2 I NTRODUCTION

This is the Environm ental Protection Agency’s (EPA or the Agency ) Final Work Plan (FWP) for the registration review of mancozeb . This work plan addresses public comments received concerning the Preliminary Work Plan (PWP) , which was posted in the mancozeb registration review docket (EPA

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non

- systemic fungicide wit h protective action on contact. Mancozeb and other EBDC fungicides, maneb (no registered uses) and metiram, have a common metabolite/degradate, ethylenethiourea (ETU). Mancozeb’s specific mode of action (MOA) is unknown and it is classified by the code

M3 (multi

- site action) by the Fungicide Resistance Action Committee (FRAC 1 ). Mancozeb is currently registered for foliar application and seed treatment on over 30 agricultural crops. Non

agricultural uses include ornamental plants in nurseries and greenhouses , home gardens, sod farms, and golf courses. Mancozeb is considered an important fungicide in many areas of agriculture, including its significant role in pest management, resistance management, and the U.S. fungicide market.

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. Changes in science, public policy, and pesticide use practices occur over time. 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. The public phase of registration review begins when the initial docket is opened for each case.

Informatio n on this program is provided on the Agency’s website

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The FWP begins with any update s since the PWP was issued. Next is a summary of substantive

comments received during the public comment period for the PWP concerning anticipated data

needs

, expected risk assessments, or the estimated timeline identified in the PWP

, and a summary of the Agency’s response s to th o se comments

. This section is followed by registration

review planned data needs, risk assessments expected to be conducted , and the projected registration review timeline for mancozeb

. Lastly, there is a discussion of next s teps.

UPDATES SINCE THE PWP WAS ISSUED

There are no additional updates on mancozeb since the PWP.

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60

- day public comment period on the Mancozeb Preliminary Work Plan , which opened on June 24, 2015 and closed on August 24, 2015 , the Agency received five public comments. Comments were submitted by t he FIFRA Endangered Species Task Force, t he Center for Biological Diversity, t he Physicians Committee for Responsible Medicine, t he Mancozeb Task Force, and t he Northwest Horticultural Council. The comments do not address

1 Fungicide Resistance Action Committee ( http://www.frac.info/index.htm ) classification available at http://www.frac.info/publication/anhang/2014%20FRAC%20Code%20List.pdf (accessed January, 2015).

2 http://www2.epa.gov/pesticide

- reevaluation3 the timeline described in the PWP, but they do address the planned ecological risk assessment and data requirements. In the PWP, EPA also solicited comments on the specific topics of environmental justice, water quality concerns , a nd trade irritants; one comment from the

Northwestern Horticultural Council w as received concerning trade irritants a nd is included

below.

Summarized below are public comments that resulted in changes to the anticipated registration review data needs, risk assessments, or timeline, or are of a broader regulatory nature. Public comments and EPA responses in their entire ty are located in the docket, EPA

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- 0291 . Summarized public comments and Agency responses related to the anticipated ecological

risk assessment or data needs are in the Review of Public Response to Mancozeb Problem

Formulation and Mancozeb: HED Response to Comments on the Registration Review Preliminary Work Plan

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Comments submitted by the Center for Biological Diversity in EPA

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1. Comment: The Center for Biological Diversity’s (CBD) comments focus on the EPA’s duty to consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) on the registration review of mancozeb in accordance with the Endangered Species Act (ESA). CBD mentions various aspects of the risk assessment process , including use of the best available data to develop endangered species risk assessments, and evaluation of effects on endangered and threatened species and their designated critical habitat. CBD also expressed concern regarding the rigor of the Agency’s preliminary determinations regarding the effects of mancozeb on endangered and threatened (listed) species and their designated critical habitat for the mancozeb registration review

.

Response: EPA has reviewed the comments from CBD on the registration re view docket opening for mancozeb and plans to address many of the concerns raised by CBD as part of the implementation plan for assessing the risks of pesticides to listed species based on the recommendations of the April 2013 National Academy of Sciences (NAS) report. EPA will address concerns specific to mancozeb in connection with the development of its final registration review decision for mancozeb.

In November 2013, the EPA, along with the Services and the USDA, released a summary of their joint Interim Approaches for assessing risk s to listed species from pesticides. The Interim Approaches were developed jointly by the agencies in response to the NAS recommendations and reflect a common approach to risk assessment shared by the agencies

as a way of addressing scientific differences between the EPA and the Services. The NAS

report 3 outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA.

