Docket Number EPA-HQ-OPP-2014-0391 

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INTRODUCTION 

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review1

 of zoxamide. Zoxamide is a non-systemic broad-spectrum benzamide 

fungicide registered for use to control fungicidal diseases (e.g., spot, downy mildew, rot, blight, 

mold, blotch) on select fruit and vegetable crops; zoxamide is registered for use on cucurbit 

vegetables (melons, pumpkin, squash, and watermelon), grapes, potatoes (white/Irish), and 

tomatoes. The proposed new use of zoxamide on the crop group onion, bulb, subgroup 3-07A was 

approved by the Agency in August 2014. Zoxamide products are used primarily in agricultural 

areas; zoxamide products have no registered residential uses. This work plan addresses public 

comments received concerning the Preliminary Work Plan (PWP), which was posted in the 

zoxamide registration review docket (EPA-HQ-OPP-2014-0391) in June 2014. 

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. Changes in science, public policy, and pesticide use practices occur over time. The 

registration review program is intended to make sure that, as the ability to assess risk evolves and 

as policies and practices change, all registered pesticides continue to meet the statutory standard. 

The public phase of registration review begins when the initial docket is opened for each case. 

Information on this program is provided on the Agency’s website.1

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

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

needs, expected risk assessments, or the estimated timeline identified in the PWP, and a summary 

of the Agency’s responses to those comments. This section is followed by registration review 

planned data needs, risk assessments expected to be conducted, and the projected registration 

review timeline for zoxamide. Lastly, there is a discussion of next steps. 

UPDATES SINCE THE PWP WAS ISSUED 

Updates on zoxamide since the June 2014 PWP include: 1) the proposed new use of zoxamide on 

the crop group onion, bulb, subgroup 3-07A was approved by the Agency in August 2014; and 2) 

the storage stability data on the cucurbit and tomato have been reviewed and determined to be 

acceptable (i.e., MRIDs 45633801, 45633802 and 45639001). 

SUMMARY OF COMMENTS AND AGENCY RESPONSES 

During the 60-day public comment period on the zoxamide Preliminary Work Plan, which opened 

on June 25, 2014 and closed on August 25, 2014, the Agency received public comments from three 

stakeholders related to zoxamide. Comments were submitted by the Center for Biological 

Diversity, the FIFRA Endangered Species Task Force and the Western Integrated Pest 

Management Center. The comments do not address the timeline described in the PWP, but they 

do address the planned ecological and human health risk assessments. In the PWP, EPA also 

solicited comments on the specific topics of environmental justice, water quality concerns, and 

 

1 http://www.epa.gov/oppsrrd1/registration_review/ 
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trade irritants. Comments on water quality concerns were expressed (though no data was 

submitted) by the Center for Biological Diversity. California pesticide use report data for 2012 

were provided by the Western Integrated Pest Management Center. No comments or information 

were received on the remaining issues. 

Summarized below are public comments that are of a broader regulatory nature. Public comments 

in their entirety are located in the docket, EPA-HQ-OPP-2014-0391. 

Comment/Response to the Center for Biological Diversity in EPA-HQ-OPP-2014-0391-0010 

Comment: The Center for Biological Diversity’s (CBD) comments focus on the EPA’s duty to 

consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the 

Services) on the registration review of zoxamide in accordance with the Endangered Species Act 

(ESA). The CBD comments mention various aspects of the risk assessment process, including use 

of the best available data to develop endangered species risk assessments, and evaluation of effects 

on endangered and threatened species and their designated critical habitat. CBD also expresses 

concern regarding the rigor of the Agency’s preliminary determinations regarding the effects of 

zoxamide on endangered and threatened (listed) species and their designated critical habitat for 

the zoxamide registration review. 

Response: EPA has reviewed the comments from CBD on the registration review docket opening 

for zoxamide and plans to address many of the concerns raised by CBD as part of the 

implementation plan for assessing the risks of pesticides to listed species based on the 

recommendations of the April 2013 National Academy of Sciences (NAS) report. EPA will 

address concerns specific to zoxamide in connection with the development of its final registration 

review decision for this pesticide. 

