Docket Number EPA-HQ-OPP-2012-0896 

www .regulations.gov 

Bromoxynil Preliminary Work Plan 

Registration Review: Initial Docket 

Case Number 2070 

March 2013 

Approved by: <:b Richard P. Keigwill)f: 

Director 

Pesticide Re-evaluation Division 

Date: 
Bromoxynil Preliminary Work Plan - Table of Contents 

Overview 3 

Anticipated Data Needs 4 

Statutory and Regulatory Authority 5 

Chemical Facts 6 

Use and Usage Information 6 

Recent Actions 7 

Anticipated Risk Assessments for Registration Review 8 

Timeline 9 

Next Steps 10 

Appendix- Additional Areas Considered in Bromoxynil's Registration Review 11 

References: 

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

based on the following documents: 

1. EFED Registration Review Problem Formulation for Bromoxynil and Bromoxynil Esters. 

N.E. Federoff and Elyssa Gelmann. January 22, 2013. 

2. Bromoxynil. Human Health Assessment Scoping Document in Support of Registration 

Review. Cassi Walls, Ph.D, Myron Ottley, Ph.D., Meheret Negussie, and Kristin Rury. 

October 31, 20 12. 

3. BEAD Chemical Profile for Registration Review: Bromoxynil and Its Esters. Bill Phillips, 

Ph.D., Jihad Alsadek, Derek Berwald, Ph.D. October 3, 2012. 

4. Bromoxynil and Esters: Review of Human Incidents (HED Incident Report). Shanna 

Recore and Elizabeth Evans. November 13, 2012. 

5. Bromoxynil and its esters (035301,035302,035303,128920) Screening Level Usage 

Analysis (SLUA). November 2, 2011. 

6. Bromoxynil octanoate PRD Label Data Report. September, 24, 2012. 

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

in the docket EPA-HQ-OPP- OPP-2012-0896 at http://www.regulations.gov. 

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OVERVIEW 

The docket for bromoxynil is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP- OPP-2012-0896). This case includes the 

active ingredients bromoxynil phenol, bromoxynil octanoate, and bromoxynil heptanoate. The 

octanoate and the heptanoate are esters of the phenol. These three active ingredients 

(collectively, "bromoxynil") are postemergence broadleaf weed herbicides that are registered for 

use in grass crops and some tolerant broadleaf crops, as well as non-crop sites. A third ester of 

bromoxynil phenol, bromoxynil butyrate (PC 035303), was previously registered with the 

Agency but currently has no active registrations and is therefore not addressed in this 

Registration Review. Bromox ynil products are used in both agricultural and 

commercial/industrial settings. This Preliminary Work Plan (PWP) document explains what 

EPA's Office of Pesticide Programs knows about bromoxynil, highlighting anticipated data and 

assessment needs, identifying the types of information that would be especially useful to the 

Agency in conducting registration review, and providing an anticipated timeline for completing 

bromox ynil' s review. 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about bromoxynil and what types of new data or 

other information would be helpful for the Agency to receive as it moves toward a decision on 

bromoxynil. 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 bromoxynil. Next, it 

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

provides chemical facts for bromoxynil, use and usage information, recent actions, the 

anticipated risk assessments, and a projected registration review timeline. Finally, the Appendix 

to this document includes identification and discussion of some areas that are considered 

generaJly in Registration Review along with some additional chemical case-specific information. 

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ANTICIPATED DATA NEEDS 

Table 1 below summarizes anticipated data needs for bromoxynil. For additional discussion of 

the anticipated data needs, see the EFED Registration Review Problem Formulation f or 

Bromoxynil and Bromoxynil Esters and Bromoxynil. Human Health Assessment Scoping 

Document in Support of Registration Review. 

