UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CllEMICAL SAFETY A~D 

POLLlITION PREVENT ION 

MEMORANDUM 

Date: 27-MAY-20 15 

SUBJECT: Acequinocyl. Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 006329 

Decision No.: 497220 

Petition No.: NIA 

DP Barcode: D423850 

Registration No.: NIA 

Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/ A Case No.: 7621 

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

MRID No.: NIA 40 CFR: § 180.599 

Sarah J. Levy, Chemist M n ti I /Ml./ /) k 

Anwar Y. Dunbar, Ph.D., Pharmfog t/" ' ~ ' l/_ 

George F. Kramer, Ph.D., Senior Chemist ;;? ~ ; /J 

James S. Miller, Environmental Health Scientist /.·~4 //Jvt.-~ 

Risk Assessment Branch I (RAB I) -

FROM: 

Health Effects Division (HED, 7509P) ///J ~ A;Jf---

THROUGH: Thurston Morton, Acting Branch Chief ( 1 ,,,v-<Yj 

RABl/HED (7509P) 

TO: Dana Friedman, Acting Team Leader/Cathryn Britton, Team Leader 

Margaret Hathaway, Chemical Review Manager 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached is HED's human health risk assessment scoping document for acequinocyl to support 

Registration Review. 

Page I of24 
Ace9uinocyl Registration Revi_ew H_uman Health Assess nt Sc~ing Document 

Table of Contents 

Executive Sun11nary ........................................................................................................................ 3 

1.0 lntroduction ............ ....... ................... .... ............. .................... .... ..................... .... ....... ...... ......... 5 

2.0 Hazard Characterization/Assessment ...................................................................... ....... ......... 5 

3.0 Residue Chemistry .......................................................................................................... ......... 6 

4.0 Dietary Exposure ..................... ................................................................................................ 6 

5.0 Residential Exposure ....................................................... ........................................................ 7 

6.0 Aggregate-Risk Assessment .................................................................................................... 8 

7 .0 Occupational Exposure ........................................................................................ ................. ... 8 

8.0 Public Health and Pesticide Epidemiology Data ..................................................................... 9 

9.0 Tolerance Assessment and International Harmonization ...................................................... 10 

I 0.0 Environmental Justice .......................................................................................................... 10 

11.0 Cumulative .................................. ............................................. .............. ... .............. ....... ... ... l 0 

12.0 I-lu1nanStudies .................... ....... ............. ........ ............. .... ............... ....... .............................. lO 

13.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions ................................... 11 

14.0 References ............ .... ....... ............................................................................................... ...... 12 

Attachment 1: Chemical Identity Table ...... .. ... .. .. ........ . .. .... .............. . .... ...... .. .. ........ 14 

Attachment 2: Acequinocyl Acute, Subchronic, Chronic, and Other Toxicity Profile ............... 15 

Attachment 3: Acequinocyl Endpoint Selection Table (from 2011 Risk Assessment) ............... 18 

Attachment 4: Summary of Registered Uses ....................................... ........................................ 20 

Attachment 5: Acequinocyl IRLS Sheet. ............. ............. ........................................................... 23 

Page 2 of24 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 3 of 24

Executive Summary

HED has prepared a scoping document to support the Registration Review of acequinocyl [2-

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

naphthoquinone. Acequinocyl is a quinoline-type miticide that is currently registered for use in 

the U.S. on a number of raw agricultural commodities (RACs) for the control of various 

phytophagous mite species. Acequinocyl is also registered for use in/on greenhouses, 

shadehouses, ornamental, floral, foliage, nursery crops, landscape ornamentals in and around 

residences, businesses, public property, schools, interiorscapes, and other non-production areas 

by commercial applicators and homeowners. 

There are no pending Pesticide Registration Improvement Act (PRIA) actions for acequinocyl. 

The most recent risk assessment, (Memo, S Levy et al., 30-NOV-2011; D389519) was a request 

for tolerance in/on succulent soybean vegetable; succulent shelled beans; cowpea forage; 

caneberry subgroup 13-07A; melon subgroup 9A; cucumber (greenhouse and field); cherry; lowgrowing berry subgroup 13-07G; small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-

07F; fruiting vegetables crop group 8 (tomatoes & peppers); edible-podded beans; hops; okra; 

and tree nut crop group 14. Note that the cucumber and caneberry field trial data were a jointreview with Canada.

HED has evaluated the status of the human health risk assessments for acequinocyl to determine 

whether sufficient data are available and whether any updates are needed to support Registration 

Review. HED has considered all available data and human health risk assessments for 

acequinocyl with respect to its toxicity, exposure, and usage databases, and the most updated 

Agency science policy and risk assessment methodologies to determine the scope of work 

necessary to support Registration Review.

The toxicity database for acequinocyl is complete and adequate to support the current 

registrations, as specified by the 2007 revised 40 CFR Toxicology Data Requirements. No 

additional data are required. HED does not anticipate the need for revisions to the endpoints, 

doses, and Safety Factors for acequinocyl during Registration Review.

The residue chemistry database is sufficient to support the current registrations. No additional 

data are required at this time. The qualitative nature of acequinocyl residues in the registered 

primary crops and ruminants is adequately understood based on acceptable apple, orange, 

eggplant, confined rotational crop, and goat metabolism studies. For purposes of the tolerance 

expression and risk assessment, HED has determined that the residues of concern in these 

commodities include parent and acequinocyl-OH; for the ruminant liver and kidney risk 

assessment, metabolite AKM-15 (2-hydroxy-3-hexanoic acid-1,4-naphtahlendione) is included 

as well. Adequate analytical enforcement methods are available. Additionally, adequate 

magnitude of the residue data (primary crops, livestock, and processed commodities) are 

available to support all registered uses. 

