### UN IT E D STATES ENVIRO NMENTAL PROTE CTION AGENCY WASHINGTON, D.C. 20460 OFF I CE OF C H EM I CA L SA F ETY A N D POL LUT I O N P RE VENTION 

### MEMORANDUM Date : S ubj ect : 22 -MAR- 20 16 

### Aceq u inocyl. Petitio n for Increasi ng the Permanent Tolerance for Residu es in / on Hops. 

### S umm ary of Ana lyt ica l C hemi stry and Re s idue D ata. PC Code: 006329 Dec i s ion No.: 505001 P etitio n No.: 5F8364 DP No .: 0427588 R eg is tra tion No.: 66330-38 R eg ul ato r y Actio n : Amend an Es tablished Tolerance Case No.: 7621 Ri sk Assess m e nt T y pe: A TXR No.: A CAS No.: 57960-19-7 40 CFR: § 180.599 MRID No.: None 

### From:
Through :
To: Geo rge F. Kramer, Ph.D. , Sen ior

## Chemist**~~** ' > Ri sk Assessment Branch 1 (RAB 1) Health Effects Division ( H ED , 7509P) Charles 

## w. Sm i th 

## m , Bran ch

### ChiC~ RAB 11 1-I ED (7509 P) Andrew ErtmanNenus Eagle, RM 1 Registration Division (RD , 7505P) 

### Exec uti ve S umm ary Arysta LifeScience is requesting to increas e the existing tol era nce for residue s of the in sect icide acequinocyl , 2-(acetyloxy)-3-dodecyl

- l ,4-naphthalenedione, and it s metabolite , 2-dodecyl

- 3- hydroxy-1,4-naphthoquinone, expressed as acequi nocy l equ ivale nt s in/on hops from 4.0 ppm to 15.0 ppm. The purpose of th e ame nded tolerance is to harmonize the value with the established maximum residue limit (MRL) in the Europea n U nion (EU). The domestic residue data for hop s were previous ly submitted and reviewed und e r PP#9E7598 ( Memo , S. Levy, 25-AU G-201 

### O; D 369100). Tolerances are currently estab li shed under 40 CFR 

### § l 80.599(a) for the combined residues of acequinocyl and its metabo lite , 2-dodecyl-3-hydroxy-l,4-naphthoquinone , expressed as acequinocyl eq uivalent s , in/on a number of plant and live stock commodities. To lerances for plant commodities range from 0.02 ppm (tr ee nuts and pistachio s) to 30 ppm (citrus oil), and tolerances for livestock commodities are es tablished at 0.02 ppm in the fat and liver of cattle, goat , horse, and sheep. The nature of acequ inoc y l res idues in apples , oranges , and eggplants is understood based on the previously subm itted and reviewed metaboli s m studies. In these crops, the metabolism of acequinocy l involves the loss of t h e acety loxy moiety to form aceq uin ocyl-OI-1, the open in g of Page I of7Acequinoc yl Summary ofAnalytical Chemistry and Re s idue Data DP# 4 27 588 the qui none ring to form AKM-18 , and the subsequent degradation of the qui none ring to yield polar metabolites that degrade to phthalic acid. Th ese data are considered sufficient for th e currently reg istered crops. For purposes of ri sk assessment and the tolerance express ion , HED has determined that the residues of concern in the currently registered crops include parent and acequi nocyl-OH (Memo , S. Levy. 07-JA N -2004 ; DP# 297872 )
. There are no livestock feedstuffs associated with hops. Therefore, no livestock metabolism data , enfo rc e ment methods, sto r age stabi lity data , o r feeding studies are required to s upport thi s petition. There are adequate residue analytical method s for enforcing tolerances for acequinocyl residues of concern in/on the proposed/registered plant commodities. These methods include two highperforrnance liquid chromatography methods with tandem mass-spectroscopy detection (HP LC/ MS / MS) for determining residues in / on fruit and nut commodities (Mo rse Methods Meth-133 and Meth-135). For eac h of these methods, residues are extracted w ith h exane o r aceton itril e (ACN)/ water and cleaned up by solvent partitioning , gel-permeation c hromatography (GPC) and/or si li ca - gel solid-phase extraction (SPE). The U.S. tolerance (4.0 ppm) is based o n three hop field trials conducted in North American Free Trade Agreement (NAFTA) Growing Zo ne I 1 ( ID , OR, WA) during the 2005 growing season. Each trial consisted of one untreated and one treated plot. At each s ite , a 1.25 lb/ gal SC fomrnlation of acequinocyl was applied to hops as two directed foliar applications during cone development at rates of 0.288-0.330 lb ai / N application, with a 19- to 28 day retreatment interval (RT I) , for a total rate of0.588-0.641 lb ai/ A (

