2 

### Mancozeb 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

................................ ................................ ................................ ..................... 10

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

.............................. 10

TIMELINE

................................ ................................ ................................ ................................ .... 13

NEXT STEPS

................................ ................................ ................................ ............................... 13

Appendix

– Addi tional Areas Considered in the Mancozeb Registration Review

................... 14

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 Mancozeb . Housenger,

Ruhman. June 11, 2015

.

2. Mancozeb: Human Health Risk Assessment Scoping Document in Support of Reg istration

Review . Drew, Lloyd, Savoia, Taylor. June 1, 2015.

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

. Evans, Recore, Christensen

. April 15, 2015

.

4. BEAD Chemical Profile for Registration Review: Mancozeb (014504)

. Chen, Doucoure,

Berwald

. January 22, 2015

.

5. Mancozeb (014504) Screening Level Usage Analysis (SLUA)

. July 28, 2014

.3 6. Environmental Fate and Effects Division Table 1 Report, Mancozeb (014504)

. July 23,

2014

.

7. Health Effects Division Master Label Report, Mancozeb (014504)

. July 23, 2014

.

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

in the docket EPA

- HQ

- OPP

- 2015

- 0291 at http://www.regulations.gov

.4 OVERVIEW

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

- HQ

- OPP

- 2015

- 0291 )

. Mancozeb is an ethylenebis dithiocarbamate (EBDC) non

- systemic fungicide with protective action on contact. Mancozeb

and other EBDC fungicid es
, 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 Committe e (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. This Preliminary Work

Plan (PWP) document explains what EPA's Office of Pe sticide Programs knows about

mancozeb

, 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 mancozeb

.

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

. 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; pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, residential, and other use rs of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for mancozeb

. Next, it discusses 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 mancozeb

. Finally, the Appendix to this document includes identification and discussion of some areas that are considered general ly

in R egistration R eview along with some additional chemical case

- specific information.

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)5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for mancozeb . 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 Mancozeb and Mancozeb: Human Health Risk Assessment Scoping Document in Support of Registration

Review

.

Table 1: Antic ipated Data Needs for the Mancozeb Registration Review

Guideline

Number 2 Study Title 2 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated 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

Non

Guideline Honey bee larval acute oral toxicity TGAI 12

2 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 A vailability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 00286 Table 1: Antic ipated Data Needs for the Mancozeb Registration Review

Guideline

Number 2 Study Title 2 Test Material Estimated

Timeframe

(Months from receipt of DCI)

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

Anticipated 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

- 014504

- 26952

860.1340 Enforcement analytical method (mancozeb & ETU in meat and milk) 3 TGAI Past due

TGAI = technical grade active ingredient; TEP = typical end

- use product ;

3 Submitted methods were deemed suitable with several revisions. EPA required submission of the revised methods,

which have not been received to date.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 cau se 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 p esticides 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 Age ncy periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website

. 4

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 information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received i n the docket during this initial comment period, the Agency will develop a F inal W ork P lan (FWP) and anticipated schedule for the registration review of mancozeb

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for mancozeb

.

Table 2: Chemical Facts for Mancozeb

PC code 014054

Case Number 0643

CAS Number 8018

- 01

- 7

Year first registered 1948 Pesticide Type Fungicide

Chemical class Ethylenebis dithiocarbamates (EBDCs)

R eregistration Eligibility Decision (R E D) September 20, 2005

Tolerance Reassessment Eligibility Decision (TRED) Not applicable as a tolerance reassessment was included in the

RED

4 http://www.epa.gov/oppsrrd1/registration_review/8 Table 2: Chemical Facts for Mancozeb

Cumulative group Mancozeb has not been identified as a member of a cumulative group 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 are addressed in a separate ETU aggregate risk assessment.

40 CFR Citation Tolerances for manc ozeb are established in § 180.176

. Dual

- use Mancozeb 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 mancozeb.

Pesticide Re

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

- 347

- 0249

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 mancozeb

. Please see the BEAD Chemical Profile for Registration Review: Mancozeb (014504) in the registration review docket

for more details

.

Table 3 : Mancozeb Use and Usage Information

Summary of Use Mancozeb is a broad

- spectrum non

- systemic protectant fungicide and an EBDC fungicide. Mancozeb’s specific mode of action (MOA) is unknown and the Fungicide Resistance Action Committee (FRAC 5 ) classifies it by th e code M3 (multi

- site action)

. There do es not appear to be signs of resistance to th is fungicide

.

