2

2,4-D Preliminary Work Plan – Table of Contents

Overview 3

Anticipated Data Needs 4

Statutory and Regulatory Authority 4

Chemical Facts 5

Use and Usage Information 6

Recent Actions 7

Anticipated Risk Assessments for Registration Review 7

Timeline 9

Next Steps 9

Appendix – Additional Areas Considered in 2,4-D’s Registration Review 10

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 2,4-D. M. Radtke, Ph.D. and F. 

Khan, Ph.D. November 15, 2012.

2. 2,4-D. Human Health Assessment Scoping Document in Support of Registration Review. 

D. Drew. December 2, 2012.

3. Chemical Profile for Registration Review: 2,4-D. B. Phillips. June 27, 2012

4. 2,4-D: Review of Human Incidents. S. Recore. September 27, 2012.

5. 2,4-D Screening Level Usage Analysis (SLUA). Biological and Economic Analysis 

Division, March 23, 2012

These and other supporting documents for the 2,4-D registration review case may be found in the 

docket EPA-HQ-OPP-2012-0330 at http://www.regulations.gov.
3

OVERVIEW

The docket for 2,4-D is now open, initiating the first public comment period for this registration 

review (docket number EPA-HQ-OPP-2012-0330). This case includes the following 10 active 

ingredients (by PC Code): 030001, 030004, 030016, 030019, 030025, 030035, 030053, 030063, 

030066, and 051505 (for chemical names associated with these PC Codes, see “2,4-D Chemical 

Facts,” below). 2,4-D is an herbicide that is registered for use on many agricultural crops, and 

in non-agricultural and industrial use sites, including residential turf. This Preliminary Work 

Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about 2,4-D, 

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 of 2,4-D.

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 2,4-D and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on 2,4-D. 

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 nonprofit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; 

commercial, institutional, residential, and other users of pesticides; or the public at large.

The PWP begins by listing the anticipated data needs for 2,4-D. Next, it discusses the statutory 

and regulatory authority for Registration Review. Then the document provides chemical facts

about 2,4-D and use and usage information, information on recent actions, the anticipated scope 

of the future risk assessments, and a projected registration review timeline. 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 2,4-D. For additional discussion of the 

anticipated data needs, see the EFED Registration Review Problem Formulation for 2,4-D and

the Human Health Assessment Scoping Document in Support of Registration Review for 2,4-D.

Table 1. Anticipated Data Needs for the Registration Review of 2,4-D

Guideline 

Number Study Title Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

835.1410 Volatility--laboratory TEP 12

835.6100

Environmental chemistry methods and associated 

independent laboratory validation for soil and 

water1

TGAI

TGAI

12

12

850.2100 Avian oral toxicity (passerine species) TGAI 12

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

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 website2

.

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 

 1

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

including renumbering and other changes for some guideline studies. The Notice of Availability for the revisions 

can be found at http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028. 2 http://www.epa.gov/oppsrrd1/registration_review/
5

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 2,4-D.

Table 2 provides a summary of the current regulatory status of 2,4-D.

Table 2. 2,4-D CHEMICAL FACTS

PC codes Name CAS Number

030001 2,4-D dichlorophenoxyacetic acid (2,4-D) 94-75-7

030004 Sodium Salt of 2,4-D (2,4-D Na) 2702-72-9

030016 Diethanolamine Salt of 2,4-D (DEA) 5742-19-8

030019 Dimethylamine Salt of 2,4-D (DMA) 2008-39-1

030025 Isopropylamine Salt of 2,4-D (IPA) 5742-17-6

030035 Triisopropanolamine Salt of 2,4-D (TIPA) 32341-80-3

030053 Butoxyethyl Ester of 2,4-D (BEE) 1929-73-3

030063 2-Ethylhexyl Ester of 2,4-D (2-EHE) 1928-43-4

030066 Isopropyl Ester of 2,4-D (IPE) 94-11-1

051505 Choline Salt of 2,4-D (Choline) 1048373-72-3

Case Number 73

Year first registered 1948

Pesticide Type Herbicide

Chemical class Phenoxy

Reregistration Eligibility 

Decision (RED)

June 1, 2005

Tolerance Reassessment 

Eligibility Decision 

(TRED)

The Agency did not issue a TRED for 2,4-D.

