2 INTRODUCTION

This is the Environmental Protection Agency’s (E PA or the Agency) Final Work Plan (FWP) for the registration review of the following active ingredients: 4 -(2,4-dichlorophenoxy) butyric acid, or 2,4-DB, and the dimethylamine salt of 2,4-DB, dimethylamine 4-(2,4-dichlorophenoxy) butyrate (2,4-DB-DMAS). 2,4-DB and 2,4-DB-D MAS (collectively, 2,4-DB) are selective systemic chlorophenoxy herbicides registered for use to control annual and perennial broadleaf weeds in alfalfa, soybeans, spearmint, peppermint, wheat, peanuts, and birdsfoot trefoil. 2,4-DB products have no registered reside ntial uses. One of the major de gradates of 2,4-DB, 2,4-D, is a registered phenoxy herbicide and is also one of the most highly used herbicides in the U.S. Another major degradate is 2,4-DCP. This wo rk plan addresses public comments received concerning the Preliminary Work Plan (PWP), which was posted in the 2,4-DB registration review docket (EPA-HQ-OPP-2013-0661).

The Agency is implementing the registration revi ew 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. Changes in science, public policy, and pesticide use practices occur over time. The registration review program is inte nded to make sure that, as the ab ility to assess risk evolves and as policies and practices change, al l registered pesticides continue to meet the statutory standard. The public phase of registration review begins when the initial docket is opened for each case. Information on this program is provided on the Agency’s website. 1

The FWP begins with any updates since the PWP wa s issued. Next is a summary of substantive comments received during the public comment peri od for the PWP concerning anticipated data needs, expected risk assessments, or the estimated timeline identified in the PWP, and a summary of the Agency’s responses to those comments. This section is followed by registration review planned data needs, risk assessments expected to be conducted, and th e projected registration review timeline for 2,4-DB. Lastly, ther e is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

There are no additional updates on 2, 4-DB since the PWP (December 2013).

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60-day public comment period on the 2,4-DB Preliminary Work Plan, which opened on December 20, 2013 and closed on February 18, 2014, the Agency received public comments
from four stakeholders. Comments were subm itted by the Central Valley Regional Water Quality Control Board, Center for Biological Divers ity, Drexel Chemical Company, and the FIFRA Endangered Species Task Force. The comments do not address the timeline described in the PWP, but they do address the planned ecological and human health risk assessments and data requirements. In the PWP, EPA also solicited comments on the specific topics of environmental justice, water quality concerns, and trade irr itants. Comments on water quality concerns were

1 http://www.epa.gov/oppsrrd1/registration_review/3 submitted by the Central Valley Regional Water Quality Control Board, but no comments or information were received on the remaining issues.

Summarized below are public comments that result ed in changes to the anticipated registration review data needs, risk assessments, or timeline, or are of a broader regulatory nature. Public comments in their entirety are locate d in the docket, EPA-HQ-OPP-2013-0661.

Comments submitted by Central Valley Region al Water Quality Control Board in EPA-HQOPP-2013-0661-0012. The Water Quality Control Board (the Board) co mments center on considerations of the Clean Water Act and preventing water quality impair ments of phenoxy family herbicides (namely, 2,4- DB and 2,4-DP). The Board states that “for th e 2,4-DB and 2,4-DP regist rations, we support the stated requirements for aquatic toxicity data, however requiring a dditional fate and toxicity data for 2,4-DCP and the consideration of cumulative risk of phenoxy herbicides and the degradates is also necessary. (...) To be thorough and to ensure a conservative risk assessment, fate & aquatic toxicity data for 2,4-DCP should be required and assessed. Additionally, clarification on the approach that will be ta ken to consider cumulative risk is ne eded because it is currently unclear
how cumulative risk would be assessed as there ar e three separate risk assessment work plans for
these herbicides.”

1. Comment: The Water Quality Control Board suggests that the Agency “require adequate fate and aquatic toxicity data for 2,4-DCP.”

Response: 2,4-DCP is a common degradate of 2,4-DB as well as 2,4-DP and 2,4-D. The problem formulation indicates th at EPA will use a tota l toxic residues approach for assessing 2,4-DB and the degradate 2,4-DCP unless suffici ent data exist to determine estimated environmental concentrations (EECs) separately.

