### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D . C . 20460

MEMORANDUM Date: 29

- September

- 20 15 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### Subject: Etoxazo le in/on Imported Oranges and Orange Oil. Summary of Analytical Chemistry and Residue Data. PC Co de: 107091 DP Barcode: 0424375 Deci s ion No.: 493877 Regi stration Nos.: not app li cable Pet iti o n No.: 4E8304 Regulatory Action: tolerances without a U .S. re gistration Risk Assess m ent T y pe: 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 (7509 P) 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 Che mS AC, per ChemSAC Standard Operating Procedures (SO P s).
S umm ary of Submitted/Rev iewed Residue C h emistry Studies

OCSPP G uid el in e Reference MRID No. 4937220 I. Breda. 0. (20 14 ). Magnitude o f the R es idu e of Et oxazo lc Following Application of 860. 15 00; 860. 1520 SMIT E on Orange, in Brazil. Report Numbers : 201400137 and Sl3-04 1l l. Unpublished study prepared by Valent U.S.A
. Corporation. 338 page s.

Page I of15Etoxazole Summary of Analytical Chemistry and Residue Data 0424375 TABLE OF CONTENTS
1. 0 EXECUT IVE SUMMARY
.. ... . .. .. .. .. .. . .. .. .. .. .. .................... .... .. .. .. .. .. ... . ... .. .. .. ... .. .. .................... .. ... .... .. .... 3 2 .0 RECOMMENDAT IONS
.. ... . .. .. .. .. .. .. .. . .. ....................... .. .. .. . .. .. .. .. .. .. .. .. ... . ... .. ... .................. ... ... ... ... ... ... .. 4

2.1 Data Deficiencie s/Data Needs
....... ........ ............................... . ... .............. ........................................... . 4 2.2 To lera nce Co n s id e rations
. ... . .. .................... .. .. . .. .. . ... . .. . ... . .. .. .. . ... ............................. .. ... ... .. .... ... ... ... ... ... 4 2
. 2.1 Enforcement Anal ytical Method
.................... .. . .. .. .. .. .. .. .. .. .. .. ... . ... .. ... .. .. ..................... .. ... .... .. 4 2
.2
.2 R eco mmended Tolerance s ...... ..... . ... . .. . .. .. .. . ... . .. .. .. . ... .. . .............................. .. .. .... .. .... .. .... ... .... . 4 2.2.3 Revision s to Petitioned-For Tolerances
. .. .. .. .. .............................. .. . ... ... .. .. ... ... ... .. .... .. ... ......... 4 2.2.4 International Ha rm o ni zation ............................................. .............. ...................................... . 4 2.3 Label Recom1nendation s ...................... .. . .. .. .. . .. .. .. .. . .. .. .. .. ........................... . ... . ... ... .. ... .. .... .. .... ............. 4 3.0 lNTRODUCTION
... .. .. ... . ... . ... . .. .. ... .......................... .. .. . .. .. . ... . ... . .. ... .. .. .. ...... .. .............................. ... ... ... .. 5

3.1 C hem ical Id e ntity
.. ... .. .. ..................... .. .. .. . .. .. .. . .. .. .. . .. .. .. . .......... ................... .. .. ... .. ... .. ... .. ... ... .... ............ 5 3.2 Phy s ical / Chemical Properties ... .. . .................... .. .. .. . .. .. .. . ... . .. .. .. .. .. .. .. . ... ...................... . .... ... .. .... ... ... ... .. 5 3.3 Pesticide Use Pattern/Directions
. .. .. .. . ... . .. .. .. . .. .. . .. ......... ............. ... . ... . ... .. .. .. ... .. ... .. ... .. .. .... .. ................. 6 4.0 METABOLISM/DEGRADATE RESIDUE PROFILE
... . ... . .. .. .. .. .. .. .. .. .. ........................ .. ... .. ... ... ... .... ... 6 5.0 RESIDUE PROF IL E
............................ ..... .......................................................... . .... ............. ... ... ........... 8

5.1 Residue Analyt.ica l Method s ................ .. .. .. . .. .. .. . .. .. .. . ... . ...... ..................................... ... .. .... .. .... ... ... .... .. 8 5.1.1 Data-C o llection Methods
.. .. . .. .. .. . .. .. .. .. .. . .. ................................. .. .. .. .. .... .. .. ... ... ... .. .................. 8 5.1.2 Food an d Dru g Adm ini stration (FDA) Multire s idue Methods (MRMs)
.... . ... ... ... .. .... ... ... ..... 8 5.1.3 To lerance-Enforceme nt Method
... . ........................ ................................................ ... ... .......... 8 5
. 1.4 Subm ittal of Ana l ytica l Referenc e Stand ards
.. .. .. . ... . .. .. ...... .. ... .. .. .. ... .............................. ... .... 9 5
. 2 Sto rage Stabi li ty ................... .. . .. .. .. .. .. . ... . ... . .. .. .. ............................................ .. .. ... .. .... .. .. ... .... .. .... .. .... ... 9 5
. 3 Residue Data
................ . ...................... .. .. .. . ...... . .. .. .. . .. .. .. . .. .. ... ..... .. .................................................. .. .. 9 5.3. I C rop Fie ld Tri a ls ..... .. . ......................................................... ................................ .... . ............. 9 5 , 3
.2 Mag nitu de of.tbe**~s due**  -Rotational Crops
.......................................... ... .. .... .. ... ... .... .. .... 10 5.3.3 Processed Food/ Feed
. .. : . .. .. . ... . .. .. .. . .. ................................................. . .... . .. .... .. ... .. .... ... .... ... .. 10 5.3.4 Meat, Milk , Po u ltry , and Eggs
...... .. .. . ...... ............................... . ............. ... ... ... . .... ... ... .. ..... .. .. 12 5
.4 Food Res id ue Profi l e .. .. .. .. . ... . ... . .. .. .. . ... . .. .. .. . .. .. .. . .. .. .. . .. .. .. . ... . .. ............................................... . ... ... ... . I 2 6.0 T OLERANCE D E RIVATION
................. .. . .............................................................. . .......... ................ 12
A TI A C H M ENT I: I NTERN ATION AL RESIDUE LIMITS
. . ...... . ... .. . ... . ... .. ... . ... .. ... .. ... .. ... ... ... ... .... .. .... .. 13 ATTACHMENT 2: OECD TOLERANCE CALCULAT IONS
.... . .. .. .. .. ... . ... .. .. .. ... .. ... . .... .. ... .. .... .. .... ... .... . 1 4 ATTACHMENT 3: CHEMlCAL ST RU CTURES
................................................................................... . 15

Page 2of 1 5Etoxazole Sum m ary of Analytical Chemistry and Residue Data 04 24375 

### 1.0 Exec utive S umma ry 

### Backg ro un d: Etoxazo l e [2-(2,6-difluorophenyl)-4 -[ 4

- ( 1 , l-dimethylethy l)

-2-ethoxypheny l]- 4,5- dihydrooxazole] is a contact acaric ide / ovicide that is currently registered 

### in the U.S. for the control of mites o n various raw agricultural commod iti es (RACs). Permanent tolerances have been estab li shed 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 al so been established for residues of etoxazole in fat (0.02 ppm) and li ver (0.0 l ppm) of ruminants and in milk fat (0.0 1 ppm). Val e nt ® U.S
. A
. Corporation has submitted a petition proposing tolerances, without a U.S. registration, for residues of etoxazo le i n/on o range , w hole fruit (0.08 ppm) and orange , oi l (1
. 8 ppm). 

### Proposed Use: Valent® submitted a translated copy of a Brazilian label (suspension-concentrate (SC); 110 g a i/L) which includes instructions for two broadcast fo l iar applications to orange trees at 89-99 g ai/ha ( 14-day pre h arvest interval (PHI ); retreatment interval ( RTI) is not indicated; see Tables 3.3
. 1 and 3.3
. 2). The Brazilian app li cation scenario i s supported by the avai lab le residue chemistry data. 

### Na ture of the R es idu e - Primary Crops/Ro tational Crops/L iv estock: Based on the availab le cotton , eggplant, orange , apple, poultry , and ruminant metabo li sm stu dies , HED concl uded that the residue of concern for to lerance e nforc ement in the proposed/registered primary crops and li vestock is etoxazo l e 

### per se . The residues of concern for risk assessme n t are defined in Table 4.0.1. An 

### adeq uate confined rotational crop study is also available. Based on these data, HED concluded that provided the total application rate is S 0.135 lb ai/acre , rotational crop restrictions wo uld no t be required
. For rates above 0.135 lb ai/acre , the Agency concluded that, without label re str i ctions , a new confined rotational crop study is requ ired; depending on the resu lt s of the confined study a field rotational crops study may also be required. 

### M a g ni tude of th e R es idue

- Proposed Crop: Th e number and geographical representation of the subm itted fie l d trial data are adequate. In addition , the petitioner submitted adequate orange processing data which indicated that the resid ues of concern concentrate in orange oil and reduc e in orange juice and dried orange pulp. All samp les were analyzed using adequate ly validated methods and sufficient storage stab il ity data are avai lable. Based on these fie ld trial and processing data, HED concl ud es that the tolerances li sted in Table 2.2.2. 1 , for residues of etoxazole 

### per se, are appropriate. A revised Section F is requested
. 

### Mag nitud e of tlz e R es idu e - Rotational Crops: Since the proposed use i s for an import to lerance, a discussion concerni n g the ma gn i tude of the residue in rotated crops i s unnecessary . 

### M a g nitud e of the Residue

- Lives to ck : Livestock to l erances for residues of etoxazo le are currently estab li s hed in/on mi lk fat (0.0 1 ppm); fat of cattle , goats, hor ses, and sheep (0. 02 ppm); and li ver of cattle, goats, horses and s h eep (0.01 pp m). The only feed commodity assoc iated with the current petition is dried orange pulp (roughage) whic h , based on revise d Table 1 (Jun-2008) , is only fed to ruminants (10% of t he diet). Based on an expected residue in dried pulp of < 0.048 ppm and s in ce the registered field com use res ulted in a 4.0-ppm stover tolerance (ro u g ha ge), HED concludes that the current petitio n does not alter the previous decisions concerning the magnitude of the residue in ruminants (D 385940, J
. Tyler, 23-Sep-201 1 ). S in ce there are no poultry or hog feed commod i t ies associated with the current petition (revised Table 1 ; Jun

-2008), a discussion co n cerning the magnitude of the res idue in poultry and hog is unnecessary . Page 3of 15Etoxazole Sum marv of Analytical Chemistry and Re sidue Data 0424375 

### 2.0 Recommendation s Provided the petitioner s ubmits a re v i se d Sec ti on F, HED concludes th at the res idue c h em i stry d atabase s upp o rt s the estab li shment of the perm a ne nt to l erances li ste d in Secti o n 2.2.2
. A hum an hea lth risk assessment is forthcomi ng . 

