2 

### Metolachlor and S-Metolachlor Prelimin ary 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 ...................................................................................................................... .............. 13

NEXT STEPS .................................................................................................................... ........... 13

Appendix – Additional Areas Considered in th e Metolachlor and S-Metolachlor Registration

Review ........................................................................................................................ .............. 14

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Registration Review Problem Formulati on for Metolachlor and S-Metolachlor. Sternberg, Koper. December 3, 2014.

2. Metolachlor and S-Metolachlor. Human He alth Scoping Document in Support of Registration Review. Kidwell, Hummel, Nieves. November 19, 2014.

3. Metolachlor: Tier I Review of Human Incidents . Evans, Recore, Christensen. September 16, 2014.

4. BEAD Chemical Profile (BCP) for Registration Review: Metolachlor Case [S-metolachlor (108800) and Metolachlor (108801)]. Yourman, Alsadek, Hill. November 6, 2014.

5. Metolachlor (108801) Screening Level Usage Analysis (SLUA) . April 21, 2014.3 6. S-Metolachlor (108801) Screening Level Usage Analysis (SLUA) . April 24, 2014.

7. EFED Table 1 Report, Metolachlor (108801). August 12, 2014

8. EFED Table 1 Report, S-Metolachlor (108800). September 16, 2014

9. HED Master Label Spreadsheet, Metolachlor (108801). August 12, 2014.

10. HED Master Label Spreadsheet, S-Metolachlor (108800). September 16, 2014.

These and other supporting documents for the meto lachlor and S-metolachlor registration review case may be found in the docket EPA-HQ-OPP-2014-0772 at http://www.regulations.gov

.4 OVERVIEW

The docket for metolachlor and S-metolachlor is now open, initiating th e first public comment period for this registration review (docke t number EPA-HQ-OPP-2014-0772). Metolachlor (PC Code 108801) is a racemic broad spectrum herb icide that consists of 50% each of the Renantiomer and the S -enantiomer, which is the herbicidal ly active isomer. S-Metolachlor (PC Code 108800) is an isomer enriched form of metolachlor, comprised of 88% S -isomer and 12%

R -isomer. Metolachlor and S-metolachlor are se lective, chloroacetanilide herbicides used primarily for grassy weed control in many agricu ltural food and feed crop s; residential lawns; commercial turf (including golf courses, spor ts fields, recreation areas, and sod farms); ornamental plants, trees, shr ubs, and vines; hedge rows; and horticultural nurseries. This Preliminary Work Plan (PWP) document explai ns what EPA's Office of Pesticide Programs knows about metolachlor and S-metolachlor, highli ghting 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 time line for completing the registration review for

metolachlor and S-metolachlor.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about metolachlor and S-metolachlor and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on metolachlor and S-metolachlor. The Agency encourages all interested stakeholders to review the PWP and Appendi x 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 co mment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information.

Interested stakeholders could include environm ental non-profit or inte rest groups; pesticide manufacturers; agricultu ral labor or commodity groups; commerc ial, institutional, residential, and other users of pesticides ; or the public at large.

The Preliminary Work Plan begins by listing th e anticipated data needs for metolachlor and Smetolachlor. Next, it discusses the statutory a nd regulatory authority fo r Registration Review. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, a nd a projected registration review timeline for metolachlor and Smetolachlor. Finally, the Appendix to this doc ument 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 n eeds for metolachlor and S-metolachlor. For

additional discussion of the anti cipated data needs, see the Registration Review Problem Formulation for Metolachlor and S-Metolachlor and Human Health Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs fo r the Metolachlor and S-Metolachlor
Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent (either metolachlor or S-metolachlor)
835.4100 Aerobic soil metabolism (2 additional soils) TGAI 24
835.4200 Anaerobic soil metabolism (3 additional soils) TGAI 24

835.4300 Aerobic aquatic metabolism (1 additional sediment system) TGAI 24

835.4400 Anaerobic aquatic metabolism (1 additional sediment system) TGAI 24

850.2100 Avian acute oral toxicity test, passerine species TGAI 12

850.7100 ECM/ILV: method and independent validation in soil and independent validation in water TGAI 12

NonGuideline Whole sediment: chronic invertebrates,

freshwater and marine TGAI 12

NonGuideline Honey bee adult chronic oral toxicity TGAI 12

NonGuideline Honey bee larval acute oral toxicity TGAI 12

NonGuideline Honey bee larval chronic oral toxicity TGAI 12

NonGuideline Residues in pollen and nectar TEP 24

NonGuideline Semi-field testing for pollinators TEP 24

850.3040 Field testing for pollinators TGAI/TEP 24
Anticipated Data Needs for the S-Metolachlor

850.4100 Seedling emergence and seedling growth (four species of dicots) TEP 12

850.4150 Vegetative vigor (four species of dicots) TEP 12

875.2100 Turf Transferable Residue TGAI 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 Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-00286 Table 1: Anticipated Data Needs fo r the Metolachlor and S-Metolachlor
Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for Metolachlor 870.3465 28-day inhalation toxicity study TGAI 24
Anticipated Data Needs for the Metolachlo r Ethanesulfonic Acid (ESA) Degradate

