## 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 Expos ure Assessment to Be Conducted for Etoxazole

. P

_ . . _ .



## ~/~~~ Jose Melendez, Chemist L) ;) 

## c:A__ 

# 2f

Justin Housenger, Biologist 

# OV

. .

**~ ~**  

### Environmental Risk Branch 5 Environmental Fate and Effects Division (7507P)

Joseph DeCant, Ecologist Michael Barrett

, Senior Chemist Keith Sappington, Senior A dvisor Environmental Risk Branch 5 Environmental Fate and Effects Division (7507P)

THROUGH: Mah Shamim, Branch Chief Environmental Risk Branch 5



# ~ Envir o nmental Fate and Eff ects 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. M easures 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 dri nking water and ecological r isk assessments in support of registration review and provide s an ove rview of the environmental fate, ecological effects , and potential risks associated with the use of Etoxazole as well as uncertain ties unique to risk assessmen t 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 ) ; mean while

, for the difluorophenyl

- U

- labeled study, it w as up to 21.4% AR. Sediment was extracted only once with methanol followed by once with methano l : 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 st udy the volatile or ganics were <0.1% AR )

. Given the uncertainties with the available data, s tudies with t wo new sediment systems should be submitted addressing these issues. EFED will make conservative assumptions, based upon the overall behavior observe d 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. T wo 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 requi rement remains unfulfilled for this chemical , pending evaluation of the available ILV s.

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 mall ard 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 hav e 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. A vailable 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 s ubacute dietary exposure basis. However, data f or one chemical, diflubenzuron for which an acute oral study with a passerine species is ava ilable, 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.

85 0.4100 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 applicatio n 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 ap plication 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 r equested 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 bi ologically meaningful increases that confounded the ability to discern where the EC 50 

### 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 ch aracterize 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 av ailable 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 ch aracterize 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 adul ts. 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 revie w 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 c an 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 indiv idual adult and larval bees. The 10

- day toxicity study with young adult bees provides no

observed adverse effect level (NOAEL) and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Data obtained from this study will be used in es timating 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 protoco l 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 expo sure 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 unce rtainties 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 fre shwater 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 th e 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 amphi pod 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 Bioaccu mulation 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 complet e , t here 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 s uch 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 residue s 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 stud ies constitutes another uncertainty since they would provide addit ional 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 t oxicological 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 the se 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 ECOS AR 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: C 21 H 23 F 2 NO 2 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: C 14 H 23 NO 2 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: C 21 H 21 F 2 NO 2 MW: 357.40 g/mol

### 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 biosynthesi s 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 n on

- 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
C 21 

### H 23 

### F 2 

### NO 2 

### ], is an a caricide/miticide growth inhibitor (IRAC 1 

### 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. W ork by
Nauen and Smagghe ( 2006 ) suggest ed that etoxazole’s mode of action is inhibition of chitin biosynthesis ( chitin is the main component of the e xoskeletons 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 inhibitors 2 

### .” Furthermore, the European Food Safety Authority (EFSA) document “Modification of E xisti ng 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 a nd 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 e toxazole 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.

I n addition, EFED considered the lates t Agency science policies and risk assessment methodologies. The structure of e toxazole , 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 label s 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, pepper s 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 etox azole, 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 spra ys, hydraulic sprayers, or ground boom sprayers. The chemical profile produced by BEAD, located in the docket, lists the use patterns of maximum exposure s 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 maxim um 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 othe r insecticides and/or miticides

. In the past, e toxazole 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 con clusions from r ecent risk assessments

, includ ing the following:

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

 Uses on c ane berry (Crop Subgroup 13

- 07 A), c ucurbit v egetables (Crop Group 9), l ow

gr owing berry (Subgroup 13

- 07G), p epper and e ggplant group (Crop Group 8), small fruit v ine

- climbing, except fuzzy kiw ifruit (Subgroup 13

- 07 F), and t ropical and sub

tropical i nedible peel (includes avocado, canistel, mango, papaya, sapodilla, black and mamey sapote, and star apple) ( D374125 + , dated 11/03/2010);

### 10

 Uses on plum, p each ( s tone f ruits), c ucumber, g reenhouse tomato , and m int (D353084, dated 03/24/2009);

 Uses on c herries, m elon, and h ops, and i ncreased rate on c otton (D341221+, dated 10/01/2007); and,

 U ses on pome fruits, strawberries, and co tton (D283732, dated 08/14/2003).



