UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: 

Subject: 

22-MAR-20 16 

Acequinocyl. Petition for Increasing the Permanent Tolerance for Residues in/on 

Hops. Summary of Analytical Chemistry and Residue Data. 

PC Code: 006329 

Decision No.: 505001 

Petition No.: 5F8364 

DP No.: 0427588 

Registra tion No.: 66330-38 

Regulatory Action: Amend an Established Tolerance 

Risk Assessment Type: A Case No.: 7621 

TXR No.: A CAS No.: 57960-19-7 

MRID No.: None 40 CFR: § 180.599 

From: 

Through: 

To: 

George F. Kramer, Ph.D., Senior Chemist~~ ' > 

Risk Assessment Branch 1 (RAB 1) 

Health Effects Division (HED, 7509P) 

Charles w. Smith m, Branch ChiC~ 

RAB 111-IED (7509P) 

Andrew ErtmanNenus Eagle, RM 1 

Registration Division (RD, 7505P) 

Executive Summary 

Arysta LifeScience is requesting to increase the existing tolerance for residues of the insecticide 

acequinocyl, 2-(acetyloxy)-3-dodecyl-l ,4-naphthalenedione, and its metabolite, 2-dodecyl-3-

hydroxy-1,4-naphthoquinone, expressed as acequinocyl equivalents in/on hops from 4.0 ppm to 

15.0 ppm. The purpose of the amended tolerance is to harmonize the value with the established 

maximum residue limit (MRL) in the European Union (EU). The domestic residue data for hops 

were previously submitted and reviewed under PP#9E7598 (Memo, S. Levy, 25-AUG-201 O; 

D369100). 

Tolerances are currently established under 40 CFR § l 80.599(a) for the combined residues of 

acequinocyl and its metabolite, 2-dodecyl-3-hydroxy-l,4-naphthoquinone, expressed as 

acequinocyl equivalents, in/on a number of plant and livestock commodities. Tolerances for 

plant commodities range from 0.02 ppm (tree nuts and pistachios) to 30 ppm (citrus oil), and 

tolerances for livestock commodities are established at 0.02 ppm in the fat and liver of cattle, 

goat, horse, and sheep. 

The nature of acequinocyl residues in apples, oranges, and eggplants is understood based on the 

previously submitted and reviewed metabolism studies. In these crops, the metabolism of 

acequinocyl involves the loss of the acetyloxy moiety to form acequinocyl-OI-1, the opening of 

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Acequinocyl Summary of Analytical Chemistry and Residue Data DP# 427588 

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. These data are considered sufficient for the 

currently registered crops. For purposes of risk assessment and the tolerance expression, HED 

has determined that the residues of concern in the currently registered crops include parent and 

acequinocyl-OH (Memo, S. Levy. 07-JAN-2004; DP# 297872). 

There are no livestock feedstuffs associated with hops. Therefore, no livestock metabolism data, 

enforcement methods, storage stability data, or feeding studies are required to support this 

petition. 

There are adequate residue analytical methods 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 

(HPLC/MS/MS) for determining residues in/on fruit and nut commodities (Morse Methods 

Meth-133 and Meth-135). For each of these methods, residues are extracted with hexane or 

acetonitrile (ACN)/water and cleaned up by solvent partitioning, gel-permeation chromatography 

(GPC) and/or silica-gel solid-phase extraction (SPE). 

The U.S. tolerance (4.0 ppm) is based on three hop field trials conducted in North American Free 

Trade Agreement (NAFT A) Growing Zone I 1 (ID, OR, WA) during the 2005 growing season. 

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

(RTI), 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. 

single application rate; IX U.S. seasonal application rate, longer preharvest interval (PHI), parent 

only) show that the U.S. tolerance level is likely 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 Recommendations and Residue Chemistry Deficiencies 

There are no residue chemistry issues that would preclude increasing the existing tolerance for 

residues of the insecticide acequinocyl in/on hops from 4.0 ppm to 15 ppm. 

860.1550 Proposed Tolerances 

A summary of the recommended tolerances along with recommendations for commodity 

definitions are presented in Table 5. 

