2

Mancozeb 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..................................................................................................................... 10

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW.............................. 10

TIMELINE.................................................................................................................................... 13

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

Appendix – Additional Areas Considered in the Mancozeb Registration Review................... 14

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 Mancozeb. Housenger, 

Ruhman. June 11, 2015.

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

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 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 (FRAC1

). 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 Pesticide 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, by sharing this information in the 

docket, to inform the public 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 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 mancozeb. 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 mancozeb. 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.

 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: Anticipated Data Needs for the Mancozeb Registration Review

Guideline 

Number2 Study Title2

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data 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 validations 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

NonGuideline Honey bee adult acute oral toxicity TGAI 12

NonGuideline Honey bee adult chronic oral toxicity TGAI 12

NonGuideline 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 Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028
6

Table 1: Anticipated Data Needs for the Mancozeb Registration Review

Guideline 

Number2 Study Title2

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

NonGuideline Honey bee larval chronic oral toxicity TGAI 12

NonGuideline Semi-field testing for pollinators TEP or TGAI 24

NonGuideline Field trial of residues in pollen and nectar TEP 24

NonGuideline 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 validations 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 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.

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. 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 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)

Reregistration Eligibility 

Decision (RED)

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 mancozeb 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 (FRAC5

) classifies it by the code M3 (multi-site 

action). There does not appear to be signs of resistance to this

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 acres 

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.frac.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 other 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 nurseries 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 

acre. 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 flowable, 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., Agria Canada, Inc., Dow AgroSciences LLC.

No. of Registrations 49 Section 3 products6, 55 Special Local Need registrations

Restricted Use No

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.

• Further information related to the importance of mancozeb for fungicide-resistance 

management.

• Any new information on alternatives to mancozeb.

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
10

• 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 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 mancozeb to the 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 documents: 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 

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.

During registration review, the 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 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 

EFED Problem Formulation and HED Scoping Document.
11

Table 4: Anticipated Risk Assessments for the Mancozeb 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 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 The 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 result 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 drinking 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 

assessments (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
12

Other

Aggregate Y Evaluates 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 will integrate the epidemiological 

findings, including information from the Agricultural 

Health Study, with the available experimental 

toxicological data.

EPA also plans to review the findings presented by a

Reach the Decision Makers group7 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 about 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 reproductive toxicity of 

mancozeb. 

Guidance for Commenters: Additional ecological information requested for this 

registration review, 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 Assessment 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.

• 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 mancozeb

registration review in Table 5 below.

Table 5: Projected Mancozeb 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. - March

Data Submission 2019 Jan. - March

60-day Public Comment Period for Draft Risk 

Assessments8

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 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, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.
14

Appendix – Additional Areas Considered in the Mancozeb 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:

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, no Total Maximum Daily Loads 

(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 Process12 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 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 10http://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.htm
15

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared 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 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. 

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 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 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, 201313 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 guidelines and the Tier 1 screening battery, please visit our 

website.14

HUMAN STUDIES:

Occupational and Residential

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 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.

AGRICULTURAL HEALTH STUDY:

Mancozeb 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, and 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 Carolina 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 overall 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 AHS 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/