Table 1: Anticipated Data Needs for the Re1,ristration Review of Bromoxynil 1 

Estimated 

Guideline Study Title 

Timeframe 

Number Test (Months from Material 2 

receipt of DCI) 

Bromoxynil (phenol) - PC Code 035301 

835.2240 Photodegradation in water 12 

835.4100 Aerobic soil metabolism 

TGAior 24 PAIRA 

835.4300 Aerobic aquatic metabolism 24 

850.6100 Environmental Chemistry Methods and Associated 

Independent Laboratory Validation 3 TGAI 12 

850.2300 A vi an reproduction 4 TGAI 24 

850.4400 Aquatic plant growth (aquatic vascular plant) 12 

TGAI 

850.4500 Aquatic plant growth (algal plant) 12 

875.2 100 Dislodgeable foliar residue and turf transferable TEP 24 Residues 

Bromoxynil octanoate - PC Code 035302 

835.4100 Aerobic soil metabolism TGAI or 24 PAIRA 

850.6 100 Environmental Chemistry Methods and Associated 

Independent Laboratory Validation 3 TGAI 12 

850.2100 A vi an oral toxicity ) TGAI 12 

875.2100 Dislodgeable foliar residue; turf transferable TEP 24 Residues 

Bromoxynil heptanoate 0 - PC Code 128920 

835.1230 Adsorption/Desorption (Batch Equilibrium) 12 

835.2 120 Hydrolysis 12 

835.2240 Photodegradation in water 12 

835.2410 Soil photolysis TGAI or 12 

835.4100 Aerobic soil metabolism 

PAIRA 

24 

835.4300 Aerobic aquatic metabolism 24 

835.4400 Anaerobic aquatic metabolism 24 

850.6 100 Environmental Chemistry Methods and Assoc iated 

Independent Laboratory Validation 3 TGAI 12 

875.2 100 Dislodgeable foliar residue and turf transferable TEP 24 Residues 

4 
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 Availability" 77 FR 38282, June 27, 2012. 

http://www.regulations. gov/#!documentDetail ;D-EPA-HO-OPPT -2009-0 J 54-0028 

2TGAI ==technical grade active ingredient; TEP =typical end-use product; PAIRA =pure active ingredient, radiolabeled 3 This ECM!ll..V request is for methods in water. 4 An avian reproduction study with bromoxynil (phenol) is an antic ipated data requirement. ln absence of these data 

if they are required, the available endpoints for bromoxynil octanoate will be used for risk assessment. 5 For this anticipated data requirement, the study is requested for a passerine species. A protocol for the study 

should be submitted to EFED for approval before the study begins. 6 The Agency will review where it is appropriate to bridge the results of environmental fate studies conducted with 

bromoxynil octanoate to bromoxynil heptanoate. If bridging is determined to be an acceptable strategy, aqueous 

photolysis, aerobic aquatic metabolism, and anaerobic aquatic metabolism, and adsorption/desorption studies using 

bromoxynil heptanoate would not be required. 

STATUTORY AND REGULATORY AUTHORITY 

The Food Quality Protection Act (FQP A) 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 1

• 

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 bromoxynil. 

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

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Table 2 provt "d es a summary o fth e current regu atory status o fb romoxym"l . 

Table 2: BROMOXYNIL CHEMICAL FACTS 

PC code Bromoxynilphenol: 035301 

Bromoxynil octanoate: 035302 

Bromoxynil heptanoate: 128920 

Case Number 2070 

CAS Number Bromoxynil phenol: 1689-84-5 

Bromoxynil octanoate: 86702-80-9 

Bromoxynil heptanoate: 56634-95-8 

Year first registered 1965 

Pesticide Type Herbicide 

Chemical class Hydroxybenzonitrile or nitrile herbicide 

Reregistration Eligibility Decision December 1998 

(RED) Chtto://www .eoa. !!ov/ooosrrd l/REDs/207 d~clf) 

Tolerance Reassessment Not applicable 

Eligibility Decision (TRED) 

Cumulative group Bromoxynil is not a member of a cumulative group and no 

cumulative risk assessment is planned. 

40 CFR Citation Tolerances for bromoxynil are established in 

40 CFR § 180.324. 

Dual-use Conventional pesticidal uses onl_y. 

Non-pesticidal uses There are no non-pesticidal uses of bromoxynil. 

