2 INTRODUCTION

This is the Environmental Protection Agency’s (E PA or the Agency) Final Work Plan (FWP) for the registration review of imazalil (PC Code 111901) and imazalil sulfate (PC Code 111902). This work plan addresses public comments r eceived concerning the Preliminary Work Plan (PWP), which was posted in the imazalil re gistration review docke t (EPA-HQ-OPP-2013-0305). Imazalil is a systemic imidazole f ungicide registered for use for control of a variety of fungal pathogens. It is used for postharvest treatment of citrus fruits and bananas (imported), seed treatment of barley, whea t, 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 a nd equipment disinfection . Imazalil has no registered residential uses.

The Agency is implementing the registration revi ew 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 th e FIFRA standard for registration. Changes in scienc e, public policy, and pesticide us e practices occur over time. The registration review program is intended to make su re that, as the ability to assess risk evolves and as policies and practices change, al l registered pesticides continue to meet the statutory standard. The public phase of registration review begins wh en the initial docket is opened for each case. Information on this program is provided on the Agency’s website. 1

The FWP begins with any updates since the PWP wa s issued. Next is a summary of substantive comments received during the public comment peri od for the PWP concerning anticipated data needs, expected risk assessments, or the estimated timeline identified in the PWP, and a summary of the Agency’s responses to those comme nts. This section is followed by registration review planned data needs, risk assessments expected to be conducted, and the projected registration review timeline for imazalil and imazalil sulfate. Lastly, there is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

Since the publication of the PWP, GLN 850.3100 (Earthworm Subchronic Toxicity Test) has been removed from the list of data requireme nts for imazalil. The Agency has received a completed 14-day earthworm toxicity study 2 referenced by the European Food Safety Authority (EFSA) 3 and is not requesting a new earthworm study at this time. Also, incorrect guideline numbers appear in the PWP for the estuarine and freshwater whole sediment chronic invertebrate toxicity studies. The GLN nu mbers provided in the PWP are for acute rather than chronic toxicity studies, which are non-guideline. The FW P has been amended to reflect this correction.

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60-day public comment period on the Imazalil and Imazalil Sulfate Preliminary Work Plan, which opened on Dec 20, 2013 and closed on Feb 18, 2014, the Agency received 4 public

1 http://www.epa.gov/oppsrrd1/registration_review/
2 The toxicity of imazalil to earthworms. Toxicity of imazalil to Eisenia foetida in an artificial soil toxicity test. Janssen Pharmaceutica, Study No. R 23 979/L19, April 1986.

3 EFSA summary document viewable at http://www.efsa.europa.eu/en/efsajournal/doc/1526.pdf.3 comments. Comments on use and usage of imazalil were submitted by the Arizona Pest Management Center, California Citrus Qua lity Council, and the Washington State Pest Management Resource Service at Washington State University Tri-Cities (Western IPM Center). Comments from the Center for Biological Diversity provided information on accessing imazalil data relevant to the protection of endange red species. The comments do not address the regulatory timeline, the planned ecological and human health risk assessments described in the PWP, or anticipated data requirements for imazalil. In the imazalil PWP, EPA also solicited comments on the specific topics of environmenta l justice, water quality concerns, and trade irritants, but no comments or inform ation were received on those issues.

No public comments resulted in changes to the an ticipated registration revi ew data needs, risk assessments, or timeline. Public comments in their entirety are located in the docket EPA-HQOPP-2013-0305. The Agency thanks all commenters for their comments and will consider the information supplied by them as EPA conducts the registration review and makes its registration review decision.

PLANNED DATA NEEDS Table 1 below summarizes the planned data needs for imazalil based on the Registration Review – Preliminary Problem Formulation for Ecolog ical Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Imazalil and Imazalil Sulfate and the Imazalil and Imazalil Sulfate: Human Health Assessment Scoping Document in Support of Registration Review. The 90-day inhalation toxicity study (GLN 870.3465) is required for both antimicrobial and conventional pesticide uses. All other studi es listed in this tabl e are for conventional pesticide uses.

Table 1: Planned Data Needs for the Imazalil & Imazalil Sulfate Registration Review 4

Guideline Number 5 Study Title Test Material Estimated Timeframe

(Months from receipt of DCI)

Imazalil – PC Code 111901 835.1410 Laboratory Volatility 6 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

4 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.