2. Comment: The Water Quality Control Board sugge sts that the Agency “consider the cumulative risk of additive toxicities, between 2,4-DB, 2,4-DP, 2,4-D and their degradates, as
well as between these herbicides and other pesticides.” In ad dition, the Board suggests that the Agency “clarify the approach that will be us ed in the cumulative risk assessment since 2,4- DB, 2,4-DP, and 2,4-D have separate risk assessment plans.”

Response: EPA agrees that expos ure to mixtures of compounds may affect the overall toxicity of any chemical. However, a quantitative ecological assessment of risks associated with mixtures requires extensive data and, currentl y, EPA does not have adequate data and has not yet developed the methodology to quantitatively assess mixtures of chemicals in the environment. Therefore, a quantitative ecological assessment of mixtures cannot be conducted at this time. However, EPA has a long term goal to develop a quantitative ecological risk assessment approach in cluding guidance on weight-of-ev idence analysis for assessing risks of pesticide mixtures. In the interim, EPA intends to qualitativ ely discuss the potential for differential exposure and toxic ity from mixtures of compounds.

Additionally, the Food Quality Protection Act (F QPA) requires the Agency to consider the
cumulative human health risks of chemicals sharing a common mechanism of toxicity. 2,4-4 DB is a member of the alkylphe noxy herbicide class of pesticid es. This class also includes MCPA, 2,4-D and 2,4-DP. Although the various phe noxy herbicides have similar structural components, EPA has not made a determination th at they have a common mode of toxic action in mammals. Therefore, a cumulative human he alth risk assessment has not been performed for these compounds.

3. Comment: The Water Quality Contro l Board submitted a comment through the docket for 2,4- DP stating that the Agency ought to consider the potential ecological risks of both 2,4-DB and 2,4-DP “in urban settings, including and in particular, the fate and aquatic toxicity impacts from the common degradate 2,4-DCP.”

Response: The Agency does not specifically evalua te ecological risk in urban settings when no residential, impermeable surface, or urban tu rf uses are registered for a given chemical. Since 2,4-DB only has agricultural applications, an urban setting-based risk assessment is not appropriate.

Comment submitted by Center for Biol ogical Diversity in EPA-HQ-OPP-2013-0661-0010. The Center for Biological Dive rsity comments focus on the EPAs independent duty under the Endangered Species Act to consult with the U.S. Fish and Wildlife Service as well as the National Marine Fisheries Service (the Services) on the regi stration review of 2,4-DB. Several listed species habitat data, including life history and spat ial distribution data, sources are provided.

1. Comment: Under the Endangered Species Act, it is EPA’s duty to consult with the Services on the reregistration of 2,4-DB and on the approval of all 2,4-DB end-use products. In addition, the EPA must make defensible “Not Likely to Adversely Affect” and “Likely to Adversely Affect” determinations as a prerequisite for defensible “Jeopardy” and “No Jeopardy”
determinations. EPA and the Serv ices must assess the adverse im pacts of 2,4-DB in critical
habitat.

Response: EPA has reviewed the comments fr om CBD on the registration review docket opening for 2,4-DB and plans to address many of the concerns raised by CBD as part of the implementation plan for assessing the risks of pesticides to listed species based on the recommendations of the April 2013 National Acad emy of Sciences (NAS) report. EPA will address concerns specific to 2,4-DB in connec tion with the development of its registration review decision for 2,4-DB.

At this time, EPA has not fully developed its ri sk assessment process for listed species. In November 2013, the EPA, along with the Services and the U.S. Department of Agriculture (USDA) released a summary of their joint Inte rim Approaches for assessing risks to listed species from pesticides. The Interim Approaches were developed jointly by the Agencies in response to the National Academy of Scien ces’ (NAS) recommendations and reflect a common approach to risk assessment shared by th e Agencies as a way of addressing scientific
differences between the EPA and the Services.

