Acequinocyl Human-Health Risk Assessment DP# 368425

Page 1 of 35

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

MEMORANDUM

Date: 26-AUG-2010

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

Fruiting Vegetables, Hops, Okra, and Edible-Podded Beans.

PC Code: 006329 DP Barcode: D368425

Decision No.: 417967 Registration No.: 66330-38

Petition No.: 9E7598 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

Allison Nowotarski, Biologist

Registration Action 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/S. Jackson, 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 fruiting vegetables, hops, okra, and edible-podded beans. 

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 

assessment was provided by Allison Nowotarski (RAB1), and the drinking water exposure 

assessment was provided by Iwona Maher of the Environmental Fate and Effects Division 

(EFED).
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 2 of 35

Recommendation for Tolerances and Registration

Pending submission of revised Sections B and F, and submission of analytical reference 

standards to the EPA National Pesticide Standards Repository, there are no residue chemistry

issues that would preclude granting a permanent registration for the requested uses of 

acequinocyl or establishment of tolerances for residues of acequinocyl and acequinocyl-OH as 

follows: 

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

Okra..................................................................................................0.70 ppm

Bean, edible podded.........................................................................0.25 ppm

Hop, dried cones ..............................................................................4.0 ppm

Registration should be conditional pending resolution of the following deficiencies:

Toxicology

 An Immunotoxicity Study.

 Acute and Subchronic Neurotoxicity Studies.

 A 28-Day Inhalation Study.

Note to PM: According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. 

Knizner), the tolerance expression for acequinocyl should be revised to state:

“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.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 3 of 35

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 Endocrine Disruption .............................................................................................. 14

3.5 Recommendation for Aggregate Exposure Risk Assessments............................. 15

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

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

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

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

4.3 Water Exposure/Risk Pathway............................................................................... 19

4.4 Dietary Exposure Analyses ..................................................................................... 20

4.4.1 Chronic Dietary Exposure Analysis........................................................ 21

4.5 Residential/Non-Occupational Exposure Pathway............................................... 21

4.5.1 Residential Handler Exposure/Risk........................................................ 22

4.5.2 Residential Post-application Exposure/Risk .......................................... 23

4.5.3 Spray Drift................................................................................................. 24

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

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

5.2 Short-Term Aggregate Risk.................................................................................... 25

5.3 Intermediate-Term Aggregate Risk ....................................................................... 25

5.4 Long-Term Aggregate Risk..................................................................................... 25

5.5 Cancer Risk .............................................................................................................. 25

6.0 CUMULATIVE RISK......................................................................................................... 25

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

7.1 Occupational Handler Exposure/Risk ................................................................... 26

7.2 Post-application Exposure/Risk.............................................................................. 28

7.3 REI ............................................................................................................................ 31

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
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 4 of 35

1.0 EXECUTIVE SUMMARY

Acequinocyl is a quinoline-type miticide that is currently registered for use on greenhouse, 

shadehouse, ornamental, floral, foliage, nursery crops, grapes, tree nuts, pome fruits, citrus fruits, 

pistachios, and strawberries, as well as for use on 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% suspension-concentrate (SC) formulation.

Under PP#9E7598, the Interregional Research Project No.4 (IR-4), on behalf of the Agricultural 

Experiment Station of AZ, CA, CO, FL, ID, NC, NJ, NY, OK, OR, TN, TX, VA, and WA, is 

requesting for the establishment of tolerances for the combined residues of the insecticide 

acequinocyl, 2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione, and its metabolite, 2-dodecyl-3-

hydroxy-1,4-naphthoquinone, expressed as acequinocyl equivalents in/on the following 

commodities:

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

Okra..................................................................................................0.70 ppm

Bean, edible podded.........................................................................0.25 ppm

Hop, dried cones ..............................................................................3.5 ppm

The end-use product proposed for use on fruiting vegetables, hops, okra and snap beans is 

KanemiteTM 15 SC Miticide, a 1.25 pounds per gallon (lb/gal) SC formulation. Up to two foliar 

applications are proposed for a maximum seasonal rate of 0.6 lb active ingredient per acre (ai/A), 

with a 7-day preharvest interval (PHI), except for okra for which a 1-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. 

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.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 5 of 35

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 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 Food Quality Protection Act (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): The HED Metabolism Assessment Review 

Committee (MARC) determined that the residues of concern in the dietary exposure and risk 

assessment are acequinocyl and acequinocyl-OH (also referred to as R1) for both tolerance 

expression and risk assessment purposes. In addition, for liver and kidney, 2-hydroxy-3-

hexanoic acid-1,4 naphthalenedione (AKM-15) was also included, but for risk assessment 

purposes only. 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. The 1-in-10-year peak concentrations of 

acequinocyl ranged from 0.18 (CA citrus) to 5.57 (FL nursery plants except roses) ppb. The 60-

day concentrations of acequinocyl ranged from 0.04 to 1.26 ppb. 

