UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 26-JUNE-2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Etoxazole. Human-Health Assessment Scoping Document in Support of Registration 

Review. 

PC Code: 1 07091 DP Barcode: D418224 

Decision No.: 488002 Registration No.: N/A 

Petition No.: N/ A Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/A Case No.: 7616 

TXR No.: N/A CAS No.: 153233-91-1 

MRID No.: N/A 40 CFR: §180.593 

FROM: Jennifer Tyler, hemis· J. ~ 1\ ~T~ JaclynPyne, Bio1ogist oi ~~ 4"7 / 

Anwar Y. Dunbar, Ph.D., harmac6fogist ~frt/' -%-- Z/W~ Risk Assessment Branch 1 (RAB 1 )/Health Effectfflivision (HED; 7509P) 

THROUGH: Charles 

George F. 

W. 

Kramer, 

Smith II

Ph.D.

I, Branch 

, Seni

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hie

Chemis

f c:=-~ ~~-.---=::::;;~IS-~ ----­

RABl!HED (7509P) 

TO: Julia Stokes 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached is HED's human-health risk assessment scoping document for etoxazole [2-(2,6-

difluorophenyl)-4-[ 4-( 1, 1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole] to support 

Registration Review. 

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Etoxazole Registrat~on Review Human-Health AssessmentJ oping Document 

Table of Contents 

Executive Summary ............................................................................ ............................................ 3 

1.0 Introduction .......................................................................................................................... 4 

2.0 Hazard Tdentification!foxicology ........................................................................................ 4 

3.0 Residue Chemistry ............................................................................................................... 6 

4.0 Dietary Exposure ................................................................................................................. 7 

5.0 Residential Exposure ........................................................................................................... 7 

6.0 Aggregate Risk Assessment. ................................................................................................ 8 

7.0 Occupational Exposure ........................................................................................................ 8 

8.0 Public Health and Pesticide Epidemiology Data ............................................................... 10 

9.0 Tolerance Assessment and International Harmonization .................................................. I 0 

10.0 Environmental Justice ........................................................................................................ 10 

11.0 Cumulative .............................................................. ........................................................... 10 

12.0 Human Studies ................................................................................................................... 11 

13.0 Risk-Assessment Updates, Data Deficiencies, and Label Revisions ................................. 11 

14.0 References .......................................................................................................................... 12 

Attachment 1: Chemical Identity Tables ..................................................................................... 13 

Attachment 2: Etoxazole Acute, Subchronic, and Chronic Toxicity Profile ............ ................... 14 

Attachment 3: Etoxazole Endpoint Selection Tables ................................................................... 18 

Attachment 4: Summary of Registered Uses ............................................................................... 19 

Attachment 5: Etoxazole IRLS Sheet. ................. ........................................................................ 20 

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Executive Summary

HED has prepared a scoping document to support Registration Review of etoxazole. Etoxazole 

is a contact acaricide/ovicide and is a member of the diphenyloxazoline class of 

insecticide/miticide. It is formulated as wettable powders (WPs), water-dispersible granules

(WDGs), emulsifiable concentrates (ECs), pressurized liquids, and pressurized gases. Etoxazole

is currently registered for use on a variety of crops and ornamentals as well as for use in 

commercial greenhouses. The current registrations include Special Local Need (SLN) 

registrations on carrots and alfalfa. There are no pending PRIA actions for etoxazole. The most 

recent quantitative human-health risk assessment was performed in 2011, and was for the use of 

etoxazole on field corn and popcorn (Memo, J. Tyler et al., 23-SEP-2011; D439804). 

HED has evaluated the status of the human-health risk assessments for etoxazole to determine 

whether sufficient data are available and whether any updates are needed to support Registration 

Review. HED has considered all available data and human-health risk assessments for etoxazole 

with respect to its toxicity, exposure, and usage databases, and the most updated Agency science 

policy and risk assessment methodologies to determine the scope of work necessary to support 

Registration Review.

The toxicity database for etoxazole is adequate for risk assessment as specified by the revised 

2007 40CFR Toxicology Data Requirements, with the exception of a subchronic inhalation 

toxicity study. During Registration Review, the endpoints, points of departure (PODs), and 

safety factors (SFs) used in the most recent human health risk assessments will be reconsidered 

based on current HED policy, the newly submitted data, and any identified data gaps.

The residue chemistry database is adequate to support current Registration Review requirements. 

Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the 

residue, and processing data are available to support the registered uses. Adequate methods are 

available for enforcement of the currently established tolerances. 

The dietary-exposure database is adequate to support current registration requirements. In the 

most recent risk assessment, chronic dietary exposures were not of concern to HED. However, 

as part of Registration Review, a revised dietary exposure analysis may be required to reflect the 

most recent dietary exposure models, potential revised estimated drinking water concentrations 

(EDWCs), and/or changes to the toxicological PODs.

There are no proposed or current registrations for products containing etoxazole that allow

residential use. Therefore, residential handler and conventional residential post-application 

exposure assessments will not be needed during Registration Review. A residential bystander 

risk assessment will be conducted.

There is sufficient information available to assess aggregate exposure. However, a new 

aggregate risk assessment will be required during Registration Review to incorporate revised 

dietary exposure analyses and/or residential exposure assessments. 

The occupational exposure database is adequate to support the Registration Review process for 

etoxazole. The most recent occupational handler and post-application exposure assessments are 

not reflective of current exposure policies and data, and did not identify risks of concern. HED 

has conducted occupational handler assessments for most of the occupational handler scenarios 

anticipated for the registered uses of etoxazole. However, during Registration Review, updated 
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occupational assessments will be conducted to reflect all currently registered uses, using current 

occupational/residential exposure (ORE) policies and/or updated if toxicological PODs as 

needed. 

The following data deficiency was identified for etoxazole:

 Toxicology: OCSPP Guideline # 870.3465, Subchronic Inhalation Toxicity Study. 

In addition, EPA anticipates conducting the following risk assessment updates during 

Registration Review:

 Toxicology: 

o Review of the submitted immunotoxicity, acute neurotoxicity, and subchronic 

neurotoxicity studies.

o Reevaluation of toxicity endpoint/dose selection, along with the Food Quality 

Protection Act (FQPA) SF based on current HED policy. 

 Residue Chemistry: 

o None.

 Dietary Exposure:

o Revised dietary exposure analysis to reflect the most recent dietary exposure 

models, potential revised EDWCs, and/or changes to the toxicological PODs. 

 Aggregate Exposure:

o New aggregate risk assessment to incorporate revised dietary exposure analyses 

and/or residential exposure assessments.

 Occupational/Residential Exposure: 

o Revised occupational handler inhalation assessments to reflect all potential 

exposure scenarios, as well as updated policies and exposure data.

o A spray drift assessment for bystanders will be conducted. A screen will be 

conducted so that the need for a volatilization assessment can be determined.

o Assessments for all uses may be updated if toxicological PODs are revised. 