Mancozeb is registered for control of many important plant diseases. Late blight and early blight are the top two diseases targeted by its use, each of which make up over one million acre s treated annually in the United States. Apple scab is among other top diseases targeted by mancozeb use, which is the most common serious apple disease worldwide, mainly controlled with fungicide sprays.

Use Sites Agricultural Use Sites: fruit, including pome fruit, tropical fruit, bananas, cranberry, grapes, and papaya; vegetables, including cucurbits, crucifers/brassica, asparagus, beets, sugar beet, carrots, lettuce, peppers, spinach, tomatoes, endive escarole, fennel, Swiss

5 Fungicide Resistance Action Committee ( http://www.f rac.info/index.htm )

Classification available at http://www.frac.info/publication/anhang/2014%20FRAC%20Code%20List.pdf (accessed January, 2015)9 Table 3 : Mancozeb Use and Usage Information

chard, garlic, leek, onion, shallot, and parsnip; herbs, including coriander, parsley, dill and arugula; nut trees, including almonds and walnuts; row crops, including corn, cotton, peanuts, potatoes, tobacco, and cereal grains (barley, oat, rye, wheat, triticale, and rice); and oth er crops, including plantain, caprifig, flax, ginseng, safflower, and sorghum. Mancozeb is also used on the seeds of row crops, flax, safflower, sorghum, and tomatoes.

Non

- Agricultural Use Sites: Mancozeb is registered for use on ornamental plants in nurs eries and greenhouses, conifers, sod farms, and commercial lawns and turf ( primarily golf courses). Summary of Usage During the 1998

- 2012 time frame, approximately 6.4 million pounds a.i. were applied on average annually to treat 4.5 million

acres at an overall average a.i. application rate of 1.4 lbs a.i. per acre. During the 2008

- 2012 time frame, approximately 6 million pounds a.i. were applied annually on average to treat 4 million

acres at an overall average a. i. application rate of 1.5 lbs a.i. per

a cre. The U.S. has therefore remained fairly constant in mancozeb

usage during the 1998

- 2012 time frame with very slight decreases in the years 2006

- 2009.

During the 2008

- 2012 time frame, mancozeb is reported to be used on over 30 crops in over 30 states. In terms of total pounds a.i. applied, mancozeb is used predominantly on potatoes (33%) and apples (23%) and used predominantly in the states of California (17%), New York (13%), Florida (12%), Michigan (12%) and Idaho (8%). Formulation Type(s) Dry flo wable, flowable concentrate, wettable powder, or dust. Application Method(s) Products can be applied via ground sprays, aircraft, chemigation, seed treaters, drenchers or dip tanks. Technical Registrant (s) Drexel Chemical Company, Cheminova, Inc., United Phosphorus,

Inc. , A gria Canada, Inc. , Dow AgroSciences LLC. No. of Registrations 49 Section 3 products 6 , 55 Special Local Need registrations

Restricted Use No

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.

• Further information related to the importance of mancozeb for fungicide

- resistance

management.

• Any new information on alternatives to mancozeb.

6 Section 3 product label s can be obtained from the Pesticide Produ ct Label System (PPLS) website

( http://oaspub.epa.gov/pestlabl/ppls.home ).10 • C onfirmation o f 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

.

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

.

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

– national, state, and county

.

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

– national, state, and county

.

• Usage/use information for non

- agricultural uses

.

• Typical application interval (days)

.

• S tate or local use restrictions

.

• F oreign technical registrants not listed above who supply technical mancozeb to th e US

market

.

RECENT ACTIONS

There are no recent actions for mancozeb.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The Agency based its human health scoping effort for mancozeb on two documents: 1) a 2013

risk assessment for a new use request on walnuts and the establishment of a tolerance for imported tangerines , and 2) the human health assessment conducted for the 2005 mancozeb

RED

. EPA based its ecological and environmental fate risk assessment problem formulation for

mancozeb on two docume nts: 1) the ecological assessment conducted in support of the 2005 RED, and 2) a 2007 assessment of the risks of mancozeb uses to the federally

- listed California Red Legged Frog

. Findings and conclusions from these risk assessments are summarized in the

R egistration 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.

During registrat ion review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species and pollinator assessment, for all

uses of mancozeb

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

residential , aggregate

, and occupational risk assessment s 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 assessment s
, as well as any changes to the standard operating p rocedures or default exposure assumptions

.