## a. Ecological Risk Assessment

The Agency has conducted multiple ecological risk assessments on e toxazole 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 s ummarized 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 Degrad at es of Concern No 1 No No NA No NA 3 Yes 2 Yes No Yes 4 R

- 8, R

- 13 5

1 Toxicity values were non

- definitive (“>”)
2 For both water column and sediment dwelling invertebrates 3 Log K OW 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 hav e 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 etoxa zole , 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). T herefore, the drinking water assessm ent results d id 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 . T ier 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

T he 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 aero bic 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 coeffic ient (K OC 

### ≥ 4910 mL/g OC 

### ), 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 mo bility classification , FAO 2000 ) in batch equilibrium studies conducted on 8 soils (K F 

### range 66

- 335 mL/g ; K FOC 

### range 4910

- 55300 mL/g OC 

### ). Due to its relatively high organic carbon sorption coefficient and octanol/water partition coefficient (K OW 

### = 331 000; log K OW 

### = 5.52), coupled with its low solubility (75 ppb) and moderate ly high persistence, etoxazole and its degradates of concern are expected to partition with the sediment phase in aquatic systems and persist in that phase

.

F ield dissipation studies, c onducted 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 cott on 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 environme nt . 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 w ere 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 bio concentrate, as expected from its relatively high octanol/water partition coefficient ( see above ) . Residues bio concentrated in r ainbow 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 i n edible tissue. Two minor degradates: R

- 2/R

- 4 and R

- 13 were <1.5% of the total residues in fish

. D epuration 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 transp ort properties of e toxazole is provided in Table 4

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

.

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

PARAMETER VALUE(S) (units) SOURCE COMMENT S

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 MRID s : 45089902

, 45089903

. –

Vapor Pressure (20°C) 7 x 10

- 6 torr

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

- 6 atm

- m 3 /mol Calculated Estimated from vapor pressure and water solubility.
Octanol

- Water Partition Coefficient (K OW ) 3.31x10 5 MRID: 45089902. Hydro ph obic

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 COMMENT S

Aqueous Photolysis Half

life (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 CO 2

. Several minor products. MRID: 46658101. Dark control

correct ed. Moderately rapid degradation pathway.

Soil Photolysis Half

- life CL from UK, t 1/2 = 19.3 days ;

Major products R

- 3 and R

- 11. MRID s : 45090020, 46299904. Moderately rapid

degradation pathway.

Aerobic Soil Metabolism Half

- life Study performed using [U

14 C

- tert

- butyl

phenyl] and [U

14 C

- difluorophenyl]

radiolabels : SL from UK 10.2

- 12.0 days. SL from CA 19.4

- 23.2 days. Studies performed using [U

14 C

- tert

b utylphenyl] radiolabel : S from Germany 12.7 days. LS from Germany 21.5 d. CL from UK 44.7 da ys. 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. MRID s : 45090019, 45090021, 45090022. Moderately rapid

degradation pathway. Unextracted resid ues 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 (25 0 C) Water clay sed iment 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 (K FO C )

Parent Etoxazole 546 0, 5230, 11000, 4910, and 18000, 23100, 55300, 14200 mL/g OC MRID s : 45090024, 45090026, 46299905, 46299906. For SL, CL, S, LS,

and SL, SL, SL and SL soils, respectively

Soil Partition Coefficient
(K F )

Parent Etoxazole 131, 68, 66, 103, and 156, 335, 193, 156 mL/g MRID s : 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 : DT 50 =8 days

