2

Zoxamide Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY................................................................... 6

CHEMICAL FACTS ...................................................................................................................... 6

USE AND USAGE INFORMATION............................................................................................ 7

RECENT ACTIONS....................................................................................................................... 8

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW................................ 8

TIMELINE.................................................................................................................................... 10

NEXT STEPS ............................................................................................................................... 10

Appendix – Additional Areas Considered in the Zoxamide Registration Review ................... 11

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Registration Review Problem Formulation for Zoxamide. R. Sternberg and F. Khan. May 

20, 2014.

2. Human Health Scoping Document in Support of Registration Review. N. Tsaur, V. Chen, 

and M. Negussie. June 4, 2014.

3. Zoxamide: Tier I Review of Human Incidents. E. Evans and S. Recore. February 11, 2014.

4. BEAD Chemical Profile (BCP) for Registration Review: Zoxamide. C. Chen, C. PaisleyJones and A. Lee. April 16, 2014.

5. Zoxamide (101702) Screening Level Usage Analysis (SLUA). April 22, 2013.

6. EFED Label Data Report. March 20, 2014
3

7. HED Master Label Report. March 20, 2014

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

the docket EPA-HQ-OPP-2014-0391 at http://www.regulations.gov.
4

OVERVIEW

The docket for zoxamide is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP-2014-0391). 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 onions (dry bulb), garlic, and 

shallots is currently under review by the Agency. Zoxamide products are used primarily in 

agricultural areas; zoxamide products have no registered residential uses. This Preliminary Work 

Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about zoxamide, 

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 zoxamide.

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 zoxamide and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on zoxamide. 

The Agency encourages all interested stakeholders to review the PWP and Appendix and to 

provide comments and additional information that will help the Agency’s decision-making process 

for this chemical. In addition to general areas on which persons may wish to comment, there are 

some areas identified in the PWP and Appendix about which the Agency specifically seeks 

comments and information. Interested stakeholders could include: environmental non-profit or 

interest groups; pesticide manufacturers; agricultural labor or commodity groups; commercial, 

institutional, residential, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for zoxamide. 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 zoxamide. 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.
5

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for zoxamide. For additional discussion of the 

anticipated data needs, see the Registration Review Problem Formulation for Zoxamide and 

Human Health Scoping Document in Support of Registration Review.

Table 1: Anticipated Data Needs for the Zoxamide Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Zoxamide

835.4100 Aerobic soil metabolism (two soils) TGAI/PAIRA2 24

835.4400 Anaerobic aquatic metabolism (two sediments) TGAI/PAIRA2 24

850.1735 Whole sediment acute toxicity invertebrates 

(freshwater) – 2 species3 TGAI 12

850.1740 Whole sediment acute toxicity invertebrates

(marine) – 1 species4 TGAI 12

850.2100 Avian acute oral toxicity test, passerine5 TGAI 12

850.4100 Seedling emergence and seedling growth (two 

species6)

TEP 12

Non-GLN Acute honey bee larvae feeding study5,7 TGAI 12

Outstanding Data Requirements from Conditional Registration(s)8

860.1380 Storage stability study9 TGAI --

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

 

1 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

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

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

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

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

6 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.

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

8 The study listed in this section was previously required as a condition of registration and is still outstanding. 

Storage stability data (Guideline 860.1380) for tomatoes were previously required as a condition of registration 

(T. Alston, DP274785, 08/30/2001). This study will not be included in the anticipated Registration Review DCI

because it is already required as a condition of registration.

9 Specifically for tomatoes and cucurbits
6

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.

10

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 zoxamide.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Zoxamide

PC code 101702

Case Number 7032

CAS Number 156052-68-5

Year first registered 2001

Pesticide Type Fungicide

Chemical class Non-systemic, broad-spectrum benzamide fungicide; FRAC group 

22 (low to medium risk for resistance development)

Reregistration Eligibility 

Decision (RED)

Because it was registered after November 1984, zoxamide was not 

subject to reregistration.

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not applicable. There is no record of a TRED.

 

10 http://www.epa.gov/oppsrrd1/registration_review/
7

Table 2: Chemical Facts for Zoxamide

Cumulative group Not applicable. EPA has not assumed that zoxamide has a common 

mechanism of toxicity with other substances.