1.0 Introduction

Etoxazole is a contact acaricide/ovicide and is a member of the diphenyloxazoline class of 

insecticide/miticide. It is formulated as WPs packaged in WSPs, WDGs, ECs, pressurized 

liquids, and pressurized gases. It is currently registered for use on a variety of crops and 

ornamentals as well as for use in commercial greenhouses. The current registrations include 

SLN registrations on carrots and alfalfa. There are no pending PRIA actions for etoxazole. The 

most recent quantitative human-health risk assessment was performed in 2011, and was for the 

use of etoxazole on field corn and popcorn (Memo, J. Tyler et al., 23-SEP-2011; D439804). 

2.0 Hazard Identification/Toxicology

Etoxazole was rapidly absorbed from the G.I. tract of rats following oral dosing. Maximum 

concentrations of radioactivity in plasma were observed within 2-4 hours of dosing for the lowdose group (5 mg/kg) and within 4-6 hours of dosing for the high-dose group (500 mg/kg). The 

half-life of etoxazole was longer in females at the low dose in comparison to males (88.8 

compared to 71.4 hours). In the high-dose groups, the half-life was longer in males in 

comparison to females (44.4 compared to 28.2 hours). Excluding the G.I. tract, concentrations of 
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radioactivity over time were generally highest in liver, lymph nodes, thyroids, and fat, and were 

lowest in brain for both sexes in each dose group. For both low- and high-dose rats, fecal 

excretion was the primary route of elimination and excretion was essentially complete within 

120 hours of dosing for both groups. With the exception of minor urinary metabolites, the 

metabolite profile in excreta was qualitatively similar between the sexes, and etoxazole was 

eliminated primarily in the feces as parent compound.

The liver is the target organ in mice, rats, and dogs through the oral route. In a 90-day toxicity 

study in dogs, increased liver weights and centrilobular hepatocellular swelling in the liver were 

observed. Similar effects were observed in a chronic toxicity study in dogs at similar doses, 

indicating that the systemic effects (mainly liver effects) occur at similar dose levels following 

short-through long-term exposure without increasing in severity. In a 90-day toxicity study in 

mice, hepatotoxicity, such as increased relative liver weight, liver enlargement, and centrilobular 

hepatocellular swelling, were observed at high doses.

Similar effects were observed at the high dose in a mouse carcinogenicity study. Subchronic and 

chronic toxicity studies in rats also produced similar effects (increased liver weights, 

centrilobular hepatocellular swelling, etc.) as seen in mice and dogs. In addition, slight increases 

in thyroid weights and incisors were observed in subchronic and chronic toxicity studies in rats 

at high doses and at terminal stages of the study. 

No quantitative or qualitative evidence of increased susceptibility was seen following in utero

exposure to rats or rabbits in developmental studies. Offspring toxicity was qualitatively more 

severe (pup mortality) than parental toxicity (increased liver and adrenal weights) at the same 

dose in the rat reproduction study. 

No toxicity was seen at the limit dose in a 28-day dermal toxicity study in rats. There is no 

evidence of immunotoxicity or neurotoxicity in any study reviewed thus far. 

HED’s Hazard Identification Assessment Review Committee (HIARC) classified etoxazole as 

“not likely” to be carcinogenic. This decision was based on weight of evidence such as the lack 

of carcinogenicity in two studies in mice, lack of carcinogenicity in one study in rats, and the 

lack of hormonal and reproductive effects in special studies. Etoxazole was not mutagenic.

Etoxazole has low acute toxicity (Toxicity Categories III and IV) via the oral, dermal, and 

inhalation routes. It is not an eye or dermal irritant or a dermal sensitizer. 

In the last risk assessment, three toxicity data gaps were identified: (1) an immunotoxicity study; 

(2) an acute neurotoxicity study; and (3) a subchronic neurotoxicity study. All three studies have 

been submitted to the agency and are pending formal review. Preliminary review suggests that 

they will not impact the endpoints for risk assessment. There is no repeated-dose inhalation 

study available for etoxazole. The agency granted a waiver for this study (Memo, A. Dunbar et 

al., 21-APR-2010; D388416). To be consistent with current practices, the Hazard Science and 

Policy Council (HASPOC) was asked to re-evaluate the need for a repeated-dose inhalation 

toxicity study for etoxazole. Using a weight of evidence approach, the HASPOC concluded that 

a subchronic inhalation study is required at this time, although HED recommends that in the 

absence of such information, a requirement for handlers of the Zeal® WDG Miticide product to 

use PF5 respirators may be adequate to address concerns about inhalation exposure (Memo, U. 

Habiba; TXR # 0056977).
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Conclusions: The toxicity database for etoxazole is adequate for risk assessment as specified by 

the revised 2007 40 CFR Toxicology Data Requirements, with the exception of a subchronic 

inhalation study. During Registration Review, the previously submitted immunotoxicity, acute 

neurotoxicity, and subchronic neurotoxicity studies will be reviewed and the endpoints, PODs, 

and SFs used in the most recent human-health risk assessments will be reconsidered based on 

current HED policy, the newly submitted data, and any identified data gaps.

3.0 Residue Chemistry

Permanent tolerances are established for residues of etoxazole in/on a variety of crops and 

livestock commodities at levels ranging from 0.01 ppm to 20 ppm (40 CFR §180.593 (a)). There 

are currently no tolerances established for etoxazole for indirect/inadvertent residues in rotational 

crops.

Adequate methods are available for enforcing the current plant and livestock tolerances. In all 

available magnitude of the residue and processing studies, samples were analyzed using either 

the current enforcement methods or a slightly modified version of current enforcement methods. 

All enforcement methods have been forwarded to the Analytical Chemistry Laboratory (ACL)

for Agency petition method validations (PMVs) (Memos, J. Tyler, 6/17/03; D290912 and 

D290914). These methods were deemed adequate by ACL for tolerance enforcement (personal 

communication, C. Stafford to D. Vogel, 11/5/07). Food and Drug Administration (FDA) 

multiresidue methods (MRMs) may be used to determine residues of etoxazole in fatty and nonfatty matrices and to determine residues of Metabolite R-3 in nonfatty matrices. The results of 

the MRM testing were forwarded to the FDA for inclusion in the Pesticide Analytical Method 

(PAM) Vol. I (Memo, J. Tyler, 6/17/03; D290919).