. Montech (Southern France) MRID s : 45250909, 45621721, _

### 14 PARAMETER VALUE(S) (units) SOURCE COMMENT S

CL: DT 50 =8 days

. Senas (Southern France)
CL: DT 50 =4 days

. Schleithal (Northern France) SiL: DT 50 =9 days

. Only R

- 8 was monitored. It was no t detected at any test interval. Bare ground in Santa Cruz Co., CA, SL;

t 1⁄2 =7.0 days, major product detected R

- 7 (generally 0

- 7.5 cm soil layer) Bare ground in Payette Co., ID, SL;

t 1⁄2 =11.7 days, major product detected R

- 7 (on ly in the 0

- 7.5 cm soil layer) Bare ground in Washington Co., MS, SiL; t 1⁄2 =<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 [ 14 C]residues were depurated
( E stimated depuration t 1⁄2 = 2.6 days for edible tissues, and 4.6

- 6.2 days for non

edible tissues

. ) MRID s : 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. R

7 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 product s. 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, R

8 and R

- 13. Three measurements were mad e using HPLC methodology, of which one was an extrapolated K OC 

### (for R

- 7). There was a pproximately a 10

- fold discrepancy between the K OC

3 2

- 2,6

- difluoro

- pheny1)

- 4

- [2

- ethoxy

- 4

- ( 1

- hydroxymethyl

- 1

- methylethyl)phenyl]

- 4,5

- dihydrooxaz ole

### 15

obtained through HPLC and a batch equilibrium study for R

- 7. Since for R

- 7 the HPLC result was extrapolated, the resul ts of the batch equilibrium study are regarded as more reliable. Of these compounds, R

- 13 appears to be the least mobile of all compounds (K OC 

### >13000 mL/g OC 

### ). No mobility data is available about R

- 11.

Table 5. Summary of available sorption / mobility st udies for etoxazole transformation products

. PARAMETER VALUE(S) (units) SOURCE COMMENT S
Organic Carbon Partition Coefficient (K OC ), Transformation Product s calculated using HPLC method R

- 3: 5130 mL/g OC R

- 4: 759 mL/g OC R

- 7: 79400* mL/g OC MRID: 45090025 *Extrapolated value

Soil Partition Coefficient (K F ), Transformation Product R

- 7 27, 98, 14 mL/g MRID: 45250906 For SL, CL and S soils, respectively Organic Carbon Partition Coefficient (K FO C ), Transformation Product R

- 7 1125, 7540, 2330 mL/g OC MRID: 45250906 For SL, CL and S soils, respectively

Soil Partition Coefficient (K F ), 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 (K FO C ), Transformation Product R

- 8 103, 351, 207 mL/g OC MRID: 45250907 For SL, CL and S soils, respectively

Soil Partition Coefficient (K F ), Transformation Product R

- 13 877, 1082, 82 mL/g MRID: 45250908 For SL, CL and S soils, respectively Organic Carbon Partition Coefficient (K FO C ), Transformation Product R

- 13 36540, 83230, 13670 mL/g OC 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. R eceptors

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 growt h 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
l iterature 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, a nd 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 (0.0 75 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/LC 50 

### 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 f reshwater 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 exposur e 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 sedimen t 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 show s increased toxicity over the fr eshwater 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).

T 

### able 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 fish 1 Acute Rainbow trout ( Oncorhynchus mykiss ) LC 50 > 37 0 μ g/L

(N/A; N/A) H ighly toxic 46059001 (Acceptable)

Chronic (Early Life

Stage) Rainbow trout NOAEC = 15

μ g/L
LOAEC = 33

μ g/L Endpoint: 89

- day length -- 45621614 ( Acceptable )

Freshwater invertebrates Acute Water Flea ( Daphnia magna ) EC 50 = 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 variegat u s ) LC 50 >160 μg /L

(N/A; N /A) Very highly

toxic 45621608

(Supplemental)

Estuarine/marine invertebrates Acute Mysid Shrimp ( Mysidopsis bahia) L C 50 = 4.42 μg /L

( 3.96

– 4.98 ; 10.3 ) Very highly

toxic 45621611

(Acceptable)

Eastern oyster ( Crassostrea virginica) L C 50 = 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 Sediment

dwelling invertebrates Sub

- chronic

(10

- day) Freshwater midge

( Chironomus riparius ) Sediment:

