2 

### Imazalil and Imazalil Sulfate Prelimin ary 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 Imazalil and Imazalil Sulfate Registration
Review ........................................................................................................................ .............. 14

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Registration Review – Preliminary Probl em Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Imazalil and Imazalil Sulfate . Christine Hartless, Ph.D., R. David Jones, Ph.D., and Laura Parsons.
12/05/13.

2. Imazalil and Imazalil Sulfate: Human Health Assessment Scoping Document in Support of Registration Review . Karlyn Middleton, Dennis McNeill y, and Zaida Figueroa. 11/21/13.

3. Imazalil and Imazalil Sulfate: Tier I Review of Human Incidents

. Elizabeth Evans and
Shanna Recore

. July 25, 2013.

4. BEAD Chemical Profile for Registration Review: Imazalil (111901) and Imazalil Sulfate (111902) . Tara Chandgoyal, Ph. D., Cynthia Doucoure, and Andrew Lee . July 30, 2013.3 5. Imazalil (111901) Screening Level Usage Analysis (SLUA) . January 22, 2013.

6. Imazalil EFED Label Data Report. June 6, 2013.

7. Imazalil HED Label Data Report . June 6, 2013.

These and other supporting documents for the im azalil and imazalil sulfate registration review case may be found in the docket EPA-HQ-OPP-2013-0305 at http://www.regulations.gov

.4 OVERVIEW

The docket for imazalil is now open, initiating the first public comment period for this registration review (docket num ber EPA-HQ-OPP-2013-0305). This case includes the following active ingredients: imazalil (PC Code 111901) and imazalil sulfate (PC Code 111902). Imazalil
is a systemic imidazole fungicide registered for use for control of a variety of fungal pathogens. It

is used for postharvest treatment of citr us fruits and bananas (importe d), seed treatment of barley, wheat, and triticale, and ornamental plants in commercial greenhouses. Imazalil also has an

antimicrobial indoor non-food use: the control of Aspergillus fumigates in egg hatching facilities and equipment disinfection

. T here are no registered residential uses for imazalil. This Preliminary Work Plan (PWP) document explai ns what EPA's Office of Pesticide Programs knows about imazalil and imazalil sulfate, highligh ting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the registration review, and providing an anti cipated timeline for completing the review for
imazalil and imazalil sulfate.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about imazalil and imazalil sulfate and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on imazalil. The Agency encourages all in terested stakeholders to review the PWP and Appendix and to provide comments and addition al 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 iden tified in the PWP and Appendix about which the Agency specifically seeks comments and informa tion. Interested stakeholders could include: environmental non-profit or interest groups; pe sticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing th e anticipated data needs for imazalil and imazalil sulfate. Next, it discusses the statutory and re gulatory authority for Regi stration Review. Then the document provides chemical facts, use and us age information, recent ac tions, the anticipated risk assessments, and a projected registration re view timeline for imazalil. Finally, the Appendix
to this document includes identification and di scussion of some areas that are considered generally in Registration Review along with some additional chem ical case-specific information.5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data n eeds for imazalil and imazalil sulfate. For
additional discussion of the anti cipated data needs, see the Registration Review – Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Imazalil and Imazalil Sulfate and Imazalil and Imazalil Sulfate: Human Health Assessment Scoping Docu ment in Support of Registration Review

.
Table 1: Anticipated Data Needs for the Imazalil & Imazalil Sulfate Registration Review 1

Guideline

Number 2 Study Title Test Material Estimated

Timeframe
(Months from receipt of DCI)

Imazalil – PC Code 111901 835.1410 Laboratory Volatility 3 TEP 12

835.4100 Aerobic Soil Metabolism TGAI or

PAIRA 24

835.6100 Terrestrial Field Dissipation TGAI 24 850.1075 Fish Acute Toxicity Test (saltwater only) TGAI 12 850.1400 Fish Early-Life Stage Toxicity Test (freshwater) TGAI 12

850.1730 Fish Bioconcentration Factor TGAI 12 850.1735 Whole Sediment Chronic Invertebrate Toxicity (Freshwater) 4 TGAI 24