The dietary-exposure database for acequinocyl is adequate to support current registration 

requirements. The most recent risk assessment provided unrefined chronic dietary (food + 

drinking water) exposure estimates that are below HED’s level of concern (LOC) for the general 

U.S. population and all population subgroups (Memo, S. Levy, 30-NOV-2011; D389990). HED 

notes that the 2011 chronic dietary assessment did not incorporate ground water estimated 

drinking water concentrations (EDWCs) modeled using the Pesticide Root Zone Model for 

GroundWater (PRZM-GW) or Surface Water Concentration Calculator (SWCC). EDWCs from 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 4 of 24

the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) model 

were used in the chronic dietary-exposure database. Furthermore, the 2011 chronic dietary 

assessment did not utilize the latest dietary exposure model or consumption database. Since this 

dietary assessment, HED adopted use of the Dietary Exposure Evaluation Model - Food 

Consumption Intake Database (DEEM-FCID, ver. 3.16), which uses food consumption data from 

the U.S. Department of Agriculture’s National Health and Nutrition Examination Survey, What 

We Eat in America, (NHANES/WWEIA) from 2003 through 2008. A revised dietary-exposure 

analysis may be required during Registration Review to reflect the most recent dietary-exposure 

models and potential revised EDWCs (specifically, use of PRZM-GW).

The most recent residential exposure assessment was conducted in June of 2010. All margin of 

exposures (MOEs) were >100 and are not of concern. See D369099 (Memo, A. Nowotarski) for 

details. In order to incorporate HED’s 2012 Residential Standard Operating Procedures (SOPs)

and policy changes for body-weight assumptions; an updated residential exposure assessment 

will be needed to support Registration Review. The need for a spray-drift and volatilization risk 

assessment for acequinocyl will also be examined during Registration Review.

There is sufficient information available to assess aggregate exposure. However, a new 

aggregate risk assessment may be required during Registration Review if a revised dietaryexposure analysis is needed to reflect potential revised EDWCs or revised residential exposure 

estimates.

The occupational exposure database is adequate to support the Registration Review process for 

acequinocyl. The most recent occupational handler and post-application exposure assessment 

(Memo, K. Lowe, 30-NOV-2011; D389991), did not identify risks of concern; however, the 

handler assessment is not reflective of all current exposure policies. Therefore, during 

Registration Review, updated occupational handler assessments will be conducted to reflect all 

currently registered uses, using current occupational/residential exposure (ORE) policies.

No data deficiencies were identified for acequinocyl. EPA notes the following risk assessment 

updates will need to be completed during Registration Review:

o Toxicology: 

o None.

o Residue Chemistry/Dietary Exposure: 

o A revised dietary-exposure analysis may be required to reflect the most recent 

dietary-exposure models and potential revised EDWCs (specifically, use of 

PRZM-GW).

o Occupational/Residential Exposure: 

o Updated occupational handler assessments will be required using current ORE 

policies to reflect all currently registered uses and maximum application rates, 

using current ORE policies.

o The need for spray drift and volatilization risk assessment for acequinocyl will be 

examined during Registration Review.

o An updated residential exposure assessment will be needed for acequinocyl 

during Registration Review to incorporate the 2012 Residential SOPs.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 5 of 24

1.0 Introduction

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

number of RACs for the control of various phytophagous mite species. Acequinocyl is also 

registered for use in/on greenhouses, shadehouses, ornamental, floral, foliage, nursery crops, 

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

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

Acequinocyl is currently registered to Arysta LifeScience North America Corporation as a 15% 

soluble-concentrate (SC) formulation. The most recent risk assessment for acequinocyl, (Memo, 

S Levy et al., 30-NOV-2011; D389519) was a request for tolerance in/on a variety of agricultural 

crops.

2.0 Hazard Characterization/Assessment

The toxicology database is complete. In the 2011 risk assessment conducted to add new uses, 

the following data gaps were identified: (1) an immunotoxicity study, (2) an acute neurotoxicity 

study, (3) a subchronic neurotoxicity study and (4) a subchronic inhalation toxicity study. The 

Hazard Science and Policy Council (HASPOC) concluded, based on a weight of evidence 

approach, that the inhalation study was not required at this time but the acute neurotoxicity study 

was required (TXR# 0056342). Since that time, the acute neurotoxicity study was submitted, 

reviewed, and found to be acceptable. Based on the results from the acute study, HASPOC 

subsequently determined that the subchronic neurotoxicity study was not required at this time 

(TXR# 0051465). In addition, an acceptable immunotoxicity study has been submitted, 

reviewed, and found to be acceptable.

Acequinocyl’s absorption, metabolism, distribution, and excretion (ADME) are well 

characterized and understood. Acequinocyl exhibits marginal absorption into the plasma (13-

16% for the 10 mg/kg low dose and 8-9% for the 500 mg/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 rats. Acequinocyl undergoes nearly complete metabolism to hydrolysis 

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

or sequestration.

Across species, durations and routes of exposure (oral and dermal), the primary effects in the 

acequinocyl hazard database are indicative of toxicity to the liver (hepatocyte vacuolization, 

brown pigmented cells and perivascular inflammatory cells in liver) and erythropoietic system 

(hemorrhage, increased clotting factor times and increased platelet counts). In an acute 

neurotoxicity study, there were no effects up to the limit dose (2000 mg/kg). In a guideline 

immunotoxicity study, there were also no effects up to the highest dose tested (45 mg/kg/day). 

In rats and rabbits, there was no evidence of increased quantitative or qualitative fetal 

susceptibility with clinical signs and gross necropsy findings seen in maternal animals at similar 

or lower doses than those producing resorptions. In the rat two-generation reproductive toxicity 

study, there was increased quantitative postnatal susceptibility. While there were no parental 

effects up to the highest dose tested, offspring effects at the mid- and high-doses consisted of 

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

mortality occurring mainly after weaning. There were no effects on reproductive parameters. 

