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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Venus Eagle

Petition #5E8422

Summary of Petition 

EPA has received a pesticide petition (5E8422) from Interregional Research Project 

Number 4 (IR-4), 500 College Road East, Suite 201W, Princeton, NJ 08540 proposing, 

pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), to amend 40 CFR part 180 by amending the existing tolerance for 

residues of 3-dodecyl-1,4-dihydro-1,4-dioxo-2-naphthyl acetate and its metabolite 2-

dodecyl-3-hydroxy-1,4-naphthoquinone expressed as acequinocyl equivalents. Arysta, in 

conjunction with IR-4, is requesting for the establishment of new tolerances on avocado, 

dry shelled beans, and squash as well as an import tolerance on tea for the combined 

residues of the insecticide acequinocyl, 2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione 

and its metabolite, 2-dodecyl-3-hydroxy-1,4-naphthoquinone (acequinocyl-OH) 

expressed as acequinocyl equivalents. The proposed new tolerances are in or on the raw

agricultural commodities: Avocado at 0.4 parts per million (ppm), Bean, dry, seed at 0.03 

ppm, Vegetable, cucurbit, group 9 at 0.2 ppm, Tea, plucked leaves at 40 ppm, Cherry 

subgroup 12-12A at 1.0 ppm, Fruit, citrus, group 10-10 at 0.20 ppm, Fruit, pome, group 

11-10 at 0.40 ppm, Nut, tree, group 14-12 at 0.02 ppm, Vegetable, fruiting, group 8-10 at 

0.70 ppm. 

The petitioner, IR-4, proposes, upon the approval of the aforementioned tolerances, to 

remove established tolerances for residues of acequinocyl in or on the following raw 

agricultural commodities: Cucumber at 0.15 ppm, Melon, subgroup 9A at 0.15 ppm, 

Cherry, sweet at 0.50 ppm, Cherry, tart at 1.0 ppm, Fruit, citrus, group 10 at 0.20 ppm, 

Fruit, pome, group 11 at 0.40 ppm, Nut, tree, group 14 at 0.02 ppm, Pistachio at 0.02

ppm, Vegetable, fruiting, group 8 at 0.70 ppm, Okra at 0.70 ppm.

EPA has determined that the petition contains data or information regarding the elements 

set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the 

sufficiency of the submitted data at this time or whether the data supports granting of the 

petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry 

1. Plant metabolism. The nature of the residues of acequinocyl in plants is adequately 

understood as studies have been conducted on three crops; apples, oranges and eggplant. 

The major residue in all plant metabolism studies is acequinocyl. A minor but significant 
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metabolite is acequinocyl-OH (2-dodecyl-3-hydroxy-1,4-naphthoquinone). The proposed 

tolerance expression is the parent, acequinocyl and its hydroxy metabolite, acequinocylOH.

2. Analytical method. The analytical method to quantitate residues of acequinocyl and 

acequinocyl-OH in/on fruit crops utilizes high pressure liquid chromatography (HPLC) 

using mass spectrometric (MS/MS) detection. The target limit of quantitation (LOQ) is 

0.01 ppm.

3. Magnitude of residues. The proposed new crop tolerances are based on residue trials 

conducted by IR-4. Tolerances for acequinocyl on cucumber and melon have already 

been established; the new residue trials on squash were conducted which would allow for 

the establishment of a tolerance for the Cucurbit Vegetables Crop Group 9. The 

proposed import tolerance for tea of 40 ppm is based on the acequinocyl tea tolerance 

listed by the Japan Food Chemical Research Foundation. In addition this assessment 

includes the increased tolerance for hops, dried cone of 15.0 ppm. A Notice of Filing to 

increase the hops, dried cone tolerance from 4.0 to 15.0 ppm was submitted by Arysta in 

May, 2015 in order to match the tolerance values established in the European Union and 

Japan.

Up to two foliar applications at 31 fl oz (0.3 lb ai) per acre are proposed for avocado, dry 

shelled beans, and squash for a maximum seasonal load of 0.6 lb active ingredient per 

acre per crop. The proposed pre-harvest interval (PHI) for dried shelled beans is 7 days 

while for squash and avocado a 1-day PHI has been proposed.