850.1740 Whole Sediment Chronic Invertebrate Toxicity (Estuarine/marine) 5 TGAI 12

850.2100 Avian Acute Oral Toxicity (passerine species) TGAI 12 850.3020 Honeybee Acute Contact Toxicity TGAI 12 850.3100 Earthworm Subchronic Toxicity Test 6 TGAI 12 850.6100 Environmental Chemistry Method and Associated Independent Laboratory Validation (soil only) TGAI 12

870.3465 90-day Inhalation Toxicity - Rat TGAI 24 875.2100 Dislodgeable Foliar Residue (DFR) Dissipation 7 TEP 24

1 For studies listed in this table th at are requested for both imazalil and imazalil sulfate (all studies listed except 875.2100: Dislodgeable Foliar Residu e Dissipation), data may be bridged between imazalil and imazalil sulfate. The preferred test material for all studies is imazalil rather th an imazalil sulfate.

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 Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0028

3 Anticipated to be required as Henry’ Law Constant > 10 -6 atm·m 3 ·mol -1 and to support greenhouse use (see problem formulation). Study must be performed at a pH above 7.

4 Requested freshwater studies are a 42-day study with Hyallela azteca and/or a 56-day study with Chironomus
dilutus or C. tentans. Both are found in Second Edition EPA/600/R-99/064, Duluth, MN.

5 Requested estuarine/marine study is a 28-day study conducted with the Amphipod Leptocheirus plumulosa found in First Edition, EPA Report 600/R-01/020, March 2001.

6 An acute 14-day earthworm ( Eisenia foetida ) toxicity study identified in the ESFA Pesticide Review for imazalil ( http://www.efsa.europa.eu/en/efsajournal/doc/1526.pdf ) may meet this data need if submitted for Agency review.

7 This study is anticipated to be required for use in conducting risk assessments for workers contacting treated ornamental plants in greenhouses. The request ed test material is imazalil (PC Code 111901).6 Table 1: Anticipated Data Needs for the Imazalil & Imazalil Sulfate Registration Review 1

Guideline

Number 2 Study Title Test Material Estimated

Timeframe
(Months from receipt of DCI)

Nonguideline Honeybee Acute Oral Toxicity TGAI 12

Imazalil Sulfate – PC Code 111902 835.1410 Laboratory Volatility 8 TEP 12

835.4100 Aerobic Soil Metabolism TGAI or

PAIRA 24

835.6100 Terrestrial Field Dissipation TGAI 24 850.1075 Fish Acute Toxicity Test (saltwater only) TGAI 12 850.1400 Fish Early-Life Stage Toxicity Test (freshwater) TGAI 12

850.1730 Fish Bioconcentration Factor TGAI 12 850.1735 Whole Sediment Chronic Invertebrate Toxicity (Freshwater) 9 TGAI 24

850.1740 Whole Sediment Chronic Invertebrate Toxicity (Estuarine/marine) 10 TGAI 12

850.2100 Avian Acute Oral Toxicity (passerine species) TGAI 12 850.3020 Honeybee Acute Contact Toxicity TGAI 12 850.3100 Earthworm Subchronic Toxicity Test 11 TGAI 12 850.6100 Environmental Chemistry Method and Associated Independent Laboratory Validation (soil only) TGAI 12

870.3465 90-day Inhalation Toxicity - Rat TGAI 24

Nonguideline Honeybee Acute Oral Toxicity TGAI 12

Outstanding Data Requirements (for Imazalil) from GDCI-111901-21683 12

860.1340 Residue Analytical Method (ILV-livestock commodities) 13 Residue of
Concern Past Due

TGAI = technical grade active ingred ient; TEP = typical end-use product

8 Anticipated to be required as Henry’ Law Constant > 10 -6 atm·m 3 ·mol -1 and to support greenhouse use (see problem formulation). Study must be performed at a pH above 7.

9 Requested freshwater studies are a 42-day study with Hyallela azteca and/or a 56-day study with Chironomus
dilutus or C. tentans. Both are found in Second Edition EPA/600/R-99/064, Duluth, MN.

