UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

July 1, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

PC Code: 107091 

DP Barcode: D418231 

SUBJECT: 

FROM: 

REVIEWED 

BY: 

Registration Review- Preliminary Problem Formulation for the Ecological Risk 

Assessment and Drinking Water Exposure Assessment to Be Conducted for 

Etoxazole . P _ . . _ . 

~/~~~ Jose Melendez, Chemist L) ;) c:A__ 2f 

Environmental 

Justin Housenger, 

Risk 

Biologist 

Branch 5 

OV . . ~ ~ 

Environmental Fate and Effects Division (7507P) 

Joseph DeCant, Ecologist 

Michael Barrett, Senior Chemist 

Keith Sappington, Senior Advisor 

Environmental Risk Branch 5 

Environmental Fate and Effects Division (7507P) 

THROUGH: Mah Shamim, Branch Chief 

Envir

Environmental 

onmental Fate 

Risk 

and 

Branch 

Effects 

5 

Division (7507P) 

~ 

TO: Julia Stokes, Chemical Review Manager 

Jill Bloom, Team Leader 

Linda Arrington, Branch Chief 

Risk Management and Implementation Branch 5 

Pesticide Re-Evaluation Division (7508P) 

Please, find attached the Preliminary Problem Formulation for the Ecological Risk Assessment 

and Drinking Water Exposure Assessment for Registration Review to be conducted for 

Etoxazole. 

1 
2

Contents

1. Executive summary................................................................................................................. 3

2. Introduction............................................................................................................................. 8

3. Use Characterization............................................................................................................... 9

4. Conclusions from Previous Risk Assessments....................................................................... 9

a. Ecological Risk Assessment .............................................................................................. 10

b. Drinking Water Exposure Assessments............................................................................. 10

c. Clean Water Act Programs ................................................................................................ 11

5. Environmental Fate and Transport........................................................................................ 11

a. Transformation Products.................................................................................................... 14

6. Receptors............................................................................................................................... 15

a. Effects to Aquatic Organisms............................................................................................ 15

b. Effects to Terrestrial Organisms........................................................................................ 19

c. Ecological Incidents........................................................................................................... 29

7. Exposure Pathways of Concern ............................................................................................ 29

8. Analysis Plan ........................................................................................................................ 31

a. Stressors of Concern .......................................................................................................... 31

b. Measures of Exposure........................................................................................................ 31

c. Measures of Effect ............................................................................................................. 31

9. Endangered Species Assessments......................................................................................... 32

10. Endocrine Disruptor Screening Program........................................................................... 32

11. Preliminary Identification of Data Gaps............................................................................ 32

a. Environmental Fate............................................................................................................ 32

b. Effects................................................................................................................................ 34

12. References.......................................................................................................................... 48
3

1. Executive summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem 

formulation for the ecological risk, environmental fate, endangered species, and drinking water 

assessments to be conducted as part of the registration review of Etoxazole. The problem 

formulation describes the methods planned to be used during the completion of drinking water 

and ecological risk assessments in support of registration review and provides an overview of the 

environmental fate, ecological effects, and potential risks associated with the use of Etoxazole as 

well as uncertainties unique to risk assessment of Etoxazole. This document also identifies 

additional studies that would be beneficial to the conduct of an ecological risk assessment to 

parent etoxazole and its degradation products. Major environmental fate and ecological effects 

data needs as well as uncertainties related to the assessment follow:

Environmental Fate Data Gaps

835.4300 Aerobic Aquatic Metabolism: No study is available. The study is required to support 

the uses of this chemical. Two sediment systems should be tested.

835.4400 Anaerobic Aquatic Metabolism: Only one sediment system is available. In the 

study, for the tert-butylphenyl-U label, the levels of unextracted radioactivity were up to 52% 

applied radioactivity (AR); meanwhile, for the difluorophenyl-U-labeled study, it was up to 

21.4% AR. Sediment was extracted only once with methanol followed by once with methanol:

0.1 M HC1, 9:1, v:v). Further, for the difluorophenyl-U-label study up to 25.4% AR was 

unidentified volatile organics (for the tert-butylphenyl-U-labeled study the volatile organics were 

<0.1% AR). Given the uncertainties with the available data, studies with two new sediment 

systems should be submitted addressing these issues. EFED will make conservative 

assumptions, based upon the overall behavior observed in the available study, with unextracted 

radioactivity included in the total toxics residues expression, in the absence of data showing that 

the unextracted residues do not include any residues of concern. Furthermore, a conservative 3x 

factor will also be added, since only one study, conducted on one sediment system, is available.

850.6100 Analytical Methods in Soil, Water and Sediment: An environmental chemistry 

method (ECM) and its associated independent laboratory validation (ILV), for the analysis of 

etoxazole and its major degradates of ecological and/or human health concern in soil, water and 

sediment should be available. Of particular importance, the degradates of concern are R-8 and 

R-13. Two methods are available in soil (ECMs were located in the MRID 45621721, which is a 

previously reviewed terrestrial field dissipation study). The corresponding ILVs are also 

available in soil, which are currently in review (MRID 45621719 and 45621720). The data 

requirement remains unfulfilled for this chemical, pending evaluation of the available ILVs.

Ecological Effects Data Gaps

850.2100 Avian acute oral toxicity test (with passerine species): Currently, there is only one 

acute oral study available for etoxazole which is conducted on the mallard duck. An avian acute 

oral toxicity study with a passerine species is therefore a data gap. At the current maximum 

seasonal application rate of etoxazole (corn, 0.135 lbs a.i/A, 2 applications, 14-day interval), an 
4

acute oral passerine study would have to show approximately 12-fold higher toxicity over parent 

etoxazole to trigger non-listed species concerns and show increased toxicity by a factor of 

approximately two to trigger listed species concerns. Available data from related chemicals

shows that this class of insecticides is generally not toxic to northern bobwhite quail and mallard 

duck on an acute oral and subacute dietary exposure basis. However, data for one chemical, 

diflubenzuron for which an acute oral study with a passerine species is available, shows

increased toxicity over both mallard and bobwhite data for that chemical. As this is the only 

acute oral study with a passerine species currently available for chemicals that are known to 

affect chitin biosynthesis, and the proximity of the endpoint of available study and the listed 

species concern LOC to be within 3X (which is potential considering species to species 

sensitivity), an acute oral study with a passerine species for etoxazole has the potential to impact 

the risk assessment.

850.4100 Seedling Emergence: There is currently one available Tier I Seedling Emergence 

study available for etoxazole which is classified as acceptable. However, this study tested at an 

application rate of 0.06 lbs a.i/A, which at the time was the maximum application rate. 

Furthermore, this study was conducted with technical grade active ingredient (TGAI). Since the 

time of that study, the maximum single application rate of etoxazole has increased 3-fold to 0.18 

lbs a.i/A (for uses on mint). A new study is requested that tests etoxazole at this higher

maximum single application rate. The study, in line with recommendations of OCSPP 850.4100, 

should test the typical end use product (TEP) of etoxazole instead of TGAI as the currently 

available study did.

850.4150 Vegetative Vigor: There is currently one available Tier I Vegetative Vigor study 

available for etoxazole which is classified as acceptable. However, this study tested at an 

application rate of 0.06 lbs a.i/A, which at the time was the maximum application rate 

Furthermore, this study was conducted with technical grade active ingredient (TGAI). Since the 

time of that study, the maximum single application rate of etoxazole has increased 3-fold to 0.18 

lbs a.i/A (for uses on mint). A new study is requested that tests etoxazole at this higher 

maximum single application rate. The study, in line with recommendations of OCSPP 850.4100, 

should test the typical end use product (TEP) of etoxazole instead of TGAI as the currently 

available study did.

850.4500 Algal Toxicity (Freshwater green algae): There is currently no algal toxicity study 

with a freshwater green algae species submitted for etoxazole that is suitable for risk assessment. 

Previously, an algal toxicity study conducted with the freshwater green algae Selenastrum 

capricornutum (MRID 45621705) was submitted but determined to be unacceptable due to initial 

cell densities being over 7 fold more than the guideline recommended initial concentration. 

Additionally, this study was conducted for 72 hours instead of the guideline recommended 96 

hours. A new study is needed to characterize the toxicity of etoxazole to freshwater green algae.

850.4550 Cyanobacteria (Anabaena flos-aquae) toxicity: In a previously submitted 

cyanobacteria toxicity study (MRID 48578302), percent increases of 26 and 32% were observed 

in the solvent control for cell density and area under the curve, respectively. While these 

differences were not determined to be statistically significant (p>0.05), they were seen as 

biologically meaningful increases that confounded the ability to discern where the EC50 level 
5

was. This was due to the fact that the limit concentration (which also contained solvent) was 

32% decreased from the negative control. A new study is needed to characterize the toxicity of 

etoxazole to cyanobacteria.

Non-guideline: Honey Bee - 21-day repeated dose larval toxicity study Acceptable acute 

contact and oral toxicity data are available for adult honey bee exposures to etoxazole; however, 

data are not available for larval toxicity. As the mode of action of etoxazole is documented in 

regulatory documents and the literature to be an insect growth regulator affecting chitin (which is 

a component of the insect exoskeleton) biosynthesis, data are needed to characterize the toxicity 

of etoxazole to terrestrial invertebrates in this stage of the life cycle. Available non-guideline 

acute contact toxicity studies to other non-Apis terrestrial invertebrates corroborate enhanced 

toxicity to larvae compared to adults. The study being requested will aid in evaluating this 

concern for honey bees which serve as a surrogate for non-target terrestrial invertebrates. A 

protocol (following the OECD draft guidance document, November 25, 2013) should be 

submitted for review and approval by the Agency prior to initiation of this study. Pending the 

results of this study, higher tiered (e.g. semi-field) studies as well as residue studies may be 

required.

Non-guideline: Honey Bee Toxicity – 10-Day Adult Chronic Toxicity Study: Bees can be 

exposed to pesticides through multiple pathways including contact with sprays and dusts and 

through ingestion of residues in food/water (e.g., pollen/nectar and water used to maintain colony 

temperature). Worker bees foraging on flowers for pollen and nectar can be repeatedly exposed 

to residues in pollen and nectar either through direct contamination of these matrices by foliar 

sprays and/or dusts through translocation of residues via systemic transport of the active 

ingredient. Residues can in turn be brought back to bee colonies where in-hive bees including 

young adult and developing brood (i.e., eggs, larvae and pupae) may be exposed. EPA guidance 

on assessing the risk of pesticides to bees identifies a suite of laboratory-based studies intended 

that serve as the foundation for screening chemical for potential acute and chronic effects to 

individual adult and larval bees. The 10-day toxicity study with young adult bees provides noobserved adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) for 

assessing chronic effects. Data obtained from this study will be used in estimating chronic risk to 

individual adult bees. Risk estimates based on these data will be considered along with other 

lines of evidence to determine whether higher-tier studies are needed at the whole colony level. 

The registrant should provide a protocol and consult with the Agency prior to study initiation.

Non-Guideline: Residues in Pollen and Nectar: Submission of studies for crops of concern 

that evaluate residues in plant parts (e.g., pollen and nectar) may be of high value depending on 

the results of the screening level risk assessment and the Tier I larval bee toxicity study. If 

refinements to the screening level risk assessment for honey bees are needed, these studies will 

allow for a more refined exposure analysis when applications are made at bloom. As this 

chemical is of low toxicity to adults, applications at bloom could contaminate pollen and nectar 

that adult foragers bring back to the colonies and then expose the brood to etoxazole. In order to 

evaluate this exposure pathway, these residue studies would assess etoxazole residues in pollen 

and nectar. The registrant should provide a protocol and consult with the Agency prior to study 

initiation.
6

850.3040: Field Testing for Pollinators: Screening level and refined Tier I risk assessments 

with the honey bee larvae may indicate the need to progress to higher tier toxicity testing under 

semi-field or field conditions in order to evaluate the toxicity of the chemical to honey bees at 

the colony level. The primary uncertainties relate to the growth and reproduction of the colonies 

and measurement endpoints that relate to brood development and production. Additional data 

may therefore be needed to test the effects of etoxazole in the field to address these uncertainties, 

consequently guideline 850.3040 is identified as a data need. The registrant should provide a 

protocol and consult with the Agency prior to study initiation.

Non-guideline: Whole sediment, chronic toxicity test to freshwater midge (Chironomus 

dilutus). There are two sub-chronic (10-day) freshwater sediment studies with the freshwater 

midge and one chronic (28-day) estuarine/marine amphipod (Leptocheirus plumulosus) study 

available for etoxazole. Available data indicate etoxazole has a high propensity to bind to the 

sediment, shows high environmental persistence, and is likely to affect growth, development, and 

reproduction of arthropods via inhibition of chitin biosynthesis. Therefore, a chronic (60-day)

life cycle sediment toxicity study with the freshwater midge is requested. A protocol should be 

submitted to the Agency prior to study initiation. This protocol should follow the guidance 

document published by the Office of Research and Development (ORD) in 2000, “Methods for 

Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with 

Freshwater Invertebrates – EPA 600/R-99/064, March 2000.”

Non-guideline: Whole sediment, chronic toxicity test to freshwater amphipod (Hyalella 

azteca). There are two sub-chronic (10-day) freshwater sediment studies with the freshwater 

midge and one chronic (28-day) estuarine/marine amphipod (Leptocheirus plumulosus) available 

for etoxazole. Available data indicate etoxazole has a high propensity to bind to the sediment, 

shows high environmental persistence, and is likely to affect growth, development, and 

reproduction of arthropods via inhibition of chitin biosynthesis. Therefore, a chronic (42-day) 

life cycle sediment toxicity study with the freshwater amphipod is requested. A protocol should 

be submitted to the Agency prior to study initiation. This protocol should follow the guidance 

document published by the Office of Research and Development (ORD) in 2000, “Methods for 

Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with 

Freshwater Invertebrates – EPA 600/R-99/064, March 2000.”

Uncertainties

Degradates of Etoxazole

Even though the environmental fate database for the parent compound was found to be

substantially complete, there is considerable uncertainty concerning the environmental fate of 

various degradates of etoxazole (some of which are relatively persistent), particularly under 

aquatic metabolism conditions. The absence of full environmental fate information about such 

degradates constitutes an uncertainty at this time. In the forthcoming Preliminary Risk 

Assessment, EFED will use the total residue approach to determine the total toxic residues and 

assume that the degradates of concern are as toxic as the parent. The total residue approach is a 

modeling strategy that requires an assumption that all residues of concern have similar physical, 

chemical, and partitioning characteristics. Application rates for the parent pesticide are used to 
7

represent the total mass loading of pesticide and its degradation product. This modeling 

approach does not consider temporal occurrence of degradation products. As will be shown in 

this document, R-8 and R-13 will be considered degradates of ecotoxicological concern.

There is also uncertainty in the role of various competing dissipation and/or degradation 

mechanisms of etoxazole. Various studies have been deemed supplemental. The lack of aquatic 

metabolism studies constitutes another uncertainty since they would provide additional 

information related to aerobic and anaerobic persistence and the anaerobic aquatic degradates. 

Submission of new studies, as required in this Problem Formulation, will clear this uncertainty.

Additionally, while there is some registrant submitted toxicological data available for most of the 

major (i.e., ≥10% formation) degradates, there was uncertainty in the analytical measurements 

for two of the degradates assessed in the freshwater fish study. ECOSAR analysis was used to 

estimate toxicity of these degradates to further corroborate the results of the degradate toxicity 

studies and to also provide estimates on taxa where the submitted studies did not characterize. 

There is uncertainty inherent in all ECOSAR estimates due to the nature of some ECOSAR 

classes having more data points associated with the estimates than others (refer to Section 6.b for 

further details). Based on the analysis presented in Section 6.b, Table 1 shows both parent 

etoxazole and the major degradates that will be included in the expression of the total toxic 

residues of ecological concern.

Table 1. Etoxazole and Its Degradates of Ecological Concern

Applicant’s 

Code Chemical’s Name and SMILES Code Structure

Etoxazole IUPAC Name: (RS)-5-tert-butyl-2-[2-(2,6-

difluorophenyl)4,5-dihydro-1,3-oxazole-4-yl] 

phenetole

CAS Name: 2-(2,6-difluorophenyl)4-[4-(1,1-

demethylethyl) 2-ethoxyphenyl-4,5-dihydrooxazole

CAS No.: 153233-91-1

Formula: C21H23F2NO2

MW: 359.4 g/mol

R-8 2-amino-2-(4-tert-butyl-2-ethoxyphenyl)ethanol

SMILES Code:

C(C1=C(C=C(C=C1)C(C)(C)C)OCC)(N([H])[H])CO[

H]

Formula: C14H23NO2

MW: 237.34 g/mol

R-13 4-(4-tert-Butyl-2-ethoxyphenyl)-2-(2,6-

difluorophenyl)-oxazole

SMILES Code:

C1(=CC=CC(=C1C2=NC(=CO2)C3=C(C=C(C=C3)C(

C)(C)C)OCC)F)F

Formula: C21H21F2NO2

MW: 357.40 g/mol

O

N

F

F

O

C

CH3

CH3

H3C

C

H2

CH3

C

CH3

CH3

H3C

C

H2

OH

NH2

O

C

H2

H3C

N

O

O

C

CH3

CH3

H3C

F

F

C

H2

H3C
8

Toxicity to Larval and Juvenile Honeybees 

Currently, there are data available that characterize the acute contact and acute oral toxicity of 

etoxazole to adult honeybees. As will be discussed in this assessment, etoxazole has an insect 

growth regulator type mode of action in which the biosynthesis of chitin (a major component of 

the insect exoskeleton) is inhibited. As such, the molting process is disrupted and toxicity would 

be anticipated to be greater for larval and juvenile honey bees. Currently available non-guideline 

studies conducted on non-Apis terrestrial invertebrates corroborate the suggestion that larval and 

juvenile insects are more sensitive to etoxazole exposure than adults. Further toxicity data is 

needed to characterize this uncertainty.

2. Introduction

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

dihydrooxazole; IUPAC name: (RS)-5-tert-butyl-2-[2-(2,6-difluorophenyl)-4,5-dihydro-1,3-

oxazol-4-yl]phenetole; CAS number 153233-91-1; PC Code 107091; and molecular formula 

C21H23F2NO2], is an acaricide/miticide growth inhibitor (IRAC1 Subgroup 10B, etoxazole is the 

sole chemical in subgroup 10B). Its chemical class is diphenyl oxazoline. It reportedly works by 

contact of the mite juvenile stages (eggs to nymphs), but does not kill adult mites. Work by 

Nauen and Smagghe (2006) suggested that etoxazole’s mode of action is inhibition of chitin 

biosynthesis (chitin is the main component of the exoskeletons of arthropods). “Etoxazole 

induced molting defects in fall armyworm larvae similar, if not identical, to those caused by 

benzoylphenylureas, a well-known class of insecticidal chitin biosynthesis inhibitors2.” 

Furthermore, the European Food Safety Authority (EFSA) document “Modification of Existing 

MRLs for Etoxazole in Cherries, Plums, and Bananas,” states that etoxazole, “is non-systemic 

and acts by inhibiting chitin biosynthesis; thereby interfering with the molting process of 

juvenile red and yellow mites. It also exhibits ovicidal activity and has a sterilizing effect on 

females.”

For more information on use and usage, please see the LUIS Report (USEPA 2014a) and BEAD 

Chemical Profile document (USEPA 2014b), both of which are located in the docket.

EFED evaluated the most recent ecological risk assessments for etoxazole in association with the 

updated toxicity, exposure, and usage information to determine if sufficient data are available 

and if further updates are needed to support registration review.

In addition, EFED considered the latest Agency science policies and risk assessment 

methodologies. The structure of etoxazole, as well as the chemical names and other identifiers 

can be found in the chemical identity table attached to this document (Appendix 1).

 

1

Insecticide Resistance Action Committee (http://www.irac-online.org/).

2 Nauen, Ralf and Smagghe, Guy. 2006. “Rapid Report – mode of action of etoxazole.” Pest Management Science, 

Vol 62, pp. 379-382.
9

3. Use Characterization

There are one Technical, and six active Section 3, six Special Local Needs (SLNs) (one in 

Nevada, one in Washington, two in Oregon, and two in Idaho) labels for etoxazole. Of the 

Section 3 labels, one is for fully enclosed greenhouse use and another is for use as a fogger 

indoors (these uses are not assessed in EFED). The remaining four Section 3 labels include a 

number of outdoor uses (listed below) and are formulated as water dispersible granules (WDG), 

emulsifiable concentrate (EC) and water soluble packets (WP). The Special Local Needs labels 

are for the states of WA, NV, ID and OR.

The following are etoxazole’s uses: the caneberry subgroup 13-07a, small fruit vine climbing 

subgroup 13-07F (except fuzzy kiwifruit), low growing berry subgroup 13-07G, peppers and 

eggplant subgroup 8-10b, alfalfa, apple, carrots, corn, cotton, cucumber, cucurbit crop group 9, 

eggplant, fruit trees (unspecified), hops, mint/peppermint/spearmint, pear, peppers, pome fruit 

crop group 11, pumpkin, squash, stone fruit crop group 12, strawberry, subtropical/ tropical 

fruits, tomato and tree nuts are among the edible crops. Meanwhile, additionally Christmas tree 

plantations, greenhouse (in use) and ornamentals are other crops. According to the Screening 

Level Usage Analysis for etoxazole, dated May 9, 2013, the major uses for the chemical are 

almonds, apples, cotton, grapes, pears, strawberries, and walnuts. The SLUA covers the years 

2004-2011 (USEPA 2014a).

It is applied aerially or by ground applications using compressed air sprays, hydraulic sprayers, 

or ground boom sprayers. The chemical profile produced by BEAD, located in the docket, lists 

the use patterns of maximum exposures for the current uses of Etoxazole. EFED will use 

application scenarios that result in maximum exposure scenarios for a given use for the risk 

assessment. Any absence of information on the labels that specifies the maximum single 

application rate, the application interval, the annual maximum rate allowed (lbs a.i./year), or 

application method may result in conservative assumptions.

It is noteworthy that the etoxazole labels do not have any limitations regarding applications of 

the chemical when honeybees are actively foraging, such as other insecticides and/or miticides. 

In the past, etoxazole has been found to be practically non-toxic to adult honeybees in a 

combination acute contact and oral toxicity study.

4. Conclusions from Previous Risk Assessments

This problem formulation updates conclusions from recent risk assessments, including the 

following:

 Use of Etoxazole on corn (DP Barcode D385424, dated 2/18/2011);

 Uses on caneberry (Crop Subgroup 13-07 A), cucurbit vegetables (Crop Group 9), lowgrowing berry (Subgroup 13-07G), pepper and eggplant group (Crop Group 8), small 

fruit vine-climbing, except fuzzy kiwifruit (Subgroup 13-07 F), and tropical and subtropical inedible peel (includes avocado, canistel, mango, papaya, sapodilla, black and 

mamey sapote, and star apple) (D374125+, dated 11/03/2010);
10

 Uses on plum, peach (stone fruits), cucumber, greenhouse tomato, and mint (D353084, 

dated 03/24/2009);

 Uses on cherries, melon, and hops, and increased rate on cotton (D341221+, dated 

10/01/2007); and,

 Uses on pome fruits, strawberries, and cotton (D283732, dated 08/14/2003).

a. Ecological Risk Assessment 

The Agency has conducted multiple ecological risk assessments on etoxazole that serve as a 

basis for this preliminary problem formulation, that are provided in the list above. The primary 

risk issues have been identified for water column and sediment dwelling invertebrates, which is 

consistent with its use as an insect growth regulator type miticide that is believed to inhibit chitin 

biosynthesis. Previous risk findings are summarized in Table 2.

Table 2. Summary of Risk Concerns Identified for Etoxazole in Previous Assessments

Birds Mammals Terr.

Plants

Terr.