B. Toxicological Profile 

The complete toxicity profile of acequinocyl was previously published in the Federal 

Register of November 17, 2010 (73 FR 70143). 

1. Acute toxicity. Acequinocyl technical has low acute, dermal and inhalation toxicity in 

laboratory animals. The oral LD50 (M/F) in the rat and mouse was > 5000 mg/kg. The 

dermal LD50 (M/F) was > 2000 mg/kg. The inhalation LC50 was reported as > 0.84 

mg/l. In the eye and dermal irritation studies, acequinocyl technical was not an eye or 

skin irritant to rabbits and was not a skin sensitizer in guinea pigs.

2. Genotoxicty. Acequinocyl was found to be negative in the Ames reverse mutation, 

mouse lymphoma, Chinese hamster lung (CHL) chromosome aberration and mouse 

micronucleus assays.

3. Reproductive and developmental toxicity.
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i. Rat teratology. Acequinocyl technical was administered by oral gavage to pregnant 

Sprague Dawley rats at dose levels of 0, 50, 150, 500 or 750 mg/kg/day. Common signs 

in the descendants included vaginal discharge, pallor, pale eyes, hypoactivity, 

piloerection, slow or irregular breathing, intra-uterine hemorrhage and blood stained 

stomach and/or intestinal contents. Maternal NOEL=150 mg/kg/day based on these signs. 

Developmental NOEL=500 mg/kg/day based on increase in certain skeletal variants that 

may be attributed to the observed maternal toxicity.

ii. Rabbit teratology. Groups of New Zealand white rabbits received acequinocyl 

technical by gavage at doses of 0, 30, 60 or 120 mg/kg/day. Maternal NOEL=60 

mg/kg/day based on reduction in maternal body weight and 5 females were sacrificed at 

120 mg/kg/day. Fetal NOEL=60 mg/kg/day due to skeletal variations in the thoracolumbar ribs.

iii. Rat reproduction study. Acequinocyl technical was fed to two generations of male and 

female Sprague Dawley rats at dietary concentrations of 0, 100, 800, or 1500 ppm (0, 7.3, 

59 or 111 mg/kg/day for males and 0, 8.7, 69 or 134 mg/kg/day for females). Systemic 

and pup NOEL=100 ppm (7.3 and 8.7 mg/kg/day). Systemic: Hemorrhage and swollen 

body parts were seen at 800 and 1500 ppm in F1 males . At 800 and 1500 ppm, treatment 

related clinical signs, hemorrhagic effects, subcutaneous bleeding on body parts and/or 

cranium and/or brain were seen in the F1 pups. At 800 and 1500 ppm toxicity seen in F2 

pups included subcutaneous bleeding on body parts and/or cranium and/or brain at 

weaning.

4. Subchronic toxicity. 

i. Rat feeding study. Fischer rats received acequinocyl technical at dietary concentrations 

of 0, 100, 400, 1600 or 3200 ppm (0, 7.57, 30.4, 120, 253 mg/kg/day, respectively for 

males and 0, 8.27, 32.2, 129, 286 mg/kg/day, respectively for females) for 13 consecutive 

weeks. Treatment related yellow brown urine in all animals of both sexes at 400 ppm 

suggested the presence of the metabolite of the test material. Macroscopic examination 

on the surviving animals revealed no treatment related abnormalities. At 3200 and 1600 

ppm, macroscopic and microscopic examination of the mortalities revealed hemorrhaging 

of muscle and other organs. NOEL=400 ppm (30.4 mg/kg/day for males and 32.2 

mg/kg/day for females). 

ii. Mouse feeding study. Groups of CD-1 (ICR) BR mice received acequinocyl technical 

by oral route at concentrations of 0, 100, 500, 1000 or 1500 ppm (0, 16, 81, 151, 295 

mg/kg/day respectively for males and 0, 21, 100, 231, 342 mg/kg/day respectively for 

females) for 13 weeks. At 100 ppm, there were hepatic histopathological lesions and an 

increase in relative liver weight. A clear NOEL for both sexes was not determined. 
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iii. Dog feeding study. Acequinocyl technical was administered via gelatin capsule to 

male and female beagle dogs at dose levels of 0, 40, 160, 640 or 1000 mg/kg/day once a 

day 7 days a week for 13 weeks. At 40, 160 and 640 mg/kg/day colored feces were 

observed in both sexes. At 160 and 640 mg/kg/day, treatment related decrease in body 

weight gain in males and an increase platelet count for females was observed. 

