2 

### Metiram Preliminary Work Plan

– Table of Contents

OVERVIEW

................................ ................................ ................................ ................................ ... 4

ANTICIPATED DATA NEEDS

................................ ................................ ................................ .... 5

STATU TORY AND REGULATORY AUTHORITY

................................ ................................ ... 7

CHEMICAL FACTS

................................ ................................ ................................ ...................... 7

USE AND USAGE INFORMATION

................................ ................................ ............................ 8

RECENT ACTIONS

................................ ................................ ................................ ....................... 9

ANTICIPATED R ISK ASSESSMENTS FOR REGISTRATION REVIEW

................................ 9

TIMELINE

................................ ................................ ................................ ................................ .... 11

NEXT STEPS

................................ ................................ ................................ ............................... 11

Appendix

– Addi tional Areas Considered in the Metiram Registration Review

...................... 12

References:

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

1. Registration Review; Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Metiram

. Hou senger, Justin; Ruhman, Mohammed. June 9, 2015.

2. Metiram: Human Health Risk Assessment Scoping Document in Support of Registration

Review

. Drew, Danette; Lloyd, Matt; Savoia, Pete; Taylor, Linda . June 2, 2015.

3. Metiram: Tier I (Scoping) Review of Human Incidents

. E vans, Elizabeth . March 24, 2015

4. BEAD Chemical P rofile (BCP) for Registration Review: Metiram (014601)

. Chandgoyal, Tara; Haddad, Sepehr; Hill, Elizabeth

. February 5, 2015

.

5. Metiram (014601) Screening Level Usage Analysis (SLUA)

. July 21, 2014

.3 6. Metiram (014601) EFED Table 1 Report

. August 14, 2014

.

7. Metiram (014601) HED Master Label Repor t. August 14, 2014

.

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

the docket EPA

- HQ

- OPP

- 2015

- 0290 at http://www.regulations.gov

.4 OVERVIEW

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

- HQ

- OPP

- 2015

- 0290 )

. Metiram is a broad

- spectrum,
f ungicide within the ethylene bisdithiocarba mate (EBDC) group of fungicides registered for agricultural application to apples (foliar) and potatoes (foliar or seed piece). Horticultural uses

include a Special Local Need use on l eatherleaf ferns (nurseries and greenhouses; Florida use

o nly). There are no registered residential uses

. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about m etiram , 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 m etiram

.

The registration review process was designed to include a public participation component to

solic it input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about m etiram and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on

m etiram

. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional information that will help the Agency’s decision

making process for this chemical. In addition to general areas on which persons may wish to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include:

environmental non

- profit or interest groups; pes ticide 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 m etiram

. Next, it

discu sses 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 m etiram

. 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 information.5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for m etiram

. Data will also be required for ethylenethiourea (ETU) , the major degradate of metiram. For additional discussion of the anticipated data needs, see the Registration Review; Problem Formulation for the Ec ological Risk Assessment and Drinking Water Exposure Assessm ent to be Conducted for Metiram and Metiram: Human Health Risk Assessment Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs for the Metiram Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated D ata Needs for the Parent Metiram

835.2120 Hydrolysis TGAI 12

835.4100 Aerobic soil metabolism TGAI 12

835.4400 Anaerobic aquatic metabolism TGAI 12

850.2100 Avian oral toxicity TGAI 12

850.2300 Avian reproduction TGAI 12

850.3020 Hone y bee acute contact and oral toxicity 2 TGAI 12

850.3030 Honey bee toxicity of residues on foliage TGAI 12

850.3040 Full

- Field Testing for Pollinators TGAI 24

850.6100 Environmental Chemistry Methods and Independent Laboratory Validation for Soil

and Water TGAI 12

860.1200 Dire ctions for Use: Bananas, Grape s , and

Potato 3 TEP 12

860.1560 Reasonable Grounds in Support of the

Petition 3 TEP 12

Non

- GLN Honey bee adult chronic oral toxicity TGAI 12

Non

- GLN Honey bee larvae chronic oral toxicity TGAI 12

Non

- GLN Field trial of residues in pollen and nectar TGAI 12

Non

- GLN (OECD Test

GLN 237) Honey bee larvae acute oral toxicity 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/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

2 This study is currently in review (MRID 494034 01). It is considered a data gap until its pending review is complete

and classification of acceptability.