A human health risk assessment will be prepared as a separate document (DP# 431305). 

Background 

Acequinocyl is a quinoline-type miticide that is currently registered for the use in the U.S. on a 

number of RA Cs for the control of various phytophagous mite species. The nomenclature of 

acequinocyl is summari zed in Table 1. The chemical structure and nomenclature of acequinocyl 

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Acequinocyl Summary of Analytical Chemistry and Residue Data DP# 427588 

and its regulated metabolite are presented in Table I, and the physicochemical properties of 

acequinocyl are presented in Table 2. 

Table 1. Nomenclature of Test Compound and Metabolites. 

0 

o7CH,(CH,),.CH, I 

OCOCH3 

Compound 0 

Common name Acequinocyl 

Company experimental names TM-41301 or AKD-2023 

IUPAC name 3-dodecyl-1 ,4-dihydro-I ,4-dioxo-2-naphthyl acetate 

CAS name 2-(acetyloxy)-3-dodecyl-1 ,4-naphthalenedione 

CAS # 57960-19-7 

End-use products/EP Kanemite·:&> 15 SC ( 1.25 lb ai/gal; EPA Reg. No. 66330-38) 

Compound 0 

o7CH,(CH,),.CH, I 

OH 

0 

Common name Acequinocyl-OH 

Company experimental names RI 

IUPAC name 2-dodecyl-3-hydroxy- 1,4-napthoquinone 

CAS name 2-dodecyl-3-hydroxy- 1,4-naphthalenedione 

CAS # 57960-31-3 

Table 2. Physicochemical Properties. 

Parameter Value Reference (MRID) 

Melting point 59.6 c 45434906 

pH 6.94 45434904 

Density 1.13 g/cm3 45434904 

Water solubility ( 20°C) 6.69 μg/L 45434906 

Solvent solubility (mg/Lat 20°C) 1,2-dichloroelhane: >250 45434904 

acetone: >250 

ethyl acetate: >250 

xylene: >250 

methanol: 6. 1 

n-heptane: 36 

n-octanol: 29.2 

Vapor pressure at 25°C 1.69 x I 0·9 pascals 45434905 

Dissociation constant (pK.) no measurable pK. 45434905 

Octanol/water partition coefficient ~6 .2 45434906 

Log(Kow) 

UY /visible absorption spectrum neutralpH:242,248,262,270,335 45434905 

(A.max. nm) acid pH: 242, 248, 265, 270, 330 

basic pH: 232, 245, 255, 275, 362 

860.1200 Directions for Use 

Kanemite® 15 SC Miticide (EPA Reg. No. 66330-38), a 1.25 lb/gal SC fomrnlation of 

acequinocyl is currently registered for use on hops. The U.S. and EU uses are summarized 

below in Table 3. 

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Acequinocyl Summary of Analytical Chemistry and Residue Data DP# 427588 

Table 3. Summary of Directions for Use of Accqui nocyl. 

Applic. Timing, Formulation App lie. Max. No. Max. Seasonal PHI Use Directions and Type, and [EPA Reg. Rate Applic. per Applic. Rate (days) Limitations' Equip. No.) (lb ai/A) Season (lb ai/A) 

Hops (U.S.) 

Postemergence, 1.25 lb/gal Minimum spray volume 

foliar SC 0.3 2 0.6 7 of 100 gal/A; minimum 

Ground only [66330-38] RTI of2 I days. 

Hops (EU) 

Postemergence, 1.25 lb/gal foliar 0.67 I 0.67 21 

Ground only SC 

1 RT! = retreatment interval. 

860.1300 Nature of the Residue - Plants & Livestock 

The qualitative nature of acequinocyl residues in fruit and nut crops is understood based on the 

available apple, orange. and eggplant metabolism studies (Memo, S. Levy. I O-MAR-2004; DP# 

284757). The data indicate that the metabolism of acequinocyl in these crops involves the loss 

of the acetyloxy moiety to form acequinocyl-OH, opening of the quinone ring to form AKM-18, 

and subsequent degradation of the quinone ring to yield polar metabolites that degrade to 

phthalic acid. 