Macroscopic and microscopic examinations on the surviving animals revealed no 

treatment related abnormalities. A clear NOEL was not determined.

iv. 28-day dermal toxicity. Groups of Sprague Dawley rats received daily dermal 

applications of acequinocyl technical at doses of 0, 40, 200 or 1000 mg/kg/day for 6 

hours/day for 28 days followed by a 14 day treatment free period only in the high dose 

group. There were no macroscopic findings. Red staining occurred on the back of the 

animals and was only seen in the morning after dosing. There was no evidence of 

systemic toxicity. NOEL=1000 mg/kg/day.

5. Chronic toxicity.

i. Dog feeding study. Beagle dogs were dosed by capsule at 0, 5, 20, 80 or 320 mg/kg/day 

for 1 year with acequinocyl technical. Minor disturbances in platelet counts were 

observed in both sexes at 80 and 320 mg/kg/day. There were no treatment related 

macroscopic histopathological findings. Colored feces and/or abnormally stained sawdust 

were observed for all treatment groups. Varying degrees of discoloration of the urine was 

observed for animals receiving 20 mg/kg/day or more. The discoloration was considered 

to be attributable to a colored metabolite of the test substance. NOEL=20 mg/kg/day.

ii Rat feeding/oncogenicity study. Groups of F344 rats received acequinocyl technical at 

dietary levels of 0, 50, 200, 800 or 1600 ppm (0, 2.25, 9.02, 36.4, 74.0 mg/kg/day for 

males and 0, 2.92, 11.6, 46.3, 93.6 mg/kg/day for females) for 2 years. NOEL=200 ppm 

(9.02 and 11.6 mg/kg/day for males and females respectively). Corneal abnormalities and 

hypertrophy of the eye were observed in 800 ppm and 1600 ppm males and 1600 ppm 

females. At 800 ppm and 1600 ppm, PT was observed to be longer in males and shorter 

in females and APTT longer in females. Reddish brown urine was observed in both males 

and females. There was no incidence of tumors.

iii. Mouse oncogenicity study. Acequinocyl technical was administered in the diet of 

Crl:CD-1(ICR)BR mice at 0, 20, 50, 150 or 500 ppm for 80 weeks. NOEL=20 ppm 

(lowest dose tested equal to 2.7 and 3.5 mg/kg/day in males and females respectively), 

based on brown pigmented cells. At 50 and 500 ppm in both sexes, there was an increase 

incidence of fatty hepatocytes. Other associated findings were increased liver weight, 

slight increase in pale livers or pale areas within livers. Glomerular amyloidosis was 

statistically increased in the 150 and 500 ppm males. Yellow brown urine was 
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consistently found in both sexes at high dose. There was no increase in the incidence of 

tumors.

6. Animal metabolism. Sprague Dawley rats were dosed orally with acequinocyl labeled 

14C-phenyl or 14C-dodecyl. Both labels were used in the single low dose (10 mg/kg) 

study. The high dose (500 mg/kg) and 14-day repeat dose studies (10 mg/kg/day) were 

conducted with 14C-phenyl acequinocyl only. Excretion was rapid, with most of the dose 

in the feces. Less than 15% of the radioactivity was found in the urine. Absorption was 

about 25-42% based on the bile duct cannulation studies, which found 20-33% of the 

administered dose in bile, plus 5-9% in urine plus cage wash. Acequinocyl was not 

detected in urine and was only a minor component (1-2%) in the feces. The major fecal 

metabolite (12-36%) was the 2-hydroxy-3-dodecyl-1,4-naphthalenedione (acequinocylOH or designated R1). Subsequent oxidation of the dodecyl chain yielded butanoic and

hexanoic acids, the only measurable identified urinary metabolites. 2-(1,2-

dioxotetradecyl)-benzoic acid comprised 19-40% of the radioactivity in the feces. There 

were no remarkable differences in metabolite disposition due to gender and no effect of 

pre-dosing for 2 weeks. The large dose slowed transit time and reduced absorption.

