Docket Number EPA-HQ-OPP-2014-0133 

www.regulations.gov 

Etoxazole Final Work Plan 

Registration Review 

Case Number 7616 

February 2015 

Approved by: <;i'hu~P ~_,)l 

Date: 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 
INTRODUCTION 

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

the registration review of etoxazole. This work plan addresses public comments received 

concerning the Preliminary Work Plan (PWP), which was posted in the etoxazole registration 

review docket (EPA-HQ-OPP-2014-0133). Etoxazole is a member ofthe diphenyloxazoline 

class of miticides/ovicides. Products containing etoxazole are registered for use to control mites 

on various agricultural sites and ornamentals. There are currently no registered or proposed 

residential uses of etoxazole. 

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 etoxazole. Lastly, there is a discussion of next steps. 

UPDATES SINCE THE PWP WAS ISSUED 

The Etoxazole Preliminary Work Plan identified a 24 month timeframe to conduct the Honey 

Bee- Adult Chronic Oral Toxicity test for registration review. The Agency upon further review 

has determined that the required timeframe to conduct this test is 12 months. 

SUMMARY OF COMMENTS AND AGENCY RESPONSES 

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

opened on September 24, 2014 and closed on November 24, 2014, the Agency received three 

public comments. Comments were submitted by Valent U.S.A. Corporation, the FIFRA 

Endangered Species Task Force (FESTF), and the Center for Biological Diversity (CBD). 

The comments from Valent U.S.A Corporation addressed data requirements, differences in 

interpretations of data, and use and usage information. The comments from FESTF identified 

Valent U.S.A Corporation as a member ofthe Task Force. CBD comments focused on the 

EPA's duty to consult the U.S. Fish and Wildlife Service and the National Marine Fisheries 

Service (the Services) in accordance with the Endangered Species Act (ESA). None of the 

submitted comments address the timeline described in the PWP, but some do address the planned 

1 http://www.epa.gov/oppsrrd 1 /registration _review/ 

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ecological and human health risk assessments and data requirements. EPA's responses to 

comments on the risk assessments and data needs, along with several other substantive 

comments, are provided in this document. In the PWP, EPA also solicited comments on the 

specific topics of environmental justice, water quality concerns, and trade irritants, but no 

comments or information were received on those issues. 

This section does not capture every comment made about the PWP and its supporting 

documents, nor all of the Agency's responses. Summarized below are public comments that 

resulted in changes to the anticipated registration review data needs, risk assessments, or 

timeline, or are of a broader regulatory nature. Public comments and EPA responses in their 

entirety are located in the docket, EPA-HQ-OPP-2014-0133. Summarized public comments and 

Agency responses related to the anticipated ecological risk assessment or data needs are in the 

Response to Public Comments on Registration Review Problem Formulation for Ecological Risk 

Assessment and Drinking Water Exposure Assessment to be Conducted for Etoxazole (January 

28, 20 15) while those relevant to the anticipated human health risk assessment or data needs are 

in the Etoxazole; Response to Comments from Valent Regarding HED's Most Recent Human 

Health Registration Review Scoping Document for Etoxazole (December 23, 2014). Comments 

relevant to etoxazole use/usage information are in the BEAD Response to Valent U. S.A. 

Corporation Comments on Etoxazole Use and Usage Information in U.S. EPA 's Etoxazole 

Registration Review Docket EPA-HQ-OPP-2014-0133 (December 16, 2014). 

Comments submitted by Valent U.S.A. Corporation in EPA-HQ-OPP-2014-0133-0012. 

1. Comment: A waiver of the 90-day inhalation toxicity study has been granted most recently 

for the greenhouse use pattern (Decision No. 447295; DP Barcode D388416). The date for 

this waiver document is incorrectly indicated as 21-Apr-201 0. The correct date is 21-Apr2011. The waiver was granted on the basis of large MOE's for product packaged in water 

soluble packages (all exceeding 1000), low exposures and low acute toxicity of the Valent 

formulated and TGA1 material. 

Response: On May 24, 201 4, the Health Effects Division's (HED) Hazard Science and 

Policy Council re-evaluated the earlier waiver granted for etoxazole subchronic inhalation 

data based on the current policy of employing a weight of evidence approach for such 

determinations (TXR#0056977). Based on that approach, HED recommended that the data 

be required. HED also has noted that the FQPA Safety Factor of lOX will be retained for the 

inhalation risk assessment in the absence of these data or other supporting information. 

2. Comment: Valent disputed the recommendations of the Environmental Fate and Effects 

Division (EFED) to require several ecological toxicity studies, and indicated that pollinator 

studies being conducted in response to EU data needs will be submitted to the Agency. 

Response: EFED expanded on the reasoning for its recommendations that the disputed data 

be required, and welcomed the submission of the European bee data, reiterating that studies 

examining the toxicity of etoxazole to honey bee brood are of particular interest since 

etoxazole is known to inhibit chitin biosynthesis. It is noted that any data developed in 

response to EU data needs will be evaluated by EPA to determine its suitability for use in the 

Agency's risk assessment. 