In November 2013, the EPA, along with the Services and the USDA, released a summary of their 

joint Interim Approaches for assessing risks to endangered and threatened (listed) species from 

pesticides. The Interim Approaches were developed jointly by the agencies in response to the 

NAS recommendations and reflect a common approach to risk assessment shared by the agencies 

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

outlines recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that EPA and the Services must conduct in connection with their 

obligations under the ESA and FIFRA. 

The joint Interim Approaches were released prior to a stakeholder workshop held on November 

15, 2013. In addition, the EPA presented the joint Interim Approaches at the December 2013 

Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues Research and Evaluation 

Group (SFIREG) meetings. The agencies also held a stakeholder workshop in April 2014, allowing 

additional opportunities for stakeholders to comment on the Interim Approaches. Additional 

workshops are planned to enhance stakeholder involvement. As part of a phased, iterative process 

for developing the Interim Approaches, the agencies will also consider public comments on the 

Interim Approaches in connection with the development of upcoming registration review 

decisions. The details of the joint Interim Approaches are contained in the white paper, Interim 

Approaches for National-Level Pesticide Endangered Species Act Assessments Based on the 
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Recommendations of the National Academy of Sciences April 2013 Report, dated November 1, 

2013. 

Given that the agencies are continuing to develop and work toward implementation of the Interim 

Approaches to assess the potential risks of pesticides to listed species and their designated critical 

habitat, the ecological problem formulation supporting this Final Work Plan for zoxamide does 

not describe the specific ESA analysis, including effects determinations for specific listed species 

or designated critical habitat, to be conducted during registration review. In the ecological problem 

formulation document for zoxamide, EPA described the screening-level risk assessment to 

determine the potential effects of zoxamide on all taxa of non-target wildlife and plants, which 

will assume that listed species and their designated critical habitats may be present in the vicinity 

of the application of zoxamide. This screening-level assessment will allow EPA to focus its future 

evaluations on the types of species where the potential for effects exists once the scientific methods 

being developed by the agencies have been fully vetted. While the agencies continue to develop a 

common method for ESA analysis, the planned screening-level risk assessment for the registration 

review of zoxamide will describe the level of ESA analysis completed for this particular 

registration review case. Once the agencies have fully developed and implemented the scientific 

methods necessary to complete risk assessments for endangered and threatened (listed) species and 

their designated critical habitats, these methods will be applied to subsequent analyses for 

zoxamide as part of completing this registration review. 

Comments submitted by FIFRA Endangered Species Task Force in EPA-HQ-OPP-2014-

0391-0012. FESTF submitted a memo with a list of studies that “fulfill data requirements spelled 

out in Pesticide Registration Notice 2000-2 and provide the best available data necessary to support 

the analysis of zoxamide use and listed species locations and potential exposure.”

Comment: FESTF submitted a comment informing the Agency that the technical registrant of 

zoxamide is a member of the FESTF (or a company having met its data compensation 

obligations) and is entitled to rely on FESTF data. 

Response: The Agency thanks FESTF for its comment and will take this under consideration. 

Comments submitted by Western Integrated Pest Management Center in EPA-HQ-OPP2014-0391-0013 

Comment: The USDA Office of Pest Management Policy has submitted California’s pesticide 

use report data for 2012 on a multiple active ingredient product (Gavel ® 75 DF Fungicide). 

Response: The Agency thanks the Western IPM Center for its comment and will take this under 

consideration. 

PLANNED DATA NEEDS 

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

Problem Formulation for Zoxamide and Human Health Scoping Document in Support of 

Registration Review. The table has been updated since the PWP to reflect completion of recent 
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data reviews by the Agency for the outstanding storage stability studies originally listed in the 

PWP. The data were acceptable. 

Table 1: Anticipated Data Needs for the Zoxamide Registration Review 

Guideline 

Number2 Study Title2 

Test Material 

Estimated 

Timeframe 

(Months from 

receipt of DCI) 

Anticipated Data Needs for the Parent Zoxamide

835.4100 Aerobic soil metabolism (two soils) TGAI/PAIRA3 24 

835.4400 Anaerobic aquatic metabolism (two sediments) TGAI/PAIRA3 24 

850.1735 Whole sediment acute toxicity invertebrates 

(freshwater) – 2 species4 TGAI 12 

850.1740 Whole sediment acute toxicity invertebrates 

(marine) – 1 species5 TGAI 12 

850.2100 Avian acute oral toxicity test, passerine6 TGAI 12 

850.4100 Seedling emergence and seedling growth (two 

species7

) TEP 12 

Non-GLN Acute honey bee larvae feeding study8 TGAI 12 

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

RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, the Agency anticipates the need to conduct a comprehensive ecological 

risk assessment, including an endangered species assessment, for all uses of zoxamide. For human 

health, EPA does not anticipate the need to conduct revised dietary and occupational risk 

assessments during registration review. An updated residential exposure assessment will be 

required if spray drift and volatilization risk assessments are deemed necessary for off-site 