A chronic aggregate dietary (food and drinking water) exposure and risk assessment was 

conducted for acequinocyl using the Dietary Exposure Evaluation Model (DEEM-FCID

TM), 

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 which 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 and water utilized 9.8% of the cPAD. The chronic dietary risk estimate for the 

highest exposed population subgroup, children 1-2 years old, is 45% 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. All risks for residential 

handlers are above the target MOE of 100 and do not exceed HED’s LOC. Post-application 

exposure is not anticipated with the proposed uses. 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 6 of 35

Occupational Exposure Estimates: Occupational handler and postapplication exposure is 

expected from the proposed uses of acequinocyl. No chemical-specific handler exposure data 

were submitted in support of this Section 3 registration. It is the policy of the HED to use data 

from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented in PHED 

Surrogate Exposure Guide (8/98) to assess handler exposures for regulatory actions when 

chemical-specific monitoring data are not available (HED Science Advisory Council for 

Exposure (ExpoSAC) Draft Standard Operating Procedure (SOP) #7, dated 1/28/99). 

All risks for occupational handlers are above the target margin of exposure (MOE) of 100 with 

the use of gloves, and do not exceed the LOC as the proposed labels already require the use of 

protective gloves as personal protective equipment. There are no risks of concern for all 

occupational post-application activities associated with the proposed uses. 

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 restrictedentry interval (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 adults and the aggregate MOEs are >100 and are, therefore, not of concern to 

HED. 

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).

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 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 7 of 35

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 postapplication 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: Past acequinocyl risk assessments rely in part on data from studies 

in which adult human subjects were intentionally exposed to a pesticide to determine their 

dermal and inhalation exposure. Many such studies, involving exposure to many different 

pesticides, comprise generic pesticide exposure databases such as PHED, the Outdoor 

Residential Exposure Task Force (ORETF) Database, and the Agricultural Reentry Task Force 

(ARTF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic 

exposure databases, and has found no clear and convincing evidence that the conduct of any of 

them was either fundamentally unethical or significantly deficient relative to the ethical standards 

prevailing at the time the research was conducted. All applicable requirements of EPA’s Rule 

for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and 

there is no regulatory barrier to continued reliance on these studies.

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

and F, and submission of analytical reference standards to the EPA National Pesticide Standards 

Repository, there are no residue chemistry issues that would preclude granting a permanent 

registration for the requested uses of acequinocyl or establishment of tolerances for residues of 

acequinocyl and acequinocyl-OH as follows: 

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

Okra..................................................................................................0.70 ppm

Bean, edible podded.........................................................................0.25 ppm

Hop, dried cones ..............................................................................4.0 ppm

Registration should be conditional pending resolution of the following deficiencies:

Toxicology

 An Immunotoxicity Study.

 Acute and Subchronic Neurotoxicity Studies.

 A 28-Day Inhalation Study.

Note to PM: According to HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 

5/27/09), the tolerance expression for acequinocyl should be revised to state:

“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.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 8 of 35

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

Provided below are the physical/chemical properties for acequinocyl; they include product 

chemistry data. 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

O

O

CH2(CH2)

10CH3

OCOCH3

O

O

CH2(CH2)

10CH3

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 10-9pascals at 250C (technical)

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

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

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.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 9 of 35

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 raw agricultural commodities 

(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 Hazard Identification Assessment Review Committee (HIARC). Meeting 

Date: October 14, 2003. TXR No. 0052234. P. Terse; 11/13/04.

 Acequinocyl. Report of the Hazard Identification Assessment Review Committee. Meeting Date: July 15, 

2003. TXR No. 0052075. R. Fricke; 8/14/03. 

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 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 

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 body

weight 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 adverse 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 10 of 35

effects 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 

chromosomal aberration assay, an in vivo mouse bone marrow micronucleus assay, and a 

bacterial DNA damage or repair assay.

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 Human-Health Risk Assessment DP# 368425

Page 11 of 35

In feces and the bile, the components identified were: (1) parent compound; (2) 2-hydroxy-3-

dodecyl-1, 4-naphthalenedione (acequinocyl-OH); (3) 2-(1,2-dioxotetradecyl)-benzoic acid 

(AKM-18); (4) conjugated acequinocyl-OH; (5) 2-hydroxy-3-butanoic acid-1,4-

naphthalenedions; and (AKM-14) (6) 4 naphthalenedione (AKM-15). The structures for these 

metabolites may be found in the Appendix, Table A-3. 

The major urinary metabolites included: (1) 2-hydroxy-3-hexanoic acid-1; 4 naphthalenedione 

(AKM-15); and (2) 2-hydroxy-3-butanoic acid-1,4-naphthalenedions (AKM-14). Neither the 

parent compound nor the hydroxy metabolite (acequinocyl-OH) was observed in the urine. 

The major components detected in plasma were: (1) parent compound; (2) acequinocyl-OH; (3) 

conjugated acequinocyl-OH; (4) AKM-14; and (5) AKM-15. 

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 point of departure (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 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 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 12 of 35

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 impact the FQPA SF.

 The dietary food and drinking water exposure 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, 

health-protective, high-end estimates of water concentrations that will not likely be 

exceeded.

3.3 Dose-Response Assessment

Tables 3.3.1 and 3.3.2 provide 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.

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- (1-30 

days) and 

Intermediate-(1-6 

months) Term 

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- (1-30 

days) Term 

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, bloodstained urinary bladder 

contents/urine).
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 13 of 35

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 vacuolation.

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

1

 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 = noobserved-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, UFDB = database uncertainty factor, UFL = uncertainty factor for lack of a NOAEL.

