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INTRODUCTION 

This is the Environmental Protection Agency’s (EPA 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-DMAS (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 residential uses. One of the major degradates 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 work 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 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. Changes in science, public policy, and pesticide use practices occur over time. 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. 

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 was issued. Next is a summary of substantive 

comments received during the public comment period 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 the projected registration 

review timeline for 2,4-DB. Lastly, there 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 submitted by the Central Valley Regional Water Quality 

Control Board, Center for Biological Diversity, 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 irritants. Comments on water quality concerns were 

 

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 http://www.epa.gov/oppsrrd1/registration_review/ 
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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 resulted 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 located in the docket, EPA-HQ-OPP-2013-0661. 

Comments submitted by Central Valley Regional Water Quality Control Board in EPA-HQOPP-2013-0661-0012. 

The Water Quality Control Board (the Board) comments center on considerations of the Clean 

Water Act and preventing water quality impairments of phenoxy family herbicides (namely, 2,4-

DB and 2,4-DP). The Board states that “for the 2,4-DB and 2,4-DP registrations, we support the 

stated requirements for aquatic toxicity data, however requiring additional 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 taken to consider cumulative risk is needed because it is currently unclear 

how cumulative risk would be assessed as there are 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 that EPA will use a total toxic residues approach for assessing 

2,4-DB and the degradate 2,4-DCP unless sufficient data exist to determine estimated 

environmental concentrations (EECs) separately. 

2. Comment: The Water Quality Control Board suggests 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 addition, the Board suggests that 

the Agency “clarify the approach that will be used 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 exposure 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, currently, 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 including guidance on weight-of-evidence analysis for assessing 

risks of pesticide mixtures. In the interim, EPA intends to qualitatively discuss the potential 

for differential exposure and toxicity from mixtures of compounds. 

Additionally, the Food Quality Protection Act (FQPA) requires the Agency to consider the 

cumulative human health risks of chemicals sharing a common mechanism of toxicity. 2,4-
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DB is a member of the alkylphenoxy herbicide class of pesticides. This class also includes 

MCPA, 2,4-D and 2,4-DP. Although the various phenoxy herbicides have similar structural 

components, EPA has not made a determination that they have a common mode of toxic action 

in mammals. Therefore, a cumulative human health risk assessment has not been performed 

for these compounds.

3. Comment: The Water Quality Control 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 evaluate ecological risk in urban settings when 

no residential, impermeable surface, or urban turf 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 Biological Diversity in EPA-HQ-OPP-2013-0661-0010. 

The Center for Biological Diversity 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 registration review of 2,4-DB. Several listed species 

habitat data, including life history and spatial 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 Services must assess the adverse impacts of 2,4-DB in critical 

habitat.

Response: EPA has reviewed the comments from 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 Academy of Sciences (NAS) report. EPA will 

address concerns specific to 2,4-DB in connection with the development of its registration 

review decision for 2,4-DB. 

At this time, EPA has not fully developed its risk 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 Interim 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 Sciences’ (NAS) recommendations and reflect a 

common approach to risk assessment shared by the Agencies as a way of addressing scientific 

differences between the EPA and the Services. 

The NAS report, available at http://www.nap.edu/catalog.php?record_id=18344, outlines 

recommendations on specific scientific and technical issues related to the development of 
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pesticide risk assessments that EPA and the Services must conduct in connection with their 

obligations under the ESA and FIFRA. The joint Interim 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 Pesticide Program Dialogue Committee (PPDC) 

and State-FIFRA Issues Research and Evaluation Group (SFIREG) meetings, allowing 

additional opportunities for stakeholders to comment on the Interim Approaches. As part of a 

phased, iterative process for developing the Interim Approaches, the Agencies will also 

consider public comments on the Interim Approaches in connection with the development of 

upcoming Registration Review decisions. The details of the joint Interim Approaches are 

contained in the white paper “Interim Approaches for National-Level Pesticide Endangered 

Species Act Assessments Based on the Recommendations of the National Academy of 

Sciences April 2013 Report,” dated November 1, 2013, available at 

http://www.epa.gov/espp/2013/nas.html. 

Comment submitted by Drexel Chemical 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 and 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 publishes 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 request a new use through the Registration 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 that “fulfill data requirements spelled out in 

Pesticide Registration Notice 2000-2 and provide the best available data necessary to support the 

analysis of 2,4-DB use and listed species locations and potential 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.
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PLANNED DATA NEEDS 

Table 1 below summarizes the planned 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 

Number2 Study Title1 

Test Material 

Estimated Timeframe 

(Months from receipt 

of DCI) 

Anticipated Data Needs

835.4100 Aerobic soil metabolism 

TGAI: 2,4-DB 

or 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 ingredient; TEP = typical end-use product 

 

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 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-HQ-OPPT-2009-0154-0028 3

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

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

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 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. 
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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 Reregistration Eligibility Decision. The most recent ecological and 

environmental fate risk assessment was completed 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 Species, 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. 

During registration review, the Agency anticipates conducting a comprehensive ecological risk 

assessment, including an endangered species assessment, 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 conducting a revised dietary risk assessment, as the 

dietary risks, including those associated with drinking 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 other new data or policy changes result in changes to the toxicological 

points of departure or uncertainty factors. 

There are no residential uses of 2,4-DB, so a residential risk assessment is not needed. The need 

for bystander drift and volatilization 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 Document; the planned assessments have not changed 

from what was included in the PWP. 
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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 were 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 identified 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. 
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TIMELINE

EPA has created the following estimated timeline 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 for Proposed Registration Review 

Decision 

2018: Oct. – Dec.**

Registration Review Decision and 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.