Inverts Fish BCF Aquatic Inverts

Aquatic 

Plants

Groundwater 

Contamination Persistence Degradates of Concern

No1 No No NA No NA3 Yes2 Yes No Yes4 R-8, R-135

1 Toxicity values were non-definitive (“>”) 

2 For both water column and sediment dwelling invertebrates

3 Log KOW of 5.52, BCF = 1600 L/kg for edible tissue, but 78% of residues were depurated after 5 days.

4 Etoxazole shows moderate persistence (weeks to months) under most testing conditions.

5 These degradates were consider in previous drinking water assessments (Section 4.b). Refer to Section 6.b for a 

rationale to include these degradates in the expression of the total toxic residues of ecological concern.

“Yes” = at least one LOC has been exceeded in previous assessments; “No” = LOCs have not been exceeded in 

previous assessments; “NA” = RQs have not been calculated previously.

b. Drinking Water Exposure Assessments

The most recent Tier 1 drinking water exposure assessment (DWA) was conducted in 2011 

(USEPA 2011), for the proposed new uses on field corn, popcorn and corn grown for seed 

production. The proposed maximum single application rate was 0.135 lb a.i./A and the seasonal 

application rate was 0.270 lb a.i./A. Based on an inspection of the new uses of etoxazole, it was 

found that the crop mint still represented the scenario with the highest exposure and 

consequently the highest EDWCs (with single application rates of 0.18 lb a.i./A and seasonal 

rates of 0.36 lb a.i./A). Therefore, the drinking water assessment results did not change from the 

previous ones. The assessment that included the use on mint (USEPA 2009) indicated that the 

Tier I Estimated Drinking Water Concentrations (EDWCs) for etoxazole and for its major 

transformation products R-8 and R-13 (as per the request of the Metabolism Assessment Review 

Committee or MARC, DP Barcode D288817, 04/23/2003), calculated using FIRST (surface 

water) and SCI-GROW (ground water) for use in the human health risk assessment were as 

shown in Table 3.
11

Table 3. Tier I Estimated Drinking Water Concentrations (EDWCs) for human health 

drinking water risk assessment for ground application of etoxazole, based on a seasonal 

application on mint of 0.36 lb a.i./A/season.

Chemical Acute EDWC Surface 

Water FIRST (ppb)

Chronic EDWC Surface 

Water FIRST (ppb)*

Acute and Chronic EDWC 

Ground Water SCI-GROW 

(ppb)*

Etoxazole 6.07 0.618 0.00346

R-8 8.03 4.08 0.742

R-13 1.63 0.063 0.000644

* Results presented in ppb of the chemical, as opposed to ppb of parent equivalent.

c. Clean Water Act Programs

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

section 303(d) of the Clean Water Act. No Total Maximum Daily Load (TMDL) criteria have 

been developed for Etoxazole (at 

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

accessed 02/14/2014). Aquatic benchmarks have not been established for etoxazole, based on 

information available at http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm

(accessed 02/14/2014). Any data submitted or otherwise located as part of the registration 

review process may be used to update aquatic life benchmarks if applicable.

5. Environmental Fate and Transport

The major routes of dissipation of etoxazole are aqueous and soil photolysis (half-lives 34 and

19.3 days, respectively), and aerobic soil metabolism (half-lives ranging from 10.2-44.7 days at 

relevant environmental temperatures, 7 measurements and 5 soils). Etoxazole is stable to 

hydrolysis at a range of environmental pHs, and compared to the aerobic conditions, the 

anaerobic metabolism is a relatively minor route of dissipation for the chemical (half-lives were 

>100 days). No aerobic aquatic metabolism studies are available at this time. The relatively 

high soil organic carbon adsorption coefficient (KOC ≥ 4910 mL/gOC), indicates that it may not be 

a direct threat to ground waters; however, previous modeling results indicated that it may reach 

significant levels in adjacent bodies of surface water. Etoxazole was slightly to hardly mobile 

(FAO mobility classification, FAO 2000) in batch equilibrium studies conducted on 8 soils (KF

range 66-335 mL/g; KFOC range 4910-55300 mL/gOC). Due to its relatively high organic carbon 

sorption coefficient and octanol/water partition coefficient (KOW = 331000; log KOW = 5.52), 

coupled with its low solubility (75 ppb) and moderately high persistence, etoxazole and its 

degradates of concern are expected to partition with the sediment phase in aquatic systems and 

persist in that phase.

Field dissipation studies, conducted in bare soils in California (Elder sandy loam soil, 

representative of a typical strawberries site), Idaho (Cashmere sandy loam soil, representative of 

a typical apples site), and Mississippi (Dundee silt loam soil, representative of a typical cotton 

site), indicated that etoxazole is relatively short lived (half-lives ranged from <1 day to 11.7 

days), when compared to the etoxazole half-life for aerobic soil metabolism. A combination of 
12

dissipation mechanisms may be playing a role in the environment. The only transformation 

product observed in the field in substantial amounts was R-7 (generally detected only in the 0-7.5 

cm soil depth), with R-3 observed in smaller amounts. It should be noted that all three terrestrial 

field dissipation studies were conducted in bare ground sites. For terrestrial field dissipation 

studies conducted in cropped sites, generally the chemicals show higher persistence than in bare 

soils.

Etoxazole shows a significant potential to bioconcentrate, as expected from its relatively high 

octanol/water partition coefficient (see above). Residues bioconcentrated in rainbow trout with 

maximum bioconcentration factors of 1600 L/kg for the edible tissue, and 3300 L/kg for whole 

fish. Etoxazole was 84.6% of the total residues in edible tissue. Two minor degradates: R-2/R-4 

and R-13 were <1.5% of the total residues in fish. Depuration was relatively rapid (half-life 2.6 

days for edible tissue and 4.6-6.2 days for non-edible tissue).

A selection of environmental fate and transport properties of etoxazole is provided in Table 4. 

The environmental fate of etoxazole degradation products is discussed in Section 5a.

Table 4. Summary of physicochemical and environmental fate and transport properties of 

etoxazole

PARAMETER VALUE(S) (units) SOURCE COMMENTS

SELECTED PHYSICAL/CHEMICAL PARAMETERS

 CAS Chemical Name 2-(2,6-difluorophenyl)-4-[4-(1,1-

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

dihydrooxazole

_ –

 Molecular Weight 359.42 g/mole _ –

 Solubility (20°C) 0.075 mg/L or ppm MRIDs: 

45089902,

45089903.

–

 Vapor Pressure (20°C) 7 x 10-6torr

The chemical lies between ‘non-volatile’ 

to ‘intermediate to high volatility’ under 

field conditions.

MRID: 

45089902.

USEPA 2010

 Henry’s Law constant

 (20°C)

8.5 x 10-6atm-m3/mol Calculated Estimated from 

vapor pressure and 

water solubility.

Octanol-Water Partition 

Coefficient (KOW)

3.31x105 MRID: 

45089902.

Hydrophobic

PERSISTENCE

 Hydrolysis Half-life 

 [pH 5, 7, 9; (20°C)]

pH 5 9.6 days (major product R-7);

pH 7 ~stable (reported 99 days is beyond 

the study duration, major product R-4);

pH 9 ~stable (reported 98 days is beyond 

the study duration, major product R-4)

MRID: 

45090017.

Not an important 

route of degradation. 

Assumed to be 

stable.
13

PARAMETER VALUE(S) (units) SOURCE COMMENTS

 Aqueous Photolysis Halflife (pH 7)28.8 days of 12 hours of sunlight/12 

hours dark;

Environmental half-life of 34 days, based 

on solar readings in Dublin, CA.

Major products are R-11 and CO2. 

Several minor products.

MRID: 

46658101.

Dark control 

corrected. 

Moderately rapid 

degradation 

pathway.

 Soil Photolysis Half-life CL from UK, t1/2 = 19.3 days;

Major products R-3 and R-11.

MRIDs: 

45090020, 

46299904.

Moderately rapid 

degradation 

pathway.

 Aerobic Soil Metabolism 

Half-life

Study performed using [U14C-tert-butylphenyl] and [U14C-difluorophenyl] 

radiolabels:

SL from UK 10.2-12.0 days.

SL from CA 19.4-23.2 days.

Studies performed using [U14C-tertbutylphenyl] radiolabel:

S from Germany 12.7 days.

LS from Germany 21.5 d.

CL from UK 44.7 days.

SL from UK at 10C, 26.2 days.

SL from UK at 30C, 2.3 days.

Various major products observed across 

studies in one or more of the soils:

R-3, R-4, R-7, R-8 and R-13.

MRIDs: 

45090019, 

45090021, 

45090022.

Moderately rapid 

degradation 

pathway. 

Unextracted residues 

were high in the 

latter test intervals in 

some of these 

studies.

 Anaerobic Soil Metabolism

Half-life

SL from UK 101.9-111.8 days.

Major products R-8 and R-11.

MRID: 

45090023.

Not a rapid 

degradation 

pathway.

 Aerobic Aquatic 

Metabolism Half-life

Not available Not Applicable –

 Anaerobic Aquatic 

Metabolism Half-life (250C)

Water clay sediment from Greenville, MS 

138-155 days. Etoxazole was associated 

with the sediment. Major products R-4 

and R-11.

MRID: 

45621718.

Not a rapid 

degradation 

pathway.

MOBILITY

 Organic Carbon Partition

 Coefficient (KFOC)

 Parent Etoxazole

5460, 5230, 11000, 4910, and 18000, 

23100, 55300, 14200 mL/gOC

MRIDs: 

45090024, 

45090026, 

46299905, 

46299906.

For SL, CL, S, LS,

and SL, SL, SL and 

SL soils, 

respectively

 Soil Partition Coefficient

 (KF)

 Parent Etoxazole

131, 68, 66, 103, and 156, 335, 193, 156 

mL/g

MRIDs: 

45090024, 

45090026, 

46299905, 

46299906.

For SL, CL, S, LS, 

and SL, SL, SL and 

SL soils, 

respectively

FIELD DISSIPATION

 Terrestrial Field Dissipation 

 Half-life

St. Martin des Bois (Northern France) 

SiCL: DT50=8 days.

Montech (Southern France)

MRIDs: 

45250909, 

45621721, 

_
14

PARAMETER VALUE(S) (units) SOURCE COMMENTS

CL: DT50=8 days.

Senas (Southern France)

CL: DT50=4 days.

Schleithal (Northern France)

SiL: DT50=9 days.

Only R-8 was monitored. It was not

detected at any test interval.

Bare ground in Santa Cruz Co., CA, SL; 

t1⁄2=7.0 days, major product detected R-7 

(generally 0-7.5 cm soil layer)

Bare ground in Payette Co., ID, SL; 

t1⁄2=11.7 days, major product detected R-7 

(only in the 0-7.5 cm soil layer)

Bare ground in Washington Co., MS, 

SiL; t1⁄2=<1 day, major product detected 

R-7 (only in 0-7.5 cm soil layer)

45621722, 

45621723

FISH BIOCONCENTRATION

Bioconcentration in Fish

(Maximum BCF)

Rainbow trout

1600 L/kg for edible tissues

4700 L/kg for non-edible tissues

3300 L/kg for whole fish

Residues were comprised mainly by 

parent etoxazole.

After 5 days depuration, 70-78% of the 

[

14C]residues were depurated

(Estimated depuration t1⁄2 = 2.6 days for 

edible tissues, and 4.6-6.2 days for nonedible tissues.)

MRIDs: 

45621615, 

46269907.

_

SL=sandy loam; CL=clay loam; S=sand; LS=loamy sand; SiCL=silty clay loam; SiL=silty loam

a. Transformation Products

Important transformation products of etoxazole, observed in amounts of greater than 10% of the 

applied radioactivity (AR), appear to be R-3, R-4, R-7, R-8, R-11, and R-13 (for structures, 

nomenclature, and more detail about amounts observed in the available studies, refer to 

Appendix A; Figure A.1 in the appendix shows the registrant-proposed degradation pathway for 

etoxazole in aerobic soils). Of these degradates, R-8 is more mobile and relatively persistent. R7 shows moderate mobility. The major transformation products were R-11 in an anaerobic soil 

metabolism study and R-11 and R-4 in an anaerobic aquatic metabolism study. Insufficient data 

are available, however to reliably calculate degradation rates, half-lives, or other persistence 

parameters for some of the degradation products. In the bioconcentration study, R-13 and a 

mixture of R-4 and R-2

3

, were minor degradates identified in fish tissue.

Table 5 summarizes the available mobility data for the degradates of etoxazole R-3, R-4, R-7, R8 and R-13. Three measurements were made using HPLC methodology, of which one was an 

extrapolated KOC (for R-7). There was approximately a 10-fold discrepancy between the KOC

 

3 2-2,6-difluoro-pheny1)-4-[2-ethoxy-4-(1-hydroxymethyl-1- methylethyl)phenyl]-4,5-dihydrooxazole
15

obtained through HPLC and a batch equilibrium study for R-7. Since for R-7 the HPLC result 

was extrapolated, the results of the batch equilibrium study are regarded as more reliable. Of 

these compounds, R-13 appears to be the least mobile of all compounds (KOC>13000 mL/gOC). 

No mobility data is available about R-11.

Table 5. Summary of available sorption / mobility studies for etoxazole transformation 

products.

PARAMETER VALUE(S) (units) SOURCE COMMENTS

 Organic Carbon Partition

 Coefficient (KOC), 

Transformation Products 

calculated using HPLC method

R-3: 5130 mL/gOC

R-4: 759 mL/gOC

R-7: 79400* mL/gOC

MRID: 45090025 *Extrapolated value

 Soil Partition Coefficient (KF), 

Transformation Product R-7

27, 98, 14 mL/g MRID: 45250906 For SL, CL and S soils, 

respectively

 Organic Carbon Partition

 Coefficient (KFOC), 

Transformation Product R-7

1125, 7540, 2330 mL/gOC MRID: 45250906 For SL, CL and S soils, 

respectively

 Soil Partition Coefficient (KF), 

Transformation Product R-8

2.48, 4.56, 1.24 mL/g MRID: 45250907 For SL, CL and S soils, 

respectively

 Organic Carbon Partition

 Coefficient (KFOC), 

Transformation Product R-8

103, 351, 207 mL/gOC MRID: 45250907 For SL, CL and S soils, 

respectively

 Soil Partition Coefficient (KF), 

Transformation Product R-13

877, 1082, 82 mL/g MRID: 45250908 For SL, CL and S soils, 

respectively

 Organic Carbon Partition

 Coefficient (KFOC), 

Transformation Product R-13

36540, 83230, 13670 

mL/gOC

MRID: 45250908 For SL, CL and S soils, 

respectively

SL=sandy loam; CL=clay loam; S=sand

*This value was extrapolated beyond the range of the reference substances.

6. Receptors

As described in the Agency's Overview Document (U.S EPA, 2004), the most sensitive endpoint 

for each taxonomic group will be used to calculate risk quotients (RQs). Assessment endpoints 

include direct toxic effects on the survival, reproduction, and growth of terrestrial and aquatic 

life as well as indirect effects such as reduction in prey base and/or modification of habitat. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature are used to evaluate the potential direct effects of etoxazole to the 

aquatic and terrestrial receptors identified in this section. This includes toxicity data on the 

technical grade active ingredient, degradates, and when available, formulated products. The open 

literature studies are identified through EPA's ECOTOX database (http://cfpub.epa.gov/ecotox/), 

which employs a literature search engine for locating chemical toxicity data for aquatic life, 

terrestrial plants, and wildlife. 

a. Effects to Aquatic Organisms

A summary of the available ecotoxicity information and the incident information for etoxazole

are provided below. Table 6 provides a summary of the taxonomic groups and the surrogate 
16

species tested to help understand potential acute and chronic ecological effects of etoxazole. In 

addition, the table provides a preliminary overview of the potential acute toxicity of etoxazole by 

providing the acute toxicity classifications. 

Etoxazole did not elicit a 50% mortality response in the freshwater and estuarine/marine fish

acute toxicity tests conducted up to the limit of solubility (0.075 mg/L, 3 of 5 concentrations 

tested were above the limit of solubility) and there were no clinical signs of toxicity reported in 

those studies. This is in contrast with the response of freshwater and estuarine/marine 

invertebrates in which a definitive EC/LC50 was achieved in all studies conducted that were 

tested below the solubility limit. Clinical signs of toxicity in these studies included lethargy and 

loss of equilibrium in surviving organisms.

On a chronic exposure basis, an early life stage study with freshwater fish yielded effects on 

larval survival, embryo viability, survival at hatch, and length. Chronic toxicity to freshwater 

invertebrates was determined to be at levels as low as 0.21 μg a.i/L with effects including 

survival, total number of young per female and growth measurements. Similarly for 

estuarine/marine invertebrates, chronic exposure of etoxazole resulted in significant reductions in 

survival, number of young per reproductive day, and growth measurements for both males and 

females. 

There are two 10-day freshwater midge studies and one 28-day estuarine/marine amphipod study 

available to characterize the toxicity of etoxazole to sediment-dwelling invertebrates. Definitive 

NOAECs were reached in the freshwater midge studies that included effects on survival in both 

the sediment and pore water compartments (10 mg a.i/kg sediment and 26 μg a.i/L, respectively). 

Effects on growth were noted at concentrations higher than the solubility limit of etoxazole in the 

pore water. The result of the estuarine/marine sediment dwelling invertebrate study shows

increased toxicity over the freshwater midge for survival, growth, and reproductive endpoints (22 

mg /kg TOC and 1 μg a.i/L for the sediment and pore water compartments, respectively).

Table 6. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for 

Etoxazole

Taxonomic 

Group Study Type Surrogate Species

Toxicity Value

(all units in 

terms of 

measured active 

ingredient)

2

Acute 

Toxicity 

Classification

Source

(Classification)

Freshwater fish1

Acute

Rainbow trout

(Oncorhynchus 

mykiss)

LC50 > 370 μg/L 

(N/A; N/A) Highly toxic 46059001(Acceptable)

Chronic 

(Early LifeStage)Rainbow trout

NOAEC = 15 

μg/L

LOAEC = 33 

μg/L

Endpoint: 89-day 

length

--

45621614

(Acceptable)

Freshwater 

invertebrates Acute Water Flea (Daphnia magna)

EC50 = 7.3 μg/L 

(6.2 – 8.5; 7.2)

Very highly 

toxic

45089914

(Acceptable)
17

Taxonomic 

Group Study Type Surrogate Species

Toxicity Value

(all units in 

terms of 

measured active 

ingredient)

2

Acute 

Toxicity 

Classification

Source

(Classification)

Chronic Water Flea 

(Daphnia magna)

NOAEC (length, 

dry weight, 

reproduction): 

0.13 μg/L

LOAEC: 0.21 

μg/L

--

46497901

(Supplemental)

Estuarine/marine 

fish Acute

Sheepshead Minnow 

(Cyprinodon 

variegatus)

LC50 >160 μg/L

(N/A; N /A)

Very highly 

toxic

45621608

(Supplemental)

Estuarine/marine 

invertebrates

Acute

Mysid Shrimp

(Mysidopsis bahia)

LC50 = 4.42 μg/L 

(3.96 – 4.98; 10.3)

Very highly 

toxic

45621611

(Acceptable)

Eastern oyster

(Crassostrea 

virginica)

LC50 = 1.1 μg/L 

(0.72 – 1.6; 1.7)

Very highly 

toxic

45621610

(Acceptable)

Chronic (life 

cycle)

Mysid Shrimp

(Mysidopsis bahia)

NOAEC 

(reproduction): 

0.32 μg/L

LOAEC: 0.71 

μg/L

--

45621612 

(Supplemental)

Freshwater 

Sedimentdwelling 

invertebrates

Sub-chronic 

(10-day)

Freshwater midge 

(Chironomus 

riparius)

Sediment:

NOAEC

(mortality) 10 mg

a.i./kg 

Pore water:

NOAEC 

(mortality): 26

μg/L

--

47837702

(Supplemental)

Freshwater 

Sedimentdwelling 

invertebrates

Chronic (28-

day)

Estuarine/marine 

amphipod 

(Leptocheirus 

plumulosus)

Sediment (OCnormalized):

NOAEC

(mortality) 22 mg

/kg TOC

Pore water:

NOAEC 

(mortality): 1

μg/L

--

47837701

(Acceptable)

Aquatic plants 

and algae Vascular Duckweed (Lemna gibba)

EC25 (all 

endpoints): >56 

μg/L

NOAEC (all 

endpoints): 56 

μg/L

--

48578301

(Supplemental)
18

Taxonomic 

Group Study Type Surrogate Species

Toxicity Value

(all units in 

terms of 

measured active 

ingredient)

2

Acute 

Toxicity 

Classification

Source

(Classification)

Nonvascular

Marine diatom 

(Navicula 

pelliculosa)

EC25 (all 

endpoints): >51.9 

μg/L

NOAEC (all 

endpoints): 51.9 

μg/L

--

48603001

(Acceptable)

1 Freshwater fish may be surrogates for aquatic-phase amphibians.

2

(95% confidence intervals; slope) if available

Table 7 shows the results of available degradate toxicity studies of etoxazole. The same five 

degradates were tested in freshwater fish and freshwater invertebrate studies with a lack of a 

50% mortality response at the single concentration tested. In the freshwater fish study, the 

analytical results of degradates R-4 and R-7 were highly unstable and therefore it was unclear 

what concentration to which the organisms were actually exposed. The results of these two 

degradates as they relate to freshwater fish are therefore unreliable. R-4 forms marginally above 

rates of 10% in available aerobic soil and anaerobic aquatic metabolism studies while R-7 was 

observed at rates of up to 70% in terrestrial field dissipation studies but is not shown to be 

persistent. The degradate toxicity study with freshwater invertebrates makes note that R-7 had 

dissipated substantially by the end of study duration of 48 hours yet the results of the study were 

still determined to be suitable for risk assessment..

Table 7. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for the 

Degradation Products of Etoxazole

Taxonomic 

Group (study 

type)

Degradate Surrogate Species

Toxicity Value

(all units in terms 

of measured active 

ingredient)

Acute

Toxicity 

Classification

Source

(Classification)

Freshwater fish

R-3

Bluegill sunfish

LC50 = >0.80 mg/L

--

45089913

(Supplemental)

R-4 Results not reliable3

R-7 Results not reliable3

R-8 LC50 = >0.88 mg/L

R-13 LC50 = >0.74 mg/L

Freshwater 

invertebrates

R-3

Water flea 

EC50 = >0.55 mg/L

--

45621609

(Supplemental)

R-4 EC50 = >1.3 mg/L

R-7 EC50 = >0.74 mg/L

R-8 EC50 = >1.4 mg/L

R-13 EC50 = >0.73 mg/L

Aquatic Nonvascular plant

R-3

Freshwater green 

algae (Selenastrum 

capricornutum)

EC50 = >1.0 mg/L

NOAEC (cell 

density): <0.11 

mg/L

--

45621704

(Supplemental)

R-7

EC50 = >0.99 mg/L

NOAEC (cell 

density): <0.07 

mg/L

--

45621702

(Supplemental)
19

Taxonomic 

Group (study 

type)

Degradate Surrogate Species

Toxicity Value

(all units in terms 

of measured active 

ingredient)

Acute

Toxicity 

Classification

Source

(Classification)

R-13

EC50 = >1.0 mg/L

NOAEC (AUC, 

growth rate): 0.079 

mg/L

--

45621703

(Supplemental)

1 Freshwater fish may be surrogates for aquatic-phase amphibians.

2 Toxicity endpoints presented, i.e., NOAEC or EC50, are the only ones available from the study.

3Analytical measurements for R-4 and R-7 were highly variable in this study and therefore the true exposure estimates are 

unavailable.

b. Effects to Terrestrial Organisms

Terrestrial studies indicated a general lack of toxicity for birds (acute oral and sub-acute dietary 

based) and mammals (acute and chronic) with acute studies reaching non-definitive endpoints. 

In one avian reproduction study with the northern bobwhite quail, etoxazole exposure in the diet 

caused significant (p<0.05) reductions in 14-day viable embryos and number of hatched chicks

(13 and 14% effects, respectively) at the highest concentration tested (958 ppm). No other 

significant effects or treatment related clinical signs of toxicity were reported. In another avian 

reproduction study with the mallard duck, there were no significant effects reported for any 

reproductive parameter up to and including the highest treatment concentration. Tier I seedling 

emergence and vegetative vigor studies are available that were not able to achieve definitive 

EC25 values based on a lack of effects up to that threshold for both studies on all crops tested. It 

is noted however that these studies were conducted using TGAI and not TEP and also tested at 

an application rate that represents one third of the current maximum labeled rate.

