2 

### Prometryn Preliminary Work Plan

– Table of Contents

Overview 3

Anticipated Data Needs 3

Statutory and Regulatory Authority 5

Chemical Facts 6

Use and Usage Information 6

Recent Actions 7

Anticipated Risk Assessment s for Registration Review 7

Timeline 9

Next Steps 10

Appendix

– Additional Areas Considered in Prometryn’s Registration Review 1 1

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. EFED Registration Review Preliminary Problem Formulation for Prometryn. Ruhman

and Mastrota. March 19 , 2013

. 2. Prometryn. Human

- Health Assessment Scoping Document in Support of Registration

Review. Lowe et al. February 28, 2013.

3. Prometryn: Review of Human Incidents. Recore and Evans. November 13, 2012.

4. BEAD Chemical Profile for Registration Review: Prometryn. Phillips et al. December 13,

2012.

5. Prometryn Screening Level Usage Report . Biological and Economic Analysis Division. September 10, 2012.

6. PRD Label Data Report: Food/Feed & Non

- Food/Non

- Feed U ses Considered in Registration Review Work Planning for P r ometryn. August 22, 2012.

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

in the docket EPA

- HQ

- OPP

- 2013

- 0032 at h ttp://www.regulations.gov

.3 OVERVIEW

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

- HQ

- OPP

- 2013

- 0032 ). Prom e tryn is a substituted

triazine herbicide registered for use on vegetable crops for control of broadleaf grasses and weeds. Prometryn is not registered for residential use. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about prometryn, highlighting anticipated da ta 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 prometryn

.

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

. 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 the following : 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 P WP begins by listing the anticipated data needs for prometryn

. It then discusses the statutory and regulatory authority for r egistration r eview , followed by the c hemical facts, use and usage information, recent actions, anticipated risk assessments, and a projected registration

review timeline for prometryn

. Finally, the Appendix to this document includes identification and discussion of some areas that are considered generally in R egistration R eview along with

some additional chemical case

- specific infor mation.

ANTICIPATED DATA NEEDS

Table 1 summarizes anticipated data needs for prometryn . For additional discussion of the anticipated data needs, see the March 1 9

, 2013 memo, EFED Registration Review Preliminary

Problem Formulation for Prometryn

, and the February 28, 2013 memo, Prometryn

. Human

Health Assessment Scoping Document in Support of Registration Revie w

. Table 2 summarizes outstanding conditional data requirements from a 2010 registration action for prometryn.4 Table 1: Anticipated Da ta Needs for Prometryn’s Registration Review 1

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for Prometryn (parent) 2

835.4100 Aerobic soil metabolism 3 TGAI or

PAIRA 24

835.4300 Aerobic aquatic metabolism 4 TGAI or

PAIRA 24

835.4400 Anaerobic aquatic metabolism TGAI or

PAIRA 24

8 50 .6100 Environmental Chemistry Methods and Associated Independent Laboratory Validation in W ater and

S oil TGAI 12

860.1480 Magnitude of the Residue

– Meat/Milk TGAI 24

870.3465 90

- day Inhalation Study

– Rat 5 TGAI 12

875.2100 Dislodgeable Foliar Residue Study TEP 12

Non

GDLN ORD Study Method EPA 600/R

- 099

- 064. Chronic Freshwater Sediment Testing ( Chironomus dilutus

or C. tentans TGAI 24

Non

GDLN ORD Study Method EPA 600/R

- 099

- 064. Chronic Freshwater Sediment Testing ( Hyallela azteca ) TGAI 24

Non

GDLN ORD Study Method EPA 600/R

- 099

- 020. Chronic Estuarine/Marine Sediment Testing ( Leptocheirus plumulosus ) TGAI 24

Anticipated Data Needs for the Prometryn Degradate Hydroxypropazine (GS

- 11526)

850.1010 Acute toxicity freshwater invertebrates Degradate 12

850.4400 Aquatic plant toxicity test using Lemna spp Degradate 12

850.5 4 00 Algal toxicity 6 Degradate 12
TGAI = technical grade active ingredient; TEP = typical end

- use product

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

– Ecological Effects Data Requirements

– including renumbering and other designations or changes for some guideline stud ies. 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 The anticipated data requirements for registration review do not include studies already required by EPA as a condition of registration or by a previous Data Call

- In notice.

