2 

### Clopyralid Preliminary Work Plan

– Table of Contents

OVERVIEW

................................ ................................ ................................ ................................ ... 4

ANTICIPATED DATA NEEDS

................................ ................................ ................................ .... 5

STATU TORY AND REGULATORY AUTHORITY

................................ ................................ ... 7

CHEMICAL FACTS

................................ ................................ ................................ ...................... 7

USE AND USAGE INFORMATION

................................ ................................ ............................ 8

RECENT ACTIONS

................................ ................................ ................................ ..................... 10

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

.............................. 10

TIMELINE

................................ ................................ ................................ ................................ .... 12

NEXT STEPS

................................ ................................ ................................ ............................... 13

Appendix

– Additional Areas Considered in the Clopyralid Registration Review

.................. 14

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 Clopyralid

. Arnold, Lin

. 2/25/14

.

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

Review. Doherty, Collantes, Middleton. 3/14/14.

3. Clopyralid: Tier I Review of Human Incidents

. Evans, Recore

. 11/20/13.

4. BEAD Chemical Profile (BCP) for Registration Review: Clopyralid Case (117401, 117403, 117404, and 117423)

. Ratnayake, Haddad, Smearman

. 1/9/14.

5. Environmental Fate and Effects Division Label Data Report Spreadsheet: PC Codes:

117401

, 117403

, 117404 and 117423

. December 12 , 2013.

6. Health Effects Division Master Label Report Spreadsheet: PC Codes: 117401, 117403,

117404 and 117423

. December 12 , 2013.3

7. Clopyralid Ground and Surface Water Data (Montana). Mulder, R. Personal communication. Montana Department of Agriculture. 12/30/13

.

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

in the docket EPA

- HQ

- OPP

- 2014

- 0167 at http://www.regulations.gov

.4

OVERVIEW

The docket for clopyralid is now open , initiating the first public comment period for this registration review (docket number EPA

- HQ

- OPP

- 2014

- 0167 )

. Clopyralid (3,6

- dichloropyridine

- 2

- carboxylic acid) is a pyridine herbicide. This case includes the clopyralid parent along with its potassium, triethanolamine , and monoethanolamine salt s

. Pyridine herbicides are auxin growth regulators, which mimic naturally

- occurring plant hormones, thereby disrupting growth processes and causing abnormal growth patterns in plants. Clopyralid is registered for use on a variet y of agricultural crops, and non

- crop use sites, including tree and sod farms, forest s
, pastures and rangelands, ornamental landscapes and nurseries , golf courses

and recreational areas

. Since clopyralid is not a restricted

- use pesticide, the Agency must ensure adequate mitigation measures are on the labels to be protective of potential homeowner

exposure. Clopyralid may be applied as a broadcast foliar or soil

- directed spray via aircraft, ground

- and hand

- held sprayer s
, granular spreader or via tree injection

. This Preliminary Work

Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about clopyralid

, 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 for clopyralid

.

The registration review process was designed to include a public participation component to solicit input from interested st akeholders. The Agency intends, b y sharing this information in the docket, to inform the public of what it knows about clopyralid and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on

c lopyralid

. 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 pe rsons may wish to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include:

environmental non

- profit or interest groups; pesticide manufactu rers; agricultural labor or commodity groups; commercial, institutional, residential, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for clopyralid

. Next, it

discusses the sta tutory and regulatory authority for R egistration R eview. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review timeline for clopyralid

. Finally, the App endix to this document includes identification and discussion of some areas that are considered generally

in R egistration R eview along with some additional chemical case

- specific information.5

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for clopyralid . For additional discussion of the anticipated data needs, see the EFED Registration Review Problem Formulation for Clopyralid

and Clopyralid. Human Health Assessment Scoping Document in Support of Reg istration

Review

.

A number of clopyralid end

- use products are co

- formulated with other registered herbicide active ingredients (e.g., 2,4

- D, dicamba, fluroxypyr and/or triclopyr) . The Agency has concerns that terrestrial plants may be more sensitive to t hese active ingredient co

- formulations than to the clopyr alid active ingredients alone. Therefore, vegetative vigor studies with co

- formulated products are anticipated to be required . Also, as a bridging strategy has not been established for clopyralid sa lts due to lack of toxicity data , vegetative vigor and seedling emergence studies are anticipated to be required for each of the four clopyralid active ingredients. Further, the Agency anticipates requiring data about how persistent clopyralid may be in c ompost, which should help inform the Agency’s understanding of the potential risk to non

- target taxa that may be posed by the application of composted material containing clopyralid residues.

