2

NAA Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 2

CHEMICAL FACTS ....................................................................................................................... 6

USE AND USAGE INFORMATION............................................................................................ 7

RECENT AND PENDING ACTIONS......................................................................................... 8

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW................................. 9

TIMELINE ................................................................................................................................... 11

NEXT STEPS ............................................................................................................................... 11

Appendix – Additional Areas Considered in the NAA Registration Review ............................... 12

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Problem Formulation for Registration Review of Napthalene acetic Acid and Its Sodium, Potassium, and 

Ammonium Salts, Ethyl Ester, and Acetamide. B. Montague and J. Melendez. November 18, 2014.

2. 1-Napthaleneacetic acid (NAA): Human Health Risk Assessment Scoping Document in Support of 

Registration Review. T. Morton et al. November 20, 2014.

3. Napthalene Acetic Acid: Tier I Review of Human Incidents. Elizabeth Evans and S. Recore. July 23, 

2014. 

4. BEAD Chemical Profile (BCP) for Registration Review: Napthalene Acetates (NAA). C. Chen, et al. 

September 23, 2014.

5. NAA Case Number 0371 (Includes PC Codes 056001, 056002, 056003, 056004, 056007, 056008). 

Screening Level Usage Analysis (SLUA). June 2, 2014.

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

docket EPA-HQ-OPP-2014-0773 at http://www.regulations.gov. 

OVERVIEW

The docket for the napthalene acetic acid (NAA) registration review case is now open, initiating the 

first public comment period for this registration review (docket number EPA-HQ-OPP-2014-0773). 

This case includes the following six active ingredients: napthalene acetamide (PC code 056001), 

napthalene acetic acid (056002), potassium 1-napthalene acetate (napthalene acetic acid, potassium 

salt; 056003), ammonium 1-napthalene acetate (napthalene acetic acid, ammonium salt, 056004), 

sodium 1-napthalene acetate (napthalene acetic acid, sodium salt, 056007), and ethyl 1-napthalene 
3

acetate (napthalene acetic acid, ethyl ester, 056008). The NAA compounds are plant growth 

regulators, used to thin pome and citrus fruit; control sprouting of citrus; delay leaf drop in 

ornamentals, such as holly; and promote rooting in plant propagation. This Preliminary Work Plan 

(PWP) document explains what EPA's Office of Pesticide Programs knows about NAA, 

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 the NAA case.

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 the NAA case and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on NAA. The 

Agency encourages all interested stakeholders to review the PWP and Appendix and to provide 

comments and additional information that will help the Agency’s decision-making process for this 

chemical. In addition to general areas on which persons may wish to comment, there are some areas 

identified in the PWP and Appendix about which the Agency specifically seeks comments and 

information. Interested stakeholders could include: environmental 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 the NAA compounds. 

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 NAA. 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.

ANTICIPATED DATA NEEDS

Table 1 summarizes anticipated data needs for NAA. For additional discussion of the anticipated 

data needs, see the November 18, 2014 memo, Problem formulation for Registration Review of Napthalene

acetic Acid and Its Sodium, Potassium and Ammonium Salts, Ethyl Ester, and Acetamide and the November 

20, 2014 memo, 1-Napthaleneacetic acid (NAA): Human Health Risk Assessment Scoping Document in 

Support of Registration Review. 
4

Table 1: Anticipated Data Needs for the NAA Registration Review

Guideline 

Number1

Study Title1

Test Material(s)2,

3

Estimated 

Timeframe

(Months from 

receipt of DCI)

830.7370 Dissociation Constants in Water

TGAI of all NAA 

compounds except 

napthalene acetic 

acid

8

830.7840

830.7860 Water Solubility

TGAI of napthalene 

acetamide and

napthalene acetic 

acid, potassium and 

ammonium salts

8

830.7550

830.7560

830.7570

Partition Coefficient (N-octanol/water) 