3 Data are anticipated to be required for two soils representing major cotton growing areas.

4 A s tudy has been submitted to EPA and is in review, but the data requirement will be considered outstanding until the review is completed and the study found to be acceptable.

5 A 28

- day study is expected to be sufficient.

6 EPA expects to require a study on freshwater algae, Pseudokirchneriella subcapita

.5 Table 2 : Outstanding Data Requirements for Prometryn 1

Guideline

Number Study Title Status

850.1350 Aquatic Invertebrate Life Cycle (Saltwater) In Review

860.1300 Nature of the Residue in Plants (Carrot or Other Root Crop) Due 4/1/2016

870.6200 Acute & Subchronic Neurotoxicity In Review

870.7800 Immunotoxicity In Review

1 These data requirements will be considered to be outstanding until they have been submitted to EPA, reviewed, and found to be acceptable. Studies in review have been submitted to the Agency as part of an ongoing registration

action.

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 Age ncy), 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 e volves 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. Informatio n on this program is provided on EPA’s website 1

.

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 F IFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40

. T he Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision. After reviewing and respondin g 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 prometryn

. Table 3 provides a summary of the current regulatory

statu s of prometryn.

1 http://www.epa.gov/oppsrrd1/registration_review/6 Table 3 : Prometryn Chemical Facts

PC code 080805

Case Number 0467

CAS Number 7287

- 19

- 6 Year first registered 1974 Pesticide Type Herbicide

Chemical class Thiomethyl Triazine Reregistration Eligibility Decision (RED) 1996

Cumulative group Not applicable . Prometryn does not share the toxicity profile of

the t riazine s in the common mechanism group.

40 CFR Citation Tolerances for prometryn are established in 40 CFR §180.222.

Dual use No, conventional pesticidal uses only

Non

- pesticidal uses None

Pesticide Re

- evaluation Division, Chemical Review Manager Christina Scheltema, Scheltema.christina@epa.gov , (703)308

- 2201 Registration Division, Product Manager Kable “Bo” Davis, davis.kable@epa.gov , (703)306

- 0415

USE AND USAGE INFORMATION

Table 4 summarizes the use and usage information for prometryn

. Please see the December 13,
2012 memo, BEAD Chemical Profile for Registration Review: Prometryn

, in the registration

review docket for more details

.

Table 4 : U se and Usage Information Summary of Use Herbicide registered for use to control of broadleaf grasses and

weeds

Use Sites * C arrots, c elery, celeriac, celtuce, cilantro, cotton, dill, fennel, okra, parsley, pigeon peas, rhubarb, and leafy vegetables ; fallow ground Summary of Usage The greatest use of prometryn is on cotton, celery (85% of crop treated), carrots, and fallow ground , based on use data from 1998

to 2011. Formulation Type(s) Dry flowable or water dispersible granular, emulsifiable and soluble liquid concentrates Application Method(s) Ground, aerial, irrigation systems Technical Registrant (s) Syngenta Crop Protection, Verolit Chemical Manufacturer’s LTD No. of Registrations 8 FIFRA Section 3 Registrations, numerous Section 24(c) S pecial Local Need Registrations

Restricted Use No
*This includes both Federal FIFRA Section 3 and Special Local Need Section 24(c) Registrations.7 Guidance for Commente rs : Additi onal areas of use and usage related information requested

for this registration r eview , and of particular interest to EPA, are described below.

• Certain pro metryn labels are unclear with respect to application parameters like t he maximum yearly rate for each application type, use site, soil type, plant height, weed size, and t he types of applications that may be applied to the same field within a year’s

time. In the absence of such information, EPA expects to approximate these parameters

in order to conduct a quantitative assessment for prometryn

. EPA will work with registrants to make s ure prometryn labels do not include any missing or ambiguous use

pa r ameters.

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

ap plication methods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum number of applications per season ; and geographic limitations on use

.

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

.

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

– national, state, and county

.

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

– national, state, and county

.

• Usage/use information for non

- agricultural uses

.

• Typical application interval (days)

.

• S tate or local use restrictions

.

• Foreign technical registrants not listed above who supply technical prometryn to the US

market

.

RECENT ACTIONS

• EPA has received a pet ition for new food uses on snap beans and dill 2 . This action is currently pending.

