UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 29-September-2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Subject: Etoxazole in/on Imported Oranges and Orange Oil. Summary of Analytical Chemistry and 

Residue Data. 

PC Code: 107091 DP Barcode: 0424375 

Decision No.: 493877 Registration Nos.: not applicable 

Petition No.: 4E8304 Regulatory Action: tolerances without a U.S. registration 

Risk Assessment Type: not applicable Case No.: 7616 

TXR No.: not applicable CAS No.: 153233-91-1 

MRID No: see below - - 40 CFR: 180.593 

From: Tom Bloem, e~ ~" . 

Risk Assessment Branch I/Health Effects Division (RABl/HED; 7509P) 

Through: Danette Drew, Chemist _\_ ~ ,,, , ~ Dennis McNeilly, Chemist .q:;}___. ~ "--- ~~m (__ 

Chemistry Science Advisory t'O~ncil (ChemSAt) HED (7509P) 

George F. Kramer, Ph.D., Senior Chemist ~ ?~;: S ..(.. 

RABl/HED (7509P) ~ 

To: Venus Eagle/Rita Kumar RMOl 

Registration Division (RD; 7505P) 

c 

This memorandum was reviewed by two peer reviewers of the HED ChemSAC, per ChemSAC 

Standard Operating Procedures (SOPs). 

Summary of Submitted/Reviewed Residue C hemistry Studies 

OCSPP Guidel ine Reference 

MRID No. 4937220 I. Breda. 0. (2014). Magnitude of the Residue of Etoxazolc Following Application of 

860. 1500; 860. 1520 SMITE on Orange, in Brazil. Report Numbers: 201400137 and Sl3-041 l l. Unpublished study prepared by 

Valent U.S.A. Corporation. 338 pages. 

Page I of15 
Etoxazole Summary of Analytical Chemistry and Residue Data 0424375 

TABLE OF CONTENTS 

1.0 EXECUTIVE SUMMARY .................................................................................................................... 3 

2.0 RECOMMENDATIONS ....................................................................................................................... 4 

2.1 Data Deficiencies/Data Needs ............................................................................................................ 4 

2.2 Tolerance Considerations .................................................................................................................... 4 

2.2.1 Enforcement Analytical Method ........................................................................................... 4 

2 .2.2 Recommended Tolerances ..................................................................................................... 4 

2.2.3 Revisions to Petitioned-For Tolerances ................................................................................. 4 

2.2.4 International Harmonization .................................................................................................. 4 

2.3 Label Recom1nendations ......................................................................................... ............................ 4 

3.0 lNTRODUCTION ............................................................................................................................. ..... 5 

3.1 Chemical Identity ................................................................................................................................ 5 

3.2 Physical/Chemical Properties ............................................................................................................. 5 

3.3 Pesticide Use Pattern/Directions ......................................................................................................... 6 

4.0 METABOLISM/DEGRADATE RESIDUE PROFILE ......................................................................... 6 

5.0 RESIDUE PROFILE .............................................................................................................................. 8 

5.1 Residue Analyt.ical Methods ............................................................................................................... 8 

5.1.1 Data-Collection Methods ....................................................................................................... 8 

5.1.2 Food and Drug Administration (FDA) Multiresidue Methods (MRMs) ............................... 8 

5.1.3 Tolerance-Enforcement Method ............................................................................................ 8 

5.1.4 Submittal of Analytical Reference Standards ........................................................................ 9 

5.2 Storage Stability .................................................................................................................................. 9 

5.3 Residue Data ....................................................................................................................................... 9 

5.3. I Crop Field Trials ................................................................................................................... 9 

5,3.2 Magnitude of.tbe ~s due -Rotational Crops ..................................................................... 10 

5.3.3 Processed Food/Feed ... : ....................................................................................................... 10 

5.3.4 Meat, Milk, Poultry, and Eggs ............................................................................................. 12 

5.4 Food Residue Profile ........................................................................................................................ I 2 

6.0 TOLERANCE DERIVATION ............................................................................................................. 12 

A TI A CHM ENT I: INTERN A TI ON AL RESIDUE LIMITS ................................................................... 13 

ATTACHMENT 2: OECD TOLERANCE CALCULATIONS ................................................................ 14 

ATTACHMENT 3: CHEMlCAL STRUCTURES .................................................................................... 15 

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Etoxazole Summary of Analytical Chemistry and Residue Data 0424375 

1.0 Executive Summary 

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

dihydrooxazole] is a contact acaricide/ovicide that is currently registered in the U.S. for the control of 

mites on various raw agricultural commodities (RACs). Permanent tolerances have been established 

for residues of etoxazole in/on plant commodities, ranging from 0.01 ppm for tree nuts to 20 ppm for 

peppermint and spearmint oils [ 40 CFR § l 80.593(a)]. Tolerances have also been established for 

residues of etoxazole in fat (0.02 ppm) and liver (0.0 l ppm) of ruminants and in milk fat (0.01 ppm). 

Valent® U.S.A. Corporation has submitted a petition proposing tolerances, without a U.S. 

registration, for residues of etoxazole in/on orange, whole fruit (0.08 ppm) and orange, oil (1 .8 ppm). 

Proposed Use: Valent® submitted a translated copy of a Brazilian label (suspension-concentrate 

(SC); 110 g ai/L) which includes instructions for two broadcast foliar applications to orange trees at 

89-99 g ai/ha (14-day preharvest interval (PHI); retreatment interval (RTI) is not indicated; see Tables 

3.3.1 and 3.3.2). The Brazilian application scenario is supported by the available residue chemistry 

data. 

Nature of the Residue - Primary Crops/Rotational Crops/Livestock: Based on the available cotton, 

eggplant, orange, apple, poultry, and ruminant metabolism studies, HED concluded that the residue of 

concern for tolerance enforcement in the proposed/registered primary crops and livestock is etoxazole 

per se. The residues of concern for risk assessment are defined in Table 4.0.1. 

An adequate confined rotational crop study is also available. Based on these data, HED concluded 

that provided the total application rate is S0.135 lb ai/acre, rotational crop restrictions would not be 

required. For rates above 0.135 lb ai/acre, the Agency concluded that, without label restrictions, a 

new confined rotational crop study is required; depending on the results of the confined study a field 

rotational crops study may also be required. 

Magnitude of the Residue - Proposed Crop: The number and geographical representation of the 

submitted field trial data are adequate. In addition, the petitioner submitted adequate orange 

processing data which indicated that the residues of concern concentrate in orange oil and reduce in 

orange juice and dried orange pulp. All samples were analyzed using adequately validated methods 

and sufficient storage stability data are available. Based on these field trial and processing data, HED 

concludes that the tolerances listed in Table 2.2.2. 1, for residues of etoxazole per se, are appropriate. 

A revised Section F is requested. 

Magnitude of tlze Residue - Rotational Crops: Since the proposed use is for an import tolerance, a 

discussion concerning the magnitude of the residue in rotated crops is unnecessary. 

Magnitude of the Residue - Livestock: Livestock tolerances for residues of etoxazole are currently 

established in/on milk fat (0.01 ppm); fat of cattle, goats, horses, and sheep (0.02 ppm); and liver of 

cattle, goats, horses and sheep (0.01 ppm). The only feed commodity associated with the current 

petition is dried orange pulp (roughage) which, based on revised Table 1 (Jun-2008), is only fed to 

ruminants (10% of the diet). Based on an expected residue in dried pulp of <0.048 ppm and since the 

registered field com use resulted in a 4.0-ppm stover tolerance (roughage), HED concludes that the 

current petition does not alter the previous decisions concerning the magnitude of the residue in 

ruminants (D385940, J. Tyler, 23-Sep-201 1 ). Since there are no poultry or hog feed commodities 

associated with the current petition (revised Table 1; Jun-2008), a discussion concerning the 

magnitude of the residue in poultry and hog is unnecessary. 

Page 3of 15 
Etoxazole Summarv of Analytical Chemistry and Residue Data 0424375 

2.0 Recommendations 

Provided the petitioner submits a revised Section F, HED concludes that the residue chemistry 

database supports the establishment of the permanent tolerances listed in Section 2.2.2. A human 

health risk assessment is forthcoming. 

2.1 Data DeficienciesfData Needs 

None. 

2.2 Tolerance Considerations 

2.2.1 Enforcement Analytical Method 

Adequate methods (gas chromatography/mass-selective detector (GC/MSD) or GC/nitrogenphosphorus detector (NPD)) are available for enforcing the current plant and livestock tolerances 

including the currently established tangerine tolerance (0303628, J. Tyler, 30-Mar-2005). Based on 

the similarity of tangerines and oranges, HED concludes that the current tolerance-enforcement 

methods are adequate to enforce the tolerances recommended herein. 

2.2.2 Recommended Tolerances 

Table 2.2.2.1 is a summary of the proposed and HED-recommended tolerances for residues of 

etoxazole per se. A revised Section F is requested. 

Table 2.2.2.1: Tolerance Summary. 

Proposed HEDCommodity Recommended Comments Tolerance (ppm) Tolerance (ppm)' 

40 CFR I 80.593(a) 

orange. whole fruit 0.08 0. 10 The commodity definition should be "orange .. and a tolerance of 0. 10 

ppm recommended to harmonize with the Codex MRL. 

The commodity definition should be "citrus. oil." Based on the orange 

orange, oi l 1.8 1.0 RAC HAFT of 0.048 ppm and the median orange oil processing factor or 

20x. a tolerance of 1.0 oom is recommended. 1 Tolerance without an U.S. registration. 

2.2.3 Revisions to Petitioned-For Tolerances 

See the comments column of Table 2.2.2.1 . 

2.2.4 International Harmonization 

There are no Canadian or Mexican maximum residue limits (MRLs) in/on the proposed commodities 

(see Attachment 1). There is a Codex MRL for residues in/on citrus (0. 10 ppm). Although the 

Organization for Economic Co-operation and Development (OECD) tolerance-calculation procedure 

indicated that a 0.08-ppm tolerance for residues in/on orange is appropriate, a tolerance for residues 

in/on orange of 0.10 ppm is recommended for purposes of harmonization. 

2.3 Label Recommendations 

None 

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Etoxazole Summary of Analytical Chemistry and Residue Data 0424375 

3.0 Introduction 

3.1 Chemical Identity 

The chemical structure and nomenclature of etoxazole is presented in Table 3. 1.1. 

Table 3.1.1: Structure and Nom enclature of Etoxazole. 

Compound 

Common name etoxazole 

Company experimental names S-1283, V-1283, Yl-530 1 

IUPAC name ( RS)-5-tert-buty 1-2-(2-(2,6-d in uoropheny 1)-4, 5-d i hydro- 1,3-oxazo 1-4-y I] pheneto le 

CAS name 2-(2,6-ditluorophenyl)-4-[ 4-( I, I -dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole 

CAS# 153233-91-1 

3.2 Physical/Chemical Properties 

Table 3.2.1 is a summary of the physical/chemical properties for etoxazole. Etoxazole has a low 

water solubility and a high Log Kow. 