7. Metabolite toxicology. NA-Remove.

8. Endocrine disruption. A standard battery of toxicity tests have been conducted on 

acequinocyl. No effects were seen to indicate that acequinocyl has an effect on the 

endocrine system.

9. Immunotoxicity. NA-Remove.

C. Aggregate Exposure 

1. Dietary exposure. 

i. Food. Tolerance-level residues and 100% CT data were used in the chronic dietary 

assessment. DEEM default processing factors were used with the exception of those for 

grape juice and raisins. As residues were reduced in both grape juice (<0.02x) and raisin 

(0.15x), separate tolerances are not required for these commodities. The DEEM ver. 7.81 

default processing factors for juice and raisin were set to “1” as concentration was shown 

not to occur (Levy et al, 2011). The chronic dietary assessment was based on the most 

recent dietary risk assessment for acequinocyl (Levy et al, 2011). 

Permanent tolerances are currently established under 40 CFR §180.599(a) for the 

combined residues of acequinocyl and its metabolite, acequinocyl-OH, expressed as 
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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. This assessment takes into account the removal of 

several established individual tolerances that have been superseded by inclusion in crop 

group tolerances or by updated commodity terminology (Federal Register Notice, May 2, 

2012).

As cowpea forage and hay are significant feedstuff for livestock (dairy cattle only), the 

maximum reasonable balanced diet (MRBD) for acequinocyl was recalculated by EPA in 

2011 using the Agency’s most recent guidance on constructing reasonably balanced 

livestock diets (Science Advisory Council for Chemistry (ChemSAC) memo, 30-JUN2008). The beef cattle MRBDs did not need to be recalculated as cowpea forage and hay 

are not beef feed items. The feeding study data indicate that the currently established 

tolerance level of 0.02 ppm for residues in cattle, goat, horse, and sheep fat is appropriate. 

Furthermore, the 0.02 ppm residue level is sufficient to cover residues of the additional 

metabolite (AKM-15) of concern in ruminant liver and kidney. The established 0.02 ppm 

residue level in cattle, goat, horse, and sheep liver are appropriate; however, the 

commodity definition should be changed to “meat byproducts” rather than “liver.” 

ii. Drinking water. There are no drinking water monitoring data available for acequinocyl 

or its metabolite acequinocyl-OH (R1), the residues of concern. Groundwater estimated 

drinking water concentrations (EDWCs) were generated by EPA for acequinocyl using 

the Screening Concentration in Ground Water (SCI-GROW) Model. Surface water 

EDWCs were generated using the Pesticide Root Zone Model/Exposure Analysis 

Modeling System (PRZM/EXAMS) model for all proposed uses except cranberry. Since 

cranberry harvesting may involve field flooding and PRZM/EXAMS is not currently 

capable to assess this type of scenario, cranberry was assessed using the provisional 

cranberry model. The most conservative EDWC value was 6.69 ppb (0.00669 ppm) 

derived via the surface water Approach #1 for the use pattern in cherries and grapes. The 

upper-bound value of 6.69 ppb was used in the DEEM-FCID model for “water, direct, all 

sources” and “water, indirect, all sources” (Levy et al, 2011).

