Acequinocyl Human-Health Risk Assessment D389519

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

MEMORANDUM

Date: 30-NOV-2011

SUBJECT: Acequinocyl; Human-Health Risk Assessment for Proposed Section 3 Uses on 

Succulent Soybean Vegetable; Succulent Shelled Beans; Cowpea Forage; 

Caneberry Subgroup 13-07A; Melon Subgroup 9A; Cucumber, Cherry; LowGrowing Berry Subgroup 13-07G; and Small Fruit Vine Climbing, Except Fuzzy 

Kiwifruit, Subgroup 13-07F.

PC Code: 006329 DP Barcode: D389519

Decision No.: 448205 Registration No.: 66330-38

Petition No.: 1E7864 Regulatory Action: Section 3

Risk Assessment Type: Single 

Chemical/Aggregate

Case No.: 7621

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

MRID No.: NA 40 CFR: §180.599

FROM: Sarah J. Levy, Chemist

Anwar Y. Dunbar, Ph.D., Pharmacologist

Kelly M. Lowe, Environmental Scientist

Risk Assessment Branch 1 (RAB1)

Health Effects Division (HED) (7509P)

THROUGH: Dana M. Vogel, Branch Chief 

George F. Kramer, Ph.D., Branch Senior Chemist

RAB1/HED (7509P)

TO: B. Madden/L. Nollen, Risk Manager (RM05)

Registration Division (RD) (7505P)

The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct dietary, occupational/residential and aggregate exposure assessments, 

as needed, to estimate the risk to human health that will result from the registered and proposed 

uses for acequinocyl on succulent soybean vegetables, succulent shelled beans, cowpea forage, 

caneberry subgroup 13-07A, melon subgroup 9A, cucumber, cherry; low-growing berry 

subgroup 13-07G, and small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F. Note 

that the cucumber and caneberry field trial data were a joint-review with Canada.

A summary of the estimated human health risks resulting from the registered and proposed uses 

for acequinocyl are provided in this document. The risk assessment, residue chemistry data 

review, and dietary exposure assessment were provided by Sarah Levy (RAB1), the hazard 

characterization was provided by Anwar Dunbar, the occupational/residential exposure 
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assessment was provided by Kelly Lowe (RAB1), and the drinking water exposure assessment 

was provided by Michael Lowit of the Environmental Fate and Effects Division (EFED).

Recommendation for Tolerances and Registration

Pending submission of revised Sections B and F, there are no toxicological, residue chemistry, or 

occupational/residential issues that would preclude granting a conditional registration for the 

requested uses of acequinocyl. Permanent tolerances should be established for residues of 

acequinocyl, including its metabolites and degradates, in or on the commodities listed below. 

Compliance with the tolerance levels specified below is to be determined by measuring only the 

sum of acequinocyl [2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione] and its metabolite, 2-

dodecyl-3-hydroxy-1,4-naphthoquinone, calculated as the stoichiometric equivalent of 

acequinocyl, in or on the commodity:

Soybean, vegetable, succulent ....................................................... 0.25 ppm

Low growing berry subgroup 13-07G1 .............................................. 0.50 ppm

Small fruit vine climbing subgroup 13-07F, except fuzzy kiwifruit1 ... 1.6 ppm

Bean, succulent shelled................................................................................. 0.30 ppm

Cowpea, forage........................................................................... 6.0 ppm

Cowpea, hay................................................................................. 18 ppm

Caneberry subgroup 13-07A............................................................ 4.0 ppm

Melon subgroup 9A........................................................................ 0.15 ppm

Cucumber...................................................................................... 0.15 ppm

Cherry, tart................................................................................. 1.0 ppm

Cherry, sweet.............................................................................. 0.50 ppm

Meat byproducts of cattle, goat, horse and sheep1 ........................... 0.02 ppm 1

 Note to RD: With the establishment of these tolerances, the following tolerances should be removed: strawberry; 

grape; and liver of cattle, goat, horse, and sheep.

Registration should be conditional pending resolution of the following deficiencies:

Toxicology

• An Immunotoxicity Study.

• Acute and Subchronic Neurotoxicity Studies.

• A 28-Day Inhalation Study.
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TABLE OF CONTENTS

1.0 EXECUTIVE SUMMARY ................................................................................................... 4

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION............................... 8

2.1 Identification of Active Ingredient ........................................................................... 8

2.2 Structural Formula of Acequinocyl and Acequinocyl-OH .................................... 8

2.3 Physical and Chemical Properties of Acequinocyl ................................................. 8

3.0 HAZARD CHARACTERIZATION/FQPA CONSIDERATIONS................................... 9

3.1 Hazard Profile ........................................................................................................... 9.

3.2 FQPA Considerations.............................................................................................. 11

3.3 Dose-Response Assessment ..................................................................................... 12

3.4 Recommendation for Aggregate Exposure Risk Assessments............................. 14

4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION ........................................ 15

4.1 Summary of Uses...................................................................................................... 16

4.2 Dietary Exposure/Risk Pathway............................................................................. 17

4.2.1 Residue Profile .......................................................................................... 17

4.3 Water Exposure/Risk Pathway............................................................................... 20

4.4 Dietary Exposure Analyses..................................................................................... 21

4.4.1 Chronic Dietary Exposure Analysis........................................................ 22

4.5 Residential/Non-Occupational Exposure Pathway............................................... 23

4.5.1 Short-term Residential Handler Risk ..................................................... 23

4.5.2 Short-term Residential Post-application Risk........................................ 23

4.5.3 Spray Drift................................................................................................. 23

4.5.4 Residential Bystander Post-application Inhalation Exposure .............. 24

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION............. 24

5.1 Acute Aggregate Risk .............................................................................................. 24

5.2 Short-Term Aggregate Risk.................................................................................... 24

5.3 Intermediate-Term Aggregate Risk ....................................................................... 26

5.4 Long-Term Aggregate Risk .................................................................................... 26

5.5 Cancer Risk .............................................................................................................. 26

6.0 CUMULATIVE RISK......................................................................................................... 26

7.0 OCCUPATIONAL EXPOSURE AND RISK ASSESSMENT........................................ 26

7.1 Short- and Intermediate-term Occupational Handler Risk................................. 27

7.2 Short- and Intermediate-term Occupational Post-application Risk................... 29

8.0 RESIDUE CHEMISTRY AND TOXICOLOGY DEFICIENCIES ............................... 31

8.1 Residue Chemistry................................................................................................... 31

8.2 Toxicology................................................................................................................. 31

8.3 Occupational and Residential Exposure................................................................ 31

APPENDIX: Toxicity Profile Tables and Metabolites. .......................................................... 32
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1.0 EXECUTIVE SUMMARY

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

number of raw agricultural commodities (RACs) for the control of various phytophagous mite 

species. Acequinocyl is also registered for use in/on greenhouses, shadehouses, ornamental, 

floral, foliage, nursery crops, landscape ornamentals in and around residences, businesses, public 

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

homeowners. Acequinocyl is currently registered to Arysta Lifescience North America 

Corporation as a 15% soluble-concentrate (SC) formulation.

Under PP#1E7864, the Interregional Research Project No.4 (IR-4), on behalf of the Agricultural 

Experiment Station of TX, CA, OR, PA, GA, NM, OK, TN, UT, MI, FL, and AZ, is requesting 

for the establishment of tolerances for 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 in/on the following 

commodities:

 Soybean, vegetable, succulent ..................................................................0.25 ppm

 Low growing berry subgroup 13-07G ......................................................0.4 ppm

 Small fruit vine climbing subgroup 13-07F, except fuzzy kiwifruit ........1.6 ppm

 Bean, succulent shelled.............................................................................0.15 ppm

 Cowpea, forage .........................................................................................9.0 ppm

 Caneberry subgroup 13-07A.....................................................................4.5 ppm

 Melon subgroup 9A ..................................................................................0.06 ppm

 Cucumber..................................................................................................0.15 ppm

 Cherry .......................................................................................................0.8 ppm

The end-use product proposed for use on the aforementioned proposed crops is KanemiteTM 15 

SC Miticide a 1.25 pounds (lb)/gallon (gal) SC formulation (alternate brand names: ShuttleTM 15 

SC Miticide, and ShuttleTM O Miticide). Up to two foliar, postemergent, ground applications are 

proposed for a maximum seasonal rate of 0.6 lb active ingredient (ai)/acre (A), with a 1-day 

preharvest interval (PHI), except for succulent shelled beans and cherries for which a 7-day PHI 

is proposed.

Hazard Assessment: Acequinocyl has low acute toxicity via the oral, dermal, and inhalation 

routes (Toxicity Categories III and IV). No ocular or dermal irritation was noted. Acequinocyl 

is not a dermal sensitizer. Acequinocyl is a known Vitamin K antagonist; therefore, it is thought 

to produce its adverse effects by disrupting the blood coagulation system, as indicated by 

increased prothrombin time, increased activated partial thromboplastin time, and internal 

hemorrhages. 

In a subchronic oral toxicity study, a 28-day dermal toxicity study, and a chronic 

feeding/oncogenicity study (all in the rat), acequinocyl increased prothrombin and activated 

partial thromboplastin times. Although clotting factors were not measured in some studies (i.e., 

rat/rabbit developmental toxicity study, mouse subchronic/chronic toxicity study, and 2-

generation reproduction rat study), internal hemorrhages were observed. In the combined 

chronic toxicity/oncogenicity study in rats, enlarged eyeballs were observed. Hepatotoxicity in 

the mouse was evidenced by histopathology and increased liver enzymes. 
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In both rat and rabbit developmental toxicity studies, acequinocyl increased the number of 

resorptions. Developmental effects (i.e., resorptions) occurred at a dose that was higher than or 

the same as the dose that caused maternal toxicity. In the 2-generation reproduction toxicity 

study in the rat, there was no evidence of reproductive toxicity, though there were notable toxic 

effects observed in offspring that were not observed in adults including swollen body parts, 

protruding eyes, clinical signs, delays in pupil development and increased mortality occurring 

mainly after weaning. A clear no-observable-adverse-effect level (NOAEL) was observed for 

these effects. 

There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity study, 

indicating that acequinocyl is "not likely" to be carcinogenic to humans. There was no concern 

for mutagenic activity as indicated by several mutagenicity studies.

Dose-Response Assessment and Food Quality Protection Act (FQPA) Decision: The HED 

Hazard Identification Assessment Review Committee (HIARC) met on October 14, 2003, to 

select endpoints for risk assessments and to evaluate the potential for increased susceptibility of 

infants and children. The Committee recommended the FQPA Safety Factor (SF) for increased 

susceptibility of infants and children be reduced to 1X because there are no residual uncertainties 

for pre- and/or post-natal toxicity. In April 2010, HED’s RAB1 toxicology team re-evaluated the 

previously determined endpoints to incorporate any newly submitted data, changes in use 

patterns, and changes in exposure scenarios. For a detailed explanation of the endpoints and 

rationale, see Section 3.3.