NOAEC (mortality) 10 mg

a. i

. /kg

Pore water: NOAEC (mortality): 26

μ g/L -- 47837702 (Supplemental)

Freshwater Sediment

dwelling invertebrates Chronic (28

-

day) Estuarine/marine

amphipod ( Leptocheirus plumulosus ) Sediment (OC

normalized) : NOAEC (mortality) 22 mg /kg TOC

Pore water: NOAEC (mortality): 1

μ g/L -- 47837701 (Acceptable)

Aquatic plants and algae Vascular Duckweed ( Lemna gibba ) EC 25 (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)

Non

vascular Marine diatom

( Navicula pelliculosa ) EC 25 (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 r esults 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 terrestri al field dissipation studies but is not shown to be persistent. The degradate toxicity study with freshwater invertebrates makes not e that R

- 7 had dissipated substantially by the end of study duration of 48 hours yet the results of the study were still de termined 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 LC 50 = >0.80 mg/L

-- 45089913 (Supplemental) R

- 4 Results not reliable 3

R

- 7 Results not reliable 3

R

- 8 LC 50 = > 0.88 mg/L
R

- 13 LC 50 = >0.74 mg/L

Freshwater invertebrates R

- 3

Water f lea EC 50 = >0.55 mg/L

-- 45621609 (Supplemental) R

- 4 EC 50 = >1.3 mg/L

R

- 7 EC 50 = >0.74 mg/L

R

- 8 EC 50 = >1.4 mg/L

R

- 13 EC 50 = >0.73 mg/L

Aquatic Non

vascular plant R

- 3 Freshwater green algae ( Selenastrum capricornutum ) EC 50 = >1.0 mg/L

NOAEC (cell density): <0.11 mg/L -- 45621704 (Supplemental)

R

- 7 EC 50 = >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 EC 50 = >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 EC 50 , are the only ones available from the study.

3 Analytical 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 hatch ed 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
EC 25 

### values based on a la ck 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 mo de 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)

Birds 1 Acute Mallard duck ( Anas platyrhynchos ) LD 50 > 2000 mg/kg

bw (N/A; N/A) Practically

non

- toxic 45089908

(Acceptable)

Sub

- acute dietary Bobwhite quail

( Colinus virginianus ) LC 50 > 5060 mg/kg

diet (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 ) LD 50 > 5000 mg/kg Toxicity Category IV 45089919

Acute Inhalation Laboratory rat LC 50 > 1.09 mg/L Toxicity Category III 45089923

Chronic Laboratory rat

( Rattus norvegicus ) NO A EL = 2000 ppm

LO A EL = Not determined Endpoint: None -- 45090007, 45090006

Insects Acute

contact/oral combination study Honey bee

( Apis mellifera
L

. ) Contact LD 50 > 200

μg/bee (N/A; N/A) Oral LD 50 > 200 μg/bee (N/A; N/A) Practically

non

- toxic 45621706

(Supplemental)

Terrestrial plants Seedling

Emergence (Tier I) Dicot

– None EC 25 > 0.060 lbs a.i/A (N/A; N/A) NOAEC = 0.060 lbs a.i/A Endpoint: N/A

-- 45621623 (Acceptable)

Monocot

– None EC 25 > 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 EC 25 > 0.060 lbs a.i/A (N/A; N/A) NOAEC = 0.060 lbs a.i/A Endpoint: N/A

-- 45621701 (Acceptable)

Monocot

– None EC 25 > 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.

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

3 An 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 etoxa zole 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

a re 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 Specie s 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
P arasitoid 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 compa red 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. 4562171 2 (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 Specie s Results synopsis MRID (Classification) apple orchard (0.5 L/ha) ( Neoseiulus californicu s ) 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 californicu s ) By 14 days, mortality in treatment was 24% Fecundity was 3.96 eggs/female and 4.69 eggs/female for the contro l 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 in dices 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 wa s 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 concentration s 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 aerobi c soil conditions

. When available, registrant submitted toxicity data for degradates were consulted. Additionally, t he ECOSAR (v1. 1 ) module of E PI S UITE (v.4. 1 ) was employed to estimate the toxicity of these degradates of etoxazole alongside the available registrant submitted data