A combination acute toxicity study to honeybees demonstrated that etoxazole was practically 

nontoxic to adults on an acute contact and acute oral basis. This finding is generally expected of 

an insect growth regulator type chemical as etoxazole where the mode of action would be 

expected to have greater activity on larvae and juvenile bees. 

Table 8. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for 

Etoxazole

Taxonomic 

Group Study Type Surrogate Species

Toxicity Value

(all units in terms 

of measured active 

ingredient)2,3

Acute 

Toxicity 

Classification

Source

(Classification)

Birds1

Acute

Mallard duck

(Anas

platyrhynchos)

LD50 > 2000 mg/kgbw (N/A; N/A)Practically 

non- toxic

45089908

(Acceptable)

Sub-acute 

dietary

Bobwhite quail

(Colinus 

virginianus)

LC50 > 5060 mg/kgdiet (N/A; N/A) Practically 

non- toxic

45089910

(Acceptable)
20

Taxonomic 

Group Study Type Surrogate Species

Toxicity Value

(all units in terms 

of measured active 

ingredient)2,3

Acute 

Toxicity 

Classification

Source

(Classification)

Chronic

Bobwhite quail

(Colinus 

virginianus)

NOAEC = 286 ppm

LOAEC = 958 ppm

--

45621606

(Supplemental)

Mammals

Acute Oral

Laboratory rat 

(Rattus 

norvegicus)

LD50 > 5000 mg/kg Toxicity 

Category IV 45089919

Acute 

Inhalation Laboratory rat LC50 > 1.09 mg/L Toxicity Category III 45089923

Chronic

Laboratory rat 

(Rattus 

norvegicus)

NOAEL = 2000 ppm

LOAEL = Not 

determined

Endpoint: None

--

45090007, 

45090006

Insects

Acute 

contact/oral 

combination 

study

Honey bee 

(Apis mellifera 

L.)

Contact LD50 > 200

μg/bee (N/A; N/A)

Oral LD50 > 200 

μg/bee (N/A; N/A)

Practically 

non-toxic

45621706

(Supplemental)

Terrestrial 

plants

Seedling 

Emergence

(Tier I)

Dicot – None

EC25 > 0.060 lbs 

a.i/A (N/A; N/A)

NOAEC = 0.060 lbs 

a.i/A

Endpoint: N/A

--

45621623

(Acceptable)

Monocot – None

EC25 > 0.060 lbs 

a.i/A (N/A; N/A)

NOAEC = 0.060 lbs 

a.i/A

Endpoint: N/A

Vegetative 

Vigor (Tier I)

Dicot – None

EC25 > 0.060 lbs 

a.i/A (N/A; N/A)

NOAEC = 0.060 lbs 

a.i/A

Endpoint: N/A

--

45621701

(Acceptable)

Monocot – None

EC25 > 0.060 lbs 

a.i/A (N/A; N/A)

NOAEC = 0.060 lbs 

a.i/A

Endpoint: N/A

1 Birds represent surrogates for terrestrial-phase amphibians and reptiles.

2Range of numbers within parentheses refers to the 95% confidence limit of the point estimate value

3An N/A under endpoint means that there was not a most sensitive species tested.

There are several non-guideline beneficial insect studies available for etoxazole. They vary from 

acute contact toxicity tests (like those conducted with the honeybee) to field tests conducted in 

infested agricultural sites. The field studies in particular assess the efficacy of etoxazole on the 

target pests while also examining the detrimental effects to beneficial insects that serve as 

predators for these pests. These results are summarized below in Table 9. The results generally 

corroborate the known mode of action of etoxazole in that adult insects are less susceptible than 

are larvae and juvenile insects, suggesting the need for larval toxicity data.
21

Table 9. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for 

Etoxazole 

Study

(application) Test Species Results synopsis MRID (Classification)

Beneficial predators 

of red mites field 

study in an infested 

apple orchard

(0.05 L/hectare)

Red Mite (target)

6 days: 44% reduction in mobile forms 

and eggs; 26 days: Recovered to 9% 

reduction

45621708

(Supplemental)

Phytoseid mite

(beneficial)

26 days: reduction of 54% of mobile 

forms

Acarophage ladybird 

(beneficial)

6 days: Number per 1,000 prey reduced 

by 33%

26 days: Recovered to 2% reduction 

Heteroptera (beneficial)

26 days: Adult and adult and larvae 

groups were reduced 54 and 50%, 

respectively

Neutroptera (beneficial) Not reduced at any sampling interval

Parasitoid Hymenoptera

(beneficial)

6 days: 27% reduction in mobile forms; 

26 days: Recovered to 6% reduction

Acute contact 

toxicity test

(55 g a.i/hectare)

Lacewing (Chrysoperia 

carnea)

- Lacewing larvae exposed to single 

application.

- 85% of population died after 13 days 

before pupation

- 5 of 6 surviving pupae emerged as 

adults

45621709

(Supplemental)

Acute contact and 

reproductive test

(55 g a.i/hectare)

Parasitic Wasp

(Aphidius Rhopalosiphi)

Adults: Mortality in control and 

treatment was 13 and 15% respectively; 

mean mummies per female was 1.0 and 

0.5 in control and treatment, 

respectively

Juvenile: Emergence by 5 days was 

100% and 96% in control and treatment 

respectively; mortality was 21 and 33% 

in control and treatment respectively; 

mean mummies per female was 5.6 and 

9.1 for control and treatment, 

respectively 

45621710

(Supplemental)

Acute contact and 

reproductive test

(55 g a.i/hectare)

Heteropteran bug (Orius 

laevigatus)

Mortality increased from 3.8% at Day 

1, to 40.4% at Day 5, to 82.7% at Day 9 

compared to 14% mortality on control; 

3 surviving females did not produce 

eggs as compared to 29.1 eggs per 

female in the control

45621711

(Supplemental)

Field study in an 

infested vineyard

(0.5 L/ha)

Predacious mite 

(Typhlodromus pyri)

Predacious mite exposed to single 

application and observed for 43 days. 

At 21 days, the residual population was 

reduced to 83.5% as compared to 

control. Gradual decrease in the 

difference between treatment and 

control continued to 64% by 43 days.

45621712

(Supplemental)

Field study in an 

infested vineyard

(0.5 L/ha)

Predacious mite 

(Typhlodromus pyri)

Predacious mite exposed to single 

application and observed for 42 days. 

By 21 days, the residual population had 

declined to 37% of the control. 

45621713

(Supplemental)

Field study in an Predacious mite Predator:prey ratio – the rate of 45621714
22

Study

(application) Test Species Results synopsis MRID (Classification)

apple orchard

(0.5 L/ha)

(Neoseiulus californicus) reduction declined to 47.4% at day 15 

to 0% at days 21-44

21 days after treatment, etoxazole 

appeared selective 

(Supplemental)

Predatory mite acute 

contact and 

reproductive test 

(0.05L 

product/hectoliter)

Predacious mite 

(Neoseiulus californicus)

By 14 days, mortality in treatment was 

24%

Fecundity was 3.96 eggs/female and 

4.69 eggs/female for the control and 

treatment group, respectively.

45621715

(Supplemental)

Predatory mite acute 

contact toxicity test

(0.05L 

product/hectoliter)

Predacious mite 

(Typhlodromus pyri)

By 96 hours, mortality in the treatment 

group was 11.5% 45621716

(Supplemental)

Predatory mite acute 

contact and 

reproductive test 

(0.05L 

product/hectare)

Predacious mite 

(Typhlodromus pyri)

1

st study:

10 days: no mortality in control and 

resistant and reference treatment 

populations; control and reference 

population fertility and offspring 

indices were 11.4 and 0.99 and 7.6 and 

0, respectively. Control and resistant 

fertility and offspring viability indices 

were 10.97 and 0.99 and 7.2 and 0.08, 

respectively. 

2

nd Study

7 days: Reference population control

eggs exposed and 25.7% hatched, 

offspring viability index was 0. 

Reference population treatment hatched 

49.1% by Day 7, offspring viability 

index was 0.97. Resistant population 

control eggs exposed hatched 24.6% by 

Day 7, offspring viability index was 0; 

resistant population treatment hatched 

27.3% hatched by Day 7, offspring 

viability index was 3.33.

45621716

(Supplemental)

Analysis of the Degradates of Etoxazole and Identification of Compounds to be Considered in 

the Total Toxic Residue (TTR)

As described in Section 5a, etoxazole degrades by various routes in the environment. Twelve

different degradation products were formed in fate studies, with six that were determined to form 

at concentrations of 10% or greater than the applied parent etoxazole (Appendix A). Figure A.1

in the appendix shows the registrant-proposed degradation pathway for etoxazole under aerobic 

soil conditions. When available, registrant submitted toxicity data for degradates were 

consulted. Additionally, the ECOSAR (v1.1) module of EPISUITE (v.4.1) was employed to 

estimate the toxicity of these degradates of etoxazole alongside the available registrant submitted 

data. ECOSAR uses structure activity relationships to predict the toxicity of compounds that 

share similar structural moieties. In cases where multiple estimates of toxicity for a particular 

taxa are predicted for a degradate, the most sensitive estimate was tabulated. 
23

For each ECOSAR class, varying numbers of data points are associated in building the structure 

activity relationship that informs the estimate of toxicity for a given ECOSAR class. While 

estimates of toxicity provided by ECOSAR are less reliable than those of actual laboratory 

studies, ECOSAR class estimates that are associated with several endpoints generally have less 

uncertainty associated with them than those ECOSAR classes that only have a few.

Table 10 shows the ECOSAR classes for each degradate for which toxicity estimates were 

predicted. These results are compared alongside registrant submitted data that is available for 

etoxazole as well as the degradates R-3, R-4, R-7, R-8, and R-13. For the freshwater fish study 

that examined the toxicity of five degradates, highly variable analytical measurements made the 

results of R-4 and R-7 unreliable and therefore these cells are blanked out in Table 10 below.

Table 10. ECOSAR predicted toxicity (μg a.i./L) of the degradates of etoxazole3

Compound 

(Chemical class)

Toxicity Endpoint (μg a.i/L)

Acute 

FW 

Fish 

LC50

Acute FW 

Invert 

EC50

Chronic 

FW Fish 

NOAEC

Chronic 

FW Invert 

NOAEC

Acute 

E/M 

Fish 

LC50

Acute 

E/M 

Invert 

LC50

Chronic 

E/M 

Invert 

NOAEC

Algae 

EC506

Parent etoxazole

Etoxazole 

(registrant 

submitted studies) 

– TGAI4

>370 7.3 15 0.13 >160 1.1 0.32 >51.9

Degradate R-3

R-3

(registrant 

submitted studies) 

>800 >550 >1000

R-3

(Imides)

16281 1440 122 225 351 65

Degradate R-4

R-4 (registrant 

submitted studies) >1300

R-4 (Amides) 12241 3801 11 131 11121 167 70

Degradate R-7

R-7 (registrant 

submitted studies) >740 >990

R-7 (aliphatic 

amines) 446 79 8.0 9.0 30

R-7 (esters) 547 793 20 206 677 127 10 198

Degradate R-8

R-8 (registrant 

submitted studies) >880 >1400

R-8

(Aliphatic amines) 21282 2690 1037 234 1977

Degradate R-13

R-13 (registrant 

submitted studies) >740 >730 >1000

R-13

(Neutral organics) 211 181 3.0 6.0 271 0.86 0.02 781

1

Indicates that chemical may not be soluble enough to measure this predicted effect

2

Indicates that this value was estimated using an acute-to-chronic ratio (ACR)
24

3The lowest toxicity estimate for a given taxa was used when estimates for more than one ECOSAR class were 

yielded for a given degradate.

4Data in this row refer to registrant submitted studies for etoxazole deemed suitable for risk estimation. These 

values are included in the table for comparison purposes against the ECOSAR predicted endpoints.

5Data are not available for freshwater green algae for etoxazole parent and therefore the results of the marine diatom 

study are provided.

Table 10 shows that when comparing registrant submitted data for the taxa available, the 

degradates of etoxazole are generally less toxic than parent although there is uncertainty in that 

statement with some degradates more than others. There is also uncertainty in the fact that 

comparisons are being made between an endpoint that is greater than the absolute value of a nondefinitive value. Several degradates returned results for ECOSAR classes that are not associated 

with a high level of data points, adding uncertainty to estimates from that class. What follows is 

an analysis of the estimates for each degradate:

R-3

There are three registrant submitted studies available to characterize the toxicity of R-3 to 

freshwater fish, invertebrates, and green algae. Relative toxicity cannot be precisely defined due 

to non-definitive endpoints but ECOSAR data suggest that R-3 may be more toxic than the 

parent in freshwater fish and invertebrates. ECOSAR indicated one chemical class for this 

degradate, which determined that R-3 is at least one order of magnitude less toxic than parent 

both on an acute and chronic basis to freshwater fish and invertebrates and on acute basis to 

estuarine/marine invertebrates. However, there is uncertainty in the ECOSAR results as the 

imides class these estimates are derived from are only associated with a few endpoints within 

ECOSAR. The uncertainty in the ECOSAR estimates is not expected to change the overall 

conclusions that the toxicity of R-3 is less than that of parent.

Environmental fate data show that R-3 forms at rates that are marginally considered to be major 

(i.e. ≥10%) with maximum formation rates of 11.7% via the soil photolysis pathway, while 

forming at slightly lower rates in the aerobic soil metabolism and terrestrial field dissipation 

studies (10.4 and 10.8%, respectively). R-3 formed at very low rates in the aquatic media 

suggesting that R-3 would not be present in the aquatic media following a drift event. It would

originate in soil environments and it would be present in aquatic environments primarily

following soil runoff events. Available data also show that R-3 is not particularly persistent, 

with all studies that showed greater than 10% formation of the applied to have less than 2% of 

the applied remain by study termination. Additionally, R-3 has an EpiSuite (v.4.1) estimated 

solubility of 1.54 mg/L. R-3 was not shown to cause any mortality up to mean measured 

concentration of 0.8 mg/L in the freshwater fish study and no mortality up to mean measured 

concentration of 0.55 mg/L in the freshwater invertebrate study. Given the low (0.18 lbs a.i/A) 

maximum single application rate of parent etoxazole, the low formation rates, the limited 

persistence of R-3, and the low toxicity observed in available studies and in ECOSAR estimates 

for R-3 as compared to parent etoxazole, R-3 is not considered to be a degradate of concern for 

ecotoxicological risk. 
25

R-4

Degradate studies for freshwater fish and freshwater invertebrates are available to characterize 

the toxicity of R-4; however, the results of R-4 in the registrant-submitted freshwater fish study 

are uncertain based on highly variable analytical measurements and are therefore not captured in 

Table 10. The results of the freshwater invertebrate study show that R-4 is at least 2 orders of 

magnitude less toxic than parent etoxazole. Results of the amide ECOSAR class indicate R-4 is 

one order of magnitude less toxic than parent to freshwater fish and invertebrates although the 

model indicates the degradate may not be soluble enough at this level to elicit an effect. Relative 

toxicity cannot be precisely defined due to non-definitive endpoints but available data do not 

indicate increased toxicity of R-4 over parent to freshwater fish and invertebrates. Chronic 

estimates of toxicity for freshwater fish indicate toxicity within an order of magnitude of parent 

and chronic estimates of toxicity to chronic freshwater invertebrates indicate 2 orders of 

magnitude less toxicity than parent.

R-4 forms via hydrolysis, aerobic soil, and anaerobic aquatic metabolism pathways. Maximum 

residues of 13% were detected in the hydrolysis study (pH 7), but there was uncertainty as to 

whether some of those residues may have been R-7. Formation rates for the other two routes of 

dissipation were both less than 13%. Available studies show R-4 to be persistent in both the 

aquatic and terrestrial environments. R-4 has the potential to exist in the aquatic environments 

by either a spray drift via hydrolysis, or soil runoff event. However, the EpiSuite estimated 

solubility of R-4 is 0.372 mg/L which is at a level in which no mortalities were observed in the 

available freshwater invertebrate study (results of freshwater fish not reliable). Despite its 

persistence and the potential to reach aquatic environments via multiple routes, the lack of acute 

toxicity at the solubility limit of R-4 as well as formation rates that are marginally considered to 

be major (i.e. ≥10%) provides justification to exclude R-4 as a degradate of concern. 

R-7

Registrant submitted studies of R-7 for freshwater invertebrates and freshwater green algae show 

toxicity at least one order of magnitude less toxic than parent. Relative toxicity cannot be 

precisely defined due to non-definitive endpoints but available data do not indicate increased

toxicity of R-7 over parent invertebrates. Estimates of toxicity from the freshwater fish study for 

R-7 are uncertain given the instability of the degradate during the study. ECOSAR estimates 

from two different classes (aliphatic amines and esters) are relatively close (no more than 1 order 

of magnitude in separation) in estimates and corroborate the limited results of the registrant 

submitted studies in that parent etoxazole is more toxic on an acute exposure basis than R-7. 

Chronic estimates for freshwater fish indicate toxicity on the same level as parent but there are 

less data points associated with the estimates of chronic toxicity for both ECOSAR classes 

utilized in this analysis. 

R-7 forms primarily through the aerobic soil metabolism and is observed in the terrestrial field 

dissipation studies. It is an uncertainty in the available hydrolysis study as to whether the 

residues at pH 7 were entirely R-4 or entirely R-7 or a mixture of the two. In the available 

aerobic soil metabolism studies, R-7 forms up to 21.6% but the residues were determined to be 

less than 4% by the end of the study 9 months later. The terrestrial field dissipation studies 
26

showed much higher rates of formation (43 – 73%), yet R-7 was not detected by study 

termination 4 months later. The concentrations in the terrestrial field dissipation study may be

somewhat misleading since they are based on the maximum parent detected concentration. If the 

maximum parent was detected at a relatively low concentration (potentially because it degraded 

fairly rapidly in the field), the percentages will appear relatively high. Despite the rates of 

formation however, available studies show R-7 is not persistent in terrestrial environments. 

Furthermore, the lack of formation in the available hydrolysis, aqueous photolysis, aquatic 

metabolism, and anaerobic soil metabolism studies indicate that R-7 is not a major degradate in 

the aquatic media.

R-8

The available freshwater invertebrate study shows R-8 to be at least 2 orders of magnitude less 

toxic than parent etoxazole while the toxicity of R-8 was determined to be at least 2.5 fold less 

toxic than parent to freshwater fish. Relative toxicity cannot be precisely defined due to nondefinitive endpoints but available data do not indicate increased toxicity of R-8 over parent to 

freshwater fish and invertebrates. ECOSAR estimates available from one class (aliphatic amines) 

corroborate the available registrant submitted acute data and also indicate that chronic toxicity to 

freshwater fish and invertebrates is at least 2 orders of magnitude less toxic than parent though 

there is uncertainty in these findings as they are based off an ECOSAR class with limited data 

associated with it.

Formation rates of 44.8% and 24.6% were observed in the aerobic soil and anaerobic soil 

metabolism studies, respectively. These residues were still fairly persistent at test termination 9 

months later for aerobic soil metabolism and 6 months later for anaerobic soil metabolism. Since 

the mobility of R-8 is higher than for etoxazole, the degradate could potentially move to adjacent 

bodies of water through runoff, both dissolved in the water and with erosion. The available 

toxicity studies observed no mortalities at the level that R-8 was tested (0.88 mg a.i/L and 1.4 mg 

a.i/L for the freshwater fish and freshwater invertebrate studies, respectively). EpiSuite 

estimates the solubility of R-8 to be 2058 mg/L and so it is uncertain as to whether an LC50

would be achieved if the study tested R-8 at a higher concentration. Furthermore, the degradate 

is shown to be more persistent in the environment than the other degradates of etoxazole 

examined thus far. Finally, this degradate was selected as being of concern for drinking water in 

the Health Effect Division’s (HED) meeting of the Residues of Concern Knowledgebase 

Subcommitee (ROCKS). Therefore, this degradate will be regarded as a stressor of concern. 

R-11

There are no registrant submitted toxicity data available for R-11. The ECOSAR estimates are 

not shown in Table 10 because ECOSAR detected an acid moiety with this degradate and 

therefore the estimates of toxicity for all taxa are further multiplied by 10 (making the estimates 

less toxic). With these adjustments, the estimates of toxicity on an acute and chronic basis are at 

least 4 orders of magnitude less toxic than parent to all taxa. 

R-11 forms via the aqueous photolysis, soil photolysis, aerobic and anaerobic soil metabolism, 

and was observed in the terrestrial field dissipation studies (overall formation rates range from 
27

16.2 – 38.2% depending on the pathway). R-11 was observed to be the maximum at the end of 

the aqueous and soil photolysis studies at 12-14 days. The short duration of the studies did not 

allow for observation of the decay of the chemical. R-11 was a maximum of 19.9% in the 

anaerobic aquatic metabolism study at 179 days, but it declined to <3% AR by study termination. 

Public data about this degradate, which is common to diflubenzuron, appears to indicate that R11 is not too persistent in the environment (http://sitem.herts.ac.uk/aeru/iupac/768.htm).

In short, given the fact that it is an acid, it will exist as an anion in the environment and should 

show low toxicity to non-target organisms, and apparent low persistence, the degradate will not be 

considered to be of ecotoxicological concern.

R-13

Available registrant submitted data show that freshwater invertebrates and freshwater green 

algae are at least one order of magnitude less sensitive to R-13 than for parent etoxazole. 

Freshwater fish were less sensitive to R-13 as compared to parent by approximately a factor of 2. 

Relative toxicity cannot be precisely defined due to non-definitive endpoints but available data 

do not indicate increased toxicity of R-13 over parent to freshwater fish and invertebrates. 

ECOSAR estimates are available from one class (neutral organics) but these results are 

associated with some uncertainty as many estimates are footnoted by the degradate might not be 

soluble at the level of the estimate. Furthermore, the neutral organics class represents baseline 

toxicity with ECOSAR noting that these estimates assume a simple non-polar narcosis model. It 

goes on to state that without empirical data on structurally similar chemicals, it is uncertain if the 

substance will present significantly higher toxicity above baseline estimates. Thus, the results of 

R-13 in ECOSAR are uncertain given that this class of compound would be expected to provide 

results that indicate less toxicity than registrant submitted data

R-13 forms at rates more than 10% by the aerobic soil metabolism pathway only (formation rates 

range from 11 – 30%); however, it was observed in all the aerobic soil metabolism studies. The 

degradate appears from available studies to be fairly persistent, with residues still being detected 

at study termination that range anywhere from 6 – 9 months. Additionally, R-13 has an EpiSuite 

estimated solubility of 0.01 mg/L and a measured solubility of 0.020 mg/L at 20oC (MRID 

45090026), which is lower than that of parent etoxazole and an estimated log KOW of 6.62, which 

is higher than parent, suggesting that this degradate is of very low mobility and has a propensity 

to sorb to soil and sediment as well as bioaccumulate. The available mobility study indicated 

that R-13 has a low mobility of the same order than the parent etoxazole. It is worth noting that 

R-13 is the only degradate that preserves the 3 rings of the parent etoxazole structure. As such, 

its mode of action may be similar to that of parent etoxazole although available data indicate it is 

less toxic to freshwater invertebrates as compared to parent. R-13 would be available in the 

aquatic media mainly in runoff events accompanied by erosion, and it would appear that it will 

be associated with the sediment phase. The newly conducted aerobic and anaerobic aquatic 

metabolism studies, conducted on etoxazole, required for registration review will shed additional 

light on the possible presence and persistence of R-13 in the aquatic environment. 
28

Conclusions: Stressors of Concern

In summary, available degradate data for freshwater fish, invertebrates, and green algae 

generally show decreased toxicity to these taxa as compared to parent etoxazole. For R-4 and R7, where the analytical results were highly variable for the freshwater fish study and therefore 

estimates of toxicity are unreliable. Despite this, ECOSAR estimates generally predict lower 

toxicity of these degradates as compared to parent etoxazole. Additionally, R-4, despite its 

possible persistence, showed formation rates that marginally exceeded 10% AR whereas R-7 

showed higher formation rates but low persistence. R-3 also had formation rates that could be 

considered marginally major as well as ECOSAR estimates corroborating submitted registrant 

data that R-3 is less toxic than parent etoxazole. R-11 is an acid degradate and therefore 

ECOSAR predicted estimates of toxicity were several orders of magnitude below that of parent 

etoxazole with environmental fate data showing a lack of persistence.