Dietary Exposure (Food + Drinking Water): A chronic aggregate dietary (food + drinking 

water) exposure and risk assessment was conducted for acequinocyl using the Dietary Exposure 

Evaluation Model (DEEM-FCIDTM), Version 2.03, which uses food consumption data from the 

U.S. Department of Agriculture’s (USDA’s) Continuing Surveys of Food Intakes by Individuals 

(CSFII) from 1994-1996 and 1998. Tolerance-level residues, DEEM ver. 7.76 default 

processing factors, and 100 percent crop treated (%CT) data were used in the chronic dietary 

assessment. An acute dietary assessment was not conducted for acequinocyl because an 

endpoint of concern attributable to a single dose was not identified; therefore, an acute reference 

dose (aRfD) was not established. A cancer dietary assessment was not conducted because 

acequinocyl was classified as not likely to be carcinogenic to humans.

For the chronic dietary assessment, the general U.S. population and all population subgroups 

have risk estimates that were not of concern to HED. The chronic dietary risk assessment shows 

that the chronic dietary risk estimates do not exceed HED’s level of concern [(LOC); i.e., <100% 

of the chronic population-adjusted dose (cPAD)]. For the general U.S. population, the exposure 

for food + drinking water utilized 13% of the cPAD. The chronic dietary risk estimate for the 

highest exposed population subgroup, children 1-2 years old, is 55% of the cPAD.

Residential Exposure/Risk: 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. The last residential 

exposure risk assessment was conducted in June 2010 (Memo, A. Nowotarski; D369099). All 

risks for residential handlers were above the target margin of exposure (MOE) of 100 and did not 

exceed the LOC. Post-application residential exposure was not anticipated for the registered 

uses, and, therefore, a quantitative residential post-application assessment was not conducted. 

HED has determined that the proposed uses will result in negligible residential exposure. 
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Occupational Exposure Estimates: The occupational handler assessment was completed 

assuming the maximum label application rate for each crop. Based on the activity use pattern, 

the duration of exposure is expected to be short-term (1 to 30 days) and intermediate-term (1 to 6 

months) for occupational scenarios; long-term exposures (greater than 6 months) are not 

anticipated based on the proposed use pattern. For the dermal route of exposure, the same points 

of departure (PODs) were chosen for short-term and intermediate-term exposures; therefore, 

risks are the same for all durations of exposure. For the inhalation route of exposure, different 

PODs were chosen for short-term and intermediate-term exposure durations. The proposed label 

requires a long-sleeved shirt, long pants, shoes plus socks, and chemical-resistant gloves as 

dermal personal-protective equipment (PPE) for all applicators and other handlers. 

Occupational handler dermal and inhalation risk estimates were calculated. For occupational 

handlers, dermal and inhalation MOEs above 100 do not exceed HED’s LOC. All risk estimates 

for occupational handlers are above the target MOE of 100 with the use of gloves, and do not 

exceed the LOC as the proposed labels already require the use of gloves as PPE. 

Occupational dermal post-application risk estimates were calculated using available chemicalspecific dislodgeable foliar residue (DFR) data. There were no risks of concern for all 

occupational post-application activities associated with the proposed uses. Since no risks of 

concern were identified, the restricted-entry interval (REI) is based on the acute toxicity of the 

active ingredient. Acequinocyl is classified in Toxicity Category III for acute dermal and acute 

inhalation. It is classified in Toxicity Category IV for primary eye irritation and primary skin 

irritation and it is not a dermal sensitizer. Therefore, the Worker Protection Standard (WPS) 

interim REI of 12 hours is adequate to protect agricultural workers from post-application

exposures to acequinocyl.

Aggregate Exposure Assessment: Acute and cancer aggregate-risk assessments were not 

performed because no appropriate endpoint was available to determine the aRfD for the general 

population or any population subgroup, and acequinocyl is classified as “Not likely to be 

Carcinogenic to Humans,” respectively. Intermediate- and long-term aggregate assessments 

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

A chronic aggregate exposure risk assessment was assessed by incorporating the drinking water 

directly into the dietary-exposure assessment. As the chronic dietary exposure estimates are not 

of concern to HED for the general U.S. population or any population subgroup, the chronic 

aggregate risk is not of concern for these populations. An aggregate risk assessment was 

performed for short-term aggregate exposure (food + drinking water + residential exposure) 

because there are residential uses. Short-term aggregate exposures and risk estimates were 

calculated for the general U.S. population and females 13-49 years old (this sub-population is the 

highest exposed adult population and can be considered protective of the other adult populations 

groups). The aggregate MOEs are >100, therefore, they do not exceed HED’s level of concern. 

Environmental Justice Considerations: Potential areas of environmental justice concerns, to 

the extent possible, were considered in this human-health risk assessment, in accordance with 

U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in Minority 

Populations and Low-Income Populations,” 

http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf).
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As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under CSFII and are used in pesticide risk assessments for all registered food uses 

of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the 

year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. These data, 

which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); 

the Agricultural Handler Exposure Task Force (AHETF) database; the Outdoor Residential 

Exposure Task Force (ORETF) database; the Agricultural Re-entry Task Force (ARTF) 

database; and MRIDs 454286-19, 456516-11, are subject to ethics review pursuant to 40 CFR 

26, have received that review, and are compliant with applicable ethics requirements. 

Descriptions of data sources as well as guidance on their use can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

Recommendation for Tolerances and Registration: Pending submission of revised Sections B 

and F, there are no toxicological, residue chemistry, or occupational/residential exposure issues 

that would preclude granting a conditional registration for the requested uses of acequinocyl. 

Permanent tolerances should be established for residues of acequinocyl, including its metabolites 

and degradates, in or on the commodities listed below. Compliance with the tolerance levels 

specified below is to be determined by measuring only the sum of acequinocyl [2-(acetyloxy)-3-

dodecyl-1,4-naphthalenedione] and its metabolite, 2-dodecyl-3-hydroxy-1,4-naphthoquinone, 

calculated as the stoichiometric equivalent of acequinocyl, in or on the commodity:

Soybean, vegetable, succulent ......................................................... 0.25 ppm

Berry, low growing, subgroup 13-07G1 ............................................. 0.50 ppm

Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F1... 1.6 ppm

Bean, succulent shelled................................................................................. 0.30 ppm

Cowpea, forage.............................................................................. 6.0 ppm

Cowpea, hay................................................................................. 18 ppm

Caneberry subgroup 13-07A............................................................ 4.0 ppm

Melon subgroup 9A........................................................................ 0.15 ppm

Cucumber...................................................................................... 0.15 ppm

Cherry, tart.................................................................................... 1.0 ppm

Cherry, sweet................................................................................. 0.50 ppm

Meat byproducts of cattle, goat, horse and sheep1 .............................. 0.02 ppm Note to RD: With the establishment of these tolerances, the following tolerances should be removed: strawberry; 

grape; and liver of cattle, goat, horse, and sheep.
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Registration should be conditional pending resolution of the following deficiencies:

Toxicology

• An Immunotoxicity Study.

• Acute and Subchronic Neurotoxicity Studies.

• A 28-Day Inhalation Study.

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

Provided below are the physical/chemical properties for acequinocyl. Most of this information 

was obtained from the acequinocyl “Pesticide Fact Sheet;” 9/26/03 

(http://www.epa.gov/opprd001/factsheets/acequinocyl.pdf).

2.1 Identification of Active Ingredient

Registrant: Arysta Lifescience North America Corporation

Trade Names: Kanemite (EPA Reg.#: 66330-38)

CAS Chemical Name: 2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione

CAS Registry No.: 57960-19-7

Common Name: Acequinocyl

PC Code: 006329

Pesticide Type: Miticide

Chemical Family: Quinoline

Target Pests: Tetranychus, Panonychus and Eutetranychus spp of 

mites

Formulation: Product- KanemiteTM 15 SC; 1.25 lb ai/gal

Types of Formulations: Technical (96.8% ai); End-Use Product (15.8%)

Empirical Formula: C24H32O4

Molecular Weight: 384.5

2.2 Structural Formula of Acequinocyl and Acequinocyl-OH

Acequinocyl Acequinocyl-OH

2.3 Physical and Chemical Properties of Acequinocyl

These physical and chemical properties are for the end-use product unless otherwise noted. 

Appearance: Pale yellow

Physical State: Liquid Suspension

Vapor Pressure: 1.69 x 10-9 pascals at 250C (technical)

Water Solubility: 6.69 μg/L at 200C (technical)

Octanol/Water Partition Coefficient (Log Kow): ≥6.2 (technical)

O

O

CH2( CH2)10 CH3

OCOCH3

O

O

CH2(CH2)10CH3

OH
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Melting Point: 59.6°C (technical)

Density: 1.13 g/cm3

Acequinocyl is a liquid at room temperature, thus, any losses due to volatilization/sublimation 

are expected to be minimal.

3.0 HAZARD CHARACTERIZATION/FQPA CONSIDERATIONS

The existing toxicological database for acequinocyl is complete and supports the establishment 

of permanent tolerances for residues of acequinocyl in/on the RACs resulting from the proposed 

uses. The toxicity profile tables also may be found in the Appendix, Tables A-1 and A-2. The 

following documents support the hazard characterization of acequinocyl:

• Acequinocyl. 2nd Report of the HIARC. Meeting Date: October 14, 2003. P. Terse, 13-NOV-2004; TXR 

No. 0052234.

• Acequinocyl. Report of the HIARC. Meeting Date: July 15, 2003. R. Fricke, 14-AUG-2003; TXR No. 

0052075. 

3.1 Hazard Profile

Acequinocyl binds to the Qo center at Complex III in the mitochondria of mite cells and, 

thereby, exerts its miticidal action by inhibiting electron transfer. Acequinocyl possesses 

moderate activity against plant mitochondrial complex III, in contrast to much higher activity 

against an insect mitochondrial complex III. There is a lack of information regarding whether or 

not acequinocyl inhibits the mammalian mitochondrial electron transfer system. 

Acequinocyl exhibits marginal absorption into the plasma (13-16% for the 10 mg/kg low dose 

and 8-9% for the 500mg/kg high dose) and relatively rapid and complete excretion (24 hours for 

the low dose and 72 hours for the high dose), primarily via the bile and feces (82.6%) in rat. 

Absorption is saturated at the high dose. Plasma kinetic data revealed peak plasma 

concentrations occurring at 2-6 hours following a single or 14-day repeated low dose and at 

approximately 24 hours for the high dose group. The elimination half-life is about 4.4-6.5 hours 

for the single day low dose group. Acequinocyl undergoes nearly complete metabolism to 

hydrolysis products and a glucuronide conjugate. There was no evidence for selective tissue 

accumulation or sequestration. 

Acequinocyl has low acute toxicity via the oral, dermal, and inhalation routes. No ocular or 

dermal irritation was noted. Acequinocyl is not a dermal sensitizer. Acequinocyl is a known 

Vitamin K antagonist and, therefore, is thought to disrupt blood coagulation. This mechanism is 

supported by effects observed in the database. 