The NAS report, available at http://www.nap.edu/cat alog.php?record_id=18344 , outlines recommendations on specific scientific and tech nical issues related to the development of5 pesticide risk assessments that EPA and the Se rvices must conduct in connection with their obligations under the ESA and FIFRA. The joint In terim Approaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the December 2013 Pe sticide Program Dialogue Committee (PPDC)
and State-FIFRA Issues Research and Eval uation Group (SFIREG) meetings, allowing additional opportunities for stake holders to comment on the Interim Approaches. As part of a phased, iterative process for developing the In terim Approaches, the Agencies will also consider public comments on the Interim Appro aches in connection with the development of upcoming Registration Review deci sions. The details of the jo int Interim Approaches are contained in the white paper “Interim Appro aches for National-Leve l Pesticide Endangered Species Act Assessments Based on the Reco mmendations of the National Academy of Sciences April 2013 Report,” date d November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html

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Comment submitted by Drexel Chem ical Company in EPA-HQ-OPP-2013-0661-0011. Drexel Chemical Company submitted a statement noting a discrepancy in registration and data requests for 2,4-DB use on clover.

1. Comment: Drexel Chemical Company noted that registration of 2,4-DB use on clover was removed some years ago. As a result, the request for additional data (860.1500: crop field trials, clover forage and hay) should be waived.

Response: The Agency has reviewed updated a nd stamped end-use product labels for 2,4-DB and has found no current registrations on clover. In order to officially remove this use, EPA is requesting registrants to submit a 6(f) voluntary cancellation request to remove the use of clover from all registrations of 2,4-DB. Once EPA pub lishes a cancellation order removing this use from all 2,4-DB labels, EPA plans to waive the data requirement for additional geographic field trial data for clover. If a 2,4- DB product registrant decides to later support a clover use, the registrant would need to reque st a new use through the Regist ration Division and this data requirement may again be required.

Comments submitted by FIFRA Endangered Species Task Force in EPA-HQ-OPP-2013-
0661-0013.
FESTF submitted a memo with a list of studies th at “fulfill data requirements spelled out in Pesticide Registration Notice 2000-2 and provide the best availabl e data necessary to support the analysis of 2,4-DB use and listed spec ies locations and pot ential exposure.”

1. Comment: FESTF submitted a comment informing the Agency that the technical registrant of 2,4-DB is a member of the FESTF (or a company having met its data compensation obligations) and is entitled to rely on FESTF data.

Response: The Agency thanks FESTF for its comment and will take this under consideration.6 PLANNED DATA NEEDS Table 1 below summarizes the planne d data needs for 2,4-DB based on the Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, the Human Health Drinking Water Exposure Assessments for 2,4-DB and 2,4-DB-DMAS . The table has been updated since the PWP to reflect completion of recent data reviews by the Agency; the outstanding studies originally listed in the PWP from previous DCIs have all been satisfied. Data listed in Table 1 are requested for both 2,4-DB an d2,4-DB-DMAS registrations. Table 1: Planned Data Needs for the 2,4-DB Registration Review

Guideline
Number 2 Study Title 1 Test Material Estimated Timeframe
(Months from receipt of DCI)

Anticipated Data Needs

835.4100 Aerobic soil metabolism

TGAI: 2,4-DBor 2,4-DBDMAS 24 835.4300 Aerobic aquatic metabolism 24 835.4400 Anaerobic aquatic metabolism 24

850.1025 Acute toxicity—oyster (estuarine/marine shell deposition) 3 12

850.1035 Acute toxicity--mysid 4 12

850.1045 Acute toxicity-- penaeid 12

850.1055 Acute toxicity—bivalve (embryo/larval) 12 850.1300 Aquatic invertebrate life cycle (freshwater) 12 850.1350 Aquatic invertebrate life cycle (saltwater) 12 850.1400 Fish early-life stage (freshwater) 12 850.1400 Fish early-life stage (saltwater) 12

850.1730 Bioconcentration in fish 12

850.2100 Avian oral toxicity, passerine species 12

850.2300 Avian reproduction 24 850.4500 Algal toxicity (freshwater diatom) 12 850.4500 Algal toxicity (marine diatom) 12 850.4550 Cyanobacteria ( Anabaena flos-aquae ) Toxicity 12

850.6100 Environmental chemistry methods and associated independent laboratory validation in water 12

860.1500 Crop field trials (clover forage and hay) 5 TEP: 2,4-DB- DMAS 24

870.3465 90–day Inhalation–rat (an adequate 28 days in life study would be expected to be sufficient) TGAI: 2,4-DB- DMAS 24