That leaves two degradates, R-8 and R-13, which despite submitted data and ECOSAR estimates 

showing less toxicity than that of parent, formation rates and persistence are higher than those of 

other degradates. In order to reduce the uncertainty of how close the toxicity endpoints of 

submitted studies and those of ECOSAR estimates were (especially as it relates to freshwater 

fish), environmental modeling was conducted to assess where the predicted residues would be as 

they relate to the submitted toxicity studies. 

Modeling was conducted on two scenarios of etoxazole that represent the highest single 

application rate and the highest seasonal application rate (mint and corn, respectively). The 

modeling input parameters were such that a total toxic residue (TTR) approach was assessed in 

which the stressor was considered to be the sum of parent etoxazole, R-8, and R-13. The results 

of the environmental modeling are summarized below in Table 11. As Table 11 indicates, there 

is the concern of parent etoxazole and the degradates R-8 and R-13 partitioning to the sediment 

based on the environmental fate properties of the compound’s TTRs, as well as for the peak and 

21-day sediment concentrations presented below. As a result, the upcoming risk assessment will 

include parent etoxazole, R-8 and R-13 in the total toxic residues. Considering R-8 and R-13 as 

additional stressors is consistent with the drinking water assessment to be provided to the Health 

Effects Division (HED) (refer to the MARC committee recommendations in DP Barcode 

D288817, dated 04/23/2003). Despite the submitted data and ECOSAR estimates of R-8 

generally showing less toxicity than parent, R-8 is shown to be persistent in available 

environmental fate data. Further information regarding the input parameters and modeling 

scenarios can be found in Appendix E.

Additionally, given the fact that chronic sediment toxicity data indicate that risk above the LOC 

is potential (as indicated by the sediment and pore water EECs as compared to the 

estuarine/marine amphipod endpoints), there is also the concern that freshwater invertebrates 

may be at risk as the result of chronic exposure. A chronic sediment toxicity test with the 

freshwater midge (Chironomus dilutus) as well as a chronic sediment study with the freshwater 

amphipod (Hyalella azteca) are needed to further characterize the toxicity of sediment dwelling 

freshwater invertebrates as a result of chronic exposure to etoxazole.
29

Table 11. Preliminary surface water estimated environmental exposure concentrations 

(EECs) for Etoxazole TTRs

Crop Scenario

Application 

Rate (lb a.i./A) 

x No. of Apps

Water Column Pore Water Sediment

Peak

(ppb)

21-day

(ppb)

60-day

(ppb)

Peak

(ppb)

21-day

(ppb)

Peak

(ppb)

21-day

(ppb)

IL corn 0.135 x 2 2.56 0.393 0.377 0.400 0.393 60.4 59.3

OR mint 0.18 x 1 1.32 0.118 0.111 0.122 0.118 18.4 17.8

c. Ecological Incidents

The ecological incident information system (EIIS) is an OPP database that houses ecological 

incidents that have been reported to the Agency. When available, EIIS includes date and 

location of an incident, type and magnitude of effects observed in various species, use(s) of 

pesticides known or suspected of contributing to the incident, and results of any chemical residue 

analysis or other analyses conducted during incident investigation. EIIS incidents are 

categorized according to the certainty that the incident resulted from pesticide exposure. The 

Avian Incident Monitoring System (AIMS) is a database administered by the American Bird 

Conservancy that contains publicly available data on reported avian incidents involving 

pesticides. Many of the incidents listed in this database are also in the EIIS. 

A search of EIIS returned no reported wildlife incidents involving etoxazole. Additionally, a 

search of the Aggregate Incident Data, the Incident Database System (IDS) and the AIMS 

database did not return any reported wildlife incidents with etoxazole. 

7. Exposure Pathways of Concern

The environmental fate properties and use patterns of etoxazole indicate that direct spray, spray 

drift, and runoff (mainly in events accompanied by erosion), represent potential transport 

mechanisms of Etoxazole to aquatic and terrestrial organisms. Leaching to groundwater and 

atmospheric deposition are not important pathways for the chemical.

Other exposure pathways to terrestrial species

Potential for Risk to Terrestrial Organisms from Drinking Water Exposure

The Screening Imbibition Program (SIP v.l.0), Released June 15, 2010) was used to calculate an 

upper bound estimate of exposure using etoxazole’s solubility (0.075 mg/L), the most sensitive 

acute and chronic avian toxicity endpoints (northern bobwhite quail LD50 of >2000 mg a.i/kg-bw 

and northern bobwhite quail NOAEC of 286 ppm, respectively) and the most sensitive acute and 

chronic mammalian toxicity endpoints (Norway rat LD50 of >5000 mg a.i/kg-bw and Norway rat 

NOAEL of 2000 ppm, respectively). Drinking water exposure alone was not determined to be a 

potential pathway of concern for both avian and mammalian species on both an acute and 

chronic basis.
30

Although drinking water exposure alone does not appear to be of concern, this does not take into 

account that when aggregated with other exposure pathways (dietary food sources, dermal,

inhalation) drinking water may contribute to a total exposure that has a potential for effects on 

non-target animals and should be explored further. Because there is a high degree of 

conservatism in the SIP 1.0 exposure estimate, there is a limited expectation that use scenarios 

not triggering a SIP 2.0 concern would contribute significantly to aggregate risks from water plus 

diet when a refined water exposure model is incorporated in the actual quantitative risk 

assessment. Detailed information about SIP v.l.0 as well as he tool can be found on the EPA's 

website at

http://www.epa.gov/pesticides/science/models/pg.htm#terrestrial.

Potential for Risk to Terrestrial Organism from Inhalation Exposure

The Screening Tool for Inhalation Risk (STIR v.l.0, November 19, 2010) was used to calculate 

an upper bound estimate of exposure using etoxazole’s vapor pressure (7 X 10-6and molecular 

weight for vapor phase exposure as well as the maximum application rate and method of 

application for spray drift. STIR incorporates results from several toxicity studies including acute 

oral and inhalation rat toxicity endpoints obtained from the "six pack," of core studies, which are 

a series of six guideline studies that are submitted to the Registration Division of the Office of 

Pesticide Programs for technical and formulated products of a pesticide (oral LD50 = >5000 mg 

a.i/kg-bw and inhalation LC50 = >1.09 mg/L) as well as the most sensitive acute oral avian 

toxicity endpoint (mallard duck oral LD50 = >2000 mg a.i/kg-bw). Based on the results of the 

STIR model, inhalation exposure alone was not determined to be a potential pathway of concern 

for avian and mammalian species on an acute basis.

Inhalation exposure via spray drift and/or vapor-phase of etoxazole alone does not appear to be 

of concern. The analysis of the inhalation route in STIR does not consider that aggregation with 

other exposure pathways such as dietary, dermal, or drinking water may contribute to a total 

exposure that has a potential for effects to non-target animals. However, the Agency does 

consider the relative importance of other routes of exposure may be potentially significant 

contributors to wildlife risk (US EPA, 2004). Detailed information about STIR v.l.0, as well as 

the tool, can be found on the EPA's website at:

http://www.epa.gov/pesticides/science/models/pg.htm#terrestrial

Dermal exposure

Potential exists for etoxazole dermal exposure to terrestrial wildlife. At the present time, the 

Agency does not have a method to quantify levels of dermal exposure from chemical

applications, but is actively working on a screening tool to account for this route of exposure.

Exposure resulting from bioaccumulation

The potential for bioaccumulation of etoxazole will also be examined in the risk assessment. 

Etoxazole shows a significant potential to bioconcentrate, as expected from its relatively high 

octanol/water partition coefficient (331,000; log KOW = 5.52). Residues bioconcentrated in 

rainbow trout with maximum bioconcentration factors of 1600 L/kg for the edible tissue, and 
31

3300 L/kg for whole fish. However, depuration was relatively rapid (half-life 2.6 days for edible 

tissue and 4.6-6.2 days for non-edible tissue). Bioaccumulation will be assessed using the results 

from bioaccumulation in fish studies, as well as the KOW (based) Aquatic BioAccumulation 

Model, version 1.0, 2009 (KABAM) 

8. Analysis Plan

a. Stressors of Concern

i. Ecological Risk Assessment

Please see the “Analysis of the Degradates of Etoxazole and Identification of Compounds to be 

Considered in the Total Toxic Residue (TTR),” in Section 6 of this assessment for a detailed 

rationale of defining the stressors of concern.

ii. Drinking Water 

The drinking water assessments conducted to support the registration review human health risk 

assessments of Etoxazole will incorporate model estimates of Etoxazole residues of concern, 

which are parent compound, R-8 and R-13 (as per the request of the Metabolism Assessment 

Review Committee or MARC, DP Barcode D288817, 04/23/03), in surface and ground waters. 

The Etoxazole residues of concern may be reevaluated pending receipt and review of additional 

environmental fate and toxicity data for Etoxazole and its degradates, and use of new models, 

such as PRZM-GW4. Each degradate will be assessed separately, given the availability of 

mobility data for each degradate of concern.

b. Measures of Exposure 

EFED will use standard available models to evaluate potential exposures to aquatic and 

terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm.

i. Available Monitoring Data

The Agency is aware of monitoring conducted by federal and state agencies and this route of 

exposure will be considered in the assessment to the extent that data on etoxazole are available

(see e.g., http://cida.usgs.gov/nawqa_public/apex/f?p=136:1:0, accessed 03/18/14).

c. Measures of Effect 

Toxicity data presented in Section 3 of this problem formulation will be used to calculate risk 

quotients. Any additional information submitted by the registrant or found in the open literature 

prior to conduct of the risk assessment will also be considered. The open literature studies are 

 

4 http://www.epa.gov/oppefed1/models/water/index.htm#przm_gw
32

identified using EPA’s ECOTOXicology database (ECOTOX) (USEPA, 2007c), which employs 

a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, 

and wildlife. The evaluation of both sources of data can also provide insight into the direct and 

indirect effects of pesticides on biotic communities from loss of species that are sensitive to the 

chemicals and from changes in structure and functional characteristics of the affected 

communities.

9. Endangered Species Assessments

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the

Agency will evaluate risks to federally listed threatened and/or endangered (listed) species from 

registered uses of pesticides in registration review. The process for evaluating potential risks to 

listed species is further described at 

http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm.

10. Endocrine Disruptor Screening Program

Etoxazole was not included in the first group of 67 chemicals issued an order to conduct Tier 1 

EDSP testing. For additional information the EDSP program, visit http://www.epa.gov/endo/.

11. Preliminary Identification of Data Gaps 

a. Environmental Fate

Table 12 and Table 13 identify environmental fate studies by MRID that offer data for each

guideline requirement, as well as study classifications and whether or not further data are needed 

in order to support risk assessment.

835.4300 Aerobic Aquatic Metabolism: The study is required to support the terrestrial uses of 

etoxazole. Two sediment systems should be selected according to 835.4300 guidance, and

tested. In the absence of data, EFED will use conservative assumptions, such as the use of twice 

the aerobic soil metabolism input value, following the current Input Parameter Guidance.

835.4400 Anaerobic Aquatic Metabolism: Only one sediment system is available. In the 

study, for one of the radiolabels, the levels of unextracted radioactivity were up to 52% AR while 

for the other radiolabel up to 25% AR were unidentified volatile organics. Two new sediment 

systems should be selected according to the 835.4400 guidance, and submitted addressing these 

issues. In the absence of data, EFED will make conservative assumptions, based upon the 

overall behavior observed in the available study, with unextracted radioactivity included in the 

total toxics residues expression. A conservative 3x factor will also be added, since there is only 

one study (sediment system) available.
33

850.6100 Environmental Chemistry Methods (ECM) and Independent Laboratory 

Validation (ILV): Methods for water, soil and sediment are required for the parent compound 

and major degradates of toxicological concern. According to the analysis presented previously

in this Problem Formulation, degradates to be considered of ecological and human health

concern are R-8 and R-13. Studies are available for the analysis in soil, which are in review. 

The data requirement will remain unfulfilled until the available studies are reviewed.

Table 12. Submitted Environmental Fate Data for Etoxazole

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Justification and Assumptions EPA 

will Make in Absence of Data

835.2120 Hydrolysis 45090017 Supplemental No ---

835.2240 Aqueous 

photolysis

45090018 Unacceptable No ---

46658101 Acceptable

835.2410 Soil photolysis 45090020, 

46299904

Acceptable No ---

835.4100 Aerobic soil 

metabolism

45090019 Acceptable No ---

45090021 Acceptable

45090022 Supplemental

835.4200 Anaerobic soil 

metabolism

45090023 Supplemental No ---

835.4300 Aerobic aquatic 

metabolism

Not available Not applicable Yes The study is required to support the uses 

of this chemical. In the absence of data, 

EFED will use conservative 

assumptions, such as the use of 2x the 

aerobic soil metabolism input value.

835.4400 Anaerobic 

aquatic 

metabolism

45621718 Supplemental Yes Two new sediment systems should be 

submitted addressing issues observed in 

a previous study. In the absence of data, 

EFED will make conservative 

assumptions, such as the use of a

conservative 3x factor, since there is 

only one study.

835.1230 Adsorption/ 

desorption and 

leaching

45090024, 

46299905

Supplemental No ---

45090026, 

46299906

Supplemental

835.1410 Volatility –

laboratory

Not available Not applicable No The vapor pressure and Henry’s Law 

Constant for etoxazole are relatively 

low.

835.6100 Terrestrial field 

dissipation

45250909 Supplemental No ---

45621721 Acceptable

45621722 Acceptable

45621723 Acceptable

835.6200 Aquatic field 

dissipation

Not available Not applicable No Etoxazole does not have aquatic uses.

850.1730 Fish 

bioconcentration

42621615, 

46269907

Acceptable No ---
34

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Justification and Assumptions EPA 

will Make in Absence of Data

840.1100 Droplet size 

spectrum

45621826 Not determined No Not yet determined. The droplet size 

spectrum data requirement is covered by 

the Spray Drift Task Force (SDTF) 

provided data.

850.6100 Analytical 

method in soil

456217211

(Two ECMs)

Not determined Yes Not yet determined; studies are in 

review. Methods for the analysis of 

etoxazole and its major soil metabolites 

are required, and in particular R-8 and 

R-13, which are of ecological and 

human health concern. The data 

requirement remains unfulfilled for 

etoxazole, pending evaluation of the 

available studies.

45621719

(ILV)

45621720

(ILV)

Analytical 

method in water

Not available Not applicable Yes Methods for the analysis of etoxazole 

and its major aquatic metabolites are 

required, and in particular R-8 and R-13, 

which are of ecological and human 

health concern.

Analytical 

method in 

sediment

Not available Not applicable Yes Methods for the analysis of etoxazole 

and its major aquatic metabolites are 

required, and in particular R-8 and R-13, 

which are of ecotoxicological and 

human health concern.

Shaded and bolded cells indicate that additional data are required for the corresponding data requirement.

1 This is a terrestrial field dissipation study, with both soil methods included and one set of data performed.

Table 13. Submitted Environmental Fate Data for the Etoxazole Degradates

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Justification and Assumptions EPA 

will Make in Absence of Data

NonguidelineMobility via 

HPLC (R-3, R-4, 

R-7)

45090025 Supplemental No ---

835.1230 Adsorption/ 

desorption (R-7)

45250906 Supplemental No ---

835.1230 Adsorption/ 

desorption (R-8)

45250907 Supplemental No ---

835.1230 Adsorption/ 

desorption (R13)

45250908 Supplemental No ---

b. Effects

Table 15, Table 16, and Table 17 identify ecological effects studies by MRID that offer data for 

each guideline requirement for parent etoxazole and the degradation products in the aquatic 
35

medium and terrestrial environment, respectively, as well as study classifications and whether or 

not further data are needed in order to support risk assessment. 

Currently, there is only one acute oral study available for etoxazole which is conducted on the 

mallard duck. The study was tested up to concentrations of 2000 mg a.i/kg-bw with no 

mortalities or clinical signs of toxicity observed in the study. Similarly, in two available acute 

dietary studies with the mallard duck and northern bobwhite quail, birds were exposed to 

concentrations of etoxazole in the diet up to 5240 mg a.i/kg-diet. As in the acute oral study, 

there were no treatment related mortalities or clinical signs of toxicity observed. An avian acute 

oral toxicity study with a passerine species is therefore a data gap.

At the current maximum labeled rate of etoxazole (mint, 0.18 lbs a.i/A, 2 applications, 21-day 

interval), an acute oral passerine study would have to show toxicity of 1 order of magnitude over 

parent etoxazole to trigger non-listed species concerns and show increased toxicity by a factor of 

two to trigger listed species concerns. 

As discussed earlier in this assessment, etoxazole has an insect growth regulator type mode that 

has been further characterized in the literature to resemble the benzoylurea class of chitin 

biosynthesis inhibitors. It was investigated as to whether chemicals in this class had data that 

would corroborate the data available for etoxazole and potentially provide insight as to whether 

an additional toxicity study with a passerine species would add substantial value to the risk 

assessment.

The chemicals recognized to be part of the benzoylurea class by the Insecticide Resistance 

Action Committee (IRAC) are listed in Table 14, which compiles detailed information about 

insecticide mode of action. The endpoints tabulated below represent supplemental and 

acceptable studies suitable for quantitative risk assessment.

Other ecological effects studies that have been determined to be data needs to support risk 

assessment for etoxazole are as follows:

850.2100 Avian acute oral toxicity test (with passerine species): Currently, there is only one 

acute oral study available for etoxazole which is conducted on the mallard duck. An avian acute 

oral toxicity study with a passerine species is therefore a data gap. At the current maximum 

seasonal application rate of etoxazole (corn, 0.135 lbs a.i/A, 2 applications, 14-day interval), an 

acute oral passerine study would have to show approximately 12-fold higher toxicity over parent 

etoxazole to trigger non-listed species concerns and show increased toxicity by a factor of

approximately two to trigger listed species concerns. Available data from other chemicals 

known to inhibit chitin biosynthesis (Table 14) shows that this group of chemicals is generally 

not toxic to northern bobwhite quail and mallard duck on an acute oral and subacute dietary 

exposure basis. However, data for one chemical, diflubenzuron for which an acute oral study 

with a passerine species is available, shows increased toxicity over both mallard and bobwhite 

data for that chemical. As this is the only available acute oral study with a passerine species 

currently available for this class of chemicals, and the proximity of the available study shows a 

trigger for listed species concern to be 3X (which is potential considering species to species 
36

sensitivity), an acute oral study with a passerine species for etoxazole has the potential to impact 

the risk assessment.

Table 14. Available avian acute data from the benzoylurea class of insecticides.

Chemical

Acute oral 

(passerine) 

mg a.i/kgbw

Acute oral 

(quail) mg 

a.i/kg-bw

Acute oral 

(Mallard) mg 

a.i/kg-bw

Sub acute 

dietary (quail)

a.i/kg-diet

Sub acute 

dietary 

(mallard)

a.i/kg-diet

Bistrifluron

Chlorfluazuron >2510 >2510 >5620 >5620

Diflubenzuron

3763 (redwinged 

blackbird)

>5000 >5000 >4640 >4640

Flucycloxuron >2000 >6000

Flufenoxuron

Hexaflumuron >2000 >2000 2201 >5200

Lufenuron >2000 >2000 >4970 >5020

Novaluron >2000 >2000 >5200 >5320

Noviflumuron >2000 4100 >5300

Teflubenzuron 

Triflumuron

850.4100 Seedling Emergence: There is currently one available Tier I Seedling Emergence 

study available for etoxazole which is classified as acceptable. However, this study tested at an 

application rate that at the time it was conducted represented the maximum application rate (0.06 

lbs a.i/A) and was conducted with technical grade active ingredient (TGAI). Since the time of 

that study, the maximum single application rate of etoxazole has increased 3-fold to 0.18 lbs 

a.i/A (for uses on mint). A new study is requested that tests etoxazole at this higher maximum 

single application rate. The study, in line with recommendations of OCSPP 850.4100, should 

test the typical end use product (TEP) of etoxazole instead of TGAI as the currently available 

study did.

850.4150 Vegetative Vigor: There is currently one available Tier I Vegetative Vigor study 

available for etoxazole which is classified as acceptable. However, this study tested at an 

application rate that at the time it was conducted represented the maximum application rate (0.06 

lbs a.i/A) and was conducted with technical grade active ingredient (TGAI). Since the time of 

that study, the maximum single application rate of etoxazole has increased 3-fold to 0.18 lbs 

a.i/A (for uses on mint). A new study is requested that tests etoxazole at this higher maximum 

single application rate. The study, in line with recommendations of OCSPP 850.4100, should 

test the typical end use product (TEP) of etoxazole instead of TGAI as the currently available 

study did.

850.4500 Algal Toxicity (Freshwater green algae): There is currently no algal toxicity study 

with a freshwater green algae species submitted for etoxazole that is suitable for risk assessment. 

Previously, an algal toxicity study conducted with the freshwater green algae Selenastrum 

capricornutum (MRID 45621705) was submitted but determined to be unacceptable due to initial 

cell densities being over 7 fold more than the guideline recommended initial concentration. 
37

Additionally, this study was conducted for 72 hours instead of the guideline recommended 96 

hours. A new study is requested to characterize the toxicity of etoxazole to freshwater green 

algae.

850.4550 Cyanobacteria (Anabaena flos-aquae) toxicity: In a previously submitted 

cyanobacteria toxicity study (MRID 48578302), percent increases of 26 and 32% were observed 

in the solvent control for cell density and area under the curve, respectively. While these 

differences were not determined to be statistically significant (p>0.05), they were seen as 

biologically meaningful increases that confounded the ability to discern where the EC50 level 

was. This was due to the fact that the limit concentration (which also contained solvent) was 

32% decreased from the negative control. A new study is needed to characterize the toxicity of 

etoxazole to cyanobacteria.

Non-guideline: Honey Bee - 21-day repeated dose larval toxicity study. Acceptable acute 

contact and oral toxicity data are available for adult honey bees exposures to etoxazole; however, 

data are not available for larval toxicity. As the mode of action of etoxazole is documented in 

regulatory documents and the literature to be an insect growth regulator mediated by chitin 

(which is a component of the insect exoskeleton) biosynthesis, data is needed to characterize the 

toxicity of etoxazole to terrestrial invertebrates in this stage of the life cycle. Available nonguideline acute contact toxicity studies to other non-Apis terrestrial invertebrates corroborate 

enhanced toxicity to larvae when to adults. The study being requested will aid in evaluating this 

concern for honey bees which serve as a surrogate for terrestrial invertebrates. A protocol 

(following the OECD draft guidance document, November 25, 2013) should be submitted for 

review and approval by the Agency prior to initiation of this study. Pending the results of this 

study, higher tiered (e.g. semi-field) studies as well as residue studies may be required.

Non-guideline: Honey Bee Toxicity – 10-Day Adult Chronic Toxicity Study: Bees can be 

exposed to pesticides through multiple pathways including contact with sprays and dusts and 

through ingestion of residues in food/water (e.g., pollen/nectar and water used to maintain colony 

temperature). Worker bees foraging on flowers for pollen and nectar can be repeatedly exposed 

to residues in pollen and nectar either through direct contamination of these matrices by foliar 

sprays and/or dusts through translocation of residues via systemic transport of the active 

ingredient. Residues can in turn be brought back to bee colonies where in-hive bees including 

young adult and developing brood (i.e., eggs, larvae and pupae) may be exposed. EPA guidance 

on assessing the risk of pesticides to bees identifies a suite of laboratory-based studies intended 

that serve as the foundation for screening chemical for potential acute and chronic effects to 

individual adult and larval bees. The 10-day toxicity study with young adult bees provides noobserved adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) for 

assessing chronic effects. Data obtained from this study will be used in estimating chronic risk to 

individual adult bees. Risk estimates based on these data will be considered along with other 

lines of evidence to determine whether higher-tier studies are needed at the whole colony level. 

