UNITED ST ATES ENVIRONMENT AL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICA L SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: 

Subj ect: 

22-MAR-2016 

Acequinocyl. Human Health Risk Assessment for the Proposed Increase in the 

Permanent Tolerance for Residues in/on Hops. 

PC Code: 006329 DP No.: 0431305 

Decision No.: 50500 l Registra tion No.: NA 

Petition No.: 5F8364 Regulatory Action: Amend an Established 

Tolerance 

Risk Assessment Type: Single Chemical/Aggregate Case No.: 762 l 

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

MRID No.: NA 40 CFR: § 180.599 

=~~~------­ George F. Kramer, Ph.D., Senior mi st~ fPt Anwar Y. Dunbar, Ph.D., Pharmacologitf::-t ~ %::_. V 

Jam

Risk 

es 

Assessment 

S. Miller, Env

Branch 

ironm

l 

ental 

(RAB 

Scientist 

I) 

r;;___} ) ) ~ 

FROM: 

Health Effects Division (HED) (7509P) 

THROUGH: C

RAB 

harle

l/

s 

HED 

W. Smi

(7509

th III

P) 

, Branch ChiefC ~ 

TO: Andrew Ertman/Venus Eagle, RM I 

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 uses of 

acequinocyl and the proposed increase of the existing tolerance for residues inion hops from 4.0 

ppm to 15.0 ppm. 

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 George Kramer (RAB I), the hazard 

characterization was provided by Anwar Dunbar, the occupational/residential exposure 

assessment was provided by James Miller (RAB I), and the drinking water exposure assessment 

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

NOTE: A human health risk scoping document for acequinocyl to support Registration Review 

was completed on 27-MAY-2015 by HED (Memo, S. Levy er al., 0423850). Jn the present 

memo, dietary, existing residential, and aggregate risks were re-evaluated based on the proposed 

increase of the existing tolerance for residues in/on hops. 

Page l of2 I 
Acequinocyl Human Health Risk Assessment 0431305 

TABLE OF CONTENTS 

1.0 EXECUTIVE SUMMARY ..................................................................................................... 3 

2.0 HED Recom1nendations ...................................................................................................... 5 

2.1 Data Deficiencies/Conditions of Registration ........................................................ 5 

2.2 Tolerance Considerations ........................................................................................ 5 

3.0 Introduction ............................ ............................................................................................. 6 

3. 1 Chemical Identity .................................................. ................ ....... ...... ... ... ............... 6 

3.2 Physical/Chemical Characteristics .......................................................................... 6 

3.3 Pesticide Use Pattern ............................................................................................... 7 

3.4 Anticipated Exposure Pathways ............................................................................. 7 

3.5 Consideration of Environmental Justice ................................................................. 7 

4.0 Hazard Characterization and Dose Response Assessment ................................................. 8 

4. 1 Summary of Toxicological Effects ......................................................................... 8 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 9 

4.3 Toxicity Endpoint and POD Selections .................................................................. 9 

5.0 Dietary Exposure and Risk Assessment ........................................................................... 10 

5. 1 Dietary Exposure/Risk Pathway ........................................................................... 11 

5.1. J Residue Profile ................................. ......................................................... 11 

5. l'.2 \Vater ~xposure/Risk Pathway ................................................................. 11 

5. ~3 ·- Di eta Ex.po~ure Analyses ....................................................................... 12 

5.1.4 l;onic,Oiet~ Exposure Analysis .......................................................... 12 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................... 13 

6. 1 Short-term Residential Handler Risk .................................................................... 13 

6.2 Short-term Residential Post-application Risk ....................................................... 14 

6.3 Spray Drift ..................................................................... ... .... ................................ 15 

6.4 Residential Bystander Post-application Inhalation Exposure ............................... 15 

7 .0 Aggregate Exposure/Risk Characterization ...................................................................... 15 

7. I Acute Aggregate Risk ........................................................................................... 15 

7 .2 Short-Term Aggregate Risk .................................................................................. 16 

7 .3 Intermediate-Term Aggregate Risk ... ..... ..... ......................................................... 16 

7.4 Long-Te1111 Aggregate Risk ................................................................................. . J 6 

7 .5 Cancer Risk ........................................................................................................... 16 

8.0 Cumulative Risk Characterization/ Assessment ................................................................ 16 

9.0 Occupational Exposure/Risk Pathway .............................................................................. 17 

Appendix A: Toxicity Profile Tables ........................................................................................... 18 

Appendix B: Greenhouse Ornamental Study Summary .............................................................. 2 1 

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Acequinocvl Human Health Risk Assessment 0431305 

1.0 EXECUTIVE SUMMARY 

Acequinocyl [2-(acetyloxy)-3-dodecyl-1 ,4-naphthalenedione)] is a quinoline-type miticide that is 

currently registered for the use in the U.S. on a number of raw agricultural commodities (RA Cs) 

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 by Arysta LifeScience North America Corporation as a 15% solubleconcentrate (SC) formulation. 

Arysta is requesting to increase the existing tolerance for residues of acequinocyl and its 

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

in/on hops from 4.0 ppm to 15.0 ppm. The purpose of the amended tolerance is to harmonize the 

value with the established maximum residue limit (MRL) in the European Union (EU). The 

domestic residue data for hops were previously submitted and reviewed under PP#9E7598 

(Memo. S. Levy, 25-AUG-20 10; 0369100). 