### 2.1 Data Deficiencie sfDa ta Nee d s None
. 

### 2.2 Tolerance Co n s ideration s 2
. 2.1 Enforcement Ana lytica l Method Ade quate methods (gas chromatograph y / mass-selective detector (GC/MSD) or GC/nitro ge nphosphorus detector (N P D)) are availabl e for e nforcing the current p lant and li vestock tolerance s including the curre ntly established tangerine tol erance ( 0303628 , 

### J. Tyler , 30 -Mar-2005). Based on the similarity of tangerines and oranges , HED conc ludes that the current to lerance -enforcement methods are adequat e to enforce the tolerances recomme nde d herein. 

### 2.2.2 Recommended Tolerances Tab l e 2
. 2
. 2 .1 i s a s umm ary of the proposed and H ED- reco mmended tolerances fo r res idu es of etoxazo le 

### per se. A rev ise d Sectio n 

### F is req ues ted. T ab le 2.2.2. 1 : To lera n ce S umm a r y. Pro po sed HEDCommodity Recommend ed Co mment s Tolerance ( ppm ) Tolerance ( ppm )' 4 0 CFR I 80.593(a) orange . whole fruit 0.08 0. 10 The commodity definition s h o uld be "o ran ge .. and a tol eran ce of 0. 10 ppm recommended to harm o ni ze with the Codex MRL. T h e commodity definition s hou l d be "c itru s. o il. " Based on the o ran g e orange , oi l 1.8 1. 0 RA C HAFT of 0.048 ppm and the m ed i an orange oil proce ss in g factor or 20x. a tolerance of 1.0 oom i s recommended
. 1 Tolerance without an U.S. r eg is tration. 

### 2.2.3 Revision s to P etitioned-For Tolerance s See the comments co l umn of Table 2.2.2 .1
. 

### 2.2.4 International Harmonization There ar e no Canad ian or Mexican ma ximum r es idu e limit s ( MRL s) in/on the p ro pose d commodit ies (see Attac hme nt 1). T he re is a Codex MRL fo r r esid ues in/on c i tru s (0. 10 pp m)
. A lt hough th e Organization for Economic Co

- operation and Deve lopment ( O EC D ) to lerance -calculation procedure indicated that a 0.08-ppm tolerance for residues in/on orange is appropriate , a tol erance for re sidues in/on orange of 0.10 ppm is recommended for purposes of harmonizati on. 

### 2.3 Labe l Recommendation s None

Pa ge 4of15Etoxazo le Summary of Analytical Chemistry and Residue D ata 0424375 

### 3 .0 Introduction 3.1 C hemic a l Ide n tity 

### The chemical struct ure and nomenclature of etoxazol e is presented in Table 3. 1.1.
Tab le 3. 1
. 1 : S tructur e and No m enclature of Etoxazole.

Compound

Common name etoxazole Co mpany experim e nta l nam es S -12 83, V-1283, Y l-53 0 1 IU PAC name ( RS) -5- tert-buty 1-2-(2-(2 ,6

- d in uorophen y 1)-4 , 5

- d ihydro- 1 , 3

- oxazo 1-4-y I] ph e ne to le CAS name 2-(2,6-ditluorophenyl)-4 -[ 4- ( I , I -dimeth y lethy l ) -2-etho xy phen y l]-4 , 5-dihydrooxazole CAS# 153233

- 91-1 

### 3.2 Phys i ca l /Chemica l Properti es 

### Table 3.2.1 is a summary of the phys ical/c hemical properties for etoxazo le . Etoxazo le ha s a lo w water so lubility and a high Log 

### Ko w. Tab l e 3.2.1: P h ys icoc h c mi ca l Properties of Etoxazo le (TGAI). Melting range 1o1.5- 102.5 °C pH 6.2 Density 1 .2389 g/ cm 3 3.99 x 1 0 · 5 g/L at 1 0 °c Wa t er so lubility 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-dichloro ethane: 402 46018505.der.wpd So lve nt so lu bi li ty (g/L a l 2 0"C) et h y l acetate: 249 n-heptane: 1 8. 7 methanol: 10 4 xy l e ne: 252 Vapo r pre ss ure at 25 °C 7.0 x Io ·6 pascal s Di ssoc iation constant (pK.} no measurable pK. Octano l / water partition coeffi c ie nt Log( K ow) 5.52 ± 0.58 at 20 °c UV/v i s ibl e absorptio n Not avai labl e .

Page 5of 1 5Etoxazole Su mmary ofAnalvtical Chemistry and Re sidue Data 0 424375 

### 3.3 Pe s ticide Use Pattern/ Direction s Va le nt® submitted a trans lated copy of a Braz ilian labe l which includes in s tructions for application to ora nge trees. Table 3
. 3. l i s a s umm a ry of the end

- use product s and target pest s and Table 3.3.2 is a s ummary of the Brazil ian orange application sce n a ri o. The Brazilian application scenario is s upported by the available re s idue chemistry dat a . T a bl e 3.3. 1 : S umm ary o f E nd -Use Prod u ct. Trade N ame 

## I Co ne . 

## I Fonnulation 

## I Label Date 

## I Tar g et Cro p s 

## I Targ et Pe s t s Smite (Brazilian label) 

## I 110 g aifL 

## I SC 

## I not provided 

## I oran g e tree s l nat mite (T e tr

a 11

yc l111 s urt icae) Table 3.3 .2: S umm ary of B ra z i li a n Orange App l icatio n Sce n a ri o.' App. T imin g: S in g le App. Max. # App. Max. Seaso na l PH I Type; and Equip. Formu l ati o n Rate: g ai/ha per Sea s on App. R ate: g a i / ha (day s ) U s e Directions and L imit ati o n s ( lb ai/ ac re) ( l b ai / ac r e) -Lab e l indicates a spray s oluti o n o f 45 m l/ JOO L( 4.95 g ai / 100 L ) be g innin g of - s pray volumes arc 1800

- 20 00 L n 1a ( 192- infe s tation: broadc as t SC 89-99 198 2 14 gal/acre ) : 5

- 10 U trcc ( 1.3-2 .6 gal/ tr ee) foliar s pray using a ( 110 g a i/L) (0
. 08

- 0.09 ) 2 (0. 18) 14 -R T I i s not s pecified: label indi c ate s that Turbo Atomizer etoxazo l e s hould be applied at the be g inning of infestation when the juvenile form s of the pest are pre s ent (ct ox azo l e doc s no t co ntrol adult mites) 1 The label s pecifi es ''c itru s (oranges )." 

### 4.0 M etabo li sm/ De g r a d a te R es idu e Profil e Tab l e 4.0.1 and the fo ll owing tex t are summaries of the residues of co ncern in plants (primary and rotational crops), pou l try, and ruminant s . See A ttachment 3 for st ru c tures. 

### Prima ry Crops: Th e qualitative nature of etoxazo le re s idue s in plant s is adequately understoo d based upon the metaboli s m s tudies on cotton , eggp lant , app le , and oran ge . 

### In each of th ese s tudi es, the major 14 C-res idu e in / on various matri ces was identified as parent co mpound. B ased on the metabolite profi l es observed in these studies , etoxazole may und e rgo photo-oxidation to yield Metabolite R-1 3. Parent and Metabolite R-1 3 then undergo op e nin g of the oxazole rin g to form a v ariety of meta b o lite s ( R-4 , R-7 , R-14 , and R-3) , and subsequent c leavage of the opened rin g forms M e tabo li t es OFB , R-8 , R-10 , R

- 11 , R-1 2 , and R-15 ( 0 283737 , J. Tyler, 3 1-Jul- 2003 ; 0 3 03628 , J
. T y ler, 30-Mar

- 2005; D307 I 78 , J. Ty ler , 6-Apr-2005). Ba sed on these data , the HEO Metaboli s m Assess m e nt Review Committee (MARC) concluded that t h e re s idue s of concern, for toleranc e e nforcement and ri s k assessmen t , are as defin e d in Table 4.0.1. 

### Livestock: The qualitative nature of etoxazole r esid ues in li vestock is und e rs tood based upon th e adequate goat and pou ltry metabo l ism studies (0283737, 

### J. Ty le r, 3 l-Jul-2003 ; 0 289666, 

### J. Tyler , 17-Jun-2003). A lth ough li vestock in both s tudie s were dosed at s imilar dietary level s ( 8- 16 ppm) for

- 4 da ys , absorption and accumulati o n was considerably g reate r in hens than in the go ats. D ata from the poultry s tud y suggest th e p o t en tial for bioaccumul ati o n of parent in eggs and fat ; w hereas, in th e goat metabolism study , th ere was no indication of 14C -r es idues accumulating in fat o r milk. Th e residue data fro m the ruminant feeding s tud y contradicts th e go at metaboli s m st ud y in that residues do app ea r to accumulate in milk 

### fat and fat. Due to it s high octanol/water coefficient 

### (Kow), etoxazo le would be expected to concentrate in 

### fat. Pa ge 6of15Etoxazole Summary of Analytical Chemistry and Resid ue Data 0424375


### In the poultry metabolism study, etoxazole was identified as the principal residue in each commodi ty, with the exception of liver, in which Metabolite R-16 was the major residue. Based on the metabolite profile in eggs and tissues, th e primary route of metabolism in poultry involves the oxidation of the tert-butyl 

### group to produce either an alcohol (Metabo li te R-2) or an acid (Metabol ite R-16) metabolite. Hydrolysis of the dihydrooxazole ring in parent and Metabolite R-16 produced Metabolites R-7 and R

- 7-C0 2 H , respectively , and further hydro lysis of the ester bond produces Metabolites R-8, and R-11. Dihydroxazole ring hydro lysis 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 dihydrooxazo l e ring and ox idation 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 4

### C-tert-butylphenyl]-etoxazole to bare sandy loam soil at 0.099 and 0.097 lb ailA, total radioactive residues were <0 .005 ppm in all commodities harv es ted 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 avai lable data would support maximum seaso nal rates up 0.135 lb ai/ A without the need for additio nal data or rotational crop restriction s, 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)
. Tab le 4.0. J: Summary of Metabolites a n d Deg r adates of Concern for Risk Assessment and Tolerance Enforceme n t. Matrix Residues of Concern Risk Assessme nt Tolerance Enforceme nt primary crops - except cotton gin byproducts and almond hull 1 ctoxazolc Primarv crops - cotton gi n byproducts and a lm ond hull ' etoxazole and R-3 poultry tissue (except li vcr)2 etoxazo l e etoxazolc c22 and poultry liv er etoxazole and R-16 milk and ruminant muscle/ fat 2 etoxazole ruminalll liver /kidnev2 etoxazole and metabolite I waler' etoxazo le, R-8 , and R-1 3 

## -- rotationa l croos 4 no decision no decision 1 0283 737, J. Tyler, 3 1-Jul-2003; 0303628 , J. Tyler, 30-Mar -2 005; 0307178. J. Tyler, 6-Apr-2005; 0289666 , J. T y l er, 17-Jun-2 003. 2 0283737. J
. Tyler. 3 l-Jul-2 003: 0289666 , J. Ty l er. I 7-Jun-20 03; 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.

