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 

~cu.c-L f> ~~ ;:p 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 

/a2- s--o;o / '-1 
Oxyfluorfen Preliminary Work Plan- Table of Contents 

OVERVIEW ...... .......................... ................................................................................................... 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 Registration Review ................ 13 

References: 

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

based on the following documents: 

1. Registration Review Problem Formulation for Oxyfluorfen. Robin Sternberg and He 

Zhong. 11103/2014. 

2. Human Health Assessment Seeping Document in Support of Registration Review. Ivan 

Nieves, Ayaad Assaad, Marquea King, Bonnie Cropp-Kohlligan, and Susan Hummel. 

10/9/1 4. 

3. Oxyfluorfen: Tier 1 Review of Human Incidents. Elizabeth Evans and Shanna Recore. 

07/17/2014. 

4. BEAD Chemical Profile (BCP) for Registration Review: Oxyfluorfen (11160l).Sunil 

Ratnayake, Rafael A. Prieto, Stephen Smearman, and Amet Jones. 1114/2014. 

5. Screening Level Usage Analysis (SLUA). 04/30/2014. 

2 
6. HED Master Label Report (Oxyfluorfen 111601). 06/30/2014. 

7. EFED Table 1 Report (Oxyfluorfen 111601). 06/30/2014. 

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

in the docket EPA-HQ-OPP-2014-0778 at http://www.regulations.gov. 

3 
OVERVIEW 

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 peroxidizing 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 planting), ornamentals, 

and residential settings. LDPHs target a specific enzyme, protoporphyrinogen oxidase, in the 

heme and chlorophyll 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 explains what EPA's Office of Pesticide Programs 

knows about oxyfluorfen, 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 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 sharing this 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 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 oxyfluorfen. Next, it 

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

provides chemical facts, use and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for oxyfluorfen. 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 

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 Health Assessment Scoping 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 Title1 Timeframe 

Number1 Test Material (Months from 

receipt of DCI) 

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 for pollinators2 TEP 24 

850.6100 Environmental Chemistry Method/Independent 

Laboratory Validation (ECM\IL V) for soil 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- Pollinator Acute Oral Toxicity- honeybee adult TGAI 12 

Guideline 

Non- Pollinator Acute Oral Toxicity- honeybee larvae TGAI 12 

Guideline 

Non- Residue analysis of nectar and pollen 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 of Availability" 77 FR 38282, June 27,201 2. 

http://www.regulations.gov/#!documentDetaii;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 of tier 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 of tier 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. 

5 
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 website.4 

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 oxyfluorfen. 

CHEMICAL FACTS 

Table 2 provides a summary of the chemical facts for oxyfluorfen. 

Table 2: Chemical Facts for Oxyfluorfen 

PC code 111601 I 

Case Number 2490 

CAS Number 42874-03-3 

Year first registered 1979 I 

Pesticide Type Herbicide 

Chemical class Diphenyl Ether 

Reregistration Eligibility October 2002 

Decision (RED) 

Tolerance Reassessment Tolerance reassessment was included in the RED. 

Eligibility Decision 

(TRED) I 

4 http://www.epa.gov/oppsrrd 1/registration _review/ 

6 
Table 2: Chemical Facts for Oxyfluorfen 

Cumulative group Not applicable. Oxyfluorfen has not been identified as a member 

of a cumulative group that shares a common mechanism of 

toxicity_. 

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 of oxyfluorfen. 

Pesticide Re-evaluation Benjamin Askin, askin.benjamin@epa.gov, 703-347-0503 

Division, Chemical 

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: Oxyjluorfen (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 of Use 

Use Sites 

Summary of Usage 

Diphenyl-ether herbicide applied pre- and post-emergence to 

control broadleaf and grassy weeds. 

The registered agricultural uses of oxyfluorfen include a wide 

range of fruits, 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 of active ingredient (a.i.) 

treating an average of2.5 million acres. 

7 
Table 3: Oxyfluorfen Use and Usage Information 

From 1998 to 2012, the total acres treated (TAT) has trended 

upwards as the number of pounds applied has shown a downward 

trend especially since the 2002 RED. 

Formulation Type(s) Emulsifiable concentrate, granular, ready to use solution, soluble 

concentrate, and flowable concentrate. 

Application Method(s) Applied as band treatment, broadcast, and by chemigation. 

Application equipment includes handheld sprayers and tractor 

mounted conventional ground sprayers. 

Technical Registrant(s) Dow AgroSciences, ADAMA, Albaugh, United Phosphorous) and 

Willowood. 

No. ofRegistrations 41 FIFRA Section 3 and 57 FIFRA 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. 

• National poundage of oxyfluorfen applied in a yearly basis on the rights-of-way and other 

nonagricultural use sites would be useful. 

• Other usage/use information for non-agricultural uses. 

• Any efficacy information, product performance information and niche uses of 

oxyfluorfen. 

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

• Median and 901

h percentile reported use rates (lbs ai/ A) from usage data - national, state, 

and county. 