Hazard Assessment: The toxicology database is complete. For all species, durations and routes 

of exposure (oral and dermal), the primary effects observed are indicative of toxicity to the liver 

(hepatocyte vacuolization, brown pigmented cells and perivascular inflammato1:y cells in liver) 

and hematopoietic system (hemorrhage, increased clotting factor times and increased platelet 

counts). In the rat and rabbit developmental toxicity studies, there was no evidence of increased 

quantitative or qualitative fetal susceptibility, with the maternal effects (clinical signs and gross 

necropsy findings) occurring at similar or lower doses than feta l resorptions. In the rat twogeneration reproductive toxicity study, 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, 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. There were no effects on reproductive parameters. There was no evidence of 

carcinogenicity, genotoxicity, or mutagenicity. In an acute neurotoxicity study, there were no 

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

effects up to the highest dose tested (45 mg/kg/day). Acequinocyl has low acute toxicity via the 

oral, dermal, and inhalation routes (Toxicity Categories Ill & IV). No ocular or dermal irritation 

was noted. Acequinocyl is not a dermal sensitizer. 

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

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

Evaluation Model (DEEM-FCID, Version 3. 16) which uses 2003-2008 food consumption data 

from the U.S. Department of Agriculture's (USDA's) National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). 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 (aRID) was not established. A cancer dietary assessment was 

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

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)]. 

Page 3 of2 I 
Aceguinocvl Human Health Risk Assessment 0431305 

For the general U.S. population, the exposure for food + drinking water utili zed 14% of the 

cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, children 

1-2 years old, is 60% of the cPAD. 

Residential Exposure Assessment: There are no proposed residential uses associated with the 

current action; however, there are existing residential uses that have been reassessed in this 

document to reflect revisions to HED's 2012 Residential SOPs 1 along with policy changes for 

body-weight assumptions. All residential handler and post-application MO Es were > 100 and are 

not of concern to HED (see Table 6.1. l ). 

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

performed because no appropriate endpoint was available to determine the aRID 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 existing residential uses. Short-term aggregate exposures and risk estimates 

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

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

populations groups). The aggregate MOEs are > 100, therefore, they do not exceed HED's LOC. 

Occupational Exposure Assessment: As there are no proposed or requested changes in the 

acequinocyl label associated with this action, a new occupational exposure assessment has not 

been performed. 

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.archives.gov/federal-register/executiveorders/pdf/12898.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 NHANES!WWEIA and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year. ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

I Available: http://www2.cpa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-proceduresresidential-pesticide 

Page 4 of2 l 
Aceguinocyl Human Health Risk Assessment 0431305 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and fann workers as well as lifestyle and traditional dietary patterns among specific 

subgroups. 

2.0 HED Recommendations 

There are no toxicological, residue chemistry, or occupational/residential exposure issues that 

would preclude increasing the existing tolerance for residues of the insecticide acequinocyl in/on 

hops from 4.0 ppm to 15 ppm. 

2.1 Data Deficiencies/Conditions of Registration 

No additional data arc required to support the proposed action. 

2.2 Tolerance Considerations 

2.2.1 Enforcement Analytical Method 

There are adequate residue analytical methods for enforcing tolerances for acequinocyl residues 

of concern inion the registered plant commodities. These methods include two highperfonnance liquid chromatography methods with tandem mass-spectroscopy detection 

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

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

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

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

2.2.2 Recommended Tolerances 

Table 2.2.2. Tolerance Summary for Aceq uinocyl. 

I Proposed Tolerance I Recommended I Comments; Correct Commodity 

Commodity (ppm) Tolerance (ppm) Definition 

40 CFR § 180.599(a) 

Hop, dried cones I 15.0 I 15 I 

2.2.3 Revisions to Petitioned-For Tolerances 

HED is recommending a change in the numerical expression of the hop, dried cones tolerance 

va lue in order to conform to current HED policy on significant figures. 

2.2.4 International Harmonization 

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

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

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

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

harmonized by this action. 

Page 5 of2 l 
Aceguinocvl Human Health Risk Assessment 0 431305 

2.3 Label Recommendations 

There are no proposed or requested changes in the acequinocyl label associated with this action. 

3.0 Introduction 

Acequinocyl is a quinoline-type miticide that is currently registered for the use to control various 

phytophagous mite species in the U.S. on a number of RACs. Tolerances are currently 

established under 40 CFR § l 80.599(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 fa t and liver of cattle, goat, horse, and sheep. 

3.1 Chemical Identity 

Table 3.1. 1. Nomenclature of Test Compound and Meta bolites. 

0 

«XCH,(CH,J,.CH, I 

OCOCH3 

Compound 0 

Common name Acequinocyl 

Company experimental names TM-41301 or AKD-2023 

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

CAS name 2-(acetylO>..'Y)-3-dodccyl-1.4-naphthalenedione 

CAS # 57960-19-7 

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

Compound 0 

«XCH,(CH,),.CH, I 

OH 

0 

Common name Acequinocyl-OH 

Company experimental names RI 

IUPAC name 2-dodecyl-3-hydroxy-1.4-napthoquinone 

CAS name 2-dodecyl-3-hydroxy-1.4-naphthalenedione 

CAS# 57960-31-3 

3.2 P hysical/Chemical Characteristics 

This information is provided in the human hea lth risk assessment scoping document for 

acequinocyl to support Registration Review, completed on 27-MA Y-2015 by HED (Memo, S. 