Page 7of15Etoxazo le Summarv of Analvtical Chemistrv and Residue Data D4 24375 

### 5.0 R es idu e Profil e 5.1 Res idue A nal y tical Methods 5.1.1 Data-C oll ec ti o n Method s T he field trial and pro cessi ng s amples were analyzed for residues of etoxazole using a highperformance liquid chro matograph y with tandem mass spectrometry detection (LC/MS/MS) method adapted from two QuEChERS multiresidue methods and Valent Method RM

- 37HM. Acceptab le method validation and concurrent recoveries were reported for samples of orange fort ifi ed with etoxazole at 0.01-0.50 ppm, for samp les of juice and dried pulp fortified at 0.0 I ppm , and for samp les of oi l fortified at 0.01-7.0 ppm , thus va lid atin g the method
. The limit of q uan t itation (LOQ; determi ned as the lowest li mit of met hod valid ati o n) was 0.0 I ppm for all matrices (limit of detection (LO D ) was 0.002 ppm). The fortification l evels used 

### in concurrent method recovery were adequate to bracket expected re sidue levels. Concu rrent recoveries and residues in treated samp les 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 acetonitri l e (ACN) fo ll owed by the addition of 5 M NaO H and a salt mixture of anhydrous MgS04, NaC l , tri so dium c itrate dihydrate , and hydrogen disodium citrate ses quihydrate. The mixture was stirred then ce ntrifu ged, and an a li quot of the extract was di luted with ACN containing 0.1 % acetic acid for LC/MS/MS ana l ys is. For oil, the sample was adjusted to pH 2:: 8 by the addition of 5 M NaOH then combin ed with ACN saturated with hexane. The salt mixture was added, and the mixture was centr i fuged. F ollowing phase sepa ration, the organic phase was co mbined with an Eppendorf salt mixture of anhydrous MgS04, and primary-secondary amine (PSA) sorbent and centrifuged. The resulting s upernatant was subjected to LC/MS/MS analy sis. 5.1.2 Food and Dru g A dmini stration (F D A) Multires idu e Methods (MRMs) FDA MRMs may be us ed to determine residues of etoxazole in fatty and non-fatty matrices and to determine residu es of Metabolite R-3 in nonfatty matrices. Etoxazole was completel y recovered from fortified samples of apple usi n g Methods 302, El with GC/NPD or Method 303, C l or C2 w i th GC/N PD
. 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 u s ing GC /NPD. However , matr i x interferences e nh anced the recoveries of R- 3 from gin byproducts. The res ult s of the MRM testing were forwarded to the FDA fo r inclu sio n in the Pesticide Analytical (PAM) Vol. I 

### (02909 1 9, J. · Tyler, I 7-Jun-2003). 5.1.3 Tolerance-Enforcement Method Adequate method s (GC/MS D or N PD ) are ava i lable for enforc i ng the current plant and livestock tolerances includ ing th e curre ntl y established tan gerine tolerance (0303628 , J. Tyler, 30-Mar2005). Based on the sim ilari ty of tangerines and oranges , HED concludes that the current tolerance enforcement methods are adequate to enforce the tolerances recommended herein.
Page 8of15Etoxazole Summary of Analvtical Chemistry and Residue Data 0424375 

### 5
. 1.4 Submittal of Analytica l Reference Standards The EPA National Pesticide Standards Repository has an etoxazo le analytical standard with an expiration date of22-Aug-2017 (emai l from G. Verdin; Biological Economi c Analysis Division; 7-May-2015). 

### 5.2 Storage Stability Table 5.2. l i s a summary of the maximum storage intervals for samples between harves t/p rocessing and extraction (samples were analyzed within 1 day of extraction). Previously submitted storage stabi li ty data indicate that etoxazole i s 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 valid ate the storage intervals/conditions for the field trial 

### and process ing data submitted as part of the current acti on.

Tab le 5.2.1: S ummary of Storage Conditions. Matrix Storage Maximum Interval of Demonstrated Storage Stability Temp. ( 0 C) Storage Duration 1 orange (RAC) 27 days Previously submitted storage stab ility data indicate that e to xazole is stable at -20° C for at l east 3.5 months in apples, 2 months in strawbe rri es, 6 month s in orange pulp, orange juice and dried pulp :S -18 IO days 12 months in orange peels, 17 months in cottonseed, and 6 month s in cotton gi n byproducts (D283737, J. Ty l e r, 31- orange oil 14-20 days Jul-20 03). These data are adequate to validate the storage interval s/ conditions employed as part of the current st ud y. 1 Interval from harvcst/processrng to extracti on. Samp l es were analyzed within 0 -1 day of extracti on. 

### 5.3 Re s idu e Data 5.3.1 

### Crop F ield Trials 493 7220l
. der1 Field trial re s idu e data were submitted from 11 field trials conducted in Brazil during the 2013 growi ng season (see Tab le 5.3.1
. 1 and the paragraph below for a summary of these data). The trials were conducted using th e proposed application rate and employed an adequately validated analytical method (storage intervals were a l so validated). Based on th e Section B submitted as pa.it of the cur rent petition , etoxazole is only registered for application to oranges grown in Brazil. Based on thi s and based on information concerning the sources for o ran ges 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: Fie l d trial residue data were submitted from 11 field trials conducted in Brazil during the 20 1 3 growing season. Each trial site cons isted of one untreated plot and one treated plot with the treated plo t receiving two broadcast airblast applications of a 110 g a i /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 we re harvested at a PH I of 14 days. In two tri als, add ition al samples were Page 9 of 15Etoxazo l e Summarv of Analvtical Chemistry and Residue Data 0424375 harvested at PH l s of 7 and 2 1 d ays to inves ti gate residue decline. Residu es (and per-trial ave rages) of etoxazo le in/on th e o ran ge RA C sa mpl es were < 0.01-0 .0 53 ppm (< 0.01-0.048 ppm ). In the res idue-decline trial s, res idu es decreased with increa s ing PHI in one trial. In the sec ond trial, residues d ecli ned af te r th e 7-day PHI , but were hi gher at the 2 1-day PHI than at the 14-day PHI. An acceptab le me th o d was u se d for re s idue quantitation and adequ ate sto r age stability data are available to valid ate th e emp l oyed in terva ls/ co nditi o n s. Table 5.3.1. 1 is a summary of t h e field trial residue data.

Table 5.3.1.1: S umma r y of Re s idues fr o m Oran ge Fie ld Trials with Etoxazo l e.

Crop Matrix Total Application Rate PHI n ' Etoxazolc Re s idues (ppm) ( lb ai /A) L g ai/ha] (days) Min. 2 

### I Max. 2 

### I LAFT3 

## I HAFT3 

### I Median 3 

## I Mcan 3 

## I SD 3 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 tri a ls. 2 Values based o n to t a l number of samples. 3 Values based on per-trial averages. LAFT =lowest average field trial. HAFT= hi ghest ave rage field trial. SD= standard deviation
.

Tabl e 5.3.1.2: Trial N u mb e r s and Geograp hi cal Loca t i on s . Country Oranges Submi11cd Requested ' Brazi l 11 2 8 Mexico 

## -- 4 Tota l 11 12 1 T he requested number and geograph ic d1stnbut1on of field trial s for oranges. accord m g to the NAFTA Guidance Document on Data Requiremen ts for Tolerances on Imported Commodi ties in the United States and Canada 12/0 5 and import data (h11p: // ageconscarch.umn.cdu/handle/l I 9741 and hllp: //apps.fas.usda.gov/ gat s/ default.as px). All countries (in which the pe s ticide is marketed or intended to be marketed) must be repre se nted if the amount that they export to orth America repre se nt s 5 % or more of imports of the subject crop into an y of th e country in which a tolerance is bein g so ug ht 2 The trial count renec ts four pairs or groups of trial s se paraicd by <20 miles that H ED has determined to be replicate trial s. 

### 5.3.2 Magn itude of the Res i due

- Rotationa l C rops S inc e the propo sed u se is for an import tol e ranc e in/on orang es and orange oi l , a discussion con c erning the ma g ni tude of the residu e in rotated cro p s is unnece ssa r y . 

### 5.3
. 3 P r ocessed Food/Fee d 4937220 1.de r2 As part of the curr ent request , the petitioner s ubmitted an orange proce ss in g study (4937220 1.der2) depicting the ma g nitud e of e to xazo le residues in/on o ran ge dried pulp , orange juice, and oran ge oil following retreatment at I x and 5x the Braz ili an app li cati o n rate. The r es ultin g data indi ca te that res id ues decreas e d in o r a n ge juice (0.9- < 0.0 5x) a nd dri e d pulp (0.9- < 0.5x) and increas ed in orange o il (7.4

- > 25x). Th ese d a ta are s ummari zed in th e paragraph below a nd Table 5.3.3. 1. No additio na l processing data are r eq uired. 49372201.der2: Orange processing data were subm itted from three trial s con du cted in Brazil during the 2013 growing seaso n. Each trial s ite co n s isted of one untreated plo t and two treated p lots w ith the treated plot receiv in g two broadcast airblast applications of a 110 g ai/L SC etoxazole formulation. At the first plot , applications were made at 99-101 g a i /ha ( l.Ox) for a total ap plication rate of 199-202 g a i / ha (1.0x) , and at the seco nd plot applications we re made at 495- Pa ge 1 0of 15Etoxazole Summary of Anal y tical Chem istrv and Residue Data 0424375 

### 509 g a i /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 vo lumes of2022-2037 L/ha ( no adjuvant was used). Oranges were harvested at a PHI of 14 days and we re processed into juice , dri ed pulp , and oi l using s imulated commercial practices. Processing was conducted at JBT FoodTech (Araraq uara , S P Brazil). Res idues of e toxazole were < 0.01

- 0.033 ppm inion RAC san1p les from the lx plo t s and < 0.012-0.204 ppm inion RAC saniples from the 5x plots. Average residues in j u i ce and dried pu lp were below the LOQ (<0.0 1 ppm) in al l samp les from all plot s and trials , and average residu es in oil from the Ix and 5x p lots , respectiv ely, were 0. 1 8 1-0 .395 and 0
. 289-4.29 ppm . A co mparison of the residues in/on orange (RAC) with those in each processed fraction indi cated that residues of etoxazole concentrated in oil (median process in g factor of > 20x), but did not concentra te in juice o r dri e d pulp (<0 .3 x). T he observed processing factors do not exceed the theoretical concent ration facto rs for citrus of 3 .3x , I OOOx, and 2x for peel , oil , and ju i ce (based o n separation into co mpon e nts ; OCSPP 860
. 1520 , Table 3). Table 5.3
. 3. 1 i s a summary of the processing data
.