There was no concern for genotoxicity or mutagenicity. There was no evidence of carcinogenic 

potential in either the rat or mouse carcinogenicity studies, or in the genotoxicity and 

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

Acequinocyl has low acute toxicity via the oral, dermal, and inhalation routes (Toxicity 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 6 of 24

Categories III & IV). No ocular or dermal irritation was noted. Acequinocyl is not a dermal 

sensitizer.

Conclusions: The toxicity database for acequinocyl is adequate for risk assessment as specified 

by the 2007 revised 40CFR Toxicology Data Requirements. HED’s HASPOC has determined 

that the subchronic neurotoxicity and inhalation studies are not required for acequinocyl at this 

time. HED does not anticipate the need for revisions to the endpoints, doses, and Safety Factors 

for acequinocyl during Registration Review.

3.0 Residue Chemistry

Tolerances are currently established under 40 CFR §180.599(a) for the combined residues of 

acequinocyl and its metabolite, 2-dodecyl-3-hydroxy-1,4-naphthoquinone, expressed as 

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

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

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

goat, horse, and sheep.

The qualitative nature of acequinocyl residues in the registered primary crops and ruminants is 

adequately understood based on acceptable apple, orange, eggplant, confined rotational crop, and 

goat metabolism studies. For purposes of the tolerance expression and risk assessment, HED has 

determined that the residues of concern in these commodities include parent and acequinocylOH; for the ruminant liver and kidney risk assessment, metabolite AKM-15 is to be included as 

well. Adequate analytical enforcement methods are available. Additionally, adequate field trial, 

processing, and storage stability data are available. HED notes that if, in the future, the 

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

translated, then HED may ask for additional plant metabolism data. 

Conclusions: The residue chemistry database is sufficient to support the current registrations. 

No additional data are required at this time. 

4.0 Dietary Exposure

A chronic dietary (food + drinking water) exposure and risk assessment was conducted for the 

2011 risk assessment for acequinocyl using DEEM-FCID, ver. 2.03, which incorporates 

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. An unrefined, chronic dietary 

exposure assessment was conducted assuming tolerance-level residues and 100% crop treated 

(%CT) for all registered commodities, and DEEM 7.81 default processing factors with the 

exception of those for grape juice and raisins (as residues were reduced in both grape juice 

(<0.02x) and raisin (0.15x), the default processing factors for these commodities were reduced to 

1x (Memo, S. Levy, 05-SEP-2007; DP#: 342805)).

Drinking water residues were generated using the PRZM/EXAMS model (M. Lowit, 07-SEP2011; D389520). The highest chronic surface water value (i.e., most conservative) of 6.69 ppb 

was incorporated directly into DEEM-FCID under the food categories “water, direct, all sources” 

and “water, indirect, all sources.” 

The chronic dietary risk assessment estimates are not of concern to HED [i.e., <100% chronic 

population-adjusted dose (cPAD)]. For the general U.S. population, the risk for food and water 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 7 of 24

utilizes 13% of the cPAD. The chronic dietary risk estimate for the highest reported exposed 

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

HED notes that the 2011 chronic dietary assessment did not utilize the latest dietary exposure 

model or consumption database. Since this dietary assessment, HED adopted use of DEEMFCID Version 3.16, which uses food consumption data from the USDA NHANES/WWEIA 

survey from 2003 through 2008. Furthermore, the assessment did not incorporate ground water 

EDWCs modeled using PRZM-GW or SWCC. The impacts of using these models to estimate 

ground water concentrations of acequinocyl will need to be considered during Registration 

Review.

Conclusions: The dietary-exposure database is adequate to support current registration 

requirements. In the most recent risk assessment, chronic dietary exposures were not of concern 

to HED. However, as part of Registration Review, a revised dietary-exposure analysis may be 

required to reflect the most recent dietary-exposure models and potential revised EDWCs

(specifically, use of PRZM-GW).

5.0 Residential Exposure

Acequinocyl is currently registered for use on landscape ornamentals in and around residences, 

businesses, public property, schools, interiorscapes, and other non-production areas by 

commercial applicators and homeowners. The last residential exposure risk assessment was 

conducted in June 2009 (A. Nowotarski, D369099) and noted again in November 2011 (Memo, 

K. Lowe, 30-NOV-2011; D389991). All risks for residential handlers were above the target 

MOE of 100 and did not exceed the LOC. 

The quantitative dermal and inhalation exposure/risk assessment developed for residential 

handlers is based on the following scenarios; mixer/loader/applicator using a low-pressure

handwand and a hose-end sprayer. The Summary of Residential Handler Non-Cancer Exposure 

and Risk Estimates for acequinocyl detailed no risk estimates of concern for any potential 

exposure scenarios, with the MOEs ranging from 2,900 to 260,000,000. See memorandums 

(Memo, K. Lowe, 30-NOV-2011; D389991)) and (Memo, S. Levy et al., 30-NOV-2011; 

D389519) for details. 

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

quantitative residential post-application assessment was not conducted in 2009. However, an 

updated residential postapplication assessment will be needed for during Registration Review to 

incorporate the 2012 Residential SOPs.

Spray Drift and Volatilization: Residential bystander exposures resulting from off-site transport 

(e.g., spray drift or volatilization) may occur as a result of applications of acequinocyl. The 

potential for spray drift may be quantitatively evaluated for each pesticide during the 

Registration Review process that ensures that all uses for that pesticide may be considered 

concurrently. The approach is outlined in the revised (2012) SOPs for Residential Risk 

Assessment – Residential Exposure Assessment Standard Operating Procedures Addenda 1: 

Consideration of Spray Drift. This document outlines the quantification of indirect nonoccupational exposure to drift.

In terms of volatilization, the agency has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 8 of 24

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analyses are required for specific chemicals.

Conclusions: An updated residential handler and postapplication exposure assessment will be

needed for acequinocyl during Registration Review to adhere to the revised (2012) SOPs for 

Residential Risk Assessments. In addition, the need for spray drift and volatilization risk 

assessment for acequinocyl will be examined during Registration Review.