Levy et al., D423850). 

Page 6 of21 
Aceguinocyl Human Health Risk Assessment 0431305 

3.3 Pesticide Use Pattern 

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

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

Table 3.3.1. 

Table 3.3. 1. Summary of Directions for Use of Accq uinocyl. 

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

Hops (U.S.) 

Postemergence, 1.25 lb/gal Minimum spray volume 

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

Ground only [66330-38] RTl of21 days. 

Hops (EU) 

Postemergence, 1.25 lb/gal foliar 0.67 I 0.67 21 

Ground only SC 

1 RTI = retreatment interval. 

3.4 Anticipated Exposure Pathways 

RD has requested an assessment of human health risk to support the proposed increase in the 

existing tolerance for residues of acequinocyl in/on hops. Humans may be exposed to 

acequinocyl in food and drinking water since acequinocyl may be applied directly to growing 

crops, and applications may result in acequinocyl reaching surface and ground water sources of 

drinking water. There are registered residential uses of acequinocyl; therefore, human exposure 

in residential or non-occupational settings is also expected. In an occupational setting, 

applicators may be exposed while handling the pesticide prior to application, as well as during 

application. There is also a potential for post-application exposure for workers re-entering 

treated fields. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed increased tolerance for residues of acequinocyl and considers the existing registered 

uses as well for the dietary and residential exposure assessments. 

3.5 Consideration of Environmental Justice 

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 I 2898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-income Populations," 

(http://www.archives.gov/federal-register/executive-orders/pdf/I 2898.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 the 

NHANES/WWEIA; 2003-2008 and are used in pesticide risk assessments for all registered food 

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

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

Page 7 of2 I 
Aceguinocyl Human Health Risk Assessment 0431305 

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 commined 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. 

4.0 Hazard Characterization and Dose Response Assessment 

4.1 Summary of Toxicological Effects 

The toxicological database is complete. In the 20 11 risk assessment (Memo, S. Levy et al., 30-

NOV-2011; D3895 I 9), 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. acute neurotoxicity 

and immunotoxicity studies were submitted and the results were incorporated into the current 

assessment. Based on the results from the acute neurotoxicity study, HASPOC determined that a 

subchronic neurotoxicity study is not required at this time (TXR# 0051465). 

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

characterized. Acequinocyl exhibits marginal absorption into the plasma (l 3-16% 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 hematopoietic 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, 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, 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. 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 Categories lIJ & IV). No ocular or dermal irritation was noted. Acequinocyl is 

not a dermal sensitizer. 

Page 8 of2 I 
Acequinocyl Human Health Risk Assessment 0 43 1305 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) 

HED's RABI risk assessment team concluded that the Food Quality Protection Act (FQPA) 

Safety Factor (SF) may be reduced to lX for all exposure scenarios. This recommendation is 

detailed in the 2011 risk assessment (Memo, S. Levy et al., 30-NOV-20 I I; 0389519). 

4.3 Toxicity Endpoint and POD Selections 

Table 4.3.1 provides the toxicological doses and endpoints used in this risk assessment. No 

changes were made from the previous risk assessment. 

Ta ble 4.3.1. Summa ry of Toxicologica l Doses a nd End points for Acequinocyl fo r Use in Dieta ry, 

Occupa tiona l, a nd Residentia l Exposure Risk Assessments. 1 

Exposure/ POD Uncertainty/FQPA Sf's RID. PAD. LOC Study and Toxicological Effects Scenario 

Acute Dietary An endpoint of concern (effect) 

(General attributable to a single dose was 

Population. not identified in the database. 

including Infants Quantification of acute risk to 

and Children) general population including 

infants and children is not 

required. 

Chronic Dietary NOAEL = 2.7 UFA= IOX ePAD = eRID = 0.027 18-monih carcinogenicity study in 

(All Populations) mg/kg/day UFu = IOX mg/kg/day mice: 

FQPASF = IX LOA EL= 7.0 mg/kg/day based on 

clinical chemistry and microscopic 

non-neoplastic lesions (brown 

pigmented cells and perivascular 

innammatory cells in liver). 

Short-term ( 1-30 NOAEL = 60 UFA= IOX LOC (residential)= Developmental toxicity study in 

days) incidental mg/kg/day UF11= !OX MOE <100 rabbits: 

oral Maternal LOAEL = 120 

mg/kg/day based on clinical signs 

(hcmaturia, reduced fecal outpuL 

body-weight loss. and reduced 

food consumption) and gross 

necropsy findings (pale lungs and 

liver. hemorrhaging uterus. nuid in 

the cecum. fur in the stomach. 

blood stained vaginal opening. 

blood-stained urinary bladder 

contents/urine). 