10 Requested estuarine/marine study is a 28-day study conducted with the Amphipod Leptocheirus plumulosa found in First Edition, EPA Report 600/R-01/020, March 2001.

11 An acute 14-day earthworm ( Eisenia foetida ) toxicity study identified in the ESFA Pesticide Review for imazalil ( http://www.efsa.europa.eu/en/efsajournal/doc/1526.pdf ) may meet this data need if submitted for Agency review.

12 The study listed in this section was previously required th rough a generic data call-in issued in April, 2005 and is

still outstanding. This study will not be included in the anticipated Registra tion Review DCI because it is already required through the earlier DCI.

13 Only an ILV is anticipated to be required. An adequate residue analytical method is available for determining the total toxic residues of imazalil in/on plant commodities but not in livestock commodities.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 Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website. 14

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration 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 docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of imazalil.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Imazalil and Imazalil Sulfate

PC code Imazalil (PC Code 111901) and imazalil sulfate (PC Code 111902)

Case Number 2325 CAS Number Imazalil: 3555-44-0; Imazalil Sulfate: 58594-72-2 Year first registered Imazalil was first re gistered by Janssen Pharmaceutica (FIFRA Section 3) in 1983. Imazalil sulfat e was registered in March, 2004. Pesticide Type Systemic fungicide

Chemical class Imidazole Reregistration Eligibility Decision (RED) Imazalil RED completed in September 30, 2003 Because it was registered after November 1984, imazalil sulfate was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Imazalil TRED completed in July 12, 2002 Because it was registered after November 1984, imazalil sulfate was not subject to reregistration.

14 http://www.epa.gov/oppsrrd1/registration_review/8 Table 2: Chemical Facts for Imazalil and Imazalil Sulfate

Cumulative group Imazalil and imazalil sulfat e are not members of a cumulative group and no cumulative risk assessment is planned.

40 CFR Citation Tolerances for imazalil and imazalil sulfate are established in 40 CFR § 180.413. Dual-use Imazalil is registered for both conventional and antimicrobial pesticidal uses. Non-pesticidal uses There are no identified non-pesticidal uses of imazalil.

Pesticide Re-evaluation Division, Chemical Review Manager Margaret Hathaway, hathaway.margaret@epa.gov , (703) 305-5076

Antimicrobials Division, Chemical Review Manager Sandra O’Neill, oneill.sandra@epa.gov , (703) 347-0141

Registration Division, Product Manager Tony Kish, kish.tony@epa.gov , (703) 308-9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for imazalil. Please see the BEAD Chemical Profile for Registration Review: Imazalil (111901) and Imazalil Sulfate (111902) in the registration
review docket for more details.

Table 3: Imazalil and Imazalil Sulfate Use and Usage Information

Summary of Use A fungicide registered for use in controlling fungal pathogens on postharvest citrus frui ts and on wheat, barley and triticale; for ornamental plants in commercial greenhouses; and in poultry
hatcheries for the control of Aspergillus fumigatus

. Use Sites Imazalil and imazalil sulfate have registered agricultural,
commercial and industrial use sites. Used for seed treatments, postharvest citrus fruit treatments, sterilization of egg hatcheries, and in commercial greenhouses. There are currently no residential uses registered for imazalil or imazalil sulfate. Summary of Usage EPA has limited usage data for imazalil and imazalil sulfate due to its non-agricultural and diffuse types of use patterns. From 2004- 2011, and average of 4000 lbs A.I. wa s used as a seed treatment for spring wheat and 2000 lbs A.I. was used as a seed treatment for winter wheat. Data for earlier or more recent years were not
available. Formulation Type(s) Imazalil: liquid ready-to-use, pressurized liquid, emulsifiable concentrate, water soluble gra nule, and in smoke candles.

Imazalil sulfate: soluble powder, water soluble granule, and a
flowable concentrate. Application Method(s) Imazalil: Applied as a seed treatment using mist-type equipment9 Table 3: Imazalil and Imazalil Sulfate Use and Usage Information

and mechanical slurries; as a postharvest treatment using a foamer, spray brush, dips, wash tanks, wax, and drenches; and using automatic and handheld foggers in poultry hatcheries as a smoke candle treatment in greenhouses fo r ornamental plants, and to disinfect equipment prior to the introduction of eggs.