The nature of the residue in plants and livestock is adequately understood based on available 

metabolism studies. The HED Metabolism Assessment Review Committee (MARC) concluded 

that only parent should be included in the tolerance expression for all plant commodities (Memo, 

J. Tyler, 4/23/03; D288817). For risk assessment purposes, only parent will be considered for 

most plant commodities; however, Metabolite R-3 (N-(2,6-difluorobenzoyl)-4-tert-butyl-2-

ethoxybenzamide) should also be included in the risk assessment for cotton gin byproducts and 

almond hulls (Memo, J. Tyler, 07/29/2003; DP#291694 and Memo, J. Tyler, 11/06/2007; 

DP#346200). For livestock commodities, the HED MARC concluded that, for ruminant muscle, 

fat, and milk, the residue of concern for tolerance expression and risk assessment is parent only. 

For ruminant liver and kidney, the residue of concern for tolerance expression is parent only, but 

both parent and Metabolite 1 (2-amino-2-(2-ethoxy-4-(1-hydroxycarbonyl-1-

methylethyl)phenyl) ethanol) should be included in the risk assessment. For poultry, the MARC 

concluded that Metabolite R-16 (2-methyl-2-{3-ethoxy-4-[2-(2,6-difluorophenyl)-4,5-dihydro1,3-oxazol-4-yl] phenyl}propionic acid) will likely to have similar toxicity to the parent; and, 

therefore, should be included in the risk assessment for liver and egg whites. Parent only is 

needed for tolerance expression.

Adequate field trial and processing data are available to support the use of etoxazole on the 

registered crops. An adequate number of trials were conducted in the appropriate geographical 

regions using the appropriate formulation applied at the maximum use rate. Registration 

requirements for magnitude of the residue in meat, milk, poultry, and eggs are fulfilled. 

These studies are also supported by adequate storage stability data. 
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Adequate confined and field rotational crop data are available to support the registered uses of 

etoxazole. HED previously concluded that the residue of concern in rotated crops is etoxazole

(Memos, J. Tyler, 9/23/11; D385940; J. Tyler, 7/31/03; D283737; J. Tyler et al, 8/7/03; D292548 

and J. Tyler, 4/6/05; D307178). 

Conclusions: The residue chemistry database is adequate to support current Registration Review 

data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage 

stability, magnitude of the residue, and processing data are available to support the registered 

uses. Adequate methods are available for enforcement of the currently established tolerances. 

4.0 Dietary Exposure

In conjunction with the most recent human-health risk assessment, a chronic dietary exposure 

assessment was conducted for the general U.S. population and various population subgroups 

using the Dietary Exposure Evaluation Model software with the Food Commodity Intake 

Database DEEM-FCID, Version 2.03 that incorporates consumption data from USDA’s 

Continuing Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and 1998. The 

assessment was unrefined, using HED-calculated residues of concern (parent and metabolites of 

concern) for livestock commodities and HED-recommended tolerance-level residues for all other 

commodities; 100% crop treated (CT) information for all commodities; empirical processing 

factors for apple juice, grape juice and raisins and 1.0x or the DEEM-FCID (ver 7.81) default 

factors were assumed for all other processed commodities.

The HED MARC concluded that the residue of concern in drinking water is the parent and two 

major metabolites, R-8 and R-13 (HED MARC, 23-APR-2003, DP D288817). Other 

metabolites identified were present at low levels, and are not expected to be more toxic than the 

parent. The Environmental Fate and Effects Division (EFED) provided Tier 1 EDWCs of 

etoxazole and the metabolites of concern (R-8 and R-13) in surface and ground water using the 

FQPA Index Reservoir Screening Tool (FIRST) and Screening Concentration in Ground Water 

(SCI-GROW) models, respectively (Memo, A. Metzger, 1/31/11; DP#386080). Drinking water 

was incorporated directly in the dietary assessment using the chronic concentration for surface 

water.

The chronic dietary exposure estimates are not of concern to HED (<100% cPAD) for the 

general U.S. population (2.7% cPAD) and all population subgroups (the most highly exposed 

population subgroup is children 1-2 years old at 11% cPAD).

Conclusions: The dietary-exposure database is adequate to support current registration 

requirements. In the most recent risk assessment, chronic dietary exposures were not of concern 

to HED. However, as part of Registration Review, a revised dietary exposure analysis may be 

required to reflect the most recent dietary exposure models, potential revised EDWCs, and/or 

changes to the toxicological PODs.

5.0 Residential Exposure 

There are no proposed or registered products containing etoxazole that would result in residential 

exposure. Therefore, a residential exposure assessment was not performed.

Spray Drift and Volatilization: Residential bystander exposures resulting from off-site transport 

(e.g., spray drift or volatilization) may occur as a result of applications of etoxazole. The 
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potential for spray drift will be quantitatively evaluated for each pesticide during the Registration 

Review process that ensures that all uses for that pesticide will be considered concurrently. The 

approach is outlined in the revised (2012) Standard Operating Procedures for Residential Risk 

Assessment (SOPs) – Residential Exposure Assessment Standard Operating Procedures Addenda 

1: Consideration of Spray Drift. This document outlines the quantification of indirect nonoccupational exposure to drift. In terms of volatilization, the agency has developed a 

Volatilization Screening Tool and a subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for specific chemicals.

Conclusions: There are no proposed or current registrations for products containing etoxazole 

that allow residential use. Therefore, residential handler and conventional residential postapplication exposure assessments will not be needed during Registration Review. A residential 

bystander risk assessment will be conducted.

6.0 Aggregate Risk Assessment

The most recent aggregate-risk assessment was performed in conjunction with the 2011 HED 

human-health risk assessment (Memo, J. Tyler et al., 23-SEP-2011; D385745). A chronic 

aggregate (food + drinking water) risk assessment was conducted. An acute aggregate risk 

assessment was not performed because an endpoint of concern attributable to a single oral dose 

was not selected for any population subgroup (including infants and children). Short- and 

intermediate-term aggregate risk assessments were not performed because there are no registered 

or proposed residential non-food uses. A cancer aggregate risk assessment was not performed 

because etoxazole is not carcinogenic. The chronic aggregate (food + drinking water) exposure 

and risk estimates did not exceed HED's level of concern (LOC).

Conclusions: There is sufficient information available to assess aggregate exposure. However, a

new aggregate risk assessment will be required during Registration Review to incorporate 

revised dietary exposure analyses and/or residential exposure assessments. 

7.0 Occupational Exposure 

Occupational handler and post-application exposures are expected based on the registered 

agricultural uses of etoxazole. Attachment 4 provides a summary of the occupational use 

pattern. Current formulations include WPs, WDGs, ECs, pressurized liquids, and pressurized 

gases. The maximum application rate is 0.18 lb ai/A, and applications can be made using aerial, 

groundboom, airblast, fogger, or handheld equipment, depending on the use site.

Based on these uses, there is a potential for exposure to etoxazole in occupational scenarios from 

handling etoxazole products during the application process (i.e., mixer/loaders, applicators, and 

mixer/loader/applicators). In addition, there is a potential for post-application worker exposure 

from entering into areas previously treated with etoxazole.