- IX). Total residues of acequinocyl and acequinocyl-OH were 1.32-2.83 ppm inion dried hop cones. The German residue data (2X U.S. si n gle application rate; IX U.S. seasonal app li cat ion rate, long er preharvest interval (PHI ), parent only) show that the U.S. tolerance level is lik ely set at too low of a level. HED notes that analysis of the U.S. data with the Organization for Economic Co-operation and Development ( OECD ) MRL Calculator would have resulted in a recommended tolerance of 7.0 ppm. Harmonization of the U.S. tolerance level with the MRL of 15 ppm is thus recommended. Regulatory R ecom mend ation s and Residue C hemistry D e fici e ncies There are no residue chemi s try issues that would preclude increasing the existing to lerance for residues of the insecticide acequinocyl in/on hops from 4.0 ppm to 15 ppm. 860
. 1550 Prop osed Tol era nces A summary of the recommended tolerance s along with recommendations for commodity definitions are presented in Tab le 5. A human health risk assessment will be prepared as a separat e document (DP# 431305).
B ackgro und Acequinocyl is a quinoline-type miticide that is currently registered fo r the use in the U.S
. on a number of RA Cs for the control of various phytophagous mite species
. Th e nomenclature of acequinocyl is s ummari zed in Table 1. The chemical s tru ct ure and nomenclature of acequinocy l Pa ge 2 of7Acequinocyl S ummary ofAnal ytica l C hem istry and Re s idu e Dat a DP # 427588 and its regulated m e tabo lite are presented in Tabl e I , and the phys ic oc hemical properties of acequinocyl are presented in Table 2.

Table 1. Nomenc lature o f Test Co mpound and M etabo l ites. 0 

# o7 CH ,(CH ,),. CH , I OCOCH 3 Co mpound 0 Co mmon name Aceq uinoc y l Co mpan y experimen t a l name s TM-41301 o r AKD

- 2023 IU PA C nam e 3 -d odecyl-1 ,4-dihydro- I ,4 -diox o - 2 -n aphthyl aceta t e CAS n am e 2

- ( acetylox y)-3-do decy l-1 , 4-naphthalened ione C A S # 57960 -19- 7 End -use product s/ EP Kanemite · :&> 15 SC ( 1 .25 lb ai /ga l ; EPA Reg. No. 66330-38) Co mpound 0 

# o7C H ,(C H ,)

,. CH , I OH 0 Co mmon nam e Acequinocyl

- OH Co mpany experimental nam es RI IUPAC name 2 -dodecyl-3-hydrox y- 1 ,4-napthoquinone C A S name 2-dodecyl

- 3-hydroxy- 1 ,4- n aph th a lened ion e C A S # 57960 -31- 3 Table 2. Ph ys i coc h emica l Prope r ties. Parameter Value Reference ( MRID ) Melting point 59.6 

## c 45434906 pH 6.94 45434904 Density 1.13 g/c m3 45434904 Water so lubility ( 20 ° C) 6.69 μ g/L 45434906 So lv e nt sol ubili ty (mg/Lat 2 0 ° C) 1 ,2 -dichloro e lh ane: > 250 45434904 aceton e: > 250 e th y l acetate: > 250 xylene: > 250 methanol: 6. 1 n-h eptane: 36 n-octanol: 29.2 Vapor pressure at 25 ° C 1.69 x I0· 9 pascals 45434905 Di ssoc iation constant (pK.) no me as urab l e pK
. 45434905 Oc tan ol/w ater partition coefficient**~6 .2**  45434906 Log(Kow) UY/ v is ibl e ab so rption s p ec trum neutra lpH :242,248,262,270,335 45434905 (A.max. nm) acid pH: 242, 248, 265, 27 0 , 330 b as ic pH : 232, 245, 255, 275, 362 