Table 3.2.1: P hysicochcmical Properties of Etoxazole (TGAI). 

Melting range 1o1.5-102.5°C 

pH 6.2 

Density 1.2389 g/cm3 

3.99 x 10·

5 g/L at 10°c 

Water solubility 7.04 x f0·

5 g/L at 20°c 

6.69 x 1 o·5 g/L at 30°C 

acetone: 309 1.2-dichloroethane: 402 46018505.der. wpd 

Solvent solubi lity (g/L a l 20"C) ethyl acetate: 249 n-heptane: 18. 7 

methanol: 104 xylene: 252 

Vapor pressure at 25°C 7.0 x I o·

6 pascals 

Dissociation constant (pK.} no measurable pK. 

Octanol/water partition coefficient Log(Kow) 5.52 ± 0.58 at 20°c 

UV/visible absorption Not available. 

Page 5of 15 
Etoxazole Summary of Analvtical Chemistry and Residue Data 0 424375 

3.3 Pesticide Use Pattern/Directions 

Valent® submitted a translated copy of a Brazilian label which includes instructions for 

application to orange trees. Table 3.3. l is a summary of the end-use products and target pests 

and Table 3.3.2 is a summary of the Brazilian orange application scenario. The Brazilian 

application scenario is supported by the available residue chemistry data. 

T a ble 3.3.1: Summary of End-Use Product. 

Trade Name I Cone. I Fonnulation I Label Date I Target Crops I Target Pests 

Smite (Brazilian label) I 110 g aifL I SC I not provided I orange trees lnat mite (Tetra11ycl111s urticae) 

Table 3.3.2: S ummary of Braz ilia n Orange Application Scena rio.' 

App. Timing: 

Single App. Max. # App. Max. Seasonal PH I 

Type; and Equip. Formulation Rate: g ai/ha 

per Season App. Rate: g ai/ha (days) Use Directions and Limitations 

(lb ai/acre) (lb ai/acre) 

-Label indicates a spray solution of 45 

ml/JOO L(4.95 g ai/ 100 L) 

beginning of -spray volumes arc 1800-2000 Ln1a ( 192-

infestation: broadcast SC 89-99 198 2 14 gal/acre): 5- 10 U trcc ( 1.3-2.6 gal/tree) 

foliar spray using a ( 110 g ai/L) (0.08-0.09) 2 (0. 18) 14 -RTI is not specified: label indicates that 

Turbo Atomizer etoxazole should be applied at the 

beginning of infestation when the juvenile 

forms of the pest are present (ctoxazole 

docs not control adult mites) 

1 The label specifies ''citrus (oranges)." 

4.0 Metabolism/Degradate Residue Profile 

Table 4.0.1 and the following text are summaries of the residues of concern in plants (primary 

and rotational crops), poultry, and ruminants. See Attachment 3 for structures. 

Primary Crops: The qualitative nature of etoxazole residues in plants is adequately understood 

based upon the metabolism studies on cotton, eggplant, apple, and orange. In each of these 

studies, the major 14C-residue in/on various matrices was identified as parent compound. Based 

on the metabolite profi les observed in these studies, etoxazole may undergo photo-oxidation to 

yield Metabolite R-1 3. Parent and Metabolite R-1 3 then undergo opening of the oxazole ring to 

form a variety of metabolites (R-4, R-7, R-14, and R-3), and subsequent cleavage of the opened 

ring forms Metabolites OFB, R-8, R-10, R- 11 , R-1 2, and R-15 (0 283737, J. Tyler, 31-Jul-2003; 

0 303628, J. Tyler, 30-Mar-2005; D307 I 78, J. Tyler, 6-Apr-2005). Based on these data, the 

HEO Metabolism Assessment Review Committee (MARC) concluded that the residues of 

concern, for tolerance enforcement and risk assessment, are as defined in Table 4.0.1. 

Livestock: The qualitative nature of etoxazole residues in livestock is understood based upon the 

adequate goat and poultry metabolism studies (0283737, J. Tyler, 3 l-Jul-2003; 0 289666, J. 

Tyler, 17-Jun-2003). Although livestock in both studies were dosed at similar dietary levels (8-

16 ppm) for - 4 days, absorption and accumulation was considerably greater in hens than in the 

goats. Data from the poultry study suggest the potential for bioaccumulation of parent in eggs 

and fat; whereas, in the goat metabolism study, there was no indication of 14C-residues 

accumulating in fat or milk. The residue data from the ruminant feeding study contradicts the 

goat metabolism study in that residues do appear to accumulate in milk fat and fat. Due to its 

high octanol/water coefficient (Kow), etoxazole would be expected to concentrate in fat. 

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Etoxazole Summary of Analytical Chemistry and Residue Data 0424375 

In the poultry metabolism study, etoxazole was identified as the principal residue in each 

commodity, with the exception of liver, in which Metabolite R-16 was the major residue. Based 

on the metabolite profile in eggs and tissues, the primary route of metabolism in poultry involves 

the oxidation of the tert-butyl group to produce either an alcohol (Metabolite R-2) or an acid 

(Metabolite R-16) metabolite. Hydrolysis of the dihydrooxazole ring in parent and Metabolite 

R-16 produced Metabolites R-7 and R-7-C02H, respectively, and further hydrolysis of the ester 

bond produces Metabolites R-8, and R-11. Dihydroxazole ring hydrolysis of R-2 also yields 

Metabolites R-24 and R-20. 

In the goat metabolism study, the limited data from liver, kidneys, urine, and feces indicate that 

etoxazole undergoes cleavage of the dihydrooxazole ring and oxidation on the tert-butyl group. 

The major residue in kidneys was the tert-butyl acid derivative of R-8 (R-8C02H, also referred to 

as Metabolite 1). This metabolite was also a major residue in liver along with Metabolite R-20. 

Based on these data, the HED MARC concluded that the residues of concern, for tolerance 

enforcement and risk assessment, are as defined in Table 4.0.1. 

Rotational Crops: An adequate confined rotational crop study is available depicting the 

potential for accumulation of inadvertent etoxazole residues in rotational crops. Following a 

single broadcast application of (

14

C-ditluorophenyl]- or (1 4C-tert-butylphenyl]-etoxazole to bare 

sandy loam soil at 0.099 and 0.097 lb ail A, total radioactive residues were <0.005 ppm in all 

commodities harvested from lettuce, radish and wheat from a - 30-day plant-back interval. 

Therefore, rotational crop restrictions are not required for use rates up to 0.1 lb ail A. 

In conjunction with the petition for use on strawberries, HED has also concluded that the 

available data would support maximum seasonal rates up 0.135 lb ai/A without the need for 

additional data or rotational crop restrictions, as a significant increase in inadvertent residues 

would not be expected from seasonal application rates up to 0.135 lb ai/A. For rates above 0.135 

lb ai/acre, the Agency concluded that, without label restrictions, a new confined rotational crop 

study is required (depending on the results of the confined study a field rotational crops study 

may also be required). 

Table 4.0. J: Summary of Metabolites and Degradates of Concern for Risk Assessment and Tolerance Enforcement. 

Matrix Residues of Concern 

Risk Assessment Tolerance Enforcement 

primary crops - except cotton gin byproducts and almond hull 1 ctoxazolc 

Primarv crops - cotton gin byproducts and almond hull ' etoxazole and R-3 

poultry tissue (except livcr)2 etoxazole etoxazolc c22 and poultry liver etoxazole and R-16 

milk and ruminant muscle/fat2 etoxazole 

ruminalll liver/kidnev2 etoxazole and metabolite I 

waler' etoxazole, R-8, and R-1 3 -- rotational croos4 no decision no decision 1 0283 737, J. Tyler, 3 1-Jul-2003; 0303628, J. Tyler, 30-Mar-2005; 0307178. J. Tyler, 6-Apr-2005; 0289666, J. Tyler, 17-Jun-2003. 2 0283737. J. Tyler. 3 l-Jul-2003: 0289666, J. Tyler. I 7-Jun-2003; 0289666, J. Tyler, l 7-Jun-2003. 3 0289666, J. Tyler, 17-Jun-2003. 

~ 0283737, J. Tyler, 3 l-Jul-2003; 0307178, J. Tyler, 6-Apr-2003; 0353394, D. Rate, I 8-Nov-2008. 

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Etoxazole Summarv of Analvtical Chemistrv and Residue Data D424375 

5.0 Residue Profile 

5.1 Residue Analytical Methods 

5.1.1 Data-Collection Methods 

The field trial and processing samples were analyzed for residues of etoxazole using a highperformance liquid chromatography with tandem mass spectrometry detection (LC/MS/MS) 

method adapted from two QuEChERS multiresidue methods and Valent Method RM-37HM. 

Acceptable method validation and concurrent recoveries were reported for samples of orange 

fortified with etoxazole at 0.01-0.50 ppm, for samples of juice and dried pulp fortified at 0.0 I ppm, 

and for samples of oil fortified at 0.01-7.0 ppm, thus validating the method. The limit of 

quantitation (LOQ; determined as the lowest limit of method validation) was 0.0 I ppm for all 

matrices (limit of detection (LOD) was 0.002 ppm). The fortification levels used in concurrent 

method recovery were adequate to bracket expected residue levels. Concurrent recoveries and 

residues in treated samples were not corrected for residues in controls. The following paragraph is 

a summary of the method. 

Briefly, the orange (RAC), orange juice, and orange dried pulp, samples were extracted with 

acetonitrile (ACN) followed by the addition of 5 M NaOH and a salt mixture of anhydrous 

MgS04, NaCl, trisodium citrate dihydrate, and hydrogen disodium citrate sesquihydrate. The 

mixture was stirred then centrifuged, and an aliquot of the extract was diluted with ACN 

containing 0.1 % acetic acid for LC/MS/MS analysis. For oil, the sample was adjusted to pH 2::8 

by the addition of 5 M NaOH then combined with ACN saturated with hexane. The salt mixture 

was added, and the mixture was centrifuged. Following phase separation, the organic phase was 

combined with an Eppendorf salt mixture of anhydrous MgS04, and primary-secondary amine 

(PSA) sorbent and centrifuged. The resulting supernatant was subjected to LC/MS/MS analysis. 

5.1.2 Food and Drug Administration (FDA) Multiresidue Methods (MRMs) 

FDA MRMs may be used to determine residues of etoxazole in fatty and non-fatty matrices and 

to determine residues of Metabolite R-3 in nonfatty matrices. Etoxazole was completely 

recovered from fortified samples of apple using Methods 302, El with GC/NPD or Method 303, 

C l or C2 with GC/NPD. Etoxazole was partially recovered from cottonseeds (fatty matrix) 

using Method 304, ES, CI or C2 with GC/NPD. Metabolite R-3 could be completely recovered 

from cotton gin byproducts using Method 302, E4 using GC/NPD. However, matrix 

interferences enhanced the recoveries of R-3 from gin byproducts. The results of the MRM 

testing were forwarded to the FDA for inclusion in the Pesticide Analytical (PAM) Vol. I 

(0290919, J.·Tyler, I 7-Jun-2003). 