5 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests

– including renumbering and other designations or changes for some guideline studies. See “Final Test 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

6 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 Table 1: Planned Data Needs for the Imazalil & Imazalil Sulfate Registration Review 4

Guideline Number 5 Study Title Test Material Estimated Timeframe

(Months from receipt of DCI) 850.1400 Fish Early-Life Stage Toxicity Test (freshwater) TGAI 12

850.1730 Fish Bioconcentration Factor TGAI 12 850.2100 Avian Acute Oral Toxicity (passerine species) TGAI 12
850.3020 Honeybee Acute Contact Toxicity TGAI 12 850.6100 Environmental Chemistry Method and Associated Independent Laboratory Validation (soil only) TGAI 12

870.3465 90-day Inhalation Toxicity - Rat 7 TGAI 24

875.2100 Dislodgeable Foliar Residue (DFR) Dissipation 8 TEP 24

Nonguideline Honeybee Acute Oral Toxicity 9 TGAI 12

Nonguideline Whole Sediment Life Cycle Toxicity Test with Estuarine Invertebrates TGAI 24

Nonguideline Sediment Life Cycle Toxicity Test with Freshwater Invertebrates ( Chironomus dilutus or C. tentans ) TGAI 24

Nonguideline Sediment Life Cycle Toxicity Test with Freshwater Invertebrates ( Hyalella azteca ) TGAI 24

Imazalil Sulfate – PC Code 111902 835.1410 Laboratory Volatility 10 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

7 This study is required for both antimicrobial and conventio nal pesticide uses. All other studies listed in this table are for conventional pesticide uses.

8 This study is required for use in co nducting risk assessments for workers c ontacting treated ornamental plants in greenhouses. The requested test ma terial is imazalil (PC Code 111901).

9 EPA does not have a guideline for the honeybee acute oral study. However, the OECD 213 guideline could be used for protocol development. A protocol must be submitted to the Agency for review and approval prior to study inception. The draft protocol must be submitted to the Agency within 90 days of receipt of this DCI.

10 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 7.5 Table 1: Planned Data Needs for the Imazalil & Imazalil Sulfate Registration Review 4

Guideline Number 5 Study Title Test Material Estimated Timeframe

(Months from receipt of DCI)
850.1730 Fish Bioconcentration Factor TGAI 12 850.2100 Avian Acute Oral Toxicity (passerine species) TGAI 12
850.3020 Honeybee Acute Contact Toxicity TGAI 12 850.6100 Environmental Chemistry Method and Associated Independent Laboratory Validation (soil only) TGAI 12

870.3465 90-day Inhalation Toxicity - Rat 11 TGAI 24
Nonguideline Honeybee Acute Oral Toxicity 12 TGAI 12

Nonguideline Whole Sediment Life Cycle Toxicity Test with Estuarine Invertebrates TGAI 24

Nonguideline Sediment Life Cycle Toxicity Test with Freshwater Invertebrates ( Chironomus dilutus or C. tentans ) TGAI 24

Nonguideline Sediment Life Cycle Toxicity Test with Freshwater Invertebrates ( Hyalella azteca ) TGAI 24

Outstanding Data Requirements (f or Imazalil) from GDCI-111901-21683 13

860.1340 Residue Analytical Method (ILV-livestock commodities) 14 Residue of Concern Data received and currently

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

11 This study is required for both antimicrobial and conventio nal pesticide uses. All other studies listed in this table are for conventional pesticide uses.

12 EPA does not have a guideline for the honeybee acute oral study. However, the OECD 213 guideline could be used for protocol development. A protocol must be submitted to the Agency for review and approval prior to study inception. The draft protocol must be submitted to the Agency within 90 days of receipt of this DCI.

13 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 an ticipated Registration Review DCI because it is already required through the earlier DCI.

14 Only an ILV is required. An adequate residue analy tical method is available for determining the total toxic residues of imazalil in/on plant commodities but not in livestock commodities.6 RISK ASSESSMENTS FOR 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 conduct 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 2 below summarizes the planned registrati on review risk assessments based on the imazalil Problem Formulation and Scoping Document and the planned assessments have not changed from what was included in the PWP.

Table 2: Planned Risk Assessments for the Imazalil & 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 ecologi cal 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.7 Table 2: Planned Risk Assessments for the Imazalil & Imazalil Sulfate Registration Review
Type of Risk Assessment Conduct? Notes 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. Other 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

.8 TIMELINE

EPA has created the following estimated timeline for the completion of the imazalil registration review in Table 3 below. The projecte d timeline has not chan ged since the PWP.

Table 3: Registration Review for Imazalil and Imazalil Sulfate – Projected Registration Review Timeline Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period Dec. 2013 – Completed
Close Public Comment Feb. 2014 – Completed Case Development
Final Work Plan June 2014 - Completed Issue DCI 2014: July – Sept. Data Submission 2016: July – Sept. 60-day Public Comment Period for Draft Risk Assessments 7 [1] 2018: Jan. - March Registration Review Decision 60-day Public Comment Period fo r Proposed Registration Review
Decision 2018: Oct. – Dec.

Registration Review Decision and Begin Post-Decision Follow-up 2019 Total (years) 6

NEXT STEPS

As noted previously, the Agency plans to requir e several environmental fa te, ecological effects, and human health studies for imazalil through a Data Call-In Notice, expected to be issued in the fall of 2014.

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

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