. E COSAR uses structure activity relationships to predict the toxicity of compounds that share similar structural moieties. In cases where multiple estimates of toxicit y for a particular taxa are pre dicted for a degradate, the m ost 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 provi ded 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 es t imates were predicted. These results are compared alongside registrant submitted data that is available for etoxazole as well as the degradate s 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 toxi city (μg a.i./L) of the degradates of etoxazole 3

Compound (Chemical class) Toxicity Endpoint (μg a.i/L)

Acute
FW Fish LC 50 Acute FW

Invert EC 50 Chronic

FW Fish NOAEC Chronic

FW Invert NOAEC Acute

E/M Fish LC 50 Acute

E/M
Invert LC 50 Chronic

E/M
Invert NOAEC Algae

EC 50 6

Parent etoxazole
Etoxazole (registrant submitted studies)

– TGAI 4 >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 ) 1628 1 1440 122 225 351 65

Degradate R

- 4
R

- 4 (registrant submitted studies) >1300

R

- 4 ( Amides ) 1224 1 380 1 11 131 1112 1 167 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) 21 1 18 1 3.0 6.0 27 1 0.86 0.02 78 1

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

4 Data 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.

5 Data are not available for freshwater green algae for etoxazole parent and therefore the results of t h e 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 grea ter than the absolute value of a non

definitive 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 es timates 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 a n acute and chronic basis to freshwater fish a n d 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 consi dered 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 d issipation 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

s olubility 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 lo w (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 toxicit y 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 s tudies 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 freshw ater 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 with in an order o f 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 1 3% 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 persisten t 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 le vel 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 just ification 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 r elatively 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 freshw ater 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 studie s, 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. T he terrestrial field dissipation studies

### 26

showed much higher rates o f 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 s ince 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 ava ilable 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 t he 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 non

definitive 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 freshwate r fish and invertebrates is at least 2 orders of magnitude less toxic th an 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. T he 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 stud ies, respectively). EpiSuite estimates the solubility of R

- 8 to be 2058 mg/L and so it is uncertain as to whether an LC 50 

### would be achieved if the study tested R

- 8 at a higher c oncentration. 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 show n 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 photolys is, soil photolysis, aerobic and anaerobic soil metabolism, and was observed in the terrestrial field dissipation studies ( overa ll 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 R

11 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

- 1 3

Available registrant submitted data show that freshwater invertebrates and freshwater gree n algae are at least on e 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 ava ilable 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 e mpirical data on structurally similar chemicals, it is uncertain if the substance will present significantly higher toxicity above baseline estimates. Th us, th e 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 st udies . 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 K OW 

### of 6.62, which is higher than parent, suggesting that this degradate is of very low mobility and has a propensity

to sor b 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 lig ht 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 R

7, 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 mar ginally 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 p arent 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 sub mitted 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 conduct ed 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

- 1 3 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 persiste nt in available environmental fate data. Further information regarding the input parame ters 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 am phipod 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 fresh water 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 s urface water estimated environmental exposure concentration s (E EC s) 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 in cident 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 e toxazole 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 S creening I mbibition P rogram (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 LD 50 

### 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 LD 50 

### of >5000 mg a.i/kg

- bw an d 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 a nd 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

.

Potentia l for Risk to Terrestrial Organism from Inhalation Exposure

The S creening T ool for I nhalation R isk (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

- 6 

### and 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 LD 50 

### = >5000 mg a.i/kg

- bw and inhalation LC 50 

### = > 1.09 mg/L ) as well as the most sensitive acute oral avian toxicity endpoint (mallard duck oral LD 50 

### = > 2000 mg a.i/kg

- bw). Based on the results of the
S TIR 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 Age ncy 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 o f etoxazole will also be examined in the risk assessment. Etoxazole shows a significant potential to bio concentrate, as expected from its relatively high octanol/water partition coefficient (331,000; log K OW 

### = 5.52) . Residues bio concentrated in

r ainbow 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 ). B ioaccumulation will be assessed using the results from bioaccumulation in fish studies, as well as the K OW 

