2

Clopyralid Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY 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 summarizes 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 salts. 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 variety of agricultural crops, and non-crop use sites, including tree and 

sod farms, forests, 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 sprayers, 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 stakeholders. The Agency intends, by 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 

clopyralid. 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 decisionmaking 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 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 Preliminary Work Plan begins by listing the anticipated data needs for clopyralid. Next, it 

discusses the statutory and regulatory authority for Registration Review. 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 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.
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 Registration 

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 these active ingredient co-formulations than to the 

clopyralid 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 salts 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 compost, 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 Registration Review1

Guideline 

Number2 Study Title

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data 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

850.41003 Terrestrial plant toxicity, seedling emergence TEP 12

850.41503 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 There 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 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 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 Registration Review1

Guideline 

Number2 Study Title

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

850.6100

Environmental chemistry methods and associated 

independent laboratory validations for soil, water,

and compost

Compost 

sourced from 

material treated 

with TEP

12

NonGuideline Dissipation Study in Compost

Compost 

sourced from 

material treated 

with TEP

12

Anticipated Data Needs for Clopyralid End-Use Products Co-formulated with other Herbicides

850.41504 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 registrants 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 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 website.

5

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 

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 clopyralid.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for clopyralid.

Table 2: Chemical Facts for Clopyralid

PC codes 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

Reregistration Eligibility 

Decision (RED)

Because it was registered after November 1984, clopyralid was 

not subject to reregistration.

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Though there is no TRED for clopyralid, clopyralid tolerances

were reassessed 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 in §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 details.

Table 3: Clopyralid Use and Usage Information

Summary of Use Clopyralid is a systemic, postemergence 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, corn (field, 

pop, and sweet), cranberries, filberts, lentils, 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, ornamental lawns and turf, ornamentals trees, 

athletic 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 wheat 
9

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 limited 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 sprayers, granular 

spreader or via tree injection.

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

Inc.

No. of Registrations 65 Section 3 products6, 42 Section 24c, and 2 Experimental Use 

Permit registrations.

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.

 Confirmation 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.

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

 Median and 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county.

 Typical application timing (date of first application and application intervals) – national, 

state, and county.

 Usage/use information for non-agricultural uses. EPA has very limited recent (post2006) usage data except for available data from 2012 for golf courses. 

o Information needed includes the pounds a.i. applied, application rates, 

application method and percent crop treated for the following: institutional 

turf, landscaping, nursery/greenhouses, and sod farms.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrants not listed 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 Product 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 certain 

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. Mitigation 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 new use request to support uses on apples, teff, brassica leafy greens, and rapeseed. 

The most recent ecological and environmental fate risk assessment was completed on clopyralid

for the same purpose. Findings and conclusions from these risk assessments are 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, the 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 toxicological 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 assessments, as well as 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.
11

Table 4: Anticipated Risk Assessments for the Clopyralid Registration Review

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 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 

Post-application N during registration review.

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 Evaluates 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 The Agency anticipates working to harmonize 

tolerances/MRLs, where possible, during 

registration review.
12

Incidents Will check 

for updates

For a discussion of reported 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 Commenters: Additional ecological information requested for this 

registration review, 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 groundwater used for 

irrigation.

 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, such as incident reports 

and environmental fate data.

 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).

 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 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 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 conventional 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 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:

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, no Total Maximum Daily Loads 

(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 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 Process10 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 result 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/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

8http://iaspub.epa.gov/tmdl_waters10/attains_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.htm
15

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 Agency 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 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.

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 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), clopyralid 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. 

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. A second list 

of chemicals identified for EDSP screening was published on June 14, 201311 and includes some 

pesticides scheduled for registration 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:

Occupational and Residential

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 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.

AGRICULTURAL HEALTH STUDY:

Clopyralid 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 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 clopyralid as 

appropriate.

 

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