TGAI of napthalene 

acetic acid, 

napthalene 

acetamide

8

830.7950 Vapor Pressure

TGAI of all salts, 

ethyl ester, and 

amide

8

835.4100 Aerobic Soil Metabolism

TGAI of napthalene 

acetic acid and 

napthalene 

acetamide

24

835.1230 Adsorption/Desorption (Batch Equilibrium)

TGAI of napthalene 

acetic acid and 

napthalene 

acetamide

24

835.4300 Aerobic aquatic metabolism

TGAI of napthalene 

acetic acid and 

napthalene 

acetamide

24

850.6100

Environmental chemistry methods and 

associated independent laboratory validations 

for water

TGAI of napthalene 

acetic acid and 

napthalene 

acetamide

12

850.1010 Acute toxicity to freshwater invertebrates TGAI, napthalene 

acetamide 12 

 

1 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

2 TGAI, technical grade active ingredient; TEP, typical end use product; PAI, pure active ingredient.

3 Testing is anticipated to be required for NAA compound(s) listed; “all NAA compounds” indicates testing is 

anticipated to be required for all 6 compounds in the NAA registration review case: napthalene acetamide, 

napthalene acetic acid, napthalene acetic acid sodium salt, napthalene acetic acid ammonium salt, napthalene acetic 

acid sodium salt, and napthalene acetic acid ethyl ester. 
5

Table 1: Anticipated Data Needs for the NAA Registration Review

Guideline 

Number1

Study Title1

Test Material(s)2,

3

Estimated 

Timeframe

(Months from 

receipt of DCI)

850.1035 Acute toxicity estuarine and marine 

invertebrates (mysid)

TGAI, napthalene 

acetamide 12

850.1075 Acute toxicity estuarine and marine fish TGAI, napthalene 

acetamide 12

850.1300 Chronic Toxicity to Freshwater Invertebrates TGAI, napthalene 

acetamide 12

850.1400 Chronic Toxicity to Freshwater Fish TGAI, napthalene 

acetamide 12

850.2300 Avian Reproduction TGAI, napthalene 

acetamide 24

850.3020 Honey Bee Adult Acute Contact Toxicity TGAI napthalene 

acetic acid 12

Nonguideline

(OECD 213)

Honey Bee Adult Acute Oral Toxicity TGAI, napthalene 

acetic acid 12

Nonguideline Honey Bee 10-day Adult Chronic Toxicity TGAI, napthalene 

acetic acid 12

Nonguideline 

(OECD 234)

Honey Bee Larval Acute Toxicity TGAI, napthalene 

acetic acid 12

Nonguideline Honey Bee Larval Chronic Toxicity TGAI, napthalene 

acetic acid 12

850.4100 Terrestrial plant toxicity, seedling emergence TEP, napthalene 

acetamide 12

850.4150 Terrestrial plant toxicity, vegetative vigor TEP, napthalene 

acetamide 12

850.4500 Aquatic Plant Toxicity Testing with 

Freshwater & Marine Diatom 

TGAI, napthalene 

acetic acid and 

napthalene 

acetamide 

12

850.4550 Aquatic Plant Toxicity Testing with Bluegreen algae

TGAI, napthalene 

acetic acid and 

napthalene 

acetamide 

12

870.3465 Subchronic inhalation study

TGAI, napthalene 

acetic acid sodium 

or potassium salt

12
6

Outstanding Data Requirements from GDCIs-056001-27426, 056002-27466, 056003-26533, 056004-

26534, 056007-27467, and 056008-274684

860.1380 Storage stability data (processed commodities 

of apples or citrus and olives)

All six NAA 

compounds 24 

860.1520 Citrus Processing Study (dried pulp, oil, and 

juice) 

All six NAA 

compounds 24 

860.1650 Analytical Reference Standards PAI, all six NAA 

Compounds 24 

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 NAA.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for the NAA case. 

 

4 The studies listed in this section were previously required through generic data call-ins issued in December 2007 

and are still outstanding. These studies will not be included in the anticipated Registration Review DCI because 

they are already required through the earlier DCI. EPA is working with the registrant to ensure that these data are 

submitted. 

5 http://www.epa.gov/oppsrrd1/registration_review/
7

Table 2: Chemical Facts for NAA – Case 0379

Summary of Compounds in Case

Chemical Name Napthalene 

acetamide

Napthalene 

acetic acid

Napthalene 

acetic acid, 

potassium 

salt 

Napthalene 

acetic acid, 

ammonimum 

salt

Napthalene 

acetic acid, 

sodium salt

Napthalene 

acetic acid, 

ethyl ester

PC codes 056001 056002 056003 056004 056007 056008

CAS Numbers 86-86-2 86-87-3 15165-79-4 25545-89-5 61-31-4 2122-70-5

Year first registered 1952 1980 1990 1969 1961 1982

Pesticide Type Plant growth regulator

Chemical class Auxins

Reregistration Eligibility 

Decision (RED)

Completed in 2004 and amended in 2007.