5.1.3 Tolerance-Enforcement Method 

Adequate methods (GC/MSD or NPD) are available for enforcing the current plant and livestock 

tolerances including the currently established tangerine tolerance (0303628, J. Tyler, 30-Mar2005). Based on the similarity of tangerines and oranges, HED concludes that the current 

tolerance enforcement methods are adequate to enforce the tolerances recommended herein. 

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Etoxazole Summary of Analvtical Chemistry and Residue Data 0424375 

5.1.4 Submittal of Analytical Reference Standards 

The EPA National Pesticide Standards Repository has an etoxazole analytical standard with an 

expiration date of22-Aug-2017 (email from G. Verdin; Biological Economic Analysis Division; 

7-May-2015). 

5.2 Storage Stability 

Table 5.2. l is a summary of the maximum storage intervals for samples between 

harvest/processing and extraction (samples were analyzed within 1 day of extraction). 

Previously submitted storage stability data indicate that etoxazole is stable at -20°C for at least 

3.5 months in apples, 2 months in strawberries, 6 months in orange pulp, 12 months in orange 

peels, 17 months in cottonseed, and 6 months in cotton gin byproducts (D283737, J. Tyler, 31-

Jul-2003). These data are adequate to validate the storage intervals/conditions for the field trial 

and processing data submitted as part of the current action. 

Table 5.2.1: Summary of Storage Conditions. 

Matrix Storage Maximum Interval of Demonstrated Storage Stability Temp. (0 C) Storage Duration 1 

orange (RAC) 27 days 

Previously submitted storage stability data indicate that 

etoxazole is stable at -20°C for at least 3.5 months in 

apples, 2 months in strawberries, 6 months in orange pulp, 

orange juice and dried pulp :S-18 IO days 12 months in orange peels, 17 months in cottonseed, and 6 

months in cotton gin byproducts (D283737, J. Tyler, 31-

orange oil 14-20 days Jul-2003). These data are adequate to validate the storage 

intervals/conditions employed as part of the current study. 1 Interval from harvcst/processrng to extraction. Samples were analyzed within 0-1 day of extraction. 

5.3 Residue Data 

5.3.1 Crop Field Trials 

493 7220l .der1 

Field trial residue data were submitted from 11 field trials conducted in Brazil during the 2013 

growing season (see Table 5.3.1.1 and the paragraph below for a summary of these data). The 

trials were conducted using the proposed application rate and employed an adequately validated 

analytical method (storage intervals were also validated). Based on the Section B submitted as 

pa.it of the current petition, etoxazole is only registered for application to oranges grown in 

Brazil. Based on this and based on information concerning the sources for oranges imported into 

the U.S., HED concludes that the numbers and locations of the submitted field trial data are 

adequate (see Table 5.3.1.2). No additional data are required to support the proposed tolerance 

in/on imported oranges. 

49372201.derl: Field trial residue data were submitted from 11 field trials conducted in Brazil 

during the 2013 growing season. Each trial site consisted of one untreated plot and one treated 

plot with the treated plot receiving two broadcast airblast applications of a 110 g ai/L SC etoxazole 

formulation at 99-104 g ai/ha (1.0-1.1 x) for a total application rate of 199-208 g ai/ha (1.0-1. l x). 

Applications were made at RTis of29-31 days and spray volumes of2013-2063 L/ha (no adjuvant 

was used). Oranges were harvested at a PHI of 14 days. In two trials, additional samples were 

Page 9 of 15 
Etoxazole Summarv of Analvtical Chemistry and Residue Data 0424375 

harvested at PH ls of 7 and 21 days to investigate residue decline. Residues (and per-trial averages) 

of etoxazole in/on the orange RAC samples were <0.01-0.053 ppm (<0.01-0.048 ppm). In the 

residue-decline trials, residues decreased with increasing PHI in one trial. In the second trial, 

residues declined after the 7-day PHI, but were higher at the 21-day PHI than at the 14-day PHI. 

An acceptable method was used for residue quantitation and adequate storage stability data are 

available to validate the employed intervals/conditions. Table 5.3.1. 1 is a summary of the field 

trial residue data. 

Table 5.3.1.1: Summary of Residues from Orange Field Trials with Etoxazole. 

Crop Matrix Total Application Rate PHI n' 

Etoxazolc Residues (ppm) 

(lb ai/ A) Lg ai/ha] (days) Min.2 I Max.2 I LAFT3 I HAFT3 I Median3 I Mcan3 I SD3 

Orange 0. 178-0.186 [ 199-208] 14 11 <0.0 1 I 0.053 I <0.0 1 I 0.048 I o.028 I 0.028 I 0.0 I 0 

1 n = number of field trials. 2 Values based on total number of samples. 3 Values based on per-trial averages. LAFT =lowest average field trial. HAFT= highest average field trial. SD= standard 

deviation. 

Table 5.3.1.2: Trial Numbers and Geographical Locations. 

Country Oranges 

Submi11cd Requested' 

Brazil 11 2 8 

Mexico -- 4 

Total 11 12 

1 The requested number and geographic d1stnbut1on of field trials for oranges. accord mg to the NAFT A Guidance Document on 

Data Requirements for Tolerances on Imported Commodities in the United States and Canada 12/05 and import data 

(h11p://ageconscarch.umn.cdu/handle/l I 9741 and hllp://apps.fas.usda.gov/gats/default.aspx). All countries (in which the 

pesticide is marketed or intended to be marketed) must be represented if the amount that they export to orth America represents 

5% or more of imports of the subject crop into any of the country in which a tolerance is being sought 2 The trial count renects four pairs or groups of trials separaicd by <20 miles that HED has determined to be replicate trials. 

5.3.2 Magnitude of the Residue - Rotational Crops 

Since the proposed use is for an import tolerance in/on oranges and orange oil, a discussion 

concerning the magnitude of the residue in rotated crops is unnecessary. 

5.3.3 Processed Food/Feed 

49372201.der2 

As part of the current request, the petitioner submitted an orange processing study (4937220 1.der2) 

depicting the magnitude of etoxazole residues in/on orange dried pulp, orange juice, and orange oil 

following retreatment at Ix and 5x the Brazilian application rate. The resulting data indicate that 

residues decreased in orange juice (0.9-<0.05x) and dried pulp (0.9-<0.5x) and increased in orange 

oil (7.4->25x). These data are summarized in the paragraph below and Table 5.3.3. 1. No additional 

processing data are required. 

49372201.der2: Orange processing data were submitted from three trials conducted in Brazil 

during the 2013 growing season. Each trial site consisted of one untreated plot and two treated 

plots with the treated plot receiving two broadcast airblast applications of a 110 g ai/L SC 

etoxazole formulation. At the first plot, applications were made at 99-101 g ai/ha (l.Ox) for a total 

application rate of 199-202 g ai/ha (1.0x), and at the second plot applications were made at 495-

Page 10of 15 
Etoxazole Summary of Analytical Chemistrv and Residue Data 0424375 

509 g ai/ha (5.0-5.lx) for a total application rate of995-1013 g ai/ha (5.0-5.lx). Applications were 

made at RTis of 31 days and spray volumes of2022-2037 L/ha (no adjuvant was used). Oranges 

were harvested at a PHI of 14 days and were processed into juice, dried pulp, and oil using 

simulated commercial practices. Processing was conducted at JBT FoodTech (Araraquara, SP 

Brazil). Residues of etoxazole were <0.01 -0.033 ppm inion RAC san1ples from the lx plots and 

<0.012-0.204 ppm inion RAC saniples from the 5x plots. Average residues in juice and dried pulp 

were below the LOQ (<0.01 ppm) in all samples from all plots and trials, and average residues in 

oil from the Ix and 5x plots, respectively, were 0.181-0.395 and 0.289-4.29 ppm. A comparison of 

the residues in/on orange (RAC) with those in each processed fraction indicated that residues of 

etoxazole concentrated in oil (median processing factor of >20x), but did not concentrate in juice 

or dried pulp (<0.3x). The observed processing factors do not exceed the theoretical concentration 

factors for citrus of 3 .3x, I OOOx, and 2x for peel, oil, and juice (based on separation into 

components; OCSPP 860.1520, Table 3). Table 5.3.3. 1 is a summary of the processing data. 

Table 5.3.3.1 : Residue Data from Orange Processing Study with Etoxazole. 

Commodity Rate Residues' (ppm)[Average] Processing factor2 Median Processing 

Factor3 

Limeira, SP, Brazil; 2013 (Sl3-04 11 l-01) 

Orange (RAC) 0.022, 0.031 (0.027] -- -- Juice ND, ND [<O.O lj <0.4x <0.3x 

Dried pulp Ix ND. ND [<0.01 ] <0.4x <0.3x 

Oil 0.383. 0.407 (0.395] 15x >20x 

Orange (RAC) 0. 194, 0.214 [0.204] -- Juice ND, ND (<0.01) <0.05x not applicable Dried pulp 5x 

ND, ND [<0.01) <0.05x 

Oi l 4.51 , 4.07 (4.29] 21x 

Sa nto Antonio de Posse, SP, Brazil; 2013 (Sl3-041 I l-02) 

Orange (RAC) (0.007), (0.008) f<0.0 1] -- Juice ND, ND [<0.01) <0.3x 

Dried pulp Ix ND, ND [<0.01) <0.3x 

Oil 0.18 1, 0.180 [0. 18 1] > 18x 

not applicable Orange (RAC) (0.004), 0.01 3 [<0.012) -- Juice ND, ND [<0.0 1) 0.9x 

Dried pulp 

5x 

ND, ND [<0.01 ) 0.9x 

Oil 0.282, 0.296 [0.289) >25x 

Limeira, SP, Brazil; 2013 (Sl3-0411 I-03) 

Orange (RAC) 0.031 , 0.035 [0.033] .. 

Juice ND, ND f<0.01] <0.3x 

Ix Dried pulp ND, ND f<0.0 1] <0.3x 

Oi l 0.235. 0.251 [0.243) 7.4x 

not applicable Orange (RAC) 0. 188. 0.147 (0. 168) .. 

Juice ND, ND [<0.01] <0.06 

Dried pulp 5x ND, ND [<0.01) <0.06 

Oil 3.85. 3.75 [3.80] 23x 1 All values are the mean of duplicate analyses. ND = Nondetectable (<LOO). The LOO was 0.002 ppm, and the LOQ was 0.0 I 

ppm. Values between the LOO and LOQ are reported in parentheses. Per trial averages were calculated by the study reviewer 

using the LOQ for values reported as <LOQ. 2 Processing Factor= [Measured residue for analyte in the processed fraction] I [Measured residue for analyte in the RAC]. NC 

=Not calculated. The processing factor could not be calculated because residues were below the LOQ in the RAC and the 

processed fraction. 3 Median processing factor for both plots and all sites. 