Intermediate- NOAEL = 16 UFA= IOX LOC (residential)= Subchronic toxicity in mice: 

tcrn1 mg/kg/day UFH= IOX MOE < IOO LOAEL = 81 mg/kg/day based on 

{ 1-6 months) hcpatocy1c vacuolization. 

incidental oral 

Short- ( 1-30 Dermal NOAEL UFA= !OX LOC (occupational/ 28-day dennal study in rats; 

days) and = 200 mg/kg/day UFH = IOX residential)= LOA EL = I 000 mg/kg/day based 

Intermediate- MOE <100 on increased cloning factor times. 

term (1-6 

months) Dermal 

Short-term ( 1-30 Oral OAEL = UFA= IOX LOC (occupational/ Developmental toxicity study in 

days) Inhalation 60 mg/kg/day UFH = IOX residential) = rabbits: 

MOE <IOO Maternal LOAEL = 120 

(inhalation mg/kg/day based on clinical signs 

absorption rate= {hcmaturia. reduced fecal outpuL 

100%) body-weight loss. and reduced 

food consumption) and gross 

necropsy findings (pale lungs and 

liver. hemorrhaging uterus, nu id in 

Page 9 of2 I 
Aceguinocvl Human Health Risk Assessment 0431305 

T able 4.3.1. Summary of Toxicological Doses a nd End points for Acequinocyl for Use in Dieta ry, 

Occuoa tiooa l, a nd Residential Exoosure Risk Asscssments.1 

Exposure/ POD Unccrtainty/FQPA SFs RID. PAD. LOC Study and Toxicological Effa:ts Scenario 

the cecum. fur in the stomach. 

blood stained vaginal opening. 

blood-stained urinary bladder 

contents/urine). 

Intermediate- Oral NOA EL = UFA= IOX LOC (occupational/ Subchronic toxicity in mice: 

( 1-6 months) 16 mg/kg/day UF11 = IOX residential)= LOA EL= 81 mg/kg/day based on 

Term Inhalation MOE <100 hepatocyte vacuolization. 

(inhalation 

absorption rate = 

100%) 

Cancer (oral. dermal. inhalation) Classilication: ··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), U 1711 = 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. Rfl) = reference dose 

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

= not applicable. 

4.3.1 Recommendation for Combining Routes of Exposures for Risk Assessment 

Based upon the use of the same oral studies and endpoints, short-term incidental oral exposures 

can be combined with short-term inhalation exposures and intermediate-term incidental oral 

exposures can be combined with intermediate-term inl1alation exposures. As different effects 

were seen in the route-specific dermal study compared to the effects seen in the oral studies used 

to select the oral and inhalation points of departure, short- and intermediate-term dermal 

exposures should not be combined with incidental oral or inhalation exposures. 

5.0 Dieta ry Exposure and Risk Assessment 

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

in this section: 

• PP# 5F8364. Acequinocyl. Petition for Increasing the Permanent Tolerance for Residues in/on Hops. 

Summary of Analytical Chemistry and Residue Data. G. Kramer, 22-MAR-2016; 0427588. 

• PP# 5F8364. Acequinocyl. Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk 

Assessment for the Proposed Increase in the Permanent Tolerance for Residues in/on Hops. G. Kramer, 

22-MAR-2016; D43 I 306. 

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

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

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

D389520. 

Arysta LifeScience is requesting to increase the existing tolerance for 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 hops from 4.0 ppm to 

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

MRL in the EU. The domestic residue data for hops were previously submitted and reviewed 

under PP#9E7598 (Memo. S. Levy, 25-AUG-2010: 0369100). 

Page l0 of2 1 
Acequinocvl Human Health Risk Assessment 0431 305 

5.1 Dietary Exposure/Risk Pathway 

5.1.l Residue Profile 

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

naphthoquinone (acequinocyl-OH), the opening of the quinone ring to form AKM- 18, and the 

subsequent degradation of the qui none ring to yield polar metabolites that degrade to phthalic 

acid. These data are considered sufficient for the currently registered crops. For purposes of risk 

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

currently registered crops include parent and acequinocyl-OH (Memo, S. Levy, 07-JAN-2004; 

DP# 297872). 

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

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

petition. 

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

Trade Agreement (NAFTA) Growing Zone 11 (ID, OR, WA) during the 2005 growing season. 

Each trial consisted of one untreated and one treated plot. At each site, a 1.25 lb/gal SC 

fonnulation of acequinocyl was applied to hops as two directed foliar applications during cone 

development at rates of 0.288-0.330 lb ai/ A/application, with a 19- to 28 day retreatment interval 

(RTI), for a total rate of0.588-0.641 lb ai/A (- IX). Total residues ofacequinocyl and 

acequinocyl-OH were 1.32-2.83 ppm in/on dried hop cones. The German residue data (2X U.S. 

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

only) show that the U.S. tolerance level is likely set at too low of a level. HED notes that 

analysis of the U.S. data with the Organization for Economic Co-operation and Development 

(OECD) MRL Calculator would have resulted in a recommended tolerance of 7.0 ppm. 

Harmonization of the U.S. tolerance level with the MRL of 15 ppm is thus recommended. There 

is currently no established Canadian MRL for acequinocyl in/on hops. 

5.1.2 Water Exposure/Risk Pathway 

The drinking water residues used in the dietary risk assessment were provided by EFED (M. 

Lowit, 07-SEP-2011: 0389520) and incorporated directly into this dietary assessment. As there 

are no proposed or requested changes in the acequinocyl label associated with this action, a new 

drinking water assessment has not been performed. Water residues were incorporated directly 

into DEEM-FCID under the food categories .. water, direct, all sources" and ·'water, indirect, all 

sources." 