Table 1: Anticipated Data Needs for the Clopyralid Registratio n Review 1

Guideline

Number 2 Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated D ata Needs for Clopyralid

835.4100 Aerobic soil metabolism (3 additional soils) TGAI 24

835.4300 Aerobic aquatic metabolism (2 sediments) TGAI 24

850.1300 Chronic freshwater invertebrate TGAI 12

850.1400 Freshwater fish early

- life stage TGAI 12

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.2300 Avian reproduction (upland game species) TGAI 24

850.4100 3 Terrestrial plant toxicity, seedling emergence TEP 12

850.4150 3 Terrestrial plant toxicity, vegetative vigor TEP 12

850.4400 Aquatic vascular plant growth TEP 12

850.4500 Aquatic non

- vascular plant growth (2 additional

species) TEP 12

850.4550 Cyanobacteria Toxicity TEP 12

1 T here are additional 40 CFR Part 158 aquatic ecotoxicology data gaps that are not anticipated to be required at this

time because they are not expected to impact the risk assessment (see Table 12 of EFED Problem Formulation)

. 2 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850

– Ecological Effects Tests

– including renumbering and other des ignations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.re gulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

3 Data are expected to be required for four typical end use products, one each containing clopyralid, clopyralid monoethanolamine salt, clopyralid triethanolamine, and clopyralid potassium.6

Table 1: Anticipated Data Needs for the Clopyralid Registratio n Review 1

Guideline

Number 2 Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

850.6100 Environmental chemistry methods and associated

independent laboratory v alidation s for soil , water,
and compost Compost

sourced from

material treated

with TEP 12

Non

Guideline Dissipation Study in Compost Compost

sourced from

material treated

with TEP 12

Anticipated D ata Needs for Clopyralid End

- Use Products Co

- formulated with other Herbicide s

850.4150 4 Terrestrial plant toxicity, vegetative vigor TEP 12
TGAI = technical grade active ingredient; TEP = typical end

- use product ;

4 Data are expected to be required for representative TEPs co

- formulated with other herbicides for the most sensitive crops from prior clopyralid studies (i.e., onion, snap bean, soybean, sunflower, tomato, and wheat ). The Agency is seeking comment from the reg istrants and other stakeholders on the number of co

- formulated products to be tested.7

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

. 5

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 additional risk analyses and data or information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will develop a F inal W ork P lan (FWP) and anticipated schedule for the registration review of clopyralid

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for clopyralid

.

Table 2: Chemical Facts for Clopyralid

PC code s 117401 (monoethanolamine salt) , 117403 (clopyralid) , 117404 (triethanolamine) , 117423 (potassium)

Case Number 7212

CAS Number 57754

- 85

- 5 (monoethanolamine salt), 1702

- 17

- 6 (clopyralid),

119308

- 91

- 7 (triethanolamine), 58509

- 83

- 4 (potassium)

Year first registered 1987 Pesticide Type Systemic herbicide

Chemical class Pyridine carboxylic acid

R eregistration Eligibility Decision (R E D) Because it was registered after November 1984, clopyralid was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) T hough t here is no TRED for clopyralid

, clopyralid tolerance s

were reassess ed through a 2002 registration action.

5 http://www.epa.gov/oppsrrd1/registration_review/8 Table 2: Chemical Facts for Clopyralid

Cumulative group Not applicable. Clopyralid has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for clopyralid are established i n § 180.431.

Dual

- use Clopyralid is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses.

Non

- pesticidal uses There are no identified non

- pesticidal uses of clopyralid.

Pesticide Re

- evaluation Division, Chemical Review Manager Steven Snyderman, snyderman.steven@epa.gov , 703

- 347

- 0249

Registration Division

, Product Manager Kathryn Montague, montague.kathryn@epa.gov, 703

- 305

- 1243

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for clopyralid

. Please see the BEAD Chemical Profile (BCP) for Registration Review: Clopyralid Case (117401, 117403, 117404, and 117423) in the registration review docket for more det ails

.

Table 3 : Clopyralid Use and Usage Information

Summary of Use Clopyralid is a systemic , postemergen ce herbicide registered for

use to control broadleaf weed species on a variety of agricultural

crops, non

- crop land such as pastures and rangeland, tree and sod farms, forests, commercial and recreational areas . Clopyralid acts

as a plant growth regulator by mimicking natural plant growth hormones (auxins). Clopyralid has a long period of residual activity and the rotational interval for some crops is 18 months.