850.4100 Seedling emergence and seedling growth (ryegrass, tomato, and carrot) TGAI 12

Anticipated Data Needs for the Metola chlor Oxanilic Acid (OA) Degradate
850.4100 Seedling emergence and seedling growth (onion) TGAI 12
TGAI = technical grade active ingredie nt; TEP = typical end-use product;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 Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website. 2

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration 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 docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of metolachlor and S-metolachlor.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for metolachlor and S-metolachlor.

Table 2: Chemical Facts fo r Metolachlor and S-Metolachlor

PC code 108801 (metolachlor) and 108800 (S-metolachlor)

Case Number 0001 CAS Number 51218-45-2 (metolachlor) and 87392-12-9 (S-metolachlor) Year first registered 1976 (metol achlor) and 2004 (S-metolachlor) Pesticide Type Broad spectrum herbicide

Chemical class Chloroacetanilide Reregistration Eligibility Decision (RED) A RED was completed for metolachlor in April 1995. Because Smetolachlor was registered after November 1984 it was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) A TRED was completed for metol achlor in June 2002. No TRED

was done for S-metolachlor.

2 http://www.epa.gov/oppsrrd1/registration_review/8 Table 2: Chemical Facts fo r Metolachlor and S-Metolachlor

Cumulative group Not applicable. Metolach lor and S-metolachlor have not been identified as members of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for metolachlor and S-metolachlor are established in §180.368.

Dual-use Metolachlor and S-metolach lor are registered for conventional pesticidal uses only and have no registered antimicrobial or biopesticidal uses. Non-pesticidal uses There are no identified non-pesticidal uses of metolachlor and Smetolachlor.

Pesticide Re-evaluation Division, Chemical Review Manager Steven Snyderman, snyderman.steven@epa.gov, 703-347-0249

Registration Division, Product Manager Kathryn Montague, monta gue.kathryn@epa.gov, 703-305-1243

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage informati on for metolachlor and S-metolachlor. Please

see the BEAD Chemical Profile (BCP) for Registration Review: Metolachlor Case [Smetolachlor (108800) and Metolachlor (108801)] in the registration review docket for more

details.

Table 3: Metolachlor and S-Metol achlor Use and Usage Information

Summary of Use Metolachlor and S-metolachlor are chloroacetamide herbicides, used to control grasses and some broadleaf weeds prior to weed emergence. They may be used preplant or post-plant on some crops to inhibit pre-emerged grasses.

For many crops, seeds can be plan ted immediately after herbicide treatment. Additionally, for cott on production, they can be used later in the season as layby herbicides, which can provide effective control of pre-emerged we eds, especially in combination with a post-emergence herbicide. Use Sites Agricultural Use Sites S-metolachlor: blueberries, citrus fruits, tree nuts, stone fruits, root and tuber vegetables, bulb vegetables, fruiting vegetables, legume vegetables, stem vegetables, seeds and sugar beets. Metolachlor: blueberries, citrus, st one fruits, figs, cilantro, ginger, melons, leafy vegetables, cole crops, bulb crops, root crops, pod crops, seed crops, grain crops, co tton, Christmas trees, and fruit

trees.9 Table 3: Metolachlor and S-Metol achlor Use and Usage Information

Non-agricultural Use Sites S-metolachlor: grasses, ornament als, airports, recreation areas,

athletic fields and roadsides. Metolachlor: airports, grasses, nurseries, ornamentals, turf,

recreation areas and roadsides. Summary of Usage Based on private market usage data from 1998-2012, Smetolachlor usage averaged approximately 28 million pounds active ingredient (a.i.) applie d annually on approximately 24 million acres treated. The average typical rate applied over this time period was 1.2 pounds a.i./acre. S-metolachlor was applied mostly on corn.