Page 11 of 15 
Etoxazole Summary of Analvtical Chemistry and Residue Data 0424375 

5.3.4 Meat, Milk, Poultry, and Eggs 

Livestock tolerances for residues of etoxazole are currently established inion milk fat (0.01 ppm); fat 

of cattle, goats, horses, and sheep (0.02 ppm); and liver of cattle, goats, horses and sheep (0.0 l ppm). 

The only feed commodity associated with the current petition is dried orange pulp (roughage) which, 

based on revised Table 1 (Jun-2008), is only fed to ruminants (10% of the diet). Based on an 

expected residue in dried pulp of <0.048 ppm and since the registered field com use resulted in a 4.0-

ppm stover tolerance (roughage), HED concludes that the current petition does not alter the previous 

decisions concerning the magnitude of the residue in ruminants (0 385940, J. Tyler, 23-Sep-2011). 

Since there are no poultry or hog feed commodities associated with the current petition (revised Table 

1; Jun-2008), a discussion concerning the magnitude of the residue in poultry and hog is unnecessary. 

5.4 Food Residue Profile 

Based on the proposed/registered application scenarios, etoxazole residues may be found in 

drinking water and crop/livestock commodities. Based on results of a fish accumulation study 

and the high octanol/water partition coefficient, EFEO indicated that etoxazole appears to have a 

high potential to bioaccumulate (Sl 600x for edible tissues; 0311941 , J. Melendez, 3 l-May2005); based on this assessment, HED included residues in fish/shellfish in the dietary exposure 

analysis (D426228, T. Bloem, 29-Sep-2015). 

6.0 Tolerance Derivation 

The petitioner has submitted adequate magnitude of the residue data to support the establishment of 

tolerances inion imported orange commodities. No additional residue data are required. Based on the 

available data and the OECD tolerance-calculation procedure (see Attachment 2). a tolerance of 0.08 

ppm for residues of etoxazole per se inion orange is appropriate. However. HED is recommending 

for an orange tolerance of0.10 ppm to harmonize with the currently-established Codex MRL 

(Canadian and Mexican MRLs are not established). HED is also recommending for an orange oil 

tolerance of 1.0 ppm based on the HAFT for oranges (0.048 ppm) and the median orange oil 

processing factor of 20x, (tolerances inion orange juice and dried pulp are unnecessary). Table 6.0. I 

is a summary of the proposed and HEO recommended tolerances. A revised Section Fis requested. 

Table 6.0.1: Tolerance Summary. 

Commodity Proposed HED-Recommended Comments Tolerance (ppm) Tolerance (ppm)1 

40 CFR 180.629(a) 

orange, whole fruit 0.08 0. 10 

orange. oil 1.8 1.0 

1 Tolerance wtthout an U.S. reg1strat1on. 

Attachment l: International Residue Limits. 

Attachment 2: OECO Tolerance Calculations. 

Attachment 3: Chemical Structures 

ROI: RAB I Chem ists (25-Mar-2014) 

T he commodity definition should be "orange .. and a tolerance of 0. 10 

loom recommended to harmonize with the Codex MRL. 

The commodity definition should be "citrus. oi1:· Based on the.: 

orange RAC HAFT of0.048 ppm and the median orange oil 

[processin_g factor of 20x. a tolerance of 1.0 ppm is recommended. 

Page 12of15 
Etoxazole Summarv of Analvtical Chemistrv and Residue Data 0424375 

Attachment 1: International Residue Limits. 

International Residue Limits: Etoxazole (107091) 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition 

us Canada Mexico2 Codex 

Etoxazole - 2-(2.6-dinuorophenyl)-4-[.l-( 1.1-dimethylethyl)- 2-(2.6-dinuorophenyl)-4-f 4-( 1.1- Etoxazole 

2-ethoxyphenyl)-4.5-dihydrooxazole dimcthylethyl)-2-ethoxyphenyl)- The residue is 

14.5-dihydrooxazole fat soluble. 

Tolerance/Maximum Residue Limit (ppm) 

Commodity1 us Canada Mcxico2 Codex 

oranges 0.08 0.1 citrus fruits orane.e. oil 1.8 

Completed: M. Negussie: 03/ 17115 .. 1 Includes only commod1t1es of interest for this action. Tolerance values are l-I E-D recommendations and not those proposed by 

the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

Page 13of 15 
Etoxazole Summarv of Analytical Chemistrv and Residue Data 

Attachment 2: OECD Tolerance Calculations. 

Compound 

Crop 

Region I Country 

GAP 

Total number of data (n) 

Percentage of censored data 

Number of non-censored data 

Lowest residue 

Highest residue 

Median residue 

Mean 

Standard d evia tion (SD ) 

Correction factor for censoring {CF) 

Proposed MRL estimate 

- Highest residue 

- Mean + 4 SD 

- CF x 3 Mean 

Unrounded MRL 

Rounded MRL 

etoxazole 

oranges 

Brazil 

2 x 99 g ai/ha 

11 

9% 

10 

0 . 010 

0 . 048 

0 . 028 

0 . 028 

0 . 010 

0 . 939 

0 . 048 

0 . 069 

0 . 079 

0 . 079 

0.08 

Residues (mg/kg) 

0 . 03 4 

0 . 010 

0 . 033 

0 . 015 

0 . 026 

0 . 048 

0 . 028 

0 . 022 

0 . 035 

0 . 025 

0 . 032 

Page 14of15 

* 

0424375 
Etoxazole Summary of Analytical Chemistry and Residue Data 

Attachment 3: Chemical Structures 

Common name/(code) 

Etoxazole 

(S-1283) 

R-3 

R-16 

Metabolite I 

tBUr5 

Chemical name 

2-(2,6-difluorophenyl)-4-[4-( I, ldimethylethyl)-2-ethoxyphenyl)-4,5-

dihydrooxazole 

N-(2,6-difluorobenzoyl)-4-tert-butyl-2-

ethoxybenzamide 

2-methyl-2-{3-ethoxy-4-[2-(2,6-

difluorophenyl)-4 ,5-d ihydro- l ,3-oxazol4-yl] phenyl}propionic acid 

2-am ino-2-(2-ethoxy-4-( I' -

hydroxycarbonyl-1 '-methylethyl)phenyl) 

ethanol 

Page 15of 15 

0424375 
Etoxazote [PC Code 107091)/Valent U.S.A. Corporation 

B.7.6 Residues Resulting from Supervised Trials 

(Annex IIA 6.3; Annex IHA 8.3) 

B.7.6.1 Residues in Target Crops 

B.7.6.1.1 Orange 

Document ID: MRID No. 49372201 

Report: Breda, 0. (2014) Magnitude of the Residue of Etoxazole Following 

Application of SMITE on Orange, in Brazil. Report Numbers: 

201400137 and S13-041 l l. Unpublished study prepared by Valent 

U.S.A. Corporation. 338 p. 

Guidelines: -EPA OCSPP Harmonized Test Guideline 860.1500 Crop Field Trials 

(August l 996) 

-PMRA Regulatory Directive DIR98-02 - Residue Chemistry Guidelines, 

Section 9 - Crop Field Trials 

-PMRA Regulatory Directive DIR2010-05 - Revisions to the Residue 

Chemistry Crop Field Trial Requirements 

-OECD Guideline 509 Crop Field Trial (September 2009) 

GLP Compliance: No deviations from the EPA regulatory requirements were reported which 

would have an impact on the validity of the study. 

Acceptability: The study is considered scientifically acceptable. The acceptability of this 

study for regulatory purposes is addressed in the forthcoming U.S. EPA 

Residue Chemistry Summary Document, DP# 424375. 

Evaluator: Tom Bloem, Chemist, Risk Assessment Branch ~~v ion 

Note: This Data Evaluation Record (DER) was originally prepared under contract by Versar. Inc. (6850 Versar Center, 

Springfie ld. VA 22 I 51 ; submitted 27-Feb-20 15. The DER has been reviewed by I JED and revised to renect current Office of 

Pesticide Programs (OPP) policies. 

EXECUTIVE SUMMARY 

Valent U.S.A. Corporation has submitted field trial data for etoxazole on orange from 11 field 

trials conducted in Brazil during the 2013 growing season. The above trial count reflects four 

pairs or groups of trials separated by <20 miles that HED has determined to be replicate trials. 

Each trial site consisted of one untreated plot and one treated plot. At each trial location, the 

treated plot received two foliar broadcast applications of a 0.92 lb ai/gal (1 10 g ai/L) suspensionconcentrate (SC) formulation of etoxazole (Smite) at 0.088-0.093 lb ai/A/application (99-104 g 

ai/ha/application) for a total application rate of 0.178-0.186 lb ai/ A (199-208 g ai/ha). 

Applications were made at retreatment intervals of 29-31 days using ground (airblast) equipment 

in spray volumes of215-221 gal/A (2013-2063 L/ha). No adjuvant was used. The petitioner 

noted that in one trial (03) a product containing etoxazole was applied as a maintenance chemical 

to the crop (rate was not specified). Oranges were harvested at a preharvest interval (PHI) of 14 

days. In two trials, additional samples were harvested at PHis of 7 and 2 1 days to investigate 

residue decline. 

EPA MR!D #: 49372201 Page I of8 
Etoxazole [PC Code I 07091 ]N alent U.S.A. Corporation 

All samples were maintained frozen at the testing facility, during shipping, and were stored 

frozen at the analytical laboratory until analysis. The maximum storage interval for samples 

between harvest and analysis was 27 days (0.9 months). Samples were analyzed on the day of 

extraction. Previously submitted storage stability data indicate that etoxazole is stable at -20°C 

for at least 3.5 months in apples, 2 months in strawberries, 6 months in orange pulp, 12 months 

in orange peels, 17 months in cottonseed, and 6 months in cotton gin byproducts (0283737, J. 

Tyler, 3 l-Jul-2003). These data are adequate to validate the storage intervals/conditions 

employed as part of the current study. 

Samples were analyzed for residues of etoxazole by high-performance liquid chromatography 

with tandem mass spectrometry detection (LC/MS/MS) using a method adapted from two 

QuEChERS multiresidue methods and Valent Method RM-37HM. Acceptable method 

validation and concurrent recoveries were reported for samples of orange fortified with etoxazole 

at 0.01-0.50 ppm, thus validating the method. The limit of quantitation (LOQ; determined as the 

lowest level of method validation, LLMV) was 0.01 ppm. The fortification levels used in 

concurrent method recovery were adequate to bracket expected residue levels. Concurrent 

recoveries and residues in treated samples were not corrected for residues in controls. 

In oranges harvested at a PHI of 14 days following two foliar broadcast applications of the 0.92 

lb ai/gal SC formulation, residues (and per-trial averages) of etoxazole were <0.01-0.053 ( <0.01-

0.048) ppm. Although relatively high residues were observed in Trial 03, which reflected 

application of a maintenance product containing etoxazole (rate was not specified), the residues 

were well within the range of observed residues. 