Table 5.3.3.1 : R es idu e Data from Oran ge Processi n g Stud y w ith Etoxazo le. Commod ity Ra te Residues ' (p pm ) [A ve r age] Processing factor2 Median Pro cess in g Factor3 Limeira, S P , B raz il ; 2013 (Sl3-04 11 l -0 1) Orange (RAC) 0.022, 0.031 (0 .027] 

## -- -- Juice ND , ND [< O.O lj < 0.4x < 0.3x Dried pulp I x <0.4x <0.3x ND. ND [<0.01 ] Oil 0.383. 0.407 (0.395 ] 15 x > 20 x Orange (RAC) 0. 1 94, 0 .214 [0.204] 

### -- Juice ND, N D ( <0.0 1) < 0.05x n ot a pplicabl e Dried pulp 5x ND, ND [< 0.0 1 ) <0.05x Oi l 4.51 , 4
. 07 (4.29] 21x Sa n to Antonio d e Po sse, SP , Brazil ; 2013 (S l 3

- 041 I l -02) Orange (RAC) (0.007), (0.00 8 ) f < 0.0 1] 

### -- Juice ND , ND [ <0.01) <0.3x Dri ed pulp Ix ND, ND [ <0.01) <0.3x Oi l 0.18 1 , 0
. 1 80 [0. 1 8 1] > 18x not a pplicabl e Orange ( RA C) (0 .00 4), 0 .01 3 [ <0.012) 

### -- Juice ND, ND [< 0.0 1) 0.9x Dri ed pulp 5x ND , N D [<0.01 ) 0.9x Oil 0 .282 , 0.296 [0.289) > 25x Limeira , S P , Brazil; 2013 (Sl3-04 11 I-03) Orange ( RA C) 0.031 , 0 .035 [0.033] . . Juice ND, ND f <0.0 1] <0.3x Ix ND , ND f < 0.0 1] <0 .3 x Dried pulp Oi l 0.235. 0.25 1 [0.243) 7.4x not applicable O range (RAC) 0. 1 88. 0.147 (0. 168) 

### .. Jui ce ND , N D [ <0.01] <0.06 Dried pulp 5x N D , N D [ <0.01) < 0.06 Oil 3.85. 3.7 5 [ 3.80 ] 23x 1 A ll values are th e mean of duplicate analyses. ND = Nondetectable (< LOO). T he LOO was 0.002 ppm, and the LOQ was 0. 0 I ppm. Valu es between the LOO and LOQ are r epo rted in parentheses. Per tria l averages were calculated by th e s tud y rev i ewe r using the LOQ for values re ported as < LOQ. 2 Proce ss in g Factor= [M easured resid ue for analyte in the processed frac tion] I [M eas ured residue for analyte in the RAC]. NC =No t calc ul ated. The processing factor co u l d not be calcu l ated because re s i d ues were be l ow th e LOQ in the RA C and th e processed frac ti on. 3 Median process in g facto r for both plots and a ll s ite s. Page 1 1 of 15Etoxazole Summary of Analvtical Chemistry and Residue Data 0424375 

### 5.3.4 Meat, Milk, Poultry , and Eggs Livestock to lerances for r esi dues of etoxazole are currently establ i shed ini o n milk fat (0 .01 ppm); 

### fat of catt le, goats, horse s, and she ep (0
. 02 ppm) ; and li ver of cattle, goats, hors es and sheep (0.0 l ppm). The only feed commod ity assoc iated with the cur rent 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 conc ludes that the current petition does not alter the previou s decisions concerning the magnitude of the residue in ruminants (0 385940, J. Tyler, 23 -S ep -2011). Si nce t he re are n o poultry or hog feed commodities associated with the current petition (revised Table 1; Jun-2008) , a discussio n concerning the ma g nitud e of the residue in poultry and hog is unnecessary. 5.4 Food Re s idue Profil e 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 , EFE O indicated that etoxazole appears to have a high potential to bioaccumulate (Sl 

### 600x for edible ti ssues; 0311941 , J. Melendez , 3 l

- May2005); based on this assessment, HED in c lud ed residues in fish/shellfish in the dietary exposure analysis (D426228, T. B loem, 29

- Sep-2015). 6.0 Tolerance Derivati on The petitioner has submitted adequate magnitude of the residue data to support the establishment of tolerances i nio n imported o range commodities. No additi onal 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 o f etoxazole 

### per se inion orange is appropriate. However. HED is recommending for an orange tolerance of0.10 ppm to harmonize w ith the currently-established Codex MRL (Canad ian and Mexican MRLs are not established). HED is also recommending for an orange oil to le ra nce of 1. 0 ppm based on the HAFT for oranges (0.048 ppm) and the median o range o il processing factor of 20x , (tolerances inion orange juice and dried pu lp are unnece ssary). Tab le 6.0. I 

### is a s ummary of the proposed and HEO recomm e nd ed to lerances. A revised Section Fis requested. Tab le 6.0.1: Tolerance S umm ary. Commodity Proposed HED-Recommended Co mments Tolerance ( ppm) Tolerance (ppm) 1 40 CF R 180.629(a ) o ran ge, whole fruit 0.08 0. 1 0
orange . oil 1.8 1.0
1 Tolerance wtthout an U.S. re g 1 strat 1 on. 

### Attachment l: International Residue Limits. Attachment 2: OECO Tolerance Calculations
. Attachmen t 3: Chem ical Structures ROI: RA B I C hem ists (25-Mar-2014) T he commodity definiti o n sh o uld be "orange
.. and a toleran ce of 0. 1 0 loom recommended to harm o ni ze with the Codex MRL. The commodity definition should be "citrus. oi1:· Ba se d on th e.: orange RAC HAFT of0.048 ppm an d the median orange oil [processin_g factor of 20x. a t o l erance of 1 .0 ppm is recommended.

Page 12of15Etoxazole Summarv o f Analvtical Chemis t rv and Residue Data 0424375 

### A ttachment 1: Inte rnat i o n al R es i d u e Lim i ts. 

### Intern atio n a l R e s id u e L im its: Eto xazo le ( 10 7 09 1)

S u mma ry of U S and International To leranc es a nd M ax imum Res id ue Lim its Re s idue Definition 

## us Canada Mexico2 Codex Etoxazole

- 2

- ( 2.6-dinuorop hen y l)-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 so luble
. Tolera nce/Maximum R es idue Limit (ppm) Commodity 1 

## us Canada Mcxico 2 Codex oranges 0.08 0
. 1 c itru s fruit s orane.e. oil 1.8 Co mpleted: M
. Neg ussie: 03 / 17115



### .. 

## - 1 Includes only commod1t1e s of intere s t for th is action. Tolerance value s are l-I E D recommenda ti ons an d no t t hose p r oposed by the ap plicant. 2 Mexico adopts US tol erances a nd/o r Codex MRLs for its export purposes.

P age 13of 1 5Etoxazole Summarv of Analytical Chemistrv and Residue Data 

### Attachment 2: OECD Tolerance Calcu lations. Compound Crop Region I Country GAP Total number of data (n) Percentage of censored data Number of non-censored data Lowest residu e Highest residue M

edian res idue Mean Standard d evi a tion ( SD ) Correction factor for censorin g {CF) Proposed MRL estimate

- High est 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

P age 14of15 * 04 24375Etoxazole Summary of Analytical Chemistry and Residue Data 

### Attachment 3: C hemical Structures Common name / (code)

Etoxa zo le ( S-1283)

R-3

R-16

Metabolite I

tB Ur5 Chemical name
2-(2,6-difluorophenyl)-4-[4-( I , ld imethy l ethyl)-2-ethoxyphenyl)-4,5- dihydrooxazole

N-(2,6 -difluorobenzoy l)-4-tert -butyl-2- ethoxybenzamide

2

- methyl-2-{3-ethoxy-4-[2-(2,6- difluorophenyl)-4 ,5 -d ihydro- l ,3-oxazol4-y l] pheny l }propion ic acid

2-am ino-2- (2 -ethox y -4- ( I'

- hydroxycarbonyl-1 '- m ethy leth yl)p hen yl) ethanol

Page 1 5of 15 0424375Etoxazote [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. (20 14) Magnitude of the Residue of Etoxazole Following Application of SMITE on Orange, in Brazil. Report Numbers: 201400137 and S13 -041 l l. 

### U npubli s hed study prepared by Valent U.S.A. Corpo ration. 338 p. 

### Guidelines: -EPA OCSPP Harmonized Test Guideline 860.1500 Crop Fie ld 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 Re sidue Chemistry Crop Field Trial Requirements -OECD Guide lin e 509 Crop Field Trial (September 2009) 

### GLP Compliance: No deviati on s from the EPA regulatory requirements we re reported w hi ch wou ld have an impact on the validity of the study. 

### Acceptability: The st ud y is considered scientifi cally acceptab l e. The acceptab ili ty 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: T hi s Data Eva lu a tion Record ( D E R) was ori g inall y pr e p a red und er contra ct by V e rsa r. In c . ( 685 0 Ve rs ar Ce nte r, Sp rin g fi e ld. VA 2 2 I 51 ; s ubmit t ed 2 7

- Fe b

- 2 0 15. Th e D ER has bee n rev i e wed by I J ED and rev i s ed to re n ec t curre nt O ffic e o f Pes ti cide Pro g ram s ( OPP) po lici es. 