Pesticide Re-evaluation Division, Margaret Hathaway, hathaway.margaret @epa. gov 

Chemical Review Manager (703) 305-5076 

Registration Division, Product Kathryn Montague, montague.kathryn @epa. gov 

Manager (703) 305-1243 

USE AND USAGE INFORMATION 

Table 3 summarizes the use and usage information for bromoxynil. Please see BEAD Chemical 

Profile for Registration Review: Bromo).y nil and Its Esters in the registration review docket for 

more details. 

Table 3: USE AND USAGE INFORMATION 

Summary of Use Registered for use as a post-emergence broadleaf weed herbicide 

that can be applied in grass crops and some tolerant broadleaf 

crops. Also registered for use against actively growing weeds in 

non-crop sites. 

Use Sites Alfalfa; fallow land; cotton; forage grasses, forage legumes, and 

other non-grass forage crops; hay; com (field, sweet, and pop); flax 

grain crops (e.g., barley, oats, rye, triticale, wheat, sorghum, proso 

millet); mints; garlic; onions; fencerows; commercial/industrial 

lawns; conservation reserve; drainage ditch ban ks; omarnental 

herbaceous plants; ornamental nonresidential lawns; golf course 

turf; grass seed production and sod farms; railroad and roadway 

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rights of way; vacant lots; outdoor industrial areas 

Summary of Usage From 2006-2010, the crops with the greatest usage ofbromoxynil 

were spring wheat, winter wheat, barley, and com. An average of 

approximately two million pounds of active ingredient was applied 

to eight million acres in that same period. 

Formulation Type(s) Wettable powder, and emulsifiable and soluble concentrates 

Application Method(s) Products can be applied by air, chemigation, and ground boom. 

Technical Registrant(s) Bayer, NuFarm, MANA, and Albaugh 

No. of Registrations Approx. 50 Section 3 products2

, 3 SLNs 

Restricted Use Yes 

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. 

• Certain bromoxynil labels are unclear with respect to application parameters like the size 

of the treated area, the extent of a treated "spot," retreatment intervals, or maximum 

annual application rates. In the absence of such information, EPA expects to 

approximate these parameters in order to conduct a quantitative assessment for 

bromoxynil. The Agency will work with registrants to make sure bromoxynillabels do 

not include any missing or ambiguous use parameters. 

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

application methods and equipment; maximum application rates; frequency of 

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

geographic limitations on use. 

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

• Median and 90lh percentile reported use rates (lbs ail A) from usage data - national, state, 

and county. 

• Application timing (date of first application and application intervals) - 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 technical bromoxynil to the US 

market. 

RECENT ACTIONS 

New uses on sorghum and grass grown for seed were approved in June and July 2011. 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW 

2 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabllppls.home). 

7 
The most recent risk assessment for bromoxynil was conducted in 2011 for a new use request. 

The most recent ecological and environmental fate risk assessment was completed in 2010 for 

the same purpose. In 2004, risks from bromoxynil to endangered or threatened Pacific salmon and 

steelhead were assessed. Findings and conclusions from these risk assessments are summarized 

in the following documents: EFED Registration Review Problem Formulation for Bromoxynil 

and Bromoxynil Esters and Bromoxynil. 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, including an endangered species assessment, for all uses of 

bromoxynil. For human health, EPA anticipates the need to conduct revised dietary and 

occupational risk assessments during registration review. If toxicological endpoints or points of 

departure are revised based on the data that are anticipated to be required for registration review, 

they will be considered in the new assessments, as well as any changes to the standard operating 

procedures or defau lt exposure assumptions. 

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

EFED Problem Formulation and HED Scoping Document. 

Table 4: Anticipated Risk Assessments for Bromoxynil's Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecological and Envlroomental Fate 

Comprehensive ecological Yes 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Incidents Yes For a discussion of bromoxynil's reported ecological 

incidents, see page 17 of the Problem Formulation. 

HIIIII8DIIealtb KiF~J'fi 

Dietary 

Food No A new dietary risk assessment may not be needed 

since changes in the Agency's assessment methods 

since the most recently conducted risk assessment are 

not anticipated to affect the risk conclusion. 