The joint Interim Approaches were released prior to a stakeholder workshop held on
November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the

3 http://www.nap.edu/catalog.php?record_id=183444 December 2013 Pesticide P rogram Dialogue Committee (PPDC) and State

- FIFRA Issues Research and Evaluation Group (SFIREG) meetings. The agencies also held stakeholder workshops in April and October 2014, allowing additional opportunities for stakeholders to comment on the Interim Ap proaches. Additional workshops are planned to enhance

stakeholder involvement. As part of a phased, iterative process for developing the Interim Approaches, the agencies will also consider public comments on the Interim Approaches in

connection with the development of upcoming Registration Review decisions. The details of the joint Interim Approaches are contained in the white paper “Interim Approaches for

National

- Level Pesticide Endangered Species Act Assessments Based on the

Recommendations of the Na tional Academy of Sciences April 2013 Report” 4 , dated
November 1, 2013.

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their desig nated critical habitat, the ecological problem formulation supporting this Final Work

Plan for mancozeb does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducte d during registration review. In the ecological problem formulation document for mancozeb

, EPA described the screening

- level risk assessment to determine the potential effects of

mancozeb on all taxa of non

- target wildlife and plants, which will assume t hat listed species and their designated critical habitats may be present in the vicinity of the application of

mancozeb

. This screening

- level assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific methods being developed by the agencies have been fully vetted. While the agencies continue to develop a common method for ESA analysis, the planned screening

- level risk assessment for the registration review of mancozeb will des cribe the level of ESA analysis completed for this particular registration review case. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical ha bitats, these methods will be applied to subsequent analyses for

mancozeb as part of completing this registration review.

Comments submitted by the FIFRA Endangered Species Task Force, L.L.C. in EPA

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. Comment: The technical registrant for mancozeb , as identified on the fact sheet included in the PWP, is Cheminova, Inc., which has recently been acquired by FMC Corporation, and Dow AgroSciences, which are FESTF member s and entitled to rely on FESTF data.

Response : EPA appreciates FESTF’s comments and will consider this information during the registration review of mancozeb

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4 h ttp://www.epa.gov/espp/2013/nas.html5 Comments submitted by the Physicians Committee for Responsible Medicine in EPA

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3. Comment: The Physicians Commi ttee for Responsible Medicine ( PCRM ) recommended that the OECD Test Guideline 223 for the Avian Acute Oral Toxicity Test be used as the protocol instead of EPA Guideline 850.2100 in the interest of reducing the numbers of animals used by up to 61%. PCRM also referred the registrant to the “Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study)” available on the Agency’s website.

Response: For studies with bobwhite quail and mallard, the Agency will accept testing under OECD Guideline 223. The Agency however recommends against the use of OECD 223 for passerine species studies, as this guideline has not been tested or validated for passerines.

4. Comment: PCRM cited data to fulfill the Agency’s needs without additional avian dietary toxicity testing under the requirement 850.2200.

Response: The data cited are from a secondary source (summary document). The document provides only the toxicity values, and does not provide the detaile d information necessary to

allow validation of the data. The Agency thanks PCRM for their comment.

Comments submitted by the Mancozeb Task Force in EPA

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. Comment: The Mancozeb Task Force submitted comments asking the Agency to r econsider the need for the pollinator studies identified in the Preliminary Work Plan. The Task Force cited data from an acute contact study on bees with mancozeb conducted by the University of California

- Riverside in which little toxicity is observed.

Re sponse: The Agency thanks the Mancozeb Task Force for their comment. EPA’s determination is that acute toxicity testing with adult bees does not necessarily reflect potential toxicity to developing larvae or chronic toxicity to adult bees. In order to con duct a Tier I assessment of pollinator risk, chronic effects to adults and larval bees are considered. The registrant may wish to consult the Office of Pesticide Programs Guidance for Assessing Pesticide Risks to Bees implemented June 23, 2014 regarding de termination for testing needs and assessment of exposure potential currently used by the Agency.

6. Comment: The Mancozeb Task Force submitted comments regarding the anticipated data needs, specifically concerning the Residue/Monitoring (market basket) study. They mention that a previously compiled market basket survey was conducted for EPA from 1989

- 1990. The Mancozeb Task Force believes that the results gleaned from that survey continue to be viable and useable for Agency dietary risk assessment purpos es

.