• Prometryn is the subject of an ongoing formal consultation with National Marine Fisheries Service under Section 7 of the Endangered Species Act. This is described in

more detail in the appendix to this document.

• EPA granted conditional registrations for the prometryn products Caparol ® 4L (EPA Registration Number 100

- 620) and Prometryn Technical (100

- 542) in January 2010. Outstanding conditional data requirements for thi s action are summarized in Table 2. OSCPP Guideline 860.1500, Magnitude of the Residue in Carrots , which was listed as an outstanding data requirement in the human health scoping document, is now fulfilled. EPA completed its review of the submitted study (MRID 48727501) and found it to be acceptable.

ANTICIPATED RISK ASSESSMENTS FOR RE GI STRATION REVIEW

The most recent comprehensive human health and ecological risk assessment s for prometryn

were completed in 2009 for the US registration of prometryn use on carrots as well as new food

2 Pesticide Registration Improvement Extension Act (PRIA) petition number 2E8052.8 registrations for use on celeriac, cilantro

, okra, parsley, and leafy greens (petioles, crop subgroup

4B ). The f indings and conclusions from these risk assessments are summarized in the March 19

, 2013 , document, EFED Reg istration Review Preliminary Problem Formulation for Prometryn and the February 28, 2013

, document, Prometryn Human

- Health Assessment Scoping Document in Support of Registration Review

.

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of

prometryn

. For human health, EPA anticipates the need to conduct revised dietary and occupational risk assessment s during registration revi ew

. 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 assessment s
, as well as any changes to the standard operating

p rocedures or default exposure assumptions

. T able 5 summarizes the anticipated registration

review risk assessments based on the EFED Problem Formulation and HED Scoping Document

.

Table 5 : Anticipated Risk Assessments for Prometryn’s Registration Review Type of Ris k Assessment Conduct ? Notes Ecological and Environmental Fate Comprehensive ecological (species to be assessed

include terrestrial and aquatic organisms ), including endangered species Y es EPA expects to include prometryn, its unextracted residues, and the degradate hydroxypropazine (GS

11526) in the anticipated ecological risk assessment. EPA expects to consider slightly different residues for plants and animals. See page 32 of the problem

formulation for details.

Incidents Will check for updates EP A has received reports of crop damage, other incidents to nontarget plants, and fish kills associated with exposure to prometryn ; these are summarized on

page s 29 and 3 0 of the Problem Formulation.

Human Health Dietary

Food Yes EPA expects to revise the 2009 dietary risk assessment for food and drinking water as part of a pending registration decision. The Agency may rely on this revised dietary assessment for registration review. Drinking water Yes EPA anticipates revising estimates of prometryn residues in drinking water. Because there is limited information regarding the toxicity of a major degradate, hydroxypropazine (GS

- 11526), EPA intends to include it as a residue of concern for drinking water along with the parent co mpound. Occupational Handlers (mixers, loaders, applicators) Yes EPA may evaluate occupational risks associated with dry flowable (DF) formulations of prometryn . EPA expects to evaluate post

- application risks for all

formulations. Post

- application Yes9 Type of Risk Assessment Conduct? Notes

Residential

Handlers No No residential uses are currently registered for

prometryn ; therefore, no residential handler or post

application assessments are necessary

. Post

- application No

Other Aggregate Yes Evaluates the combined risk from dietary and residential exposures. Any aggregate assessment for prometryn would be limited to residues in food and

water.

Cumulative No Although prometryn is a triazine, and certain triazine pesticides were identified as a common

- mechanism group (CMG), it has been excluded from the triazine CMG because it does not share the toxicity profile of

the CMG triazines.

Tolerances Yes The tolera nce expression for prometryn in 40 CFR §180.222 needs to be updated to reflect current Agency policies and to ensure that it covers the prometryn metabolites and degradates of concern.

Incidents Will check for updates At this time, there does not appear to be a concern for human poisonings, based on the low frequency and severity of incident cases reported for prometryn 3

.

Guidance for Commente rs : Additional ecological i nformation r equested for this registration

r eview , and of particular interest to EPA, is described below.

• Registrants are requested to check the detailed/summary label information provided in the Prometryn P roblem F ormulation document , Tables 1

- 3 and Appendix A

, for accuracy and

to then comment accordingly

.