3 
3. Comment: Under "Use Sites" Valent requests to add the use of Popcorn and Field corn 

grown for seed. The use sites of alfalfa and carrots should be specified as "alfalfa grownfor 

seed only" and "carrots grown for seed only. " 

Response: BEAD has amended the BEAD Chemical Profile (BCP) to add popcorn, field 

com, alfalfa, and carrots grown for seed. The amended BCP has been posted to the 

etoxazole registration review docket. 

Comments submitted by FESTF in EPA-HQ-OPP-2014-0133-0011. 

4. Comment: Valent US.A. Corporation, the sole registrant of technical grade etoxazole, is a 

FESTF member and is entitled to rely on the FESTF data. 

Response: The Agency thanks FESTF for its comment, and will consider the FESTF data 

during the etoxazole registration review. 

Comments submitted by CBD in EPA-HQ-OPP-2014-0133-0010. 

5. Comment: The CBD 's comments focus on the EPA 's duty to consult with the US. Fish and 

Wildlife Service and the National Marine Fisheries Service (the Services) on the registration 

review of etoxazole 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 etoxazole on endangered and threatened (listed) species and their designated 

critical habitat for the etoxazole registration review. 

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

opening for etoxazole 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 ofthe April2013 National Academy of Sciences (NAS) report. EPA will 

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

registration review decision for etoxazole. 

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 National Academy of Sciences' (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 report2 outlines recommendations 

on specific scientific and technical issues related to the development of pesticide risk 

2 http://www.nap.edu/catalog.php?record _ id= 18344 

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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 stakeholder 

workshops in April and October 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 ESA Assessments Based on the Recommendations of the National 

Academy of Sciences April2013 Report,"3 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 Etoxazole 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 etoxazole, 

EPA described the screening-level risk assessment to determine the potential effects of 

Etoxazole 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 

Etoxazole. 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 etoxazole will describe the level ofESA 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 etoxazole as part of completing this registration review. 

PLANNED DATA NEEDS 

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

Review- Preliminary Problem Formulationfor the Ecological Risk Assessment and Drinking 

Water Exposure Assessment to Be Conducted for Etoxazole, Etoxazole. Human-Health 

Assessment Scoping Document in Support of Registration Review, Etoxazole; Response to 

Comments from Valent Regarding HED 's Most Recent Human Health Registration Review 

Scoping Document for Etoxazole, BEAD Response to Valent US.A. Corporation Comments on 

Etoxazole Use and Usage Information in US. EPA 's Etoxazole Registration Review Docket 

EPA-HQ-OPP-2014-0133, and the Response to Public Comments on Registration Review 

3 http://www.epa.gov/espp/20 13/nas.html 

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Problem Formulation for Ecological Risk Assessment and Drinking Water Exposure Assessment 

to be Conducted for Etoxazole. The planned data needs have not changed from what was 

included in the PWP. 

Table 1: Planned Data Needs for the Etoxazole Registration Review 

Estimated 

Guideline Study Title Timeframe 

Number" Test (Months from Material receipt of DCI) 

Planned Data Needs for Etoxazole (parent) 

835.4300 Aerobic Aquatic Metabolism (Two sediment TGAI 24 

systems should be tested) 

835.4400 Anaerobic Aquatic Metabolism (Two sediment TGAI 24 systems should be tested) 

850.2100 Avian Acute Oral Toxicity Test (with passerine TGAI 12 species)5 

Field Testing for Pollinators (Higher Tier 

850.3040 Toxicity Testing under semi-field or field TEP 24 

conditions)6

•

7 

850.4100 Seedling Emergence & Seedling Growth4

•

8 TEP 12 

850.4150 Vegetative Vigor4

•

8 TEP 12 

850.4500 Algal Toxicity (Freshwater green algae)4 TGAI 12 

850.4550 Cyanobacteria Toxicity (Anabaena jlos-aquae t TGAI 12 

Environmental Chemistry Methods and 

850.6100 Associated Independent Laboratory Validations TGAI 12 

in soi ~ water, and sediment 

Non- Honey Bee: 21-day, repeated dose, larval chronic TGAI 12 Guideline toxicity test6

•

7 

Non- Honey Bee Toxicity: 1 0-day Adult Chronic Oral TGAI 12 Guideline Toxicity Study6

•

7 

Non- Residues in Pollen and Nectar (Higher Tier TEP 36 Guideline Testing under semi-field or field conditions)6

•

7 

NonWhole sediment, chronic toxicity (60-Day) test to 

Guideline freshwater midge (Chironomus dilutus)6 (ORD TGAI 24 

Study Method: EPA 600/R-099-064) 

NonWhole sediment, chronic toxicity (42-Day) test to 

Guideline freshwater amphipod (Hyalella azteca)6 (ORD TGAI 24 

Study Method EPA 600/R-099-064) 

870.3465 90-Day inhalation Toxicity9 TGAI 24 

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Planned Data Needs for the Degradates R-8 and R-13 

Estimated 

Guideline Timeframe 

Number' Study Title Test (Months from Material receipt of DCI) 