T able 4 below summarizes the anticipated registration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document

.11 Table 4: Anticipated 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 and pollinators 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 T he Agency anticipates needing 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 res ult in significantly greater risk estimates than determined in

the most recent assessment

. ETU is the drinking water residue of concern. The anticipated environmental fate data needs identified for mancozeb parent and

ETU in Table 1 are expected to be used to determine

the estimated drinkin g water concentrations for ETU. Drinking water Y

Occupational Handlers (mixers, loaders, applicators) Y EPA intends to conduct 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 Y12 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.

Cumulative N Mancozeb has not been identified as a member of a cumulative group 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 w ill integrate the epidemiological findings

, including information from the Agricultural Health Study, with the available experimental toxicological data

.

EPA also plans to review t he findings presented by a Reach the Decision Makers group 7 in a May 29, 20 14 meeting with the Agency. A summary of the meeting

and the submitted paper entitled, “ An Updated Look
at Mancozeb: Concerns about Farmworker Reproductive Health ” , can be found in the mancozeb public docket. Th is paper contains a systematic

identificati on, evaluation, and integration of in vitro

, in vivo , and epidemiology studies regarding the potential developmental and rep roductive toxicity of

mancozeb

.

Guidance for Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

• The registrant is requested to review the labeled use section (3.1) on pages 9

- 12 of Registration Review

– Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Ass essment to be Conducted for Mancozeb and provide

7 The Reach the Decision Makers Fellowship program is a training fellowship administered through the University of

California at San Francisco’s Program on Reproductive Health and the Environment.13 answers to the questions stated therein. The registrant can provide a response in the public comment period for the mancozeb docket opening.

• Ec ological incidents (non

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

.

• Water quality m onitoring data (see Appendix for further details)

.

TIMELINE

EPA has created the following estimated timeline for the completion of the mancozeb registration review in Table 5 below

.

Table 5: Projected Mancozeb Registration Review Timeline

Activities Estimated Dat e 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.

- March

Data Submission 201 9 Jan.

- March

6 0

- day Public Comment Period for Draft Risk

Assessments 8 20 20 July

– Sept.

Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision 202 1 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 mancozeb

.

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

.14 

### Appendix

– Additional Areas Considered in the Mancozeb 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 marke ts, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

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

. 9 In addition, n o T otal Maximum Daily Load s (TMDL) have been developed for mancozeb

. 10 More information on impaired water bodies and

TMDLs can be found at the Agency’s website

. 11 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 12 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 inco me, 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 mancozeb compared to the general population. Please

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

10 http://iaspub.epa. gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

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

12 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm15 comment if you are aware of any sub

- populations that may have atypical, unusually high

exposure compare d to the general population.

ENDANGERED SPECIES :

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

conducted for mancozeb

. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of mancozeb 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 o r 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.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

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

, 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), mancozeb 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 t o 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 scre ening 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 ho rmonal 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 subs tance, 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 th e 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 13 and includes some

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.16 pesticides 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 gui delines and the Tier 1 screening battery, please visit our

website. 14

HUMAN STUDIES :

Occupationa l and Residentia l

Past mancozeb 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 gen eric pesticide exposure databases such as the Pesticide Ha ndlers 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 t hese 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 resea rch was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been

satisfied , and t here is no regulatory barrier to continued reliance on these studies

.

AGRICULTURAL HEALTH STUDY :

Man cozeb is among several agricultural chemicals included in the Agricultural Health Study (AHS). The AHS began in 1993 and is a collaboration of the National Institute of Environmental Health Sciences (NIEHS), the National Cancer Institute (NCI), the EPA, a nd the National Institute for Occupational Safety and Health (NIOSH). Designed as a large long

- term epidemiological study, the AHS collects and analyzes data on the health and work practices of nearly 90,000 farmers and their families in Iowa and North Ca rolina who enrolled in the study before any disease developed. The study focuses particularly on farmers' exposure to 50 chemicals including many of the most widely used pesticides. As data are collected over a period of years, scientists can compare ove rall health outcomes for people who differ in whether they have had exposure to various chemicals. While these comparisons cannot conclusively demonstrate how exposure affects health, they can show some statistical associations. More

information on the A HS can be found at: http://aghealth.nci.nih.gov . EPA is monitoring the results of the AHS and will consider this study in the registration review of mancozeb as appropriate.

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