40 CFR Citation Tolerances for zoxamide are established in 40 CFR §180.567. 

Tolerances for zoxamide are established in grapes, grapes (raisins), 

tomato, and vegetable (cucurbit group 9). Tolerances for combined 

residues of zoxamide and metabolites are established in potato, 

potato (granules/flakes), potato (wet peel) and proposed in onion 

(subgroup 3-07A).

Dual-use Zoxamide 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 zoxamide.

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Tanja Crk

crk.tanja@epa.gov

(703) 308-8202

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 zoxamide. Please see the BEAD Chemical 

Profile (BCP) for Registration Review: Zoxamide in the registration review docket for more 

details.

Table 3: Zoxamide Use and Usage Information

Summary of Use Broad-spectrum fungicide registered for use on potatoes, tomatoes, 

cucurbits, and grapes. 

Use Sites Agricultural use sites. There are no registered non-agricultural 

uses. 

Summary of Usage Zoxamide usage averaged approximately 11,000 pounds of a.i. 

annually on approximately 80,000 acres of surveyed agricultural 

land (2003-2012). Applications to potatoes account for the 

majority of usage across this time period.

The average a.i. rate for all agricultural crops from 2008-2012 was 

0.16 lbs per acre. The top crops with the highest average a.i. rate 

(i.e., 0.17 lbs per acre) are tomatoes and pumpkins.

Formulation Type(s) Zoxamide is formulated as an 80% wettable powder in water 

soluble packets (Zoxium® 80WSP; Reg. No. 10163-6413), and an 

8.3% water dispersible granule co-formulated with mancozeb, 

66.7% (Gavel ®75DF; Reg. No. 10163-6414). 

Application Method(s) Zoxamide can be applied with ground equipment, including 

chemigation, or by air. In addition to foliar applications, seed 

treatment is possible with Gavel ®75DF.
8

Table 3: Zoxamide Use and Usage Information

Technical Registrant(s) Gowan

No. of Registrations 3 Section 3 Products11: Reg. No. 10163-6413 (TEP), -6414 (TEP), 

-6415 (TGAI)

0 Section 24c Registrations

Restricted Use No

Additional areas of use and usage related information requested for this registration review, 

and of particular interest to EPA, are described below.

 Any future use/usage data on crops such as grapes, which currently have no usage reported 

in Proprietary Data.

RECENT ACTIONS

A new use request on onions (dry bulb), garlic, and shallots is under review.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment was conducted based on current 

risk and exposure assessment policies and do not indicate risk estimates of concern. The most 

recent ecological and environmental fate risk assessment was completed in 2013. Findings and 

conclusions from these risk assessments are summarized in the Registration Review Problem 

Formulation for Zoxamide and Human Health 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 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 

transport characterization of non-residential uses of zoxamide. Furthermore, during the 

Registration Review process, HED will evaluate whether or not the US is able to harmonize

tolerances with Codex. 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 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home).
9

Table 4: 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 determined 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.
10

TIMELINE

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

review in Table 5 below.

Table 5: Projected Zoxamide Registration Review Timeline

Activities Estimated Date

Opening the Docket

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

Close Public Comment 2014 – August

Case Development

Final Work Plan 2014 – November

Issue DCI 2015 Jan. - March

Data Submission 2017 Jan. - March

60-day Public Comment Period for Draft Risk 

Assessments[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

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 zoxamide.

 

[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.
11

Appendix – Additional Areas Considered in the Zoxamide 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:

Zoxamide is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act.

12

 In addition, no Total Maximum Daily Loads (TMDL) 

have been developed for zoxamide.

13

 More information on impaired water bodies and TMDLs 

can be found at the Agency’s website.

14 The Agency invites submission of water quality data 

for this pesticide. To the extent possible, submissions should include the key data elements noted 

in the OPP Guidance for Submission of State and Tribal Water Quality Monitoring Data15 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 zoxamide 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.

ENDANGERED SPECIES:

 

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

13http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

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

15 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
12

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

conducted for zoxamide. The ecological risk assessment planned during registration review will 

allow the Agency to determine whether use of zoxamide 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 most recent registration decision for zoxamide, 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), zoxamide 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, 201316 and includes some 

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. 

 

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

chemicals.
13

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.17

HUMAN STUDIES:

Occupational

Past zoxamide 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) and the Agricultural Reentry 

Task Force (ARTF) 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.

 

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