2 Non-dietary exposure. 

i. Residential Handler: Acequinocyl is currently registered for use on landscape 

ornamentals in and around residences, businesses, public property, schools, 

interiorscapes, and other non-production areas by commercial applicators and 

homeowners. Therefore, there is the potential for residential handler exposure when 

applying to landscape ornamentals and ornamental or fruit trees. Based upon the 

proposed use pattern, the following two residential handler scenarios were assessed by 

EPA (Lowe, 2007):
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(1) mixing/loading/applying liquids with low pressure handwand 

(2) mixing/loading/applying liquids with hose-end sprayer 

Because no chemical-specific data were available with which to assess potential exposure 

to pesticide handlers, the estimates of exposure were based upon surrogate study data 

from the ORETF and PHED. 

New residential handler exposure and risk assessments were conducted using the EPA 

2012 Residential SOPs which contain updated surrogate unit exposures and input 

parameters. As in 2007, homeowner handler assessments are based on the assumption 

that individuals are wearing shorts, short-sleeved shirts, socks, and shoes. Residential 

handler exposure scenarios are considered to be short-term only, due to the infrequent use 

patterns associated with homeowner products. 

Table 1 presents the exposure/risks for residential short-term dermal and inhalation 

exposures. Based on the residential handler assessment, there are no risks of concern for 

residential handlers (i.e., MOEs > 100).

Table 1: Residential Handler Exposure and Risks 

Dermal and

Inhalation Unit 

Exposures (mg/lb 

ai)1

Application 

Rate 

(lb ai/gallon)2

Amount 

Handled 

Daily1

(gallons)

Doses (mg/kg/day)3 MOEs4

Mixer/Loader/Applicator – Manually Pressurized Handwand 

Dermal

63

0.00125 5

Dermal

0.00492

Dermal

40,635

Inhalation

0.0018

Inhalation

1.4E-06

Inhalation

4.27E+07

Mixer/Loader/Applicator –Hose-End Sprayer

Dermal

58 

0.00125 11

Dermal

0.00997

Dermal

20,000

Inhalation

0.0014 

Inhalation

2.4E-06

Inhalation

 2.49E+08

1From 2012 EPA Residential SOPs

3Application rate is the maximum application rate determined from the label for 

acequinocyl
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2Dose (mg/kg/day) = Unit exposure (mg/lb ai) x App Rate (lb ai/gal) x Amount 

Handled (gal/day) x % Absorption (100%) /Body weight (80 kg) 

4MOE = NOAEL/Dose; where the short-term dermal NOAEL = 200 mg/kg/day and 

short-term inhalation NOAEL = 60 mg/kg/day

ii. Residential Post-Application: With respect to residential post-application exposures, 

new HED policy (2012 Residential SOPs) specifies that there is potential for postapplication dermal exposure following applications to residential landscape ornamentals 

and trees, either by adults or children between the ages of 6 and 11; therefore, a new 

residential post-application assessment was conducted.

Using the input parameters provided in Table 2-3 of the 2012 Residential SOPs, dermal 

re-entry exposure for adults and children to treated ornamentals and treated trees was 

calculated. The exposures were compared to the dermal NOAEL of 200 mg/kg/day to 

generate a margin of exposure. All margins of exposure exceed 100, indicating 

acceptable risk.

Table 2: Residential Post-Application Dermal Risks

Use Scenario

Application 

Rate1

(lb ai/A)

TC 

(cm2/hr)

Exposure 

Time (hr)

Dermal Dose 

(mg/kg/day)2 MOE3

Adults

Garden re-entry

0.21

8400 2.2 0.1359 1,470

Tree re-entry 1700 1.0 0.0125 2,148

Children (6 to <11 years)

Garden re-entry

0.21

4600 1.1 0.0931 15,986

Tree re-entry 930 0.5 0.00855 23,378

1Application rate = 0.00125 lb ai/gallon x 5 gallons/day ÷ 0.03 A (spot treatment)

2Daily dose = DFR x TC x ET ÷ BW (80 kg adults; 32 kg children) DFR = 25% of the 

application rate

3MOE = NOAEL/Dermal Dose where the short-term dermal NOAEL = 200 mg/kg/day 

D. Cumulative Effects 

There is no information available to indicate that toxic effects produced by acequinocyl 

are cumulative with those of any other compound. Arysta LifeScience North America, 

LLC will submit information, if necessary, for EPA to consider concerning potential 

cumulative effects of fluoxastrobin consistent with the schedule established by EPA at 62 
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Federal Register 42020 (Aug. 4, 1997) and other EPA publications pursuant to the Food 

Quality Protection Act.

