxyfluorfen. For human health, EPA anticipates, among other data needs, the need for a subchronic dermal toxicity study on rabbits and a chemical specific dislodgeable foliar residue study on bulb vegetables during registration review. If toxicological endpoints or points ofdeparture 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. Oxyfluorfen is the residue ofconcern for tolerance expression and/or risk assessment in crops, livestock and drinking water. Banana and cotton gin byproducts field trial data (GLN 860.1 500) were submitted in response to the 2002 Reregistration Eligibilit y Decision (RED) and will be eva luated during Registration Review. Cacao bean field trial data (GLN 860. 1500) were a lso required in the RED ; however, HED has re-evaluated the residue chemistry database for oxyfluorfen and will translate available coffee field trial data to support the existing uses of oxyfluorfen on cacao beans (D42325 1). Table 4 below summarizes the anticipated registration review risk assessments based on t he EFED Problem Formulation and HED Scoping Document.



### 9Table 4: Anticipated Risk Assessments for the Oxyfluorfen Registration Review Type of Risk Assessment Conduct? Notes Ecolo_gical and Environmental Fate I Comprehens i ve ecological y (species to be assessed include terrestrial and aquatic organisms), including endangered spec i es Incidents y Review of the Agency's ecological inc i dent databases identified a total of 25 discreet ecological incidents associated with oxy fl uorfen (involving plants and an i mals). In addition, the Agency a l so has 42 aggregate counts of incidents associated with oxyfluorfen ( i nvolv i ng

p lants). Human Health Dietary Food y The Agency's most recent dietary assessment was in 2002. An acute dietary r isk assessment was not conducted due to a lack of an acute end point, chron i c d i etary risk estimates were not of concern. A revised drink i ng water assessment i s anticipated for registration review to reflect updated models and any changes based on ant i cipated fate data requirements. Therefore a revised dietary analysis is anticipated , includ i ng cancer and non - cancer endpoints, for the oxyfluorfen registrat i on review. Dr i nk i ng water y See above. Occupational Handlers (mixers, loaders, y The previous occupational exposure assessment app l icators) covered all scenarios relevant t o oxyfluorfen and no occupational handler or post

- application risk es t i mates of concern were identified with use of appropriate personal protecti v e equipment (PPE) ( i .e., label required chemica l - res i stant gloves). However, the oxyfluorfen registration review will include updated hand l er analysis to reflec t current policies and anticipated toxicology data (a subchronic

dermal tox i c i ty study is anticipated to be required) .10Post-application 

### y The oxyfluorfen registration review will also include a revised post-application (worker) analysis to reflect anticipated exposure data (dislodgeable foliar residue (DFR) data). Residential Handlers 

### y The most current residential risk assessment did not identify risks ofconcern6

. However, updates to HED's Residential SOPs7 (2012) have been made along with policy changes for body weight assumptions. Therefore, the residential exposure risk assessment will be updated during Registration Review. Post-application 

### y The need for spray drift and volatilization risk assessments for oxyfluorfen will be examined during the Regist ration Review process. Other Aggregate 

### y There are no current aggregate risks estimates of concern. Updated aggregate assessments may be conducted based on updates to either the dietary or residential analysis. Cumulative N The Agency has not made a common mechanism of toxicity finding as to oxyfluorfen and any other substances, and oxyfluorfen does not appear to produce a toxic metabolite produced by other substances
. The Agency has not assumed that oxyfluorfen has a common mechanism oftoxicity with other substances. Tolerances 

### y The current tolerance expression for oxyfluorfen may be updated during registration review. However, since there are no oxyfluorfen MRLs established under CODEX or Mexico and current tolerance values are harmonized with Canadian MRLs (exclud ing Canadian MRLs with no U.S. equivalents), no further harmonization is anticipated. Incidents 

### y The Agency reviewed its human health incident databases and found few human health incidents other than several associated with Ortho Fence & Grass Edger Formula II. Due to the proportion ofreported incidents associated with this product, the Agency may further evaluate this particular product during registration review. It should be noted that Ortho Fence & Grass Edger Formula II also contains the active ingredient glyphosate, isopropylamine salt.

11TIMELINE EPA has c r eated the following est i mated time li ne for the completion of the oxyfluorfen registration review in Table 5 below . Table 5 : Projected Oxyfluorfen Registration Review Timeline Activities I Estimated Date Opening the Docket Open Docket and 60 - day Public Comment Period 2014 December Close Public Comment 2015 February Case Deve l opment I Final Work Plan I 2015 May Issue DCI I 2015 Ju l y

- Sep t ember Data Submiss i on 2017 Ju l y

- Sep t ember 60 - day Public Comment Period for Draft Risk 2019 January

- March Assessments 8 Reg i stratio n Review Decision

60 - day Public Comment Period fo r Proposed 20 19 October - December Registration Review Decision Reg i strat i on Review Decision and Begin Post - Decision 2020 F o ll ow-up Total (years) I 5 NEXT STEPS I

After the 60-day public comment per i od closes, the Agency w ill rev i ew and respond to any comments r ece i ved in a timely manner and then issue a Final Work Plan for the registration review of oxyfluorfen. 6 Oxyfluorfen: Second Rev i sed Occupational and Residential Non-Cancer and Cancer Exposure and Risk Assessments for the Reregistration Eligibil i ty Dec i sio n (RED) Document. T. Dole. 05 / 0 1 / 2002. D281831 7 Available: http: // www.epa.gov / pest i cides / science / res i dential - e xposure

