2

Metiram Preliminary 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....................................................................................................................... 9

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

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

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

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

References:

This Preliminary Work Plan summarizes 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. Housenger, 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. Evans, Elizabeth. March 24, 2015

4. BEAD Chemical Profile (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 Report. August 14, 2014.

These and other supporting documents for the metiram 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, 

fungicide within the ethylene bisdithiocarbamate (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 leatherleaf ferns (nurseries and greenhouses; Florida use 

only). There are no registered residential uses. This Preliminary Work Plan (PWP) document 

explains what EPA's Office of Pesticide Programs knows about metiram, 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 metiram.

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 metiram and what types of new data or other 

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

metiram. 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 decisionmaking process for this chemical. In addition to general areas on which persons may wish to 

comment, there are some areas identified in the PWP and Appendix about which the Agency 

specifically seeks comments and information. Interested stakeholders could include:

environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for metiram. Next, it 

discusses the statutory and regulatory authority for Registration Review. Then the document 

provides chemical facts, use and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for metiram. Finally, the Appendix to 

this document includes identification and discussion of some areas that are considered generally 

in Registration Review along with some additional chemical case-specific information.
5

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for metiram. 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 Ecological 

Risk Assessment and Drinking Water Exposure Assessment 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 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data 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 Honey bee acute contact and oral toxicity2 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 Directions for Use: Bananas, Grapes, and 

Potato3 TEP 12

860.1560 Reasonable Grounds in Support of the 

Petition3 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 Availability” 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 49403401). 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, D267866, 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 

Number1 Study Title1

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-014601-260814

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 outstanding. 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 product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time.

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website.

5

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The Agency 

will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of metiram.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for metiram.

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)

Reregistration Eligibility 

Decision (RED)

August 2005

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not applicable. Tolerance reassessment was included in the RED.

Cumulative 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 metiram are established in 40 CFR §180.217(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 leaf ferns.

Use Sites Agricultural Use Sites: include apples and potatoes

Non-Agricultural Use Site: 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 

treated. 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 applied by aircraft and ground application 

methods.

Technical Registrant(s) BASF Corporation

No. of Registrations 2 Section 3 products6; 1 Section 24(c) Special Local Needs 

(SLNs) product.

Restricted Use No

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

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

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

• 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 pound a.i. 

applied, application timing and acres treated.

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

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

and county.

• Typical application timing (date of first application and application intervals) – national, 

state, and county.

• Usage/use information for non-agricultural uses.

• Typical application interval (days).

• State or local use restrictions.

• 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 metiram was completed June 

2007 for the establishment of import tolerances on grapes and bananas. The most recent 

comprehensive ecological and environmental fate risk assessment was completed in June 2005 in 

support of the metiram Reregistration Eligibility Decision (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 for 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, the Agency anticipates the need to conduct a comprehensive

ecological risk assessment, including an endangered species assessment, for all uses of metiram.

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

occupational risk assessments during registration 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 assessments, as well as any changes to the standard operating 

procedures or default exposure assumptions.

Table 4 below summarizes the anticipated registration review risk assessments based on the 

Preliminary Problem Formulation and Human Health Assessment Scoping Document.
10

Table 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 aquatic exposure Estimated 

Environmental Concentrations (EECs) of the parent 

metiram and its degradate, EBIS.

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

metiram, see 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 

Post-application Y performed for all currently registered metiram uses.

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 assessment 

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. See page 16 of the Scoping Document and 

the Metiram: Tier I (Scoping) 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 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 metiram 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 January – March

Data Submission 2019 January – March 

60-day Public Comment Period for Draft Risk 

Assessments7

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

2022

Total (years) 7

NEXT STEPS

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of metiram.

 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 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.
12

Appendix – Additional Areas Considered in the Metiram Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to 

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern.

Water Quality:

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 Loads (TMDL) 

have been developed for metiram.

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 Process11

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 metiram 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.htm
13

ENDANGERED SPECIES:

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

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

allow the Agency to determine whether use of metiram has “no effect” or “may affect” federally 

listed threatened or endangered species (listed species) or their designated critical habitats. When 

an assessment concludes that a pesticide’s use “may affect” a listed species or its designated 

critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National 

Marine Fisheries Service (the Services), as appropriate.

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 effects in different 

taxonomic groups. As part of its reregistration decision for metiram, EPA reviewed these data 

and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), metiram is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 201312 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 metiram risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure.

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural 

Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force 

(ORETF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic 

exposure databases, and has found no clear and convincing evidence that the conduct of any of 

them was either fundamentally unethical or significantly deficient relative to the ethical 

standards prevailing at the time the research was conducted. All applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.

Occupational

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

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure.

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED) 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/