• Typical application timing (date of first application and application intervals) -national, 

state, and county for oxyfluorfen uses. 

• Typical application intervals (days). 

• State or local use restrictions. 

• Foreign technical registrants not listed above who supply technical oxyfluorfen to the US 

market. 

RECENT ACTIONS 

• There are no recent actions for oxyf)uorfen. 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW 

The most recent comprehensive human health risk assessment for oxyfluorfen was completed 

2002 in preparation for the Reregistration Eligibility Decision. The most recent ecological and 

environmental fate risk assessment was completed for a 20085 litigation assessment for the 

California red-legged frog and before that an ecological risk assessment was conducted for the 

Reregistration Eligibility Decision on May 2, 2002. 

5 http://epa.gov/espp/litstatus/effects/redleg-frog/index.html 

8 
Findings 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 registration review, the Agency anticipates the need to conduct a comprehensive 

ecological risk assessment, for all uses of oxyfluorfen. 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 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. 

Oxyfluorfen is the residue of concern 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 Eligibility Decision (RED) and will be 

evaluated during Registration Review. Cacao bean field trial data (GLN 860. 1500) were also 

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 (D423251). 

Table 4 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document. 

9 
Table 4: Anticipated Risk Assessments for the Oxyfluorfen Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecolo_gical and Environmental Fate I 

Comprehensive ecological y 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Incidents y Review of the Agency's ecological incident databases 

identified a total of 25 discreet ecological incidents 

associated with oxyfluorfen (involving plants and 

animals). 

In addition, the Agency also has 42 aggregate counts 

of incidents associated with oxyfluorfen (involving 

plants). 

Human Health 

Dietary 

Food y The Agency's most recent dietary assessment was in 

2002. An acute dietary risk assessment was not 

conducted due to a lack of an acute end point, chronic 

dietary risk estimates were not of concern. 

A revised drinking water assessment is anticipated for 

registration review to reflect updated models and any 

changes based on anticipated fate data requirements. 

Therefore a revised dietary analysis is anticipated, 

including cancer and non-cancer endpoints, for the 

oxyfluorfen registration review. 

Drinking water y See above. 

Occupational 

Handlers (mixers, loaders, y The previous occupational exposure assessment 

applicators) covered all scenarios relevant to oxyfluorfen and no 

occupational handler or post-application risk 

estimates of concern were identified with use of 

appropriate personal protective equipment (PPE) (i.e., 

label required chemical-resistant gloves). 

However, the oxyfluorfen registration review will 

include updated handler analysis to reflect current 

policies and anticipated toxicology data (a subchronic 

dermal toxicity study is anticipated to be required). 

10 
Post-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 of concern6. 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 Registration 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 of toxicity 

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 

(excluding 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 of reported 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. 

11 
TIMELINE 

EPA has created the following estimated time line 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 Development I 

Final Work Plan I 2015 May 

Issue DCI I 2015 July - September 

Data Submission 2017 July - September 

60-day Public Comment Period for Draft Risk 2019 January - March 

Assessments8 

Registration Review Decision 

60-day Public Comment Period for Proposed 20 19 October - December 

Registration Review Decision 

Registration Review Decision and Begin Post-Decision 2020 

Follow-up 

Total (years) I 5 

NEXT STEPS I 

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 oxyfluorfen. 

6 Oxyfluorfen: Second Revised Occupational and Residential Non-Cancer and Cancer Exposure and Risk 

Assessments for the Reregistration Eligibility Decision (RED) Document. T. Dole. 05/0 1/2002. D281831 7 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html 8 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. 

12 
Appendix- Additional Areas Considered in the Oxyfluorfen 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 ofMRLs or disparities between U.S. 

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

the nature of the concern. U.S. permanent tolerances for residues of oxyfluorfen are established 

under 40 CFR § 180.381 inion a number of crop 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 of impairment for two water bodies (Gilsizer Slough and 

Live Oak Slough in California) listed as impaired under section 303(d) of the 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 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 Management Process10 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 

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

10 http://www.epa.gov/oppsrrd 1/registration review/water quality sop.htm 

13 
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 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 species determination has not been 

conducted 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 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 June 5, 2013, the Center for Biological Diversity and the Pesticide 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 States 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-legged frog (CLRF) 

(Rana aurora draytonii) (USEPA, 2008) 11 • The Agency made a Likely to Adversely Affect 

(LAA) determination for the CRLF from the 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 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 reregistration decision for oxyfluorfen, 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 408(p ), oxyfluorfen is 

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

11 http://epa.gov/espp/litstatus/effects/redleg-frog/index.html 

14 
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 I 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. A second list 

of chemicals identified for EDSP screening was published on June 14, 2013 12 and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. 

Oxyfluorfen is on List 2. List 2 represents the next set of chemicals for which EPA intends to 

issue test orders/data call-ins in the near future. For further information on the status of the 

EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the 

Tier 1 screening battery, please visit our website. 13 

HUMAN STUDIES: 

Occupational and Residential 

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 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 Ru1e 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. 

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