During that same time frame metolachlor usage averaged approximately 9 million pounds a.i. applied annually on approximately 6 million acres. The average typical rate applied over this time period was 1.50 pounds a.i./acre. Metolachlor was found to be applied mostly on corn. Formulation Type(s) Granular, emulsifiable /flowable/soluble concentrate, solutionready to use and as pressurized liquid. Application Method(s) Metolachlor products ar e applied aerially (fixed wing and rotary aircraft) and low volume applica tion through water spray while Smetolachlor products are applied both on the ground and aerially. Technical Registrant(s) Metol achlor: Makhteshim-Agan of North America Inc., Drexel Chemical Company, and Sipcam Agro USA, Inc. S-metolachlor: Syngenta Crop Protection, LLC No. of Registrations Metol achlor: 35 Section 3 products 3 (of which 3 technical registrations) and 2 Spec ial Local Needs (SLNs) S-metolachlor: 46 Section 3 products (of which 3 technical registrations) and 105 SLNs

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 Usage information would be helpful on crops where metolachlor and S-metolachlor is registered but not surveyed, such as lentils (S -metolachlor), tritical e (S-metolachlor), and figs (metolachlor) and non-agricu ltural use sites such as gras ses. This may improve future assessments conducted by the Agency related to the use and importance of metolachlor

and S-metolachlor.

 Confirmation of the following label information: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of

3 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).10 application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

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

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

 Typical application timing (date of first applic ation and application in tervals) – national, state, and county.

 Usage/use information for non-agricultural uses.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrant s not listed above who supply technical metolachlor and Smetolachlor to the US market.

RECENT ACTIONS

A new use on corn, field, forage and stover (increased toleran ce); corn, pop, stover; and corn, sweet, forage and stover (increased tolerance) was added for S-metolachlor in April 2014 (79 FR 17436).

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for metolachlor was completed in 2003 in preparation for the Tolerance Reassessm ent Eligibility Decision (TRED) and for Smetolachlor was completed in 2013 to establish hi gher tolerances for corn forage and stover. The most recent ecological and environmental fa te risk assessment for metolachlor and Smetolachlor was completed in 2012 for a new use registration of S-metol achlor on cilantro and garden beet leaves. Findings a nd conclusions from these risk assessments are summarized in the Registration Review Problem Formulation for Metolachlor and S-Metolachlor and Metolachlor

and S-metolachlor: Human Health Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of

metolachlor and S-metolachlor. For human heal th, EPA anticipates the need to conduct revised dietary, occupational, resident ial, aggregate, and occupati onal risk assessments during registration review. If toxico logical endpoints or points of de parture are revised based on the data that are anticipated to be required for regist ration review, they will be considered in the new assessments, as well as any changes to the sta ndard operating procedures or default exposure assumptions.

Table 4 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.11 Table 4: Anticipated Risk Assessment s for the Metolachlor and S-Metolachlor 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 Although degradates Ethanesulfonic Acid (ESA) and Oxanilic Acid (OA) are less toxic than parent metolachlor/S-metolachlor, they are more persistent and are formed to a significant extent. Consequently, data are needed for the metolachlor degradates ESA and OA; these data have been listed in table 1.

Incidents Will check for updates For a discussion of reporte d ecological incidents for metolachlor and S-metolachlor, see page 28 of the

Problem Formulation.

Human Health Dietary

Food Y The most current risk as sessments do not indicate risk estimates of concern, however, if there are changes to the toxicological points of departure (PODs) or Uncertainty Factors (UFs) or significant changes to the Estimated Drinking Water Concentrations (EDWCs) an updated assessment will be needed. Drinking water Y

Occupational Handlers (mixers, loaders, applicators) Y Though previous occupational handler and postapplication exposure assessments did not identify risks of concern, registration review may include updated estimates based on current policies and PODs/UFs may change base d on the anticipated data requirements. Post-application Y

Residential

Handlers Y S-metolachlor is not intended for homeowner purchase or use (only registered for use by professional/commercial a pplicators), therefore a

residential handler assess ment is not anticipated. However, registration review may include updated estimates based on current policies and PODs/UFs may change based on the anticipated data requirements. An updated post-application exposure assessment may be needed during registration review dependent upon the inform ation received in the anticipated Turf Transf erable Residue study. The need for a bystander assessment may also be needed

and will be revisited at the time of the risk

assessment. Post-application Y12 Table 4: Anticipated Risk Assessment s for the Metolachlor and S-Metolachlor Registration Review Type of Risk Assessment Conduct? Notes

Other Aggregate Y Evaluates the combined risk from dietary and residential exposures. Though no aggregate risks of concern were identified in the most recent assessment, an updated assessment may be needed to include any significant change that might occur for toxicological PODs, FQPA and uncertain ty factors, dietary exposure estimates or EDWCs.

Cumulative N Metolachlor and S-metolachlor are not members of a cumulative group. Tolerances Y No changes to tolerances are anticipated at this time, since the tolerance expre ssion is in accord with current guidance and is compatible with the Canadian expression. However, U.S. to lerance levels are higher for certain crops and should be examined during registration review to determine if numerical harmonization is possible.