In the rat subchronic oral toxicity study, the primary effects included pallor, swelling of the eyes 

and limbs, decreased motor activity, piloerection, reddish urine, increased activated partial 

thromboplastin time, increased prothrombin time, and internal hemorrhages. In the mouse 

subchronic oral toxicity study, effects included pallor, sunken eyes, labored/irregular breathing, 

hunched posture, piloerection, weight loss, and hepatic vacuolization (blood coagulation profile 

was not evaluated in this study). In the dog subchronic oral toxicity study, toxic effects included 

reduced body-weight gains, reduced food efficiency, decreased total protein, increased 

triglyceride levels, elevated platelet counts, elevated reticulocytes, increased prothrombin time, 

and decreased liver and heart weights (absolute). In the rat 28-day dermal toxicity study, the 
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primary effects were red-stained treated skin area, increased prothrombin time, increased 

activated partial prothromboplastin time, increased fibrinogen levels, and increased heart weights 

(absolute and relative to the body weight).

In the rat chronic oral studies, toxic effects included enlarged eyeballs, increased prothrombin 

time, and increased activated partial thromboplastin time. In the mouse chronic oral toxicity 

study, hepatotoxicity was indicated by increased liver enzyme levels (alanine and aspartate 

aminotransferase), increased liver weight, hepatocyte vacuolization, and hepatocyte fatty 

deposition (blood clotting was not evaluated in this study). In the dog chronic toxicity study, 

effects included elevated prothrombin time, increased reticulocyte/platelet count, reduced bodyweight gain, and reduced food efficiency. 

In the rat prenatal developmental toxicity study, maternal toxicity resulted in pale eyes, 

piloerection, red vaginal discharge, and internal hemorrhage at the lowest-observable adverseeffects level (LOAEL; 500 mg/kg/day), whereas developmental toxicity was indicated by 

increased resorptions and fetal variations (750 mg/kg/day). In the rabbit, maternal toxicity 

produced body-weight loss, reduced fecal output, reduced food consumption, pale lungs/liver, 

internal hemorrhaging, hair loss, and blood-stained urine (120 mg/kg/day). The developmental 

toxicity study in rabbits identified an increased number of complete resorptions (120 mg/kg/day). 

In the rat two-generation reproductive toxicity study, both the maternal and reproductive toxicity 

LOAELs were not observed; however, the LOAEL for parental males was 58.9/69.2 mg/kg/day 

based on hemorrhagic effects. The offspring systemic LOAEL was also 58.9 mg/kg/day. 

Though the offspring LOAEL was similar to that of parental male’s, there were effects specific 

to the pups which, in addition to the hemorrhagic effects noted in both generations, included 

swollen body parts, protruding eyes, clinical signs, delays in pupil development, and increased 

mortality occurring mainly after weaning. 

Previously, HED’s HIARC concluded that exposure to acequinocyl does not pose a neurotoxicity 

concern. First, acequinocyl is a known Vitamin K antagonist; neurotoxic compounds of similar 

structure were not identified. Second, although two studies showed effects that could be 

indicative of neurotoxicity, HIARC considered these as secondary because they were observed at 

very high doses. In the 2-generation reproduction study, significant reduction in startle response 

in F2 pups was observed in the mid- and high-dose groups (58.9/69.2 mg/kg/day and 111.2/133.5 

mg/kg/day). However, other functional development tests (such as a pupillary reflex test at 21 

days post partum, an open field exploration test at 35-48 days post partum and a water maze test 

with a learning phase and a memory phase at 35-48 days post partum) that were performed on

pups did not show significant differences as compared to control values even at the highest 

dosage level. In the rat subchronic oral toxicity study, neurotoxicity signs, such as decreased 

motor activity, piloerection, and hunched posture, were observed at the high dose (252.7/286.0 

mg/kg/day), but in the presence of clinical signs including wasting, swelling of the orbit and 

limbs, pallor, and reddish urine. Furthermore, all rats in this 252.7/286.0 mg/kg/day (3200 ppm) 

group died or were sacrificed moribund in the first three weeks of treatment.

There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity study, 

indicating that acequinocyl is "not likely" to be carcinogenic to humans.

There was no concern for mutagenic activity as indicated by several mutagenicity studies, 

including a bacterial (Salmonella, E. coli) reverse-mutation assay, an in vitro mammalian 
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chromosomal-aberration assay, an in vivo mouse bone marrow micronucleus assay, and a 

bacterial DNA damage or repair assay.

3.2 FQPA Considerations

HED’s RAB1 risk assessment team concluded that based on toxicological considerations and 

the residue assumptions used in the dietary and residential exposure analyses, the FQPA SF may 

be reduced to 1X. This recommendation is based on the following considerations:

• There are no residual uncertainties for pre- and post-natal toxicity.

• There is potential evidence of neurotoxicity or neuropathology in the 2-generation 

reproduction study as well as the rat subchronic neurotoxicity study, however these 

toxicities are not considered to be primary effects since they occur in the presence of 

more severe systemic effects in both studies. Therefore, although an acute and 

subchronic neurotoxicity studies are now required as a part of new data requirements in 

the 40CFR §158 for conventional pesticide registration, the agency does not believe that 

conducting these studies will result in a lower POD than that currently used for overall 

risk assessment, and therefore, a database uncertainty factor (UFDB) is not needed to 

account for lack of these studies. 

• There is no evidence of increased susceptibility of rat or rabbit fetuses to in utero

exposure to acequinocyl. In the 2-generation reproduction study, more severe effects 

were observed in the offspring, however these effects were observed at the same doses as 

parental effects, and a clear NOAEL was established which is being used in endpoint 

selection.

• The toxicology database for acequinocyl does not show any evidence of treatment-related 

effects on the immune system. The overall weight of evidence suggests that this 

chemical does not directly target the immune system. An immunotoxicity study is 

required as a part of new data requirements in the 40 CFR Part 158 for conventional 

pesticide registration; however, the Agency does not believe that conducting a functional 

immunotoxicity study will result in a lower POD than that currently in use for overall risk 

assessment, and therefore, a UFDB is not needed to account for the lack of this study.

• A 28-day inhalation study is not available; however, the EPA has determined that the 

additional FQPA SF is not needed. Residential inhalation risk was estimated by 

calculating exposure using the Agency's Residential Standard Operating Procedures 

(SOPs). For chemicals with low vapor pressure (7.5 x 10-5 mmHg or below for outdoor 

uses at 20-300C), these standard assumptions are expected to overestimate the exposure 

via the inhalation route. Acequinocyl is such a compound (1.69 x 10-11 mmHg at 250C) 

and exposure through the inhalation route is expected to be minimal. Therefore, the risk 

estimate is conservative and is considered protective and the additional FQPA SF is not 

needed. 

• Since all calculated inhalation MOEs for residential handlers are significantly greater 

than HED’s LOC (MOE >100), the lack of an inhalation study will not affect the FQPA 

SF.

• The dietary food (tolerance-level residues, 100% crop treated) and drinking water 

exposure (modeled) assessments will not underestimate the potential exposures for 

infants and children; and the residential use (ornamentals) is not expected to result in 

post-application exposure to infants and children.

• The dietary drinking water assessment utilizes model-generated water concentration 

values and associated modeling parameters that are designed to provide conservative, 
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health-protective, high-end estimates of water concentrations that will not likely be 

exceeded.

3.3 Dose-Response Assessment

Table 3.3.1 provides the toxicity endpoints used in this risk assessment.

Table 3.3.1. Summary of Toxicological Doses and Endpoints for Acequinocyl for Use in Dietary, Occupational, and 

Residential Exposure Risk Assessments.1

Exposure/

Scenario POD Uncertainty/FQPA SF RfD, PAD, LOC Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including Infants 

and Children)

N/A N/A N/A An endpoint of concern (effect) 

attributable to a single dose was 

not identified in the database. 

Quantification of acute risk to 

general population including 

infants and children is not 

required.

Chronic Dietary 

(All Populations)

NOAEL = 2.7 

mg/kg/day

UFA = 10x

UFH =10x

FQPA SF = 1X

cPAD = cRfD = 0.027 

mg/kg/day 

18-month carcinogenicity study in 

mice;

LOAEL = 7.0 mg/kg/day based on 

clinical chemistry and microscopic 

nonneoplastic lesions (brown 

pigmented cells and perivascular 

inflammatory cells in liver).

Short-term 

(1-30 days) 

incidental oral

NOAEL=60 

mg/kg/day

UFA = 10x

UFH =10x

LOC (residential) = 

MOE <100 

Developmental toxicity study in 

rabbits;

Maternal LOAEL = 120 

mg/kg/day based on clinical signs 

(hematuria, reduced fecal output, 

body weight loss, and reduced 

food consumption) and gross 

necropsy findings (pale lungs and 

liver, hemorrhaging uterus, fluid in 

the cecum, fur in the stomach, 

blood stained vaginal opening, 

blood-stained urinary bladder 

contents/urine).

Intermediateterm 

(1-6 months) 

incidental oral

NOAEL = 16 

mg/kg/day

UFA = 10x

UFH =10x

LOC (residential) = 

MOE <100 

Subchronic toxicity in mice;

LOAEL = 81 mg/kg/day based on 

hepatocyte vacuolization.

Short- (1-30 

days) and 

Intermediateterm (1-6 

months) Dermal

Dermal NOAEL 

= 200 mg/kg/day

UFA = 10x

UFH =10x

LOC (occupational/

residential) = 

MOE <100 

28-day dermal study in rats;

LOAEL = 1000 mg/kg/day based 

on increased clotting factor times.

Short-term (1-30 

days) Inhalation

Oral 

NOAEL=60 

mg/kg/day

(inhalation 

absorption 

rate=100%)

UFA= 10x

UFH=10x

LOC (occupational/

residential) = 

MOE <100 

Developmental toxicity study in 

rabbits;

Maternal LOAEL = 120 

mg/kg/day based on clinical signs 

(hematuria, reduced fecal output, 

body weight loss, and reduced 

food consumption) and gross 

necropsy findings (pale lungs and 

liver, hemorrhaging uterus, fluid in 

the cecum, fur in the stomach, 

blood stained vaginal opening, 

blood-stained urinary bladder 

contents/urine).
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Table 3.3.1. Summary of Toxicological Doses and Endpoints for Acequinocyl for Use in Dietary, Occupational, and 

Residential Exposure Risk Assessments.1

Exposure/

Scenario POD Uncertainty/FQPA SF RfD, PAD, LOC Study and Toxicological Effects

Intermediate-

(1-6 months) 

Term Inhalation

Oral NOAEL = 

16 mg/kg/day

(inhalation 

absorption

rate=100%)

UFA = 10x

UFH = 10x

LOC (occupational/

residential) = 

MOE <100 

Subchronic toxicity in mice;

LOAEL = 81 mg/kg/day based on 

hepatocyte vacuolization.

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans.”

1 Point of Departure (POD) = A data point or an estimated point that is derived from observed doseresponse data and used to mark the beginning of extrapolation to determine risk associated with lower 

environmentally relevant human exposures. UF = uncertainty factor, UFA = extrapolation from animal to human 

(interspecies), UFH = potential variation in sensitivity among members of the human population (intraspecies), FQPA 

SF = FQPA Safety Factor, NOAEL = no-observed-adverse-effect level, LOAEL = lowest-observed-adverse-effect 

level, RfD = reference dose (a = acute, c = chronic), PAD = population-adjusted dose, MOE = margin of exposure, 

LOC = level of concern, N/A = Not Applicable.