### EXECU TIVE SUMMARY Valent U .S.A. Corporation has s ubmitted field tri al data for etoxazo le on orange from 11 field trial s conduct e d in Brazil during the 2013 growing season . The above trial count reflects four pair s or groups of trials separated by <20 miles that HED has determined to be rep licat e trials. Each trial site consisted of one untreate d plot and one treate d plot. At each trial locatio n , the treated plot received two fo li ar broad cast ap plic ations of a 0
. 92 lb ai / gal (1 10 g ai /L) s uspension

concentrate (SC) formu lati on of etoxaz ole (Smite) at 0.088-0.093 lb a i/ A/app lic atio n (99-104 g ai/h a/application) for a total application rate of 0.178-0.186 lb a i / A (199

- 208 g ai/ha). Applications were made at retreatment interva ls of 29-31 days using ground (airb last) equi pment in spray volume s of215-221 gal/ A (2013-2063 L/ha). No adjuvant was used. The peti ti oner note d t hat in on e trial (03) a product containing etoxazo le was applied as a maintenance che mi ca l to the crop (rate was not spec ifi ed). Oranges were harvested at a preharvest interva l ( P HI) of 14 days . In two trials , additiona l samp les were h arvested at PHi s of 7 and 2 1 days to investigate re s idue decline.

EPA MR!D # : 49 3 72201 Page I of8Etoxazole [PC Code I 07091 ] N alent U.S.A. Corporation 

### All samples were maintained froze n at the testing fac ili ty , during shippi ng , and were stored frozen at the analytica l laborato r y until analysis. The maximum storage interval for samples between h arvest and an alys is was 27 days (0.9 months). Samp l es were ana lyzed on the day of ex t raction. Prev i ous ly s ubmitted storage stab ility data indicate that etoxazo l e is stable at
- 20°C for at least 3.5 months in app les, 2 months in strawberries, 6 months in o range 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 w ith tandem mass spectrometry detection (LC/ MS/MS) u s in g a meth od adapted from two QuEChERS mu ltiresi du e methods and Valent Method RM-37HM. Acceptable method va lidation and co ncurrent recover ies were reported fo r sam ples of orange fort ifi e d with etoxazole at 0.01-0.50 ppm, thu s va lidating the method. The li mit of quantitation (LOQ; determined as the lo west l evel of method validation, LLMV) was 0.01 ppm. The fortification levels used in concurrent method recovery we re adequate to bracket expected residue levels. Concurrent recoveries and residues in treated samples were not corrected for residues in co ntro l s. In o ran ges harvested at a PHI of 14 da ys followi ng two fo liar broadcast applicat ion s of the 0.92 lb ai/gal SC form ul at ion, residues (and per-trial averages) of etoxazo le were < 0.01-0.053 (< 0.0 1

- 0.048) ppm. A lthoug h relatively high res id ues were observed i n Trial 03 , which reflected appl ication of a maintena nc e pro du ct containing etoxazole (rate was not specifie d) , the residu es we r e well within the range of observed residues. In the residue decline tria ls , res idues decreased with increasing PHI in one tri al. In the second trial , residues declined after the 7- da y PH I, but were higher at the 21-day PHI than at the 14-day PHI. I. 

### MATERIALS AND METHODS A. MATERIALS

T ab le B. 7.6. 1.1

- 1. No m e ncl a ture fo r E to xazo lc. Com m on n a me e tox azol e Id entity 2- ( 2.6-difluoropheny l)-4-(4- ( I. l-dim e th y le th y l }- 2- e th ox yphen y l]-4.5-dihy droox azo lc CAS no. I 53233-91

- I Co mpan y experimenta l nam e V- 1 283 Other sy non y ms (if applicab le) S- 1283 OC. H ,

# (C**,l «~** 
F -vEPA MRJD # : 49372201 Page 2 of8Etoxazo l e [PC Code 10709 1) Nalent U.S.A. Corporatio n 

### B. Study Design 1. 

### Test Proced ure A total of 11 re s idue trial s in/on orange we re conducted in Brazil with a 0.92 lb ai/gal (110 g ai /L) SC fo rmulation during the 2013 growing season. Th e trial s separa ted by <2 0 mile s hav e been assesse d for independenc e as detail ed in the tabl e below. HED has de termined that four pairs or gro up s of trial s constitute sing le trial s w ith replicate sam ples for purposes of OCSPP 860
. 1500 data requiremen t s . Field trial location s are summarized in Tabl e B.7.6.1.1-2. Locations and deta iled use patt erns for th e trials are provided in Table B.7
. 6
. 1
. 1-3.
In depende nt T ri a l Determination' Tria l Nos. D ifferences Decision 01. 03,04,05.06 , 07: VaricN: 0 1 and04: Repl ic ates (Same Location) 0 1 and04: Valencia 05 a nd 06: Repl icates 05 and 06: Pera M urch a 03 a nd 07: Separate due to variety 03: Pera Coroa 07: Rubi 02 and 08 Vari ety: Separate d ue to varie t y (<20 miles) 02: Fo lh a Murcha 08: Pera Coroa 10 and 11 Varie tv: Replicates (Same location) Both Va l encia 12 and 16 VaricN: 1 3, 1 4, 1 6: Replicates (Same location) 1 3, 14
. 16: Valencia 12 and 15 : Separate due to vari ety 13 , 14, 15 12: Pera Rio (Same loca tion) 15: Rubi 1 A ll assessments are based on the replicate trial guidance presented in draft memo 568
_ Critcria for Ind ependence ofTrials 04 / 23 / 2013 (EPA and PMRA).

Tab l e B.7.6.1.1-2
. Tria l N umb e r s and Geograph ical Location s. Country Oranges Submitted R eq uested' Brazi l I 1 2 8 Mex ico 

## -- 4 Total 11 12 1 T he requested number and geograph ic distribution of field trial s for oranges. according to th e NA FT A Guidance Document on Data Requir eme nt s for Tolerances on Imp orted Commodities in the United States and Canada, 12/ 05 and import data (http: //ageco n search.u mn.edu/lumd l c/ 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 m arketed) mu s t be represe nted if the amount that they export to North America represents 5% or more of imports of t he s ubject crop into any of the coun t ry in which a t olerance is being soug ht. 2 The trial count reflects four pairs or gro u ps of tria l s separated by <20 miles that I-LED has determined to be replicate trials.
T ab l e B.7.6.1.1

- 3. Stud y Use P attern.

Location: City. Volume Rate per Retreat- To ta l Rate State/Province, End

- use Method of App lication ; {gal / A) App li cati on ment ( lb a i / A) Surfactant/ Country : Year Product' Timing of Application (lb ai / A) Inte rval Ad ju vant (Trial ID) [ L/ha] [g ai/ ha] (days) [g ai/lia] Limeira, SP, 0.92 lb 1. Fo li a r broadcast ; BBCH 89 218 (2037) 0.090 [101) 

### -- 0. 1 80 None Brazi l : 2013 (S l 3- 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 of8Etoxazole [PC Code I07091 ]Nalent U.S.A
. Corporation Table B.7.6.1.1-3. Study U se Pattern.

Location: City. Volume Rate per Retreat- Total Rate S tate/ Provin ce. End-use Method of Application: (gal//\) Application mcnt ( lb ai/ A) S ur factant/ Co untry ; Yea r Product ' Tim in g of Application ( lb ai / A} Int erva l Adjuvant

(Trial ID) f L/ha] [g a i / hal (days) [g a i / ha] Santo Antonio de 0.92 lb 1
. Foliar broadcast: BBC I I 84 216 (2022) 0.089 [ 1 00] 

### -- 0. 1 78 None Posse, S P. Brazil: ai/g a l SC 2. Foliar broadcast: BBCI I 89 2 1 6 (2022) 0.088 [99J 31 [199) 20 1 3 (S l 3

- 041 l l02) Limeira. S P. 0.92 lb I
. Foliar broadcast: BBCI I 89 2 1 8 [2037] 0.090 [1011 

## -- 0.180 one Brazil: 2013 (S l3- ai/ gal SC 2. Foliar broadcast: BBCH 89 218 [2037) 0.090 [ I OI] 31 (202) 04 111- 03) Limeira. SP. 0.92 lb I
. Fol iar broadcast: BBCH 89 216 (2019) 0.089 [1 00 1 

### -- 0.178 None Brazil ; 20 1 3 (S l 3- ai /g a l SC 2. Fo liar broadcast: BBC I 1 89 2 1 6(20 1 9 ) 0.089 [1 00] 3 1 (200) 04111 -04) Lim e ira, SP, 0.92 lb I
. Fo l iar broadcast: BBCH 84 2 18 (2037) 0.090 [1011 

## -- 0. 180 None Brazi l : 20 1 3 (S l3- ai /ga l 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: BB C H 89 2 16 [2024) 0
. 089 [1 00) 

## -- 0.178 one Brazil: 20 1 3 (S l3

- ai/ gal SC 2. Foliar broadcast: BB C H 89 216 (2024) 0.089 [100) 31 (200] 04111

- 06) Limeira. SP. 0
. 92 lb I
. Foliar broadcast: BB C H 89 216(2024] 0.089 [ 100] 

### -- 0.178 one Brazil: 2013 (Sl3- ai/ gal SC 2. Fo liar broadcast: BBCH 89 2161.2024 1 0.089 (100) 31 [200] 04 111- 07) Mogi Mirim, S P , 0.92 lb I
. foliar broadcast; BBC! I 89 2 18 [204 11 0.090 11 011 

## -- 0. 1 80 None 13r

az il ; 20 1 3 (S l 3- a i /g al SC 2
. Foliar broadcas t: BB C! I 89 2 1 8 ( 204 1] 0.090 (101) 3 1 [202) 04 111- 08) Aguai, S P , Brazil : 0.92 lb I
. Foliar broadcast: BBCH 89 2 1 8 [2041) 0.090 (IOI] 

### -- 0. 1 80 None 20 13 (S 1 3

- 04 I I 1- ai /g al SC 2. Foliar broadcast: BB C ! I 89 2 18 [2 04 1] 0.090 ( 1 0 1) 3 1 [202] 09) Boa**Espcran~a** do 0.92 lb I. Foliar b r oadcast: BB C I I 86 215 (20 1 3] 0.089 [ IOO] 

### -- 0.178 one Sul. SP. Brazil: ai/ gal 

### c 2. Foliar broadcast: BBCH 89 2 15120 1 3] 0.089 [100] 29 (200) 2013 (S 1 3

- 04 I I I

- 10) Boa**Esperan~a** do 0.92 lb I
. Foliar broadcast: BBCI I 86 2 15 ( 20 1 3) 0.089 [1 00 1 

### -- 0. 1 78 None Su l
. SP
. B raz il: ai/ gal SC 2. Fo li ar broadcast; BBC! I 89 2 15 ( 20 1 3 ] 0.089 [100] 29 [200J 20 1 3 (S l3-041 I I11 ) Tabatinga, SP. 0.92 lb I
. Foliar broadcast: BBC I I 87 2 18 [20 37 1 0.090 11 0 11 