Table 5.1.2.1. Recommended EOWCs of Aceouinocvl Derived from the Previous Uses. 

EDWCs from Surface Water Sources (ug/L)1•

2 

Drinking water Proposed Approach I Approach 2 

source (model) Use/ ccnario3 (assume no accquinocyl degradation) (combined acequinocvl and RI ) 

l-in-10· I -in- I 0-year 30-year l-in-1 0- I-in- I 0-year 30-ycar 

year acute chronic mean year acute chronic mean 

Surface water 6.69 6.69 6.69 

0.42 0.26 (PRZM/EXAMS) Cherry/MI cherry (25.89)

4 ( 17.84)4 ( I 0.19)4 5.59 

Surface water Small fruit (vine 6.69 6.69 6.69 

4.22 0.38 0.27 (PRZM/EXAMS) climbing, except fuzzy (23. 12)4 ( 15.34)4 (9.57)4 

Page 11 of2 I 
Aceguinocvl Human Health Risk Assessment 0431305 

kiwifrnit. I 3-07F) y 

grape 

Surface water Cranberry/Provisional 3.81

5 (Provisional 4.24 3.75 -- 1.365 -- Cranberry Model) Cranberry Model 

Groundwater A 11 proposed uses 3.6 x 10·

3 s 3.6 x 10-

3 :::3.6 x 10-3 3.6 x 10·3 s 3.6 x 10-1 s 3.6 x 10-3 

(SCIGROW) 1 Bolded values are the recommended EDWCs by EFED. 

! A default PCA of 0.87 was applied. 3 Maximum of two applications of0.3 lb ai/A for all proposed uses. 

~ EDWC (shown in parentheses) exceeds the solubility limit of acequinocyl (6.69 μg/L at 20°C): thc.Tcfore. the recommended 

EDWC is 6.69 ppb. 

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

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

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

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

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

value assures a conservative assessment. 

5.1.3 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 aRID 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 DEEM-FCID, 

Version 3 .1 6, which incorporates 2003-2008 consumption data from USDA· s 

NHANES/WWEIA. The 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 EPA-defined 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, but for acute 

exposure assessment are retained as individual consumption events. Based on analysis of the 

2003-2008 NHANES/WWEIA consumption data, which took into account dietary patterns and 

survey respondents, HED concluded that it is most appropriate to report risk for the following 

population subgroups: the general U.S. population, all infants (<I-year old). children 1-2 years 

old. children 3-5 years old, children 6-12 years old, youth 13-19 years old. adults 20-49 years 

old, females 13-49 years old, and adults 50-99 years old. 

5.1.4 Chronic Dietary Exposure Ana lysis 

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

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

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

U.S. population and various population subgroups. DEEM ver. 7.81 default processing factors 

were used with the exception of those for grape juice and raisins. As residues were reduced in 

both grape juice ( <0.02X) and raisin (O. l 5X), separate tolerances are not required for these 

commodities. The DEEM ver. 7.81 default processing factors for juice and raisin were set to l as 

concentration was shown not to occur (Memo, S. Levy, 05-SEP-2007; DP#: 342805). Drinking 

Page l2of2 1 
Aceguinocyl Human Health Risk Assessment 0431305 

water was incorporated directly into the dietary assessment using the chronic concentration for 

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

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

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

for the general U.S. population (14% cPAD) and all population subgroups. The most highly 

exposed population subgroup is children 1-2 years old at 60% 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 5.1.4.1. Summa ry of Dietary (Food + Drinking Water) Exposure and Risk for Aceq uinocyl. 

Chronic Dietary1 

Population Subgroup Dietary Exposure % cPAD (mg/kg/day) 

U.S. Population (total) 0.0037 11 14 

All Infants (< I year old) 0.006769 25 

Children 1-2 years old 0.016168 60 

Children 3-5 years old 0.011083 41 

Children 6-12 years old 0.005226 19 

Youth 13-19 years old 0.002605 10 

Adults 20-49 years old 0.002758 10 

Adults 50+ years old 0.002615 10 

Females 13-49 years old 0.002624 10 1 Chronic dietary endpoint of0.027 mg/kg/day applies to the general U.S. populauon and all populauon subgroups. The values 

for the highest exposed population are boldcd. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 

There are no proposed residential uses associated with the current action; however, there are 

existing residential uses that have been reassessed in this document to reflect revisions to HED's 

2012 Residential S0Ps2 along with policy changes for body weight assumptions. The revision of 

residential exposures will impact the human health aggregate risk assessment for acequinocyl. 

The algorithms used to estimate exposure and dose for residential handlers can be found in the 

2012 Residential SOPs. 

6.1 Short-term Residential Handler Risk 

Acequinocyl is currently registered for use on landscape ornan1entals in and around residences, 

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

commercial applicators and homeowners. Short-term residential handler dermal and inhalation 

exposure from applying acequinocyl to trees and ornamentals with handheld equipment was 

reassessed for this action to reflect the 2012 Residential SOPs. All MO Es were > 100 and are not 

of concern to HED (see Table 6.1.1). 

2 Ava i lable:lill.P.://www .epa.gov/pesticides/scicncc/rcsidential-exposure-sop. htm I 

Page 13 of21 
Aceguinocyl Human Health Risk Assessment 0431305 

Table 6.1.1. Summary of Residential Handler Exposure and Risk. 