Acute Dietary Endpoint: The aRfD for the general population, including infants and children, 

was not established because an endpoint of concern attributable to a single dose was not 

identified. Therefore, this assessment is not necessary.

Chronic Dietary Endpoint: The chronic reference dose (cRfD) of 0.027 mg/kg/day was derived 

from the chronic carcinogenicity study in mice. An UF of 100 (10-fold for interspecies 

extrapolation and 10-fold for intraspecies variability) was applied to the NOAEL of 2.7 

mg/kg/day to generate the cRfD. The LOAEL of 7.0 mg/kg/day is based on clinical chemistry 

and microscopic non-neoplastic lesions (brown-pigmented cells and perivascular inflammatory 

cells) in the liver. The FQPA SF of 1X is applicable for chronic dietary risk assessment. 

Therefore, the cPAD is equal to the RfD and is 0.027 mg/kg/day. The lowest NOAEL in the 

database was derived from this study, and this study is thus appropriate for the chronic reference 

dose. It is also appropriate for both the expected duration of exposure and the route of exposure.

Short-Term Incidental Oral Endpoint: The short-term incidental endpoint was derived from the 

development rabbit study where the maternal NOAEL was 60 mg/kg bw/day. The maternal 

LOAEL was 120 mg/kg bw/day based on treatment-related clinical signs leading to premature 

sacrifice (hematuria, reduced fecal output, body weight loss, and reduced food consumption) and 

gross necropsy findings (pale lungs and liver, hemorrhaging uterus, fluid in the cecum, fur in the 

stomach, blood stained vaginal opening, blood-stained urinary bladder contents/urine). This 

study is relevant for the duration of exposure, and is protective of the populations of concern. 

Intermediate-Term Incidental Oral Endpoint: The intermediate-term incidental or endpoint is 

based on hepatocyte vacuolization seen in the 90-day oral study in mice observed at the LOAEL 

of 81 mg/kg/day (NOAEL = 16 mg/kg/day).based upon hepatocyte vacuolization observed in 

male and female mice at the LOAEL of 81/ 100 mg/kg/day. The endpoint is appropriate for the 

route, duration of exposure (1-6 months) and populations of concern. Corneal effects seen in rats 

at 800 ppm (36.41 mg/kg/day and 46.20 mg/kg/day for male and female, respectively) would 

also be protected by this dose (NOAEL, 16 mg/kg/day).

 

Dermal Absorption: No dermal-absorption factor was necessary for the short- and intermediateterm dermal assessments since the endpoint was based on a dermal study. However, HIARC 

selected a dermal-absorption rate of 15% for the long-term dermal assessment. The dermal 

penetration study yielded absorptions of 12.23%, 19.75% and 14.77% at 168 hours (doses were 
Acequinocyl Human-Health Risk Assessment D389519

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0.1, 0.01, and 0.001 mg/cm2, respectively). Because a higher dermal absorption value (20%) 

was observed at the mid-dose than observed at the lowest dose (15%), HIARC selected a 15% 

dermal-absorption value that was based on the average absorption values at the three doses at 

168 hours (7 days).

Short- and Intermediate-Term Dermal Endpoints: The short- and intermediate-term dermal 

endpoints are based on increased clotting factor times seen in the rat 28-day dermal toxicity 

study at the LOAEL of 1000 mg/kg/day (NOAEL = 200 mg/kg/day). This study is ideal for this 

exposure scenario because it is the route specific study, it matches the durations of exposure (1-

30 days and 1-6 months), and it is consistent with the mechanism of action for this active 

ingredient. The LOC for occupational exposure is for a MOE of <100.

Short-Term Inhalation Endpoint: The short-term inhalation endpoint is based on the maternal 

NOAEL of 60 mg/kg/day in the developmental study in rabbits. The NOAEL of 60 mg/kg/day 

was based on clinical signs (hematuria, reduced fecal output, body-weight loss, and reduced food 

consumption) and gross necropsy findings (pale lungs and liver, hemorrhaging uterus, fluid in 

the cecum, fur in the stomach, blood stained vaginal opening, blood-stained urinary bladder 

contents/urine) at the LOAEL of 120 mg/kg/day. Because HIARC selected an oral NOAEL for 

short-term inhalation exposure assessment, a conservative 100% oral equivalent inhalation 

absorption factor is assumed. This study is relevant for the duration of exposure and is 

protective of pregnant females from the above-mentioned effects, which are consistent with 

mechanism of action for this active ingredient. 

Intermediate-Term Inhalation Endpoint: The intermediate-term inhalation endpoint is based on 

hepatocyte vacuolization seen in the 90-day oral study in mice observed at the LOAEL of 81 

mg/kg/day (NOAEL = 16 mg/kg/day). Because HIARC selected an oral NOAEL for

intermediate-term inhalation exposure assessment, a conservative 100% oral equivalent 

inhalation absorption factor is assumed. This study is relevant for the duration of exposure (90-

days). The LOC for occupational exposure is for a MOE of <100.

Long-Term Dermal and Inhalation Endpoints: Since the uses under consideration in the current 

risk assessment do not include long-term dermal or inhalation exposures, long-term dermal and 

inhalation risk assessments were not performed.

Based on the available toxicity database and the Agency's current practices, the inhalation risk 

for acequinocyl was assessed using an oral toxicity study. The Agency sought expert advice and 

input on issues related to this route-to-route extrapolation approach (i.e., the use of oral toxicity 

studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and Rodenticide 

Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009. The Agency received the 

SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, re-examine and develop new 

policies and procedures for conducting inhalation risk assessments, including route-to-route 

extrapolation of toxicity data. If any new policies or procedures are developed, then the Agency 

may revisit the need for an inhalation toxicity study for acequinocyl and/or a re-examination of 

the inhalation toxicity risk assessment.

3.4 Recommendation for Aggregate Exposure Risk Assessments

Since short- and intermediate-term inhalation endpoints are based on oral studies, dietary 
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exposure will be aggregated to inhalation exposure for all populations/durations. 

4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION

Please refer to the following documents for detailed considerations of the material summarized 

in this section: 

• PP#: 1E7864. Petition for Use on Succulent Soybean Vegetable; Succulent Shelled Beans; Cowpea 

Forage; Caneberry Subgroup 13-07A; Melon Subgroup 9A; Cucumber, Cherry; Low-Growing Berry 

Subgroup 13-07G; and Small Fruit Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F. Summary 

of Analytical Chemistry and Residue Data. S. Levy, 30-NOV-2011; D389989.

• PP#: 1E7864. Acequinocyl. Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk 

Assessment for the Section 3 Registration Action Use on Succulent Soybean Vegetable; Succulent Shelled 

Beans; Cowpea Forage; Caneberry Subgroup 13-07A; Melon Subgroup 9A; Cucumber; Cherry; LowGrowing Berry Subgroup 13-07G; and Small Fruit Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-

07F. S. Levy, 30-NOV-2011; D389990.

• Acequinocyl: Occupational and Residential Exposure/Risk Assessment for Proposed Use on Succulent 

soybean; Low growing berry subgroup 13-07G; Small fruit vine climbing (except fuzzy kiwifruit, 

subgroup 13-07F); Succulent bean; Cowpea forage; Caneberry (subgroup 13-07A); Melon (subgroup 9A); 

Cucumber (greenhouse and field), and Cherry. K. Lowe, 30-NOV-2011; D389991. 

• Acequinocyl: Drinking Water Assessment to Support Proposed New IR-4 Uses (Succulent Soybean 

Vegetable, Low Growing Berry, Small Fruit Vine Climbing - Except Fuzzy Kiwifruit, Succulent Shelled 

Beans, Cowpea Forage, Caneberry, Melon, Cucumber, and Cherry). M. Lowit et al., 07-SEP-2011;

D389520.

Acequinocyl is a quinoline-type miticide registered for use in the U.S. on a number of RACs for 

the control of various phytophagous mite species. 

Under PP#1E7864, the IR-4, on behalf of the Agricultural Experiment Station of TX, CA, OR, 

PA, GA, NM, OK, TN, UT, MI, FL, and AZ, is requesting for the establishment of tolerances for 

combined residues of the insecticide acequinocyl and its metabolite, 2-dodecyl-3-hydroxy-1,4-

naphthoquinone (acequinocyl-OH), expressed as acequinocyl equivalents in/on the following 

commodities:

 Soybean, vegetable, succulent ..................................................................0.25 ppm

 Low growing berry subgroup 13-07G ......................................................0.4 ppm

 Small fruit vine climbing subgroup 13-07F, except fuzzy kiwifruit ........1.6 ppm

 Bean, succulent shelled.............................................................................0.15 ppm

 Cowpea, forage .........................................................................................9.0 ppm

 Caneberry subgroup 13-07A.....................................................................4.5 ppm

 Melon subgroup 9A ..................................................................................0.06 ppm

 Cucumber..................................................................................................0.15 ppm

 Cherry .......................................................................................................0.8 ppm

No new data were submitted to support tolerances on succulent soybean vegetables, low-growing 

berry 13-07G crop subgroup, or small fruit vine climbing subgroup 13-07F, except fuzzy 

kiwifruit. The petitioner has requested that existing tolerances be expanded to their respective 

crops or crop groups.
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4.1 Summary of Uses

The petitioner provided a draft label for KanemiteTM 15 SC Miticide (EPA Reg. No. 66330-38), a 

1.25 lb/gal SC formulation of acequinocyl. This acequinocyl formulation is currently registered 

for use on several fruit and nut crops, fruiting vegetables, okra, edible-podded beans, and hops. 

Table 4.1.1 provides a summary of the proposed use patterns.

Table 4.1.1. Summary of Proposed Directions for Use of Acequinocyl.

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations1

Bean, succulent shelled

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 30 gal/A; minimum 

RTI of 14 days. Do not 

allow grazing on cowpea 

forage within 7 days of 

last treatment.

Caneberry subgroup 13-07A

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 50 gal/A; minimum 

RTI of 21 days.

Melon subgroup 9A

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 30 gal/A; minimum 

RTI of 21 days.

Cucumber

Postemergence, 

foliar; Ground 

only; 

Groundboom 

(field); 

Handheld 

sprayers 

(greenhouse)

1.25 lb/gal 

SC

[66330-38]

0.3 or 0.12 2 0.6 1

Minimum spray volume 

of 30 gal/A; minimum 

RTI of 21 days. The use 

of an adjuvant or 

surfactant is prohibited.

Cherry

Postemergence, 

foliar;

Ground only; 

Airblast

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 40 gal/A; for optimal 

control, use a minimum 

of 150 gal/A; minimum 

RTI of 14 days. Do not 

use in alternate row 

middle applications. 1

 RTI = retreatment interval. 2

 Label indicates a minimum of 30 gal/A. Application rate = 0.3 lb ai/A ÷ 30 gal/A = 0.01 lb ai/gal.