The registrant should provide a protocol and consult with the Agency prior to study initiation.
38

Non-Guideline: Residues in Pollen and Nectar: Submission of studies for crops of concern 

that evaluate residues in plant parts (e.g., pollen and nectar) may be of high value depending on 

the results of the screening level risk assessment and the Tier I larval bee toxicity study. If 

refinements to the screening level risk assessment for honey bees are needed, these studies will 

allow for a more refined exposure analysis when applications are made at bloom. As this 

chemical is of low toxicity to adults, applications at bloom could contaminate pollen and nectar 

that adult foragers bring back to the colonies and then expose the brood to etoxazole. In order to 

evaluate this exposure pathway, these residue studies would assess etoxazole residues in pollen 

and nectar. The registrant should provide a protocol and consult with the Agency prior to study 

initiation.

850.3040: Field Testing for Pollinators: Screening level and refined Tier I risk assessments 

with the honey bee larvae may indicate the need to progress to higher tier toxicity testing under 

semi-field or field conditions in order to evaluate the toxicity of the chemical to honey bees at 

the colony level. The primary uncertainties relate to the growth and reproduction of the colonies 

and measurement endpoints that relate to brood development and production. Additional data 

may therefore be needed to test the effects of etoxazole in the field to address these uncertainties, 

consequently guideline 850.3040 is identified as a data need. The registrant should provide a 

protocol and consult with the Agency prior to study initiation.

Non-guideline: Whole sediment, chronic toxicity test to freshwater midge (Chironomus 

dilutus). There are two sub-chronic (10-day) freshwater sediment studies with the freshwater 

midge and one chronic (28-day) estuarine/marine amphipod (Leptocheirus plumulosus) available 

for etoxazole. Available data indicates etoxazole has a high propensity to bind to the sediment, 

shows high environmental persistence, and is likely to affect growth, development, and 

reproduction of arthropods via inhibition of chitin biosynthesis. Therefore, a chronic (60-day) 

life cycle sediment toxicity study with the freshwater midge is requested. A protocol should be 

submitted to the Agency prior to study initiation. This protocol should follow the guidance 

document published by the Office of Research and Development (ORD) in 2000 (Methods for 

Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with 

Freshwater Invertebrates – EPA 600/R-99/064, March 2000)

Non-guideline: Whole sediment, chronic toxicity test to freshwater amphipod (Hyalella 

azteca). There are two sub-chronic (10-day) freshwater sediment studies with the freshwater 

midge and one chronic (28-day) estuarine/marine amphipod (Leptocheirus plumulosus) available 

for etoxazole. Available data indicates etoxazole has a high propensity to bind to the sediment, 

shows high environmental persistence, and is likely to affect growth, development, and 

reproduction of arthropods via inhibition of chitin biosynthesis. Therefore, a chronic (42-day) 

life cycle sediment toxicity study with the freshwater amphipod is requested. A protocol should 

be submitted to the Agency prior to study initiation. This protocol should follow the guidance 

document published by the Office of Research and Development (ORD) in 2000 (Methods for 

Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with 

Freshwater Invertebrates – EPA 600/R-99/064, March 2000).
39

Table 15. Submitted Aquatic Ecological Effects Data for Etoxazole

OCSPP

Guideline Data Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Justification and 

Assumptions EPA will 

Make in Absence of Data

850.1010 Freshwater 

invertebrate 

acute toxicity

45089914 Acceptable

No

--

46059001 Acceptable

850.1025

850.1035

850.1045

850.1055

Saltwater 

invertebrate 

acute toxicity 

45621611 Acceptable

No

--

45621610 Acceptable

46732201 Acceptable

--

850.1075 Freshwater fish 

acute toxicity

45089911 Unacceptable

No

--

45089912 Unacceptable

46059001 Acceptable

850.1075 Saltwater fish acute 

toxicity 45621608 Supplemental No

--

850.1300 Freshwater 

invertebrate 

life cycle 

45621613 Unacceptable

No

--

46497901 Supplemental

850.1350 Saltwater 

invertebrates 

life cycle 

45621612 Supplemental No

 --

850.1400 Freshwater fish 

early-life stage 45621614 Acceptable No --
40

OCSPP

Guideline Data Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Justification and 

Assumptions EPA will 

Make in Absence of Data

850.1400 Saltwater fish 

early-life stage No data submitted No --

850.1500 Fish life cycle No data submitted No --

850.1735 10-day Freshwater 

Sediment Toxicity 

study

45621707 Supplemental No

--

850.1735 10-day Freshwater 

Sediment Toxicity 

study

47837702 Supplemental No

--

Nonguideline42-day whole 

sediment life cycle 

toxicity test to 

freshwater 

amphipod

No data submitted Yes

EFED will presume risk at 

the level shown in the 

chronic marine/estuarine test 

for freshwater organisms.

Nonguideline60-day whole 

sediment life cycle 

toxicity test to 

freshwater midge

No data submitted Yes

EFED will presume risk at 

the level shown in the 

chronic marine/estuarine test 

for freshwater organisms.

Nonguideline28-day 

estuarine/marine 

sediment toxicity 

study

47837701 Acceptable No

--

850.4400 Aquatic plant 

Toxicity Test using 

Lemna spp.

48578301 Supplemental No

--

850.4500 Algal toxicity 48578303 Acceptable No Although the studies on 

freshwater and marine 

diatoms are suitable for risk 

assessment, currently 

available studies on 

freshwater green algae and 

cyanobacteria are not suitable 

for quantitative risk 

assessment and are 

recommended.

850.4500 Algal toxicity 48603001 Supplemental Yes 

(freshwater 

green algae)

850.4550 Cyanobacteria 48578302 Supplemental Yes EFED will presume risk for 

listed non-vascular aquatic 

plants in the absence of a noeffect level. The methods 

should include etoxazole and 

its degradates of ecological 

and human health concern.

NonguidelineFreshwater 

Invertebrate 

Microcosm study

45621616 Supplemental No --
41

Table 16. Aquatic Ecological Effects Data for the Degradation products of Etoxazole

OCSPP

Guideline Data Requirement Submitted Studies (MRID)

Study 

Classifications

Are data needed for 

risk assessment?

850.1075 Freshwater fish acute toxicity 45089913 Supplemental No

850.1010 Freshwater invertebrate acute toxicity 

(degradates R-3, R-4, R-7, R-8, and 

R-13)

45621609 Supplemental No

850.4500

Freshwater aquatic plant growth –

algae (R-3) 45621704 Supplemental No

Freshwater aquatic plant growth –

algae (R-7) 45621702 Supplemental No

Freshwater aquatic plant growth –

algae (R-13) 45621703 Supplemental No

Table 17. Submitted Terrestrial Ecological Effects Data for Etoxazole

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for 

risk 

assessment?

Justification and Assumptions 

EPA will Make in Absence of 

Data

850.2100 Avian oral 

toxicity

45089908 Acceptable Yes

Data from an upland game bird 

or waterfowl species AND a 

passerine species is needed for 

avian risk assessment. Analysis 

provided above indicates 

potential increased sensitivity 

for passerines to this class of 

chemicals.

850.2200 Avian dietary 

toxicity 

45089909 Acceptable

No

--

45089910 Acceptable

850.2300 Avian 

reproduction

45621606 Supplemental

No

45621607 Acceptable

850.3020 Honey bee acute 

contact and oral 

toxicity

45621706 Acceptable No

--

NonguidelineHoney Bee 

Toxicity – 10-

Day Adult 

Chronic 

Toxicity Study: 

No data submitted Yes

Nonguideline

Honey Bee - 

21-day repeated 

dose larval 

toxicity study

No data submitted Yes
42

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for 

risk 

assessment?

Justification and Assumptions 

EPA will Make in Absence of 

Data

NonGuideline

Residues in 

Pollen and 

Nectar

No data submitted Yes

--

850.3040 Field Testing for 

Pollinators No data submitted Yes

--

850.4100

Seedling 

Emergence and 

Seedling Growth

45621623 Acceptable Yes

Current study used an 

application rate that is no lower 

than the maximum labeled rate. 

In the absence of a new study, 

EFED will conservatively 

assume that application rate to 

be the EC25. A new study 

should be tested with a typical 

end use product instead of 

technical grade active ingredient

at the current labeled maximum 

application rate.

850.4150 Vegetative 

Vigor 45621701 Acceptable Yes

Current study was tested up to 

an application rate that is no 

lower than the maximum labeled 

rate. EFED will conservatively 

assume that application rate to 

be the EC25. A new study 

should be tested with a typical 

end use product instead of

technical grade active ingredient

at the current labeled maximum 

application rate.

Nonguideline

Predatory mite 

field study 45621708 Supplemental No

Lacewing -

Acute contact 

toxicity

45621709 Supplemental No

Predatory mite –

Acute contact 

and reproductive 

test

45621710 Supplemental No

Heteropteran 

bug – Acute 

contact and 

reproduction test

456211711 Supplemental No

Predatory mite –

Field study 45621712 Supplemental No
43

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for 

risk 

assessment?

Justification and Assumptions 

EPA will Make in Absence of 

Data

Predatory mite –

Field Study 

(Non-target 

effects)

45621713 Supplemental No

Neoseilus 

californicus -

field study

45621714 Supplemental No

Neoseilus 

californicus -

Acute contact 

and reproductive 

test

45621715 Supplemental No

Typhlodromus 

pyri – Acute 

contact (adults)

45621716 Supplemental No

Typhlodromus 

pyri - Acute 

contact and 

reproduction test

45621717 Supplemental No

Shaded and bolded cells indicate that additional data are required for the corresponding data requirement.
44

Guideline Number: None

Study Title: Whole sediment: Chronic invertebrates freshwater – 60-day Freshwater Midge 

(Chironomus dilutus) and 42-day Freshwater amphipod (Hyalella azteca)

Rationale for Requiring the Data

No chronic sediment toxicity tests for freshwater or marine invertebrates have been submitted 

to satisfy the Agency’s updated data requirements for outdoor uses in 40 CFR Part 158 

(October 26, 2007). For sediment studies involving etoxazole, tests on Hyalella and 

Chironomus dilutus are requested. Although both are freshwater species, Hyalella and 

Chironomus differ substantially in their ecological niche (i.e., epibenthic vs. infaunal species)

and physiology. 

o Benthic organisms inhabit sediment environments that may be exposed to runoff or spray drift from etoxazole applications used in agricultural settings

o Previous studies have identified a potential adverse effect for freshwater and 

estuarine/marine aquatic organisms based on water column toxicity values. 

Therefore, there is uncertainty associated with that estimate that can be reduced 

using data from a toxicity test with benthic organisms. 

Practical Utility of the Data

How will the data be used? 

Data from sediment toxicity studies will be used to estimate potential risks to benthic 

organisms associated with uses of etoxazole. The data will reduce uncertainties associated 

with the current risk assessment for benthic species and will improve our understanding of the 

potential effects of etoxazole.

How could the data impact the Agency’s future decision-making?

Although there was uncertainty in estimating the effect of etoxazole on benthic organisms in 

the previous assessment, there was a potential risk associated with adverse effects identified 

for freshwater acute and chronic organisms. Acceptable data for benthic organisms will 

reduce the uncertainty from the previous assessment If the data indicates that registered 

etoxazole usage may pose a risk of adverse effects to non-target benthic organisms above the 

Agency Level of Concern, the Agency may explore decision options to mitigate this risk. The 

lack of these data will limit the flexibility the Agency and registrants have in coming into 

compliance with the Endangered Species Act, and could result in use restrictions for etoxazole

which may otherwise be avoided, or which are unnecessarily severe.
45

Study Title: Honey Bee Toxicity – 10-Day Adult Chronic Toxicity Study

Guideline Number: Non-guideline

Rationale for Requiring the Data

Bees can be exposed to pesticides through multiple pathways including contact with sprays 

and dusts and through ingestion of residues in food/water (e.g., pollen/nectar and water used to 

maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be 

repeatedly exposed to residues in pollen and nectar either through direct contamination of 

these matrices by foliar sprays and/or dusts through translocation of residues via systemic 

transport of the active ingredient. Residues can in turn be brought back to bee colonies where 

in-hive bees including young adult and developing brood (i.e., eggs, larvae and pupae) may be 

exposed. EPA guidance on assessing the risk of pesticides to bees identifies a suite of 

laboratory-based studies intended that serve as the foundation for screening chemical for 

potential acute and chronic effects to individual adult and larval bees. The 10-day toxicity 

study with young adult bees provides no-observed adverse effect level (NOAEL) and lowestobserved adverse effect level (LOAEL) for assessing chronic effects. Data obtained from this 

study will be used in estimating chronic risk to individual adult bees. Risk estimates based on 

these data will be considered along with other lines of evidence to determine whether highertier studies are needed at the whole colony level. The registrant should provide a protocol and 

consult with the Agency prior to study initiation.

Practical Utility of the Data

How will the data be used?

Chronic toxicity data for honey bees will be used to identify potential risks to terrestrial 

invertebrates resulting from chronic exposure in the adult stage to etoxazole. The data will 

reduce uncertainties associated with the current risk assessment for terrestrial invertebrates and 

will improve the Agency’s understanding of the potential chronic effects of etoxazole on 

terrestrial invertebrate species at the adult stage. If chronic adult toxicity data are not 

submitted for honey bees, then risk to terrestrial invertebrates from chronic exposure will be 

presumed under the assumption that prolonged exposures may take place at the adult stage of 

the life cycle.

How could the data impact the Agency’s future decision-making?

If future endangered species risk assessments are performed without these data, the Agency 

would have to assume that etoxazole “may affect” listed terrestrial invertebrate species directly 

(and listed species from other taxa indirectly), and use of etoxazole and its formulated 

products may need to be restricted in areas where listed species could be exposed. The lack of 

these data will limit the flexibility of the Agency and the registrants for compliance with the 

Endangered Species Act and could result in use restrictions for etoxazole use that are 

unnecessarily severe.
46

Study Title: Honey Bee - 21-day repeated dose larval toxicity study Guideline 

Number: Non-guideline

Rationale for Requiring the Data

Acceptable acute contact and oral toxicity data are available for adult honey bees exposures to 

etoxazole; however, data are not available for larval toxicity. As the mode of action of etoxazole 

is documented in regulatory documents and the literature to be an insect growth regulator by 

way of chitin biosynthesis, data is needed to characterize the toxicity of etoxazole to terrestrial 

invertebrates in this stage of the life cycle. Available non-guideline acute contact toxicity 

studies to other non-Apis terrestrial invertebrates corroborate enhanced toxicity to larvae as 

compared to adults. The study being requested will aid in evaluating this concern for honey 

bees which serve as a surrogate for terrestrial invertebrates. A protocol (following the OECD 

draft guidance document, June 25, 2013) must be submitted for review and approval by the 

Agency prior to initiation of this study. Pending the results of this study, higher tiered (e.g.,

semi-field) studies as well as residue studies may be required.

Practical Utility of the Data

How will the data be used?

Larval toxicity data for honey bees will be used to identify potential risks to terrestrial 

invertebrates resulting from exposure in the larval stage to etoxazole. The data will reduce 

uncertainties associated with the current risk assessment for terrestrial invertebrates and will 

improve the Agency’s understanding of the potential effects of etoxazole on terrestrial

invertebrate species at the larval stage. If larval toxicity data are not submitted for honey bees, 

then risk to terrestrial invertebrates from acute contact exposure will be presumed under the 

assumption that exposures may take place at the larval stage of the life cycle.

How could the data impact the Agency’s future decision-making?

If future endangered species risk assessments are performed without these data, the Agency 

would have to assume that etoxazole “may affect” listed terrestrial invertebrate species directly 

(and listed species from other taxa indirectly), and use of etoxazole and its formulated products 

may need to be restricted in areas where listed species could be exposed. The lack of these data 

will limit the flexibility of the Agency and the registrants for compliance with the Endangered 

Species Act and could result in use restrictions for etoxazole use that are unnecessarily severe.
47

Study Title: Residues in Pollen and Nectar / Field Residue Analysis Study

Guideline Number: Non-guideline

Test Substance: Etoxazole

Rationale for Requiring the Data

Applications at bloom may result in exposure to honey bee brood. Given the low toxicity to 

adults, potential contamination of pollen and nectar from applications at bloom may allow 

adult foragers to bring contaminated pollen and nectar back to the hives, which would then

result in exposure to the brood. If Tier I screening for risks to honey bees, which is based on 

conservative estimates and assumptions of exposure, yields risk of concern, then the Agency

will consider the need for studies that analyze residues in multiple crops based on certain 

selective criteria in order to refine the exposure. The protocol will depend on application type 

and crop. The registrant should consult the Agency on the design of the protocol prior to the 

initiation of the study.

Practical Utility of the Data

How will the data be used?

The data will be used to assess exposure and risk of etoxazole to non-target listed and nonlisted terrestrial invertebrate species, including bee pollinators. These data would allow the 

Agency to refine the screening level risk assessment for pollinating bees. Exposure data is an 

integral part of determining the potential for risk to pollinating bees through direct exposure 

from their food sources.

How could the data impact the Agency’s future decision-making?

EPA is required by section 7(a)(2) of the ESA to ensure that any action it authorizes or takes 

“...is not likely to jeopardize the continued existence of any endangered or threatened species 

or result in the destruction or adverse modification of critical habitat” and “to use the best 

scientific data available” in carrying out this obligation. The data EPA intends to call in are 

necessary to inform the determination required by the ESA as to whether continued 

registration of a pesticide is not likely to jeopardize the species or its critical habitat. The lack 

of these data will limit the flexibility that the Agency and registrants have in coming into 

compliance with the ESA and could result in use restrictions which are unnecessarily severe. 

In addition, the lack of these data may result in an uncertain assumed risk and potential 

mitigation of etoxazole formulations under FIFRA.
48

12. References 

Food and Agriculture Organization of the United Nations. 2000. FAO PESTICIDE DISPOSAL 

SERIES 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of 

pesticides that influence processes in the soil. Editorial Group, FAO Information Division: 

Rome, 2000. http://www.fao.org/DOCREP/003/X2570E/X2570E00.htm.

Nauen, R. and G. Smagghe. 2006. Mode of action of etoxazole. Pest. Manag. Sci., 62: 379–382. 

doi: 10.1002/ps.1192

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs. United States Environmental Protection Agency (USEPA). Environmental Fate 

and Effects Division. Office of Pesticide Programs. Available at 

http://www.epa.gov/espp/consultation/ecorisk-overview.pdf (accessed 02/19/2014).

USEPA. 2009. Tier I Estimated Drinking Water Concentrations of Etoxazole, and Its 

Transformation Products R-8 and R-13, for the Use in the Human Health Risk Assessment: 

IR-4 Petition for the Use of the Chemical on Stone Fruits (Group 12), Indoor Grown 

Tomato, Cucumber and Mint. Memorandum from Jose Melendez to Debra Rate (RD) dated 

February 10, 2009 (DP Barcode D352617).

USEPA. 2010. Guidance for Reporting on the Environmental Fate and Transport of the Stressors of 

Concern in Problem Formulations for Registration Review, Registration Review Risk 

Assessments, Listed Species Litigation Assessments, New Chemical Risk Assessments, and 

Other Relevant Risk Assessments. Memorandum from Donald Brady dated January 25, 2010 

(http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_spec

ies_reregistration_workgroup/esa_reporting_fate.htm).

USEPA. 2011. Tier I Estimated Drinking Waters Concentrations of Etoxazole, and Its 

Transformation Products R-8 and R-13, for the Use in the Human Health Risk Assessment: 

Section 3 Application for the Use of the Chemical on Field Corn, Pop Corn and Corn Grown 

for Seed Production. Memorandum from Jose Melendez to Autumn Metzger (RD) and 

Dana Vogel (HED), dated January 31, 2011 (DP Barcode D386080).

USEPA. 2013. Screening Level Usage Analysis (SLUA) (for Etoxazole). Office of Pesticides 

Program. Biological and Economic Analysis Division. Dated May 9, 2013.

USEPA. 2014a. Etoxazole (107901) Label Use Report Package in Support of Registration Review. 

Prepared by R. Prieto. Office of Pesticides Program. Biological and Economic Analysis 

Division. Issued April 7, 2014.

USEPA. 2014b. BEAD Chemical Profile for Registration Review: Etoxazole, 107091. Prepared by 

N. Mallampalli, C. Doucoure, and M. Kaul. Office of Pesticides Program. Biological and 

Economic Analysis Division. Issued May 5, 2014.

Refer to Appendix B for the “Etoxazole Fate and Ecological Effects Bibliography”.
49

Appendix A. Nomenclature and Structures for Etoxazole and Its Major Degradates

For a figure of the proposed degradation pathway under aerobic soil conditions, see Figure A.1 at the end of this appendix.