- sop .html 8 The r eg ulations 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. 12

### Appendix- Additional Areas Considered in the Oxyfluorfen Registration Review PUBLIC COMMENTS AND FEEDBACK: Guidance for Commenters: The areas below highlight topics ofspecial interest to the Agency where your comments, data submissions, or reference to sources ofadditional information could be ofparticular 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 ofMRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature ofthe concern. U.S
. permanent tolerances for residues ofoxyfluorfen are established under 40 CFR 

### §180.381 inion a number ofcrop and livestock raw agricultural commodities. The tolerance expression will need to be updated to reflect RED's Interim Guidance on Tolerance Expressions (5/27/09, S
. Knizner). No maximum residue limits (MRLs) for residues of oxyfluorfen have been established by Codex or Mexico. Excluding Canadian MRLs with no U.S. equivalent, the remaining Canadian MRLs are fully harmonized with U.S. tolerances. See Attachment 4. Water Quality: Oxyfluorfen is identified as a cause ofimpairment for two water bodies (Gilsizer Slough and Live Oak Slough in California) listed as impaired under section 303(d) ofthe Clean Water Act No Total Maximum Daily Load (TMDL) criteria have been developed for oxyfluorfen. Aquatic benchmarks have been established for chemical oxyfluorfen and are available at http://www.epa.gov /oppefedl/ecorisk ders/aguatic life benchmark.htm
. More information on impaired water bodies and TMDLs can be found at EPA's website.9 The Agency invites submission ofwater quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A ofthe OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP 's Registration Review RiskAssessment and Management Process 10 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments. Environmental Justice: EPA seeks to achieve environmentaljustice, the fair treatment and meaningful involvement ofall people, regardless ofrace, color, national origin, or income, in the development, implementation, and enforcement ofenvironmental laws, regulations, and policies. To help address potential

9 http://www.epa.gov /owow/tmdl/ 10 http://www.epa.gov /oppsrrd 1/registration review /water quality sop.htm 13environmental justice issues, the Agency see k s information on any groups or segments of th e popu l at ion who, as a result of their locat ion , cultural practices, or other facto r s , may have atypical, unusually high exposure to oxyfluorfen 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 spec ies determination has not been cond u cted for oxyfluorfen. The ecological risk assessment planned during registration review

will allow the Agency to determine whether use of oxyfluorfen has "no effect" or "may affect" federally li sted threatened or endangered spec ies (listed species) or thei r designated critical**habitats~** When an assessment concludes t hat 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 June 5, 2013, the Center for Biological Diversity and th e Pestic i de Action Network North America filed an amended complaint in its lawsuit in the United States District Court for the Northern District of California, against the EPA for allegedly failing to undergo consultation with the United S tat es Fish and Wildlife Service and the National Marine Fisheries Service regarding the effects of over 50 pesticides, including oxyfluorfen on over 100 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.) . The Agency conducted a 2008 litigation**a~sessment** for the California red- l egged frog (CLRF) (Rana aurora draytonii) (US E PA, 2008) 11 • The Agency made a Likel y to Adverse ly Affect (LAA) determination for the CRLF from t he use of oxyfluorfen. Additionally, the Agency determined that there is the potential for modification of CRLF designated critical habitat from the use of oxyfluorfen. ENDOCRINE DISRUPTOR SCREENING PROGRAM : As required by FIFRA and FFDCA, EPA reviews n um erous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies includ e acute, subchronic and chronic to xicity, including assessments of carcinogenicity, neurotoxicity, developmental, r eproductive, and general or systemic toxicity. These st ud ies 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 rati os in offspring . For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects i n different taxonomic groups. As part of its reregistration decision for oxyfluorfen, EPA reviewed these data and selected the most sensitive endpoints for rele vant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 4 08(p ), oxyfluorfen is subject to the endocrine screening part of th e Endocrine Disruptor Screening Program (EDSP). 11 http: // epa.gov / espp / litstatus / effects / r e dleg-frog/index . html 14EPA 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 I consists ofa battery of 11 screening assays to identify the potential ofa 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 ofthe EDSP where EPA will determine which, ifany, ofthe 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 of67 chemica ls, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list ofchemicals identified for EDSP screening was published on June 14, 2013 12 and includes some pesticides scheduled for regist ration review and chemicals found in water
. Neither ofthese lists should be construed as a list ofknown or likely endocrine disruptors. Oxyfluorfen is on List 2. List 2 represents the next set ofchemica ls for which EPA intends to issue test orders/data call-ins in the near future. For further information on the status ofthe EDSP, the policies and procedures, the lists ofchemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 13 HUMAN STUDIES: Occupational andResid ential The October 2002 RED and April 2002 risk assessment relied 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), the Agricultural Reentry Task Force (ARTF) Database, and the 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 convincing evidence that the conduct ofany ofthem was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was conducted. All applicable requirements ofEPA ' s Ru1e for the Protection ofHuman Subjects ofResearch (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

12 See http ://www.regulations. gov/#! documentDetaii;D=EPA-HO-OPPT-2009

-0477-0074 for the final second list of

chemicals. 13 http :// www.epa.gov/endo / 15