Incidents Will check for updates Due to the low frequency of reported incidents there does not appear to be a concern at this time that

would warrant further inve stigation. For a discussionof reported human incidents for metolachlor and Smetolachlor, see page 11 of the Scoping Document

and the Metolachlor: 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.

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).

 Label clarification is needed on some labe ls that includes the absence of a maximum single application rate, minimum application in tervals, maximum number of applications allowed per year (and crop cycl e, if applicable), a maximu m annual application rate (in lbs a.i./year), ornamental band treatment use ap plication rate in lb ai/A, and application method on labels. The absence of this information on the labels may result in conservative assumptions and maximum exposure scenarios for the given uses in the risk

assessment.13 TIMELINE

EPA has created the following estimated timeline for the completion of the metolachlor and Smetolachlor registration re view in Table 5 below.

Table 5: Projected Metolachlor and S-Met olachlor 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 – Sept. Data Submission 2017 July – Sept. 60-day Public Comment Period for Draft Risk

Assessments 4 2019 Jan. - March

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision 2019 Oct. – Dec.

Registration Review Decisi on 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 i ssue a Final Work Plan for the registration

review of metolachlor and S-metolachlor.

4 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 Metolachlor and SMetolachlor Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, 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, provi ding as much specificity as possible regarding

the nature of the concern.

Water Quality:

Metolachlor and S-metolachlor ar e not identified as a cause of impairment for any water bodies listed as impaired under secti on 303(d) of the Clean Water Act. 5 In addition, no Total Maximum Daily Loads (TMDL) have been developed for metolachlor and S-metolachlor. 6 More information on impaired water bodies and TM DLs can be found at the Agency’s website. 7 The Agency invites submission of wat er 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 Im paired Water Body and Other Water Quality Data in OPP’s Registration Review Risk A ssessment and Management Process 8 in order to ensure they can be used quantitatively or qualitativel y in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposur e to metolachlor and S-metolach lor 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.

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

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.htm15 ENDANGERED SPECIES:

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

conducted for metolachlor and S-metolachlor. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of metolachlor and Smetolachlor has “no effect” or “may affect” fe derally listed threatened or endangered species (listed species) or their designated critical ha bitats. 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.

On June 5, 2013, the Center for Biological Dive rsity and the Pesticide Action Network North America filed an amended complaint in its lawsu it in the United States District Court for the Northern District of California, against the EPA for allegedly failing to undergo consultation

with the United States Fish and Wildlife Serv ice and the National Marine Fisheries Service regarding the effects of over 50 pesticides, incl uding metolachlor and S-metolachlor, on over 100 endangered and threatened species throughout the United States (C enter for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.)

.

A previous endangered species a ssessment was conducted for metolachlor and S-metolachlor in 2006 through a litigation assessment for 26 evolutiona rily significant units of listed salmonids in the Pacific Northwest, 2007 as pa rt of litigation assessments for the Barton Springs salamander and California red legged frog, and a 2010 litigati on assessment for the San Francisco Bay area species, delta smelt and California tiger salamander.

ENDOCRINE DISRUPTOR SCREENING PROGRAM:

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent registration decision for metolachlor and Smetolachlor, EPA reviewed these data and selected the mo st sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), metolachlor and S-me tolachlor are subject to the e ndocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a16 chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 pest icide active ingredient s and 9 inert ingredients. A second list

of chemicals identified for EDSP sc reening was published on June 14, 2013 9 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists

should be construed as a list of know n or likely endocri ne disruptors.

Metolachlor is on List 1 for which EPA has r eceived all the required Tier 1 assay data. The Agency is currently reviewing all of the assay da ta received for the appropriate List 1 chemicals and planning to make the conclusions of thos e reviews available in early 2015. The degradates

metolachlor-ESA and metolachlor-OA are on List 2. List 2 represents the next set of chemicals

for which EPA intends to issue test orders/data cal l-ins in the near future. S-metolachlor is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP nor List 2. Accordingly, as part of re gistration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for S-metolachlor. For further information on the status of the EDSP, the policies and procedures, th e lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 10

HUMAN STUDIES:

Occupational

Past metolachlor and S-metolachlor risk assessments rely in part on data from studies in which adult human subjects were intent ionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, invo lving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the Agricultural Reentry Task For ce (ARTF) 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 fundame ntally unethical or significantly deficient relative to the ethical st andards prevailing at the time the research was conducted. All applicable requir ements of EPA’s Rule for the Protection of Hu man Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued

reliance on these studies.

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

chemicals.

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