Occupational Handlers: There is the potential for inhalation exposure to occupational handlers 

from the currently registered use pattern of etoxazole. In the most recent exposure assessment 

for etoxazole, assessments were conducted for mixers/loaders, applicators, and flaggers for aerial 

and groundboom applications of a wettable powder formulation (packaged in water-soluble 

packets) (Memo, A. Nowotarski, 15-AUG-2011, D385939). The assessment was based an 
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application rate of 0.135 lb ai/A, and maximum area treated per day or gallons handled for the 

proposed uses. Handler's exposure and risk were calculated at baseline (long pants, a longsleeved shirt, no chemical-resistant gloves, and no respirator) and with personal-protective 

equipment (PPE) when necessary (e.g., chemical-resistant gloves, respirators, and engineering 

controls). Inhalation risk estimates were not of concern (i.e., MOEs ≥ 100) with baseline 

protection.

Based on a review of the registered labels for etoxazole for this scoping document, HED has 

conducted occupational handler assessments for most of the occupational handler scenarios 

anticipated for the registered uses of etoxazole. However, during Registration Review, updated 

occupational assessments will be conducted to reflect all currently registered uses, using current 

ORE policies and/or updated if toxicological PODs as needed.

Occupational Post-Application

Dermal: Typically, it is possible for agricultural workers to have post-application exposure to 

pesticide residues during the course of typical agricultural activities. However the Agency did 

not identify a dermal toxicological endpoint; therefore, an assessment for dermal post-application 

exposure was not conducted. 

Inhalation: Based on the Agency's current practices, a quantitative occupational post-application 

inhalation exposure assessment was not performed for etoxazole at this time primarily because it 

has a low acute inhalation toxicity (Toxicity Category III), a low vapor pressure (<1.0 x 10-8

mmHg), and is applied at a low use rate (0.135 lb ai/A). However, there are multiple potential 

sources of post-application inhalation exposure to individuals performing post-application 

activities in previously treated areas. These potential sources include volatilization of pesticides 

and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force (ARTF) and may, as appropriate, develop 

policies and procedures, to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency's risk assessments. If new 

policies or procedures are put into place, then the Agency may revisit the need for a quantitative 

occupational post-application inhalation exposure assessment for etoxazole.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for etoxazole. The most recent occupational handler and post-application 

exposure assessments are not reflective of current exposure policies and data, and did not 

identify risks of concern. HED has conducted occupational handler assessments for most of the 

occupational handler scenarios anticipated for the registered uses of etoxazole. However, during 

Registration Review, updated occupational assessments will be conducted to reflect all currently 

registered uses, using current ORE policies and/or updated if toxicological PODs as needed. 
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8.0 Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for etoxazole (Memo, E. Evans and S. 

Recore, 08-APR-2014; D418223) and concluded that based on the low frequency and low 

severity of incident cases of etoxazole reported to either the OPP Incident Data System (IDS) or 

Sentinel Event Notification System for Occupational Risk (SENSOR)-Pesticides, there does not 

appear to be a concern at this time that would warrant further investigation. The Agency will 

continue to monitor the incident information and if a concern is triggered, additional analysis 

will be included in the risk assessment.

9.0 Tolerance Assessment and International Harmonization

U.S. permanent tolerances (listed in 40 CFR 180.593) and Canadian, Mexican, and Codex 

Maximum Residue Limits (MRLs) are summarized in Attachment 5. Canada and Codex have 

established MRLs for residues of etoxazole in/on several raw agricultural and livestock 

commodities, but several are not harmonized with U.S. tolerances (commodities with different 

tolerance are bolded in the table). There are no Mexican MRLs for etoxazole. The U.S. residue 

definition is harmonized with Canada and Codex. During Registration Review, HED may look 

into the possibility of harmonizing with Canada and Codex for the commodities with differing 

tolerances.

10.0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

most recent etoxazole human-health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations1

.” The OPP typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human-health risk assessments, including, but not 

limited to, people who obtain drinking water from sources near agricultural areas, the variability 

of diets within the U.S., and people who may be exposed when harvesting crops. Should these 

highest exposures indicate potential risks of concern, OPP further refines the risk assessments to 

ensure that the risk estimates are based on the best available information.

11.0 Cumulative 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, 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. For the purposes of this tolerance action, therefore, EPA has 

assumed that etoxazole does not have a common mechanism of toxicity with other substances. 

For information regarding EPA’s efforts to determine which chemicals have a common 

mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy 

statements released by EPA’s Office of Pesticide Programs concerning common mechanism 

determinations and procedures for cumulating effects from substances found to have a common 

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

 

1 http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf
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12.0 Human Studies

Past etoxazole 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), the Outdoor 

Residential Exposure Task Force (ORETF) Database, and the 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.

13.0 Risk-Assessment Updates, Data Deficiencies, and Label Revisions

The following data deficiency was identified for etoxazole:

 Toxicology: OCSPP Guideline # 870.3465, Subchronic Inhalation Toxicity Study. 

In addition, EPA anticipates conducting the following risk assessment updates during 

Registration Review:

 Toxicology: 

o Review of the submitted immunotoxicity, acute neurotoxicity, and subchronic 

neurotoxicity studies.

o Reevaluation of toxicity endpoint/dose selection, along with the FQPA SF based 

on current HED policy. 

 Residue Chemistry: 

o None.

 Dietary Exposure:

o Revised dietary exposure analysis to reflect the most recent dietary exposure 

models, potential revised EDWCs, and/or changes to the toxicological PODs. 

 Aggregate Exposure:

o New aggregate risk assessment to incorporate revised dietary exposure analyses 

and/or revised residential exposure assessments.

 Occupational/Residential Exposure: 

o Revised occupational handler inhalation assessments to reflect all potential 

exposure scenarios, as well as updated policies and exposure data.

o Assessments for all uses may be updated if toxicological PODs are revised.

o A spray drift assessment for bystanders will be conducted. A screen will be 

conducted so that the need for a volatilization assessment can be determined.
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14.0 References

HED Memoranda Relevant to Registration Review.

Author Barcode Date Title

M. Dow D273223 10-JUL-2002 ETOXAZOLE - Exposure/Risk Assessment for Pesticide Handlers and 

Agricultural Workers from the Use of Etoxazole on Ornamental Plants In 

Greenhouses, Lath and Shadehouses

J. Tyler D283737 31-JUL-2003 Etoxazole. Registration for Use on Cotton, Pome fruits, Strawberries and 

Imported Oranges.

M. Dow D288816 5-AUG-2003 ETOXAZOLE - Exposure and Risk Assessment for Pesticide Handlers and 

Agricultural Workers from the Use of Etoxazole On Cotton, Pome Fruit 

and Strawberry.