In the residue decline trials, residues decreased with increasing PHI in one trial. In the second 

trial, residues declined after the 7-day PHI, but were higher at the 21-day PHI than at the 14-day 

PHI. 

I. MATERIALS AND METHODS 

A. MATERIALS 

T able B.7.6.1.1- 1. Nomencla ture for Etoxazolc. 

Common na me etoxazole 

Identity 2-(2.6-difluorophenyl)-4-(4-( I. l-dimethylethyl}-2-

ethoxyphenyl]-4.5-dihydrooxazolc 

CAS no. I 53233-91 -I 

Company experimental name V- 1283 

Other synonyms (if applicable) S-1283 

OC.H, 

(C ,l «~ 

F -vEPA MRJD #: 49372201 Page 2 of8 
Etoxazole [PC Code 10709 1)Nalent U.S.A. Corporation 

B. Study Design 

1. Test Procedure 

A total of 11 residue trials in/on orange were conducted in Brazil with a 0.92 lb ai/gal (110 g 

ai/L) SC formulation during the 2013 growing season. The trials separated by <20 miles have 

been assessed for independence as detailed in the table below. HED has determined that four 

pairs or groups of trials constitute single trials with replicate samples for purposes of OCSPP 

860.1500 data requirements. Field trial locations are summarized in Table B.7.6.1.1-2. 

Locations and detailed use patterns for the trials are provided in Table B.7.6.1.1-3. 

Independent T ria l Determination' 

Trial Nos. Differences Decision 

01. 03,04,05.06, 07: VaricN: 0 1 and04: Replicates 

(Same Location) 0 1 and04: Valencia 05 and 06: Replicates 

05 and 06: Pera Murcha 03 and 07: Separate due to variety 

03: Pera Coroa 

07: Rubi 

02 and 08 Variety: Separate due to variety 

(<20 miles) 02: Folha Murcha 

08: Pera Coroa 

10 and 11 Varietv: Replicates 

(Same location) Both Valencia 

12 and 16 VaricN: 13, 14, 16: Replicates 

(Same location) 13, 14. 16: Valencia 12 and 15: Separate due to variety 

13, 14, 15 12: Pera Rio 

(Same location) 15: Rubi 

1 All assessments are based on the replicate trial guidance presented in draft memo 568_ Critcria for Independence of Trials 

04/23/2013 (EPA and PMRA). 

Table B.7.6.1.1-2. Tria l N umbe rs and Geographical Locations. 

Country Oranges 

Submitted Requested' 

Brazil I 12 8 

Mexico -- 4 

Total 11 12 

1 The requested number and geographic distribution of field trials for oranges. according to the NA FT A Guidance Document on 

Data Requirements for Tolerances on Imported Commodities in the United States and Canada, 12/05 and import data 

(http://ageconsearch.umn.edu/lumd lc/l l 974 l and http://apps.fm;.usda.gov/gats/dcfault.aspx). All countries (in which the 

pesticide is marketed or intended to be marketed) must be represented if the amount that they export to North America represents 

5% or more of imports of the subject crop into any of the country in which a tolerance is being sought. 2 The trial count reflects four pairs or groups of trials separated by <20 miles that I-LED has determined to be replicate trials. 

T able B.7.6.1.1 -3. Study Use P attern. 

Location: City. Volume Rate per Retreat- Total Rate State/Province, End-use Method of Application; {gal/A) Application ment (lb ai/A) Surfactant/ 

Country: Year Product' Timing of Application (lb ai/A) Interval Adjuvant 

(Trial ID) [L/ha] [g ai/ha] (days) [g ai/lia] 

Limeira, SP, 0.92 lb 1. Foliar broadcast; BBCH 89 218 (2037) 0.090 [101) -- 0. 180 None 

Brazil: 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCH 89 218 [2037] 0.090 [101) 3 1 (202] 

0411 1-0 I) 

EPA MRlD #: 49372201 Page 3 of8 
Etoxazole [PC Code I 07091 ]Nalent U.S.A. Corporation 

Table B.7.6.1.1-3. Study Use Pattern. 

Location: City. Volume Rate per Retreat- Total Rate State/Province. End-use Method of Application: (gal//\) Application mcnt (lb ai/A) Surfactant/ 

Country; Year Product' Timing of Application (lb ai/A} Interval Adjuvant 

(Trial ID) fL/ha] [g ai/hal (days) [g ai/ha] 

Santo Antonio de 0.92 lb 1. Foliar broadcast: BBCI I 84 216 (2022) 0.089 [100] -- 0. 178 None 

Posse, SP. Brazil: ai/gal SC 2. Foliar broadcast: BBCI I 89 2 16 (2022) 0.088 [99J 31 [199) 

2013 (S l3-041 l l02) 

Limeira. SP. 0.92 lb I. Foliar broadcast: BBCI I 89 2 18 [2037] 0.090 [1011 -- 0.180 one 

Brazil: 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCH 89 218 [2037) 0.090 [IOI] 31 (202) 

04 111-03) 

Limeira. SP. 0.92 lb I. Foliar broadcast: BBCH 89 216 (2019) 0.089 [1 001 -- 0.178 None 

Brazil; 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCI 1 89 2 16(20 19) 0.089 [1 00] 3 1 (200) 

04111 -04) 

Limeira, SP, 0.92 lb I. Foliar broadcast: BBCH 84 2 18 (2037) 0.090 [1011 -- 0. 180 None 

Brazil: 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCH 86 2 18 (2037] 0.090 [I OIJ 3 1 [202] 

04 111-05) 

Limcira. SP. 0.92 lb I. Foliar broadcast: BBCH 89 2 16 [2024) 0.089 [1 00) -- 0.178 one 

Brazil: 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCH 89 216 (2024) 0.089 [100) 31 (200] 

04111 -06) 

Limeira. SP. 0.92 lb I. Foliar broadcast: BBCH 89 216(2024] 0.089 [ 100] -- 0.178 one 

Brazil: 2013 (Sl3- ai/gal SC 2. Foliar broadcast: BBCH 89 2161.20241 0.089 (100) 31 [200] 

04111-07) 

Mogi Mirim, SP, 0.92 lb I. foliar broadcast; BBC! I 89 2 18 [204 11 0.090 11 011 -- 0. 180 None 

13razil; 2013 (S l3- a i/gal SC 2. Foliar broadcast: BBC! I 89 2 18 (2041] 0.090 (101) 3 1 [202) 

04 111-08) 

Aguai, SP, Brazil: 0.92 lb I. Foliar broadcast: BBCH 89 2 18 [2041) 0.090 (IOI] -- 0. 180 None 

20 13 (S 13-04 I I 1- ai/gal SC 2. Foliar broadcast: BBC! I 89 2 18 [204 1] 0.090 ( 10 1) 3 1 [202] 

09) 

Boa Espcran~a do 0.92 lb I. Foliar broadcast: BBCI I 86 215 (20 13] 0.089 [ IOO] -- 0.178 one 

Sul. SP. Brazil: ai/gal c 2. Foliar broadcast: BBCH 89 2 1512013] 0.089 [100] 29 (200) 

2013 (S 13-04 I I I -

10) 

Boa Esperan~a do 0.92 lb I. Foliar broadcast: BBCI I 86 2 15 (2013) 0.089 [1 001 -- 0. 178 None 

Sul. SP. Brazil: ai/gal SC 2. Foliar broadcast; BBC! I 89 2 15 (2013] 0.089 [100] 29 [200J 

2013 (S l3-041 I I11 ) 

Tabatinga, SP. 0.92 lb I. Foliar broadcast: BBCI I 87 2 18 [20371 0.090 11 0 11 -- 0. 180 None 

Brazil; 2013 (S l3-

04 111-12) 

ailgal SC 2. Foliar broadcast: Bl3CI I 89 2 18 (2037] 0.090 [IO I] 29 [202] 

ltapolis, SP. 0.92 lb I. Foliar broadcast: BBCH 87 221 [20631 0.093 [104] - 0.186 one 

Brazil: 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCH 89 221 (2063] 0.093 (1 04] 29 [208] 

04 111-13) 

ltapolis, SP. 0.92 lb I. Foliar broadcast: BBCH 88 2 18 [2041] 0.090 [IOI] -- 0. 180 one 

Brazil: 2013 (S13- ai/gal SC 2. Foliar broadcast: BBCH 89 2 18 (204 1] 0.090 [101] 29 (202] 

041 11-1 4) 

ltapolis. SP, 0.92 lb I. Foliar broadcast: 13BCH 86 218 [20371 0.090 [IOI] -- 0. 180 None 

Braz il; 2013 (S l3- ai/gal SC 2. Foliar broadcast: BBCH 89 2 18 (2037] 0.090[I011 29 [202] 

04 111-15) 

Tabatinga. SP. 0.92 lb I. Foliar broadcast: BBCI I 85 2 19 [205 1) 0.091 11 021 -- 0. 182 None 

Brazil: 2013 (S 13- ai/gal SC 2. Foliar broadcast: BBCI I 86 2 19 [2051] 0.091 [102] 29 [204] 

04 111-16) 

1 0.92 lb ai/gal (110 g ai/L) SC fomrnlation of etoxazole (Smi te~ 

EPA MRlD #: 4937220 I Page 4 of8 
Etoxazole [PC Code I 07091 ]Nalent U.S.A. Corporation 

Oranges were grown and maintained according to typical agricultural practices. Irrigation was 

not used at any trial. No unusual weather conditions were reported to have adversely affected 

crop growth or yields during the study. The petitioner noted that in one trial (03) a product 

containing etoxazole was applied as a maintenance chemical to the crop (rate was not specified). 

Sample Handling and Preparation 

Single control and duplicate treated samples were harvested from all trials at a 14-day PHI. 

Additional samples were collected at PHis of 7 and 21 days at two trials to investigate residue 

decline. Samples were placed in frozen storage at the field sites within 24 hours of harvest and 

were shipped within 1-7 days of harvest to the analytical laboratory, Eurofins Agroscience 

Services Brazil (lndaiatuba, SP, Brazil). At the analytical laboratory, san1ples were 

homogenized in the presence of dry ice and were stored frozen -18 °C) until extraction for 

analysis. 

2. Description of Analytical Procedures 

Samples were analyzed for residues of etoxazole by LC/MS/MS using a method adapted from 

two QuEChERS multiresidue methods and Valent Method RM-37HM. A complete description 

of the method was included in the submission. 

Briefly, samples were extracted with acetonitrile (ACN) followed by the addition of 5 M NaOH 

and a salt mixture of anhydrous MgS04, NaCl, trisodium citrate dihydrate, and hydrogen 

disodium citrate sesquihydrate. The mixture was stirred then centrifuged, and an aliquot of the 

extract was diluted with ACN containing 0.1 % acetic acid for LC/MS/MS analysis. 

The LOQ (determined as the LLMV) was 0.01 ppm. The limit of detection (LOD) was 0.002 

ppm. 