Based on the structural similarity of acequinocyl-OH to parent and the presence of acequinocylOH at quantifiable levels in crops, the HED Metabolism Assessment Review Committee 

(MARC) concluded that parent and acequinocyl-OH are the residues of concern for risk 

assessment and tolerance expression in apples, oranges, and eggplant commodities (Memo, S. 

Levy, 07-JAN-2004; DP# 297872). HED translated these results to hops and edible-podded 

beans as these two crops are low-consumption food items. However, if in the future the 

petitioner requests new uses where apple, orange, and eggplant metabolism data cannot be 

translated, HED may ask for additional plant metabolism data. 

There are no livestock feedstuffs associated with hops. Therefore, data requirements for 

livestock metabolism are not relevant to this tolerance petition. 

860.1340 Residue Analytical Methods 

Adequate analytical methods are available for enforcing acequinocyl tolerances in/on the 

registered plant commodities (Memo, D. Soderberg 23-MA Y-2006; DP# 321753; Memo, S. 

Levy, 25-JUN-2008; DP#s 35 1336 & 353313). These methods include two LC/MS/MS methods 

for determining acequinocyl 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 enforcement method for hops (Memo. S. Levy, 25-AUG-20 IO; DP#380302). 

860.1360 Multiresiduc Methods 

Acceptable MRM method testing data were submitted for acequinocyl and acequinocyl-OH, and 

Page 4 of7 
Acequinocyl Summary of Analytical Chemistry and Residue Data DP# 427588 

these data were forwarded to the U.S. FDA for further evaluation (Memo, S. Levy, I 8-FEB2004; DP#: 298917). Acequinocyl was adequately recovered from fortified apples using Method 

302, E l + Cl with GC/electron-capture detector (ECD), but was not recovered using Method 303 

or 304 due to poor recoveries from the Florisil cleanup. Acequinocyl-OH was completely 

recovered from fortified apples using Method 402, E 1 or E2 + Cl with GC/ECD, but was not 

recovered using Methods 302, 303, or 304. 

860.1380 Storage Stability 

To support the sample storage conditions and durations. a concurrent storage stability study was 

conducted in conjunction with the analysis of the field trial samples. Untreated samples of dried 

hop cones were fortified with acequinocyl or acequinocyl-OH at 0.10 ppm and stored frozen. 

Residues of acequinocyl and acequinocyl-OH were relatively stable in/on hop dried cones stored 

frozen for up to 411 days. 

860.1480 Meat, Milk, Poultry, and Eggs 

There are no livestock food/feed items of regulatory concern associated with hops; therefore, a 

discussion of livestock residues is not germane to this petition. 

860.1500 Crop Field Trials 

Reference European Food Safety Authority (EFSA) Journal 20I0;8(12): 1937 

In support to the MRL application, the applicant submitted eight outdoor supervised residue 

trials carried out in Germany from 2005 to 2006. The studies were in compliance with the 

intended GAP (see Table 3), a single application at 0.61 -0.62 lb ail A. The supervised residue 

trial san1ples were analyzed within 18 months of harvest. Storage stability data are available to 

support the storage intervals and conditions incurred by the subject field trial samples. Sample 

analysis carried out by liquid chromatography with tandem mass spectroscopy (LC-MS/MS) and 

the method was validated on hops cones at the limit of quantitation (LOQ) of 0.1 ppm. 

Acequinocyl residues in dry hop cones ranged from 0.49 to 9.7 ppm. The results of the residue 

trials are summarized in Table 4. EFSA concluded that the data were sufficient to derive an 

MRL of 15 ppm. 

Table 4. Summa ry of Residues from German Hop Trials with Acequinocyl. 

App. Rate (lb PHI Acequinocyl Residues (ppm) 

Crop Matrix ai/A) (days) n Min. Max. LAFT1 HAFT1 Median 

Dried Hop 0.61-0.62 2 1 8 0.49 9.7 0.49 9.7 2.6 

Cones 

1 LAFT = lowest average fi eld rrial, HAFT= highest average fi eld trial, SD = standard deviation. 

n = number of field trials. 