## -- 0. 1 80 No ne Brazil; 2013 (S l 3

- 04 111-12 ) ailga l SC 2. Fo li ar broadcast: Bl3CI I 89 2 1 8 (2037] 0.090 [IO I ] 29 [202 ] ltapoli s, SP. 0.92 lb I. Foliar broadcast: BBC H 87 221 [20631 0.093 [104] 

### - 0.186 one Brazil: 2013 (S l3- ai/gal SC 2. Fol iar broadcast: BBCH 89 221 (2063] 0
. 093 (1 04] 29 [208] 04 111-1 3) ltapolis , SP
. 0.92 lb I. Foliar broadcast: BBCH 88 2 1 8 [ 204 1] 0.090 [IOI] 

## -- 0. 18 0 one Brazil: 20 1 3 (S 1 3- ai /g a l SC 2. Fo l iar broadcast: BBCH 89 2 18 (204 1] 0.090 [101] 29 (202] 041 11-1 4) lta po li s . SP, 0.92 l b I. F o liar broadcast: 13BCH 86 2 18 [2037 1 0.090 [IOI] 

### -- 0. 1 80 No ne Braz il ; 20 1 3 (S l 3

- ai/ga l SC 2. Foliar broadcast: BB C H 89 2 1 8 (203 7] 0.090[I011 29 [202 ] 04 111-15 ) Tabati nga. SP. 0.92 lb I
. Folia r broadcast: BBCI I 85 2 1 9 [205 1) 0.091 11 021 

### -- 0. 182 None Brazil: 2013 (S 1 3

- ai /g al SC 2. Foliar broadcast: BBCI I 86 2 1 9 [2051] 0.09 1 [102] 29 [204] 04 111-1 6) 1 0.92 lb ai/gal ( 110 g ai/L) SC fomrnlation of etoxazole**(Smi te~** 

E PA MRlD # : 49 37220 I Pa ge 4 of8Etoxazole [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 growt h 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 spec ified). 

### Sample Ha ndlin g and Preparation Sing le control and duplicate treated samples were harvested from all trials at a 14-da y PHI. Additional samp l es were collected at PHis of 7 and 21 days at two tria ls to in vestigate 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 harv est to the analytical laboratory, Euro fins Agroscience Services Brazil (lndaiatuba, SP, Brazil). At the analytical laborator y, san1p les 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 m et hod was included in the submission. Briefly , samp l es were extracted with acetonitrile (ACN) followed by the a ddition of 5 M NaOH and a salt mixture of anhydrous MgS04, NaC l , trisodium citrate dihydrate, and hydrogen disodium citrate ses q uihydrate. 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 (de termined as the LLMV) was 0
. 01 ppm. The limi t of detection (LOD) was 0.002 ppm. 

### II. RESULTS AND DISCUSSION Method performance was eva luated during method va lid at ion 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 th e acceptable range of 70

- 120%; therefore, the method was considered valid for the analysis of etoxazole residues in orange (Tab le 8.7.6.1.1-4). The fortification l eve ls bracketed the measured residues. Concurrent recoveries were not corrected for apparent resid ues in controls. The detector response was linear (coefficient of determination, 

## r2 

## = 0.9982) within th e range of 2.5 -8 0 ng/mL. Representative chromatograms of control samples, fortified samp les , and treated samples were provided. The control chromatograms generall y had no peaks of interest above the chromatographi c background
. The fortified samp le 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 re sid ue values in the treated samples were not corrected fo r apparent residues in controls.

EPA MRID # : 49372201 Page5of8Etoxazole [PC Code 107091]Nalent U.S.A
. C orporati on T a b l e B. 7.6. 1.1-4
. S umm a r y o f M e th o d V a li d a t io n a nd P roce d ural/Co n c urre nt R ecove ri es o f E t oxazo le fr o m Ora n ge. Matrix 

# I Fo rtification 

# I Sample s ize 

# I Recoveri es' 

# I Mean ± Std
. Dev
. Level (ppm) (n) (%) (%) M eth od va l id a t io n O range 

### I 0.0 1-0 .50 

### I 30 

### I 79.6-119.2 

## I 97.6 ± 11.2 Co ncu rre n t r ecove ri es Orange 

### I 0.01 

### I 4 

### I I 03.0 -11 6.2 

## I 1 06.6 ± 6A 1 Concurrent recoverie s we r e not corrected for apparent re sidues in controls. Samples were stored frozen for a maximum of 27 days (0.9 months) from harvest to extract ion (Table B. 7 .6. 1
. 1 -5). Samp les we r e anal yzed on the d ay of extractio n . Previously sub mi tted storage stab i lity data in d icate t h at e toxazole is stable at
- 20°C for at least 3.5 mo nt h s in app l es, 2 m onth s in strawb erri es, 6 mo nth s in o r a nge pul p , 12 months in o r a nge pee l s, 17 mon th s in cottonseed, and 6 month s in cotton g i n byproducts (0283737, J. Tyler, 3 l -Ju l -2003)
. Th ese data are adequate to validate the storage intervals/conditions employed as part of the current study.

Tab le B .7. 6
. 1.1

- 5
. Su mm ary o f Storage Co n di t io n s. Matrix Storage Ac tu al Storage Int erval of Demonstrated Storage Stability Temp. ( 0 C) Duration' Orange '.S -18 8-27 days Prev iou sly submi tted storage s tability data indi cate that etoxazo le is s tab le at
- (0.3-0.9 mo nth s) 20°C for at l eas t 3.5 mo nth s in apples , 2 month s in s trawberri es. 6 month s in orange pulp
. 12 month s in orange pee l s, 17 m onth s in cot1011seed. and 6 month s in cotton g in byproducts (0283737. J
. Tyler. 3 1-J ul-2003 ). The se data arc adequate to va lid ate the storage interval s/ conditions emp loyed as part of th e current s tud y. 1 Inte rva l from harvest to ex traction. Sampl es were analyzed on the day ofextraction. The results from th e s ubmitted fie ld trials are prese nted in Tables B.7.6.1.1-6 and B.7.6.1.1-7. In oranges harvested at a PHI of 14 days fo ll owing two fo liar broadcast applications of the 0.92 lb ai / ga l SC formulat ion , re s idues (and per- trial averages) of etoxazo le were < 0.01-0.053 (< 0.01- 0.048) ppm. A lthoug h re lat ively high res idue s were observed i n Trial 03 , w hi c h re fl ec ted app lication of a mai nte nance produc t co n tai nin g etoxazole (rate was not specified), th e residues were we ll with in the range of obse r ved res i d u es . In the res idue decline trials , residues decrease d with increasing PHI in one trial. ln the second trial, residues declin ed after the 7

- day PHI , bu t were highe r at the 2 1- day PH I than at the 14-day PHI.

EPA MRlD #: 49372 2 0 I Page 6 of8Etoxazole [PC Code I 07091 ]Nale nt U
. S
. A
. Corpo ration
Tab le B .7.6.1.1 -6. R es idu e Data fro m Oran ge Fie ld T ri a ls with Etoxazo le. 1 Location: City, Zone Orange Matrix Rate PH I Et oxazole Residues 3 (ppm ) State / Prov in ce. Variety (lb ai/ A) (days) [Average] Countr y; Year (Tria l [g ai/ha) ID) 2 Limeira, SP, Orazil; N I A Valencia Fruit 0.178

- 0. 1 80 14 0.022, 0.031, 0.039, 0
. 042 20 1 3 (S 1 3 -041 I l-01 ) (200-202] (0.034 ) a nd (S l3-04111-04 ) Limeira. SP. 13razil; N I A Valencia Fru it 0. 178 (200] 7 0.080, 0.080 (0.080) 2013 (S13

- 04 1 I l-04) 21 0.023, 0.027 (0.025] ID ecl in e i nterval s ! Santo Antonio de N I A Fo lha Fruit 0.178 (199) 14 (0.007), (0.008) [ <0.0 1] Posse, SP, Brazi l ; 2013 Murcha (S 1 3-041 1 1 -02) Limeira, SP, Brazil: N I A Pera Coroa Fru it 0.180 [202] 14 0.03 1 , 0.035 [0.033) 2013 (S l 3

- 0411 l-03 ) Limeira, SP, Brazil ; N I A Pera Murcha Frui t 0. 178-0. 180 14 0.016 , (0.008), 0.015, 0.0 1 7 2013 (Sl3-041 l l-05) [200

- 202) [ <0.0 1 5 ) a nd (Sl3-04 1 I l-06) Lime ira, SP, Brazil; N I A Pera Mureha Fruit 0.180 [202) 7 0.107 , 0. 106 [0.107) 20 1 3 (S 1 3

- 04 111-05) 21 0.030, 0.020 [ 0.025] !Decli n e inte r va l s! Lim ei ra, S P
. Brazi l ; N I A Rubi Fruit 0.178 [ 200) 1 4 0.024. 0
. 021 ro.0261 2013 (S l 3-041 I l- 07) Mogi Mirim, SP , N I A Pera Coroa Frui t 0.180 [202) 14 0.053, 0.042 [0 .048) Brazil: 2013 (S l 3

- 04 111- 08) Aguai. SP. Brazil: 2013 N I A Va l e nci a F ruit 0. 1 80 [202] 14 0.024, 0.031 (0.028] (S 13

- 04 I 11-09) Boa**Esperan~a** do Sul, N I A Valencia Fruit 0. 178 [200) 14 0.0 1 6, 0.0 1 6, 0.025, 0.029 SP. Brazil; 20 1 3 (S l 3- [0.0 22) 0411 1- lO)a nd (S l 3-0411 l-11 ) Tabatin ga, SP. Brazil; N I A Pera Rio Fruit 0. 1 80 [ 202) 14 0.042, 0.027 [0.035] 2013 (S 13-0411 l- 12} ltapolis. SP , Brazil; N I A Valencia Frui t 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 l 3-04 11 l-1 4) [ 0.025) a nd Tabatinga, SP. Brazil: 2013 (S 13

- 04 111 -16) Itapolis, SP. Brazil; N I A Rubi Fruit 0.180 [202) 14 0.030, 0.033 [0.032) 20 1 3 (S 1 3

- 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 const itute si ng l e trials with replicate samp l es for purposes of OCSPP 860.1500 data requi reme nts: 01 and 04; 05 and 06; 10 and 11 ; and 1 3, 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 th e 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 of8Etoxazole [PC Code 10 709 1] Na lent U.S .A. Corpora ti on
Table B. 7.6. 1.J- 7. Summary of Resi due s from Orange Fie ld Trials with Etoxazole. Crop Matrix Total Application Rate PHI n' Etoxazolc Re s idues (ppm) (lb ai /A) [g ai / ha] (days) Min
. 2 

### I Max .2 

### I LAFT3 

### I I IAFT3 

### I Median 3 

### I Mean 3 

### I 

### so i 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 trial s. 2 Values based on total number of s amples. l Values based on per-trial averages. LAFT = lowest average field trial. I IAFT = highest average field trial. SD =standard deviation. 