2 15% Dermal-absorption factor – derived from dermal-penetration study.

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 

determined on the basis of 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 derive 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- and Intermediate-Term Incidental Oral Endpoints: Since there are no residential uses 

under consideration in the current risk assessment, where there may be potential short- or 

intermediate term incidental oral exposures, these risk assessments were not performed.

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 

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
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 14 of 35

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 Endocrine Disruption

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a 

“naturally occurring estrogen, or other such endocrine effects as the Administrator may

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 15 of 35

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group 

of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list 

of chemicals was selected based on the potential for human exposure through pathways such as 

food and water, residential activity, and certain post-application agricultural scenarios. This list 

should not be construed as a list of known or likely endocrine disruptors.

Acequinocyl was not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/

3.5 Recommendation for Aggregate Exposure Risk Assessments

Since short- and intermediate-term inhalation endpoints are based on oral studies, dietary

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#: 9E7598. Acequinocyl. Petition for Use on Fruiting Vegetables, Hops, Okra, and Edible-Podded 

Beans. Summary of Analytical Chemistry and Residue Data. D369100. S. Levy, 8/25/10.

 PP#: 9E7598. Acequinocyl. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessment for the Section 3 Registration Action Use on Fruiting Vegetables, Hops, Okra, and EdiblePodded Beans. D369101. S. Levy, 8/25/10.

 Acequinocyl: Occupational and Residential Exposure/Risk Assessment for Proposed Use on Fruiting 

Vegetables Crop Group 8 (Tomatoes & Peppers), Edible Podded Beans, Hops, and Okra. DP Barcode: 

369099. A. Nowotarski. 6/10/10.

 Acequinocyl and its Degradate, Acequinocyl-OH (R1), Drinking Water Assessment in Support of IR-4 

New Uses Registration for Fruiting Vegetables (Crop Group 8), Okra, Edible Podded Beans, and Hops.

D368426 and 368579. I. Maher et al., 4/29/10.

Acequinocyl is a quinoline type miticide registered for use in the U.S. on pome fruits, citrus 

fruits, grapes, tree nuts, pistachios, and strawberries for the control of various phytophagous mite 

species.

Under PP#9E7598, the Interregional Research Project No.4 (IR-4), on behalf of the Agricultural 

Experiment Station of AZ, CA, CO, FL, ID, NC, NJ, NY, OK, OR, TN, TX, VA, and WA, is 

requesting for the establishment of tolerances for the combined residues of the insecticide 

acequinocyl, 2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione, and its metabolite, 2-dodecyl-3-

hydroxy-1,4-naphthoquinone, expressed as acequinocyl equivalents in/on the following 

commodities:

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

Okra..................................................................................................0.70 ppm
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 16 of 35

Bean, edible podded.........................................................................0.25 ppm

Hop, dried cones ..............................................................................3.5 ppm

4.1 Summary of Proposed 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. The acequinocyl formulation, which is currently

registered for use on several fruit and nut crops, is proposed for use on 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.

Commodity

Trade Name 

(EPA Reg. 

No.)

Application 

Timing, 

Type, 

Equipment

Application 

Rate

(lb ai/A)

Maximum 

Number 

Applications

Per Season

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

PHI1

(days)

Use Directions and 

Limitations1

Fruiting 

vegetable 

crop group 8 

(tomato and 

pepper)

KanemiteTM 

15 SC Ground 0.3 2 0.6 7 RTI: 21 days, minimum GPA: 100

Edible 

podded bean

Hop

Okra 1

1

PHI = preharvest interval, RTI = retreatment interval, GPA = gallons of water volume per acre.

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 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. 

No rotational crop restrictions are specified on the label. The label requires applicators and other 

handlers to wear long-sleeved shirt and long pants, chemical-resistant gloves, and shoes plus 

socks.

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 generally supported by the 

submitted field trial data; however, the data for fruiting vegetables supports a 1-day PHI for all 

fruiting vegetables. The petitioner may reduce the proposed PHI for fruiting vegetables from 7 

days to 1 day, based on field trial data. The submitted fruiting vegetable data do support the 1-

day PHI proposed for okra. 

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 adjuvant-use 

restriction. An adequate confined rotational crop study was previously submitted, reflecting the 

maximum proposed use pattern for rotated crops (fruiting vegetables and edible-podded beans). 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 17 of 35

These data support a 30-day plant-back interval (PBI) for all non-labeled crops. A revised 

Section B should be submitted incorporating the rotational crop restriction.

4.2 Dietary Exposure/Risk Pathway

4.2.1 Residue Profile

Nature of the Residue-Plants: The nature of acequinocyl residues in apples, oranges, and 

eggplants is understood based on the previously submitted and reviewed metabolism studies. In 

these crops, the metabolism of acequinocyl involves the loss of the acetyloxy moiety to form 

acequinocyl-OH, 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, HED has determined that the residues 

of concern in these commodities include parent and acequinocyl-OH (Memo, S. Levy, 07-JAN2004; DP# 297872).

Nature of the Residue-Livestock: There are no livestock feedstuffs associated with the proposed 

crop uses addressed herein. Therefore, no livestock metabolism data, enforcement methods, 

storage stability data, or feeding studies are required to support this petition.