### 860.1200 Direction s for Use Kan e mite ® 15 SC Miti c ide (EPA Reg. No. 66330-38), a 1.25 lb/ gal SC fomrnlation of acequinocyl is currently reg istered for use on hop s . The U.S. and EU u ses a r e summarized below in Table 3. Pa ge 3 of7Acequinocyl Summary of Analytical Chemi stry and R esidue Data DP# 427588
Tab le 3. S u m mary of Direct io n s for Use o f Accqui nocyl. Applic. Tim in g, Formulation App lie. Max. No. Max. Seasonal PHI Use Directions and Type , and [EPA R e g. Rate Applic. per Applic. Rat e (day s ) Limitations' Equip. No.) ( lb ai /A) Season ( lb ai/ A) Hop s (U.S.) Postemergence , 1.25 lb /gal Minimum spray volume foliar S C 0.3 2 0.6 7 of 100 gal/A; minimum Ground on ly [66330- 3 8] RTI of2 I days. Hop s (E U ) Po stemergence , 1.25 lb / gal foliar 0.67 I 0.67 21 Ground only SC 1 RT! = retreatment interval.


### 860.13 00 Na tu re o f th e Res idu e - P lan ts & 

### L ivestoc k The qualitative nature of acequinocyl residues in fruit and nut crops is understood based on the available apple , orange. and eggplant m etabo li sm studies (Memo , S. Levy. I O-MA R-2 004; DP# 284757). The data indi cate that the metabolism of acequinocyl in these crops in vo lves the lo ss of the acetyloxy moiety to form acequinocyl-OH, opening of the quinone ring to form AKM-18 , and s ubsequ e nt degradation of the quinone rin g to y ie ld polar metabolites that degrade to phthalic acid. Based on the structura l similarity of acequinocyl-OH to parent and the presence of acequinocylOH at quantifiable levels in crops , the HED Metabolism Assessment Rev iew Committee (MARC) concluded that parent and acequinocyl-OH are the residues of concern for risk assessme nt and tolerance express ion in apples , oranges , and eggplant commodities (Memo, S. Levy , 07 -JA N

- 2004; DP # 297872). HED translated these results to hops and ed ibl e - podded beans as these two c rops a re low-consumpti on food items. However , if in the future the petitioner reque s ts new u ses where apple, orange, and eggplant metabolism data cannot be trans lated, HED may ask for add it ional plant metabo li sm data. There are no li vestock feedstuffs associated w ith hops. Therefore, data requirements for li vestock metabolism are not relevant to this tolerance petition.


### 86 0 .134 0 R es i du e An a ly t ica l Me th o d s Adequate analytical methods are available for e n fo rci ng acequinocyl to leranc es in/on the re g istered p lant commodities (Memo, D. Soderbe rg 23-MA Y-2006 ; DP # 321753; Memo, S. Levy , 25 -JUN- 2008 ; DP #s 35 1336 & 353313). These methods include two LC/MS/MS method s for determinin g acequ in ocyl and acequinocyl-OH residues in fruit crops (Morse Method # Meth133 , revision # 3) and nut crops (Morse Method # Meth-135)
. Method # Meth-135 , Revision # 3 , is a suitable enfo rcement method for hops (Memo. S. Levy , 25

- AUG

- 20 IO; DP# 380302).