Table A-1. Etoxazole and Its Major Environmental Degradates

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)A

Final %AR 

(study 

length, day)

PARENT

Etoxazole (S-1283, 

Oxazole)

IUPAC Name: (RS)-5-tertbutyl-2-[2-(2,6-

difluorophenyl)4,5-

dihydro-1,3-oxazole-4-yl] 

phenetole

CAS Name: 2-(2,6-

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

demethylethyl) 2-

ethoxyphenyl-4,5-

dihydrooxazole

SMILES Code:

C1(=CC=CC(=C1C2=NC(

CO2)C3=C(C=C(C=C3)C(

C)(C)C)OCC)F)F

CAS No.: 153233-91-1

Formula: C21H23F2NO2

MW: 359.42 g/mol

Hydrolysis1 45090017 Not applicable 80.7 (30)

Aq photolysis3 46658101 31.2 (20)

Aq photolysis4 46658101 36.6 (14)

Soil photolysis3 45090020, 

46299904

39.2 (12.25)

Soil photolysis4 35.4 (12.29)

Aerobic soil3 45090019 0.9 (269)

Aerobic soil4 45090019 1.2 (269)

Aerobic soil3 45090021 1.5 (272)

Aerobic soil4 45090021 1.2 (272)

Aer soil (S)3, 6 45090022 3.0 (180)

Aer soil (LS)3, 6 45090022 4.8 (180)

Aer soil (CL)3, 6 45090022 8.3 (180)

Anaerobic soil3 45090023 42.2 (120)

Anaerobic soil4 45090023 43.0 (120)

Anaerobic aquat3 45621718 23.1 (362)

Anaerobic aquat4 45621718 21.0 (362)

Terr dissipation 45250909 Not detected 

(119)

Terr dissipation 45621721 Not detected 

(122)

Terr dissipation 45621722 Not detected 

(136)

Terr dissipation 45621723 Not detected (29)

ETOXAZOLE TRANSFORMATION PRODUCTS

O

N

F

F

O

C

CH3

CH3

H3C

C

H2

CH3
50

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)

A

Final %AR 

(study 

length, day)

R-3

N-(2,6-Difluorobenzoyl)-

4-tert-butyl-2-

ethoxybenzamide

SMILES Code:

C1(=CC=CC(=C1C(NC(C

2=C(C=C(C=C2)C(C)(C)

C)OCC)=O)=O)F)F

Formula:C20H21F

2NO3

MW: 361.39 g/mol

Hydrolysis

1 45090017 Not determined Not determined

Aq photolysis

3 46658101 1.1 (3) Not detected (20)

Aq photolysis

4 46658101 1.1 (7) Not detected (14)

Soil photolysis

3 45090020, 

46299904

9.0 (12.25) 9.0 (12.25)

Soil photolysis

4 11.7 (12.29) 11.7 (12.29)

Aerobic soil

3 45090019 1.5 (120) 0.7 (269)

Aerobic soil

4 45090019 1.5 (120) 0.9 (269)

Aerobic soil

3 45090021 7.0 (120) 1.1 (272)

Aerobic soil

4 45090021 7.9 (120) 0.9 (272)

Aer soil (S)

3, 6 45090022 7.5 (30) 0.7 (180)

Aer soil (LS)

3, 6 45090022 6.6 (30) 0.5 (180)

Aer soil (CL)

3, 6 45090022 10.4 (61) 1.2 (180)

Anaerobic soil

3 45090023 0.4 (120)7 0.4 (120)

Anaerobic soil

4 45090023 0.7 (5) 0.1 (120)

Anaerobic aquat

3 45621718 Not detected Not detected

Anaerobic aquat

4 45621718 Traces Traces

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 7.9 (7) Not detected 

(122)

Terr dissipation 45621722 10.8 (7) Not detected 

(136)

Terr dissipation 45621723 Not detected

(all intervals)

Not detected (29)

R-4

N-(2,6-Difluorobenzoyl)-

2-amino-2-(4-tert-butyl-2-

ethoxyphenyl) ethane

SMILES Code:

C1(=CC=CC(=C1C(NC(C

2=C(C=C(C=C2)C(C)(C)

C)OCC)CO[H])=O)F)F

Formula:C21H25F

2NO3

MW: 377.43 g/mol

Hydrolysis

1 45090017 13.0 (30)2 13.0 (30)2

Aq photolysis

3 46658101 4.9 (15) 4.3 (20)

Aq photolysis

4 46658101 4.0 (10) 2.9 (14)

Soil photolysis

3 45090020, 

46299904

3.3 (9.84) 2.9 (12.25)

Soil photolysis

4 3.6 (7.38) 3.2 (12.29)

Aerobic soil

3 45090019 4.4 (90) 1.0 (269)

Aerobic soil

4 45090019 1.5 (180) 0.8 (269)

Aerobic soil

3 45090021 0.3 (120) 1.1 (272)

Aerobic soil

4 45090021 0.2 (14) Not detected 

(272)

Aer soil (S)

3, 6 45090022 11.9 (30) 5.1 (180)

Aer soil (LS)

3, 6 45090022 9.8 (30) 9.5 (180)

Aer soil (CL)

3, 6 45090022 7.2 (120) 4.0 (180)

Anaerobic soil

3 45090023 3.2 (120) 3.2 (120)

Anaerobic soil

4 45090023 2.7 (120 2.7 (120)

Anaerobic aquat

3 45621718 12.4 (362) 12.4 (362)

FF

C

NH

O

CO

O

CH

2

CH

3

CC

H

3

CH

3C

H

3

FF

C

ONH

O

CH

2

CH

3

CC

H

3

CH

3C

H

3

CH

2

HO
51

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)

A

Final %AR 

(study 

length, day)

Anaerobic aquat

4 45621718 10.4 (305) 9.02 (362)

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not detected

(all intervals)

Not detected 

(122)

Terr dissipation 45621722 Not detected

(all intervals)

Not detected 

(136)

Terr dissipation 45621723 Not detected

(all intervals)

Not detected (29)

R-7

2-amino-2-(4-tert-butyl-2-

ethoxyphenyl)ethyl-2' ,6'-

difluorobenzoate 

hydrochloride

SMILES Code:

C1(=CC=CC(=C1C(=O)O

CC(C2=C(C=C(C=C2)C(

C)(C)C)OCC)N([H])[H])F

)F

Formula:C21H25F

2NO3

MW: 377.43 g/mol

Hydrolysis

1 45090017 See footnote 1 See footnote 1

Aq photolysis

3 46658101 1.8 (11) 0.8 (20

Aq photolysis

4 46658101 1.1 (0) 1.0 (14)

Soil photolysis

3 45090020, 

46299904

4.4 (7.38) 2.7 (12.25)

Soil photolysis

4 4.8 (12.29) 4.8 (12.29)

Aerobic soil

3 45090019 11.5 (7) 3.3 (269)

Aerobic soil

4 45090019 21.6 (7) 3.2 (269)

Aerobic soil

3 45090021 7.3 (14) 1.1 (272)

Aerobic soil

4 45090021 6.7 (14) 0.5 (272)

Aer soil (S)

3, 6 45090022 3.3 (14) 1.5 (180)

Aer soil (LS)

3, 6 45090022 8.3 (120) 4.0 (180)

Aer soil (CL)

3, 6 45090022 6.9 (180) 6.9 (180)

Anaerobic soil

3 45090023 4.5 (90) 4.1 (120)

Anaerobic soil

4 45090023 5.2 (120) 5.2 (120)

Anaerobic aquat

3 45621718 4.11 (123) 1.98 (362)

Anaerobic aquat

4 45621718 4.17 (31) 2.42 (362)

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 72.8 (0) Not detected 

(122)

Terr dissipation 45621722 42.5 (1) Not detected 

(136)

Terr dissipation 45621723 70.9 (1) Not detected (29)

R-8

2-amino-2-(4-tert-butyl-2-

ethoxyphenyl)ethanol

SMILES Code:

C(C1=C(C=C(C=C1)C(C)

(C)C)OCC)(N([H])[H])CO

[H]

Formula:C14H23NO

2

Hydrolysis

1 45090017 Not determined Not determined

Aq photolysis

3 46658101 3.5 (20) 3.5 (20)

Aq photolysis

4 46658101 Not applicable Not applicable

Soil photolysis

3 45090020, 

46299904

1.5 (9.84) 1.4 (12.25)

Soil photolysis

4 Not applicable Not applicable

Aerobic soil

3 45090019 44.8 (60) 28.6 (269)

Aerobic soil

4 45090019 Not applicable Not applicable

Aerobic soil

3 45090021 0.2 (180) Not detected 

(272)

FF

C

OO

CH

2

NH

2OH2C

CH

3

CC

H

3

CH

3C

H

3

CC

H

3

CH

3

H

3

C

CH

2

OH

NH

2

OCH2

H

3

C
52

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)

A

Final %AR 

(study 

length, day)

MW: 237.34 g/mol Aerobic soil

4 45090021 Not applicable Not applicable

Aer soil (S)

3, 6 45090022 44.2 (61) 37.3 (180)

Aer soil (LS)

3, 6 45090022 38.5 (61) 29.9 (180)

Aer soil (CL)

3, 6 45090022 14.6 (120) 13.1 (180)

Anaerobic soil

3 45090023 24.6 (120) 24.5 (120)

Anaerobic soil

4 45090023 Not applicable Not applicable

Anaerobic aquat

3 45621718 6.05 (362) 6.05 (362)

Anaerobic aquat

4 45621718 Not applicable Not applicable

Terr dissipation 45250909 Not detected Not detected

Terr dissipation 45621721 Not detected

(all intervals)

Not detected 

(122)

Terr dissipation 45621722 Not detected

(all intervals)

Not detected 

(136)

Terr dissipation 45621723 Not detected

(all intervals)

Not detected (29)

R-11 (DFB ) 2,6

-Difluorobenzoic acid

SMILES Code:

C1(=CC=CC(=C1C(O[H])

=O)F)F

Formula:C

7

H

4

F

2

O

2

MW: 158.11 g/mol

Hydrolysis

1 45090017 Not determined Not determined

Aq photolysis

3 46658101 Not applicable Not applicable

Aq photolysis

4 46658101 30.2 (14) 30.2 (14)

Soil photolysis

3 45090020, 

46299904

Not applicable Not applicable

Soil photolysis

4 12 (12.29) 12 (12.29)

Aerobic soil

3 45090019 Not applicable Not applicable

Aerobic soil

4 45090019 2.1 (30) 0.2 (269)

Aerobic soil

3 45090021 Not applicable Not applicable

Aerobic soil

4 45090021 0.8 (120) 0.2 (272)

Aer soil (S)

3, 6 45090022 Not applicable Not applicable

Aer soil (LS)

3, 6 45090022 Not applicable Not applicable

Aer soil (CL)

3, 6 45090022 Not applicable Not applicable

Anaerobic soil

3 45090023 Not applicable Not applicable

Anaerobic soil

4 45090023 38.2 (120) 38.2 (120)

Anaerobic aquat

3 45621718 Not applicable Not applicable

Anaerobic aquat

4 45621718 19.9 (179) 2.26 (362)

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not detected

(all intervals)

Not detected 

(122)

Terr dissipation 45621722 Not detected

(all intervals)

Not detected 

(136)

Terr dissipation 45621723 16.2 (10) Not detected (29)

4-tert-Butyl-2-

ethoxybenzoic acid

Hydrolysis

1 45090017 Not determined Not determined

Aq photolysis

3 46658101 5.6 (11) 3.7 (20)
53

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)A

Final %AR 

(study 

length, day)

R-12 (t-BE-benzoic 

acid) SMILES Code:

C(C1=C(C=C(C=C1)C(C)

(C)C)OCC)(=O)O[H]

Formula: C13H18O3

MW: 222.29 g/mol

Aq photolysis4 46658101 Not applicable Not applicable

Soil photolysis3 45090020, 

46299904

7.9 (12.25) 7.9 (12.25)

Soil photolysis4 Not applicable Not applicable

Aerobic soil3 45090019 4.0 (269) 4.0 (269)

Aerobic soil4 45090019 Not applicable Not applicable

Aerobic soil3 45090021 Not determined Not determined

Aerobic soil4 45090021 Not applicable Not applicable

Aer soil (S)3, 6 45090022 8.5 (180) 8.5 (180)

Aer soil (LS)3, 6 45090022 3.8 (61) 1.2 (180)

Aer soil (CL)3, 6 45090022 6.0 (30) 2.3 (180)

Anaerobic soil3 45090023 Not determined Not determined

Anaerobic soil4 45090023 Not applicable Not applicable

Anaerobic aquat3 45621718 0.37 (305) 0.21 (362)

Anaerobic aquat4 45621718 Not applicable Not applicable

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not determined Not determined

Terr dissipation 45621722 Not determined Not determined

Terr dissipation 45621723 Not determined Not determined

R-13 4-(4-tert-Butyl-2-

ethoxyphenyl)-2-(2,6-

difluorophenyl)-oxazole

SMILES Code:

C1(=CC=CC(=C1C2=NC(

=CO2)C3=C(C=C(C=C3)

C(C)(C)C)OCC)F)F

Formula: C21H21F2NO2

MW: 357.40 g/mol

Hydrolysis1 45090017 <0.9 (7) Not detected

(30)

Aq photolysis3 46658101 Not detected Not detected

Aq photolysis4 46658101 Not detected Not detected

Soil photolysis3 45090020, 

46299904

3.0 (12.25) 3.0 (12.25)

Soil photolysis4 1.9 (7.38-9.79) 1.2 (12.29)

Aerobic soil3 45090019 11.7 (60) 7.1 (269)

Aerobic soil4 45090019 10.9 (60) 7.2 (269)

Aerobic soil3 45090021 30.0 (62) 9.4 (272)

Aerobic soil4 45090021 26.6 (62) 6.6 (272)

Aer soil (S)3, 6 45090022 9.1 (180) 9.1 (180)

Aer soil (LS)3, 6 45090022 8.4 (120) 7.1 (180)

Aer soil (CL)3, 6 45090022 19.1 (180) 19.1 (180)

Anaerobic soil3 45090023 1.8 (120) 1.8 (120)

Anaerobic soil4 45090023 1.4 (40, 120) 1.4 (120)

Anaerobic aquat3 45621718 Not detected Not detected

Anaerobic aquat4 45621718 Traces Traces

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not detected

(all intervals)

Not detected 

(122)

N

O

O

C

CH3

CH3

H3C

F

F

C

H2

H3C
54

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)

A

Final %AR 

(study 

length, day)

Terr dissipation 45621722 8.3 (0) Not detected 

(136)

Terr dissipation 45621723 Not detected

(all intervals)

Not detected (29)

R-15

4-tert-Butyl-2-

ethoxybenzamide

SMILES Code: 

C(C1=C(C=C(C=C1)C(C)

(C)C)OCC)(=O)N([H])[H]

Formula:C13H19NO

2

MW: 221.30 g/mol

Hydrolysis

1 45090017 Not determined Not determined

Aq photolysis

3 46658101 1.7 (20) 1.7 (20)

Aq photolysis

4 46658101 Not applicable Not applicable

Soil photolysis

3 45090020, 

46299904

3.7 (12.25) 3.7 (12.25)

Soil photolysis

4 Not applicable Not applicable

Aerobic soil

3 45090019 3.2 (269) 3.2 (269)

Aerobic soil

4 45090019 Not applicable Not applicable

Aerobic soil

3 45090021 2.0 (100) 1.1 (272)

Aerobic soil

4 45090021 Not applicable Not applicable

Aer soil (S)

3, 6 45090022 3.1 (180) 3.1 (180)

Aer soil (LS)

3, 6 45090022 3.7 (180) 3.7 (180)

Aer soil (CL)

3, 6 45090022 6.3 (30) 2.6 (180)

Anaerobic soil

3 45090023 Not determined Not determined

Anaerobic soil

4 45090023 Not applicable Not applicable

Anaerobic aquat

3 45621718 Not detected Not detected

Anaerobic aquat

4 45621718 Not applicable Not applicable

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not determined Not determined

Terr dissipation 45621722 Not determined Not determined

Terr dissipation 45621723 Not determined Not determined

R-16

2-methyl-2-{3-ethoxy-4-

[2-(2',6-difluoropheny1)-

4,5-dihydro-,3 -0xazole-4-

yllphenyl} propionic

Acid

SMILES Code: 

C1(=CC=CC(=C1C2=NC(

CO2)C3=C(C=C(C=C3)C(

C)(C(=O)O[H])C)OCC)F) F

Formula:C21H21F

2NO4

MW: 389.40 g/mol

Hydrolysis

1 45090017 Not determined Not determined

Aq photolysis

3 46658101 Not determined Not determined

Aq photolysis

4 46658101 Not determined Not determined

Soil photolysis

3 45090020, 

46299904

Not determined Not determined

Soil photolysis

4 Not determined Not determined

Aerobic soil

3 45090019 Not determined Not determined

Aerobic soil

4 45090019 Not determined Not determined

Aerobic soil

3 45090021 2.8 () 0.3 (272)

Aerobic soil

4 45090021 1.3 (62) Not detected 

(272)

Aer soil (S)

3, 6 45090022 Not determined Not determined

Aer soil (LS)

3, 6 45090022 Not determined Not determined

Aer soil (CL)

3, 6 45090022 Not determined Not determined

Anaerobic soil

3 45090023 Not determined Not determined

O

CC

H

3

CH

3

H

3

C

C

CH

2

H

3

C

O

NH

2
55

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)A

Final %AR 

(study 

length, day)

Anaerobic soil4 45090023 Not determined Not determined

Anaerobic aquat3 45621718 Not detected Not detected

Anaerobic aquat4 45621718 Not detected Not detected

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not determined Not determined

Terr dissipation 45621722 Not determined Not determined

Terr dissipation 45621723 Not determined Not determined

R-20 2-Ethoxy-4-(1-

hydroxymethyl-1-

methylethyl)benzoic acid

SMILES Code:

C(C1=C(C=C(C=C1)C(C)

(CO[H])C)OCC)(=O)O[H]

Formula: C13H18O4

MW: 238.29 g/mol

Hydrolysis1 45090017 Not determined Not determined

Aq photolysis3 46658101 Not detected Not detected

Aq photolysis4 46658101 Not applicable Not applicable

Soil photolysis3 45090020, 

46299904

Not determined Not determined

Soil photolysis4 Not applicable Not applicable

Aerobic soil3 45090019 Not determined Not determined

Aerobic soil4 45090019 Not applicable Not applicable

Aerobic soil3 45090021 Not determined Not determined

Aerobic soil4 45090021 Not applicable Not applicable

Aer soil (S)3, 6 45090022 Not determined Not determined

Aer soil (LS)3, 6 45090022 Not determined Not determined

Aer soil (CL)3, 6 45090022 Not determined Not determined

Anaerobic soil3 45090023 Not determined Not determined

Anaerobic soil4 45090023 Not applicable Not applicable

Anaerobic aquat3 45621718 Not detected Not detected

Anaerobic aquat4 45621718 Not applicable Not applicable

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not determined Not determined

Terr dissipation 45621722 Not determined Not determined

Terr dissipation 45621723 Not determined Not determined

DFBA (DFB amide) 2,6-Difluorobenzamide

SMILES Code:

C1(=CC=CC(=C1C(=O)N

([H])[H])F)F

Formula: C7H5F2NO

MW: 157.12 g/mol

Hydrolysis1 45090017 Not determined Not determined

Aq photolysis3 46658101 Not applicable Not applicable

Aq photolysis4 46658101 8.6 (14) 8.6 (14)

Soil photolysis3 45090020,

46299904

Not determined Not determined

Soil photolysis4 Not applicable Not applicable

Aerobic soil3 45090019 Not applicable Not applicable

Aerobic soil4 45090019 Not determined Not determined

Aerobic soil3 45090021 Not applicable Not applicable

Aerobic soil4 45090021 0.8 (180) 0.6 (272)

Aer soil (S)3, 6 45090022 Not applicable Not applicable

Aer soil (LS)3, 6 45090022 Not applicable Not applicable

F

F

C

NH2

O
56

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type Ref.

(MRID)

Maximum 

%AR (day)A

Final %AR 

(study 

length, day)

Aer soil (CL)3, 6 45090022 Not applicable Not applicable

Anaerobic soil3 45090023 Not applicable Not applicable

Anaerobic soil4 45090023 Not determined Not determined

Anaerobic aquat3 45621718 Not applicable Not applicable

Anaerobic aquat4 45621718 Not detected Not detected

Terr dissipation 45250909 Not determined Not determined

Terr dissipation 45621721 Not determined Not determined

Terr dissipation 45621722 Not determined Not determined

Terr dissipation 45621723 Not determined Not determined

CO2

Carbon dioxide

SMILES Code: C(=O)=O

Formula: CO2

MW: 44.01 g/mol

Hydrolysis1 45090017 Not applicable Not determined

Aq photolysis3 46658101 12.6 (20)

Aq photolysis4 46658101 3.7 (14)

Soil photolysis3 45090020, 

46299904

6.6 (12.25)5

Soil photolysis4 8.7 (12.29)5

Aerobic soil3 45090019 <15.9 (269)

Aerobic soil4 45090019 56.17 (269)

Aerobic soil3 45090021 40.5 (272)

Aerobic soil4 45090021 46.8 (272)

Aer soil (S)3, 6 45090022 Not determined

Aer soil (LS)3, 6 45090022 Not determined

Aer soil (CL)3, 6 45090022 Not determined

Anaerobic soil3 45090023 Not determined8

Anaerobic soil4 45090023 Not determined8

Anaerobic aquat3 45621718 Not detected

Anaerobic aquat4 45621718 18.1 (362)

Terr dissipation 45250909 Not applicable

Terr dissipation 45621721 Not applicable

Terr dissipation 45621722 Not applicable

Terr dissipation 45621723 Not applicable

A Bolded values indicate a major degradate was formed.

B Percentages in terrestrial field study represent the ratio of degradate concentration to the maximum parent concentration, both in the top layer of soil.

1 The hydrolysis results presented are for the pH 7 (200C) run. These are the closest to relevant environmental conditions. R-7 was a major degradate at pH 5. R-4 and R-13 were 

minor degradates in the same pH 5 solution.

2

It was unclear whether R-4 and R-7 were present at the same time. The study authors stated that only R-4 was a major degradate at pH 7.

3

and 4 These superscripts refer to the [tert-butylphenyl14C]- and [difluorophenyl14C]-etoxazole, respectively.

5 The study author reported that almost all the volatile radioactivity was CO2.

6 Three soils were tested: sand (S), loamy sand (LS), and clay loam (CL).

7 This degradate was observed at 0.4% AR in several intervals.

8 The total volatiles were <0.76% AR.

O C O
57

Figure A.1. Registrant-postulated degradation pathway for etoxazole under aerobic 

conditions
58

Appendix B. Etoxazole Fate and Ecological Effects Bibliography

107091 Etoxazole Fate Chemistry Bibliography

161-1 Hydrolysis

MRID Citation Reference

45090017 Elsom, L. (1996) The Hydrolysis of YI-5301: Lab Project Number: YMA 9/950390: 

200000090. Unpublished study prepared by Huntingdon Life Sciences Ltd. 78 p.

161-2 Photodegradation-water

MRID Citation Reference

45090018 Elsom, L. (1997) (Carbon 14)-YI-5301 Photodegradation in Water: Lab Project Number: 

YMA 27A/962751: 9700237. Unpublished study prepared by Huntingdon Life Sciences Ltd. 

120 p. 

46658101 Gohre, K. (2005) Photodegradation of (Carbon 14) Etoxazole in Buffered Water. Project 

Number: 200500201, VP/27262, V/04/27262. Unpublished study prepared by Valent U.S.A. 

Corporation. 240 p.

161-3 Photodegradation-soil

MRID Citation Reference

45090020 Elsom, L. (1996) S-1283 Photodegradation on Soil: Lab Project Number: SMO 

453/960258: 9700170. Unpublished study prepared by Huntingdon Life Sciences Ltd. 135 

p. 

46299904 Rose, A. (2004) S-1283: Photodegradation on Soil: Valent's Responses to Data Evaluation 

Report for MRID Number 45090020. Project Number: VP/27781, 200400137. Unpublished 

study prepared by Valent U.S.A. Corporation. 20 p.

162-1 Aerobic soil metabolism

MRID Citation Reference
59

45090019 Girkin, R. (1997) (Carbon 14)-S-1283 Aerobic Soil Metabolism and Route of Degradation: 

Lab Project Number: SMO 447/962199: 9700212. Unpublished study prepared by 

Huntingdon Life Sciences Ltd. 104 p. 

45090021 Assaf, N. (1999) Metabolism of (tert-butylphenyl-(carbon 14) and (difluorophenyl-(carbon 

14) S-1283 in Aerobic Soil: Lab Project Number: VP-11906: 9900268. Unpublished study 

prepared by Valent USA Corp. 239 p. 

45090022 Dean, G. (1997) (Carbon 14)-S-1283 Rate of Degradation in Four Soils: Lab Project 

Number: 9700168: SMO 446/961212. Unpublished study prepared by Huntingdon Life 

Sciences Ltd. 121 p. 

162-2 Anaerobic soil metabolism

MRID Citation Reference

45090023 Girkin, R. (1997) (Carbon 14)-S-1283 Anaerobic Soil Metabolism: Lab Project Number: 

SMO 445/952710: 200000094. Unpublished study prepared by Huntingdon Life Sciences 

Ltd. 110 p. 

162-3 Anaerobic aquatic metab.

MRID Citation Reference

45621718 Assaf, N. (1993) Anaerobic Aquatic Metabolism of (tert-Butylphenyl-(Carbon-14)) Etoxazole 

and (Difluorophenyl-(Carbon-14)) Etoxazole: Lab Project Number: VP-12153: 200100200: 

V-98-12153. Unpublished study prepared by Valent U.S.A. Corporation. 180 p. 

163-1 Leaching/adsorption/desorption

MRID Citation Reference

45090024 Elsom, L. (1996) (Carbon 14)-S-1283 Adsorption/Desorption on Soil: Lab Project Number: 

SMO 520/961812: 200000091. Unpublished study prepared by Huntingdon Life Sciences 

Ltd. 74 p. 

45090025 Betteley, J. (1997) Metabolites R-3, R-4 and R-7 of S-1283 Determination of Soil 

Adsorption Coefficient (Koc) by HPLC: Lab Project Number: SMO 535/961611: 200000093. 

Unpublished study prepared by Huntingdon Life Sciences Ltd. 23 p. 

45090026 Jalal, M. (2000) Soil Adsorption/Desorption of Etoxazole (S-1283) and its Metabolite, R-13: 

Lab Project Number: VP-20925: 200000166. Unpublished study prepared by Valent USA 

Corp. 164 p. 

45250906 Elsom, L. (1997) (Carbon-14)-R-8 Adsorption/Desorption on Soil: Lab Project Number: 

SMO 524/963360: 9700166. Unpublished study prepared by Huntingdon Life Sciences Ltd. 