Magnitude of the Residue-Plants: The submitted magnitude of the residue data for tomatoes, 

peppers, edible-podded beans, and hops are adequate. 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 incorporating an adjuvant-use restriction. The 

Agency’s tolerance spreadsheet as specified by the Guidance for Setting Tolerances Based on 

Field Trial Data SOP (August 2009 version) was used to determine the appropriate tolerance 

levels. The field trial data will support tolerances of: 0.70 ppm for fruiting vegetables; 0.70 ppm 

for okra; 0.25 ppm for edible-podded beans; and 4.0 ppm for dried hop cones.

It is noted that the proposed PHI for fruiting vegetables is 7 days whereas the field trials reflect a 

1-day PHI. Residue decline trials for tomato and pepper demonstrate that residues generally

decline with later sampling intervals; therefore, the proposed/recommended tolerance will likely

overestimate anticipated residues of acequinocyl and acequinocyl-OH in/on fruiting vegetables. 

The available data support the proposed tolerances for fruiting vegetables, okra, and ediblepodded beans; however, the proposed tolerance for hop dried cones is too low.

Magnitude of the Residue in Processed Food and Feed: An adequate tomato processing study

is available and supports the proposed use on fruiting vegetables. The tomato processing study is 

adequate. The results indicate that residues of acequinocyl and acequinocyl-OH did not 

concentrate in paste and puree processed from tomato fruits bearing quantifiable residues of 

acequinocyl. No tolerances are required for tomato processed matrices. 

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

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

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

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

and nut commodities (Morse Methods Meth-133, Revision #4 and Meth-135, Revision #3)
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 18 of 35

(Memo, S. Levy, 8/25/10; DP#: 380302). 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). 

Residue data from the current field trial and processing studies were obtained using the approved 

enforcement methods, Meth-135 (tomato, pepper and hops) and Meth-133 (snap beans) with 

minor modifications. The methods are adequate for data collection based on acceptable method 

validation and concurrent method recovery data for tomato and its processed matrices, pepper, 

and snap beans. However, the data-collection method yielded consistently low recoveries 

(~53%) for acequinocyl-OH in dried hop cones; therefore, residues of the metabolite from the 

hop field trials were corrected for low recoveries. The validated limit of quantitation (LOQ) was 

0.010 ppm for acequinocyl and 0.025 ppm for acequinocyl-OH in/on tomato and pepper; 0.020 

ppm each for acequinocyl and acequinocyl-OH in/on edible-podded beans; and 0.10 ppm for 

acequinocyl in/on hop dried cones. 

The available analytical standards for acequinocyl and acequinocyl-OH at the EPA National 

Pesticide Standards Repository (personal communication with Dallas Wright, ACB, 4/30/10) 

expired on 4/19/10 and 4/20/10, respectively. This is a deficiency. The petitioner should either 

recertify the lot in the repository and send in an updated certificate of analysis (COA), or submit 

new standards (different lot #) if the previous lots will not be recertified.

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, 2/18/04; DP#: 298917).

Storage Stability in Plants: The submitted concurrent storage stability data for tomato, snap 

bean, and hops is adequate to support the storage intervals and conditions incurred by the field 

trial studies. In addition, the concurrent storage stability data for the parent acequinocyl is 

adequate to support the sample storage intervals and conditions for the pepper field trials and 

tomato processing studies. It is noted that zero-day data were not provided. IR-4 is reminded 

that storage stability studies should always include a zero-day sampling interval to establish the 

residue levels present at the time samples are placed into storage [see OPPTS 860.1380(d)(6)(i)]. 

The concurrent storage stability data indicate problems with the stability of acequinocyl-OH in 

peppers and processed tomato paste and puree. Because zero-day samples were not analyzed, 

determination of residue levels present at the time samples were placed in frozen storage could 

not be made. In addition, an insufficient number of time points were analyzed in order to 

establish how much of the residue (acequinocyl-OH) was lost at various time points. 

However, because residues of acequinocyl-OH in the pepper field trial were <10% of the parent 

value or were <LOQ, correction for 51% decline would not affect the results. Furthermore, in 

the tomato processing study, because there were quantifiable residues of the parent in the RAC 

and residues of acequinocyl-OH in the RAC were nonquantifiable, HED believes that any

concentration of acequinocyl-OH residues would not significantly increase the total residue level. 

Therefore, HED is not requesting additional storage stability data at this time. 

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 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 19 of 35

(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.

Proposed and Recommended Tolerances: The proposed and recommended tolerances for the 

combined residues of acequinocyl are listed below in Table 4.2.1.1 (a revised Section F should 

be submitted). There are no established or proposed Codex, Canadian, or maximum residue 

limits (MRLs) for acequinocyl.

The field trial data for tomato and pepper are considered adequate to support a crop group 

tolerance. The tomato, bell pepper and non-bell pepper datasets were separately entered into the 

tolerance spreadsheet (rev. 8/09) in the Agency’s Guidance for Setting Pesticide Tolerances 

Based on Field Trial Data; see Appendix I. The proposed tolerance (0.70 ppm) for the fruiting 

vegetable group 8 is appropriate. No tolerances are required for tomato paste or puree.