Imazalil Sulfate: Applied as a postharvest treatment using dip and wash tanks, drenchers, and in a queous line and storage wax line spray applications, as well as in non-recovery spray and water spray brush applications. Technical Registrant(s) Imazalil: Certis Eur ope B.V., Janssen Preservation & Material Protection (PMP), and Makhteshim Chemical Works Ltd

Imazalil Sulfate: Janssen Preservation & Material Protection (PMP) No. of Registrations Imazalil: 15 Section 3 products 15
Imazalil Sulfate: 3 Section 3 products

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 Confirmation of the following label informati on: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

 Labeling clarification on which combinations of two treatments are included in postharvest applications, and confirmation on whether three treatments are ever applied
on citrus.

 For egg hatchery uses, information about handl er process and potential inhalation risks. What type of equipment is used in hatcheri es for imazalil application: an automatic or a handheld fogger?

 Use distribution ( e.g. , acreage and geographical distri bution of relevant use sites).

 Median and 90 th percentile reported use rates (lbs a i/A) from usage data – national, state, and county. Information about citrus uses is especially sought. No ting that imazalil is not a typical field crop with a specific use in pounds per acre, the Agency also asks for confirmation the quantity of imazalil used to treat a given volume of fruit (i.e. volume A.I. and dilution factor data). In the case of wax treatments, the Agency seeks
information on whether the volume A.I. indi cated is per treatment or for two wax treatments combined, in the case of citr us receiving both a pre- and post-storage

treatment.

 Post-treatment residue informa tion, especially about lemons.

15 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).10  Typical application timing (date of first applic ation and application in tervals) – 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 a bove who supply technical imazalil and imazalil
sulfate to the US market.

RECENT ACTIONS

The RED for imazalil was completed on September 30, 2003. Imazalil sulfate was first registered in 2004. There are no recent appr oved actions for imazalil or imazalil sulfate.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for imazalil was completed on February 7, 2002 in preparation for the imazalil Re registration Eligibility Decision. The most recent ecological and environmental fate risk assessment was completed on April 18, 2001 for the same purpose. No ecological or human hea lth risk assessments have been conducted by the Agency for imazalil sulfate, and no endangered species assessments have been conducted for either imazalil or imazalil sulfate. Findings and conclusions from these risk assessments are
summarized in the Registration Review – Preliminary Probl em Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Imazalil and Imazalil Sulfate and Imazalil and Imazalil Sulfate: Human He alth Assessment Scoping Document in Support of Registration Review

.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an endange red species assessment, for all uses of imazalil and imazalil sulfate. For human health, EPA anti cipates the need to condu ct revised dietary and occupational risk assessments during registration re view. If toxicologica l endpoints or points of departure are revised based on the data that are an ticipated 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 regi stration review risk assessments based on the
EFED Problem Formulation and HED Scoping Document.11 Table 4: Anticipated Risk Assessments for the Imazalil and Imazalil Sulfate 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 Yes Assessments are needed for both imazalil and imazalil
sulfate.

Incidents Will check for updates There are no reported ecol ogical incidents for imazalil
or imazalil sulfate.

Human Health Dietary Food Yes HED may need to update the dietary exposure estimates with more recent monitoring data for citrus commodities than the percent crop treated information and monitoring data used in HED’s dietary
assessment for the 2003 RED. Drinking water Yes A new drinking wa ter assessment will be needed to incorporate the use of the most current drinking water models. At the time of registration review, HED will include any updates in th e modeled drinking water residues in the new dietary exposure assessment. Occupational Handlers (mixers, loaders, applicators) Yes Updated occupational ha ndler exposure assessments will be required under regi stration review based on revisions to the Agency’s scenario-specific surrogate handler exposure data and updated exposure assessment methodologies. Post-application Yes Chemical-specific data to evaluate post-application exposure associated with the greenhouse uses on
ornamentals are needed to support registration review. The information/data will be incorporated into a revised post-application expos ure and risk assessment for occupational workers.