General label restrictions include: (i) do not apply through any type of irrigation system; (ii) do 

not apply by air; (iii) do not apply within 75 feet of aquatic areas; and (iv) not for indoor 

residential use. The product may be combined with most commonly used pesticides with the 

exception of strongly alkaline material, which can reduce activity; combination with Phos-ethyl 

(fosetyl) is prohibited. Broad-spectrum insect control may be obtained by tank-mixing the SC 
Acequinocyl Human-Health Risk Assessment D389519

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acequinocyl product with other miticide/insecticide products; a spray mix compatibility and 

phytotoxicity trial under local conditions should first be conducted. A 12-hour REI is specified. 

The label requires applicators and other handlers to wear a long-sleeved shirt and long pants and 

shoes plus socks, plus chemical-resistant gloves.

Rotational crop restrictions are as follows: food and feed crops not listed on the proposed label 

must not be planted within 30 days of the last KanemiteTM 15 SC application.

Conclusions: The proposed use directions are adequate to allow for evaluation of the submitted 

residue data relative to the proposed uses. The proposed uses are supported by the submitted 

field trial data. Furthermore, the submitted field trial data reflect applications made without the 

use of a spray adjuvant. A revised Section B should be submitted incorporating an adjuvantuse restriction. An adequate confined rotational crop study was previously submitted, reflecting 

the maximum proposed use pattern for rotated crops. The available data support a 30-day PBI 

for all non-labeled crops, which is reflected on the proposed label.

4.2 Dietary Exposure/Risk Pathway

4.2.1 Residue Profile

Nature of the Residue: 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 acequinocylOH, the opening of the quinone ring to form AKM-18, and the subsequent degradation of the 

quinone ring to yield polar metabolites that degrade to phthalic acid. For purposes of risk 

assessment and the tolerance expression, the HED Metabolism Assessment Review Committee 

(MARC) has determined that the residues of concern in these commodities include parent and 

acequinocyl-OH (Memo, S. Levy, et al., 07-JAN-2004; D297872).

The qualitative nature of acequinocyl residues in ruminants is understood based on an adequate 

goat metabolism study (Memo, S. Levy, 10-MAR-2004; D284757). The metabolism of 

acequinocyl in goats appears to involve the loss of the acetyloxyl moiety to form acequinocylOH and partial cleavage of the dodecyl side chain to form AKM-15. Opening and degradation 

of the quinone ring was also evidenced by the presence of AKM-18 and phthalic acid. The 

MARC concluded that for tolerance expression, the residues of concern in livestock commodities 

include parent and acequinocyl-OH. For risk assessment purposes, the residues of concern in 

livestock commodities are parent and acequinocyl-OH (for liver and kidney, metabolite AKM-15 

is to be included as well (Memo, S. Levy, et al., 07-JAN-2004; D297872). 

Metabolism data on poultry are not required at the present time as none of the proposed or 

existing uses of acequinocyl are on crops having regulated poultry feedstuffs.

Magnitude of the Residue-Plants: IR-4 submitted adequate field trial data in support of the 

proposed uses on succulent shelled beans, caneberry, cantaloupe, cherry, and cucumber. The 

field trials reflect the proposed use patterns and an adequate number of field trials were 

conducted in major crop growing regions. The submitted field trial data reflect applications 

made without the use of a spray adjuvant. A revised Section B should be submitted 

prohibiting the addition of adjuvants to the spray solution. The Organization for Economic 

Co-operation and Development (OECD) maximum residue limit (MRL) calculator was used to 
Acequinocyl Human-Health Risk Assessment D389519

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determine the appropriate tolerance levels. The field trial data will support tolerances of: 0.30 

ppm for residues in/on bean, succulent shelled; 6.0 ppm for residues in/on cowpea, forage; 18 

ppm for residues in/on cowpea, hay; 4.0 ppm for residues in/on caneberry subgroup 13-07A; 

0.15 ppm for residues in/on melon subgroup 9A; 1.0 ppm for residues in/on cherry, tart; 0.50 

ppm for residues in/on cherry, sweet; and 0.15 ppm for residues in/on cucumber. A revised 

Section F should be submitted. 

No new data were submitted to support tolerances on succulent soybean vegetables, low-growing 

berry 13-07G crop subgroup, or small fruit climbing vine subgroup 13-07F, except fuzzy 

kiwifruit. However, existing established tolerances in 40 CFR §180.599 should be extended to 

support these crop group tolerances. HED recommends that that the tolerance for residues at 

in/on edible-podded beans should be extended to soybean, vegetable, succulent; the tolerance for 

residues in/on strawberries should be extended to the low-growing berry 13-07G subgroup; and 

the tolerance for residues in/on grapes should be extended to small fruit vine climbing subgroup 

13-07F, except fuzzy kiwifruit. See Table 4.2.1.1 for details.

There are no processed food/feed items associated with the proposed uses. Therefore, data 

requirements for this guideline are not relevant to this tolerance petition.

Magnitude of the Residue-Livestock: Based on the potential dietary exposure of livestock to 

acequinocyl residues from the current and proposed uses, the dietary burden was re-evaluated. 

The re-evaluated dietary burden indicates that the currently established tolerance level of 0.02 

ppm for residues in cattle, goat, horse, and sheep fat are 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 is appropriate; however, the commodity definition should be changed to “meat 

byproducts” rather than “liver.” With the establishment of the cattle, goat, horse, and sheep 

tolerance in meat byproducts, RD should remove the tolerance (40 CFR §180.599) for liver. 

Furthermore, the meat byproducts tolerance of 0.02 ppm is adequate to cover residues in the 

kidney of cattle, goats, horses, and sheep. A revised Section F should be submitted.

Residue Analytical Method for Crops: There are adequate residue analytical methods for 

enforcing tolerances for acequinocyl residues of concern in/on the proposed/registered 

commodities. These methods include two high-performance liquid chromatography methods 

with tandem mass-spectroscopy detection (HPLC/MS/MS) for determining residues in/on plant 

commodities (Morse Methods Meth-135 and #Meth-133, revision #3). 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). In the current field trials, residues of acequinocyl and acequinocyl-OH were 

determined using a modified version of Morse Method #Meth-133, revision #3. The method 

limit of quantitation (LOQ; based on the lowest level of method validation (LLMV)) for 

succulent shelled beans was 0.02 ppm for each analyte. The LOQs (based on the LLMV) for 

cantaloupe were 0.015 ppm for acequinocyl, and 0.01 ppm for acequinocyl-OH. For cherries, 

cucumbers, and caneberries, the LOQ (based on the LLMV) was 0.01 for each analyte. The 

method was adequately validated in conjunction with the analysis of field trial samples. 

Analytical reference standards for acequinocyl and acequinocyl-OH are currently available at the 

EPA National Pesticide Standards Repository (electronic communication with Theresa Cole, 31-

OCT-2011) with expiration dates of June, 2012. 
Acequinocyl Human-Health Risk Assessment D389519

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The data requirements for multiresidue (MRM) methods are fulfilled. Certain MRM protocols 

resulted in acceptable recoveries. The MRM testing data have been forwarded to the U.S. Food 

and Drug Administration (FDA) for further evaluation (Memo, S. Levy, 18-FEB-2004; 

D298917).

Storage Stability in Plants: The submitted concurrent storage stability data for the subject crops 

are adequate to support the storage intervals and conditions incurred by the field trial studies. 

Confined Accumulation in Rotational Crops: An adequate confined rotational crop study was 

previously submitted. These data reflect the maximum proposed use pattern for rotated crops 

(fruiting vegetables and edible-podded beans); the results indicate that residues of acequinocyl 

do not accumulate in rotated crops. These data support a 30-day PBI for all non-labeled crops, 

which is reflected on the proposed label.

Proposed and Recommended Tolerances: There are currently no established Codex, Canadian, 

or Mexican MRLs for acequinocyl residues in/on cucumbers or caneberries. Data for these crops 

were jointly reviewed by the U.S. and Canada. The data support tolerance levels of 0.15 ppm 

and 0.40 ppm, respectively. These levels are harmonized between the U.S. and Canada.

 

Canada has a MRL of 0.5 ppm for residues in/on strawberries. The OECD Calculator shows that 

the data support a tolerance of 0.40 ppm for residues in/on the low-growing berry subgroup 13-

07G (which includes strawberries); however, in order to harmonize with Canada, HED 

recommends establishing a tolerance of 0.50 ppm for residues in this subgroup. Canada also has 

a MRL for residues of 0.02 ppm in/on meat byproducts of cattle, goat, horse, and sheep. HED is 

recommending for the same tolerance level as Canada; therefore, harmonization will not be an 

issue. The proposed and HED-recommended tolerances are listed in Table 4.2.1.1.

The petitioner should submit a revised Section F with the appropriate commodity definitions 

and/or HED-recommended tolerance levels listed in Table 4.2.1.1. Furthermore, the Section F 

should state the following (as it appears in 40 CFR §180.599): “Tolerances are established for 

residues of acequinocyl, including its metabolites and degradates, in or on the commodities in the 

table below. Compliance with the tolerance levels specified below is to be determined by 

measuring only the sum of acequinocyl [2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione] and its 

metabolite, 2-dodecyl-3-hydroxy-1,4-naphthoquinone, calculated as the stoichiometric 

equivalent of acequinocyl, in or on the commodity.” A revised Section F should be submitted.

Table 4.2.1.1. Tolerance Summary for Acequinocyl.

Commodity Proposed Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments; 

Correct Commodity Definition

Soybean, vegetable, succulent 0.25 0.25 Established edible-podded 

bean tolerance extended to 

soybean, vegetable, succulent.

Low-growing berry subgroup 

13-07G

0.4 0.50 Established strawberry 

tolerance extended for a 

subgroup tolerance. With 

establishment of this subgroup 

tolerance, the strawberry 

tolerance should be removed.

Berry, low growing, subgroup 

13-07G
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Table 4.2.1.1. Tolerance Summary for Acequinocyl.

Commodity Proposed Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments; 

Correct Commodity Definition

Small fruit vine climbing subgroup 13-

07F, except fuzzy kiwifruit

1.6 1.6 Established grape tolerance 

extended for a subgroup 

tolerance. With establishment 

of this subgroup tolerance, the 

grape tolerance should be 

removed.

Fruit, small vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

Bean, succulent shelled 0.15 0.30

Cowpea, forage 9.0 6.0

Cowpea, hay -- 18

Caneberry subgroup 13-07A 4.5 4.0

Melon subgroup 9A 0.06 0.15

Cucumber 0.15 0.15

Cherry

0.8 1.0 Cherry, tart

-- 0.50 Cherry, sweet

Liver of cattle, goat, horse, and sheep1 -- 0.02 Meat byproducts of cattle, 

goat, horse and sheep 1 A tolerance of 0.02 ppm is already established under 40 CFR §180.599; however, the commodity definition should be changed 

to meat byproducts to cover residues in liver and kidney.

4.3 Water Exposure/Risk Pathway

Environmental Fate Assessment: Acequinocyl appears to undergo fairly rapid transformation 

in most aquatic and terrestrial environments. It undergoes hydrolysis with a half-life of a few 

hours to less than 2 days under neutral and alkaline pH conditions. However, it is stable at acidic 

pH conditions. Photodegradation in water appears to be the main route of degradation in aquatic 

environments, with half-lives occurring in less than 15 minutes in sterile lab and river water. 