### III
. CONCLUS I ONS The orange field trial s a re considered scientifically acceptab le . In oranges harve s ted at a PHI of 14 days following two foliar broadcast applications of the 0.92 lb a i / ga l SC fonnulation, residues (and per-trial averages) of etoxazole were < 0.01-0.053 ( < 0.01-0.048) ppm. Although relatively high residues were observ ed 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 seco nd trial , residues declined after the 7-day PHI , but were higher at the 2 I-d ay PHI than at the 14-day PHI. An acceptable method was used for re sidue quantitation and adequate storage stab ility data are available to valid ate the emp loye d interval s/cond ition s. 

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

EPA MRJD # : 49372201 Pa ge 8 of8Etoxazole (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 Di s tribution 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 Sl3-04 1 l l. Unpublished study prepared by Valent U.S.A. Corporation. 338 p. EPA OCSPP Harmonized Test Guide line 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
. Eva luator: Tom Bloem , Chemist , Risk**Assess1'~V** Branch l/Health Effects Division No te: This Data Evaluation Record ( DER) was origin a ll y

# prepa~e?cont~**;;;>,** Inc. (6850 Versar Center, Sprin g fi e ld , VA 22151; s ubmitted 2/27 / 15. The DER has been reviewed by 1-IED and revi sed lo reflect current Office of Pesticide Programs (O PP) policies. EXECUTIVE SUMMARY Valent U.S.A. Corporati on has subm i tted 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 s ite rec e ived two fo li ar 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 p l ot applications were made at exaggerated (5x) rates of 0.442-0.454 lb ai/N application (495-509 g ai/ha/application) for a total app li cation rate of 0.888-0.904 lb ai/A (995-1013 g ai/ha)
. App li cations were made at retreatment intervals of 3 1 days using ground (airblast) equipment in spray volumes of 216 -218 gal/ A (2022-203 7 L/ha). No E PA MRID # : 49372201 Page I of8Etoxazo le [PC Code 107091]Nalent U.S.A. Corporation adjuvant was used
. T h e pet it ioner noted that in one trial ( 03) a product containing etoxazole was app li ed as a mainte n ance chemica l to the crop (rate was not sp ecified). Oranges were harve sted at a prehar vest interva l (PHI) of 14 days and we r e processed into juic e, dried pulp , and oil using s imulated commercial practices. Proc ess in g wa s conducte d at JBT FoodTech (Ara raquar a, SP Brazi l). Adequate descriptions of th e proces s ing proce dures we re provid e d , including materia l balanc e su mm aries. Samples of orange (RAC) for analysis were maintai ned froze n at the t es tin g facilities and during s h ip p in g to the analytical laboratory. Samples of orange intended for proc ess ing were shipped under ambient co nditi o n s from th e field sites t o th e process in g facility and were stored frozen at th e process in g faci li ty fo ll ow in g proc ess in g and dur in g shipping to the ana lytical l aborato ry. A ll sam ple s were stored frozen at the analyt ica l laborato ry prior to ana l ys i s. Processing was co mpl ete d within 1 -3 days of harve s t. Th e max im um storage interval s fo r sa mpl es between harvest/proce ss ing and ex traction were 15 day s for orange and 20 day s fo r processed commod iti es . Samples were analyzed w ithin 1 day of extract i o n . Previously s u bm i tted s tora ge stability data indicate that e toxazo l e is stab l e at -20 °C for a t least 3
. 5 months in apples , 2 mo nth s in strawberries, 6 mon th s in orange pulp , 12 months in orange peel s , 17 months in cottonseed , and 6 months in cotton gin byproducts ( 0 283737 , J. T y ler, 31-Jul-2003). The se data are ad eq uate to val idate the storage intervals/ conditio n s employed as part of the current s tud y. Sam ple s we re a na l yzed for res idu es of e to xazo le by high-performance liquid chroma tograp h y wi th tandem m ass spec trom e try detection (LC/MS/MS) u s in g a method adapted from two QuEChE R S multiresidue methods and Valent Met h od RM- 37 HM
. Accep tabl e method validation and concurre n t recoveri es we r e reported for samp les of orange fortified with e toxazole at 0.01-0.50 ppm , for samples of ju ice and dried pulp fo rtifi ed at 0.0 I ppm , and for sampl es of o il fortified at 0.01-7 .0 ppm , thus va lid at ing the method. The lim it of quantitation ( LOQ; determined as the lowes t level of m e th od validation , LLMV) was 0.01 ppm fo r all matric es . The fort i ficat ion levels u se d in co nc urrent m etho d recovery were adequate to bracket expec ted re s idue leve ls . Concurrent recoveries and re s idu es in t r eate d samp l es were not correc te d for res idue s in co n trols. In orange (RAC) harv es ted at a 14

- day PHI in three trial s conducted in Brazil r e flectin g tw o fo li a r broadcast application s of th e 0.92 lb ai/gal ( 110 g a i / L) SC formulation of etoxazole at tot a l rate s of 0.178-0.180 lb a i / A (199

- 202 g ai/ha ; 1 x plot) and 0.888-0. 904 lb 

### ai lA (995

- 1013 g ai/ha; 5x plot) , a ve rage residu es were < 0
. 01-0 .0 33 ppm i nio n sam ples from th e l x plots and < 0.012-0.204 p p m in/on samples from the 5x plots. Average resid ue s in juice and dried pulp were belo w th e LOQ ( < 0.0 1 ppm) in all samp le s from all plots and trial s , and a verage res idue s in oil from the I x and 5x plots , respective ly , were 0.181

- 0.395 and 0.289-4.29 ppm. A co mparison of the re s idues in/on orange (RAC) with those in eac h processe d fraction indi cat ed th at re s idue s of etoxazole conce ntrated in oi l ( me dian processing factor of > 20x), but did not co nce ntrate in juice or drie d pulp (<0.3x). T he observed proc ess in g factors do not exceed th e theoretical co ncentration factors for citrus of 3
. 3x, 1 OOOx, and 2x fo r peel , oil, and juice (based o n se paration into components ; OCSPP 860.1520, T able 3).

EPA MRID # : 4937220 1 Page 2 of8Etoxazo le [P C Code 107091)Nalent U.S.A. Corpo r ation 

### I. MATERIALS AND METHODS A
. MAT E RIALS

Table B.7
. 7.3 .1

- 1. Nomenclature for .Etoxazole. Co mmon n a me Etoxazole Id ent i ty 2-(2 , 6-difluorophenyl)-4-[4-( l , l-dimethylethyl)-2- ethoxypheny l)-4,5

-di h yd ro oxazo l e CAS n o. 153233-91- 1 Co mpan y experimenta l nam e V-1283 Other sy non y ms ( if applicable) S- 1283 OCH , 

# ( CH),-C &1tJ

-**~ ~**  

## I F**~** 

### B. Study Design l. 

### Test Procedure Location and detailed use patte rn for the trial is prov ided in Table B
. 7.7.3. 1- 2.

T a bl e B .7.7. 3.1-2. Study Use Pattern. Loca tion : End -u se Plot Method of Application / Volume R ate per Relreatment Total City, Product 1 Timin g ofApplication (gal/ A) App li cation Interval Rate S tate / Pro v ine [ L/ ha) (lb ai / A) ( days) (lb e: Year [g ai/ha] ai/ A) (T rial ID ) f g ai/ha] Limeira, SP. 0.92 lb 2 ( Ix) I
. Fo li a r broadcast: BBCI I 89 218 [2037] 0.090 (1 0 1) 

### -- 0.180 Brazi l ; 20 1 3 ai/ ga l 2. Fo li ar broadc as t ; BBCl-1 89 2 18 [2037] 0.090 [I OI] 31 [202 ] (S 1 3

- 04 I I I - SC 3 (5x) I. Fo li ar broadcast ; BBCl-1 89 218 [2037] 0.450 [504] 0.904 0 1) 

### -- 2. Fo li ar broadcas t; BBCl-1 89 218 [20 37] 0.454 (509] 3 1 [1013] Santo 0.92 lb 2 ( I x) I
. Fo li ar broadcas t ; BBCH 84 2 1 6 f2022l 0.089 [ 1 00] 

## -- 0. 178 Antonio de ai /ga l 2. Foliar broadcas t; BBCH 89 2 16 [2022 ] 0.088 ( 99] 3 1 [199] Po sse, SP. SC 3 ( 5 x) I. Fo liar broadcast ; BB C H 84 2 1 6 (2 022 ) 0.446 [500] 0.888 Brazil: 20 1 3 

## -- (S l 3-0411 1- 2. Foliar broadcas t: BBCl-I 89 216(2022] 0.442 [495] 31 [ 995] 02) Limeira. S P , 0.92 lb 2 ( Ix) 1. F o li ar broadcast ; BBCH 89 218 [2037) O.o90 [I OI] 

### -- 0.180 Brazi l : 20 1 3 ai / gal 2. Foliar broadcast: BBCH 89 218 [2037] 0.090 [1011 3 1 (202] ($ 1 3-04 111- SC 3 (5x) 1
. Fo li ar broadcast: BBCH 89 218 [2037] 0.450 [504] 0.899 03) 

### -- 2. Foliar broadca s t: BBCH 89 218 (20 37] 0.450 (504] 3 1 (I 008] 1 0.92 lb ai/ ga l ( 110 g ai / L) SC formulation of etoxazo l e**(Smite~** 

### The petitio n er noted that in one trial (03) a product containing etoxazo le 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 of8Etoxazole [PC Code 107091]Na lent U .S.A. Corporation 

### Sample Handling and Preparation S in g l e control a nd duplicate treated samples of orange (RAC) for analysis were harvested from each plot at all trials at a 14-day PHI ; a sing le control and bulk treated samples (103 -1 14 kg) for processing were a l so harve s ted from each p lot at all trials at a 14-day PHI. Samples for analysis were placed in frozen s tora ge at the field s ites 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 sam pl es intended for processing were shippe d under ambient conditions o n the day of harvest to the processing faci lity , JBT FoodTech (A raraquar a , SP Brazil) ; samples were sto red under ambient conditions for up to 22 hours prior to initiation of processing. Proc essi ng was completed within 1 -3 days of harvest, after wh ich samp les were placed in frozen storage (temperature un specified). The processed commodity samp les were s hipped frozen on dry ice via air freight within 0-13 days of proce ss in g to the analytical laboratory
. We note th at although the petitioner reported that whole fruit subsamp les were collected and placed in frozen sto rage at the processing facility, it does not appear that these samp le s were slipped to the laboratory for analysis. At the analytical laboratory , samp le s of o ran ge, juice , and dried pulp were homogenized in the presence of dry ice ; s amples of oil required no additional preparation. Samp les were s tored frozen ( :;:: -18 ° C) until extraction for analysis. 