Environmental Chemistry Methods and R-8 and 850.6100 Associated Independent Laboratory Validations R-13 12 

in soil, water, and sediment 

TGAI = Techmcal grade of the acttve mgred1ent; TEP = Typ1cal end-use product; 4 On June 27,2012, EPA announced certain revisions in harmonized guideline series 850 -Ecological Effects 

Tests- including renumbering and/or removal of the tier designation for some guideline studies. See "Final 

Test Guidelines; OCSPP 850 Series; Notice of Availability" 77 FR 38282, June 27, 20 12. 

htto://www .regulations.gov/#!documentDetail :0 ·EPA-HO-OPPT -2009-0 154-0028 5 Data are recommended for a passerine species. A protocol does not need to be submitted provided that the 

study adhere to the parameters outlined in the guidance available at: 

http://www .epa.gov/pesticides/science/efed/policy _guidance/team_ authors/terrestrial_ biology_ tech_ team/pass 

erine _ ocspp850 _ 2100 _avian_ oral_ tox.pdf 6 A protocol is expected to be submitted for review and approval by the Agency prior to initiation of this study. 7

on June 19, 20 14, new pollinator risk assessment guidance was provided for evaluating the potential risk of 

pesticides to bees, particularly honey bees (Apis rnellifera). The Agency risk assessment guidance for bees can 

be found at: http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance. 8 New studies are recommended at the highest maximum single application rate with TEP as test material instead 

of the TGAI. 

9This data requirement can be fulfilled with a 28-day study. 

RISK ASSESSMENTS FOR REGISTRATION REVIEW 

During registration review, the Agency will conduct a comprehensive ecological risk assessment, 

including an endangered species assessment, for all uses of etoxazole. For human health, EPA 

will conduct revised dietary, residential, and occupational risk assessments during registration 

review. If toxicological endpoints or points of departure are revised based on the data that are 

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 registration review risk assessments based on the 

Registration Review- Preliminary Problem Formulation for the Ecological Risk Assessment and 

Drinking Water Exposure Assessment to Be Conducted for Etoxazole and Etoxazole. HumanHealth Assessment Scoping Document in Support of Registration Review. The planned 

assessments have not changed from what was included in the PWP. 

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Table 2: Planned Risk Assessments for tbe Etoxazole Registration Review 

Type of Risk Assessment Conduct? Notes 

Eco~nGV.I and Eavironmental Fate 

Comprehensive ecological y The risk assessment will include parent 

(species to be assessed include etoxazole and the degradates R-8 and R-13, 

terrestrial and aquatic using the total toxic residue approach. 

organisms), including 

endangered species 

Incidents Will check For a discussion of reported ecological 

for updates incidents for etoxazole, see page 29 of the 

Problem Formulation. 

Human Health 

Dietary 

Food y A revised dietary exposure analysis may be 

needed to reflect the most recent dietary 

exposure models and relevant new data. 

Drinking water y The drinking water assessment will include 

the etoxazole parent and the degradates R-8 

and R -13. The assessment will reflect 

potentially revised estimated drinking water 

concentrations (EDWCs) and any relevant 

new data, as needed. 

Occupational 

Handlers (mixers, loaders, y An updated occupational handler risk 

applicators) assessment will be conducted to reflect all 

currently registered uses, new policies, and 

any relevant new data, as needed. 

Post-application y An occupational post-application risk 

assessment will be conducted to reflect all 

currently registered uses, new policies, and 

any relevant new data, as needed. 

Residential 

Handlers N There are no proposed or current registrations 

for products containing etoxazole that allow 

residential use. 

Post -application y A bystander risk assessment for exposures 

from drift will be conducted. A screen will be 

conducted so that the need for a volatilization 

assessment can be determined. 

Other 

Aggregate y Evaluates the combined risk from dietary and 

residential exposures. A new aggregate risk 

assessment will be required to incorporate a 

revised dietary risk assessment, if needed. 

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Table 2: Planned Risk Assessments for the Etoxazole Registration Review 

Cumulative N EPA has not made a common mechanism of 

toxicity finding for etoxazole and any other 

substances; and etoxazole does not appear to 

produce a toxic metabolite produced by other 

substances. 

Tolerances y EPA will evaluate the possibility of 

harmonizing tolerances with Canada and 

Codex MRLs. 

Incidents Will check For a discussion of reported human incidents 

for updates for Etoxazole, see page 10 of the Scoping 

Document and the Etoxazole: Tier I Review of 

Human Incidents. 

TIMELINE 

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

review in Table 3 below. The projected timeline has not changed since the PWP. 

Table 3: Registration Review for Etoxazole- Projected Registration Review Timeline 

Activities Estimated Date 

O_pening the Docket 

Open Docket and 60-day Public Comment Period September 2014- Completed 

Close Public Comment November 2014- Completed 

Case Development 

Final Work Plan February 2015- Completed 

Issue DCI April- June 2015 

Data Submission April - June 2018 

60-day Public Comment Period for Draft Risk AssessmentsY October- December 2019 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration July- September 2020 

Review Decision 

Registration Review Decision and Begin Post-Decision 2021 

Follow-up 

Total (years) 7 

9The regulattons governing Regtstration 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. 

NEXT STEPS 

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

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

between April and June 2015. 

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