3 860 .1200 and 860.1560 for bananas and grapes were identified data requirements under the review of petition 9E6006 (T. Goodlow, 6/14/07, D 267866

, Metiram: Human Health Risk Assessment for PP#9E6006. Petition for the Establishment of Import Tolerances on Grapes and Bananas ).6 Table 1: Anticipated Data Needs for the Metiram Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Non

- GLN (OECD Test

GLN 75) Semi

- field testing for pollinators TGAI

24

Non

- GLN Residue/Monitoring (Market Basket) Study TGAI 36

Anticipated Data Needs for the Degradate ETU

835.4100 Aerobic soil metabolism Degradate 12

835.4300 Aerobic aquatic metabolism Degradate 12

835.4400 Anaerobic aquatic metabolism Degradate 12

850.6100 Analytical method in soil (ECM/ILV) Degradate 12

Outstanding Data Requirements from GDCI

- 014601

- 26081 4

870.3700 Prenatal developmental toxicity study (rabbits) TGAI 12

TGAI = technical grade active ingredient; TEP = typical end

- use product ; GLN = Guideline

4 The study listed in this section was previously required through a generic data call

- in issued in July 2007 and is

still out standing. This study will not be included in the anticipated Registration Review DCI because it is already required through the earlier DCI.7 STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program

. All pesticides distributed or sold in the United States (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on prod uct labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the

environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in t he 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 pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

, and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40

. 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 infor mation 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 fo r the registration review of m etiram

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for m etiram

.

Table 2: Chemical Facts for Metiram

PC code 014601

Case Number 0664

CAS Number 9006

- 42

- 2; 96

- 45

- 7

Year first registered 1948 Pesticide Type Fungicide

Chemical class Ethylenebis Dithiocarbamates (EBDCs)

R eregistration Eligibility Decision (R E D) August 2005

Tolerance Reassessment Eligibility Decision (TRED) Not applicable. Tolerance reassessment was included in the RED.

Cumul ative group Not applicable . Metiram has not been identified as a member of a cumulative group that shares a common mechanism of toxicity

.

5 http://www.epa.gov/oppsrrd1/registration_review/8 Table 2: Chemical Facts for Metiram

40 CFR Citation Tolerances for m etiram are established in 40 CFR §180. 21 7(a)

. Dual

- use Metiram is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses.

Non

- pesticidal uses There are no identified non

- pesticidal uses of metiram.

Pesticide Re

- evaluation Division, Chemical Review Manager Brittany Pruitt, pruitt.brittany@epa.gov , 703

- 347

- 0289

Registration Division

, Product Manager Hope Johnson, johnson.hope@epa.gov

, 703

- 305

- 5410

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for Metiram

. Please see the BEAD Chemical Profile (BCP) for Registration Review: Metiram in the registration review docket for more

details

.

Table 3: Metiram Use and Usage Information

Summary of Use Metiram is a broad spectrum fungicide that belongs to the ethylene bisdithiocarbamate (EBDC) group of fungicides

. Metiram is used to control scab and rust diseases on apples, early and late blight diseases on potatoes, and anthracnose disease on

leather le af ferns

. Use Sites A gricultural U se S ites : include apples and potatoes

Non

- Agricultural U se S ite : ornamental non

- flowering plants

There is one Special Local Need (SLN) use in Florida on

leatherleaf fern. Summary of Usage During the 1998

- 2012 time frame, usage averaged approximately 765,000 a.i. applied annually on approximately 400,000 acres

tr eated. The average a.i. rate during this time was 1.91 lbs

a.i./acre. Formulation Type(s) Dry flowable and water dispersible granules

. Application Method(s ) Products can be applie d by aircraft and ground application

methods. Technical Registrant (s) BASF Corporation No. of Registrations 2 Section 3 products 6 ; 1 Section 24(c) Special Local Needs (SLNs) product.

Restricted Use No

6 Section 3 product labels can be obtained from the Pesticide Pr odu ct Label System (PPLS) website

( http://oaspub.epa.gov/pestlabl/ppls.home ).9 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.

• Confirmation of the following label information: sites of application; formulations; application methods and equipment; maximum application rates; frequency of application, application intervals, and maximum number of applications per season; and geographic limitations on use.

• Use/usage information on non

- agricultural use of metiram in Florida in term of poun d a.i. applied, application timing and acres treated.

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

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

– national, state, and county.

• Typical application timing (date of first application and application intervals)

– national, state, and county.

• Usage/use information for non

- agricultural uses.

• Typical application interval (days).

• State or local use restrictions.

• Foreign technical registrants not listed above who supply technical metiram to the U

. S

. market.