71 p. 
60

45250907 Elsom, L. (1997) (Carbon-14)-R-8 Adsorption/Desorption on Soil: Lab Project Number: 

SMO 522/963359: 9700166. Unpublished study prepared by Huntingdon Life Sciences Ltd. 

74 p. 

45250908 Elsom, L. (1996) (Carbon-14)-R-13 Adsorption/Desorption on Soil of R-13: A Soil 

Metabolite of S-1283: Lab Project Number: SMO 523/962178: 200000092. Unpublished 

study prepared by Huntingdon Life Sciences Ltd. 73 p. 

46299905 Rose, A. (2004) (Carbon 14)-1283 Adsorption/Desorption on Soil: Valent's Responses to 

Data Evaluation Report for MRID Number 45090024. Project Number: VP/27764, 

200400133. Unpublished study prepared by Valent U.S.A. Corporation. 12 p.

46299906 Jalal, M. (2004) Soil Adsorption/Desorption of Etoxazole (S-1283) and Its Metabolite R-13: 

Valent's Response to Data Evaluation Report for MRID Number 45090026. Project 

Number: VP/27772, 200400138. Unpublished study prepared by Valent U.S.A. 

Corporation. 12 p.

164-1 Terrestrial field dissipation

MRID Citation Reference

45250909 Burden, A. (1997) S-1283: Dissipation from Four Field Soils: Lab Project Number: CHE 

1481/6: 9800038: ER-97-13. Unpublished study prepared by Covance. 141 p. 

45621721 Assaf, N. (2002) Terrestrial Field Soil Dissipation of Etoxazole on Bare Ground in 

California: Lab Project Number: 20271: 200200025. Unpublished study prepared by Valent 

U.S.A. Corporation and Plant Sciences, Inc. 661 p. 

45621722 Schreier, T. (2002) Terrestrial Field Dissipation of Etoxazole on Bare Ground in Idaho: Lab 

Project Number: 22154: 200200007: V-22154-00-A. Unpublished study prepared by Valent 

U.S.A. Corporation. 564 p. 

45621723 Schreier, T. (2002) Terrestrial Field Dissipation of Etoxazole on Bare Ground in Mississippi: 

Lab Project Number: 22162: 200200008: RM-37SM. Unpublished study prepared by Valent 

U.S.A. Corporation. 499 p. 

165-1 Confined rotational crop

MRID Citation Reference

45621724 Jalal, M.; Lee, T. (1999) A Confined Accumulation in Rotational Crops Study on 

(Difuorophenyl-(Carbon-14)) S-1283 and (tert-Butylphenyl-(Carbon-14) S-1283 Using 

Wheat, Lettuce and Radish: Lab Project Number: VP-12090: 9900279: V-98-12090. 

Unpublished study prepared by Valent U.S.A. Corporation. 118 p. {OPPTS 860.1850} 

165-4 Bioaccumulation in fish

MRID Citation Reference
61

46299907 Rose, A. (2004) S-1283: Bioaccumulation in Rainbow Trout: Valent's Responses to Data 

Evaluation Report for MRID Number 45621615. Project Number: VP/27799, 200400139. 

Unpublished study prepared by Valent U.S.A. Corporation. 17 p.

45621615 McEwen, A.B. 1997. S-1283: Bioaccumulation in rainbow trout. Unpublished

study performed by Huntingdon Life Sciences Ltd., Cambridgeshire, England, and 

sponsored by Valent U.S.A. Corporation, Walnut Creek, California. Laboratory Project ID: 

SMO 5091963017. Study experimental start date November 7, 1995, and experimental end 

date September 12, 1996 (p. 28). Final report issued on June 27, 1997.

201-1 Droplet size spectrum

MRID Citation Reference

45621826 Hewitt, A. (2001) Atomization Droplet Size Spectra for V-1283 72 WDG: Lab Project 

Number: VP-23122: 200100201. Unpublished study prepared by Stewart Agricultural 

Research Services, Inc. 39 p.

850.6100 Environmental Chemistry Methods

MRID Citation Reference

45621719

Stearns, J. (2002) Independent Laboratory Validation of Valent Method RM-37S-2, 

"Determination of Etoxazole, R3 and R13 Metabolites in Soil": Lab Project Number: V23157: 200200013: RM-37S-2. Unpublished study prepared by Valent U.S.A. Corporation. 

49 p. {OPPTS 850.7100} 

45621720

Stearns, J. (2002) Independent Laboratory Validation of Valent Method RM-37SM, 

"Determination of Etoxazole, R4, R7, R8 and R11 in Soil": Lab Project Number: V-24045: 

200200014: RM-37SM. Unpublished study prepared by Valent U.S.A. Corporation. 84 p. 

{OPPTS 850.7100} 

107091 Etoxazole Eco Effects Bibliography

71-1 Avian Single Dose Oral Toxicity

MRID Citation Reference

45089908 Rodgers, M. (1996) S-1283: Acute Oral Toxicity (LD50) to Mallard Duck: Lab Project 

Number: SMO 470/952534: 9700176. Unpublished study prepared by Huntingdon Life 

Sciences Ltd. 20 p. 
62

71-2 Avian Dietary Toxicity

MRID Citation Reference

45089909 Rodgers, M. (1998) S-1283: Dietary (LD50) to the Mallard Duck: Lab Project Number: SMO 

558/982498: 9800120. Unpublished study prepared by Huntingdon Life Sciences Ltd. 38 p. 

45089910 Rodgers, M. (1996) YI-5301 Subacute Dietary Toxicity (LC50) to the Bobwhite Quail: Lab 

Project Number: YMA 24/950924: 200000072. Unpublished study prepared by Huntingdon 

Life Sciences Ltd. 35 p. 

71-4 Avian Reproduction

MRID Citation Reference

45621606 Rodgers, M. (1997) S-1283: Effects on Reproduction in Bobwhite Quail After Dietary 

Administration: Lab Project Number: SMO 512/961721. Unpublished study prepared by 

Huntingdon Life Sciences, Ltd. 253 p. {OPPTS 850.2300} 

45621607 Rodgers, M. (1999) S-1283: Effects on Reproduction in Mallard Duck After Dietary 

Administration: Lab Project Number: SMO 557/984779: SMO/557. Unpublished study 

prepared by Huntingdon Life Sciences, Ltd. 226 p. {OPPTS 850.2300} 

46299901 Pensyl, J. (2004) S-812: Effects on Reproduction in Bobwhite Quail After Dietary 

Administration: Valent's Responses to Data Evaluation Report for MRID Number 45621606. 

Project Number: VP/27801, 200400134. Unpublished study prepared by Valent U.S.A. 

Corporation. 8 p.

72-1 850.1075 Acute Toxicity to Freshwater Fish

MRID Citation Reference

45089911 Bell, G. (1996) S-1283: Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus): Lab 

Project Number: SMO 473/960069: 9700174. Unpublished study prepared by Huntingdon 

Life Sciences Ltd. 44 p. 

45089912 Bell, G. (1996) S-1283: Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss): Lab 

Project Number: SMO 444(C)/960068: 9700173. Unpublished study prepared by 

Huntingdon Life Sciences Ltd. 43 p. 

45089913 Collins, M. (1998) Screening Study to Establish the Relative Acute Toxicity of Five 

Metabolites of S-1283 to Bluegill Sunfish (Lepomis macrochirus) Under Static-Renewal 

Conditions: Lab Project Number: 98-1-7222: 9800330. Unpublished study prepared by 

Springborn Labs., Inc. 108 p. 

46059001 Lima, W. (2003) Etoxazole - Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under 

Flow-Through Conditions. Project Number: 13048/6393, 200300246. Unpublished study 

prepared by Springborn Smithers Laboratories. 50 p.
63

46059002 Lima, W. (2003) Etoxazole - Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus) Under 

Flow-Through Conditions. Project Number: 13048/6394, 200300247. Unpublished study 

prepared by Springborn Smithers Laboratories. 49 p.

72-2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

45089914 Putt, A. (1996) S-1283 TG--Acute Toxicity to Daphnids (Daphnia magna) Under FlowThrough Conditions: Lab Project Number: 96-7-6587: 200000148. Unpublished study 

prepared by Springborn Labs., Inc. 75 p. {OPPTS 850.1010} 

45621609 Collins, M. (1998) Screening Study to Establish the Relative Acute Toxicity of Five 

Metabolites of S-1283 to Daphnids (Daphnia magna) Under Static Conditions: Lab Project 

Number: 98-1-7220. Unpublished study prepared by Springborn Laboratories. 106 p. 

MRID Citation Reference

46460801

data 

waiver

Pensyl, J. (2004) Etoxazole Data Waiver Requests: Toxicity to Aquatic Organisms (6 

Studies). Project Number: VP/28433, 200400375. Unpublished study prepared by Valent 

U.S.A. Corp. 9 p.

72-3 Acute Toxicity to Estuarine/Marine Organisms

MRID Citation Reference

45621608 Dionne, E. (2000) Etoxazole Technical Grade--Acute Toxicity to Sheepshead Minnow 

(Cyprinodon varigatus) Under Flow-Through Conditions: Lab Project Number: 12709.6184: 

020499/FIFRA/OPPTS/FT-SHM. Unpublished study prepared by Springborn Laboratories, 

Inc. 54 p. {OPPTS 830.1075} 

45621610 Dionne, E. (2000) Etoxazole Technical Grade--Acute Toxicity to Eastern Oysters 

(Crassostrea virginica) under Flow-Through Conditions: Lab Project Number: 12709.6182. 

Unpublished study prepared by Springborn Laboratories, Inc. 66 p. {OPPTS 850.1025} 

850.1025 Oyster acute toxicity test (shell deposition)

MRID Citation Reference

46460801

data 

waiver

Pensyl, J. (2004) Etoxazole Data Waiver Requests: Toxicity to Aquatic Organisms (6 

Studies). Project Number: VP/28433, 200400375. Unpublished study prepared by Valent 

U.S.A. Corp. 9 p.

46732201 Cafarella, M. (2005) Zeal Miticide - Acute Toxicity to Eastern Oyster (Crassostrea virginica) 

Under Flow-Through Conditions. Project Number: 12709/6237, 200600006. Unpublished 

study prepared by Valent U.S.A. 62 p.
64

72-4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

MRID Citation Reference

45621612 Lima, W. (2002) (Carbon 14) Etoxazole--Life-Cycle Toxicity Test with Mysids (Americamysis 

bahia): Lab Project Number: 12709.6192: 081400/FIFRA/MYSID-LC/VALENT. Unpublished 

study prepared by Springborn Laboratories, Inc. 91 p. 

45621614 Sousa, J. (1996) S-1283 TG--Early Life-Stage Toxicity Test with Rainbow Trout 

(Oncorhynchus mykiss): Lab Project Number: 96-2-6390: 10348.0795.6105.121. 

Unpublished study prepared by Springborn Laboratories, Inc. 103 p. {OPPTS 850.1400} 

46299902 Pensyl, J. (2004) [14 Carbon] Etoxazole - Life Cycle Toxicity Test with Mysids 

(Americanmysis Bahia): Valent's Responses to Data Evaluation Report for MRID 45621612. 

Project Number: VP/27828, 200400135. Unpublished study prepared by Valent U.S.A. 

Corporation. 7 p.

850.1300 Daphnid chronic toxicity test

MRID Citation Reference

46497901 Putt, A. (2005) Etoxazole - Full-Life Cycle Toxicity Test with water Fleas Daphnia magna 

Under Flow-Through Conditions. Project Number: 13048/6443, 200500035. Unpublished 

study prepared by Springborn Smithers Laboratories. 97 p.

72-6 Aquatic org. accumulation

MRID Citation Reference

45621615 McEwen, A. (1997) S-1283: Bioaccumulation in Rainbow Trout: Lab Project Number: SMO 

509/963017. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 144 p. {OPPTS 

850.1730} 

72-7 Simulated or Actual Field Testing

MRID Citation Reference

45621616 Schanne, C. (2001) Etoxazole 110 g/L SC Formulation: Indoor Aquatic Microcosm Study 

of the Ecological Effects on Daphnia magna: Lab Project Number: 1043.001.310. 

Unpublished study prepared by Springborn Laboratories (Europe) AG. 176 p. 

122-1 Seed Germination/Seedline Emergence and Vegetable Vigor

MRID Citation Reference
65

45621623 Chetram, R. (1998) Tier 1 Seedling Emergence Nontarget Phytotoxicity Study Using 

Etoxazole: Lab Project Number: ABC NO: 97687: 97687: VP-11911. Unpublished study 

prepared by ABC Laboratories California. 157 p. 

45621701 Chetram, R. (1998) Tier 1 Vegetative Vigor Nontarget Phytotoxicity Study Using 

Etoxazole: Lab Project Number: 97688: 9800171: VP-11910. Unpublished study prepared 

by ABC Laboratories California. 176 p. 

46299903 Rose, A. (2004) S-1283: Algal Growth Inhibition: Valent's Responses to Data Evaluation 

Report for MRID Number 45621705. Project Number: VP/27828, 200400136. Unpublished 

study prepared by Valent U.S.A. Corporation. 8 p.

122-2 Aquatic plant growth

MRID Citation Reference

45621702 Hoberg, J. (1998) R-7--Toxicity to the Freshwater Green Alga, Selenastrum 

capricornutum: Lab Project Number: 98-2-7232: 200200033. Unpublished study prepared 

by Springborn Laboratories, Inc. 83 p. {OPPTS 850.5400} 

45621703 Hoberg, J. (1998) R-13--Toxicity to the Freshwater Green Alga, Selenastrum 

capricornutum: Lab Project Number: 98-2-7237. Unpublished study prepared by 

Springborn Laboratories, Inc. 70 p. {OPPTS 850.5400} 

45621704 Hoberg, J. (1998) R-3--Toxicity to the Freshwater Green Alga, Selenastrum 

capricornutum: Lab Project Number: 98-2-7233: 200200032. Unpublished study prepared 

by Springborn Laboratories, Inc. 69 p. 

45621705 Bell, G. (1996) S-1283: Algal Growth Inhibition: Lab Project Number: SMO 444(A)/960070: 

9700175. Unpublished study prepared by Huntingdon Life Sciences Ltd. 38 p. {OPPTS 

850.5400}

850.5400 Algal toxicity, Tiers 1 and II

MRID Citation Reference

48578301 Porch, J.; Kendall, T.; Krueger, H. (2011) Etoxazole: A 7-Day Static Renewal Tier I Toxicity 

Limit Test with Duckweed (Lemna gibba G3). Project Number: 263A/117B, VP/37665, 

201100319. Unpublished study prepared by Wildlife International, Ltd. 64p.

48578302 Porch, J.; Kendall, T.; Krueger, T. (2011) Etoxazole: A 96-Hour Tier I Toxicity Limit Test 

with the Freshwater Alga (Anabaena flos-aquae). Project Number: 201100318, 263A/116B, 

VP/37663. Unpublished study prepared by Wildlife International, Ltd. 54p.

48578303 Porch, J.; Kendall, T.; Krueger, H. (2011) Etoxazole: A 96-Hour Tier I Toxicity Limit Test 

with the Freshwater Diatom (Navicula pelliculosa). Project Number: 201100320, 

263A/118C, VP/37668. Unpublished study prepared by Wildlife International, Ltd. 55p.
66

48603001 Porch, J.; Kendall, T.; Krueger, H. (2011) Etoxazole: A 96-Hour Tier 1 Toxicity Limit Test 

with the Marine Diatom (Skeletonema costatum). Project Number: 201100347, 263A/119A, 

VP/37670. Unpublished study prepared by Wildlife International, Ltd. 57p.

141-1 Honey bee acute contact

MRID Citation Reference

45621706 Wiles, J. (1996) YI-5301: Acute Toxicity to Honey Bees (Apis mellifera): Lab Project 

Number: YMA 30/961664: 9700165. Unpublished study prepared by Huntingdon Life 

Sciences Ltd. 24 p. {OPPTS 850.3020} 

143-1 Toxicity to Predator and Parasite Insects

MRID Citation Reference

45621708 Valla, J. (1997) Assessment of the Practical Medium Term Consequences of PHF 9502 

(Philagro France) on the Predators of the Red Mite (P. ulmi) and on Other Auxilliary 

Entomophages in Apple Orchards: Lab Project Number: ACTA:VAR9701: 200200012. 

Unpublished study prepared by S.R.P.V./F.R.E.D.E.C. Languedoc--Roussilon. 13 p. 

45621709 Thompson, B. (1997) A Laboratory Evaluation of the Effects of the Acaricide PHF 9502, 

Containing 110 G/L Etoxazole, On the Lacewing Chrysoperia carnea: Lab Project Number: 

JSC-97-1: 200100348. Unpublished study prepared by University of Southampton, School 

of Biological Sciences. 19 p. 

45621710 Nickless, A. (1997) A Laboratory Study to Evaluate the Effects of the PHF 9502, Containing 

110 G/L Etoxazole (S-1283) on the Adult and Juvenile Life Stages of the Parasitic Wasp 

Aphidius rhopalosiphi: Lab Project Number: ER-97-21: 200100342: HMA 180. Unpublished 

study prepared by Ecotox Limited. 58 p. 

45621711 Tessier, C.; Austin, H. (1997) A Laboratory Study to Evaluate the Effects of the PHF 9502 

Containing 110 G/L Etoxazole (S-1283) on the Heteropteran Bug Orius laevigatus: Lab 

Project Number: ER-97-18: 200100343: 96028. Unpublished study prepared by Ecotox 

Limited. 34 p. 

45621712 Lacote, E. (1997) Non-Intentional Effects on T. pyri: Lab Project Number: 69220: 

200100347. Unpublished study prepared by S.R.P.V. Rhones Alpes. 14 p. 

45621713 Rivenez, M. (1997) Non Target Effects on T. pyri: Lab Project Number: P396011: 

200100363. Unpublished study prepared by Service Regional De La Protection (S.R.P.V.) 

des Vegetaux "Midi-Pyrenees". 12 p. 

45621714 Bourgouin, B.; Brun, V. (1997) Non Target Effects of PHF 9502 on Neoseiulus californicus: 

Lab Project Number: CV22ARBO: 200100365. Unpublished study prepared by Service 

Regional De La Protection (S.R.P.V.) des Vegetaux "Midi-Pyrenees". 14 p. 

45621715 Bourgouin, B.; Brun, V.; Lavielle, C. (1997) Potter Tower Test PHF 9502 on Neoseiulus 

californicus (Adults) Potter Tower Test with Mite Rearing: Lab Project Number: 

CV20ARBO: 200100366. Unpublished study prepared by S.R.P.V./F.R.E.D.E.C. 

Languedoc-Rousillon. 9 p. 
67

45621716 Bourgouin, B.; Brun, V.; Lavielle, C. (1997) Potter Tower Test PHF 9502 on Typhylodromus 

pyri (Adults): Lab Project Number: CV21ARBO: 200100364. Unpublished study prepared 

by S.R.P.V./F.R.E.D.E.C. Languedoc-Rousillon. 7 p. 

45621717 Auger, P. (1993) Study of Unintentional Effect of the Product PHF 9502 on Two Population 

of T. pyri: Lab Project Number: 200100341. Unpublished study prepared by 

S.R.P.V./F.R.E.D.E.C. Languedoc-Rousillon. 14 p. 

850.1740 Whole sediment: acute marine invertebrates

MRID Citation Reference

46652902 Rose, A. (2005) Waiver Request - Etoxazole Acute and Chronic Sediment Toxicity Testing. 

Project Number: VP/29671, 200500217, VP/28741. Unpublished study prepared by Valent 

U.S.A. Corporation. 52 p.

850.1790 Chironomid Sediment Toxicity Test

MRID Citation Reference

46652902 Rose, A. (2005) Waiver Request - Etoxazole Acute and Chronic Sediment Toxicity Testing. 

Project Number: VP/29671, 200500217, VP/28741. Unpublished study prepared by Valent 

U.S.A. Corporation. 52 p.

45621707 Putt, A. (1998) (Carbon-14)-S-1283--Acute Toxicity to Midge (Chironomus riparius) During a 

10-Day Sediment Exposure Under Static Renewal Conditions: Lab Project Number: 98-1-

7227: 200100350: 111997/ASTM/163/S-1283. Unpublished study prepared by Huntingdon 

Life Sciences Ltd. 125 p. 

850.1735 Whole sediment: acute freshwater invertebrates

MRID Citation Reference

47837702 Picard, C. (2008) Etoxazole Technical Grade- 10-Day Toxicity Test Exposing Midge 

(Chironomus dilutus) to a Test Substance Applied to Sediment under Static-Renewal 

Conditions. Project Number: 12709/6265, VP/32285. Unpublished study prepared by 

Springborn Smithers Laboratories. 114 p.

Marine Invertebrate Sediment Toxicity Test

47837701 Picard, C. (2008) Etoxazole Technical Grade - 28-Day Toxicity Test Exposing Estuarine 

Amphipods (Leptocheirus plumulosus) to a Test Substance Applied to Sediment Following 

EPA Test Methods. Project Number: 12709/6266, VP/32292, 200900009. Unpublished 

study prepared by Springborn Smithers Laboratories. 91 p.
68

Appendix C. SIP Output

Table 1. Inputs

Parameter Value

Chemical name Etoxazole

Solubility (in water at 25oC; mg/L) 0.075

Mammalian LD50 (mg/kg-bw) 5000

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg-bw) 100

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Avian LD50 (mg/kg-bw) 2000

Avian test species mallard duck

Body weight (g) of "other" avian species

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 958

Bobwhite quail NOAEC (mg/kg-diet) 286

NOAEC (mg/kg-diet) for other bird species

Body weight (g) of other avian species

NOAEC (mg/kg-diet) for 2nd other bird species

Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 0.0129 0.0129

Adjusted toxicity value (mg/kg-bw) 3845.8028 76.9161

Ratio of exposure to toxicity 0.0000 0.0002

Conclusion*

Drinking water exposure 

alone is NOT a potential 

concern for mammals

Drinking water exposure 

alone is NOT a potential 

concern for mammals

Table 3. Avian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 0.0608 0.0608

Adjusted toxicity value (mg/kg-bw) 1038.4508 30.4013

Ratio of exposure to acute toxicity 0.0001 0.0020

Conclusion*

Drinking water exposure 

alone is NOT a potential 

concern for birds

Drinking water exposure 

alone is NOT a potential 

concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when 

aggregated with other routes (i.e., diet, inhalation, dermal), pesticide exposure through drinking water may contribute 

to a total exposure that has potential for effects to non-target animals.
69

Appendix D. STIR Output

Input

Application and Chemical Information

Enter Chemical Name Etoxazole

Enter Chemical Use

Is the Application a Spray? (enter y or n) y

If Spray What Type (enter ground or air) ground

Enter Chemical Molecular Weight (g/mole) 359.42

Enter Chemical Vapor Pressure (mmHg) 7.00E-06

Enter Application Rate (lb a.i./acre) 0.6

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 2000

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC50 (mg/L) 1.09

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.35E-01

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.70E-02

Adjusted Inhalation LD50 1.75E+00

Ratio of Vapor Dose to Adjusted Inhalation LD50 9.71E-03 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose 

(mg/kg) 6.34E-02

Ratio of Droplet Inhalation Dose to Adjusted 

Inhalation LD50 3.62E-02 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.35E-01

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.14E-02

Adjusted Inhalation LD50 6.49E+01

Ratio of Vapor Dose to Adjusted Inhalation LD50 3.30E-04 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose 

(mg/kg) 7.97E-02

Ratio of Droplet Inhalation Dose to Adjusted 

Inhalation LD50 1.23E-03 Exposure not Likely Significant

**NOTE**: When entering values, 

press the "Enter" key in order to 

update linked cells.
70

Appendix E. Etoxazole Preliminary EECs Including the Total Toxic 

Residues

Half-lives were recalculated, including the residues of ecological concern, R-8 and R-13. Two 

PRZM/EXAMS runs were performed for the scenarios that appeared to show the highest 

exposure. Table E1 shows the input parameters utilized. Table E2 shows the results.

