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 Assessment s 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 summarize s 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 Scree ning 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 name s associated with these PC Codes, see “2,4

- D Chemical
Facts

, ” below ). 2,4

- D is an herbicide that is registered for u se 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 a ssessment 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 desig ned to include a public participation component to solicit input from interested stakeholders. The Agency intends, b y 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 t hat 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 informa tion. 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 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 act ions, 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 R egistration R eview alon g 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

water 1 T GAI
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 envi ronment 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

s ure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website 2

.
The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicid e, 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

. T he 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 additi onal 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/oppsrr d1/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 F inal W ork P lan (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
R eregistration Eligibility Decision (R E D) 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

- 12436 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 n on

- agricultural use sites

. 2,4

- D is an auxin

- like plant hormone wi th the mechanism of action like that of the in vivo plant growth regula tor 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 u ses 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 a pplication equipment including fixed

- wing aircraft, backpack sprayers, band sprayers, boom sprayer s, 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 2 4 (c) s 3

Restricted Use No

Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , 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 application s ; formulation types ; application methods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum number of applications per season ; and geographic limitation s on use

.

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

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

( http://oaspub.epa.gov/pestlabl/ppls.home ).7 • M edian and 90 th percentile reported use rates (lbs ai/ 1000 sq ft ) from usage data

– national, state, and county

• A pplication timing (date of first application and application intervals)

– national, state, and county

• Usage/use information for non

- agricultural uses

• Typical application interval (days)

• S tate or local use restrictions

• F oreign technical registrants not listed above who supply technical 2,4

- D to the US market

RECENT ACTIONS

None.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

T he most recent ecological and environmental fate risk assessment s 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 fo r 2,4

- D. Findings and conclusio ns 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, t he 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 assessment s during reg istration review

. If toxicological endpoints or points of departure are revised, they will be considered in the new assessment s , in addition to any changes to the standard operating p rocedures 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

Eco logical 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 (m ixer s, loader s, applicators ) Y

Post

- application Y Residential
Handlers Y
Post

- application Y Other Aggregate Y E valuates 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 Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

• Ec ological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

.

• Water quality m onitoring data (see Appendix for further details)

.

Additional human health information requested for this registration review, and of particular interest to EPA, is de scribed below.

• I ncidents 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
D ecision 201 7

– January

- March

Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2017 Total (years) 5

NEXT STEPS

After the 6 0

- 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 C ommenters: The areas below highlight topics of special interest to th e Agency where your comments, data submissions, or reference to sou rces of additional information c ould 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 r esidue limits (MRL s ) 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 market s, 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 bodies 4

. N o Total Maximum Daily Load s (TMDL) have been developed for 2,4

- D or the organochlorine pesticides as a group 5 . More informa tion on impaired water bodies and TMDLs can be found at the Agency’s website 6

. 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 Process 7 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Aqua tic 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 en vironmental 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 hav e 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.htm11 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 co nsult 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 St ates 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 regardin g 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 :

A s 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, neurotoxicit y, 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 maturatio n, 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 select ed 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 effect s 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 est rogen, 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 whic h, 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 e ffect.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 iner t 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 b e 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 web site 8

.
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 :

Occupationa l and Residentia l

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 e xposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Ha ndlers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Database , and the Outdoor Reside ntial 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. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied , and t here is no r egulatory 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 Na tional 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 wh o 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 heal th 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.