6.0 Aggregate-Risk Assessment

Acute and cancer aggregate-risk assessments were not performed because no appropriate 

endpoint was available to determine the acute reference dose (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 post-application exposure 

of more than 30-day duration. Chronic (long-term) aggregate risk is made up only of dietary 

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

analysis, see Section 4.0 for details. 

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 and post application

exposure is expected. Short-term aggregate risk is made up of average dietary exposures from 

food and drinking water sources, and dermal and inhalation residential exposures. The females 

13-49 years old population is the highest exposed adult population and can be considered 

protective of the other adult populations groups. The aggregate (MOEs) were 2,500 for the U.S. 

population and 2,600 for females 13-49 years old. The aggregate MOEs are >100, therefore, 

they do not exceed HED’s LOC.

Conclusions: There is sufficient information available to assess aggregate exposure. However, 

as part of Registration Review, a revised aggregate exposure assessment may be needed to 

reflect a revised dietary-exposure analysis and/or an updated residential exposure assessment

(See Sections 4.0 and 5.0, respectively, for more details). 

7.0 Occupational Exposure

Acequinocyl is registered for use in/on a variety of crops and landscape ornamentals; and, based 

on this registered use pattern, there is a potential for occupational handler and post-application 

exposure to acequinocyl. The most recent occupational exposure assessment for acequinocyl 

was conducted in 2011 (Memo, K. Lowe, 30-NOV-2011; D389991). See Attachment 4 for a 

summary of the registered use patterns. Handler exposure is expected to be short- and 

intermediate-term based on information provided on registered labels (e.g., two 

applications/season with a retreatment interval (RTI) of 14 and 21 days). The proposed preharvest intervals (PHIs) range from 1 to 7 days. The restricted entry interval (REI) specified on 

the label is 12 hours. Acequinocyl registered labels require mixers, loaders, and other handlers 

to wear long-sleeved shirt and long pants, chemical-resistant gloves, and shoes plus socks. The 

labels also require applicators to wear long-sleeved shirt and long pants, and shoes plus socks. 

Occupational Handlers: There is the potential for dermal and inhalation exposure to 

occupational handlers from the currently registered use pattern of acequinocyl. In the most 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 9 of 24

recent exposure assessment for acequinocyl (Memo, K. Lowe, 30-NOV-2011; D389991) and 

(Memo, S. Levy et al., 30-NOV-2011; D389519), dermal and inhalation assessments were 

conducted for mixers/loaders, applicators for groundboom, airblast, and handheld sprayer 

applications of an SC formulation. Application by air or through any type of irrigation system is 

prohibited. The maximum application rate range is 0.01 to 0.3 lb ai/A. Dermal and inhalation 

risk estimates were not of concern (i.e., MOEs ≥ 100) with baseline protection. 

Based on a review of the registered labels and the most recent risk assessment (Memo, S. Levy et 

al., 30-NOV-2011; D389519), HED has conducted occupational handler assessments for the 

occupational handler scenarios anticipated for the registered uses of acequinocyl. However, the 

scenarios were not assessed based on current ORE SOPs and policies; therefore, an updated 

assessment will be required during Registration Review. 

Occupational Post-Application

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

at a rate of 0.3 lb ai/A). The point of departure for the dermal route of exposure is the same for 

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

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

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

successive applications to avoid resistance issues. 

Chemical-specific dislodgeable-foliar residue (DFR) data for apples and chrysanthemums were 

used as surrogates for all crops in the occupational post-application assessments. All agricultural 

crop scenarios resulted in MOEs greater than 100 on day 0 and are not of concern.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for acequinocyl. The most recent occupational handler and post-application 

exposure assessments did not identify risks of concern; however, the occupational handler 

assessment is not reflective of current exposure policies. Therefore, during Registration Review, 

updated occupational assessments may be conducted to reflect all currently registered uses, using 

current ORE policies. 

8.0 Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for acequinocyl (Memo, S. Recore and E. 

Evans, 10-FEB-2015; D425575) and concluded that because there were no incident cases 

reported for acequinocyl to either the OPP Incident Data System (IDS) or Sentinel Event 

Notification System for Occupational Risk (SENSOR)-Pesticides, there does not appear to be a 

concern at this time that would warrant further investigation. The Agency will continue to 

monitor the incident information and if a concern is triggered, additional analysis will be 

included in the risk assessment.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 10 of 24

9.0 Tolerance Assessment and International Harmonization

U.S. permanent tolerances (listed in 40 CFR §180.547) and maximum residue limits (MRLs) are 

summarized in Attachment 3.

Conclusions: Residue definitions and MRLs for acequinocyl have not been established by 

Codex. The U.S. and Canadian residue definitions are harmonized. Tolerance/MRL levels for 

residues are harmonized with Canada, with the exception of citrus and pome fruits. There are 

several U.S. tolerances for which there are no Canadian MRLs. Canada has established MRLs 

for residues in milk and ruminant meat; however, U.S. tolerances are not established for residues 

in these livestock commodities. Mexico adopts U.S. tolerances and/or Codex MRLs for export 

purposes. 

10.0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

most recent acequinocyl human health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populationsa

.” The OPP typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human health risk assessments, including, but not 

limited to, people who obtain drinking water from sources near agricultural areas, the variability 

of diets within the U.S., and people who may be exposed when harvesting crops. Should these 

highest exposures indicate potential risks of concern, OPP further refines the risk assessments to 

ensure that the risk estimates are based on the best available information.

11.0 Cumulative

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 for 

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 assumed that acequinocyl does not have 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/.

12.0 Human Studies

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 the Pesticide Handlers Exposure Database (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 

 

a http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 11 of 24

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.