Acequinocyl also undergoes fast degradation in terrestrial environments. The half-lives for 

aerobic biotransformation on soil are less than 2 days under laboratory conditions and under field 

conditions, acequinocyl applied to bare plots dissipated with half-lives ranging from 2 hrs in 

California to 14 hours in New York. 

Acequinocyl can reach surface water via spray drift and less likely via runoff. Due to its high Kd

values it is expected to exhibit low mobility in soil and low potential to leach into groundwater. 

Once acequinocyl has entered surface water, it is not likely to persist as it will hydrolyze to form 

hydroxy-acequinocyl (also known as R-1).

Surface and Ground Water Estimated Drinking Water Concentrations (EDWCs): For the 

aquatic exposure modeling, both parent and metabolite (acequinocyl-OH) concentrations were 

estimated in the surface and ground water to address the toxicity concerns associated with the 

acequinocyl-OH degradate. There are no drinking water monitoring data available for either 

acequinocyl or acequinocyl-OH. Groundwater EDWCs were generated 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 (cranberries are part of the low 
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growing berries subgroup, 13-07G). Cranberry harvesting may involve field flooding and 

PRZM/EXAMS is not currently parameterized to assess this type of scenario; therefore, 

cranberry was assessed using the provisional cranberry model (note that since the provisional 

cranberry model only uses a one year simulation, the highest 30-year annual average 

concentration is not available for the cranberry scenario).

Similar to previous drinking water assessments provided by EFED, two approaches were used in 

performing the drinking water assessment for proposed acequinocyl uses. In Approach #1, 

acequinocyl was conservatively assumed to be stable to all routes of degradation to account for 

the uncertainties associated with the environmental fate data. In Approach #2, total (acequinocyl 

+ acequinocyl-OH) residues were modeled with the assumption that the half-lives of acequinocyl 

and R1 are valid and the total toxic residues were modeled to address toxicity concerns with R1. 

The EDWCs are summarized below in Table 4.3.1. Surface water EDWCs for the proposed uses 

are higher than those previously reported for both approaches. The ground water EDWC for the 

current assessment is the same as the last assessment.

Table 4.3.1. Recommended EDWCs of Acequinocyl Derived from the Previous Uses.

Drinking water 

source (model)

Proposed 

Use/Scenario3

EDWCs from Surface Water Sources (ug/L)

1,2

Approach 1

(assume no acequinocyl degradation)

Approach 2

(combined acequinocyl and R1)

1-in-10-

year acute

1-in-10-year 

chronic

30-year 

mean

1-in-10-

year acute

1-in-10-year 

chronic

30-year 

mean

Surface water

(PRZM/EXAMS) Cherry/MI cherry

6.69

(25.89)4

6.69 

(17.84)4

6.69

(10.19)4 5.59 0.42 0.26

Surface water

(PRZM/EXAMS)

Small fruit (vine 

climbing, except fuzzy 

kiwifruit, 13-07F)/NY 

grape

6.69

(23.12)4

6.69 

(15.34)4

6.69 

(9.57)4 4.22 0.38 0.27

Surface water

(Provisional 

Cranberry Model)

Cranberry/Provisional 

Cranberry Model 4.24 3.75 -- 3.815 1.365 --

Groundwater 

(SCIGROW) All proposed uses 3.6 x 10-3 <3.6 x 10-3 <3.6 x 10-3 3.6 x 10-3 <3.6 x 10-3 <3.6 x 10-3

1

 Bolded values are the recommended EDWCs by EFED. 2

 A default PCA of 0.87 was applied. 3

 Maximum of 2 applications of 0.3 lb ai/A for all proposed uses. 4

 EDWC (shown in parentheses) exceeds the solubility limit of acequinocyl (6.69 μg/L at 20°C); therefore, the 

recommended EDWC is 6.69 ppb. 

5

 Based on a one-year simulation; 1-10-year calculation is not applicable.

Since the surface water EDWCs are higher than the groundwater EDWC, HED selected the 

surface water value for use in the chronic dietary assessment. The EDWC derived via Approach 

#1 represents the upper-bound value (6.69 ppb) while that derived via Approach #2 represents 

the lower-bound value (1.36 ppb). The 6.69 ppb value was used in this dietary assessment as this 

value assures a conservative assessment.

4.4 Dietary Exposure Analyses

An acute dietary assessment was not conducted for acequinocyl because an endpoint of concern 

attributable to a single dose was not identified; therefore, an aRfD was not established and an 

acute dietary assessment is not necessary. A cancer dietary assessment was not conducted 

because acequinocyl was classified as not likely to be carcinogenic to humans.
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An acequinocyl chronic dietary exposure assessment was conducted using the DEEM-FCIDTM, 

Version 2.03, which incorporates consumption data from USDA’s CSFII, 1994-1996 and 1998. 

The 1994-96, 98 data are based on the reported consumption of more than 20,000 individuals 

over two non-consecutive survey days. Foods “as consumed” (i.e., apple pie) are linked to EPAdefined food commodities (i.e., apples, peeled fruit - cooked; fresh or N/S; baked; or wheat flour 

- cooked; fresh or N/S, baked) using publicly available recipe translation files developed jointly 

by USDA/ARS and EPA. For chronic exposure assessment, consumption data are averaged for 

the entire U.S. population and within population subgroups. Based on analysis of the 1994-96, 

98 CSFII consumption data, which took into account dietary patterns and survey respondents, 

HED concluded that it is most appropriate to report risk for the following population subgroups: 

the general U.S. population, all infants (<1 year old), children 1-2, children 3-5, children 6-12, 

youth 13-19, adults 20-49, females 13-49, and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (i.e., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate.

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent 

of the cPAD. This procedure is performed for each population subgroup.

4.4.1 Chronic Dietary Exposure Analysis

The DEEM-FCIDTM analysis estimates the dietary exposure of the U.S. population and various 

population subgroups. The chronic dietary exposure assessment (using tolerance level residues 

and 100% CT information for all registered and proposed uses) was conducted for the general 

U.S. population and various population subgroups. DEEM ver. 7.81 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 (Memo, S. Levy, 05-SEP-2007; DP#: 342805).

Drinking water was incorporated directly into the dietary assessment using the chronic 

concentration for surface water generated by the PRZM/EXAMS model. The highest chronic 

surface water value (i.e., most conservative) of 6.69 ppb was used for this assessment. 

This assessment concludes that the chronic dietary exposure estimates are not of concern to HED 

for the general U.S. population (13% cPAD) and all population subgroups. The most highly 

exposed population subgroup is children 1-2 years old at 55% of the cPAD. The use of 

anticipated residues (ARs), empirical processing factors, and %CT data would refine further 

HED’s exposure and risk estimates; however, refinement is not needed at this time.

Table 4.4.1.1. Summary of Dietary (Food + Drinking Water) Exposure and Risk for Acequinocyl.

Population Subgroup

Chronic Dietary1

Dietary Exposure

(mg/kg/day) % cPAD

U.S. Population (total) 0.003627 13

All Infants (<1 year old) 0.006513 24

Children 1-2 years old 0.014761 55

Children 3-5 years old 0.010370 38

Children 6-12 years old 0.005172 19
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Table 4.4.1.1. Summary of Dietary (Food + Drinking Water) Exposure and Risk for Acequinocyl.

Population Subgroup

Chronic Dietary1

Dietary Exposure

(mg/kg/day) % cPAD

Youth 13-19 years old 0.002825 11

Adults 20-49 years old 0.002525 9.4

Adults 50+ years old 0.002473 9.2

Females 13-49 years old 0.002563 9.5 1 Chronic dietary POD of 0.027 mg/kg/day applies to the general U.S. population and all population subgroups. The 

values for the highest exposed population are bolded.

4.5 Residential/Non-Occupational Exposure Pathway

4.5.1 Short-term Residential Handler Risk

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. Residential handler exposure from applying 

acequinocyl to trees and ornamentals with handheld equipment was assessed in June 2010 (A. 

Nowotarski, D369099). All MOEs were >100 and are not of concern to HED (see Table 

4.5.1.1).

Table 4.5.1.1. Summary of Residential Handler Exposure and Risk.

Scenario Residential Handler Dose 

(mg/kg/day) Residential Handler MOE

Mixer/Loader/Applicator – Liquid Formulation 

with Low-Pressure Handwand 

Dermal

Baseline: 0.005

Inhalation

Baseline: 2.3E-07

Dermal

Baseline: 40,000

Inhalation

Baseline: 2.6E+08

Mixer/Loader/Applicator – Liquid Formulation 

with Hose-End Sprayer (ORETF-- fruit trees 

and ornamentals)

Dermal

Baseline: 0.07

Inhalation

Baseline: 2.9E-06

Dermal

Baseline: 2,900

Inhalation

Baseline: 2.1E+07

4.5.2 Short-term Residential Post-application Risk

Post-application exposure was not anticipated for the registered residential uses; and therefore, a 

quantitative post-application assessment was not conducted. 

4.5.3 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for acequinocyl. The 

Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical-by-chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 
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developing a policy on how to appropriately apply the data and the AgDRIFT® computer model 

to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic 

methods. After the policy is in place, the Agency may impose further refinements in spray-driftmanagement practices to reduce off-target drift with specific products with significant risks 

associated with drift.

4.5.4 Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative residential bystander post-application 

inhalation exposure assessment was not performed for acequinocyl at this time. However, 

volatilization of pesticides may be a potential source of post-application inhalation exposure to 

individuals nearby to pesticide applications. The Agency sought expert advice and input on 

issues related to volatilization of pesticides from its FIFRA SAP in December 2009. The 

Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures, 

to identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for acequinocyl.

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard, or the risks themselves can be aggregated. When aggregating exposures and 

risks from various sources, HED considers both the route and duration of exposure.

5.1 Acute Aggregate Risk

An endpoint of concern was not identified to quantify acute-dietary risk to the general population 

or to any population subgroup. Since an acute hazard does not exist, an acute aggregate 

assessment was not performed. 

5.2 Short-Term Aggregate Risk

Short-term aggregate risk is made up of dietary and non-dietary sources of exposure. Since 

acequinocyl has a residential use on ornamentals, adult residential handler exposure is expected. 

Short-term aggregate risk is made up of average dietary exposures from food and drinking water 

sources, and dermal and inhalation residential exposures. The females 13-49 years old 

population is the highest exposed adult population and can be considered protective of the other 

adult populations groups; therefore, this population subgroup is shown below in Table 5.2.1, as 

well as the general U.S. population.

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

exposure assessment (see Table 4.4.1.1). Residential exposure estimates are conservative 

estimates due to the standard assumptions that were built into the calculations. Residential 

exposure estimates were taken from Table 4.5.1.1. The short-term aggregate risk calculations for
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both the general U.S. population and the females 13-49 years old sub-population are shown 

below in Table 5.2.1 and are not of concern to HED. 
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Table 5.2.1. Short-Term Aggregate Risk Calculations.