J. Tyler D292548 7-AUG-2003 PP#: 2F6420. Etoxazole in/on Cotton, Strawberry, Pome Fruit and 

Imported Mandarin Oranges.

M. Dow D313939 3-MAR-2005 ETOXAZOLE - Exposure/Risk Assessment for the Proposed Use of 

Etoxazole on Grape and Tree Nuts Including Pistachio.

J. Tyler D330258 30-MAR-2005 Etoxazole. Registration for Use on Grapes and Tree Nuts, including 

Pistachios

J. Tyler D307178 6-APR-2005 Etoxazole in/on Cotton, Pome fruits, Strawberries and Imported Oranges. 

Review of Amendment Dated 6/18/04 Submitted in Response to the Health 

Effects Division’s (HED’s) Memo of 7/31/03 (D283737).

M. Dow D341212 2-JUL-2007 ETOXAZOLE - Occupational Exposure/Risk Assessment for the Proposed 

Uses of Etoxazole on Cherry, Melon and Hops.

J. Tyler D335334 15-AUG-2007 PP#: 6E7150. Etoxazole in/on Cherries, Hops, and Melon Subgroup 9A.

S. Levy D346199 14-NOV-2007 PP# 6E7150. Etoxazole. REVISED: Registration for Use on Cherries, 

Hops, and Melon Subgroup 9A.

M. Dow D353080 24-JUN-2008 ETOXAZOLE – Occupational Exposure/Risk Assessment for the 

Proposed Use of Etoxazole on Greenhouse Tomato, Cucumber, Peach, 

Plum and Mint.

D. Rate D387610 18-NOV-2008 Etoxazole; Petition for Tolerances and Uses on Stone Fruits, Cucumber, 

Tomato, and Mint.

M. Dow D367031 22-JUL-2009 ETOXAZOLE – Human, Occupational Exposure/Risk Assessment for the 

Proposed Use of Etoxazole in Total Release Greenhouse Fogger.

J. Tyler D339039 31-JUL-2009 Etoxazole in/on Grapes and Tree Nuts, including Pistachios. Review of 

Waiver Request for Grape Processing Study Submitted in Response to 

Residue Chemistry Deficiencies Identified in D303628 (J. Tyler, 3/30/05).

D. Rate D378452 4-AUG-2010 Petition for Tolerances and Uses on Peppers (Bell and Non-bell); 

Squash/Cucumbers (Subgroup 9B); Avocado; Tropical and Subtropical 

Fruits (Inedible Peel); Caneberry Subgroup 13-07A; Small Fruit Vine 

Climbing, Except Kiwifruit, Subgroup 13-07F; Low-growing Berry, 

Subgroup 13-07G; and Tea. 

W. Wassell D380307 20-OCT-2010 PP# 6E7150. Etoxazole. Registration for Use on Cherries, Hops, and 

Melon Subgroup 9A. 

A. Nowotarski D378458 10-NOV-2010 (Revised) Etoxazole: Exposure/Risk Assessment for IR-4 Requested 

Registration of Etoxazole on Peppers/Eggplant, Low Growing Berry 

Subgroup (13-07G), Small Fruit Vine Climbing Subgroup (13-07F), 

Squash/Cucumber Subgroup (9B), Tropical Fruits and Tree Fruits, 

Caneberry Subgroup (13-07A).

D. Rate D373916 2-DEC-2010 Etoxazole; Human Health Risk Assessment for Proposed Tolerances and 

Uses on Peppers (Bell and Non-bell); Squash/Cucumbers (Subgroup 9B); 

Avocado; Tropical and Subtropical Fruits (Inedible Peel); Caneberry 

Subgroup 13-07A; Small Fruit Vine Climbing, Except Kiwifruit, Subgroup 

13-07F; Low-growing Berry, Subgroup 13-07G; and Tea. 

J. Tyler D387610 13-MAY2011Etoxazole in/on Stone Fruits, Cucumber, Tomato, and Mint. 

Review of Plum Processing Study Submitted in Response to 

Residue Chemistry Deficiencies Identified in D353394 (D. 

Rate, 18-NOV-2008).

A. Nowotarski D385939 15-AUG-2011 Etoxazole: Occupational and Residential Exposure/Risk Assessment for 

Proposed Uses on Field Corn and Popcorn.

J. Tyler D385940 23-SEP-2011 Etoxazole. Human-Health Risk Assessment for Proposed Uses in/on Field 

Corn and Pop Corn.

cc: J. Tyler (RAB1), J. Pyne (RAB1), A. Dunbar (RAB1)

RDI: RAB1 (5/21/14), C. Smith (5/21/14)

J. Tyler:S10943:PY-S:(703)305-5564:7509P:RAB1
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Attachment 1: Chemical Identity Tables.

Table A.1.1. Nomenclature of Etoxazole.

Compound

Common name Etoxazole

Company experimental names S-1283, V-1283, YI-5301

IUPAC name (RS)-5-tert-butyl-2-[2-(2,6-difluorophenyl)-4,5-dihydro-1,3-oxazol-4-yl]phenetole

CAS name 2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole

CAS # 153233-91-1

Table A.1.2. Physicochemical Properties of Etoxazole (Technical Grade Active Ingredient (TGAI)).

Parameter Value References

Melting range 101.5-102.5C

46018505.der.wpd

pH 6.2

Density 1.2389 g/cm3

Water solubility 3.99 x 10-5

at 10C

7.04 x 10-5at 20C

6.69 x 10-5at 30C

Solvent solubility (g/L at 20C) acetone: 309 1,2-dichloroethane: 402

ethyl acetate: 249 n-heptane: 18.7

methanol: 104 xylene: 252

Vapor pressure at 25C 7.0 x 10-6 pascals

Dissociation constant (pKa) no measurable pKa

Octanol/water partition coefficient Log(KOW) 5.52 ± 0.58 at 20C

UV/visible absorption Not available.
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Attachment 2: Etoxazole Acute, Subchronic, and Chronic Toxicity Profile.

2.1 Toxicology Data Requirements.

The requirements (40 CFR 158.340) for food and non-food uses for etoxazole are in Table A.1. 

Use of the new guideline numbers does not imply that the new (1998) guideline protocols were 

used.

Table A.2.1. Toxicological Data Requirements for Etoxazole.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 28-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

no

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

no

no

no

in review

in review

no

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

no

in review

Special Studies for Ocular Effects

Acute Oral (rat)...........................................................

Subchronic Oral (rat) ..................................................

Six-month Oral (dog)..................................................

no

no

no

no

no

no
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2.2 Toxicity Profiles.

TABLE A.2.2. Acute Toxicity of Etoxazole Technical Grade Active Ingredient (TGAI).