### (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 assessment s 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 Comm ittee 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

- GW 4 

### . 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 p otential 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 e toxazole 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 ad ditional 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, 2007 c ), 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 commun ities 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 Speci es 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 8 35.4400 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 requ ired 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. S tud ies are avail able for the analysis in soil, which are in review

. The data requirement will remain unfulfilled until the available stud ies 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 . I n 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 45621721 1

( Two ECMs) Not determined Yes Not yet determined; studies are in review. Methods for the analysis of etoxazole and its major soil meta bolites 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

Non

guideline Mobility via

HPLC (R

- 3, R

- 4,
R

- 7) 45090025 Supplemental No

---

835.123 0 Adsorption/

desorption (R

- 7) 45250906 Supplemental No

---

835.123 0 Adsorption/

desorption (R

- 8) 45250907 Supplemental No

---

835.123 0 Adsorption/

desorption (R

13) 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 classifica tions 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 investig ated 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 th e risk

assessment.

T he 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 be low 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 to xicity 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 maxim um 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 to xicity 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 spec ies 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 c lass of insecticides.

Chemical Acute oral

(passerine) mg a.i/kg

bw 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 (red

winged 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 o f 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 concentrati on.

### 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 statist ically significant (p>0.05), they were seen as biologically meaningful increases that confounded the ability to discern where the EC 50 

### level was. This was due to the fact that the limit concentration (which also contained solvent) was 32% decreased from t he 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 b ees 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 i nsect exoskeleton) 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 cor roborate 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 2 5, 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 t hrough 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 identifie s 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 ef

fect 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 an d 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 protoc ol 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) estuari ne/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 follo w 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

- guideli ne : 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) avail able 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 Offi ce 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 --

Non

guideline 42

- 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.

Non

guideline 60

- 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.

Non

guideline 28

- 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 a l gae and cyanobacteria are not suitable for quantitative risk assessment and are recommended. 850.4500 Algal toxicity 48603001 Supplemental Y es (freshwa ter green algae)

850.4550 Cyanobacteria 48578302 Supplemental Yes EFED will presume risk for listed non

- vascular aquatic plants in the absence of a no

effect level. The methods should include etoxazole and its degradates of ecological and human health concern.

Non

guideline Freshwater

Invertebrate Microcosm study 45621616 Supplemental No

--

### 41

Table 1 6 . 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 .45 00 Freshwater aquatic plant g rowth

–

algae (R

- 3) 45621704 Supplemental No

Freshwater aquatic plant g rowth

– algae (R

- 7) 45621702 Supplemental No

Freshwater aquatic plant g rowth

– 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 --

Non

guideline Honey Bee

Toxicity

– 10

- Day Adult Chronic Toxicity Study: No data submitted Yes

Non

guideline 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

Non

Guideline Residues in

Pollen and
Nectar No data submitted Yes --

850.3040 Field Testing for

Pollinators No data submitted Yes --

850.4100 S eedling

E mergence 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 EC 25 . 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 V egetative

V igor 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 EC 25

. 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.

Non

guideline 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 Hyale lla 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 environment s that may be exposed to run

off or spray drift from etoxazole ap plications 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 to xicity 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 unc ertainties 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 ben thic 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 dec ision options to mitigate this risk. T he 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 avo ided, 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 pol len 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 i ncluding 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 fo r 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 lowest

observed adverse effect level (LOAEL) for assessing chronic effects. Da ta 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. 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 chroni c 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 prolong ed 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 dat a 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 la rval 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 wh ich 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 etoxazo le 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 multipl e 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 Ut ility 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 non

listed terrestrial in vertebrate species, including bee pollinators. These data would allow the Agency to refine the sc reening 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 h abitat” 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/consulta tion/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 Che mical 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 St ressors 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 o f 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 Eto xazole). 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 R eg i stration Revi ew: E toxaz ole

, 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



## Appendi x 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

- 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

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: C 21 H 23 F 2 NO 2 MW: 359.4 2 g/mol Hydrolysis 1 45090017 Not applicable 80.7 (30) Aq photolysis 3 46658101 31.2 (20) Aq photolysis 4 46658101 36.6 (14) Soil photolysis 3 45090020,