Population Dietary MOE1 Residential Dermal 

MOE2

Residential Inhalation 

MOE2

Aggregate

MOE3

U.S. Population 17,000 2,900 21,000,000 2,500

Females 13-49 years 

old 23,000 2,900 21,000,000 2,600

1 Dietary MOE = short-term oral NOAEL (60 mg/kg/day) ÷ chronic dietary exposure. 2 Residential MOEs are from Table 4.5.1.1. The “liquid with hose-end sprayer handler” scenario was used as the MOEs 

for this scenario are lower (i.e., more conservative) than the “liquid with low-pressure handwand handler” scenario. 3 Aggregate MOE (dietary and residential) = 1÷((1÷MOEdietary)+(1÷MOEdermal)+(1÷MOEinhalation); LOC = 100.

5.3 Intermediate-Term Aggregate Risk

Intermediate-term aggregate risk was not calculated since the use pattern is not expected to result 

in residential handler or post-application exposure of more than 30-day duration. 

5.4 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 4.4.1.1) 

represents chronic aggregate exposure.

5.5 Cancer Risk

Aggregate cancer risk was not calculated because acequinocyl is not considered to be a 

carcinogen.

6.0 CUMULATIVE RISK

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to acequinocyl and any other substances and acequinocyl does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that acequinocyl has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

7.0 OCCUPATIONAL EXPOSURE AND RISK ASSESSMENT

The proposed uses are on agricultural crops; therefore, there is the potential for occupational 

handler and post-application exposure. Please refer to the following document for detailed 

considerations of the material summarized in this section:

• Acequinocyl: Occupational and Residential Exposure/Risk Assessment for Proposed Use on Succulent 

soybean; Low growing berry subgroup 13-07G; Small fruit vine climbing (except fuzzy kiwifruit, subgroup 

13-07F); Succulent bean; Cowpea forage; Caneberry (subgroup 13-07A); Melon (subgroup 9A); Cucumber 

(greenhouse and field), and Cherry. K. Lowe, 30-NOV-2011; D389991.
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7.1 Short- and Intermediate-term Occupational Handler Risk

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: 

1) Mixing/loading liquids in support of groundboom operations, 

2) Applicators using open-cab groundboom equipment,

3) Mixing/loading/applying liquids via backpack sprayers,

4) Mixing/loading/applying liquids via mechanically-pressurized handgun, and 

5) Mixing/loading/applying liquids via manually pressurized handwand. 

For pesticide handlers, HED presents estimates of dermal exposure for “baseline” (i.e., workers 

wearing a single layer of work clothing consisting of a long-sleeved shirt, long pants, shoes plus 

socks, and no protective gloves), as well as for “baseline” and the use of protective gloves or 

other PPE, as might be necessary. The acequinocyl product labels direct mixers, loaders, 

applicators, and other handlers to wear long-sleeved shirt and long pants, chemical-resistant 

gloves, and shoes plus socks. 

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include the 

PHED (Version 1.1), the AHETF database, the ORETF database, or other registrant-submitted 

occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting handler exposure that are used in this assessment, known as “unit exposures”, are 

outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html. 

Typically, HED completes short- and intermediate-term assessments for occupational scenarios 

in all cases because these kinds of exposures are likely and acceptable use/usage data are not 

available to justify deleting intermediate-term scenarios. Based on use data and label 

instructions, HED believes that occupational exposures may occur over a single day or up to 

weeks at a time for many of the use-patterns and that intermittent exposure over several weeks 

may also occur. Some applicators may apply these products over a period of weeks, because 

they are commercial applicators who are completing multiple pesticide applications for multiple 

clients. Long-term exposures are not expected; therefore, a long-term assessment was not 

conducted. 

Table 7.1.1 provides a summary of the estimated exposures and risks to occupational pesticide 

handlers. An MOE ≥100 is adequate to protect occupational pesticide handlers. Since all the 

estimated MOEs are >100 with baseline protection, the proposed uses are not of concern for 

HED.
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Table 7.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Acequinocyl (with baseline protection). 

Exposure Scenario Crop or Target Application 

Rate2 

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term 

MOEs5

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Mixer/Loader

Mixing/Loading Liquids for 

Groundboom Applications

soybeans 0.3 

lb ai/A

200

acres 0.22 0.000219 0.19 0.00019 1,100 ST: 320,000IT: 85,000

small fruit and berry, 

succulent bean, cowpea 

forage, melon, 

cucumber (field)

0.3

lb ai/A

80

acres 0.22 0.000219 0.075 0.000075 2,700 ST: 800,000

IT: 210,000

Mixing/Loading Liquids for 

Airblast Applications cherries 0.3lb ai/A

40

acres 0.22 0.000219 0.038 0.000038 5,300 ST: 1,600,000IT: 430,000

Applicator

Applying Sprays via 

Groundboom Equipment

soybeans 0.3

lb ai/A

200

acres 0.0786 0.00034 0.067 0.00029 3,000 ST: 210,000IT: 55,000

small fruit and berry, 

succulent bean, cowpea 

forage, melon, 

cucumber (field)

0.3

lb ai/A

80

acres 0.0786 0.00034 0.027 0.00012 7,400 ST: 510,000

IT: 140,000

Applying Sprays via 

Airblast Equipment cherries 0.3lb ai/A

40

acres 1.77 0.00471 0.3 0.00081 660 ST: 74,000IT: 20,000

Mixer/Loader/Applicator

Mixing/Loading/Applying 

Liquids with Backpack 

Sprayer

Greenhouse cucumbers 0.01 

lb ai/gallon

40 gallons 13.2 0.14 0.075 0.0008 2,700 ST: 75,000

IT: 20,000

Mixing/Loading/Applying 

Liquids with Manuallypressurized Handwand40 gallons 100 0.03 0.57 0.00017 350 ST: 350,000

IT: 93,000

Mixing/Loading/Applying 

Liquids with Mechanicallypressurized Handgun 

Sprayer

1000 gallons 3.5 0.12 0.5 0.017 400 ST: 3,500

IT: 930

1. Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011). 

2. Applic. Rate. = Maximum rate listed on proposed Kanemite label (Reg. No. 66330-38).

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised September 25, 2001.

4. Dose (mg/kg/day) = Unit Exposure (mg/lb ai) * Application Rate * Area treated or Amount handled ÷ Body Weight (70 kg). 

5. MOE = NOAEL ÷ Dose. NOAEL = 200 (dermal), 60 (short-term inhalation), or 16 (intermediate-term inhalation) mg/kg bw/day.

6. Baseline = Long-sleeve shirt, long pants, and no gloves (dermal); no respirator (inhalation).
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7.2 Short- and Intermediate-term Occupational Post-application Risk

Dermal

HED expects that post-application exposure will occur since acequinocyl is applied postemergence as a foliar spray. Post-application exposure is expected to be short- and intermediateterm based on information provided on proposed labels (e.g., maximum of two sprays per season 

at a rate of 0.3 lb ai/A). The POD for the dermal route of exposure is the same for short- and 

intermediate-term exposure durations, so the risk estimate is protective of both durations of 

exposure. It is not anticipated that there would be long-term exposure from the greenhouse 

cucumber use since the label recommends that the proposed product not be used in successive 

applications to avoid resistance issues. 

The following inputs and assumptions were used in the post-application exposure calculations:

• Exposure Duration: 8 hours per day

• Body Weight: 70 kg

• Dermal TCs from the Science Advisory Council for Exposure (ExpoSAC) Policy 

Number 3. 

• Chemical-specific DFR data 

o Chrysanthemums in greenhouses (MRID 454286-19)

o Apples (MRID 456516-11)

It is the policy of HED to use the best available data to assess post-application exposure. 

Sources of generic post-application data, used as surrogate data in the absence of chemicalspecific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting post-application exposure that are used in this assessment, known as “transfer 

coefficients,” are presented in the “ExpoSAC Policy 3” 

(http://www.epa.gov/pesticides/science/exposac_policy3.pdf), which, along with additional 

information about the ARTF data, can be found at http://www.epa.gov/pesticides/science/postapp-exposure-data.html.

Chemical-specific DFR data were available for acequinocyl; however, the data were not for the 

currently proposed crops. Since DFR data are not available for the specific crops currently 

proposed for acequinocyl, the available data were used as surrogates. Based on a review of the 

available data, it was decided that the DFR data for chrysanthemums in greenhouses would be 

used as a surrogate for cucumbers in greenhouses, and the DFR data for apples would be used for 

all other proposed field crops. 

All agricultural crop scenarios resulted in MOEs greater than 100 on day 0 and are not of 

concern. Table 7.2.1 presents the risk estimates for all crops for the highest transfer coefficient 

associated with that crop; this represents the activities with the highest estimated risk. 
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Table 7.2.1: Dermal Post-application Exposure and Risk Using Chemical-Specific DFR Data.

Crop Group Proposed Crop

Highest Transfer Coefficient 

for Crop (cm2/hr) 

and Associated Activity

Days after 

Treatment

Study 

Test 

Site

Chemicalspecific 

DFR1

(ug/cm2)

Dermal 

Dose2

(mg/kg/day)

MOE3

Field/row 

crop, 

low/medium

Succulent 

soybean, 

succulent bean, 

cowpea forage

1,900 

(irrigation; hand set) 0

CA 0.217 0.047 4,200

NY 0.613 0.130 1,500

WA 0.435 0.094 2,100

Berry, low

Low growing 

berries 

subgroup 13-

07G

1,900 

(irrigation; hand set) 0

CA 0.217 0.047 4,200

NY 0.613 0.130 1,500

WA 0.435 0.094 2,100

Vine trellis

Small fruit, 

subgroup 13-

07F,

Caneberry crop 

subgroup 13-

07A

19,300 

(girdling, turning) 0

CA 0.217 0.480 420

NY 0.613 1.4 150

WA 0.435 0.960 210

Vegetable, 

cucurbit

Melon subgroup

9A,

Cucumber 

(field)

1,900 

(irrigation; hand set) 0

CA 0.217 0.047 4,200

NY 0.613 0.130 1,500

WA 0.435 0.094 2,100

Vegetable, 

greenhouse

Cucumber 

(greenhouse)

1,200

(Hand harvesting, Pinching, 

Pollination, Hand pruning, 

Scouting, Turning, 

Tying/Training, Hand 

weeding, Propagating)

0 CA 0.617 0.085 2,400

Tree, “fruit,” 

deciduous Cherry 3,600 

(thinning fruit) 0

CA 0.217 0.089 2,200

NY 0.613 0.250 790

WA 0.435 0.180 1,100

1 Chemical-specific DFR = measured chrysanthemum DFR data for greenhouse cucumbers and predicted apple DFR data for all other crops. 

Application rate in studies = proposed application rate; therefore, no adjustment of the DFR data was necessary.

2 Dermal Dose = [DFR (ug/cm2

) x TC (cm2/hr) x 0.001 mg/ug x 8 hrs/day] ÷ body weight (70 kg).