II. RESULTS AND DISCUSSION 

Method performance was evaluated during method validation and by use of concurrent recovery 

samples by fortifying untreated samples with etoxazole at 0.01-0.50 ppm for method validation 

and 0.01 ppm for concurrent recovery. Recoveries were within the acceptable range of 70-

120%; therefore, the method was considered valid for the analysis of etoxazole residues in 

orange (Table 8.7.6.1.1-4). The fortification levels bracketed the measured residues. 

Concurrent recoveries were not corrected for apparent residues in controls. 

The detector response was linear (coefficient of determination, r2 = 0.9982) within the range of 

2.5-80 ng/mL. Representative chromatograms of control samples, fortified samples, and treated 

samples were provided. The control chromatograms generally had no peaks of interest above the 

chromatographic background. The fortified sample chromatograms contained only the analyte of 

interest, and peaks were symmetrical and well defined. Apparent residues in controls were 

below the LOQ ( <0.01 ppm). The reported residue values in the treated samples were not 

corrected for apparent residues in controls. 

EPA MRID #: 49372201 Page5of8 
Etoxazole [PC Code 107091]Nalent U.S.A. Corporation 

T a b le B. 7.6.1.1-4. Summa ry of Me thod Va lid a t ion a nd P roced ural/Concurrent Recoveries of Etoxazole 

from Ora nge. 

Matrix I Fortification I Sample size I Recoveries' I Mean ± Std. Dev. 

Level (ppm) (n) (%) (%) 

Method valida tion 

Orange I 0.01-0.50 I 30 I 79.6-119.2 I 97.6 ± 11.2 

Concu rrent recoveries 

Orange I 0.01 I 4 I I 03.0-11 6.2 I 106.6 ± 6A 

1 Concurrent recoveries were not corrected for apparent residues in controls. 

Samples were stored frozen for a maximum of 27 days (0.9 months) from harvest to extraction 

(Table B.7.6. 1.1-5). Samples were analyzed on the day of extraction. Previously submitted 

storage stability data indicate that etoxazole is stable at -20°C for at least 3.5 months in apples, 2 

months in strawberries, 6 months in orange pulp, 12 months in orange peels, 17 months in 

cottonseed, and 6 months in cotton gin byproducts (0283737, J. Tyler, 3 l-Jul-2003). These data 

are adequate to validate the storage intervals/conditions employed as part of the current study. 

Table B.7.6.1.1-5. Summary of Storage Conditions. 

Matrix Storage Actual Storage Interval of Demonstrated Storage Stability 

Temp. (0C) Duration' 

Orange '.S-18 8-27 days Previously submitted storage stability data indicate that etoxazole is stable at -

(0.3-0.9 months) 20°C for at least 3.5 months in apples, 2 months in strawberries. 6 months in 

orange pulp. 12 months in orange peels, 17 months in cot1011seed. and 6 months 

in cotton gin byproducts (0283737. J. Tyler. 3 1-Jul-2003). These data arc 

adequate to validate the storage intervals/conditions employed as part of the 

current study. 

1 Interval from harvest to extraction. Samples were analyzed on the day of extraction. 

The results from the submitted field trials are presented in Tables B.7.6.1.1-6 and B.7.6.1.1-7. In 

oranges harvested at a PHI of 14 days following two foliar broadcast applications of the 0.92 lb 

ai/gal SC formulation, residues (and per-trial averages) of etoxazole were <0.01-0.053 ( <0.01-

0.048) ppm. Although relatively high residues were observed in Trial 03, which refl ected 

application of a maintenance product containing etoxazole (rate was not specified), the residues 

were well within the range of observed residues. 

In the residue decline trials, residues decreased with increasing PHI in one trial. ln the second 

trial, residues declined after the 7-day PHI, but were higher at the 2 1-day PHI than at the 14-day 

PHI. 

EPA MRlD #: 4937220 I Page 6 of8 
Etoxazole [PC Code I 07091 ]Nalent U.S.A. Corporation 

Table B.7.6.1.1-6. Residue Data from Orange Field Trials with Etoxazole. 1 

Location: City, Zone Orange Matrix Rate PH I Etoxazole Residues3 (ppm ) 

State/Province. Variety (lb ai/A) (days) [Average] 

Country; Year (Trial [g ai/ha) 

ID)2 

Limeira, SP, Orazil; NIA Valencia Fruit 0.178-0. 180 14 0.022, 0.031, 0.039, 0.042 

2013 (S 13-041 I l-01 ) (200-202] (0.034) 

a nd (S l3-04111-04) 

Limeira. SP. 13razil; NIA Valencia Fruit 0. 178 (200] 7 0.080, 0.080 (0.080) 

2013 (S13-04 1 I l-04) 21 0.023, 0.027 (0.025] I Decline intervals! 

Santo Antonio de NIA Fol ha Fruit 0.178 (199) 14 (0.007), (0.008) [<0.0 1] 

Posse, SP, Brazi l; 2013 Murcha 

(S 13-041 1 1-02) 

Limeira, SP, Brazil: NIA Pera Coroa Fruit 0.180 [202] 14 0.03 1, 0.035 [0.033) 

2013 (S l3-0411 l-03) 

Limeira, SP, Brazil; NIA Pera Murcha Fruit 0. 178-0. 180 14 0.016, (0.008), 0.015, 0.017 

2013 (Sl3-041 l l-05) [200-202) [<0.015) 

a nd (Sl3-04 1 I l-06) 

Limeira, SP, Brazil; NIA Pera Mureha Fruit 0.180 [202) 7 0.107, 0. 106 [0.107) 

2013 (S13-04111-05) 21 0.030, 0.020 [0.025] 

!Decline inte rvals! 

Limeira, SP. Brazi l; NIA Rubi Fruit 0.178 [200) 14 0.024. 0.021 ro.0261 

2013 (S l3-041 I l-07) 

Mogi Mirim, SP, NIA Pera Coroa Fruit 0.180 [202) 14 0.053, 0.042 [0.048) 

Brazil: 2013 (S l3-

04 111-08) 

Aguai. SP. Brazil: 2013 NIA Valencia Fruit 0. 180 [202] 14 0.024, 0.031 (0.028] 

(S 13-04 I 11-09) 

Boa Esperan~a do Sul, NIA Valencia Fruit 0. 178 [200) 14 0.016, 0.0 16, 0.025, 0.029 

SP. Brazil; 2013 (S l3- [0.022) 

0411 1-lO)and 

(S l3-0411 l-11 ) 

Tabatinga, SP. Brazil; NIA Pera Rio Fruit 0. 180 [202) 14 0.042, 0.027 [0.035] 

2013 (S 13-0411 l- 12} 

ltapolis. SP, Brazil; NIA Valencia Fruit 0.180-0. 186 14 0.045, 0.039, 0.012, 0.020, 0.015, 

2013 (S l3-041 I l-13) [202-208] 0.017 

a nd (S l3-04 11 l-1 4) [0.025) 

a nd Tabatinga, SP. 

Brazil: 2013 (S 13-

04111 -16) 

Itapolis, SP. Brazil; NIA Rubi Fruit 0.180 [202) 14 0.030, 0.033 [0.032) 

20 13 (S 13-04 11 1-1 5) 

1 A 0.92 lb ai/gal ( 11 0 g ai/L) SC fomrnlation was used. 2 HED has determined that the following trial pairs/groups constitute single trials with replicate samples for purposes of OCSPP 

860.1500 data requirements: 01 and 04; 05 and 06; 10 and 11 ; and 13, 14, and 16. 3 All values arc the mean of duplicate analyses. The LOO was 0.002 ppm, and the LOQ was 0.0 I ppm. Values between the 

LOO and LOQ are reported in parentheses. Per trial averages were calculated by the study reviewer using the LOQ for values 

reported as <LOQ. 

EPA MRJD #: 49372201 Page 7 of8 
Etoxazole [PC Code 10709 1]Nalent U.S.A. Corporation 

Table B. 7.6.1.J-7. Summary of Residues from Orange Field Trials with Etoxazole. 

Crop Matrix Total Application Rate PHI n' Etoxazolc Residues (ppm) 

(lb ai/A) [g ai/ ha] (days) Min.

2 I Max.2 I LAFT3 I I IAFT3 I Median3 I Mean3 I soi 

Orange 0. 178-0.186 I 199-208] 14 11 <0.01 I o.osJ I <0.01 I o.048 I o.02s I 0.028 I 0.010 1 n = number of field trials. 2 Values based on total number of samples. 

l Values based on per-trial averages. LAFT = lowest average field trial. I IAFT = highest average field trial. SD =standard 

deviation. 

III. CONCLUSIONS 

The orange field trials are considered scientifically acceptable. In oranges harvested at a PHI of 

14 days following two foliar broadcast applications of the 0.92 lb ai/gal SC fonnulation, residues 

(and per-trial averages) of etoxazole were <0.01-0.053 (<0.01-0.048) ppm. Although relatively 

high residues were observed in Trial 03, which reflected application of a maintenance product 

containing etoxazole (rate was not specified), the residues were well within the range of 

observed residues. 

In the residue decline trials, residues decreased with increasing PHI in one trial. In the second 

trial, residues declined after the 7-day PHI, but were higher at the 2 I-day PHI than at the 14-day 

PHI. 

An acceptable method was used for residue quantitation and adequate storage stability data are 

available to validate the employed intervals/conditions. 

REFERENCES 

0283737, J. Tyler, 3 l-Jul-2003 

EPA MRJD #: 49372201 Page 8 of8 
Etoxazole (PC Code 107091]Nalent U.S.A. Corporation 

B.7.7 

B.7.7.1 

B.7.7.2 

B.7.7.3 

B.7.7.3.1 

Document ID: 

Report: 

Guidelines: 

Effects of Industrial Processing and/or Household Preparation 

(Annex IIA 6.5; Annex DIA 8.5) 

Nature of the Residue 

(Annex IIA 6.5.1; Annex IHA 8.5.1) -Not a data requirement in North America 

Distribution of the Residue in Peel/Pulp 

(Annex IIA 6.5.2; Annex IIIA 8.5.2) 

These data were not included in the study. 

Magnitude of Residues on Set of Representative Processes 

(Annex IIA 6.5.3; Annex llIA 8.5.3) 

Orange 

MRID No. 49372201 

Breda, 0. (2014) Magnitude of the Residue of Etoxazole Following 

Application of SMITE on Orange, in Brazil. Report Numbers: 

201400137 and Sl3-041 l l. Unpublished study prepared by Valent 

U.S.A. Corporation. 338 p. 

EPA OCSPP Harmonized Test Guideline 860.1520 Processed Food/Feed 

(August 1996) 

PMRA Regulatory Directive DIR98-02- Residue Chemistry Guidelines, 

Section IO - Processed Food/Feed 

OECD Guideline 508 Magnitude of the Pesticide Residues in Processed 

Commodities (October 2008) 

GLP Compliance: No deviations from the EPA regulatory requirements were reported which 

would have an impact on the validity of the study. 