Drinking water Yes 

Occupational 

Handlers (mixers, loaders, Yes 

applicators) 

Post -application Yes 

Residential 

Handlers No There are no residential uses of bromoxynil. 

Post-application No 

Other 

8 
Aggregate Yes Evaluates the combined risk from food and drinking 

water exposures. 

Cumulative No Bromoxynil is not a member of a cumulative group 

and no cumulative risk assessment is planned. 

Tolerances Yes Tolerances for bromoxynil are listed in 40 

CFR§180.324. 

Incidents No There is not a concern at this time that would warrant 

fmther investigation. The Agency will continue to 

monitor the incident information and, if a concern is 

triggered, additional analysis will be included in the 

risk assessment. For a discussion of bromoxynil's 

reported human incidents, see page 10 of the Scoping 

Document. 

Guidance for Commenters: Additional ecological information requested for this 

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

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

mammalian mortalities) not already reported to the Agency. 

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

TIME LINE 

EPA has created the following estimated timeline for the completion of bromoxynil's registration 

review in Table 5 below. 

Table 5: Projected Registration Review Timeline 

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period 2013 - March 

Close Public Comment 2013 - May 

Case Development 

Final Work Plan 2013 - August 

Issue DCI 2014 - April - June 

Data Submission 2016 - April - June 

60-day Public Comment Period for Draft Risk Assessments 2017 - Oct. - Dec. 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration Review Decision 2018- April - June 

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

Total {years) 6 

NEXT STEPS 

9 
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 bromoxynil. 

10 
Appendix- Additional Areas Considered in Bromoxynil's Registration 

Review 

PUBLIC COMMENTS AND FEEDBACK: 

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

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

be of particular use. 

Trade Irritants: 

Through the registration revie'!V process, the Agency intends to solicit information on trade 

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

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

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

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

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

the nature of the concern. 

Water Quality: 

Bromoxynil is not identified as a cause of irTlfairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act . In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for bromoxynil4

• More information on impaired water bodies and 

TMDLs can be found at the Agency's website5

. 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 Procesi in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments. 

Environmental Justice: 

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

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

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

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

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

atypical, unusually high exposure to bromoxynil 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. 

3 http://iaspub.epa.gov/tmdl waters I 0/anains nation cy.cause detail 303d?p cause group icl=885 4

http://iaspub.epa.gov/tmdl waters I 0/attains nation.tmdl pollutant detail?p pollutant group id=885&p pollutant 

group name-PESTICIDES 3 hnp://www.epa.gov/owow/tmdl/ 

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

11 
ENDANGERED SPECIES: 

A risk assessment that suppmts a complete endangered species determination has not been 

conducted for bromoxynil. The ecological risk assessment planned during registration review 

will allow the Agency to determine whether bromoxynil's use has "no effect" or "may affect" 

federally listed threatened or endangered species (listed species) or their designated critical 

habitats. When an assessment concludes that a pesticide's use "may affect" a listed species or its 

designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service 

and/or National Marine Fisheries Service (the Services), as appropriate. 

On January 19, 2011, the Center for Biological Diversity and the Pesticide Action Network 

North America filed a lawsuit in the United States District Court for the Northern District of 

California, against the Environmental Protection Agency (EPA) for allegedly failing to undergo 

consultation with the United States Fish and Wildlife Service and the National Marine Fisheries 

Service regarding the effects of over 350 pesticides, including bromoxynil, on over 200 

endangered and threatened species throughout the United States (Center for Biological Diversity, 

et al. v. EPA, et al., No. C 11 -00293 (N.D.Cal.). 

ENDOCRINE DISRUPTOR SCREENING PROGRAM: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

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

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

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

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

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

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

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

taxonomic groups. As part of its most recent registration decision for bromoxynil, 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), 

bromoxynil is subject to the endocrine screening part of the Endocrine Disrupter Screening 

Program (EDSP). 

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

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

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

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

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

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

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

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

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

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

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

12 
Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Betw~en 

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. Bromoxynil is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for bromoxynil. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website7

• 

HUMAN STUDIES: 

Occupational 

Past bromoxynil risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

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

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

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

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

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

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

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

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

these studies. 

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

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