Guideline No. /Study Type MRID No. Results Toxicity Category

870.1100 / Acute Oral 45089919 LD50 >5000 mg/kg IV

870.1200 / Acute Dermal 45089921 LD50 >2000 mg/kg II

870.1300 / Acute Inhalation 45089923 LC50 >1.09 m/L III

870.2400 / Primary Eye Irritation 45089925 Not an eye irritant IV

870.2500 / Primary Dermal Irritation 45089927 Not a dermal irritant IV

870.2600 / Dermal sensitization 45089929 Not a dermal sensitizer N/A

TXR# 0051659, P. Shah, 19/MAR/2003.

TABLE A.2.3. Subchronic, Chronic, and Geno- Toxicity Profile for Etoxazole.

Guideline No./ 

Study Type

MRID No. (year)/Classification/Doses Results

870.3100

90-Day oral toxicity 

rodents (rat)

45089935, 45089934 (1995)

Acceptable/guideline

0, 100, 300, 1000, or 3000 ppm

M: 0, 6.12, 18.28, 61.8, or 183.7 mg/kg/day 

F: 0, 6.74, 20.50, 69.0 or 204.8 mg/kg/day

NOAEL = 61.8/69.0 mg/kg/day (M/F).

LOAEL = 183.7/204.8 mg/kg/day (M/F), based upon 

increases in hepatic enzyme levels, increased liver 

weights and centrilobular hepatocellular swelling in 

both sexes and liver enlargement in females only.

870.3100

90-Day oral toxicity 

rodents (rat)

45089931 (1998)

Acceptable/guideline

0, 5000, or 10000 ppm

M: 0, 300.4, or 610 mg/kg/day 

F: 0, 336.6, or 692 mg/kg/day

NOAEL = not determined.

LOAEL = 300.4/336.6 mg/kg/day (M/F), based upon 

clinical signs, clinical chemistry, increased liver 

weights, and histopathology.

870.3100

90-Day oral toxicity 

rodents (mouse)

45089936 (1994), 45089938 (1992)

Acceptable/guideline

0, 100, 400, 1600 or 6400 ppm

M: 0, 13.42, 55.13, 213.6, or 878.4 mg/kg/day 

F: 0, 15.15, 62.00, 250.5, or 994.5 mg/kg/day

NOAEL = 213.6/250.5 mg/kg/day (M/F).

LOAEL = 878.4/994.5 mg/kg/day (M/F), based upon 

periportal hepatocellular necrosis, increased alkaline 

phosphatase levels, accompanied by increased relative 

liver weight, liver enlargement, and centrilobular 

hepatocellular swelling.

870.3150

90-Day oral toxicity 

in nonrodents (dog)

45089933 (1995), 45089932 (1992)

Acceptable/guideline

0, 200, 2000, or 10000 ppm

M: 0, 5.33, 53.7, or 268 mg/kg/day

F: 0, 5.42, 55.9, or 277 mg/kg/day

NOAEL = 5.33/5.42 mg/kg/day (M/F).

LOAEL = 53.7/55.9 mg/kg/day (M/F), based upon 

clinical signs (vomiting foamy fluid and mucous stool), 

clinical chemistry, increased liver weights, and 

centrilobular swelling in the liver and acinar cell 

atrophy in the prostate.

870.3200

21/28-Day dermal 

toxicity (rabbit)

45089941 (1999)

Acceptable/guideline

M & F: 0 or 1000 mg/kg/day

NOAEL = 1000 mg/kg/day (M/F).

LOAEL = not determined.

No systemic effects noted.

870.3700a

Prenatal 

developmental 

toxicity in rodents 

(rat)

45090005 (1994), 45090004 (1993)

Acceptable/guideline

F: 0, 40, 200, or 1000 mg/kg/day

Maternal NOAEL = 1000 mg/kg/day.

LOAEL = not determined.

Developmental NOAEL = 1000 mg/kg/day.

LOAEL = not determined.

870.3700b

Prenatal 

developmental 

toxicity in 

nonrodents (rabbit)

45090003, 45090002 (1994) Acceptable/guideline

F: 0, 40, 200, or 1000 mg/kg/day

Maternal NOAEL = 200 mg/kg/day.

LOAEL = 1000 mg/kg/day based upon liver 

enlargement and decreased body weight gains and food 

consumption.

Developmental NOAEL = 200 mg/kg/day.

LOAEL = 1000 mg/kg/day based upon increased 

incidences of 27 presacral vertebrae and 27 presacral 

vertebrae with 13th ribs in the fetuses.

870.3800

Reproduction and 

fertility effects (rat)

45090007 (1996), 45090006 (1993)

Acceptable/guideline

0, 80, 400, or 2000 ppm

M/F: 0, 5.59/6.59, 28.17/33.37, or 139.1/158.7 

mg/kg/day

Parental/Systemic NOAEL = 28.17/33.37 mg/kg/day.

LOAEL = 139.1/158.7 mg/kg/day (M/F), based upon 

increased liver weights in the P and F1 males and 

increased adrenal weights in the P females.

Offspring/Systemic NOAEL = 28.17/33.37 mg/kg/day.

LOAEL = 139.1/158.7 mg/kg/day (M/F), based upon 

pup mortality.

Reproductive NOAEL = 139.1/158.7 mg/kg/day.

LOAEL = not determined.

870.4300 45250903, 45089937 (1996) NOAEL = 64 mg/kg/day (M/F).
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TABLE A.2.3. Subchronic, Chronic, and Geno- Toxicity Profile for Etoxazole.

Guideline No./ 

Study Type

MRID No. (year)/Classification/Doses Results

Combined chronic 

toxicity/ 

carcinogenicity 

rodents (rat)

Unacceptable/guideline

0, 4, 16, or 64 mg/kg/day nominal M: 0, 4.01, 16.1, 

or 64.4 mg/kg/day

F: 0, 4.03, 16.1, or 64.5 mg/kg/day

LOAEL = not determined.

Equivocal evidence of carcinogenicity.

870.4300

2-Year 

feed/carcinogenic 

(rat)

45571802 (2001)

Acceptable/guideline

0, 50, 5000, 10000 ppm

M/F: 0/0, 1.83/2.07, 187/216, 386/445 mg/kg/day

NOAEL = 1.83/2.07 mg/kg/day (M/F).

LOAEL = 187/216 (M/F), based upon effects on the 

incisors including abnormal amelogenesis.

No evidence of carcinogenicity.

870.4100b

Chronic toxicity 

nonrodents (dog)

45089942 (1996)

Acceptable/guideline

0, 200, 1000 or 5000 ppm

M: 0, 4.62, 23.5, or 116 mg/kg/day

F: 0, 4.79, 23.8, or 117 mg/kg/day

NOAEL = 4.62/4.79 mg/kg/day (M/F).