Response: The Agency thanks the Mancozeb Task Force for their comment. The Mancozeb Task Force however is asked to provide specific information demonstrating the relevancy of

the 1989

- 1990 market basket survey for use in current assessments. Given th e age of the survey, any changes in application techniques, typical rates, handling, storage, and transportation could result in incurring different residue levels in food today than those6 reported in the older survey. To allow for the continued use of the market basket survey, specific data must be submitted to illustrate that the survey results remain representative of present EBDC usage. This would include providing comparisons (across time) of typical rates, EBDC usage totals, application techniques/tim ing, percent crop treated data, commercial practices (handling, storage and transportation), and the capabilities of analytic al

methods to detect residues. In the event that the continued use of the market basket survey cannot be justified

, the Agency will rely on residue data from available c ontrolled studies (field trial and processing studies), which will likely result in significantly greater risk estimates, until a new survey can be provided.

Comments submitted by the Northwestern Horticultural Counci l (NHC) in EPA

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. Comment: Indonesia and Russia, who are among the top export markets for U.S. tree fruits,

do not have a maximum residue limits (MRL) for mancozeb residues in apples (Indonesia) and pears (Russia) . These countries are top export markets for Northwest growers; therefore, we request that EPA work with its counterpart agencies to open access to these markets.

Response: During registration review, the Agency will work to minimize trade irritants and harmonize US tolerances with MRLs with its trading partners, to the extent feasible (and consistent with domestic law). To facilitate this, the Agency works with the United St ates Department of Agriculture Foreign Agricultural Service and the United States Trade Representative to identify potential trade irritants. EPA is currently working with some of the countries identified by Northwest Horticultural Council to assist with t he development of

science

- based MRLs.7 PLANNED DATA NEEDS

Table 1 below summarizes the planned data needs for mancozeb based on the Registration

Review

– Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Mancozeb and Mancozeb: Human Health Risk Assessment Scoping Document in Support of Registration Review

, Review of Public Response to
Mancozeb Problem Formulation and Mancozeb: HED Response to Comments on the Registration Review Preliminary Work Plan

. The planned data needs have not changed from

what was included in the PWP

.

Table 1: Planned Data Needs for the Mancozeb Registration Review

Guideline

Number 5 Study Title 5 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Planned D ata Needs for the Parent Mancozeb

835.2120 Hydrolysis TGAI 12

835.4400 Anaerobic aquatic metabolism TGAI 24

850.2100 Avian acute oral toxicity (passerine species and upland game or waterfowl species ) TGAI 12

850.2200 Avian dietary toxicity (upland game and waterfowl species) TGAI 12

850.3040 Field testing for pollinators TEP 24

850.4100 Terrestrial plant toxicity, seedling emergence TEP 12

850.4150 Terrestrial plant toxicity, vegetative vigor TEP 12

850.4400 Aquatic plant growth (using Lemna spp.) TGAI 12

850.4500 Algal toxicity (Freshwater and marine diatom) TGAI 12

850.4550 Cyanobacteria toxicity TGAI 12

850.6100 Environmental chemistry methods and associated independent laboratory v alidation s for soil and

water TGAI 12

860.1480 Ruminant feeding study TGAI 24

860.1500 Crop field trials (tobacco, safflower seed or propagation stock treatment data) TEP 24

860.1520 Processing studies (wheat, barley, oats, potatoes) TEP 24

860.1850 Confined rotational crop study TEP 24

Non

Guideline Honey bee adult acute oral toxicity TGAI 12

Non

Guideline Honey bee adult chronic oral toxicity TGAI 12

5 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

Gu idelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

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Guideline

Number 5 Study Title 5 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Non

Guideline Honey bee larval acute oral toxicity TGAI 12

Non

Guideline Honey bee larval chronic oral toxicity TGAI 12

Non

Guideline Semi

- field testing for pollinators TEP or TGAI 24

Non

Guideline Field trial of residues in pollen and nectar TEP 24

Non

Guideline Residue/Monitoring (market basket) study TEP 36

Planned Data Needs for the ETU Degradate

835.4100 Aerobic soil metabolism Degradate 24

835.4300 Aerobic aquatic metabolism Degradate 24

835.4400 Anaerobic aquatic metabolism Degradate 24

850.6100 Environmental chemistry methods and associated independent laboratory v alidation s for soil Degradate 24

Outstanding Data Requirements from Mancozeb GDCI

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860.1340 Enforceme nt analytical method (mancozeb and ETU in meat and milk) 6 TGAI Past due