Okra has been recommended to be added as a member of the fruiting vegetable group 8; 

however, until okra has been officially added to the crop group, a separate tolerance is required. 

The tomato and pepper field trial data will support the proposed tolerance (0.70 ppm) for okra. 

The snap bean and hop dried cone data are adequate, and were entered into the tolerance 

spreadsheet to determine the appropriate tolerances; see Appendix I. The proposed tolerance 

(0.25 ppm) for edible-podded beans is appropriate; however, the tolerance proposed for hop dried 

cones is too low and should be increased to 0.40 ppm.

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

Table 4.2.1.1. Tolerance Summary for Acequinocyl.

Commodity Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments; 

Correct Commodity Definition

Vegetable, fruiting, group 8 0.70 0.70

Okra 0.70 0.70

Bean, edible podded 0.25 0.25

Hop, dried cones 3.5 4.0

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 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 20 of 35

hydroxy-acequinocyl (also known as OH-AKD 023, 2-hydroxy-3-dodecyl-1,4-napthelenedione 

(HDNQ), and R-1).

Surface and Ground Water Estimated Drinking Water Concentrations (EDWCs): There are 

no drinking water monitoring data available for acequinocyl or its metabolite acequinocyl-OH 

(R1), the residues of concern. Groundwater and surface water estimated drinking water 

concentrations (EDWCs) were generated for acequinocyl using the Screening Concentration in 

Ground Water (SCI-GROW) and Pesticide Root Zone Model/Exposure Analysis Modeling 

System (PRZM/EXAMS) models, respectively. Two approaches were used in performing the 

drinking water assessment for the 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 + acequinocylOH) residues were modeled with the assumption that the metabolite acequinocyl-OH (referred to 

as the R1 degradate in this assessment) is of toxicological concern. The highest PRZM-EXAMS 

surface water modeling estimates were obtained for the Pennsylvania tomato scenario for the 

chronic values. The modeled EDWCs for ground and surface water are summarized in Table 

4.3.1.

Table 4.3.1. Ground and Surface Water EDWCs for Acequinocyl.

Approach #1 and #2

Groundwater EDWC for 

Acequinocyl + R1 (ppb)

Surface Water

Approach #1

Acequinocyl

Approach #2

Acequinocyl + R1

1-in-10-Year Chronic Mean 

Concentration (ppb)

1-in-10-Year Chronic Mean 

Concentration (ppb)

0.0036 2.45 0.29

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 (2.45 ppb) while that derived via Approach #2 represents 

the lower-bound value (0.29). The 2.45 ppb value was used in the dietary modeling 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.

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: 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 21 of 35

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-FCID

TM 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. 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 2.45

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 (9.8% cPAD) and all population subgroups. The most highly

exposed population subgroup is children 1-2 years old at 45% 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 and Drinking Water) Exposure and Risk for Acequinocyl.

Population Subgroup

Chronic Dietary1

Dietary Exposure

(mg/kg/day)

% cPAD

U.S. Population (total) 0.002657 9.8

All Infants (< 1 year old) 0.005584 21

Children 1-2 years old 0.012193 45

Children 3-5 years old 0.008046 30

Children 6-12 years old 0.003657 14

Youth 13-19 years old 0.001855 6.9

Adults 20-49 years old 0.001758 6.5

Adults 50+ years old 0.001811 6.7

Females 13-49 years old 0.001808 6.7

1 Chronic dietary endpoint of 0.027 mg/kg/day applies to the general U.S. population and all population subgroups. 

The values for the highest exposed population for each type of risk assessment should be bolded.

4.5 Residential/Non-Occupational Exposure Pathway

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 assessment was 

conducted in September of 2007 (Memo, K. Lowe, 9/6/07, D332006, 337473) and showed no 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 22 of 35

risks of concern to HED (i.e., MOEs >100). The assessment provided in this document reflects 

changes to the short- and intermediate-term dermal and inhalation endpoints.

4.5.1 Residential Handler Exposure/Risk

There is potential for residential handler exposure from the registered uses on landscape 

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

other non-production areas by commercial applicators and homeowners. Homeowner handlers 

are expected to complete all tasks associated with the use of a pesticide product including mixing 

and loading (if needed), and application. Based upon the proposed use pattern, the following 

residential handler scenarios have been assessed:

(1) Mixing/loading.applying liquids with low-pressure handwand (ORETF- fruit trees and 

ornamentals); and

(2) Mixing/loading/applying liquids with hose-end sprayer (ORETF- fruit trees and 

ornamentals).

No chemical-specific data were available with which to assess potential exposure to pesticide 

handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data 

available from the ORETF. Homeowner handler assessments are based on the assumption that 

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

exposure scenarios are considered to be short-term only, due to infrequent use patterns associated 

with homeowner products. 

Daily dermal or inhalation handler exposures are estimated for each applicable handler task with 

the application rate, the area treated in a day, and the applicable dermal or inhalation unit 

exposure using the following formula: 

Daily Exposure (mg ai/day) = Unit Exposure (mg ai/lb ai handled) x Application Rate (lbs ai/gallon) x Amount 

Handled (gal/day)

Where: 

Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is 

available for dermal absorption or amount inhaled that is available for 

inhalation absorption;

Unit Exposure = Unit exposure value (mg ai/lb ai) derived from August 1998 PHED data 

or from ORETF data;

Application Rate = Normalized application rate (lb ai/gal); and

Daily Area Treated = Normalized amount handled (gal/day). 