Acceptability: The study is considered scientifically acceptable. The acceptability of this 

study for regulatory purposes is addressed in the forthcoming U.S. EPA 

Residue Chemistry Summary Document, DP# 424375. 

Evaluator: Tom Bloem, Chemist, Risk Assess1'~V Branch l/Health Effects Division 

Note: This Data Evaluation Record (DER) was originally prepa~e?cont~;;;>, Inc. (6850 Versar Center, 

Springfi eld, VA 22151; submitted 2/27/ 15. The DER has been reviewed by 1-IED and revised lo reflect current Office of 

Pesticide Programs (OPP) policies. 

EXECUTIVE SUMMARY 

Valent U.S.A. Corporation has submitted a processing study for etoxazole on orange from three 

trials conducted in Brazil during the 2013 growing season. At each trial location, two treated plots 

at each site received two fo liar broadcast applications of a 0.92 lb ai/gal (110 g ai/L) suspensionconcentrate (SC) formulation of etoxazole (Smite). At the first plot, applications were made at 

0.088-0.090 lb ai/Napplication (99-101 g ai/ha/application) for a total application rate of 0.178-

0.180 lb ai/A (199-202 g ai/ha), and at the second plot applications were made at exaggerated (5x) 

rates of 0.442-0.454 lb ai/Napplication (495-509 g ai/ha/application) for a total application rate of 

0.888-0.904 lb ai/A (995-1013 g ai/ha). Applications were made at retreatment intervals of 31 

days using ground (airblast) equipment in spray volumes of 216-218 gal/ A (2022-203 7 L/ha). No 

EPA MRID #: 49372201 Page I of8 
Etoxazole [PC Code 107091]Nalent U.S.A. Corporation 

adjuvant was used. The petitioner noted that in one trial (03) a product containing etoxazole was 

applied as a maintenance chemical to the crop (rate was not specified). Oranges were harvested at 

a preharvest interval (PHI) of 14 days and were processed into juice, dried pulp, and oil using 

simulated commercial practices. Processing was conducted at JBT FoodTech (Araraquara, SP 

Brazil). Adequate descriptions of the processing procedures were provided, including material 

balance summaries. 

Samples of orange (RAC) for analysis were maintained frozen at the testing facilities and during 

shipping to the analytical laboratory. Samples of orange intended for processing were shipped 

under ambient conditions from the field sites to the processing facility and were stored frozen at 

the processing facility following processing and during shipping to the analytical laboratory. All 

samples were stored frozen at the analytical laboratory prior to analysis. Processing was 

completed within 1-3 days of harvest. The maximum storage intervals for samples between 

harvest/processing and extraction were 15 days for orange and 20 days for processed commodities. 

Samples were analyzed within 1 day of extraction. Previously submitted storage stability data 

indicate that etoxazole is stable at -20°C for at least 3.5 months in apples, 2 months in strawberries, 

6 months in orange pulp, 12 months in orange peels, 17 months in cottonseed, and 6 months in 

cotton gin byproducts (0 283737, J. Tyler, 31-Jul-2003). These data are adequate to validate the 

storage intervals/conditions employed as part of the current study. 

Samples were analyzed for residues of etoxazole by high-performance liquid chromatography with 

tandem mass spectrometry detection (LC/MS/MS) using a method adapted from two QuEChERS 

multiresidue methods and Valent Method RM-37HM. Acceptable method validation and 

concurrent recoveries were reported for samples of orange fortified with etoxazole at 0.01-0.50 

ppm, for samples of juice and dried pulp fortified at 0.0 I ppm, and for samples of oil fortified at 

0.01-7.0 ppm, thus validating the method. The limit of quantitation (LOQ; determined as the 

lowest level of method validation, LLMV) was 0.01 ppm for all matrices. The fortification levels 

used in concurrent method recovery were adequate to bracket expected residue levels. Concurrent 

recoveries and residues in treated samples were not corrected for residues in controls. 

In orange (RAC) harvested at a 14-day PHI in three trials conducted in Brazil reflecting two foliar 

broadcast applications of the 0.92 lb ai/gal ( 110 g ai/L) SC formulation of etoxazole at total rates 

of 0.178-0.180 lb ai/ A (199-202 g ai/ha; 1 x plot) and 0.888-0. 904 lb ail A (995-1013 g ai/ha; 5x 

plot), average residues were <0.01-0.033 ppm inion samples from the lx plots and <0.012-0.204 

ppm in/on samples from the 5x plots. Average residues in juice and dried pulp were below the 

LOQ (<0.01 ppm) in all samples from all plots and trials, and average residues in oil from the Ix 

and 5x plots, respectively, were 0.181 -0.395 and 0.289-4.29 ppm. 

A comparison of the residues in/on orange (RAC) with those in each processed fraction indicated 

that residues of etoxazole concentrated in oil (median processing factor of >20x), but did not 

concentrate in juice or dried pulp (<0.3x). 

The observed processing factors do not exceed the theoretical concentration factors for citrus of 

3.3x, 1 OOOx, and 2x for peel, oil, and juice (based on separation into components; OCSPP 

860.1520, Table 3). 

EPA MRID #: 4937220 1 Page 2 of8 
Etoxazole [PC Code 107091)Nalent U.S.A. Corporation 

I. MATERIALS AND METHODS 

A. MATERIALS 

Table B.7.7.3.1 -1. Nomenclature for .Etoxazole. 

Common na me Etoxazole 

Identity 2-(2,6-difluorophenyl)-4-[4-(l, l-dimethylethyl)-2-

ethoxyphenyl)-4,5-dihydrooxazole 

CAS no. 153233-91-1 

Company experimental name V-1283 

Other synonyms (if applicable) S-1283 

OCH, (CH),-C&1tJ - ~ ~ 

I 

F ~ 

B. Study Design 

l. Test Procedure 

Location and detailed use pattern for the trial is provided in Table B.7.7.3. 1-2. 

T a ble B.7.7.3.1-2. Study Use Pattern. 

Location : End-use Plot Method of Application/ Volume Rate per Relreatment Total 

City, Product1 Timing of Application (gal/A) Application Interval Rate 

State/Provine [L/ha) (lb ai/A) (days) (lb 

e: Year [g ai/ha] ai/A) 

(Trial ID) fg ai/ha] 

Limeira, SP. 0.92 lb 2 ( Ix) I. Foliar broadcast: BBCI I 89 218 [2037] 0.090 (1 0 1) -- 0.180 

Brazil; 2013 ai/gal 2. Foliar broadcast; BBCl-1 89 2 18 [2037] 0.090 [I OI] 31 [202] 

(S 13-04 I I I - SC 3 (5x) I. Foliar broadcast; BBCl-1 89 218 [2037] 0.450 [504] 0.904 0 1) --

2. Foliar broadcast; BBCl-1 89 218 [2037] 0.454 (509] 3 1 [1013] 

Santo 0.92 lb 2 ( Ix) I. Foliar broadcast; BBCH 84 2 16 f2022l 0.089 [100] -- 0. 178 

Antonio de ai/gal 2. Foliar broadcast; BBCH 89 2 16 [2022] 0.088 (99] 3 1 [199] 

Posse, SP. SC 3 (5x) I. Foliar broadcast; BBCH 84 2 16 (2022) 0.446 [500] 0.888 Brazil: 2013 -- (S l3-0411 1- 2. Foliar broadcast: BBCl-I 89 216(2022] 0.442 [495] 31 [995] 

02) 

Limeira. SP, 0.92 lb 2 ( Ix) 1. Foliar broadcast; BBCH 89 218 [2037) O.o90 [I OI] -- 0.180 

Brazil: 2013 ai/gal 2. Foliar broadcast: BBCH 89 218 [2037] 0.090 [1011 3 1 (202] 

($ 13-04 111- SC 3 (5x) 1. Foliar broadcast: BBCH 89 218 [2037] 0.450 [504] 0.899 03) -- 2. Foliar broadcast: BBCH 89 218 (2037] 0.450 (504] 3 1 (I 008] 

1 0.92 lb ai/gal ( 110 g ai/L) SC formulation of etoxazole (Smite~ 

The petitioner noted that in one trial (03) a product containing etoxazole was applied as a 

maintenance chemical to the crop (rate was not specified). 

Surfactant 

I 

Adjuvam 

None 

None 

None 

None 

None 

None 

EPA MRJD #: 4937220 1 Page 3 of8 
Etoxazole [PC Code 107091]Na lent U.S.A. Corporation 

Sample Handling and Preparation 

Single control and duplicate treated samples of orange (RAC) for analysis were harvested from 

each plot at all trials at a 14-day PHI; a single control and bulk treated samples (103-1 14 kg) for 

processing were also harvested from each plot at all trials at a 14-day PHI. Samples for analysis 

were placed in frozen storage at the field sites witlin - 5.5 hours of harvest and were slipped 

frozen within 2-4 days of harvest to the analytical laboratory, Eurofins Agroscience Services 

Brazil (Indaiatuba, SP, Brazil). Bulk samples intended for processing were shipped under 

ambient conditions on the day of harvest to the processing facility, JBT FoodTech (Araraquara, 

SP Brazil); samples were stored under ambient conditions for up to 22 hours prior to initiation of 

processing. Processing was completed within 1-3 days of harvest, after which samples were 

placed in frozen storage (temperature unspecified). The processed commodity samples were 

shipped frozen on dry ice via air freight within 0-13 days of processing to the analytical 

laboratory. We note that although the petitioner reported that whole fruit subsamples were 

collected and placed in frozen storage at the processing facility, it does not appear that these 

samples were slipped to the laboratory for analysis. At the analytical laboratory, samples of 

orange, juice, and dried pulp were homogenized in the presence of dry ice; samples of oil 

required no additional preparation. Samples were stored frozen (:;::-18 °C) until extraction for 

analysis. 

Sample Processing 

The processing procedures simulated commercial operations of orange production as closely as 

possible to generate the required fractions of orange (RAC) and the processed fractions of juice, 

dried pulp, and oil, with some variations to commercial methods. Adequate descriptions of 

processing procedures were provided, including material balance summaries. A processing 

flowchart for orange processed fractions, copied without alteration from MRID 49372201, is 

presented in Figure B.1. 

EPA MR10 #: 4937220 1 Page 4 of 8 
Etoxazole [PC Code I 07091 ]Nalent U.S.A. Corporation 

FIGURE B.1. Processing Flowchart for Orange Juice, Dried Pulp, and Oil. 

Around SO k!! l====~::>i I. w:i~ wuh •,1;a1er 

wbolt frrut and b:'mbe\ 

.:. Exuaction w11h JBT HP 391. stmcfard i-----~ 

.---------\ configurat:on HP 2H2L 0-WC). usuig 1------.. ·· ·· 

M.1..'ttllre of water and ou is 

betng de<: anted ( etlZ) mes can 

be 3~d and centnfuge can 

be U!.ed u oe<:essa.ry) 

~fi:aure of Juice and Pulp 

being rorwarded to step 3 

~---__, . Separa11.oo ~ Fuusber JBT 

Di-,ca1ded frncuoas 

(001 10 be sampled} 

• P~J 

• Core 

• ~li.'Cllltt$ f 

~eland core 

• Fro 

,..----,ieCT35. w1th 0.0 1··lll!Kh·· 1------.. 