Cumulative group None

40 CFR Citation Tolerances for NAA are established in 40 CFR §180.155. 

Dual-use NAA compounds are registered for conventional pesticidal uses only. There are no 

registered antimicrobial or biopesticide uses.

Non-pesticidal uses There are no identified non-pesticidal uses of NAA.

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Christina Scheltema, scheltema.christina@epa.gov; (703)308-2201.

Registration Division, 

Product Manager

Shaja Joyner, joyner.shaja@epa.gov, (703)308-3194.

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for NAA. Please see the BEAD Chemical Profile 

(BCP) for Registration Review: Napthalene Acetates (NAA) in the registration review docket for more 

details.

Table 3: NAA Use and Usage Information

Summary of Use Plant growth regulator for use on pome fruits, citrus, avocados, olives, mango, and 

other tropical fruit. Thinning agent to control fruit size and quality. Sometimes used 

to control sprouting and growth of side shoots or suckers

Use Sites Apples, pears, olives, citrus, avocados, mango, mamey sapote, rambutan, commercial 

ornamental, and nursery crops.

Summary of Usage Between 1998 and 2012, an approximate total of ~ 7000 lbs of NAA compounds 

(except napthalene acetic acid)6 was applied to ~180,000 acres. The greatest usage is 

on apples and pears grown on the West coast of the US (6,600 lbs applied to 175,000 

acres). 

Formulation Type(s) Varies by NAA compound – may be formulated as a flowable concentrate, wettable 

powder, ready-to-use solution, soluble concentrate, or emulsifiable concentrate. See 

p. 3 of the BEAD Chemical Profile for specific information. 

Application Method(s) Ground or air; may also be applied as a foliar dip treatment (for plant cuttings).

 

6 EPA has no national usage data for napthalene acetic acid. 
8

Table 3: NAA Use and Usage Information

Technical Registrant(s) AMVAC (all compounds), Valent Biosciences (napthalene acetic acid, sodium salt 

only)

No. of Registrations Varies by compound: 2 for napthalene acetamide; 15 for napthalene acetic acid; 7 for 

napthalene acetic acid, potassium salt; 5 for napthalene acetic acid, ammonium salt; 3 

for napthalene acetic acid, sodium salt; and 5 for napthalene acetic acid, ethyl ester 

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.

 EPA has no data on agricultural use of napthalene acetic acid and no national data on nonagricultural usage for any of the six NAA compounds in this case. 

 EPA requests data on total pounds of napthalene acetic acid (all compounds) applied in the 

US, important uses, application rates, and percent crop treated. 

 Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum single and annual application rates; number 

of applications per year; frequency of application, application intervals, maximum number of 

applications per season, and number of seasons per year; 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.

 Typical application interval (days).

 State or local use restrictions.

 Names and contact information for foreign registrants (not listed above) who supply 

technical grade active ingredient for any of the compounds in the NAA case.

RECENT AND PENDING ACTIONS

NAA registrations were amended in 2013 to add new food uses on avocado, mango, mamey sapote, 

and rambutan and to update the crop group tolerance for pome fruit (fruit, pome, Group 11-10). See 

78FR30218 for details. In 2011, FIFRA Section 18 Emergency Exemptions were granted to Idaho 

for the use of napthalene acetic acid, potassium salt, on potato seed pieces and for the use of 

napthalene acetic acid, sodium salt, on potato foliage. In 2012, a FIFRA Section 3 Registration was 

granted for the use of napthalene acetic acid, potassium salt on potato seed pieces.