The daily dermal or inhalation dose is calculated by normalizing the daily exposure by body

weight and adjusting, if necessary, with an appropriate dermal or inhalation absorption factor 

using the following formula: 

Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x (Absorption Factor (%/100) / Body Weight (kg)

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a 

given scenario (mg ai/kg bw/day);
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 23 of 35

Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is 

available for dermal absorption or amount inhaled that is 

available for inhalation absorption;

Absorption Factor = A measure of the amount of chemical that crosses a biological 

boundary such as the skin or lungs (% of the total available 

absorbed); and

Body Weight = Body weight determined to represent the population of interest 

in a risk assessment (kg).

Non-cancer dermal and inhalation risks for each applicable handler scenario are calculated using 

a MOE, which is a ratio of the NOAEL to the daily dose. All MOE values were calculated using 

the formula below:

MOE = NOAEL or LOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day)

Table 4.5.1.1 presents the exposure/risks for residential handler short-term dermal and inhalation 

exposures at baseline. Based on HED’s residential handler assessment, there are no risks of 

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

Table 4.5.1.1. Residential Handler Dermal and Inhalation Exposures and Risks.

Dermal and

Inhalation Unit 

Exposures 

(mg/lb ai)

Application Rate

(lb ai/gallon)1

Amount Handled 

Daily 

(gallons)2

Doses 

(mg/kg/day)3 MOEs4

Mixer/Loader/Applicator – Liquid with Low-Pressure Handwand (ORETF--fruit trees and ornamentals)

Dermal

Baseline5: 56 0.00125 5

Dermal

Baseline: 0.005

Dermal

Baseline: 40,000

Inhalation

Baseline6: 0.0026

Inhalation

Baseline: 2.3E-07

Inhalation

Baseline: 2.6E8

Mixer/Loader/Applicator – Liquid with Hose-End Sprayer (ORETF-- fruit trees and ornamentals)

Dermal

Baseline: 39 0.00125 100

Dermal

Baseline: 0.07

Dermal

Baseline: 2,900

Inhalation

Baseline: 0.0016

Inhalation

Baseline: 2.9E-06

Inhalation

Baseline: 2.1E7

1 Application rates are the maximum application rates determined from proposed labels for acequinocyl.

2 Amount handled per day values are HED estimates of acres treated per day based on ExpoSAC SOP #9 “Standard Values for Daily 

Acres Treated in Agriculture,” industry sources, and HED estimates.

3 Dose (mg/kg/day) = Unit exposure (mg/lb ai) x App Rate (lb ai/gal) x Amount Handled (gal/day) x %Absorption (100% dermal 

and 100% inhalation) / Body weight (70 kg). 

4 MOE = NOAEL/Dose; where the short-term dermal NOAEL = 200 mg/kg/day and short-term inhalation NOAEL = 60 mg/kg/day.

5 Baseline Dermal: short-sleeve shirt, short pants, and no gloves.

6 Baseline Inhalation: no respirator.

4.5.2 Residential Post-application Exposure/Risk

Dermal: With respect to the registered residential uses on landscape ornamentals, current HED 

policy (see ExpoSAC minutes from 8/19/99 and 10/11/01) specifies that no significant dermal 

post-application exposure is anticipated from landscape ornamentals, either by residents or 

professional applicators; therefore, no residential dermal post-application assessment was 

conducted.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 24 of 35

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

inhalation exposure assessment (including bystander exposure) was not performed for 

acequinocyl at this time. However, volatilization of pesticides may be a potential source of postapplication 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.

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 

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 drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

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 dietary endpoint was not identified, an acute 

hazard does not exist and an acute aggregate assessment was not performed. 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 25 of 35

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 adult 50+ years old population is 

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

populations groups; therefore, this sub-population 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

both the general U.S. population and the adults 50+ years old sub-population are shown below in 

Table 5.2.1 and are not of concern to HED. 

Table 5.2.1. Short-Term Aggregate Risk Calculations.

Population Dietary MOE1 Residential Dermal 

MOE2

Residential Inhalation 

MOE2

Aggregate

MOE3

U.S. Population 23,000 2,900 21,000,000 2,600

Adults 50+ years old 33,000 2,900 21,000,000 2,700

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 postapplication 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 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 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 26 of 35

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 Fruiting 

Vegetables Crop Group 8 (Tomatoes & Peppers), Edible Podded Beans, Hops, and Okra. DP Barcode: 

369099. A. Nowotarski. 6/9/10.

7.1 Occupational Handler Exposure/Risk

Potential occupational exposure scenarios include: 1) mixing/loading liquids in support of 

groundboom operations, and 2) applicators using open-cab groundboom equipment. Application 

through irrigation or aerial systems is prohibited. 

No chemical-specific data are available with which to assess potential exposure to pesticide 

handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data 

available in PHED (8/1998). For pesticide handlers, it is HED standard practice to present 

estimates of dermal exposure for “baseline”; that is, for 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 personal-protective equipment 

(PPE) as might be necessary. The proposed product label involved in this assessment directs 

applicators and other handlers to wear long-sleeved shirt and long pants, socks, shoes, and 

chemical-resistant gloves made of waterproof material. 