Application Unit Exposure Amount Residential Residential Scenario Rate llandled Handler Dose 

(lb ai/gal) (mg/lb ai) (gals) (mg/kl!,/day) Handler MOE 

Mix er/Loader/ Appl ieator - Dermal: Dermal: 

Liquid Fonnulation with Dermal: 63 0.0049 41.000 

0.00125 5 Manually-pressurized Inhalation: 0.018 Inhalation: Inhalation: Hand wand 0.00000 14 43.000.000 

Dermal: Dermal: 

Mix er/Loader/ Appl ieator - Dermal: 58 0.01 20.000 

Liquid Fonnulation with 0.00125 11 

Hose-End Sprayer Inhalation: 0.0014 Inhalation: Inhalation: 

0.00000024 250.000.000 

Dermal: Dermal: 

Mixer/Loader/Applicator - Dermal: 130 0.0 1 20.000 

Liquid Formulation with 0.00125 5 

Backpack Inhalation: 0. 14 Inhalation: Inhalation: 

0.0000 11 5.500.000 

Dermal: Dermal: 

Mixer/Loader/Applicator- Dermal: 58 0.0045 44.000 

Liquid Fonnulation with 0.00125 5 

Sprinkler Can Inhalation: 0.0014 Inhalation: Inhalation: 

0.000000 11 550.000.000 

6.2 Short-term Residential Post-application Risk 

Short-term post-application dermal exposure is anticipated for the registered residential uses; 

however, a quantitative post-application assessment has not been previously conducted. 

Consistent with the 20 12 Residential SOPs, HED assessed residential post-application exposure 

from contacting trees and ornamentals previously treated with acequinocyl for this action. 

Chemical-specific dislodgeable-foliar residue (OFR) data are available for acequinocyl for 

chrysanthemums in greenhouses (MRID 45428619) and these DFR data were used in the postapplication dermal exposure assessment. Based on an analysis of the chrysanthemum data, the 

R2 value is low (0.4 17), indicating that the test product may not dissipate according to first-order 

kinetics in greenhouses; therefore, the measured DFR value was used so as to not underestimate 

risk. In addition, the DFR value was adjusted to reflect the maximum appli cation allowed on the 

label (0. 125 lb ai/A) as compared to the application rate used in the DFR study (0.3 lb ai/A). The 

measured average Day-0 residue from the study was 0.617 ug/cm2 or 0.257 ug/cm2 once adjusted 

for application rate. Appendix B provides a sununary of the study. 

All MO Es were > 100 and are not of concern to HED (see Table 6.2.1). 

Table 6.2.1. Summary of Residentia l Post-application Exposur e a nd Risk. 

Transfer /\bsorbcd Dermal 

Scenario Lifcstage DFRt Coefficient Exposure Dermal MOE (ug/cm2) (em2/hr) Time (hr) Dose (rounded) ( mj.!/kg, day) 

Post-application Adult 8400 2.2 0.059 3.400 

Gardens 6 < 11 yrs 4600 I. I 0.04 1 4.900 

0.257 

Post-application Adult 1.700 I 0.005 37.000 

Trees 6 < 11 yrs 930 0.5 0.004 54.000 

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Aceguinocyl Human Health Risk Assessment 0431305 

6.3 Spray Drift 

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground appli cation methods (e.g., ground boom and 

a irblast) employed for acequinocyl. The Agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), 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).3 The Agency has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process, which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration o/Spray Dr(ft. This document outlines the quantification 

of indirect non-occupational exposure to drift. 

6.4 Residential Bystander Post-application Inhalation Exposure 

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

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

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP's final report 

on March 2, 20 l 0 

(http:! /arch ive.epa.gov/scipoly/sap/meetings/web/pdf/ 1203 09meetingmi nutes.pdf). The Agency 

has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-201 4-02 I 9). During Registration 

Review, the Agency will utilize this analysis to detem1ine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further ana lysis is required for acequinocyl. 

7.0 Aggregate Exposure/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. 

7.1 Acute Aggregate Risk 

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

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

assessment was not performed. 

3 Available: http://www2.epa.gov/reducing-pesticide-drif1 

Page l5of2 1 
Acequinocyl Human Health Risk Assessment 0431305 

7.2 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. Dermal post-application residential 

exposures were not included in the short-term aggregate as different effects were seen in the 

route-specific dermal study compared to the effects seen in the oral studies used to select the oral 

and inhalation points of departure. 

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

exposure assessment (see Table 5.1.4.1 ). Residential exposure estimates are conservative 

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

exposure estimates were taken from Table 6.1.1. The short-term aggregate risk calculations are 

shown in Table 7.2. 1 and are not of concern to HED. 

Ta ble 7.2.1. Short-Term APore1rnte Risk Calculations. 

Dietary Residential Inhalation Aggregate Exposure Aggregate Population Exposure Exposure (mg/kg/day) MOE3 

(mg/kg/day)' (mg/kg/day)2 

Adults 20-49 years old 0.002758 0.000011 0.00275869 22,000 1 From Table 5.1.4.1. 2 Residential exposure from Table 6.1. 1 ··Mixer/Loader/Applicator- Liquid Fonnulation with 13ackpack"' scenario. 3 Aggregate MOE = short-term oral NOAEL (60 mg/kg/day) + aggregate exposure. 