### Sample Processing The processin g pro ced ures s imulated commercial operations of orange production as closely as possib le 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 procedure s were provided , including material balance summaries. A processing flowchart for orange processed fractions , cop ied w ithout alteration from M RID 49372201, is presented in F igure B.1.

E PA MR10 # : 49 37220 1 Page 4 of 8Etoxazole [PC Co de I07091 ]Nalent U.S.A. Corporation
F I GURE B.1. Processing Flowchart for Oran ge Juice, Dried Pulp , and Oil.

Around SO k!!**l====~::>i** I.**w:i~** wuh •,1;a1er wbo lt frrut and b:'mbe \

.: . Exuaction w11h JBT HP 3 9 1. s tm c fard**i-----~** .---------\ c onfigurat:on HP 2H2L 0-WC). usuig 1------..**·· ··**  M.1..'ttllre o f w ater and o u is betng de<: anted ( etlZ) me s can be**3~d** and centnfuge can be U!. ed u oe<:e ssa.ry)**~fi:aure** o f Juic e and Pulp being rorwarded t o step 3**~---__, .**  Separa11. o o**~** Fuusber JBT Di-,ca1ded frn c u o as ( 001 1 0 be sampled } •**P~J** • C o re •**~li.'Cllltt$ f** **~eland** core • Fro

,..----, ieCT3 5. w1th 0.0 1 ·· lll!Kh ·· 1------..

2. De sc ription of A n a ly tic a l Procedures Samples were analyzed for residues of etoxazo le by LC/MS/ MS u sing a method adapted from two QuEC h ERS multires idue methods and Valent M ethod RM-371-lM. A comp l ete description of the method was included in th e submiss i on. For orange, juice, and dried pulp, samples were extracted with acetonitrile (ACN) fo ll owed by the addit ion of 5 M NaOI

- I and a sal t mixture of anhydrous MgS04, NaCl , trisodium c itrate 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 analys i s. For oil, the s ample was adjusted to pH 

### 2: 8 by the addition of 

### 5 M NaO H then combined with ACN sa turated with hexane. The salt mixture was added , and the mixture was centrifuged. Following phase separation, the organic phase was comb in ed wi th an Eppendorf salt mixture of anh yd ro u s MgSQ4, and primary

- secondary amine (PSA) so rbent and ce ntrifu ged. The resulting s upernatant wa s s ubjected to LC/MS/MS analysis. The LOQ (determ in ed as the LLMV) was 0.0 l ppm. The limit of detection (LOO) was 0.002 ppm.
EPA MRID #: 4937220 I P age5of8Etoxazole [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 va li dation, samp les of orange (RAC) and oil were fortified with etoxazole at 0.01

- 0.50 and 0.01-7.0 ppm, respectively. For concurrent recovery, samp les 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 reco veries 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 oi l. Representative chromatograms of control samples, fortified samp les, 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 interes t, 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 res idues in controls
.

Table B.7.7.3.1-3. Sum mary of Method Validation a nd Procedu r al/C onc ur re nt R ecoveries of Etoxazo le from Orange Matrices. Matrix Fortification Sample size Recoveries' Mean ± Std. Dev. Level (ppm) (n) (%) (% ) Metho d va l idation 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 Co n curr ent recoveries O ran ge 0.01 4 103.0-116.2 106.6 ± 6.4 Juice 0.01 4 80.1-105.9 92.4 ± 12.9 Dri ed 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 recoverie s were not co rrected for apparent re s idu e s m control s . 

### Processing was completed within 1-3 days of harvest. The maximum storage intervals for samp les between harves t/process ing 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. Pre vio usly submitted s torage stability data indicate that etoxazole is stab l e at -20°C for at least 3.5 months in apples, 2 months in strawberries, 6 months in orange pu lp, 12 months in orange peels, 17 months in cottonseed , and 6 months in cotton gin byproducts (D283737 , J. 

### Tyl e r, 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 of8Etoxazo le (P C Code I0709 1 ]Na le nt U
. S.A
. Co rp o r atio n

Table 8.7.7.3
. 1

- 4. S umm ary of Storage Condition s . M a tri x S torag e Actual Storage Inte rva l o f Dem o ns trated S torag e Stability Te mp. ( 0 C) Durat io n 1 Orange ( RA C)**18** 15 days Pre viou s l y s ubmitt ed s torage s ta bilit y da ta indic ate that etoxazol e is J u i ce and dri ed pulp 10 days s table a t -20° C fo r at leas t 3.5 m onth s in a ppl es . 2 months in Oi l 14

-20 d ays s trawberri es . 6 month s in oran ge pulp. 12 month s in orange peels
. 17 month s in c ott o nseed. a nd 6 mo nth s in co tton g in by products ( 028373 7
. J. Ty ler. 3 l -Jul-2 003). T hes e d ata are ad equ ate to validate the s torag e in terv a ls/co nditi on s e mpl oye d as part o f the current study . 1 Int e rva l fro m harvest/pr ocess in g to e xtraction. Samp l es were anal yzed within 0-1 d ay of ex traction
. R es idu es fo und in s ampl es and proc ess in g fact o rs are g ive n in Tab le B.7.7 .3 .1

- 5. In orang e ( RAC ) harves te d at a 14-day PH I in three trial s condu c te d in Braz il re fl ec tin g two fo li ar b roa dcas t appli cat io n s of th e 0
. 92 lb a i / gal ( 1 10 g ai /L ) SC fo rmulation of e toxazol e at total rate s o f 0.178

- 0
. 1 80 lb ai / A ( 1 9 9-202 g ai/ha ; lx plot) and 0.888-0. 9 04 lb a i/A (995-1013 g ai/ha ; 5x pl o t) , av e rage res idue s w e r e < 0.01-0
. 03 3 ppm in/on s ampl es fro m th e l x p lot s and < 0.0 1 2-0.204 ppm in/o n sa mpl es fro m the 5x plots. A ve ra ge res idu es in jui ce a nd dri e d pulp were below the LOQ ( < 0.0 I ppm ) in a ll s ample s from all p lots and tri a ls , and ave rage r es idue s in oil from th e 1 x and 5x p lo ts , res p ec ti ve ly , we re 0.181-0. 3 95 and 0 .2 8 9 -4. 29 ppm. A comparis o n of th e res idu es in/o n oran ge (RAC) wi th th ose in each processe d fraction indicate d that re s id ues of etoxazo le co n ce ntrated in oi l ( me dian p roce s s in g facto r of > 2 0x) , bu t did no t conce n trate in j ui ce or d ri e d pulp ( <0.3x)
.

T a b l e B .7.7 .3. 1 -5. R e s idue Data from Orange Proce ss in g Stud y w ith E toxa z ole. Commodi ty Pl o t Re s idues • (ppm)[ A vc rag c] Process in g Facto r2 Median Pro cess in g Facto r3 L im eira , SP , Brazil; 2013 (5 1 3 -041 11

- 0 1) Ora nge ( R AC) 2 ( I x) 0
. 022. 0
. 03 1 [ 0
. 027 1 

## -- -- Jui ce ND, ND [<0.0 ll < 0 .4x < 0.3x Dri e d pulp ND. ND [<0.0 1I < 0.4x < 0.3x O i l 0
. 383 , 0.407 [0.395 ] 15x > 20x O ra ng e ( RA C) 3 (5x) 0 .1 94
. 0.2 14 ( 0.204 1 

## -- J u i ce N D , N D (< 0.0 1] <O.OSx .. ·- 

# .. Dri ed pulp ND , ND [ <0.0 1] < 0
. 05x 

### - O i l 4.5 1 , 4.07 [4.29] 2 1 x r S a nt o Anto nio de P osse, SP, Brazil; 2013 (Sl3-041 I l-02) O r

a nge ( RA C) 2 ( I x} (0.007 ), (0.008 ) [ <0.01] 

### -- Jui ce N D , ND [ <0.0 1 ] NC ..**~~---** Dri ed pu lp N D, N D ( <O.O ll NC Oil 0 .181 , 0. 180 1 0. 181] > 1 8 x**~** 

### - O range (RAC) 3 (5x) (0
. 004 )
. 0.0 13 (< 0.0 12 1 

## -- Juice N D. N D r < 0.0 1] 0.9x D r ied pu lp N D. N D [< 0.0 1I 0. 9 x**~** O il 0
. 282. 0 .29 6 [0.289 ] > 25x " Limeir a, S P, Brazil ; 2013 ( S l 3 -041 1l

- 0 3 ) Ora n ge ( RAC) 2 ( I x) O .oJ I. O.Q3 5 [0.0 3 3 ] 

## -- - -· J u ice ND. N D 1 < 0.0 1] < 0 .3 x Dri ed pu lp ND, N D [<0.01 I < 0. 3x O il 0.235 , 0.25 1 [ 0.243) 7
. 4x
E

PA MRIO # : 493722 0 I Pa g e 7 of8Etoxazole [PC Code 10709l]Nalenr U.S .A. Co rporation

Ta b le B.7.7.3. 1 -5. Res id u e Da t a fr om O r a n ge P r ocess in g Stu dy w i t h Etoxazo le. Com modity Plot Rcsiducs 1 (ppm)[Average] Processing Factor2 Median Processing Fac t or3 Orange (RAC) 3 (5x) 0.188, 0.147 f 0. 1681 

## -- Juic e 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 va lu es 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. Pe r trial averages were calculated by th e 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 facto r could not be calculated because residues were below the LOQ in the RAC and the processed frac ti on. 3 Median processing factor for both plots a nd all sites. 

### III. C O NCLUS I ONS The orange processing study is considered scientifically acceptab l e. 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 residue s 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 residue s in juice and dried pulp were below the LOQ (< 0.01 ppm) in all samples from all p lots and trials, and average residues in o il from the Ix and 5x plots , respecti vely, were 0.181-0.395 and 0.289-4.29 ppm. A comparison of th e res idues in/on orange (RAC) with those i n each processed fraction indicated that residues of etoxazole concentrated 

### in oi l (median processing factor of >2 0x) , 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 i nto 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/c onditions. 

### REFERENCES D283737 , J. Tyler, 31-Jul-2003

EPA MRID #: 49372201 Page8of8