Daily handler exposures are estimated for each applicable handler task with the application rate, 

the area treated in a day, and the applicable unit exposure using the following formula:

Daily Exposure (mg ai/day) = Unit Exposure (mg ai/lb ai handled) x Application Rate (lbs ai/area) x Daily Area 

Treated (area/day)

Where:

Daily Exposure = Amount (mg ai/day) inhaled that is available for inhalation absorption;

Unit Exposure = Unit exposure value (mg ai/lb ai) derived from August 1998 PHED data;

Application Rate = Normalized application rate based on a logical unit treatment, such as acres; and

Daily Area Treated = Normalized application area based on a logical unit treatment such as acres 

(A/day).

The daily dermal or inhalation dose is calculated by normalizing the daily exposure by body

weight and adjusting, if necessary, with an appropriate inhalation absorption factor using the 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 27 of 35

following formula:

Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x (Absorption Factor (%/100)) / Body Weight (kg)

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given 

scenario (mg ai/kg body weight/day);

Daily Exposure = Amount (mg ai/day) deposited on surface of skin that is available for 

dermal absorption, or the amount inhaled that is available for inhalation 

absorption;

Absorption Factor = A measure of the amount of chemical that crosses a biological boundary 

such as the skin or lungs (% of the total available absorbed); and

Body Weight = Body weight determined to represent the population of interest in a risk 

assessment (kg).

Based on the use pattern and information provided on the labels, (i.e., 2 applications per season 

and 21-day RTI), short- and intermediate-term exposures are expected and were assessed. Longterm exposures are not expected; therefore, a long-term assessment was not conducted.

Non-cancer dermal and inhalation risks for each applicable handler scenario are calculated using 

an MOE, which is a ratio of the NOAEL to the daily dose. All MOE values were calculated 

using the formula below:

MOE= NOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day)

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. 
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 28 of 35

1 Application rates are the maximum application rates determined from proposed labels for acequinocyl.

2 Amount handled per day values are HED estimates of acres treated per day based on ExpoSAC SOP #9 “Standard Values for Daily 

Acres Treated in Agriculture,” industry sources, and HED estimates.

3 Baseline Dermal: Long-sleeve shirt, long pants, and no gloves.

4 Baseline Inhalation: no respirator.

5 Dose (mg/kg/day) = Unit exposure (mg/lb ai) x App Rate (lb ai/acre or lb ai/gallon) x Area Treated (acres/day) or Amount 

Handled (gallons) / Body weight (kg). 

6 MOE = NOAEL/dose; where the short- and intermediate-term dermal NOAEL = 200 mg/kg/day; short-term inhalation NOAEL = 60 

mg/kg/day; intermediate-term inhalation NOAEL = 16 mg/kg/day.

7 Combined MOE = NOAEL (xx mg/kg/day) / Combined dermal + inhalation dose (mg/kg/day).

7.2 Post-application Exposure/Risk

Dermal: HED expects that post-application dermal exposure will occur since acequinocyl is 

applied as a foliar spray. Post-application exposure is expected to be short-term based on 

information provided on the proposed label. In addition, since the short and intermediate-term 

points of departure are the same, short-term risk estimates are protective of intermediate term 

exposures. Post-application exposures have been assessed using dermal transfer coefficients

(TCs) from HED’s ExpoSAC Policy Number 3.1 “Agricultural Transfer Coefficients” (August, 

2000). Table 7.2.1 summarizes the scenarios assessed. In addition, the following assumptions 

were used in the calculations: 

• Exposure Duration = 8 hours per day

• Body Weight = 70 kg

• Dislodgeable Foliar Residue (DFR) = No DFR data are available for acequinocyl 

for the proposed uses. Therefore, this assessment uses HED’s default assumption that 

Table 7.1.1. Occupational Dermal and Inhalation Exposures and Risks.

Crop or 

Target

App. 

Rate 

(lb 

ai/A)1

Area 

Treated 

Daily or 

Amount 

Handled 

(A/day)2

Dermal and 

Inhalation Unit 

Exposures (mg/lb ai)

Short- and 

Intermediate-term

Doses (mg/kg/day)5

MOEs6 Combined

MOEs7

ShorttermInt.-

term

ShorttermInt.-

term

Mixing/Loading Liquid Concentrates for Groundboom Applications (PHED)

Fruiting 

vegetable 

crop group 

8 (tomato 

and pepper) 0.3 80

Dermal

Baseline3: 2.9

Dermal

Baseline: 0.15

Dermal

Baseline:

1300

1,300 1,300

Edible 

podded 

bean Inhalation

Baseline4: 0.0012

Inhalation

Baseline: 0.00041

Inhal.

Baseline: 

150,000 

Inhal.

Baseline: 

Hop 39,000

Okra

Applying Sprays via Groundboom Equipment

Fruiting 

vegetable 

crop group 

8 (tomato 

and pepper) 0.3 80

Dermal

Baseline: 0.014

Dermal

Baseline: 0. 00072

Dermal

Baseline: 

280,000

130,000 51,000

Edible 

podded 

bean Inhalation

Baseline: 0.00074

Inhalation

Baseline: 

0.00025

Inhal.