E. Safety Determination 

1. US Population.

i. Short-Term Aggregate Risk: Short-term aggregate risk is made up of average dietary 

exposures from food and drinking water sources, and dermal and inhalation residential 

exposures. Since acequinocyl has a residential use on ornamentals, adult residential 

handler exposure and post-application exposure is possible. In addition, there is potential 

for children between the ages of 6 and 11 to come into dermal contact with foliar 

residues. Based on the chronic dietary exposure, the “total US population” is the highest 

exposed adult population and can be considered protective of the other adult subgroups; 

therefore, this population was chosen for the aggregate risk assessment along with 

children, ages 6 to 12, as this most closely matches the subgroup that has potential for 

residential exposure through dermal post-application activities. The results of the shortterm aggregate risk assessment are shown in Table 3.

Dietary (food and drinking water) exposure is based on a Tier 1 (unrefined) chronic 

dietary exposure assessment (see Table 2). Residential exposure estimates are 

conservative estimates due to the standard assumptions that were built into the 

calculations. Residential exposure estimates were taken from Tables 1 and 2. The shortterm aggregate risk calculations for the general U.S. population and children, 6 to 12 

years old, are shown below in Table 3. Both aggregate MOEs are greater than 100 and 

therefore are not of concern. 

Table 3: Short-Term Aggregate Risk Calculations.

Population Dietary MOE1 Residential 

Dermal MOE2

Residential 

Inhalation MOE2

Aggregate

MOE3

U.S. 

Population 16,211 1,370 4.27E+07 1,263

Children, 6 to 

12 years 12,002 2,148 NA 1,822

1

 Dietary MOE = short-term oral NOAEL (60 mg/kg/day)  chronic dietary exposure.

2

 Residential MOEs are from Tables 3 and 4. The “hose-end sprayer” scenario was used 

for the general US population as the MOE for this scenario is lower (more conservative) 

than the “manually pressurized handwand” MOE; the hose-end sprayer dermal dose was 

added to the garden reentry dose. For children, the garden reentry dermal dose was used 

as the MOE for this scenario is lower than for tree reentry.
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3

 Aggregate MOE (dietary and residential) = 

1((1MOEdietary)+(1MOEdermal)+(1MOEinhalation)); LOC = 100.

ii. Intermediate-Term Aggregate Risk: Intermediate-term aggregate risk was not 

calculated since the use pattern is not expected to result in residential handler or postapplication exposure of more than 30-day duration. 

iii. Long-Term Aggregate Risk: Chronic (long-term) aggregate risk is made up only of 

dietary sources; therefore, the chronic exposure estimates provided in the chronic dietary 

exposure analysis (see Table 4) represents chronic aggregate exposure.
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Table 4. Summary of Tier 1 Estimates of Exposure and Risk from Chronic Dietary 

Exposure to Acequinocyl

Population 

Subgroup

Chronic1

Dietary Exposure

(mg/kg/day) % cPAD

Total U.S. Population 0.003912 14.5

All Infants (< 1 year) 0.006399 23.7

Non-Nursing Infants (< 1 year 

old) 0.007950 29.4

Children (1-2 years) 0.015811 58.6

Children (3-5 years) 0.011082 41.0

Females (13-49 years) 0.002923 10.8

Youths (13-19 years) 0.002766 10.2

Adults (20-49 years) 0.003020 11.2

Adults (50+ years) 0.002981 11.0

1The chronic dietary cPAD of 0.027 mg/kg/day applies to the general U.S. population 

and all population subgroups.

2. Infants and children. The short-term aggregate risk calculations for the general U.S. 

population and children, 6 to 12 years old, are shown below in Table 3. Both aggregate 

MOEs are greater than 100 and therefore are not of concern. 

F. International Tolerances

Codex maximum residue levels (MRLs) are not yet established for acequinocyl.