13.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

No data deficiencies were identified for acequinocyl. EPA notes the following risk assessment 

updates will need to be completed during Registration Review:

o Toxicology: 

o None. 

o Residue Chemistry/Dietary Exposure: 

o A revised dietary-exposure analysis may be required to reflect the most recent 

dietary-exposure models and potential revised EDWCs (specifically, use of 

PRZM-GW).

o Occupational/Residential Exposure: 

o Updated occupational handler assessments will be required using current ORE 

policies to reflect all currently registered uses and maximum application rates, 

using current ORE policies.

o The need for spray drift and volatilization risk assessment for acequinocyl will be 

examined during Registration Review.

o An updated residential exposure assessment will be needed for acequinocyl 

during Registration Review to incorporate the 2012 Residential SOPs.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 12 of 24

14.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

S. Levy D260953 18-FEB-2004 PP# 2F06440 and 3F06595. Multiresidue Method Testing of 

Acequinocyl. 

S. Levy D284757 10-MAR-2004

Acequinocyl. Registration for Use on Pome Fruits, Citrus, 

Almonds, Pistachios, and Strawberries. Summary of Analytical 

Chemistry and Residue Data.

S. Levy/P. Terse D297872 07-JAN-2004

Acequinocyl. Report of the Metabolism Assessment Review 

Committee (MARC). Meeting Date: 17-DEC-2003. TXR#: 

0052294

D. Soderberg D321753 23-MAY-2006

Acequinocyl: Response to Submission of MRID#s 46602001, 

46602002 and 46602003 by Morse Laboratories Addressing a 

Need for Confirmation of Acequinocyl in Fruits, Almonds and 

Livestock Tissues.

S. Levy D330439 05-SEP-2007

Acequinocyl. PP#s: 6F7040 and 7F7176. Petitions for Uses on 

Tree Nuts and Grapes. Summary of Analytical Chemistry and 

Residue Data. 

S. Levy D351336 25-JUN-2008

Acequinocyl; Review of Petitioner’s Amendment Dated 28-JAN2008 Submitted in Response to the Health Effects Division (HED) 

Memoranda, DP#: 284757 (dated 10-MAR-2004).

S. Levy D369100 25-AUG-2010

Acequinocyl. Petition for Use on Fruiting Vegetables, Hops, 

Okra, and Edible-Podded Beans. Summary of Analytical 

Chemistry and Residue Data. 

S. Levy D380302 25-AUG-2010

Acequinocyl; Response to the Health Effects Division (HED) 

Review of 25-JUN-2008 (Memoranda, DP#s D351336 & 

D353313).

A. Nowotarski D369099 26-JUNE-2010 Acequinocyl; Human-Health Risk Assessment for Proposed 

Section 3 Uses on Fruiting Vegetables, Hops, Okra, and EdiblePodded Beans.

K. Lowe D389991 30-NOV-2011 Acequinocyl: Occupational and Residential Exposure/Risk 

Assessment for Proposed Use on Succulent soybean; Low 

growing berry subgroup 13-07G; Small fruit vine climbing (except 

fuzzy kiwifruit, subgroup 13-07F); Succulent bean; Cowpea 

forage; Caneberry (subgroup 13-07A); Melon (subgroup 9A); 

Cucumber (greenhouse and field), and Cherry.

S. Levy et al., D389519 30-NOV-2011 Acequinocyl; Human-Health Risk Assessment for Proposed 

Section 3 Uses on Succulent Soybean Vegetable; Succulent 

Shelled Beans; Cowpea Forage; Caneberry Subgroup 13-07A; 

Melon Subgroup 9A; Cucumber, Cherry; Low-Growing Berry 

Subgroup 13-07G; and Small Fruit Vine Climbing, Except Fuzzy 

Kiwifruit, Subgroup 13-07F.

M. Dow D290655 10-JUN-2003 Dissipation of Dislodgeable Foliar Residues of Acequinocyl and 

its Metabolite Following Application of Kanemite SC to Apples 

(MRID No.: 456516-11). MRID# 454286-19

S. Levy D389989 30-NOV-2011

Acequinocyl. Petition for Use on Succulent Soybean Vegetable; 

Succulent Shelled Beans; Cowpea Forage; Caneberry Subgroup 

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

Berry Subgroup 13-07G; and Small Fruit Vine Climbing, Except 

Fuzzy Kiwifruit, Subgroup 13-07F. Summary of Analytical 

Chemistry and Residue Data. 

S. Recore and E. 

Evans D425575 10-FEB-2015 Acequinocyl: Tier I Review of Human Incidents.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 13 of 24

Attachments:

Attachment 1: Chemical Identity Table.

Attachment 2: Acequinocyl Acute, Subchronic, Chronic, and Other Toxicity Profile.

Attachment 3: Acequinocyl Endpoint Selection Table.

Attachment 4: Summary of Registered Uses.

Attachment 5: Acequinocyl International Residue Limit Status Sheet.

cc: S. Levy (RAB1)

RDI: RAB1 (18-FEB-2015), D. Vogel (27-FEB-2015)

S. Levy:S10953:PY-S:(703)305-0783:7509P:RAB1
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 14 of 24

Attachment 1: Chemical Identity Table.

Table A.1. Test Compound Nomenclature Acequinocyl.

Compound

O

O

CH2(CH2)

10

CH3

OCOCH3

Common name Acequinocyl

Company experimental name TM-41301 or AKD-2023

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

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

CAS # 57960-19-7

End-use products KanemiteTM 15 SC (1.25 lb ai/gal; EPA Reg. No. 66330-38)

Compound

O

O

CH2(CH2)

10

CH3

OH

Common name Acequinocyl-OH

Company experimental names R1

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

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

CAS # 57960-31-3

Compound

Company experimental names AKM-15

IUPAC name 2-hydroxy-3-hexanoic acid-1,4-naphtahlendione

Table A.2. Physicochemical Properties of the Technical Grade Test Compound Acequinocyl.