2. Description of Analytical Procedures 

Samples were analyzed for residues of etoxazole by LC/MS/MS using a method adapted from 

two QuEChERS multiresidue methods and Valent Method RM-371-lM. A complete description 

of the method was included in the submission. 

For orange, juice, and dried pulp, samples were extracted with acetonitrile (ACN) followed by 

the addition of 5 M NaOI-I and a salt mixture of anhydrous MgS04, NaCl, trisodium citrate 

dihydrate, and hydrogen disodium citrate sesquihydrate. The mixture was stirred then 

centrif1.1ged, and an aliquot of the extract was diluted with ACN containing 0.1 % acetic acid for 

LC/MS/MS analysis. 

For oil, the sample was adjusted to pH 2:8 by the addition of 5 M NaOH then combined with 

ACN saturated with hexane. The salt mixture was added, and the mixture was centrifuged. 

Following phase separation, the organic phase was combined with an Eppendorf salt mixture of 

anhydrous MgSQ4, and primary-secondary amine (PSA) sorbent and centrifuged. The resulting 

supernatant was subjected to LC/MS/MS analysis. 

The LOQ (determined as the LLMV) was 0.0 l ppm. The limit of detection (LOO) was 0.002 

ppm. 

EPA MRID #: 4937220 I Page5of8 
Etoxazole [PC Code 107091}/Valent U.S.A. Corporation 

II. RESULTS AND DISCUSSION 

Method performance was evaluated during method validation and by use of concurrent recovery 

samples. For method validation, samples of orange (RAC) and oil were fortified with etoxazole 

at 0.01 -0.50 and 0.01-7.0 ppm, respectively. For concurrent recovery, samples of untreated 

orange, juice, dried pulp, and oil were fortified at 0.01 ppm. Recoveries were within the 

acceptable range of 70-120%; therefore, the method was considered valid for the analysis of 

etoxazole residues in orange matrices (Table B.7.7.3.1-3). The fortification levels bracketed the 

measured residues. Concurrent recoveries not corrected for apparent residues in controls. 

The detector response was linear (coefficient of determination, r2 2:0.9914) within the range of 

2.5-80 ng/mL for fruit, juice, and dried pulp and 1-40 ng/mL for oil. Representative 

chromatograms of control samples, fortified samples, and treated samples were provided. The 

control chromatograms generally had no peaks of interest above the chromatographic 

background. The fortified sample chromatograms contained only the analyte of interest, and 

peaks were symmetrical and well defined. Apparent residues in controls were below the LOQ 

in/on all matrices except oil, in which residues of 0.2 ppm were observed in the sample from 

Trial 03. The reported residue values in the treated samples were not corrected for apparent 

residues in controls. 

Table B.7.7.3.1-3. Summary of Method Validation a nd Procedur al/Concurrent Recoveries of Etoxazole 

from Orange Matrices. 

Matrix Fortification Sample size Recoveries' Mean ± Std. Dev. 

Level (ppm) (n) (%) (%) 

Method validation 

Orange 0.01 -0.50 30 79.6-1 19.2 97.6 ± 11.2 

Oil 0.01 -7.0 30 70.0-85.3 75. 1± 4.80 

Concurrent recoveries 

Orange 0.01 4 103.0-116.2 106.6 ± 6.4 

Juice 0.01 4 80.1-105.9 92.4 ± 12.9 

Dried pulp 0.01 4 74.8-80.4 77.4 ± 2.34 

Oi l 0.01 4 74.5-82.5 78.9 ± 3.59 1 Concurrent recoveries were not corrected for apparent residues m controls. 

Processing was completed within 1-3 days of harvest. The maximum storage intervals for 

samples between harvest/processing and extraction were 15 days for orange RAC and 20 days 

for processed commodities (Table B.7.7.3.1-4). Samples were analyzed within 1 day of 

extraction. Previously submitted storage stability data indicate that etoxazole is stable at -20°C 

for at least 3.5 months in apples, 2 months in strawberries, 6 months in orange pulp, 12 months 

in orange peels, 17 months in cottonseed, and 6 months in cotton gin byproducts (D283737, J. 

Tyler, 31-Jul-2003). These data are adequate to validate the storage intervals/conditions 

employed as part of the current study. 

EPA MRJD #: 49372201 Page 6 of8 
Etoxazole (PC Code I 0709 1 ]Nalent U.S.A. Corporation 

Table 8.7.7.3.1-4. S ummary of Storage Conditions. 

Matrix Storage Actual Storage Interval of Demonstrated Storage Stability 

Temp. (0C) Duration1 

Orange (RAC) 18 15 days Previously submitted storage stability data indicate that etoxazole is 

Juice and dried pulp 10 days stable at -20°C for at least 3.5 months in apples. 2 months in 

Oi l 14-20 days strawberries. 6 months in orange pulp. 12 months in orange peels. 17 

months in cottonseed. and 6 months in cotton gin byproducts (0283737. 

J. Tyler. 3 l-Jul-2003). These data are adequate to validate the storage 

intervals/conditions employed as part of the current study. 

1 Interval from harvest/processing to extraction. Samples were analyzed within 0-1 day of extraction. 

Residues found in samples and processing factors are given in Table B.7.7.3.1-5. In orange 

(RAC) harvested at a 14-day PHI in three trials conducted in Brazil reflecting two fo liar 

broadcast applications of the 0.92 lb ai/gal (110 g ai/L) SC formulation of etoxazole at total rates 

of 0.178-0.180 lb ai/A (199-202 g ai/ha; lx plot) and 0.888-0.904 lb ai/A (995-1013 g ai/ha; 5x 

plot), average residues were <0.01-0.033 ppm in/on samples from the l x plots and <0.012-0.204 

ppm in/on samples from the 5x plots. Average residues in juice and dried pulp were below the 

LOQ ( <0.0 I ppm) in all samples from all plots and trials, and average residues in oil from the 1 x 

and 5x plots, respectively, were 0.181-0.395 and 0.289-4.29 ppm. 

A comparison of the residues in/on orange (RAC) with those in each processed fraction indicated 

that residues of etoxazole concentrated in oil (median processing factor of >20x), but did not 

concentrate in juice or dried pulp ( <0.3x). 

T a ble B.7.7.3.1-5. Residue Data from Orange Processing Study with Etoxazole. 

Commodity Plot Residues• (ppm)[A vcragc] Processing Factor2 Median Processing 

Factor3 

Limeira, SP, Brazil; 2013 (5 13-041 11 -0 1) 

Orange (RAC) 2 ( Ix) 0.022. 0.03 1 [0.0271 -- -- Juice ND, ND [<0.0 ll <0.4x <0.3x 

Dried pulp ND. ND [<0.0 1 I <0.4x <0.3x 

Oil 0.383, 0.407 [0.395] 15x >20x 

Orange (RAC) 3 (5x) 0.1 94. 0.2 14 (0.2041 -- Juice ND, ND (<0.01] <O.OSx .. ·- .. 

Dried pulp ND, ND [<0.01] <0.05x -

Oil 4.51, 4.07 [4.29] 2 1x r 

Santo Antonio de Posse, SP, Brazil; 2013 (Sl3-041 I l-02) 

Orange (RAC) 2 ( Ix} (0.007), (0.008) [<0.01] -- Juice ND, ND [<0.01] NC .. ~~---

Dried pulp ND, ND (<O.O ll NC 

Oil 0.181 , 0. 180 10. 181] > 18x ~ - Orange (RAC) 3 (5x) (0.004). 0.013 (<0.0121 -- Juice ND. ND r<0.01] 0.9x 

Dried pulp ND. ND [<0.01 I 0.9x ~ 

Oil 0.282. 0.296 [0.289] >25x " 

Limeira, SP, Brazil; 2013 (Sl3-041 1 l-03) 

Orange (RAC) 2 ( Ix) O.oJ I. O.Q35 [0.033] -- - -· Juice ND. ND 1<0.0 1] <0.3x 

Dried pulp ND, ND [<0.01 I <0.3x 

Oil 0.235, 0.25 1 [0.243) 7.4x 

EPA MRIO #: 4937220 I Page 7 of8 
Etoxazole [PC Code 10709l]Nalenr U.S.A. Corporation 

Tab le B.7.7.3.1-5. Resid ue Data from O ra nge P rocessing Study with Etoxazole. 

Commodity Plot Rcsiducs 1 (ppm)[Average] Processing Factor2 Median Processing 

Factor3 

Orange (RAC) 3 (5x) 0.188, 0.147 f0. 1681 -- Juice ND, ND·[<0.0 1] <0.06 

Dried pulp ND, ND [<0.01] <0.06 

Oil 3.85. 3.75 (3.80J 23x 

1 All values are the mean of duplicate analyses. ND= Nondetectable (<LOO). The LOO was 0.002 ppm, and the LOQ was 0.0 I 

ppm. Values between the LOD and LOQ arc reported in parentheses. Per trial averages were calculated by the study reviewer 

using the LOQ for values reported as <LOQ. 2 Processing Factor = [Measured residue for analyte in the processed fraction] I [Measured residue for analyte in the RAC]. NC = 

Not calculated. The processing factor could not be calculated because residues were below the LOQ in the RAC and the 

processed fraction. 3 Median processing factor for both plots and all sites. 

III. CONCLUSIONS 

The orange processing study is considered scientifically acceptable. In orange (RAC) harvested 

at a 14-day PHI in three trials conducted in Brazil reflecting two foliar broadcast applications of 

the 0.92 lb ai/gal (110 g ai/L) SC formulation of etoxazole at total rates of 0.178-0.180 lb a i/A 

( 199-202 g ai/ha; lx plot) and 0.888-0.904 lb ai/A (995-1013 g ai/ha; 5x plot), average residues 

were <0.01-0.033 ppm in/on samples from the lx plots and <0.012-0.204 ppm in/on samples 

from the 5x plots. Average residues in juice and dried pulp were below the LOQ (<0.01 ppm) in 

all samples from all plots and trials, and average residues in oil from the Ix and 5x plots, 

respectively, were 0.181-0.395 and 0.289-4.29 ppm. 

A comparison of the residues in/on orange (RAC) with those in each processed fraction indicated 

that residues of etoxazole concentrated in oil (median processing factor of >20x), but did not 

concentrate in juice or dried pulp (<0.3x). 

The observed processing factors do not exceed the theoretical concentration factors for citrus of 

3.3x, lOOOx, and 2x for peel, oil, and juice (based on separation into components; OCSPP 

860.1520, Table 3). 

An acceptable method was used for residue quantitation and adequate storage stability data are 

available to validate the employed intervals/conditions. 

REFERENCES 

D283737, J. Tyler, 31-Jul-2003 

EPA MRID #: 49372201 Page8of8