Use Sites Agricultural use sites include : alfalfa, apples, almonds, asparagus, barley, beans, canola, chestnuts, cherries, cole crops, co rn (field, pop, and sweet), cranberries, filberts, l entils, macadamia nuts, mint, oats, pasture, rangeland, peas, peaches, pecans, pistachio nuts, potatoes, safflower, sorghum, soybeans, spinach, strawberries, sugar beets, sunflower, teff, wheat, and walnuts.

Non

- agricultural use sites include : sod farms, forests, tree farms, pastures and rangeland, cemeteries, farm buildings, fencerows, industrial sites, ornamen tal lawns and turf, ornamentals trees,
athleti c fields, golf fairways, parks, and rights

- of

- way. Summary of Usage Based on private market usage data of agricultural use from 1998

- 2012, usage averaged approximately 880,000 pounds active ingredient (a.i.) applied annually on approximately 10.5 million acres treated. The average a.i. rate over this time period was 0.084 pounds a.i./acre. During 2008

- 2012, major agricultural usage includes corn ( 430,000 annual average pounds) , spring wheat9 Table 3 : Clopyralid Use and Usage Information

(317,000), barley (58,000), winter wheat (47,200) and pasture land (25,600).

Available non

- agricultural usage data for clopyralid is l imited and

dated. Formulation Type(s) Emulsifiable concentrate, soluble concentrate, ready

- to

- use solution , wettable powder and water dispersible granules. Application Method(s) Products can be applied as a broadcast foliar or ground

- directed

spray by aircraft, ground

- or hand

- held sprayer s
, granular spreader or via tree injection

. Technical Registrant (s) Albaugh Inc., Dow Agrosciences LLC, and United Phosphorus

Inc. No. of Registrations 65 Section 3 products 6 , 42 Section 24c, and 2 Experimental Use Permit registrations.

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.

 C onfirmation of the following label information : sites of application ; formulations ; application methods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum number of applications per season ; and geographic limitations on use

.

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

.

 M edian and 90 th percentile reported use rates (lbs ai/ A ) from usage data

– national, state, and county

.

 Typical a pplication timing (date of first application and application intervals)

– national, state, and county

.

 Usage/use information for non

- agricultural uses

. EPA has very limited recent (post

2006) usage data except for available data from 2012 for golf courses.

o Information needed includes the pounds a.i. applied, appl ication rates, application method and percent crop treated for the following: institutional turf, landscaping, nursery/greenhouses, and sod farms.

 Typical application interval (days)

.

 S tate or local use restrictions

.

 F oreign technical registrants not liste d above who supply technical clopyralid to the US

market

.

 Current proprietary databases do not contain survey data about registered agricultural sites such as mint, lentils, and macadamia nuts, and usage data for all sites such as the pounds a.i. applied, application method, percent of the crop treated and application rates

would be beneficial.

6 Section 3 product labels can be obtained from the Pesticide Produ ct Label System (PPLS) website ( http://oaspub.epa.gov/pestlabl/ppls.home ).10

RECENT ACTIONS

A preliminary review of clopyralid labels indicates that a label amendment may be needed to clarify the Restricted Entry Interval (REI) and Personal Protection Equipment (PPE) for cer tain clopyralid registrations. As clopyralid acid is classified as Toxicity Category I for eye irritation,

all agricultural products should, according to the Worker Protection Standard guidelines, have an

REI of 48 hours

. The Agency anticipates working with registrants to amend clopyralid labels that do not specify a 48

- hour REI and to consider ways to protect homeowners applying clopyralid in consideration of the Toxicity Category 1 for eye irritation

. Mitig ation discussions could include making all clopyralid products restricted use pesticides (RUPs).

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for clopyralid was completed in

2012 for a ne w use request to support uses on apples, teff, brassica leafy greens, and rapeseed.

T he most recent ecological and environmental fate risk assessment was completed on clopyralid for the same purpose . Findings and conclusions from these risk assessments a re summarized in

the EFED Registration Review Problem Formulation for Clopyralid and Clopyralid. 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 clopyralid

. For human health, EPA anticipates the need to conduct revised dietary and aggregate risk assessments during registration review

. If toxicol ogical endpoints or points of departure are

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

, they will be

considered in the new assessment s
, as well as any changes to the standard operating p rocedures or default exposu re assumptions

.