7.3 Intermediate-Term Aggregate Risk 

lntem1ediate-tenn aggregate risk was not calculated since the use pattern is not expected to result 

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

7.4 Long-Term Aggregate Risk 

Chronic (long-term) aggregate risk is made up only of dietary sources; therefore, the chronic 

exposure estimates provided in the chronic dietary exposure analysis (see Table 5. I .4.1) 

represents chronic aggregate exposure. 

7.5 Cancer Risk 

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

carcinogen. 

8.0 Cumulative Risk Characterization/Assessment 

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

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

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

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

EPA has not assumed that acequinocyl has a common mechanism of toxiciry 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 

Page 16 of2 I 
Acequinocyl Human Health Risk Assessment 0431305 

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 (http://www.epa.gov/pesticide-science-and-assessingpesticide-risks/ cumulative-assessment-risk-pesticides). 

9.0 Occupational Exposure/Risk Pathway 

As there are no proposed or requested changes in the acequinocyl label associated with this 

action, a new occupational handler and post-application exposure assessment has not been 

performed. 

List of Appendices: 

Appendix A. Toxicity Profile Tables 

Appendix B. Greenhouse Ornamental DFR Study Summary 

cc: G. Kramer (RAB I) 

R.Dl: RABI (2/10/ 16) 

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

Page 17 of21 
Aceguinocyl Human Health Risk Assessment D43 1305 

Appendix A: Toxicity Profile Tables. 

Table A-l. Acute Toxicity of Acequinocyl. 

Guideline Study Type MRJD #(s) Results Tox icity Category No. 

870.1 100 Acute Oral (rat) 45435011 LDso >5000 mg/kg IV 

(8 1-1) 

870.1 200 Acute Dermal 4543501 2 LDso >2000 mg/kg Ill 

(8 1-2) 

870. 1300 Acute Inhalation 454350 13 LCso > 0.84 mg/L Ill 

(81-3) 

870.2400 Primary Eye Irritation 45435014 Not an eye irritant IV 

(8 1-4) 

870.2500 Primary Skin Irritation 454350 15 Not a de rmal irritant IV 

(8 1-5 ) 

87.2600 Dermal Sensitization 45435016 Not a dermal sensitizer NIA 

(8 1-6) 

Table A-2. Toxicity Profile for Acequinocyl. 

Guideline No. ; 

Study Type MRlD (year); Doses; Classification Results 

870.3 100 45673701 ( 1995): NOAEL (M/F) = 1612 1 mg/kg/day: LOAEL 

(M/F) = 81 /I 00 mg/kg/day based on 

90-Day Oral Toxicity 0, I 00. 500. 1000 ppm hepatocyte vacuolization. 

Rodents-MOUSE 

M: 0. 16. 81. 15 1 mg/kg/day 

F: 0. 21. I 00. 23 1 mg/kg/day 

Acceptable/Guideline 

870.3100 4553 1904 ( 1998): NOAEL (M/F) = 30.4/32.2 mg/kg/day: 

LOAEL (M/F) = 11 9.5/129.2 mg/kg/day 

90-Day Oral Toxicity 0. I 00. 400. 1600. 3200 ppm: based on increased prothrombin times in 

Rodents-RAT M:. 7.6. 30.4, 119.5, 252.7 mg/kg/day males and increased activated partial 

F: 0. 8.3. 32.2, 129.2. 286.0 mg/kg/day thromboplastin times in both sexes. 

Acceptable/Guidel ine 

870.3150 45531905 (1995): NOAEL (M/F) = 40140 mg/kg/day: LOAEL 

(M/F) = 160/160 mg/kg/day based on 

90-Day Oral Toxicity 0. 40, 160, 640. I 000 mg/kg/day decreased body-weight gains and reduced 

Nonrodcnts-DOG food cfticiencics in males and fo r female 

Acceptable/Guideline beagle dogs based on increased platelet 

counts. 

870.3200 4553 1906 ( 1999): Systemic NOAEL = 200 mg/kg/day: 

LOA EL = 1000 mg/kg/day based on 

28-Day Dermal Tox icity- 0. 40. 200, I 000 mg/kg/day increased dolling factor times (increased 

RAT prothrombin time. increased activated partial 

Acceptable/Guideline prothromboplastin time. increased 

fibrin ogcn levels). 

Dermal NOA EL = 1000 mg/kg/day: 

LOA EL = not establ ished. 

870.3700a 4553 1908. 45651706 ( 1995); Maternal NOAEL = 150 mg/kg/day: 

LOAEL = 500 mg/kg/day based on signs of 

Prenatal Developmental in 0. 50, 150. 500. 750 mg/kg/day internal hemorrhage and increased incidence 

Rodents-RAT of clinical signs (pale eyes. piloercction, red 

Acceptable/Guidcl ine vaginal discharge). 

Developmental NOAEL = 500 mg/kg/day 

mg/kg/day: LOA EL = 750 mg/kg/day based 

on increased resorptions. 

Page 18 of2 1 
Aceguinocyl Human Health Risk Assessment 

Table A-2. Toxicity Profile for Acequinocyl. 