### 860.136 0 M u lti r es i d u c Me th od s Accepta ble MRM method testing data were s ubm itted for acequinocy l and acequinocyl-OH , and Page 4 of7Acequinocyl Summary of Analytical Chem istry and Residue Data DP # 427588 the se data were forwarded to the U.S. F D A fo r fu rth e r eva luation (Memo , S. Le vy, I 8-FEB2004; DP# : 2989 1 7). Ace quinocyl was adequatel y reco ve red from fortified apples u si ng Method 302, E l + Cl with GC/ e lectron-capture detecto r (EC D ), bu t was not recovered using Method 303 or 304 due to poor recoveries from the Florisil c lean up. Acequinocyl-OH was com pl ete l y recovered from fortified a ppl es us i ng M ethod 402 , E 1 or E2 + Cl with GC/EC D , but was not r ecover e d usin g M e th ods 302, 303, or 304.


### 8 60
. 13 8 0 S tora ge S t a bili ty To su pport the samp l e s torage condit i ons an d duration s . a co ncurrent stora ge s tability study was conducted in conjunction w ith the analysi s of th e field tri a l sam ples . U ntreated sam ples of dried hop cones we r e fortified w ith acequ i no cy l or aceq uin ocy l-OH at 0.10 ppm a nd sto red frozen. Res idu es of acequ ino cy l and acequinocyl-OH we re relat ive ly stab l e in / on h o p dried cones stored fro ze n for up to 411 day s . 

### 8 60 .1480 Me at , M ilk, Po u ltry, a nd Eggs Th e re are no li ves tock food/ feed ite m s of regulat ory co ncern associated w ith hops ; therefore , a di scuss ion of live s tock res idues is not germane to this petition.


### 860
. 1500 C rop F ie ld Tri a ls Reference European Foo d Safety Authority (EFSA) J ournal 20I0;8(12): 1 937 In s upport to the MRL a pplication , the appli cant s ubmitted eig ht ou t door s upervi se d residue trials carried out in Germany from 2005 to 2006. The s tudies we re in co mpliance w ith the intended GAP (see Tab l e 3), a si ngle application at 0.61

- 0.62 lb ail A. The s up e r v ise d re s idu e trial san1pl es were analy ze d within 18 months of ha r vest. Storage s tab i lity data ar e availabl e to s upport the storage inte r va ls and conditions incurre d by th e subject field trial samples. Sample a nalysis carried out b y liqu id chro m atograp hy with tandem mass spect roscopy (LC -MS/MS) and the method was va lidate d on hops cone s at th e limit of quantitation (LOQ) of 0.1 ppm. Acequ in ocy l resi du es in dry hop cones ranged from 0.49 to 9.7 ppm . Th e res ult s of the residue trial s are summarized in Table 4. EFSA conc lud ed that the data were s uffici e nt to derive an MRL of 15 ppm. Ta bl e 4. S umma ry o f Res idu es fro m Ge rman Hop T r ia ls with Aceq u in ocy l
. App. Rate ( l b PHI Aceq uin ocyl R esidues (p pm) Crop Matri x ai/A) ( days) n Min. Max. LAFT 1 HAFT 1 Median Dried H op 0.61-0.6 2 2 1 8 0.49 9
. 7 0.49 9.7 2 .6 Co nes 1 LAFT = lowest average fi e ld rri a l , H AFT= hi ghest average fi e ld trial , SD = s tand ard deviati o n . n = number of field tri a ls. M ea

n 

## s o• 3.6 3
. 5



### Conclus ion s: Th e U
. S
. to lerance (4
. 0 ppm ) is ba sed on three hop fi e ld tr ial s co ndu c ted in NAFTA Gro wing Zone 11 (ID, OR, WA) duri ng th e 2005 grow in g seaso n . E ach trial consisted of one untreated and one treated plot. At eac h s ite. a 1.25 lb / gal SC fonn ul ati on of acequinocyl was applied to hop s as two directed foliar ap pl i cat i o n s during cone d eve l o pment at rates of 0
. 288

- 0.330 lb 

### ai l A/app li ca tion , with a 19- to 28 day RTI , for a total rate of 0.588-0.641 lb a i / A Page 5 of7Aceguinocyl Summary of Anal yti cal C hemi s try and Re sidue Data DP # 427588 (

- 1 X). Total residues of acequino c yl and acequinocy l-OH we r e 1. 32

- 2.83 ppm in/o n dried hop cones . Th e German res idu e data (2 X U.S. si ng le app li cat io n rate; l X U.S. s easo nal application rate , longer PHI , parent o nl y) sh ow that the U.S. tolerance level i s like ly set at too lo w of a l eve l. HED notes that analysis of the U
. S. data w ith th e OEC D C alcu lator wou ld h ave resulted in a recommended tolerance of 7
. 0 ppm. Harmoni zati o n o f the U .S. toleran ce leve l with the MRL of 15 ppm i s thu s reco mm e nd e d.