LOAEL = 23.5/23.8 mg/kg/day (M/F), based upon 

increased alkaline phosphatase activity, increased liver 

weights, liver enlargement (females), and incidences of 

centrilobular hepatocellular swelling in the liver.

78-Week 

Carcinogenic 

Mouse

45571801 (2001)

Acceptable/guideline

0, 2250, 4500 ppm

M/F: 0/0, 242/243, 484/482 mg/kg/day

NOAEL = 242/243 (M/F).

LOAEL = 484/482 (M/F), based on a slight increase in 

the incidence of a fatty change in the centrilobular 

hepatocytes in males.

870.4200b

Carcinogenicity 

mouse

45090001 (1996)

Unacceptable/guideline

0, 15, 60, or 240 ppm 

M: 0, 15.1, 60.1, or 241 mg/kg/day

F: 0, 15.1, 60.5, or 243 mg/kg/day

NOAEL = 241/243 mg/kg/day (M/F).

LOAEL = not determined.

No evidence of carcinogenicity.

Non-guideline

13-week study: 

Effect on 

proliferative 

activity of testicular 

interstitial cells in 

rat

45089939 (1996)

Acceptable/non-guideline

0 or 3000 ppm

Test performed in conjunction with subchronic oral 

toxicity test in rats (MRID 45089935)

A toxic level of the test substance did not affect the 

proliferative activity of testicular interstitial cells.

Gene Mutation

870.5100

reverse gene 

mutation assay in 

bacteria

45250905 (1992)

Acceptable/guideline

When tested up to cytotoxic levels, there was no 

evidence of induced mutant colonies over background.

Gene Mutation

Non-guideline

reverse gene 

mutation assay in 

bacteria

45090015 (1999)

Acceptable/non-guideline

When tested up to cytotoxic levels, there was no 

evidence of induced mutant colonies over background.

Gene Mutation 

870.5300

in vitro forward 

gene mutation assay 

in mouse lymphoma 

cells

45090013 (1996)

Acceptable

When tested up to cytotoxic levels, mutagenic in the 

presence of S9 activation and equivocal for 

mutagenicity in the absence of S9 activation.

Cytogenetics 

870.5375

in vitro mammalian 

cytogenetics assay 

45250904 (1994)

Acceptable/guideline

When tested up to cytotoxic levels, not clastogenic in 

the presence or absence of S9 activation.

870.5395

bone marrow 

micronucleus assay 

45090010 (1996)

Acceptable

There was no significant increase in the frequency of 

micronucleated polychromatic erythrocytes in bone 

marrow after any treatment time.
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TABLE A.2.3. Subchronic, Chronic, and Geno- Toxicity Profile for Etoxazole.

Guideline No./ 

Study Type

MRID No. (year)/Classification/Doses Results

870.5550

unscheduled DNA 

synthesis in primary 

rat hepatocytes/ 

mammalian cell 

cultures

45090014 (1997)

Acceptable

When tested up to cytotoxic levels, there was no 

evidence that unscheduled DNA synthesis was induced 

by the test substance.

870.6200a

Acute 

Neurotoxicity (Rat)

48769402 (2011)

Classification Pending; data in review

0, 100, 500, 2000 mg/kg

Systemic NOAEL = 2000 mg/kg.

Systemic LOAEL was not established.

Neurotoxicity NOAEL 2000 mg/kg.

Neurotoxicity LOAEL was not established.

870.6200b

Subchronic 

Neurotoxicity (Rat)

48769403 (2012)

Classification Pending; data in review

0, 1500, 5000 and 15000 ppm

(0, 84.6/101.4, 282/334, 858/1034 mg/kg/day 

[M/F])

Systemic NOAEL = 858/1034 mg/kg/day [M/F].

Systemic LOAEL was not established.

Neurotoxicity NOAEL = 858/1034 mg/kg/day [M/F].

Neurotoxicity LOAEL was not established.

870.7485

Metabolism and 

pharmacokinetics

45090016 (1996)

Acceptable

50, 500 mg/kg

Within 168 hours of administering a single oral dose of 

[

14C-butylphenyl]- or [14C-oxazole]-etoxazole at 5 or 

500 mg/kg, 92.0-97.6% of the administered dose was 

recovered from male and females rats. [14C]-Etoxazole 

was rapidly absorbed from the G.I. tract of rats 

following oral dosing. Maximum concentrations of 

radioactivity in plasma were observed within 2-4 hours 

of dosing for the low-dose groups and within 4-6 hours 

of dosing for the high-dose groups. Excluding the G.I. 

tract, concentrations of radioactivity over time were 

generally highest in liver, lymph nodes, thyroid, and fat, 

and were lowest in brain for both sexes in each dose 

group. For each tissue, the actual concentrations of 

radioactivity were similar between the two 14C-labels, 

but concentrations in tissues of males were generally 

1.5-2x higher than in females from the same group. For 

both low- and high-dose rats, fecal excretion was the 

primary route of elimination and excretion of the 14Cdose was essentially complete within 120 hours of 

dosing. 

870.7800

28-Day 

Immunotoxicity 

(Rat)

48769406 (2011)

Classification Pending; data in review

0, 1000, 5000 and 15000 ppm

(0, 82.2, 418, 1211 mg/kg/day [F])

Systemic NOAEL = 1211 mg/kg/day.

Systemic LOAEL was not established.

Immunotoxicity NOAEL = 1211 mg/kg/day.

Immunotoxicity LOAEL was not established.
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Attachment 3: Etoxazole Endpoint Selection Tables.

Table A.3.1. Summary of Toxicological Doses and Endpoints for Etoxazole for Use in Human-Health Risk 

Assessments.

Exposure Scenario Point of 

Departure

Uncertainty/ FQPA 

Safety Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General population, 

including infants and 

children)

N/A N/A N/A A dose and endpoint attributable to a 

single dose were not identified in the 

database including the developmental 

toxicity studies.

Acute Dietary 

(Females 13-49 years 

of age)

N/A N/A N/A A dose and endpoint attributable to a 

single dose were not identified in the 

database including the developmental

toxicity studies.

Chronic Dietary (All 

populations)

NOAEL = 4.62 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

cPAD = cRfD = 

0.046 mg/kg/day 

Chronic Oral Toxicity Study- Dog

LOAEL = 23.5 mg/kg/day based upon 

increased alkaline phosphatase activity, 

increased liver weights, liver 

enlargement (females), and incidences of 

centrilobular hepatocellular swelling in 

the liver.

Inhalation

Short- (1-30 days), 

Intermediate- (1-6 

months), and LongTerm (>6 months)

NOAEL = 4.62 

mg/kg/day

(inhalationabsorption rate = 

100%)

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential/ 

Occupational 

LOC for MOE = 

100

Chronic Oral Toxicity Study- Dog

LOAEL = 23.5 mg/kg/day based upon 

increased alkaline phosphatase activity, 

increased liver weights, liver 

enlargement (females), and incidences of 

centrilobular hepatocellular swelling in 

the liver.