T able 4 below summarizes the anticipated registration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document

.11

Table 4: Anticipated Risk Assessments for the Clopyralid Registration Review

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 Will check for updates For a discussion of reported ecological incidents

for clopyralid , see page 15 of the Problem

Formulation.

Human Health Dietary

Food Y The Agency anticipates conducting an updated dietary assessment to incorporate new estimated drinking water concentrations. Drinking water Y

Occupational Handlers (mixers, loaders, applicators) N The need for a spray drift and volatilization risk assessment for clopyralid will be examined during registration review. Post

- application N

Residential

Handlers N The need for a spray drift and volatilization risk assessment for clopyralid will be examined during registration review. Post

- application N

Other Aggregate Y E valuates the combined risk from dietary and residential exposures.

Cumulative N/A Clopyralid has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

Tolerances Y T he Agency anticipates work ing to harmonize tolerances/MRLs, where possible, during registration review.12

Incidents Will check for updates For a discussion of repo rted human incidents for

clopyralid, see page 10 of the Clopyralid. Human Health Assessment Scoping Document in Support of Registration Review

. Due to the low frequency and generally low severity of incident cases reported for clopyralid there does not appear to be a concern at this time that would warrant further investigation.

Guidance for Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

 A prospective groundwater monitoring study or studies to refine groundwater modeling inputs for the Pesticide Root Zone Model for Groundwater (PRZM

- GW) model would be

useful to better understand risk from clopyralid residues in g roundwater used for irrigat ion.

 The application of clopyralid to vegetative matter that is subsequently used as compost or animal feed has been found to retain clopyralid residues and affect non

- target plants. The Agency is interested in additional information about this issue, su ch as incident reports

and environmental fate data

.

 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 d etails)

.

 Some use patterns of clopyralid are not sufficiently characterized to permit ready calculation of a maximum application rate per acre, or else involve very broad use sites.

More information about the items listed on page 6 of EFED Registration Review Problem Formulation for Clopyralid would reduce uncertainty regarding such uses in the risk

assessment

.

TIMELINE

EPA has created the following estimated timeline for the completion of the clopyralid registration review in Table 5 below

.

Table 5: Projected Clopyralid Registration Review Timeline

Activities Estimated Date
Opening the Docket

Open Docket and 60

- day Public Comment Period 2014

– March

Close Public Comment 2014

– May
Case Development

Final Work Plan 2014

– August

Issue DCI 2014 Oct.

– Dec.

Data Submission 2016 Oct.

– Dec.13 Table 5: Projected Clopyralid Registration Review Timeline

Activities Estimated Date

60

- day Public Comment Period for Draft Risk

Assessments [1] 2018 April

- June

Registration Review Decision

60

- day Public Comment Period for Proposed
Registration Review Decision 2019 Jan.

- March

Registration Review Decision and Begin Post

- Decision

Follow

- up 2020

Total (years) 6

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 clopyralid

.

[1] The regulations governing Registration Review generally require the Agency to provide a public comment period of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For convention al pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.14



### Appendix

– Additional Areas Considered in the Clopyralid Registration

Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the 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 residue 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 marke ts, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

Clopyralid is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 7 In addition, n o Total Maximum Daily Load s (TMDL) have been developed for clopyralid

. 8 More information on impaired water bodies and

TMDLs can be found at the Agency’s website

. 9 The Agency invites submission of water quality data for this pesticide. To the extent possib le, 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 10 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a resul t of their location, cultural practices, or other factors, may have atypical, unusually high exposure to clopyralid compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusually high

exposure compared to the general population.

7 http://iaspub.epa.gov/t mdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

8 http://iaspub.epa.gov/tmdl_waters10/a ttains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

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

10 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm15

ENDANGERED SPECIES :

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

conducted for clopyralid

. The ecological risk assessment planned during registration review will

allow the A gency to determine whether use of clopyralid 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 liste d 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.

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, neurotoxici ty, 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 maturati on, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for cloypralid

, 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), clopyra lid 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 wild life 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 batt ery 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 caus ed by the substance, and

establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data c all

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 11 and includes some pesticides scheduled for regist ration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

11 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.16

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists , the test guidelines and the Tier 1 screening battery, please visit our

website. 12

HUMAN STUDIES :

Occupationa l and Residentia l

Past clopyralid 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 gen eric pesticide exposure databases such as the Pesticide Ha ndlers 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 t hese 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 resea rch 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 regulatory barrier to continued reliance on these studies

.

AGRICULTURAL HEALTH STUDY :

Clo pyralid 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 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 o verall 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 clopyralid as appropriate.

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