 

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 3

 Test substance should be technical grade or a pure active ingredient radiolabelled 

4

 Acute sediment tests with the midge Chironomus dilutus and freshwater amphipod Hyalella azteca 5

 Acute sediment test with the estuarine/marine amphipod Leptocheirus plumulosus 6

 The anticipated DCI will require submission of a protocol prior to study initiation. 

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 Seedling emergence testing is anticipated for corn and ryegrass only. For corn, a study that defines a NOAEC (i.e., 

a concentration that is not statistically different from the negative control for all assessed endpoints) is needed. For 

ryegrass, a Tier II test is anticipated to be needed. 

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 For reference material on the screening-level risk assessment process for honey bees, see the following: 

“White Paper in Support of the Proposed Risk Assessment Process for Bees” as submitted to the FIFRA Scientific 

Advisory Panel: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0543-0004 

Guidance on assessing risks to pollinators: http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf
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transport characterization of non-residential uses of zoxamide. 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. Furthermore, during the Registration Review process, 

EPA will evaluate whether or not the US is able to harmonize tolerances with Codex. 

Table 2 below summarizes the anticipated registration review risk assessments based on the 

Registration Review Problem Formulation for Zoxamide and Human Health Scoping Document 

in Support of Registration Review. 
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Table 2: Anticipated Risk Assessments for the Zoxamide Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecological and Environmental Fate 

Comprehensive ecological 

including endangered species 

Yes Species to be assessed include terrestrial and aquatic 

organisms. 

The assessment will be quantitative, whereby all 

degradates will be included in the total toxic residues 

approach. 

Incidents Will check for 

updates 

For a discussion of ecological incident databases see 

page 17 of the Problem Formulation. Currently, there 

are no reported ecological incidents. 

Human Health 

Dietary 

Food No Dietary (food and drinking water) exposure 

assessment did not exceed the level of concern for the 

general U.S. population, infants, and children. 

Updated drinking water and dietary exposure risk 

assessments are not anticipated to be needed at this 

time. 

Drinking water 

Occupational 

Handlers (mixers, loaders, 

applicators) 

No Existing occupational handler dermal exposure and 

risk assessments reflect current policy and procedures 

for the existing agricultural uses. Updates are not 

anticipated to be needed at this time. 

Post-application 

Residential 

Handlers No An updated residential exposure assessment may be 

required if spray drift and volatilization risk 

assessments are deemed necessary for off-site 

transport characterization of non-residential uses of 

zoxamide 

Post-application 

Other 

Aggregate No Evaluates the combined risk from dietary and 

residential exposures. 

Cumulative No EPA has not assumed that zoxamide has a common 

mechanism of toxicity with other substances 

Tolerances No During the Registration Review process, HED will 

evaluate whether or not the US is able to harmonize 

with Codex. 

Incidents Will check for 

updates 

For a discussion of human incident information for 

zoxamide, see page 6 of the Scoping Document and 

the Zoxamide: Tier I Review of Human Incidents. 

Currently, there are no reported human incidents. 
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TIMELINE 

EPA has created the following estimated timeline for the completion of the zoxamide registration 

review in Table 3 below. 

Table 3: Registration Review for Zoxamide – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period June 2014 – Completed 

Close Public Comment Aug. 2014 – Completed 

Case Development 

Final Work Plan Dec. 2014 - Completed 

Issue DCI 2015: Jan.- March 

Data Submission 2017: Jan.- March 

60-day Public Comment Period for Draft Risk Assessments9[1] 2018: July – Sept. 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration Review 

Decision 

2019: April - June 

Registration Review Decision and Begin Post-Decision Follow-up 2020 

Total (years) 6 

NEXT STEPS 

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

and human health studies for zoxamide through a Data Call-In Notice, expected to be issued in 

Jan-March 2015. 

 

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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.