Cancer (oral, dermal, 

inhalation)

HED classified etoxazole as “not likely to be carcinogenic to humans” according to EPA Proposed 

Guidelines for Carcinogen Risk Assessment (April 10, 1996).

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning 

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no-observed adverse-effect level. 

LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = populationadjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
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Attachment 4: Summary of Registered Uses. 

Table A.4.1. Summary of Registered Uses for Etoxazole.

Crop/Use Site Product 

(Formulation)

Application 

Method

Maximum 

App Rate 

(lb/ai/A)

REI 

(hours)

Agricultural Crops

Apple EC Ground 0.11 24

Caneberry subgroup 13-07A DF/WDG, WP Ground 0.135 12

Corn, field and pop DF/WDG, WP Ground, aerial 0.135 12

Cotton DF/WDG, WP Ground, aerial 0.045 12

EC 24

Cucumber (greenhouse) PRL Fogger 0.056 2

Cucurbit vegetables (Crop Group 9) DF/WDG, WP Ground, aerial 0.135 12

Eggplant (greenhouse) PRL Fogger 0.056 2

Hops DF/WDG, WP Ground 0.18 12

Low growing berry (subgroup 13-07G) DF/WDG, WP Ground 0.135 12

Mint (peppermint and spearmint) DF/WDG, WP Ground, aerial 0.18 12

Mint (peppermint and spearmint; greenhouse) PRL Fogger 0.056 2

Pepper and Eggplant (Subgroup 8-10B) DF/WDG, WP Ground 0.135 12

Pear EC Ground 0.11 24

Pepper (greenhouse) PRL Fogger 0.056 2

Pome fruit (Crop group 11) DF/WDG, WP Ground 0.135 12

Pome fruit (apple and pear; greenhouse) PRL Fogger 0.056 2

Pumpkin (greenhouse) PRL Fogger 0.056 2

Small fruit vine climbing, except fuzzy kiwifruit 

(Subgroup 13-07F)

DF/WDG, WP Ground 0.135 12

Squash (greenhouse) PRL Fogger 0.056 2

Stone fruit (Crop Group 12) DF/WDG, WP Ground 0.135 12

Stone fruit (except plum; greenhouse) PRL Fogger 0.056 2

Strawberry EC Ground 0.11 24

Tree nuts (Crop Group 14) DF/WDG, WP Ground 0.135 12

Tree nuts (almonds and pecans; greenhouse) PRL Fogger 0.056 2

Tropical and Sub-tropical Fruit (Inedible Peel) DF/WDG, WP Ground, aerial 0.135 12

Tomato (Greenhouse-grown) DF/WDG Boom sprayer, 

handwand (high 

and low pressure), 

backpack

0.125 12

PRL Fogger 0.056 2

Non-agricultural Crops

Christmas trees DF/WDG, WP Ground, aerial 0.135 12

Non-bearing fruit trees DF/WDG, WP Ground 0.135 12

Ornamentals (greenhouse) PRGS Aerosol, fog or 

fumigation

24

PRL Total release 0.056 2

WDG Ground 0.1 12

24(c)

Alfalfa WP Ground, aerial 0.135 12

Carrot (including tops) WP Ground, aerial 0.135 12
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Page 20 of 21

Attachment 5: Etoxazole IRLS Sheet.

Table A.5.1. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

40 CFR 180.593:

(a) General. Etoxazole (2-(2,6-

difluorophenyl)-4-[4-(1,1-

dimethylethyl)-2-ethoxyphenyl]-4,5-

dihydrooxazole) 

2-(2,6-difluorophenyl)-4-

[4-(1,1-dimethylethyl)

-2-ethoxyphenyl]-4,5-

dihydrooxazole

etoxazole. The 

residue is fat 

soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex2

Almond, hulls 2.0 3

Apple, wet pomace 0.50 

Avocado 0.20

Berry, low growing, subgroup 13-07G 0.50 0.5 strawberries

Caneberry subgroup 13-07A 1.5

Canistel 0.20

Cattle, fat 0.02 

Cattle, liver 0.01 0.01 (*) edible 

offal 

(mammalian)

Corn, field, forage 0.80

Corn, field, grain 0.01

Corn, field, refined oil 0.03

Corn, field, stover 4.0

Corn, pop, grain 0.01

Corn, pop, stover 4.0

Cotton, gin byproducts 1.0 

Cotton, undelinted seed 0.05 0.05 

Fruit, pome, group 11 0.20 0.2 apples, Asian pears, 

crabapples, loquats, 

mayhaws, pears, quinces

0.07 pome 

fruits

Fruit, small vine climbing, except fuzzy 

kiwifruit, subgroup 13-07F

0.50 0.5 grapes 0.5

Fruit, stone, group 12, except plum 1.0

Goat, fat 0.02 

Goat, liver 0.01 0.01 (*) edible 

offal 

(mammalian)

Grape, raisin 1.5 1.5

Hop, dried cones 7.0 15 hops dry

Horse, fat 0.02 

Horse, liver 0.01 

Mango 0.20

Melon subgroup 9A 0.20

Milk, fat 0.01 0.01 (*)

Nut, tree, group 14 0.01 0.01 almond nuts, beechnuts, 

black walnuts, Brazil nuts, 

butternuts, cashew nuts, 

chestnuts, chinquapin nuts, 

English walnuts, hazelnuts 

(filbert), hickory nuts, 

macadamia nuts, pecan nuts, 

pistachio nuts

0.01

Papaya 0.20

Pepper/eggplant subgroup 8-10B 0.20

Peppermint, oil 20

Peppermint, tops 10 15 mints
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Page 21 of 21

Table A.5.1. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

Pistachio 0.01 0.01 (*) tree 

nuts

Plum 0.15

Plum, prune, dried 0.30

Sapodilla 0.20

Sapote, black 0.20

Sapote, mamey 0.20

Sheep, fat 0.02 

Sheep, liver 0.01 0.01 (*) edible 

offal 

(mammalian)

Spearmint, oil 20

Spearmint, tops 10 15 mints

Squash/cucumber subgroup 9B 0.02 0.02 cucumber

Star apple 0.20

Tangerine1 0.10 

Tea, dried* 15 15 tea, green, 

black (black 

fermented and 

dried)

Tomato 0.20

MRLs with NO US Equivalent

Citrus fruits 0.1

Meat (from mammals other than marine 

mammals)

0.01 (*) (fat)

Completed: M. Negussie; 04/14/2014

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2* = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated 

commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have 

not been finalized by the CCPR and the CAC.