Cumulative group The Agency has not identified 2,4-D as a member of a cumulative 

group.

40 CFR Citation Tolerances for 2,4-D are established in 40 CFR 180.142.

Dual-use Conventional pesticidal uses only

Non-pesticidal uses None

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Jill Bloom, bloom.jill@epa.gov, (703) 308-8019

Registration Division, 

Product Manager

Kathryn Montague, montague.kathryn@epa.gov, (703) 305-1243
6

USE AND USAGE INFORMATION

Table 3 summarizes use and usage information for 2,4-D. Please see the Chemical Profile for 

Registration Review: 2,4-D and the 2,4-D Screening Level Usage Analysis (SLUA) in the 

registration review docket for more details.

Table 3. Use and Usage Information

Summary of Use 2,4-D and its derivatives are herbicides registered for many 

agricultural and non-agricultural use sites. 2,4-D is an auxin-like

plant hormone with the mechanism of action like that of the in vivo

plant growth regulator indole acetic acid. 2,4-D effects its control 

on weeds via disrupting the flow in the vascular system. 2,4-D is 

also registered for use in post-harvest applications to citrus fruits. 

Use Sites Registered uses include forage grasses (pasture, hay and silage), 

corn, soybean, small grains (such as rice, barley, oats, wheat rye, 

etc.), fallowland, sugarcane, citrus, grape, pecan, forest trees, 

ornamental plants, ornamental turf, and aquatic sites (ditch banks, 

irrigation systems, lakes, ponds, etc.). 

Summary of Usage Between 2000 and 2010, usage averaged approximately 29 million 

pounds active ingredient (lbs a.i.)/year for 55 million acres treated.

Formulation Type(s) Emulsifiable concentrates, granules, soluble concentrates/solids, 

water dispersible granules, and wettable powders. 

Application Method(s) Broadcast and directed applications may be made with application 

equipment including fixed-wing aircraft, backpack sprayers, band 

sprayers, boom sprayers, granule applicators, ground-directed 

sprayers, hand held sprayers, helicopters, and injection equipment.

Technical Registrant(s) Dow AgroSciences, NuFarm, AGRO GOR, and PBI Gordon 

No. of Registrations Over 625 Section 3 registrations and 30 24(c)s

3

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.

• Certain 2,4-D product 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. EPA expects to approximate these parameters in order to 

conduct a quantitative assessment for 2,4-D. The Agency will work with registrants to 

clarify use parameters, with the goal of reducing uncertainties in the risk assessments, 

and future assessments will be conducted according to updated use parameters.

• Additional label information that may be important for defining use parameters: 

specialty applications; formulation types; 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)

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
7

• Median and 90th percentile reported use rates (lbs ai/1000 sq ft) 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 2,4-D to the US 

market

RECENT ACTIONS

None.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent ecological and environmental fate risk assessments for 2,4-D were completed in

2005 (in support of the Reregistration Eligibility Decision, or RED), and in 2009 (for the 

California red-legged frog and Alameda whipsnake endangered species assessment). The most 

recent comprehensive human health risk assessment for 2,4-D was completed in 2005 in support 

of the RED for 2,4-D. Findings and conclusions from these risk assessments are summarized in 

the EFED Registration Review Problem Formulation for 2,4-D and the 2,4-D. 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 2,4-D.

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

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

departure are revised, they will be considered in the new assessments, in addition to any changes 

to the standard operating procedures or default exposure assumptions.

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

EFED Problem Formulation and HED Scoping Document.
8

Table 4. Anticipated Risk Assessments for the Registration Review of 2,4-D

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Y 

Incidents Y For a discussion of ecological incidents associated 

with the use of 2,4-D, see pages 21-22 of the Problem 

Formulation.

Human Health

Dietary

Food Y

Drinking water Y

Occupational

Handlers (mixers, loaders, 

applicators)

Y

Post-application Y

Residential

Handlers Y

Post-application Y

Other

Aggregate Y Evaluates the combined risk from dietary and 

residential exposures.