46299904 39.2 (12.25) Soil photolysis 4 35.4 (12.29)
Aerobic soil 3 45090019 0.9 (269)
Aerobic soil 4 45090019 1.2 (269)
Aerobic soil 3 45090021 1.5 (272)
Aerobic soil 4 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 soil 3 45090023 42.2 (120)
Anaerobic soil 4 45090023 43.0 (120) Anaerobic aquat 3 45621718 23.1 (362) Anaerobic aquat 4 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

### 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: C 20 H 21 F 2 NO 3 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: C 21 H 25 F 2 NO 3 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)

### 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: C 21 H 25 F 2 NO 3 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: C 14 H 23 NO 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)

### 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: C 13 H 18 O 3 MW: 222.29 g/mol Aq photolysis 4 46658101 Not applicable Not applicable Soil photolysis 3 45090020,

46299904 7.9 (12.25) 7.9 (12.25) Soil photolysis 4 Not applicable Not applicable
Aerobic soil 3 45090019 4.0 (269) 4.0 (269)
Aerobic soil 4 45090019 Not applicable Not applicable
Aerobic soil 3 45090021 Not determined Not determined
Aerobic soil 4 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 soil 3 45090023 Not determined Not determined
Anaerobic soil 4 45090023 Not applicable Not applicable Anaerobic aquat 3 45621718 0.37 (305) 0.21 (362) 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

- 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: C 21 H 21 F 2 NO 2 MW: 357.40 g/mol Hydrolysis 1 45090017 <0.9 (7) Not detected (30) Aq photolysis 3 46658101 Not detected Not detected Aq photolysis 4 46658101 Not detected Not detected Soil photolysis 3 45090020,

46299904 3.0 (12.25) 3.0 (12.25) Soil photolysis 4 1.9 (7.38

- 9.79) 1.2 (12.29)
Aerobic soil 3 45090019 11.7 (60) 7.1 (269)
Aerobic soil 4 45090019 10.9 (60) 7.2 (269)
Aerobic soil 3 45090021 30.0 (62) 9.4 (272)
Aerobic soil 4 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 soil 3 45090023 1.8 (120) 1.8 (120)
Anaerobic soil 4 45090023 1.4 (40, 120) 1.4 (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 Not detected (all intervals) Not detected

(122)

### 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: C 13 H 19 NO 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

- dihydr o

- ,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: C 21 H 21 F 2 NO 4 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

### 55

Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum

%AR (day) A 

### Final %AR

(study length , day )

Anaerobic soil 4 45090023 Not determined Not determined Anaerobic aquat 3 45621718 Not detected Not detected Anaerobic aquat 4 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: C 13 H 18 O 4 MW: 238.29 g/mol Hydrolysis 1 45090017 Not determined Not determined Aq photolysis 3 46658101 Not detected Not detected Aq photolysis 4 46658101 Not applicable Not applicable Soil photolysis 3 45090020,

46299904 Not determined Not determined Soil photolysis 4 Not applicable Not applicable
Aerobic soil 3 45090019 Not determined Not determined
Aerobic soil 4 45090019 Not applicable Not applicable
Aerobic soil 3 45090021 Not determined Not determined
Aerobic soil 4 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 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 

### DFBA (DFB amide) 2,6

- Difluorobenzamide

SMILES Code: C1(=CC=CC(=C1C(=O)N ([H])[H])F)F

Formula: C 7 H 5 F 2 NO MW: 157.12 g/mol Hydrolysis 1 45090017 Not determined Not determined Aq photolysis 3 46658101 Not applicable Not applicable Aq photolysis 4 46658101 8.6 (14) 8.6 (14) Soil photolysis 3 45090020,

46299904 Not determined Not determined Soil photolysis 4 Not applicable Not applicable
Aerobic soil 3 45090019 Not applicable Not applicable
Aerobic soil 4 45090019 Not determined Not determined
Aerobic soil 3 45090021 Not applicable Not applicable
Aerobic soil 4 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