Residential Handlers No There are no registered residential uses for imazalil. Post-application No There are no register ed residential uses at this time. However, residential exposure s from off-site transport (e.g., spray drift or volat ilization) may occur as a result of imazalil applicati ons to agricultural fields. The Agency may conduct a spray drift assessment and
examine the need for a vo latilization assessment for imazalil during Registration Review.

Other12 Aggregate Yes Evaluates the combined risk from dietary and residential exposures. Du ring registration review, updated aggregate assessments will be needed to include any potential update s to exposure from food and drinking water, revi sed regulatory endpoints, points of departure (P oDs) and uncertainty factors/safety factors (UF/SFs). Cumulative No Imazalil is not a member of a cumulative group and no cumulative risk assessment is planned.

Tolerances Yes Tolerances for residues of imazalil and imazalil sulfate are established in 40 CFR § 180.413; the tolerance expression will be revised to reflect current policy. Harmonization may not be possible due to
differences in residues of concern for enforcement

purposes. Incidents Will check for updates For a discussion of reported human incidents for imazalil and imazalil sulfate, see page 14 of the Scoping Document and the Imazalil and Imazalil Sulfate: Tier I 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 alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).13 TIMELINE

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

Table 5: Projected Imazalil and Imaza lil Sulfate Registration Review Timeline

Activities Estimated Date
Opening the Docket
Open Docket and 60-day Public Comment Period 2013 – December

Close Public Comment 2014 – February
Case Development

Final Work Plan 2014 – May

Issue DCI 2014 July – Sept.

Data Submission 2016 July – Sept.
60-day Public Comment Period for Draft Risk

Assessments [1] 2018 Jan. - March

Registration Review Decision
60-day Public Comment Period for Proposed Registration Review Decision 2018 July – Sept.

Registration Review Decisi on and Begin Post-Decision Follow-up 2019

Total (years) 6

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 i ssue a Final Work Plan for the registration
review of imazalil a nd imazalil sulfate.

[1] 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 Imazalil and Imazalil Sulfate Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, 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, provi ding as much specificity as possible regarding
the nature of the concern.

Water Quality:

Imazalil is not identified as a cause of impairme nt for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 16 In addition, no Total Maximum Daily Loads (TMDL) have been developed for imazalil. 17 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 18 The Agency invites submission of water quality data for this pesticide. To the extent possible, data shoul d conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: In clusion of Impaired Water Body and
Other Water Quality Data in OPP’s Registratio n Review Risk Assessment and Management

Process 19 in order to ensure they can be used quant itatively or qualitativel y in pesticide risk

assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to imazalil and imazalil sulfate 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.

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

17 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

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

19 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm15 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been
conducted for imazalil and imazalil sulfate. Th e ecological risk assessment planned during registration review will allow the Agency to de termine whether use of imazalil has “no effect” or “may affect” federally listed threatened or endang ered species (listed species) or their designated
critical habitats. When an assessment conclude s that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Ag ency will consult with the U.S. Fish and Wildlife
Service and/or National Marine Fisheries Service (the Serv ices), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent registration decision for imazalil, EPA reviewed these data and selected the most sensitive endpoint s for relevant risk assessment scenarios from the existing hazard database. Imazalil sulfate was registered in 2004 on the basis of risk assessments previously conducted for imazalil. As required by FFDCA section 408(p), both imazalil and imazalil sulfate are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 pest icide active ingredient s and 9 inert ingredients. A second list16 of chemicals identified for EDSP sc reening was published on June 14, 2013 20 and includes some pesticides scheduled for registration review and chemicals found in water

. 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, pleas e visit our website. 21

HUMAN STUDIES:

Occupational

Past imazalil risk assessments rely in part on da ta from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Imazalil sulfate was registered in 2004 on the ba sis of assessments previously conducted for imazalil. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pestic ide Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Databa se. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databa ses, 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 prevai ling at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subj ects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on
these studies.

20 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

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