Baseline: 

240,000

Inhal.

Baseline: 

63,000 Hop

Okra
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 29 of 35

20% of the application rate is available on Day 0 (i.e., 12 hours after application) and the 

residue dissipates at a rate of 10% per day.

Table 7.2.1. Anticipated Post-application Activities and Dermal TCs.

Proposed Crops Policy Crop Group 

Category

Application 

Rate (lb ai/A)

TCs (cm2/hr) Activities

Tomato

Fruiting vegetable 

group 8

0.3

1000 Pruning (hand), staking, 

thinning, training, tying

700 Irrigation, scouting

500 Weeding (hand)

Bell Pepper 0.3

1000 Harvest (hand), staking, tying

700 Irrigation, scouting

500 Weeding (hand), thinning

Chili Pepper 0.3

1000 Harvest (hand), pruning 

(hand), thinning

700 Irrigation, scouting

500 Weeding (hand)

Okra 0.3

1000 Harvest (hand), staking, tying

700 Irrigation, scouting, pruning 

(hand)

500 Weeding (hand), thinning 

Hops Bunch/bundle 0.3

2000 Harvest (hand and mech), 

stripping, training

1300 Scouting

100 Irrigation, weeding (hand)

Edible-Podded 

Bean

Field/ row crop, low/ 

medium

0.3

2500 Harvest (hand)

1500 Irrigation, scouting

100 Weeding (hand), thinning

Equations/Calculations:

Daily dermal exposures were calculated on each post-application day after application using the 

following equation:

Daily Dermal Doset = [DFRt (μg/cm2) x 0.001 mg/μg x TC (cm2/hr) x DA x ET (hrs)] / BW (kg)

Where,

DFRt = dislodgeable foliage residue on day "t" (ug/cm2);
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 30 of 35

TC = transfer coefficient (cm2/hr);

DA = dermal absorption factor (100%);

 ET = exposure time (8 hr/day); and

BW = body weight (70 kg).

Once daily exposures are calculated, the calculation of daily absorbed dose and the resulting 

MOEs use the same algorithms that are described above for the handler exposures. These 

calculations are completed for each day or appropriate block of time after application.

HED has determined that short-term dermal risk estimates are not of concern (i.e., MOEs >100) 

on the day of treatment (i.e., Day 0) for all post-application exposure activities. Table 7.2.2

presents a summary of occupational dermal post-application risks associated with use of 

acequinocyl.

The information in the table is based on proprietary and non-proprietary data.

1 NOAEL/Daily Dose (Short-term NOAEL = 200 mg/kg/day).

Inhalation: Based on the Agency's current practices, a quantitative occupational postapplication 

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

are multiple potential sources of postapplication inhalation exposure to individuals performing 

postapplication activities in previously treated fields. 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. The Agency received the SAP’s final report on 3/2/10 

(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 postapplication 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 

postapplication 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 

postapplication inhalation exposure assessment for acequinocyl.

Table 7.2.2. Post-application Risk Estimates for Acequinocyl.

Crop

Grouping

Application 

Rate

(lb ai/A)

TC

(cm2/hr)

DFR 

(ug/cm2)

Days After 

Treatment MOE1

Fruiting 

vegetable 

group 8

0.3

1000

0.67 0

(12 hours)

2600

700 3700

500 5200

Bunch/

bundle 0.3

2000

0.67 0

(12 hours)

1300

1300 2000

100 26000

Field/row crop,

Low/

medium

0.3

2500

0.67 0

(12 hours)

1000

1500 1700

100 26000
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 31 of 35

7.3 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 

not a dermal sensitizer. Therefore, the WPS interim REI is adequate to protect agricultural 

workers from post-application exposures to acequinocyl. 

8.0 RESIDUE CHEMISTRY AND TOXICOLOGY DEFICIENCIES

8.1 Residue Chemistry

 Revised Section F.

 Revised Section B.

 Analytical reference standards for the acequinocyl and acequinocyl-OH must be 

submitted to the EPA National Pesticide Standards Repository.

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; A. Nowotarski

RDI: RAB1 Branch (09-JUN-2010); RAB1 Chemists (09-JUN-2010)

S. Levy: S10953: PY1:703-305-0783; 7509P:RAB1
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 32 of 35

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 

mg/kg/day; LOAEL = 750 mg/kg/day based 

on increased resorptions.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 33 of 35

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, 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, 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 FertilityRAT

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.
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 34 of 35

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 

MICE

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/cm2dose 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

O

O

CH2(CH2)

10CH3

OCOCH3

Acequinocyl-OH

(Metabolite R1)

2-dodecyl-3-hydroxy-1,4-

naphthalenedione

O

O

CH2(CH2)

10CH3

OH

AKM-18 2-(1,2-dioxotetradecyl)-benzoic 

acid

O

O

O

OH

(CH2)

11CH3
Acequinocyl Human-Health Risk Assessment DP# 368425

Page 35 of 35

AKM-15 2-hydroxy-3-hexanoic acid-1, 4 

naphthalenedione

O

O

OH

COOH

AKM-14 2-hydroxy-3-butanoic 

acid-1,4-naphthalenedions

O

O

CH2

OH

(CH2) CH 9CH3

OH