### 860.1520 Processed Food a nd Fee d There are no processed foo d ite m s of re g ul atory inte res t for hop s. Therefore , res idue data pertaining t o pro cessed co mmoditie s are not ge rm an e to this toleranc e petition.


### 860.1650 S ubmittal of Anal ytical R efere n ce S t a ndard s A nal ytical s tand ard s fo r aceq uinoc yl and it s metabo li te 2 -dodec y l- 3 -h ydroxy- 1 , 4- naphthoquinone , wi th expiration dates of 08-MA Y-2017 , are currently available in the EPA Nati o nal P esticide Standards Repos itory (pe rso nal communication s with Gregory Ve rdin , AC B , 06-JUN-20 1 5 & 1 9-JAN-20 1 6).


### 860.1850 and 1900 Co nfined and F ield Accumulation in Rotational Cro p s Hops are not t y pi ca ll y a ro tate d crop. Th e refo re, data re quirement s fo r rotationa l crops are not relevant to thi s tolerance petition
. 

### 86 0
. 1550 Proposed To lera nc es R esi due definition s and MRL s for acequinocyl have not been estab li s hed by Co d ex. The U.S. and Canadi an re s idu e de finition s are harmoni ze d. The r e is currently no es tabli shed Canadian MRL for acequinocy l in/on hop s. The U.S. and EU re s idue definition s are not harmoni ze d as th e U.S. r es idu e d efi niti o n in cludes a metabolite ; however , th e tolerance/MRL leve ls wi ll be harmonized by thi s action.

T able 7. T ole r a n ce S ummary fo r Aceq u i n ocy l. 

# I Proposed To lerance 

# I Recommended Commod ity (p pm ) Tolerance (ppm) 40 CFR § 1 80.599(a) Hop , dried cones 

## I 15.0 

## I 15
Attachment I: Internati ona l R es idue Limit Statu s Sheet

RD!: RAB I C hem is ts (20- J AN-20 1 6) cc: G. Kramer G. F. Kramer:S I 0957:PY-S:(703)305-5079:7509P:RAB I Pa g e 6 of7 

# I Comments; Co rrect Comm o dity De

finiti o n 

## IAcequinocyl Summa ry of Analytical Ch emistry and Residu e Data DP # 427588 

### Attac hme nt 1 : Intern at i o n a l Re s idue Lim its 

### I nternational R es idu e Limit s Acequinocy l (006329 ; 6/ 22115) Su mm a ry of U.S. Tol e ran ces a nd Inte rnation a l MRL s. 

### U.S. C a n ada Mex ico 2 Codex Res idu e D e finiti o n : 40 CFRl 80.599 2-(acetyloxy) -3-dodec y l-1 ,4- None (a) Compliance with the tolerance levels specified naphthalenedione , including below is to be detennined by measuring only the th e merabolite 2

-dodecyl-3- s um of acequinocyl [2 -(acetylox y) -3-dodec y l-1 ,4- h y droxy-1 ,4

- naphthalenedione] and it s metabolite, 2-dodecyl-3- naphthalenedione hydroxy-1 ,4-naphthoquinone. calculated as th e stoichiometric equivalent of acequinocy l Co mm od ity Tolerance (00 111 ) /Maximum R esi du e Limit ( mg/kg) Co mm o di ty• 

### U.S. Ca n a d a Mex ico 2 Codex Hop, dried cones 15 1 Includes only commoditie s of interest for this action. To lerance values should be the HED recommendations and not those proposed by the applicant. 2 Mexico adopts U S tolerances and/or Codex MRLs for it s ex pon purposes.

Pa gc7o f7