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

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

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0028

3 Only one of the two study guidelines 850.1025 or 850.1055 is anticipated to be required.

4 Only one of the two study guidelines 850.1035 or 850.1045 is anticipated to be required,

5 Trials anticipated as needed, by Region (number of trials): Region 1 (1), Region 2 (1), Region 4 (1), Region 5 (3),

Region 6 (1), Region 7 (1), Region 8 (1), and Region 9 (1). Consider the EPA response to the Drexel Chemical Company for further details on this data requirement.7 RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for 2,4-DB was completed in 2004 in preparation for the Reregist ration Eligibility Decision. The most recent ecological and environmental fate risk assessment was comple ted in 2004 for the same purpose. Findings and
conclusions from these risk assessments are summarized in the Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Sp ecies, and Human Health Drinking Water Exposure Assessments for 2,4-DB and 2,4-DB-DMAS and 2,4-DB: Human Health Risk Assessment Scoping Document in Support of Registration Review

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During registration review, the Agency anticipa tes conducting a comprehensive ecological risk assessment, including an endangered species asse ssment, for all uses of 2,4-DB. The Agency does not anticipate conducting a new drinking water exposure assessment unless a new dietary
risk assessment is called for.

For human health, EPA does not anticipate conducti ng a revised dietary risk assessment, as the dietary risks, including those associated with dr inking water, represent only a small portion of the population adjusted doses (PADs). However, updated dietary exposure assessments may be needed upon submission of required residue data that are expected to be required for this registration review, or if or othe r new data or policy ch anges result in changes to the toxicological points of departure or uncertainty factors.

There are no residential uses of 2,4-DB, so a resi dential risk assessment is not needed. The need for bystander drift and volatilizat ion risk assessments will be evaluated during registration
review.

Table 2 below summarizes the planned registration review risk assessments based on the EFED Problem Formulation and HED Scoping Documen t; the planned assessments have not changed
from what was included in the PWP.8 Table 2: Planned Risk Assessments for the 2,4-DB Registration Review

Type of Risk Assessment Conduct? Notes
Ecological and Environmental Fate Comprehensive ecological Yes Species to be assessed include terrestrial and aquatic organisms, including endangered species.

Incidents Will check for updates Incidents are low in number. For a complete discussion of reported ecological incidents for 2,4-DB, see page 13 of the Problem Formulation.
Human Health Dietary
Food Not likely Previous risk estimates we re less than 3% of the PAD for the most sensitive population, for both
acute and chronic risks. Drinking water

Occupational Handlers (mixers, loaders, applicators) Yes If assessment parameters or SOPs change. Post-application
Residential
Handlers No There are no residential uses of 2,4-DB. Post-application
Other
Drift or volatilization risk Potentially EPA is currently developing guidance on how best
to assess these risks. Aggregate (combined risk from dietary and residential exposures.) Not likely The dietary and residential risk assessments are not likely to change, thus it is unlikely that an aggregate risk assessment will be conducted.
Cumulative
No 2,4-DB has not been identif ied as a member of a cumulative group that shares a common mechanism of toxicity in mammals.
Tolerances Likely If supported by residue data submitted during registration review.
Incidents
Will check for updates Incidents are low in number and severity. For a complete discussion of reported human incidents for 2,4-DB, see page 11 of the Scoping Document
and 2,4-DB: Tier I Review of Human Incidents

.9 TIMELINE

EPA has created the following estimated timelin e for the completion of the 2,4-DB registration
review in Table 3 below. The projected timeline was incorrect in the PWP and has been updated
to reflect the correct dates.

Table 3: Registration Review for 2,4-DB – Projected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period Dec. 2013 – Completed

Close Public Comment Feb. 2014 – Completed
Case Development

Final Work Plan June 2014 - Completed

Issue DCI 2014: July – Sept.

Data Submission 2016: July – Sept.
60-day Public Comment Period for Draft Risk Assessments 2018: Jan. - March *
Registration Review Decision 60-day Public Comment Period fo r Proposed Registration Review

Decision 2018: Oct. – Dec. **

Registration Review Decision a nd Begin Post-Decision Follow-up 2019
Total (years) 6

* The PWP dates for the draft risk assessment public comment period were 2018 Oct-Dec

** The PWP dates for the proposed registration review public comment period were 2018 Jul-Sept

NEXT STEPS

As noted previously, the Agency plans to require several environmental fate, ecological effects, and human health studies for 2,4-DB through a Data Call-In Notice, expected to be issued in September 2014.