TGAI = technical grade active ingredient; TEP = typical end

- use product ;

RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, t he Agency will conduct a comprehensive ecological risk assessment, including an endangered species and pollinator assessment, for all uses of mancozeb

. For human health, EPA will conduct revised dietary, residential

, aggregate, and occupational risk

assessment s during registration review

. If toxicological endpoints or points of departure are

revised b ased on the data that are 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

.

Table 2 below summarizes the planned registration review risk assessments based on the EFED

Problem Formulation and HED Scoping Document and the planned assessments have not changed from what was included in the PWP

.

6 Submi tted methods were deemed suitable with several revisions. EPA required submission of the revised methods,

which have not been received to date.9 Table 2: Planned Risk Assessments for the Mancozeb Registration Review

Type of Risk Assessment Conduct ? Notes

Eco logical and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms ), including endangered species Y

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

mancozeb , see page 42 of the Problem Formulation.

Human Health Dietary

Food Y The Agency is requiring additional residue/monitoring data to support the mancozeb dietary assessment. Until adequate updated market

basket data are submitted, the Agency will rely on data from available controlled studies (e.g., field trial data, processing studies), which will likely result in significantly greater risk estimates than determined in

the most recent assessment. ETU is the drin king water residue of concern. The planned environmental fate data needs identified for mancozeb parent and ETU in Table 1 are expected to be used to determine the estimated drinking water concentrations for ETU. Drinking water Y

Occupational

Handlers (mixers, loaders, applicators) Y EPA plans on conducting a comprehensive quantitative handler and post

- application occupational

risk assessme nts (cancer and non

- cancer), using the Agency’s updated exposure assessment methodology

. Post

- application Y

Residential

Handlers Y EPA expects to revise the residential assessment only if endpoints, methodologies or use patterns change.

Post

- application Y

Other Aggregate Y E valuates the combined risk from dietary and residential exposures. The Agency may conduct a revised aggregate assessment if there are significant changes to estimated residues in food or drinking

water.10 Cumulative N Mancozeb has not been identified as a member of a cumulative grou p that shares a common mechanism of toxicity. However, mancozeb does produce a toxic metabolite, ETU, which is produced by other EBDC compounds. Risks from combined exposures to ETU from all EBDC compounds will be addressed in a separate ETU aggregate risk assessment.
Tolerances Y

Incidents Will check for updates For a discussion of reported human incidents for mancozeb, see page 18 of the Scoping Document and

the Mancozeb: Tier I (Scoping) Review of Human

Incidents

. EPA plans to conduct a Tier II assessment of the human health effects of mancozeb, given the number of epidemiological findings. This Tier II assessment will integrate the epidemiological findings, including information from the Agricultural Health Study, with the available experiment al toxicological data.

EPA also plans to review the findings presented by a Reach the Decision Makers group 7 in a May 29, 2014 meeting with the Agency. A summary of the meeting and the submitted paper entitled, “ An Updated Look
at Mancozeb: Concerns abou t Farmworker Reproductive Health ”, can be found in the mancozeb public docket. This paper contains a systematic identification, evaluation, and integration of in vitro

, in vivo , and epidemiology studies regarding the potential developmental and reproducti ve toxicity of

mancozeb.

TIMELINE

EPA has created the following estimated timeline for the completion of the mancozeb registration review in Table 3 below

. The projected timeline has not changed since the PWP.

Table 3: Registration Review for Mancozeb

– Projected 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

– December

7 The Reach the Decision Makers Fellowship program is a training fellowship administered through the University o f California at San Francisco’s Program on Reproductive Health and the Environment.11 Issue DCI 2016 Jan.

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Data Submission 2019 Jan.

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6 0

- day Public Comment Period for Draft Risk

Assessments 8 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

As noted previously, the Agency plans to require several environmental fate, ecological effects,

and human health studies for mancozeb through a D ata C all

- I n Notice , expected to be issued in early 2016

.

8 The regulations governing Registration Review generally require the Agency to provide a public comment period

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, t he Agency plans to provide a 60 calendar day public comment period generally for draft risk assessment s

.