3 MOE = NOAEL (200 mg/kg/day)/ Dermal Dose (mg/kg/day). 

Inhalation 

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment was not performed for acequinocyl at this time. However, there are 

multiple potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated areas. These potential sources include volatilization 

of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its FIFRA 

SAP in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for acequinocyl.

REI 

Acequinocyl is classified in Toxicity Category III for acute dermal and acute inhalation. It is 

classified in Toxicity Category IV for primary eye irritation and primary skin irritation and it is 
Acequinocyl Human-Health Risk Assessment D389519

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not a dermal sensitizer. Therefore, the WPS interim REI of 12 hours is adequate to protect 

agricultural workers from post-application exposures to acequinocyl. The proposed label lists a 

REI of 12 hours. 

8.0 RESIDUE CHEMISTRY AND TOXICOLOGY DEFICIENCIES

8.1 Residue Chemistry

• Revised Section F.

• Revised Section B.

8.2 Toxicology

• An Immunotoxicity Study.

• Acute and Subchronic Neurotoxicity Studies.

• A 28-Day Inhalation Study.

8.3 Occupational and Residential Exposure

• None.

cc: S. Levy (RAB1); A. Dunbar (RAB1); K. Lowe (RAB1)

RDI: RAB1 Branch (23-NOV-2011); RAB1 Chemists (09-NOV-2011)

S. Levy: S10953: PY1:703-305-0783; 7509P:RAB1
Acequinocyl Human-Health Risk Assessment D389519

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APPENDIX: Toxicity Profile Tables and Metabolites.

Table A-1. Acute Toxicity of Acequinocyl.

Guideline

No. Study Type MRID #(s) Results Toxicity Category

870.1100

(81-1) Acute Oral (rat) 45435011 LD50 >5000 mg/kg IV

870.1200

(81-2) Acute Dermal 45435012 LD50 >2000 mg/kg III

870.1300

(81-3) Acute Inhalation 45435013 LC50 >0.84 mg/L III

870.2400

(81-4) Primary Eye Irritation 45435014 Not an eye irritant IV

870.2500

(81-5 ) Primary Skin Irritation 45435015 Not a dermal irritant IV

87.2600

(81-6) Dermal Sensitization 45435016 Not a dermal sensitizer N/A

Table A-2. Toxicity Profile for Acequinocyl.

Guideline No.; 

Study Type MRID (year); Doses; Classification Results

870.3100 

90-Day Oral Toxicity 

Rodents-MOUSE 

45673701 (1995); 

0, 100, 500, 1000 ppm

M: 0, 16, 81, 151 mg/kg/day 

F: 0, 21, 100, 231 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 16/21 mg/kg/day; LOAEL 

(M/F) = 81/100 mg/kg/day based on 

hepatocyte vacuolization.

870.3100 

90-Day Oral Toxicity 

Rodents-RAT

45531904 (1998);

0, 100, 400, 1600, 3200 ppm; 

M: , 7.6, 30.4, 119.5, 252.7 mg/kg/day 

F: 0, 8.3, 32.2, 129.2, 286.0 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 30.4/32.2 mg/kg/day; 

LOAEL (M/F) = 119.5/129.2 mg/kg/day 

based on increased prothrombin times in 

males and increased activated partial 

thromboplastin times in both sexes.

870.3150 

90-Day Oral Toxicity 

Nonrodents-DOG

45531905 (1995);

0, 40, 160, 640, 1000 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 40/40 mg/kg/day; LOAEL 

(M/F) = 160/160 mg/kg/day based on 

decreased body-weight gains and reduced 

food efficiencies in males and for female 

beagle dogs based on increased platelet 

counts.

870.3200

28-Day Dermal ToxicityRAT

45531906 (1999); 

0, 40, 200, 1000 mg/kg/day 

Acceptable/Guideline

Systemic NOAEL = 200 mg/kg/day; 

LOAEL = 1000 mg/kg/day based on 

increased clotting factor times (increased 

prothrombin time, increased activated partial 

prothromboplastin time, increased 

fibrinogen levels).

Dermal NOAEL = 1000 mg/kg/day; 

LOAEL = not established.

870.3700a 

Prenatal Developmental in 

Rodents-RAT

45531908, 45651706 (1995); 

0, 50, 150, 500, 750 mg/kg/day

Acceptable/Guideline 

Maternal NOAEL = 150 mg/kg/day; 

LOAEL = 500 mg/kg/day based on signs of 

internal hemorrhage and increased incidence 

of clinical signs (pale eyes, piloerection, red 

vaginal discharge).

Developmental NOAEL = 500 mg/kg/day; 

LOAEL = 750 mg/kg/day based on 

increased resorptions.
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Table A-2. Toxicity Profile for Acequinocyl.

Guideline No.; 

Study Type MRID (year); Doses; Classification Results

870.3700b 

Prenatal Developmental in 

Nonrodents-RABBIT 

45531907, 45651705 (1995); 

0, 30, 60, 120 mg/kg/day 

Acceptable/Guideline

Maternal NOAEL = 60 mg/kg/day; LOAEL

= 120 mg/kg/day based on treatment-related 

clinical signs leading to premature sacrifice 

(hematuria, reduced fecal output, bodyweight loss, and reduced food consumption) 

and gross necropsy findings (pale lungs and 

liver, hemorrhaging uterus, fluid in the 

cecum, fur in the stomach, blood stained 

vaginal opening, blood-stained urinary 

bladder contents/urine, and hair loss).

 

Developmental NOAEL = 60 mg/kg/day; 

LOAEL = 120 mg/kg/day based upon 

increased number of complete resorptions.

870.3800 

2-Generation Reproduction 

and Fertility-RAT

45531909 (1997);

0, 100, 800, 1500 ppm;

M: 0, 7.3, 58.9, 111.2 mg/kg/day 

F: 0, 8.7, 69.2, 133.5 mg/kg/day

Acceptable/Guideline

Parental NOAEL (M/F): 111.2/ 133.5 

mg/kg/day; 

LOAEL (M/F) = not established 

Offspring NOAEL (M/F): 7.3-8.2/8.7 

mg/kg/day; LOAEL (M/F) = 58.9/69.2 

based on hemorrhagic effects, swollen body 

parts, protruding eyes, clinical signs, delays 

in pupil development and increased 

mortality post weaning.

Reproductive NOAEL (M/F): 124/136 

mg/kg/day; LOAEL (M/F) = not 

established.

870.4100b 

Chronic Toxicity-DOG

45531910 (1996); 

0, 5, 20, 80, 320 mg/kg/day 

Acceptable/Guideline

NOAEL (M/F) = 80/80 mg/kg/day.

LOAEL (M/F) = 320/320 mg/kg/day based 

on premature sacrifice (inappetence, bodyweight loss).

870.4300

Chronic/ CarcinogenicityMOUSE

45531911 (1994);

0, 20, 50, 150, 500 ppm ;

M: 0, 2.7, 7.0, 20.3, 66.0 mg/kg/day 

F: 0, 3.5, 8.7, 26.3, 86.00 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 2.7/3.5 mg/kg/day.

LOAEL (M/F) = 7.0/8.7 mg/kg/day based 

on clinical chemistry and microscopic nonneoplastic lesions (brown pigmented cells 

and perivascular inflammatory cells in 

liver).

870.4300 

Chronic/

Carcinogenicity-RAT 

45531912 (1997);

0, 50, 200, 800 or 1600 ppm;

M: 0, 2.25, 9.02, 36.41, 74.00 mg/kg/day 

F: 0, 2.92, 11.61, 46.2, 93.56 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 2.25/46.20 mg/kg/day

LOAEL (M/F) = 9.02/93.56 mg/kg/day 

based on enlarged eyeballs in male and 

female rats (coagulopathy).

870.5100

Gene Mutation

45435101 (1998);

19.5, 39.1, 78.1, 156, 313, 625, 1250, 2500 or 

5000 μg/plate in the presence and absence of 

mammalian metabolic activation (S9-mix) 

and additionally at 9.77 μg/plate without S9-

mix.

Acceptable/Guideline

There was no evidence of induced mutant 

colonies over background.

870.5300

Gene Mutation

45435102 (1998);

5-7 doses ranging from 10-320 μg/mL

Acceptable/Guideline

There was no clear evidence of biologicallysignificant induction of mutant colonies over 

background.
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Table A-2. Toxicity Profile for Acequinocyl.

Guideline No.; 

Study Type MRID (year); Doses; Classification Results

870.5375

Chromosome Aberration

45435103 (1998);

0, 150, 300, 600, or 1200 μg/mL for 24 or 48 

hours without metabolic activation (S9-mix) 

and to concentrations of 0, 481, 963, 1925 or 

3850 μg/mL (highest concentration is 

equivalent to 10mM) for 6 hours with S9-

mix. 

Acceptable/Guideline

There was no evidence of chromosome 

aberrations induced over background.

870.5395

Mammalian Erythrocyte 

Micronucleus Test in 

MOUSE

45435104 (1993);

0, 1250, 2500, or 5000 mg/kg body weight

Acceptable/Guideline

There was no statistically significant

increase in the frequency of micronucleated 

polychromatic erythrocytes in mouse bone 

marrow at any dose or harvest time.

870.7485

Metabolism-RAT

45435105, 45531913 (1997); 

single oral doses of 10 or 500 mg/kg (phenyl 

label) or 10 mg/kg (dodecyl label), and 14-

day repeated 10 mg/kg dose (phenyl label).

Acceptable/Guideline

Acequinocyl exhibits marginal absorption, 

relatively rapid and complete excretion 

primarily via the bile and feces, and 

undergoes nearly complete metabolism to 

hydrolysis products and a glucuronide 

conjugate. There was no evidence for 

selective tissue accumulation or 

sequestration of 2023 (acequinocyl) or its 

metabolites in rats.

870.7600

Dermal Penetration-RAT 

45435106(2000); 

0, 0.001, 0.01, 0.1, 1.0 mg/cm2

Acceptable/Guideline

Percent of dose absorbed decreased with 

exposure concentration indicating that 

saturation of absorption at/or about the high 

dose. Absorption at 168 hours was 12.23%, 

19.75%, and 14.77% for the 0.1, 0.01, and 

0.001 mg/cm2 dose groups, respectively.

Table A-3. Structures of Acequinocyl and Its Metabolites.

Common 

Name/Code Chemical Name Chemical Structure

Acequinocyl 2-(acetyloxy)-3-dodecyl-1,4-

naphthalenedione

Acequinocyl-OH

(Metabolite R1)

2-dodecyl-3-hydroxy-1,4-

naphthalenedione

AKM-18 2-(1,2-dioxotetradecyl)-benzoic 

acid

O

O

CH2( CH2)10 CH3

OCOCH3

O

O

CH2( CH2)10 CH3

OH

O

O

O

OH

( CH2)11 CH3
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Table A-3. Structures of Acequinocyl and Its Metabolites.

Common 

Name/Code Chemical Name Chemical Structure

AKM-15 2-hydroxy-3-hexanoic acid-1, 4 

naphthalenedione

AKM-14 2-hydroxy-3-butanoic 

acid-1,4-naphthalenedions

O

O

OH

COOH

O

O

CH2

OH

( CH2) CH 9 CH3

OH