Cumulative N The Agency has not identified 2,4-D as a member of a 

cumulative group.

Tolerances Y

Incidents Y For a discussion of human incidents associated with 

the use of 2,4-D, see page 15 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).

Additional human health information requested for this registration review, and of particular 

interest to EPA, is described below.

• Incidents not already reported to the Agency, especially those thought to be associated 

with drift or volatilization.
9

TIMELINE

Table 5 below shows the Agency’s projections for the 2,4-D registration review timeline.

Table 5. Registration Review for 2,4-D– Projected Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2012 - December

Close Public Comment 2013 - February

Case Development

Final Work Plan 2013 - May

Issue DCI 2014 - January-March

Data Submission 2015 - January-March

Open 30-day Public Comment Period for Draft Risk Assessments 2016 – July-September

Registration Review Decision

60-day Public Comment Period for Proposed Registration Review 

Decision

2017 – January-March

Registration Review Decision and Begin Post-Decision Follow-up 2017

Total (years) 5

NEXT STEPS

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 2,4-D.
10

Appendix – Additional Areas Considered in the Registration Review of 2,4-D

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 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:

2,4-D by itself is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act, but 2,4-D is an organochlorine pesticide, and this 

group of pesticides have been identified as a cause of impairment in several water bodies4

. No 

Total Maximum Daily Loads (TMDL) have been developed for 2,4-D or the organochlorine 

pesticides as a group5

. More information on impaired water bodies and TMDLs can be found at

the Agency’s website6

. 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 Process7 in order 

to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Aquatic Life Benchmarks for the 2,4-D acid and salts have been published and can be found at:

(http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm#benchmarks).

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 2,4-D compared to the general population. Please 

 4 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

5

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

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

7 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
11

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 2,4-D. The ecological risk assessment planned during registration review will 

allow the Agency to determine whether the use of 2,4-D 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 2,4-D, 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 reregistration decision for 2,4-D, 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), 2,4-D is subject to the 

endocrine screening part of the Endocrine Disruptor 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. 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. 2,4-D was included on 

that list and has been issued an order to conduct the Tier 1 testing. Once all required Tier 1 and 

Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk 

assessment purposes will be examined and a new risk assessment performed if necessary. 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 

website8.

EPA has received all required final study reports and data from the Tier 1 battery of tests for 

2,4-D. EPA waived the in vivo mammalian Tier 1 tests for 2,4-D due to the availability of a 

newly-submitted extended one generation reproduction study with 2,4-D. The submitted 

studies will be evaluated using a weight of the evidence approach to determine if any additional 

Tier 2 testing of 2,4-D is necessary. 

HUMAN STUDIES:

Occupational and Residential

Past 2,4-D 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), 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 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.

Chemical-specific Human Studies

Past 2,4-D risk assessments have relied in part on data from a human dermal absorption (in vivo)

study that involved intentional exposure to 2,4-D. The study was considered for determining the 

dermal absorption factor in previous 2,4-D risk assessments. EPA reviewed this study and 

determined that there was no clear evidence that the conduct was fundamentally unethical. 

AGRICULTURAL HEALTH STUDY:

2,4-D is among several agricultural chemicals included in the Agricultural Health Study (AHS). 

The AHS began in 1993 and is a collaboration of the National Institute of Environmental Health 

 8 http://www.epa.gov/endo/
13

Sciences (NIEHS), the National Cancer Institute (NCI), the EPA, and the National Institute for 

Occupational Safety and Health (NIOSH). Designed as a large long-term epidemiological study, 

the AHS collects and analyzes data on the health and work practices of nearly 90,000 farmers 

and their families in Iowa and North Carolina who enrolled in the study before any disease 

developed. The study focuses particularly on farmers' exposure to 50 chemicals including many 

of the most widely used pesticides. As data are collected over a period of years, scientists can 

compare overall health outcomes for people who differ in whether they have had exposure to 

various chemicals. While these comparisons cannot conclusively demonstrate how exposure 

affects health, they can show some statistical associations. More information on the AHS can be

found at: http://aghealth.nci.nih.gov. EPA is monitoring the results of the AHS and will consider 

this study in the registration review of 2,4-D as appropriate.