### 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 soil 3 45090023 Not applicable Not applicable
Anaerobic soil 4 45090023 Not determined Not determined Anaerobic aquat 3 45621718 Not applicable Not applicable Anaerobic aquat 4 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 

### CO 2 Carbon dioxide

SMILES Code: C(=O)=O

Formula: CO 2 MW: 44.01 g/mol Hydrolysis 1 45090017 Not applicable Not determined Aq photolysis 3 46658101 12.6 (20) Aq photolysis 4 46658101 3.7 (14) Soil photolysis 3 45090020,

46299904 6.6 (12.25) 5 Soil photolysis 4 8.7 (12.29) 5
Aerobic soil 3 45090019 < 15.9 (269)
Aerobic soil 4 45090019 56.17 (269)
Aerobic soil 3 45090021 40.5 (272)
Aerobic soil 4 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 soil 3 45090023 Not determined 8
Anaerobic soil 4 45090023 Not determined 8 Anaerobic aquat 3 45621718 Not detected Anaerobic aquat 4 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, bo th in the top layer of soil.

1 The hydrolysis results presented are for the pH 7 (20 0 C) run. These are the closest to relevant en vironmental 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

- butylphenyl

14 C]

- and [difluorophenyl

14 C]

- etoxazole, respectively.

5 The study author reported that almost all the volatile radioactivity was CO 2

. 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.

### 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 Evalua tion

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.



## 16 3

- 1 Leach ing /adsorp tion /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. (20 00) 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 Pro ject 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 Hu ntingdon 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.

46299 906 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

Cali fornia: 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: 221 54: 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., Cambr idgeshire, 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 Ju ne 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: V

23157: 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 Etoxaz ole 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 Toxici ty 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 Flow

Through 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.

MR ID 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 Inhibi tion: 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 Fr eshwater 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:

9 700175. 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 Ti er 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

- 9 7

- 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 Ef fects 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) Po tter 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.; Lav ielle, 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 marin e 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. Unpubli shed 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 25 o C; mg/L) 0.075

Mammalian LD 50 (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 LD 50 (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 LD 50 (mg/kg bw) 2000 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC 50 (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/m 3 ) 1.35E

- 01

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.70E

- 02

Adjusted Inhalation LD 50 1.75E+00

Ratio of Vapor Dose to Adjusted Inhalation LD 50 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 LD 50 3.62E

- 02 Exposure not Likely Significant

Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 1.35E

- 01

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 2.14E

- 02

Adjusted Inhalation LD 50 6.49E+01

Ratio of Vapor Dose to Adjusted Inhalation LD 50 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 LD 50 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 T otal T oxic
R esidue s

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 E 1. 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 M iticide

, 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.

K d (ml/g) 151 MRID: 45090024, 45090026, 46299905, 46299906 Represents the average K d value among eight values ranging from 66 to 335 ml/g;
the K d model was utilized because it represents the mobility of etoxazole better than K OC

. Binding is not correlated with OC.

Aerobic S oil Metabolism (days)

= 370 MRID: 45090019, 45090021, 45090022 90 th 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, t 90,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

.

### 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 photo

transformation half

- life. Molecular Weight (g/mole) 359.42 Product Chemistry

--- Vapor Pressure (torr) 7 x 10

- 6 MRID: 45089902

--- Henry’s Law Constant (atm

- m 3 /mol) 8.5 x 10

- 6

--- Estimated from vapor pressure and water solubility.

EXAMS Environment Pond298.exv

--- Default for pond scenario, as opposed to index reservoir. Field Size EPA pond

--- 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 E 2 . Surface waters estimated environmental exposure concentrations (E EC s) 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 p resented 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 th e 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 (effectiv e 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 negli gi ble (1380.2 days).The main source of dissipation in the benthic region is metab olism (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 Concentratio ns (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 E 1. 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

- i n

- 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 2.41 E

- 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 3.2 2E

- 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 4.09 E

- 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 2.4 9E

- 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

–

Variabl e 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

- 0 2 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 ha lflife (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 Contri bution 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 par titioning 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 = photolys is 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
1.1 90 = 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