Table E1. Input parameters utilized in PRZM/EXAMS for Etoxazole

Parameter (units) Value(s)1 Sources Comments

Output File Name ETOXAZOLE --- ---

Chemical Name Etoxazole Label ---

Application Rate Kg a.i./ha

0.151 for corn

0.202 for mint

lb a.i./A

0.135 for corn

0.18 for mint

Maximum allowed by the 

label and supplemental label 

for ZEAL® WDG Miticide, 

EPA Reg. No. 59639-123

Number of Applications 

Allowed

IL corn – 2

OR mint – 1

Maximum allowed by 

the label.

Zeal Miticide label.

Interval between 

Applications (days)

IL corn – 14

OR mint – not applicable

Minimum allowed by 

the label.

Zeal Miticide label.

Crop Names and Days of 

Application (day-month)

IL corn – 10-06

OR mint – 15-06

Corn includes pop, field 

and corn grown for seed 

production. Mint 

includes peppermint and 

spearmint.

PHI: corn 21 days and mint 7 

days. IL corn crop emergence 

May 1, maturity Sept. 21, 

harvest Oct. 20. OR mint crop 

emergence April 15, maturity 

July 25, harvest August 1.

Kd (ml/g) 151 MRID: 45090024, 

45090026, 46299905, 

46299906

Represents the average Kd

value among eight values 

ranging from 66 to 335 ml/g; 

the Kd model was utilized 

because it represents the 

mobility of etoxazole better 

than KOC. Binding is not 

correlated with OC.

Aerobic Soil Metabolism 

(days)

= 370

MRID: 45090019, 

45090021, 45090022

90th percentile confidence 

bound on the mean half-life 

value: three values are 

available: 234 days and 525

days at 20°C, and 66.3 days at 

25°C; respective half-lives 

corrected to 25°C are 165

days, 371 days and 66.3 days; 

mean = 200.77 days, std. dev. 

= 155.47 days, n = 3, t90,n-1 = 

1.886

Method of Application IL corn – aerial

OR mint – aerial

Zeal Miticide label.

Buffer Zone (ft.) 0 Zeal Miticide label.

Application Efficiency 

(fraction)

IL corn and OR mint – 0.95 Value for aerial 

applications.

---

Spray Drift (fraction) IL corn and OR mint –

0.125

Default for fine to 

medium droplet sizes.

---

Solubility in Water (ppm) 0.0754 MRID: 45089902 and 

45089903

Solubility at 20oC.

t t

t s

n

input

n

 



1 2

90 1

/

,

( )
71

Parameter (units) Value(s)1 Sources Comments

Aerobic Aquatic 

Metabolism (days)

740 Not available. No data are available, and the 

compound is relatively stable 

to hydrolysis; therefore, 2x the 

aerobic soil metabolism input 

is used.

Anaerobic Aquatic 

Metabolism (days)

636 MRID: 45621718 3X the single available value 

212 days x 3 = 636 days

Hydrolysis at pH 7 99 MRID: 45090017 Etoxazole shows relatively 

high stability in pH 7 solution.

Aqueous Photolysis (days) 34 MRID: 46658101 Environmental phototransformation half-life.

Molecular Weight (g/mole) 359.42 Product Chemistry ---

Vapor Pressure (torr) 7 x 10-6 MRID: 45089902 ---

Henry’s Law Constant

(atm-m3/mol)

8.5 x 10-6--- Estimated from vapor pressure 

and water solubility.

EXAMS Environment Pond298.exv --- Default for pond scenario, as 

Field Size EPA pond --- opposed to index reservoir.

Runoff None --- ---

PRZM Scenario and Metfile IL corn – w14842.dvf

OR mint – w24232.dvf

As suggested by the 

shell for the SWCC.

---

Incorporation Depth (cm) 0.0 Zeal Miticide label.

CAM (Chemical 

Application Method)

2 Zeal Miticide label. 2 = linear foliar based on crop 

canopy.

IPSCND (Condition for 

disposition of pesticide 

remaining on foliage after 

harvest)

1 Zeal Miticide label. 1 = pesticide remaining on 

foliage is converted to surface 

application to the top soil 

layer

FEXTRC, Foliar extraction 0.5 --- ---

PLDKRT, Decay rate on 

foliage

0 --- ---

PLVKRT, Volatilization 

rate from foliage

0 --- ---

UPTKF, Uptake factor 0 --- ---

1 Data were selected according to EFED Guidance on Input Parameters v.2.1, dated October 22, 2009 and 

approved November 10, 2009.

Table E2. Surface waters estimated environmental exposure concentrations (EECs) for 

Etoxazole

Application 

Rate (lb a.i./A) 

x No. of Apps

Water Column Pore Water Sediment

Crop Scenario

Peak

(ppb)

21-day

(ppb)

60-day

(ppb)

Peak

(ppb)

21-day

(ppb)

Peak

(ppb)

21-day

(ppb)

IL corn 0.135 x 2 2.56 0.393 0.377 0.400 0.393 60.4 59.3

OR mint 0.18 x 1 1.32 0.118 0.111 0.122 0.118 18.4 17.8

IL Corn Summary of Water Modeling of Etoxazole and the USEPA 

Standard Pond

Estimated Environmental Concentrations for Etoxazole are presented in Table 1 for the USEPA 

standard pond with the ILCornSTD field scenario. A graphical presentation of the year-to-year 

peaks is presented in Figure 1. These values were generated with the Surface Water Calculator 

(Version 1.092). Critical input values for the model are summarized in Table 2.
72

This model estimates that about 3.8% of Etoxazole applied to the field eventually reaches the 

water body. The main mechanism of transport from the field to the water body is by erosion 

(43% of the total transport), followed by spray drift (33%), and runoff (24%).

In the water body, pesticide dissipates with an effective water column half life of 12.1 days. 

(This value does not include dissipation by transport to the benthic region; it includes only 

processes that result in removal of pesticide from the complete system.) The main source of 

dissipation in the water column is volatilization (effective average half life = 14 days), followed 

by hydrolysis (99 days), photolysis (1605.7 days), and metabolism (1620.9 days).

In the benthic region, pesticide dissipation is negligible (1380.2 days).The main source of 

dissipation in the benthic region is metabolism (effective average half life = 1393.1 days) 

followed by hydrolysis (149589.1 days). The vast majority of the pesticide in the benthic region 

(99.93%) is sorbed to sediment rather than in the pore water.

Table E3. Estimated Environmental Concentrations (ppb) for Etoxazole.

Peak (1-in-10 yr) 2.56

4-day Avg (1-in-10 yr) 0.399

21-day Avg (1-in-10 yr) 0.393

60-day Avg (1-in-10 yr) 0.377

365-day Avg (1-in-10 yr) 0.273

Entire Simulation Mean 0.223

Table E4. Summary of Model Inputs for Etoxazole.

Scenario ILCornSTD

Koc (ml/g) 151

Water Half Life (days) @ 25 °C 740

Benthic Half Life (days) @ 25 °C 636

Photolysis Half Life (days) @ 40 °Lat 34

Hydrolysis Half Life (days) 99

Soil Half Life (days) @ 25 °C 370

Foliar Half Life (days) 0

Molecular Wt 359.42

Vapor Pressure (torr) 7e-6

Solubility (mg/l) 0.0754
73

Figure E1. Yearly Peak Concentrations - Corn

OR Mint Summary of Water Modeling of Etoxazole and the USEPA 

Standard Pond

Estimated Environmental Concentrations for Etoxazole are presented in Table 1 for the USEPA 

standard pond with the ORmintSTD field scenario. A graphical presentation of the year-to-year 

peaks is presented in Figure 1. These values were generated with the Surface Water Calculator 

(Version 1.092). Critical input values for the model are summarized in Table 2.

This model estimates that about 1.8% of Etoxazole applied to the field eventually reaches the 

water body. The main mechanism of transport from the field to the water body is by spray drift 

(70% of the total transport), followed by runoff (24%), and erosion (5.5%).

In the water body, pesticide dissipates with an effective water column half life of 12.6 days. 

(This value does not include dissipation by transport to the benthic region; it includes only 

processes that result in removal of pesticide from the complete system.) The main source of 

dissipation in the water column is volatilization (effective average half life = 14.7 days), 

followed by hydrolysis (99 days), photolysis (1337.5 days), and metabolism (1803.2 days).

In the benthic region, pesticide dissipation is negligible (1533.9 days).The main source of 

dissipation in the benthic region is metabolism (effective average half life = 1549.8 days) 

followed by hydrolysis (149589.1 days). The vast majority of the pesticide in the benthic region 

(99.93%) is sorbed to sediment rather than in the pore water.

Table E5. Estimated Environmental Concentrations (ppb) for Etoxazole.

Peak (1-in-10 yr) 1.32

4-day Avg (1-in-10 yr) 0.122

21-day Avg (1-in-10 yr) 0.118

60-day Avg (1-in-10 yr) 0.111

365-day Avg (1-in-10 yr) 0.854E-01

Entire Simulation Mean 0.748E-01

Table E6. Summary of Model Inputs for Etoxazole.
74

Scenario ORmintSTD

Koc (ml/g) 151

Water Half Life (days) @ 25 °C 740

Benthic Half Life (days) @ 25 °C 636

Photolysis Half Life (days) @ 40 °Lat 34

Hydrolysis Half Life (days) 99

Soil Half Life (days) @ 25 °C 370

Foliar Half Life (days) 0

Molecular Wt 359.42

Vapor Pressure (torr) 7e-6

Solubility (mg/l) 0.0754

Figure E2. Yearly Peak Concentrations - Mint

IL Corn Output File from the SWCC –

Variable Volume Water Model, Version 0.0

*******************************************

Performed on: 4/25/2014 at 13:29

Peak 1-in-10 = 2.56 ppb

Chronic 1-in-10 = 0.273 ppb

Simulation Avg = 0.223 ppb

4-day avg 1-in-10 = 0.399 ppb

21-day avg 1-in-10 = 0.393 ppb

60-day avg 1-in-10 = 0.377 ppb

90-day avg 1-in-10 = 0.367 ppb

Benthic Pore Water Peak 1-in-10 = 0.400 ppb

Benthic Pore Water 21-day avg 1-in-10 = 0.393 ppb

Benthic Conversion Factor = 151. -Pore water (ug/L) to (total mass, ug)/(dry 

sed mass,kg)

Benthic Mass Fraction in Pore Water = 0.662E-03

YEAR Peak 4-day 21-day 60-day 90-day Yearly Avg Benthic Pk Benthic 21-day
75

 1 1.23E+00 2.40E-01 2.32E-01 2.20E-01 2.09E-01 1.01E-01 2.41E-01 2.32E-01

 2 1.11E+00 2.42E-01 2.33E-01 2.17E-01 2.12E-01 1.76E-01 2.43E-01 2.33E-01

 3 1.53E+00 2.69E-01 2.63E-01 2.51E-01 2.41E-01 1.83E-01 2.70E-01 2.63E-01

 4 1.24E+00 2.79E-01 2.70E-01 2.50E-01 2.43E-01 1.96E-01 2.80E-01 2.70E-01

 5 1.36E+00 3.80E-01 3.72E-01 3.58E-01 3.44E-01 2.87E-01 3.81E-01 3.72E-01

 6 2.06E+00 3.30E-01 3.25E-01 3.10E-01 3.08E-01 2.57E-01 3.31E-01 3.25E-01

 7 1.72E+00 3.28E-01 3.21E-01 3.01E-01 2.89E-01 2.35E-01 3.29E-01 3.21E-01

 8 3.46E+00 3.94E-01 3.88E-01 3.73E-01 3.54E-01 2.46E-01 3.97E-01 3.88E-01

 9 1.78E+00 3.47E-01 3.42E-01 3.35E-01 3.25E-01 2.49E-01 3.48E-01 3.42E-01

10 1.61E+00 3.72E-01 3.58E-01 3.45E-01 3.44E-01 2.74E-01 3.73E-01 3.58E-01

11 1.47E+00 3.21E-01 3.14E-01 3.02E-01 3.02E-01 2.38E-01 3.22E-01 3.14E-01

12 1.17E+00 2.82E-01 2.73E-01 2.70E-01 2.70E-01 2.17E-01 2.82E-01 2.73E-01

13 1.22E+00 3.64E-01 3.53E-01 3.33E-01 3.26E-01 2.55E-01 3.65E-01 3.53E-01

14 1.59E+00 3.97E-01 3.85E-01 3.62E-01 3.44E-01 2.62E-01 3.98E-01 3.85E-01

15 1.93E+00 3.51E-01 3.42E-01 3.32E-01 3.22E-01 2.56E-01 3.53E-01 3.42E-01

16 1.49E+00 3.07E-01 2.96E-01 2.87E-01 2.76E-01 2.29E-01 3.08E-01 2.96E-01

17 1.13E+00 3.23E-01 3.15E-01 2.98E-01 2.88E-01 2.21E-01 3.24E-01 3.15E-01

18 1.17E+00 3.08E-01 2.97E-01 2.79E-01 2.67E-01 2.18E-01 3.09E-01 2.97E-01

19 1.46E+00 3.02E-01 2.92E-01 2.71E-01 2.59E-01 2.05E-01 3.03E-01 2.92E-01

20 1.37E+00 2.93E-01 2.86E-01 2.79E-01 2.69E-01 2.15E-01 2.94E-01 2.86E-01

21 2.78E+00 4.16E-01 4.10E-01 3.98E-01 3.84E-01 2.70E-01 4.18E-01 4.10E-01

22 2.21E+00 4.07E-01 3.94E-01 3.78E-01 3.69E-01 2.84E-01 4.09E-01 3.94E-01

23 1.35E+00 3.19E-01 3.09E-01 2.91E-01 2.88E-01 2.36E-01 3.20E-01 3.09E-01

24 1.14E+00 2.38E-01 2.33E-01 2.28E-01 2.19E-01 1.94E-01 2.39E-01 2.33E-01

25 1.31E+00 2.70E-01 2.66E-01 2.55E-01 2.49E-01 1.96E-01 2.71E-01 2.66E-01

26 2.40E+00 3.66E-01 3.55E-01 3.38E-01 3.26E-01 2.43E-01 3.67E-01 3.55E-01

27 1.14E+00 2.51E-01 2.44E-01 2.57E-01 2.70E-01 2.11E-01 2.51E-01 2.44E-01

28 1.11E+00 2.07E-01 2.00E-01 1.84E-01 1.90E-01 1.57E-01 2.09E-01 2.00E-01

29 1.09E+00 1.97E-01 1.90E-01 1.82E-01 1.81E-01 1.46E-01 1.97E-01 1.90E-01

30 2.58E+00 3.99E-01 3.95E-01 3.85E-01 3.74E-01 2.39E-01 4.00E-01 3.95E-01

*************************************************************************************************

***

Effective compartment halflives averaged over simulation duration:

zero washout 0

water col metab halflife (days) = 1620.87497697542

hydrolysis halflife (days) = 99.0394695318479

photolysis halflife (days) = 1605.74218895468

volatile halflife (days) = 14.0418800036001

total water col halflife (days) = 12.1135423334334

zero burial 0

benthic metab halflife (days) = 1393.07633156266

benthic hydrolysis halflife (days) = 149589.064680698

total benthic halflife (days) = 1380.22274734038

***********************************************************************

Fractional Contribution of Transport Processes to Waterbody & Total Mass (kg):

Due to Runoff = 0.2377 0.8178 

Due to Erosion = 0.4332 1.491 

Due to Drift = 0.3291 1.132 

******* Inputs *******

 111.9 = oc partitioning coefficient

 740.0 = water column half Life

 25.00 = reference temp for water column degradation

 636.0 = benthic Half Life

 25.00 = Reference temp for benthic degradation

 2.000 = Q ten value

 34.00 = photolysis half life

 40.00 = reference latitude for photolysis study

 99.00 = hydrolysis half life

 359.4 = molecular wt

 0.7000E-05 = vapor pressure

 0.7540E-01 = solubility

 0.1000E+06 = field area

 0.1000E+05 = water body area

 2.000 = initial depth

 2.000 = maximum depth

 2 1=vvwm, 2=usepa pond, 3 = usepa reservoir, 4 = const vol no flow, 5 = const vol 

w/flow 

F T = burial, else no burial
76

 4.800 = mass transfer coefficient 

 0.1000E-07 = PRBEN

 0.5000 = benthic compartment depth

 0.5000E-01 = benthic porosity

 0.5000 = benthic bulk density

 1.350 = OC frcation in benthic sediment

 0.4000E-01 = DOC in benthic compartment

 5.000 = benthic biomass

 0.6000E-02 = DFAC

 1.190 = SS

 30.00 = chlorophyll

 0.5000E-02 = OC frcation in water column SS

 0.4000E-01 = DOC in water column

 5.000 = biomass in water column

Mint Output File from the SWCC –

Variable Volume Water Model, Version 0.0

*******************************************

Performed on: 4/25/2014 at 13:39

Peak 1-in-10 = 1.32 ppb

Chronic 1-in-10 = 0.854E-01 ppb

Simulation Avg = 0.748E-01 ppb

4-day avg 1-in-10 = 0.122 ppb

21-day avg 1-in-10 = 0.118 ppb

60-day avg 1-in-10 = 0.111 ppb

90-day avg 1-in-10 = 0.106 ppb

Benthic Pore Water Peak 1-in-10 = 0.122 ppb

Benthic Pore Water 21-day avg 1-in-10 = 0.118 ppb

Benthic Conversion Factor = 151. -Pore water (ug/L) to (total mass, ug)/(dry 

sed mass,kg)

Benthic Mass Fraction in Pore Water = 0.662E-03

YEAR Peak 4-day 21-day 60-day 90-day Yearly Avg Benthic Pk Benthic 21-day

 1 1.26E+00 6.31E-02 6.14E-02 5.78E-02 5.52E-02 2.66E-02 6.33E-02 6.14E-02

 2 1.29E+00 9.01E-02 8.77E-02 8.24E-02 7.85E-02 5.38E-02 9.04E-02 8.77E-02

 3 1.31E+00 1.08E-01 1.05E-01 9.83E-02 9.37E-02 6.93E-02 1.08E-01 1.05E-01

 4 1.31E+00 1.06E-01 1.03E-01 9.65E-02 9.17E-02 6.97E-02 1.07E-01 1.03E-01

 5 1.31E+00 1.16E-01 1.12E-01 1.05E-01 1.00E-01 7.88E-02 1.16E-01 1.12E-01

 6 1.31E+00 1.14E-01 1.11E-01 1.03E-01 9.79E-02 7.66E-02 1.14E-01 1.11E-01

 7 1.31E+00 1.08E-01 1.05E-01 9.84E-02 9.35E-02 7.07E-02 1.09E-01 1.05E-01

 8 1.31E+00 1.13E-01 1.10E-01 1.03E-01 9.87E-02 7.69E-02 1.13E-01 1.10E-01

 9 1.31E+00 1.15E-01 1.12E-01 1.05E-01 1.00E-01 8.12E-02 1.15E-01 1.12E-01

10 1.32E+00 1.21E-01 1.18E-01 1.10E-01 1.05E-01 8.39E-02 1.22E-01 1.18E-01

11 1.31E+00 1.14E-01 1.12E-01 1.05E-01 1.02E-01 7.94E-02 1.15E-01 1.12E-01

12 1.31E+00 1.14E-01 1.11E-01 1.04E-01 9.88E-02 7.65E-02 1.15E-01 1.11E-01

13 1.31E+00 1.12E-01 1.09E-01 1.02E-01 9.71E-02 7.70E-02 1.12E-01 1.09E-01

14 1.32E+00 1.22E-01 1.18E-01 1.11E-01 1.06E-01 8.56E-02 1.22E-01 1.18E-01

15 1.31E+00 1.14E-01 1.11E-01 1.05E-01 1.00E-01 7.79E-02 1.15E-01 1.11E-01

16 1.31E+00 1.12E-01 1.09E-01 1.03E-01 9.87E-02 7.47E-02 1.13E-01 1.09E-01

17 1.30E+00 1.04E-01 1.02E-01 9.55E-02 9.12E-02 6.87E-02 1.05E-01 1.02E-01

18 1.31E+00 1.14E-01 1.11E-01 1.05E-01 1.00E-01 7.77E-02 1.15E-01 1.11E-01

19 1.31E+00 1.14E-01 1.11E-01 1.03E-01 9.88E-02 7.87E-02 1.14E-01 1.11E-01

20 1.32E+00 1.21E-01 1.17E-01 1.10E-01 1.05E-01 8.27E-02 1.21E-01 1.17E-01

21 1.33E+00 1.26E-01 1.22E-01 1.15E-01 1.10E-01 9.20E-02 1.26E-01 1.22E-01

22 1.32E+00 1.25E-01 1.22E-01 1.15E-01 1.09E-01 8.76E-02 1.26E-01 1.22E-01

23 1.32E+00 1.20E-01 1.17E-01 1.10E-01 1.05E-01 8.30E-02 1.21E-01 1.17E-01

24 1.31E+00 1.13E-01 1.11E-01 1.05E-01 9.98E-02 7.81E-02 1.14E-01 1.11E-01

25 1.31E+00 1.15E-01 1.12E-01 1.04E-01 9.91E-02 7.67E-02 1.16E-01 1.12E-01

26 1.31E+00 1.07E-01 1.03E-01 9.66E-02 9.17E-02 6.93E-02 1.07E-01 1.03E-01

27 1.30E+00 1.06E-01 1.03E-01 9.71E-02 9.27E-02 7.03E-02 1.06E-01 1.03E-01

28 1.31E+00 1.14E-01 1.11E-01 1.03E-01 9.77E-02 7.64E-02 1.14E-01 1.11E-01

29 1.30E+00 1.05E-01 1.02E-01 9.45E-02 8.96E-02 6.88E-02 1.06E-01 1.02E-01

30 1.31E+00 1.12E-01 1.09E-01 1.02E-01 9.69E-02 7.55E-02 1.13E-01 1.09E-01

*************************************************************************************************

***

Effective compartment halflives averaged over simulation duration:
77

zero washout 0

water col metab halflife (days) = 1803.23437329016

hydrolysis halflife (days) = 99.0394695318479

photolysis halflife (days) = 1337.51818379660

volatile halflife (days) = 14.6755891394187

total water col halflife (days) = 12.5723598959034

zero burial 0

benthic metab halflife (days) = 1549.80683974668

benthic hydrolysis halflife (days) = 149589.064680698

total benthic halflife (days) = 1533.91482456643

***********************************************************************

Fractional Contribution of Transport Processes to Waterbody & Total Mass (kg):

Due to Runoff = 0.2423 0.2609 

Due to Erosion = 0.0545 0.5867E-01

Due to Drift = 0.7033 0.7575 

******* Inputs *******

 111.9 = oc partitioning coefficient

 740.0 = water column half Life

 25.00 = reference temp for water column degradation

 636.0 = benthic Half Life

 25.00 = Reference temp for benthic degradation

 2.000 = Q ten value

 34.00 = photolysis half life

 40.00 = reference latitude for photolysis study

 99.00 = hydrolysis half life

 359.4 = molecular wt

 0.7000E-05 = vapor pressure

 0.7540E-01 = solubility

 0.1000E+06 = field area

 0.1000E+05 = water body area

 2.000 = initial depth

 2.000 = maximum depth

 2 1=vvwm, 2=usepa pond, 3 = usepa reservoir, 4 = const vol no flow, 5 = const vol 

w/flow 

F T = burial, else no burial

 4.800 = mass transfer coefficient 

 0.1000E-07 = PRBEN

 0.5000 = benthic compartment depth

 0.5000E-01 = benthic porosity

 0.5000 = benthic bulk density

 1.350 = OC frcation in benthic sediment

 0.4000E-01 = DOC in benthic compartment

 5.000 = benthic biomass

 0.6000E-02 = DFAC

 1.190 = SS

 30.00 = chlorophyll

 0.5000E-02 = OC frcation in water column SS

 0.4000E-01 = DOC in water column

 5.000 = biomass in water column