• Ec ological incidents (non

- target plant damage and avian, fish, reptilian, amphibian

, and mammalian mortalities) not already reported to the Agency

.

• Water quality m onitoring data (see the Appendix of this document for further details)

.

TIMELINE

EPA has created the f ollowing estimated timeline for the completion of prometryn’s registration

review in Table 6

.

3 See the November 13, 2012 memo, Prometryn: Review of Human Incidents

, for details.10 Table 6 : Projected Registration Review Timeline

Activities Estimated Dat e Opening the Docket Open Docket and 60

- day Public Comment Period 2013

– March

Close Public Comment 2013

– May Case Development

Final Work Plan 2013

– August

Issue DCI 2014

– April

- June

Data Submission 2016

– April

- June

6 0

- day Public Comment Period for Draft Risk Assessments 2017

– Oct

- Dec. Registration Review Decision

60

- day Public Comment Period for Proposed Registration

Review Decision 2018

– April

- June

Registration Review Decision and Begin Post

- Decision Follow

up 2019

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 prometryn.11 

### Appendix

– Additional Areas Considered in Prometryn’s Registration Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference to sou rces of additional information c ould be of particular use.

Trade Irritants:

Through the registration review proc ess, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency

will work to harmonize tolerances and international maximum residue limits (MRL s ) and may modify tolerance levels to do so, when possible

. Growers and other stakeholders are asked to

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

Prometryn has been i dentified as a cause of impairment for 10 miles of the Salt Slough, an upstream tributary of the San Joaquin River in California , as defined under section 303(d) of the

Clean Water Act . Prometryn has not been identified as the cause of impairment for any other water body; no additional listings were found on EPA’s webs i te 4

. Aquatic benchmarks have been established for prometryn, based on information from the 1996 RED, and may be found on

EPA’s website 5

. However, no Total Maximum Daily Loads (TMDL) have been developed for

prometryn, according to information provided on the website 6 . More information on impaired

water bodies and TMDLs can be found on EPA’s website

. 7 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 8 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

environment al 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

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

5 http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

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

8 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 atypical, unusually high exposure to prometryn 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 :

EPA has not conducted a risk assessment that supports a complete endangered species

determin ation for prometryn

. The ecological risk assessment planned during registration review will allow the Agency to determine whether prometryn’s use has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their d esignated 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 (th e Services), as appropriate.

EPA completed a regional, species

- specific endangered species risk assessment evaluating the potential effect of prometryn on Pacific Salmonids in 2002 and is currently in consultation with

the National Marine Fisheries Servic e (NMFS)

. This assessment and subsequent consultation are in response to litigation (Washington Toxics Coalition vs. EPA) concerning the effects of

– pesticides on Pacific salmon and steelheads in Washington, Oregon, and California. NMFS is currently scheduled to co mplete a biological opinion on prometryn and Pacific S almonids by

June 2013. In 2009, the Agency also completed an endangered species risk assessment evaluating the potential effects of prometryn on the California red

- legged frog, in response to litigatio n concerning the direct and indirect effects of several pesticides on the California red

legged frog (Center for Biological Diversity vs. EPA). EPA initiated formal consultation with

the US Fish and Wildlife Services (USFWS) on prometryn in 2009. For mor e details, please see EPA’s endangered species website, http://www.epa.gov/oppfead1/endanger/litstatus/wtc/index.htm

.

On January 19, 2011, the Center for Biological Diversity an d the Pesticide Action Network

North America filed a lawsuit in the United States District Court for the Northern District of California, against the Environmental Protection Agency (EPA) for allegedly failing to undergo

consultation with the United States Fish and Wildlife Service and the National Marine Fisheries Service regarding the effects of over 350 pesticides, including prometryn , on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity,

et al. v. E PA, et al., No. C 11

- 00293 (N.D.Cal.)

.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxici ty, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturati on, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for prometryn, EPA reviewed13 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), prometry n 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 wildli fe 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 batter y 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 cal l

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Prometryn is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

ins, requiring the submission of EDSP screening assays for prometryn. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lis ts, the test guidelines and the Tier 1 screening battery, please visit the EPA website 9

.

HUMAN STUDIES :

Past prometryn 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 PHED and the Agricultural Reentry Task Force (ARTF) Database.

EPA has reviewed all the studie s 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.

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