RECENT ACTIONS

There are no recent actions for metiram

.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for m etiram was completed June

2007 for the e sta blishment of i mport t olerances on g rapes and b ananas

. T he most recent comprehensive ecological and environmental fate risk assessment was completed in June 2005 in support of the metiram Reregistration Eligibility Decis ion (RED)

. In addition an endangered species assessment for the federally listed California Red Legged Frog was completed in October

2007. Findings and conclusions from these risk assessments are summarized in the Registration
Review; Problem Formulation f or the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Metiram and Metiram: 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 m etiram

. For human health, EPA anticipates the need to conduct revised dietary, residential

, and occupational risk assessment s during regist ration review

. If toxicological endpoints or points of departure are revised based on the data that are anticipated to be required for registration review

, they will be considered in the new assessment s
, as well as any changes to the standard operating

pro cedures or default exposure assumptions.

T able 4 below summarizes the anticipated registration review risk assessments based on the Preliminary Problem Formulation and Human Health Assessment Scoping Document

.10 T able 4: Anticipated Risk Assessments for the Metiram 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 A Total Toxic Residue (TTR) approach will be taken

to estimate the a quatic e xposure Estimated

Environmental C oncentrations (EECs) of the parent metiram and its degradate, EBIS.

Incidents Will check for updates For a discussion of reported ecological incidents for

m etiram , se e page 40 of the Problem Formulation.

Human Health Dietary

Food Y The dietary risk assessment may need to be updated if the toxicology endpoints, uncertainty factors, or drinking water exposure estimates change. Drinking water Y

Occupational Handlers (mixers, loaders, applicators) Y An updated handler and post

- application occupational risk assessments (cancer and non

- cancer) will be performed for all currently registered metiram uses. Post

- application Y

Residential

Handlers N There are no residential or homeowner uses registered for metiram; therefore a quantitative assessment is not anticipated to be performed for residential handlers or residential (non

- occupational) post

- application

exposure. It’s anticipated that a spray drift assessmen t will be performed. The Agency will evaluate the need

for a volatilization assessment during registration

review. Post

- application Y

Other Aggregate Y Because there are no homeowner or residential uses, an aggregate assessment will consist of food and drinking water only. An updated aggregate (food and drinking water) assessment may be needed if the toxicology endpoints, uncertainty factors, or drinking water exposure estimates change.

Cumulative N Metiram has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

Tolerances Y During registration review, the Agency will evaluate

the need to harmonize tolerances with Canadian MRLs and the need to update the current tolerance expressions.11 Incidents Will check for updates There are currently no incident cases reported for

metiram. S ee page 16 of the Scoping Document and

the Metiram: Tier I (Scoping) Review of Huma n 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.

• Ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian a nd mammalian mortalities) not already reported to the Agency

.

• Water quality monitoring data (see Appendix for further details)

.

TIMELINE

EPA has created the following estimated timeline for the completion of the m etiram registration

review in Table 5 below

.

Table 5: Projected Metiram Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60

- day Public Comment Period 2015

– June

Close Public Comment 2015

– August Case Development

Final Work Plan 2015

– November

Issue DCI 2016 Jan uary

– Mar ch

Data Submission 2019 January

– March

60

- day Public Comment Per iod fo r Draft Risk

Assessments 7 2020 July

– Sept.

Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision 2021 April

- June

Registration Review Decision and Begin Post

- Decision

Follow

- up 202 2

Total (years) 7

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 m etiram

.

7 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 CF R Part 155.53(c). For conventional pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.12 

### Appendix

– Additional Areas Considered in the Metiram 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 process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency

will work to harmonize tolerances and international maximum residue limits (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:

Metiram is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 8 In addition, no Total Maximum Daily Load s (TMDL) have been developed for m etiram

. 9 More information on impaired water bodies and TMDLs can be found at the Agency’s website

. 10 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 11
in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to m etiram 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

.

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

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

group_name=PESTICIDES

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

11 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm13 ENDANGERED SPECIES :

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

conducted for m etiram

. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of m e tiram 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 hab itat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

A previous endangered species assessment for the California red

- legged frog was conducted in

October 2007

.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology,

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive e ffects in different taxonomic groups. As part of its reregistration decision for m etiram

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

hazard database. However, as required by FF DCA section 408(p), m etiram 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. Ti er 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal

systems. Chemicals that go through Tier 1 screening and are found to have the pote ntial 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 endocrin e

- 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 issu ed test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 12 and includes some pesticides

12 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.14 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. 13

HUMAN STUDIES :

Occupational and Residential

Past m etiram risk assessments rely in part on data from studies in which adult human subjects

were inte ntionally 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), t he Agricultural Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convincing eviden ce 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 Subj ects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

Occupational

Past m etiram 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 gene ric pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (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 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.

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