Parameter Value Reference

Melting point Crystal modification 1: 98.7°C 

Crystal modification 2: 96.7°C

Memo, S. Malak, 29-APR2004, D298191; MRID 

pH 5.19 (2% suspension in 0.1% NaCl) 45854501

Density 1.13 g/mL

Water solubility (20°C) 0.13 mg/L (constant from pH 4 to pH 9)

Solvent solubility (mg/L at 20°C)

Acetone: >250 g/L 

Acetonitrile: >250 g/L 

Ethyl Acetate: >250 g/L 

Dichloromethane: >250 g/L 

n-Heptane: 23 g/L

1-Octanol: 60 g/L

2-Propanol: 110 g/L

Xylene: >250 g/L

Vapor pressure at 25°C 1 x 10-5 Pa (7.5 x 10-8 mmHg)

Dissociation constant (pKa)

No acid or base properties between pH 2 and 

pH 12

Octanol/water partition coefficient Log(KOW) 4.55 at 20°C

UV/visible absorption spectrum Molar absorption coefficient 23,360 L/mol 

cm at 214 nm (neutral)
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 15 of 24

Attachment 2: Acequinocyl Acute, Subchronic, Chronic, and Other Toxicity Profile.

Table B.1. Acute Toxicity of Acequinocyl.

Guideline No. Study Type MRID # 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 B.2. Subchronic, Chronic and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (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 (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 (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 

toxicity (rat)

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 

(rat)

45531908, 45651706 

(1995); 

0, 50, 150, 500, 750 

mg/kg/day

Acceptable/Guideline 

Maternal NOAEL = 150 mg/kg/day; LOAEL = 

500 mg/kg/day based on signs of internal 

hemorrhage and increased incidence of clinical 

signs (pale eyes, piloerection, red vaginal 

discharge).

Developmental NOAEL = 500 mg/kg/day; 

LOAEL = 750 mg/kg/day based on increased 

resorptions. 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 16 of 24

Table B.2. Subchronic, Chronic and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700b Prenatal 

developmental in 

(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 Reproduction and 

fertility effects

(rat)

45531909 (1997);

0, 100, 800, 1500 ppm;

M: 0, 7.3, 58.9, 111.2 

mg/kg/day 

F: 0, 8.7, 69.2, 133.5 

mg/kg/day

Acceptable/Guideline

Parental NOAEL (M/F): 111.2/ 133.5 

mg/kg/day; 

LOAEL (M/F) = not established.

Offspring NOAEL (M/F): 7.3-8.2/8.7 

mg/kg/day; LOAEL (M/F) = 58.9/69.2 based 

on hemorrhagic effects, swollen body parts, 

protruding eyes, clinical signs, delays in pupil 

development and increased mortality post 

weaning.

Reproductive NOAEL (M/F): 124/136 

mg/kg/day; LOAEL (M/F) = not established.

870.4100b Chronic toxicity 

(dog)

45531910 (1996); 

0, 5, 20, 80, 320 

mg/kg/day 

Acceptable/Guideline

NOAEL (M/F) = 80/80 mg/kg/day.

LOAEL (M/F) = 320/320 mg/kg/day based on 

premature sacrifice (inappetence, body-weight 

loss).

870.4200 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).

No evidence of carcinogenicity.

870.4300 Carcinogenicity

(mouse)

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).

No evidence of carcinogenicity.

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.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 17 of 24

Table B.2. Subchronic, Chronic and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

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.

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 10 mM) for 

6 hours with S9-mix. 

Acceptable/Guideline

There was no evidence of chromosome 

aberrations induced over background.

870.5395 Mammalian 

Erythrocyte 

Micronucleus Test 

(mouse)

45435104 (1993);

0, 1250, 2500, or 5000 

mg/kg body weight

Acceptable/Guideline

There was no statistically significant increase in 

the frequency of micronucleated polychromatic 

erythrocytes in mouse bone marrow at any dose 

or harvest time.

870.6200a Acute 

neurotoxicity 

screening battery

49346001 (2013);

0, 150, 500, or 2000 

mg/kg

Acceptable/Guideline

Neurotoxicity NOAEL = 2000 mg/kg/day.

The neurotoxicity LOAEL was not observed.

Systemic NOAEL = 2000 mg/kg/day.

The systemic LOAEL was not observed.

870.7485 Metabolism and 

pharmacokinetics

(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.

870.7800 Immunotoxicity

(mouse)

48660604 (2011)

0, 100, 250, and 500 ppm 

(0, 10, 24, and 45 

mg/kg/day [F])

Immunotoxicity NOAEL = 500 ppm (45 

mg/kg/day).

The immunotoxicity LOAEL was not observed.

Systemic NOAEL = 500 ppm (45 mg/kg/day).

The systemic LOAEL was not observed.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 18 of 24

Attachment 3: Acequinocyl Endpoint Selection Table (from 2011 Risk Assessment).

Table C.1. Summary of Toxicological Doses and Endpoints for Use in Acequinocyl 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 

non-neoplastic lesions (brown 

pigmented cells and perivascular 

inflammatory cells in liver).

Short-term 

(1-30 days) 

incidental oral

NOAEL = 60 

mg/kg/day

UFA = 10X

UFH =10X

LOC (residential) = 

MOE <100 

Developmental toxicity study in 

rabbits;

Maternal LOAEL = 120 mg/kg/day 

based on clinical signs (hematuria, 

reduced fecal output, body weight 

loss, and reduced food consumption) 

and gross necropsy findings (pale 

lungs and liver, hemorrhaging 

uterus, fluid in the cecum, fur in the 

stomach, blood stained vaginal 

opening, blood-stained urinary 

bladder contents/urine).

Intermediate-term 

(1-6 months) 

incidental oral

NOAEL = 16 

mg/kg/day

UFA = 10X

UFH = 10X

LOC (residential) = 

MOE <100 

Subchronic toxicity in mice;

LOAEL = 81 mg/kg/day based on 

hepatocyte vacuolization.

Short- (1-30 days) 

and Intermediateterm (1-6 months) 

Dermal

Dermal 

NOAEL = 

200 

mg/kg/day

UFA = 10X

UFH = 10X

LOC (residential) = 

MOE <100 

28-day dermal study in rats;

LOAEL = 1000 mg/kg/day based on 

increased clotting factor times.