Mean so• 

3.6 3.5 

Conclusions: The U.S. tolerance (4.0 ppm) is based on three hop field trials conducted in 

NAFTA Growing Zone 11 (ID, OR, WA) during the 2005 growing season. Each trial consisted 

of one untreated and one treated plot. At each site. a 1.25 lb/gal SC fonnulation of acequinocyl 

was applied to hops as two directed foliar appl ications during cone development at rates of 

0.288-0.330 lb ail A/application, with a 19- to 28 day RTI, for a total rate of 0.588-0.641 lb ai/A 

Page 5 of7 
Aceguinocyl Summary of Analytical Chemistry and Residue Data DP# 427588 

(- 1 X). Total residues of acequinocyl and acequinocyl-OH were 1.32-2.83 ppm in/on dried hop 

cones. The German residue data (2X U.S. single application rate; l X U.S. seasonal application 

rate, longer PHI, parent only) show that the U.S. tolerance level is likely set at too low of a level. 

HED notes that analysis of the U.S. data with the OECD 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. 

860.1520 Processed Food and Feed 

There are no processed food items of regulatory interest for hops. Therefore, residue data 

pertaining to processed commodities are not germane to this tolerance petition. 

860.1650 Submittal of Analytical Reference Standards 

Analytical standards for acequinocyl and its metaboli te 2-dodecyl-3-hydroxy- 1,4-

naphthoquinone, with expiration dates of 08-MA Y-2017, are currently available in the EPA 

National Pesticide Standards Repository (personal communications with Gregory Verdin, ACB, 

06-JUN-2015 & 19-JAN-2016). 

860.1850 and 1900 Confined and Field Accumulation in Rotational Crops 

Hops are not typically a rotated crop. Therefore, data requirements for rotational crops are not 

relevant to this tolerance petition. 

860.1550 Proposed Tolerances 

Residue definitions and MRLs for acequinocyl have not been established by Codex. The U.S. 

and Canadian residue definitions are harmonized. There is currently no established Canadian 

MRL for acequinocyl in/on hops. The U.S. and EU residue definitions are not harmonized as the 

U.S. residue definition includes a metabolite; however, the tolerance/MRL levels will be 

harmonized by this action. 

Table 7. Tolerance Summary fo r Acequinocyl. I Proposed Tolerance I Recommended 

Commodity (ppm) Tolerance (ppm) 

40 CFR §180.599(a) 

Hop, dried cones I 15.0 I 15 

Attachment I: International Residue Limit Status Sheet 

RD!: RAB I Chemists (20-JAN-20 16) 

cc: G. Kramer 

G. F. Kramer:S I 0957:PY-S:(703)305-5079:7509P:RAB I 

Page 6 of7 

I Comments; Correct Commodity 

Definition 

I 
Acequinocyl Summary of Analytical Chemistry and Residue Data DP# 427588 

Attachment 1: International Residue Limits 

International Residue Limits 

Acequinocyl (006329; 6/22115) 

Summary of U.S. Tolerances and International MRLs. 

U.S. Canada Mex ico2 Codex 

Residue Definition: 

40 CFRl 80.599 2-(acetyloxy)-3-dodecyl-1 ,4- None 

(a) Compliance with the tolerance levels specified naphthalenedione, including 

below is to be detennined by measuring only the the merabolite 2-dodecyl-3-

sum of acequinocyl [2-(acetyloxy)-3-dodecyl-1 ,4- hydroxy-1 ,4-

naphthalenedione] and its metabolite, 2-dodecyl-3- naphthalenedione 

hydroxy-1 ,4-naphthoquinone. calculated as the 

stoichiometric equivalent of acequinocyl 

Commodity Tolerance (00111 )/Maximum Residue Limit (mg/kg) 

Commodity• U.S. Canada Mex ico2 Codex 

Hop, dried cones 15 1 Includes only commodities of interest for this action. Tolerance values should be the H ED recommendations and 

not those proposed by the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its expon purposes. 

Pagc7of7