In 2014, EPA received a petition to establish a tolerance for napthalene acetic acid, ethyl ester, in/on 

pomegranate. This action is currently undergoing Agency review. 
9

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment7for NAA was completed on January 

2013 in to support the petition for new food uses on avocado, mango, and the other crops 

previously mentioned. The most recent ecological and environmental fate risk assessment8 was 

completed in 2012 for the same new use petition described above. Findings and conclusions from 

these risk assessments are summarized in the November 18, 2014 Problem Formulation for Registration 

Review of Napthalene Acetic Acid and Its Sodium, Potassium and Ammonium Salts, Ethyl Ester and Acetamide 

and the November 20, 2014 1-Napthalene acetic acid (NAA): Human Health Risk 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 NAA and for all 

compounds in the NAA case except for napthalene acetic acid ethyl ester, whose current use is 

limited to spot treatment. For human health, EPA anticipates the need to conduct revised 

occupational risk assessments during registration review. However, the Agency does not anticipate 

conducting new dietary or residential risk assessments unless drinking water exposure estimates 

change. In addition, 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 summarizes the anticipated registration review risk assessments based on the EFED 

Problem Formulation and HED Scoping Document.

 

7 Napthalene acetates Human Health Risk Assessment for a Proposed Use on Avocado, Mano, Mamey Sapote, 

Rambutan, and updating crop group Fruit, Pome, Group 11-10. January 16, 2013.

8 Application for Registration of New Uses of 1-Napthalene acetic acid (NAA), Sodium 1-Napthalene acetate, and 

Ethyl 1-Napthalene acetate on Rambutan, Avocado, Mamey Sapote and Mango, and Inclusion of the Pome Fruits 

Crop Group 11-10. October 12, 2012. 
10

Table 4: Anticipated Risk Assessments for the NAA 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 

Yes The anticipated ecological risk assessment will focus on 

napthalene acetic acid, its salts, and acetamide. Exposure to 

napthalene acetic acid ethyl ester is currently limited to spot 

treatment. 

Incidents Will check 

for updates

Only one ecological incident has been reported; it was 

associated with a product containing the sodium salt that was 

also applied with several other pesticides. For a discussion 

of this reported ecological incident, see page 25 of the 

Problem Formulation.

Human Health

Dietary

Food No The 2013 risk assessment concluded that dietary risk 

estimates were not of concern. However, the dietary risk 

assessment may be updated if the toxicology endpoints, 

uncertainty factors, or drinking water exposure estimates 

change.

Drinking water No

Occupational

Handlers (mixers, loaders, applicators) Yes The anticipated risk assessment will consider data from the 

Post-application inhalation toxicity study that is anticipated to be required. 

Residential

Handlers No

Post-application No

Other

Aggregate Yes Evaluates the combined risk from dietary and residential 

exposures.

Cumulative No At this time, the EPA has not made a common mechanism 

finding for the NAA case and any other substances. Further, 

NAA does not appear to produce a toxic metabolite 

produced by other substances. Therefore, EPA does not 

anticipate conducting a cumulative risk assessment during 

the NAA registration review. 

Tolerances Yes EPA will consider the storage stability and processing data 

(required under a previous DCI) to determine the need for 

changes to the NAA tolerances.

Incidents Will check 

for updates

For a discussion of reported human incidents for NAA, see 

the memo, Napthalene Acetic Acid, Tier I Review of Human 

Incidents.

Guidance for Commenters: Additional ecological information requested for this registration 

review, and of particular interest to EPA, is described below.

 Unpublished environmental fate or effects data for any of the NAA compounds. 

 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).
11

TIMELINE

EPA has created the following estimated timeline for the completion of the NAA registration review

in Table 5 below.

Table 5: Projected NAA Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2014 – December

Close Public Comment 2015 – February

Case Development

Final Work Plan 2015 – May

Issue DCI 2015 July – September

Data Submission 2017 July – September

60-day Public Comment Period for Draft Risk Assessments9 2019 January – March

Registration Review Decision

60-day Public Comment Period for Proposed Registration 

Review Decision

2019 October – December

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 NAA.

 

9 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.
12

Appendix – Additional Areas Considered in the NAA 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:

The NAA compounds are not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act.

10

 In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for NAA.

11

 More information on impaired water bodies and 

TMDLs can be found at the Agency’s website.

12 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 Process13 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 any of the NAA compounds 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.

ENDANGERED SPECIES:

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

conducted for NAA. The ecological risk assessment planned during registration review will allow 

 

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

11http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

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

13 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
13

the Agency to determine whether use of NAA 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 NAA, 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), NAA 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, 201314 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. 

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.15

 

14 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

15 http://www.epa.gov/endo/
14

HUMAN STUDIES:

Occupational and Residential

Past NAA 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.