Short-term (1-30 

days) Inhalation

Oral NOAEL

= 60 

mg/kg/day

(inhalation 

absorption 

rate = 100%)

UFA = 10X

UFH = 10X

LOC (residential) = 

MOE <100 

Developmental toxicity study in 

rabbits;

Maternal LOAEL = 120 mg/kg/day 

based on clinical signs (hematuria, 

reduced fecal output, body weight 

loss, and reduced food consumption) 

and gross necropsy findings (pale 

lungs and liver, hemorrhaging 

uterus, fluid in the cecum, fur in the 

stomach, blood stained vaginal 

opening, blood-stained urinary 

bladder contents/urine).

Intermediate-

(1-6 months) 

Term Inhalation

Oral NOAEL 

= 16 

mg/kg/day

(inhalation 

absorption 

rate=100%)

UFA = 10X

UFH = 10X

LOC (residential) = 

MOE <100 

Subchronic toxicity in mice;

LOAEL = 81 mg/kg/day based on 

hepatocyte vacuolization.

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

1

 Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 19 of 24

exposures. UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential 

variation in sensitivity among members of the human population (intraspecies), FQPA SF = FQPA Safety Factor, 

NOAEL = no-observed-adverse-effect level, LOAEL = lowest-observed-adverse-effect level, RfD = reference dose 

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

concern, N/A = not applicable.

Table C.2. Summary of Toxicological Doses and Endpoints for Acequinocyl for Use in Occupational Human 

Health Risk Assessments.1

Exposure/

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

Short- (1-30 

days) and 

Intermediateterm (1-6 

months) 

Dermal

Dermal 

NOAEL = 200 

mg/kg/day

UFA = 10X

UFH =10X

LOC 

(occupational) = 

MOE <100 

28-day dermal study in rats;

LOAEL = 1000 mg/kg/day based on 

increased clotting factor times.

Short-term (1-

30 days) 

Inhalation

Oral NOAEL =

60 mg/kg/day

(inhalation 

absorption rate

= 100%)

UFA = 10X

UFH = 10X

LOC 

(occupational) = 

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).

Intermediate-

(1-6 months) 

Term 

Inhalation

Oral NOAEL = 

16 mg/kg/day

(inhalation 

absorption rate

= 100%)

UFA = 10X

UFH = 10X

LOC 

(occupational) = 

MOE <100 

Subchronic toxicity in mice;

LOAEL = 81 mg/kg/day based on 

hepatocyte vacuolization.

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

1

 Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential 

variation in sensitivity among members of the human population (intraspecies), FQPA SF = FQPA Safety Factor, 

NOAEL = no-observed-adverse-effect level, LOAEL = lowest-observed-adverse-effect level, MOE = margin of 

exposure, LOC = level of concern, N/A = not applicable.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 20 of 24

Attachment 4: Summary of Registered Uses.

Table D.1. Summary of Proposed Directions for Use of Acequinocyl.

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Max. 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations1

Bean, succulent shelled

(Chickpea, Garbanzo bean, Sweet lupine, White Lupine, White sweet lupine, Grain lupine, Kidney bean, Lima 

bean, Mung bean, Navy bean, Pinto bean, Snap bean, Waxbean, Broad bean, Fava bean, Asparagus bean, 

Blackeyed pea and Cowpea)

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 30 gal/A; minimum 

RTI of 14 days. Do not 

allow grazing on cowpea 

forage within 7 days of 

last treatment.

Edible podded beans

(Runner bean, Snap bean, Wax bean, Asparagus bean, Chinese longbean, Moth bean, Yardlong bean, Jackbean, 

and Sword bean)

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Succulent Soy Vegetable (Edamame)

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Hops

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Caneberry subgroup 13-07A

(Blackberry; Loganberry; Raspberry, black and red; Wild raspberry; Cultivars, Varieties, and/or Hybrids of these)

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 50 gal/A; minimum 

RTI of 21 days.

Small Fruit Climbing Subgroup, Except Fuzzy Kiwifruit – Subgroup 13-07F

(Amur river grape; Gooseberry; Grape; Kiwifruit, Hardy; Maypop; Schisandra berry’ Cultivars, varieties, ans/or 

hybrids of these)

Postemergence, 

foliar;

Ground only; 

Airblast

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 100 gal/A; for optimal 

control, use a minimum

of 150 gal/A; minimum 

RTI of 21 days. Do not 

use in alternate row 

middle applications.

Low Growing Berries – Subgroup 13-07G

(Bearberry; bilberry; Blueberry, lowbush; Cloudberry; Cranberry; Lingonberry; Muntries; Partridgeberry; 

Strawberry; Cultivars, varieties, and/or hybrids of these)
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 21 of 24

Table D.1. Summary of Proposed Directions for Use of Acequinocyl.

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Max. 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations1

Postemergence, 

foliar;

Ground only;

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Fruiting Vegetables (Except Cucurbits)

(Eggplant, Groundcherry, Pepino, Pepper – includes Bell pepper, Chili pepper, Cooking pepper, Pimento, Sweet 

pepper; Tomatillo, and Tomato)

Postemergence, 

foliar;

Ground only; 

Groundboom 

(field); 

Handheld 

sprayers 

(greenhouse)

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Melon subgroup 9A

(Muskmelon, Cantaloupe, Casaba, Santa Clause melon, Crenshaw melon, Honeydew melon, Honey balls, Persian 

melon, Golden pershaw melon, Mango melon, Pineapple melon, Snake melon, and Watermelon)

Postemergence, 

foliar;

Ground only; 

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 30 gal/A; minimum 

RTI of 21 days.

Cucumber, Gherkin

Postemergence, 

foliar; Ground 

only; 

Groundboom 

(field); 

Handheld 

sprayers 

(greenhouse)

1.25 lb/gal 

SC

[66330-38]

0.3 or 0.12 2 0.6 1

Minimum spray volume 

of 30 gal/A; minimum 

RTI of 21 days. 

