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 summarize s the Environmental Protection Agency's current position
based on the f

ollowing 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 Hea lth 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 Regi stration 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 do cuments 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), potas sium 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

- napthalene3

ace tate ( napthalene acetic acid, et h yl ester

, 056008). The NAA compounds are plant growth regulators, used to thin pome and citrus fruit; control sprouting of citrus; delay l eaf drop in ornamentals, such as holly; and promote rooting in plant propagation. T his 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 encou rages 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, t here 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 c ompounds

. Next, it discusses the statutory 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 NAA

. Finally, the Appendix to this
document inclu des identification and discussion of some areas that are considered generally in

R egistration R eview 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

-

Napth aleneacetic 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

Number 1 Study Title 1 Test Material (s) 2
, 3 Estimated

Timeframe
(Months f

rom receipt of DCI)

830.7370 Dissociation Constant s 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

83 0.7560

830.7570 Partition Coefficient (N

- octanol/water) TGAI of n apthalene 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 naptha lene
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 chemist ry methods and

associated independent laboratory validations
for water TGAI of napthalene
acetic acid and napthalene
acetamide 12

850.10 10 Acute toxicity to freshwater invertebrates TGAI , napthalene
acetamide 12

1 On June 27, 2012, EPA announced certain revisions in harmonized gui deline 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 T esting 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 sodi um 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

Number 1 Study Title 1 Test Material (s) 2
, 3 Estimated

Timeframe
(Months f

rom receipt of DCI)

850.1035 Acute toxicity estuarine and mar ine

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 Fr eshwater 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

Non

guideline ( OECD 213 ) Honey Bee Adult Acute Oral Toxicity TGAI, napth alene
acetic acid 12

Non

guideline Honey Bee 10

- day Adult Chronic Toxicity TGAI, napthalene
acetic acid 12

Non

guideline (OECD 234

) Honey Bee Larval Acute Toxicity TGAI, napthalene
acetic acid 12

Non

guideline Honey Bee Larval Chronic Toxicity TGAI, na pthalene
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 & Mar ine Diatom TGAI, napthalene
acetic acid and napthalene
acetamide 12

850.4550 Aquatic Plant Toxicity Testing with Blue

green algae TGAI, napthalene
acetic acid and napthalene
acetamide 12

870.3465 Subchronic inhalation study TGAI, napthalene

acetic a cid sodium or potassium salt 126

Outstanding Data Requirements from GDCIs

- 056001

- 27426, 056002

- 27466, 056003

- 26533, 056004

- 26534, 056007

- 27467, and 056008

- 27468 4

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, a ll 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 n ot 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 regist ered 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, t he Agency periodically reevaluates pesticides to make sure 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 pursua nt 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 regist ration 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 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

- in s issued in December 2007
and are stil l 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/opps rrd1/registration_review/7 Table 2: Chemical Facts for NAA

– Case 0379

Summary of Compounds in Case

Chemical Name N apthalene
acetamide N apthalene

acetic acid N apthalene

acetic acid, potassium
salt N apthalene

acetic acid,

ammonimum
salt N apthalene

acetic acid,
sodium salt N apthalene

acetic acid, ethyl ester

PC codes 0 56001 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

R eregistration Eligibility

Dec ision (R E D) C ompleted in 200 4 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 antim icrobial 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@ep a.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, commerc ial 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 w as applied to ~ 180, 000 acres. The greatest usage is on apples and pears grown on the West coa st 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 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.

 EPA has no data on ag ricultural use of napthalene acetic acid and no national data on non

agricultural 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, applicati on rates, and percent crop treated.

 C onfirmation 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 applica tion, application intervals, maximum number of applications per season , and number of seasons per year ; and geographic limitations on use

.

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

.

 M edian and 90 th percentile repo rted 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

.

 Typical application in terval (days)

.

 S tate or local use restrictions

.

 Names and contact information for f oreign 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 w ere 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, pota ssium 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 assessment 7 for NAA was completed on January 2013 in to support the petition for new food uses on avocado, mango, and the other crops previously mentioned

. T he most recent ecological and environmenta l fate risk assessment 8 was completed in 20 12 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, t he Agency anti cipates 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 spo t treatment

. For human health, EPA anticipates the need to conduct revised occupational risk assessment s during registration review

. However, the Agency does not anticipate conducting new dietary or residential risk assessments unless drinking water expo sure estimates change

. I n addition, i f 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

assessment s , as well as any changes to the standard operating procedures or default exposure assumptions.

T able 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 . Janua ry 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 Fru i ts Crop Group 11

- 10. Octobe r 12, 2012.10 Table 4: Anticipated Risk Assessments for the NAA Regi stration 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 asses sment 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

associate d 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 o f the
Problem Formulation.

Human Health Dietary

Food No The 2013 risk assessment conclu ded 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, lo aders, applicators) Yes The anticipated risk assessment will consider data from the inhalation toxicity study that is anticipated to be required. Post

- application

Residential

Handlers No

Post

- application No

Other Aggregate Yes Evaluates the com bined 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 substanc es. T herefore, 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 change s 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 Commente rs: Additional ecological i nformation r equested for this registration

r eview , 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

mam malian 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

6 0

- day Public Comment Period for Draft Risk Assessments 9 2019 January

– March Registration Review Decision

60

- day Public Comment Period for Proposed Registration

Review Decision 2019 October

– De cember

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 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, t he Agency plans to provide a 60 calendar day public comment period generally for draft risk assessment s

.12



### Appendix

– Additional Areas Considered in the NAA Registration Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your c omments, 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, t ake 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 o n 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 identif ied 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 f

ound 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 Process 13 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environm ental 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 potent ial 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 comp ared 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.c ause_detail_303d?p_cause_group_id=885

11 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_det ail?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.htm13

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

F isheries 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 acu te, 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 i ts most recent registration decision for NAA

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from t he 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

t hrough 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 chemi cals. 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 p ublished on June 14, 2013 14 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 fr om 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 dat abases, 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 requir ements 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.