Cherry

Postemergence, 

foliar;

Ground only; 

Airblast

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 40 gal/A; for optimal 

control, use a minimum 

of 150 gal/A; minimum 

RTI of 14 days. Do not 

use in alternate row 

middle applications.

Okra

Postemergence, 

foliar;

Ground only;

Groundboom

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 1

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Tree Nuts (Almonds, Beech Nut, Brazil Nut, Butter Nut, Cashew, Chestnut, Chinquapin, Filbert, Hickory Nut, 

Macadamia nut, Pecan, Black Walnut, and English Walnut) and Pistachios
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 22 of 24

Table D.1. Summary of Proposed Directions for Use of Acequinocyl.

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Max. 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations1

Postemergence, 

foliar; Ground 

only;

Airblast

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 100 gal/A; for optimal 

control, use a minimum

of 150 gal/A; minimum 

RTI of 21 days. Do not 

use in alternate row 

middle applications.

Citrus 

(Calamondin, Citrus citron, Citrus hybrids, Grapefruit, Kumquat, Lemon, Lime, Mandarin, Sour orange, Sweet 

orange, Pummelo and Satsuma Mandarin)

Postemergence, 

foliar; Ground 

only;

,Airblast

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 7

Minimum spray volume 

of 100 gal/A; for optimal 

control, use a minimum

of 150 gal/A; minimum 

RTI of 21 days. 

Pome Fruits 

(Apples, Crabapples, Loquat, Mayhaw, Pear, Oriental Pear and Quince)

Postemergence,

foliar; Ground 

only;

,Airblast

1.25 lb/gal 

SC

[66330-38]

0.3 2 0.6 14

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 21 days. 

Production and Landscape Ornamentals

(Ornamental plants growing in interiorscapes, arboretums, field nursery plantings, container nurseries, forest 

nurseries, residential and commercial landscapes, greenhouses, commercial lath and shade houses, parks and 

recreation areas and areas surrounding schools)

Postemergence, 

foliar;

Ground only;

Handheld 

equipment

1.25 lb/gal 

SC

[66330-38]

0.13 2 0.26 14

Minimum spray volume 

of 100 gal/A; minimum 

RTI of 14 days. Not for 

indoor residential use.
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 23 of 24

Attachment 5: Acequinocyl IRLS Sheet.

Table E.1. Summary of U.S. Tolerances and International MRLs. 

U.S. Canada Mexico1 Codex

Residue Definition:

40CFR180.599

(a) General. 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.

2-(acetyloxy)-3-dodecyl-1,4-

naphthalenedione, including the metabolite 2-

dodecyl-3-hydroxy-1,4-naphthalenedione

None

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

Commodity U.S. Canada Mexico1 Codex

Almond, hulls 2.0

Apple, wet pomace 1.0

Bean, edible podded 0.25

Bean, succulent shelled 0.30

Berry, low growing, subgroup 13-

07G

0.50 0.5 strawberries

Caneberry subgroup 13-07A 4.0 4 blackberries, loganberries, raspberries, 

wild raspberries

Cattle, fat 0.02 0.02

Cattle, meat byproducts 0.02 0.02

Cherry, sweet 0.50

Cherry, tart 1.0

Citrus, oil 30 30

Cowpea, forage 6.0

Cowpea, hay 18

Cucumber 0.15 0.15

Fruit, citrus, group 10 0.20 0.35 calamondins, citrus citron, citrus 

hybrids, grapefruits, kumquats, lemons, 

limes, oranges, satsuma mandarin, tangerine 

(mandarin)

Fruit, pome, group 11 0.40 0.3 apples, Asian pears, crabapples, loquats, 

mayhaws, pears, quinces

Fruit, small vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F

1.6

Goat, fat 0.02 0.02

Goat, meat byproducts 0.02 0.02

Hop, dried cones 4.0

Horse, fat 0.02 0.02

Horse, meat byproducts 0.02 0.02

Melon subgroup 9A 0.15
Acequinocyl Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 24 of 24

Nut, tree, group 14 0.02 0.02 African tree nuts, almond nuts, 

beechnuts, black walnuts, Brazil nuts, 

Brazilian pine nuts, bunya nuts, bur oak nuts, 

butternuts, Cajou nuts, candlenuts, cashew 

nuts, chestnuts, chinquapin nuts, coconuts, 

coquito nuts, dika nuts, English walnuts, 

ginkgo nuts, Guiana chestnuts, hazelnuts 

(filbert), heartnuts, hickory nuts, Japanese 

horse-chestnuts, macadamia nuts, mongongo 

nuts, monkey-pot nuts, monkey puzzle nuts, 

Okari nuts, Pachira nuts, peach palm nuts, 

pecan nuts, pequi nuts, Pili nuts, pine nuts, 

pistachio nuts, Sapucaia nuts, tropical almond 

nuts, yellow horn nuts

Okra 0.70 0.7

Pistachio 0.02 0.02 

Sheep, fat 0.02 0.02

Sheep, meat byproducts 0.02 0.02

Soybean, vegetable, succulent 0.25

Vegetable, fruiting, group 8 0.70 0.7 African eggplants, bell peppers, bush 

tomatoes, coconas, currant tomatoes, 

eggplants, garden huckleberries, goji berries, 

groundcherries, martynias, naranjillas, 

nonbell peppers, okras, pea eggplants, 

pepinos, roselles, scarlet eggplants, 

sunberries, tomatillos, tomatoes, tree 

tomatoes

MRLs with NO US Equivalent

Meat of cattle 0.02

Meat of goats 0.02

Meat of horses 0.02

Meat of sheep 0.02

Milk 0.02

Completed by: M. Negussie; 01/14/15

1 Mexico defers to US tolerances and/or Codex MRLs for its export purposes.