Guideline No.; 

Study Type 

870.3700b 

Prenata l Developmental in 

Non rodents-RABBIT 

870.3800 

Two-Generation 

Reproduction and FertilityRA T 

870.4100b 

Chronic Toxicit)-DOG 

870.4300 

Chronic/ CarcinogenicityMOUSE 

870.4300 

Chronic/ 

Carcinogenicity-RAT 

870.5100 

Gene Mutation 

870.5300 

Gene Mutation 

MRID (year); Doses; Classification 

-15531907, 45651705 ( 1995): 

0. 30. 60. 120 mg/kg/day 

Acceptable/Guidel ine 

4553 1909 (1997): 

0. I 00. 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 

4553 1910 ( 1996): 

0. 5. 20. 80. 320 mg/kg/day 

Acceptable/Guideline 

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 

-155319 12 ( 1997): 

0. 50. 200. 800. or 1600 ppm: 

M: 0. 2.25. 9.02. 36.41. 7-1.00 mg/kg/day 

F: 0. 2.92. 11.61. -16.2. 93.56 mg/kg/day 

Acceptable/Guideline 

45435 10 I ( 1998): 

19.5, 39.1 , 78.1. 156. 3 13. 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 

-15435102 ( 1998): 

5-7 doses ranging from I 0-320 pg/mL 

Acceptable/Guideline 

Page 19 of2 I 

0 431305 

Results 

Maternal NOAEL = 60 mg/kg/day; LOAEL 

= 120 mg/kg/day based on treatment-related 

c linical signs leading to premature sacrifice 

(hcmaturia, reduced feca l outpuL body 

weight loss. and reduced food consumption) 

and gross necropsy findings (pale lungs and 

liver. hemorrhaging uterus, tluid in the 

cecum. fur in the stomach. blood stained 

vaginal opening. blood-stained urinary 

bladder contcnLSlurinc, and hair loss). 

Developmental NOA EL= 60 mg/kg/day; 

LOAEL = 120 mg/kg/day based upon 

increased number of complete resorptions. 

Parental NOAEL (M/F): 7.3/8.7 mg/kg/day: 

LOAEL (M/F) = 58.9/69.2 based on 

increased incidences of hemorrhagic effects 

in F1 males. 

Offspring OAEL (MJF): 7.3/8.7 

mg/kg/day: LOA EL (M/f) = 58.9/69.2 

based on hemorrhagic effects. swollen body 

pans. protruding eyes. clinical signs. delays 

in pupil development and increased 

mortality post weaning. 

Reproductive NOA EL (M/F): 124/ 136 

mg/kg/day: LOA EL (M/F) = not 

established. 

NOAEL (M/F) = 80180 mg/kg/day. 

LOA EL (NVF) = 320/320 mg/kg/day based 

on premature sacrifice (inappetence. bodyweight loss). 

OAEL (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 innammatory cells in 

liver). 

NOAEL (M/ F) = 2.25/46.20 mg/kg/day 

LOAEL (Nl/F) = 9.02/93.56 mg/kg/day 

based on enlarged eyeballs in male and 

female rats (coagulopathy). 

There was no evidence of induced mutant 

colonies over background. 

There was no clear evidence ofbiologicallysignificant induction of mutant colonies over 

background. 
Acequinocvl Human Health Risk Assessment 0431305 

Table A-2. Toxicity Profile fo r Accquinocyl. 

Guideline No.; 

Study Ty pe MRJD (year); Doses; Classification Res ults 

870.5375 45435103 ( 1998): There was no evidence of chromosome 

aberrations induced over background. 

Chromosome Aberration 0. 150, 300, 600. or 1200 μg/m I, 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-

mlX. 

Acceptable/Guideline 

870.5395 45435104 (1993): There was no statistically significant 

increase in the frequency ofmicronucleatcd 

Mammalian Erythrocyte 0. 1250. 2500. or 5000 mg/kg body weight polychromatic erythrocytes in mouse bone 

Micronucleus Test in marrow at any dose or harvest time. 

MICE Acceotable/Guideline 

870.7485 45435105. 45531913 ( 1997): Acequinocyl exhibits marg inal absorption. 

relatively rapid and complete excretion 

Metabolism-RAT Single oral doses of 10 or 500 mg/kg (phenyl primarily via the bile and feces. and 

label) or 10 mg/kg (dodccyl label). and 14- undergoes nearly complete metabolism to 

day repeated 10 mg/kg dose (phenyl label). hydrolysis products and a glucuronide 

conjugate. There was no evidence for 

Acceptable/Guideline selective tissue accumulation or 

sequestration of 2023 (acequinocyl) or its 

metabol ites in rats. 

870.7600 45435 106(2000): Percent of dose absorbed decreased with 

exposure concentration indicating that 

Dermal Penetration-RAT 0. 0.001. 0.01. 0. 1. 1.0 mg/cm2 saturation of absorption at/or about the high 

dose. Absorption at 168 hours was 12.23%. 

Acceptable/Guideline 19.75%. and 14. 77% for the 0.1 , 0.0 I. and 

0.00 I mg/cm2 dose groups. resoectivelv. 

Page 20 of2 I 
Aceguinocvl Human Health Risk Assessment 0431305 

Appendix B: Greenhouse Ornamental Study Summary. 

Dissipation of Dislodgeab/e Foliar Residues of Acequinocy/ and its Metabolite Following 

Application of Kanemite SC to Chrysanthemum in the Greenhouse (MRJD No.: -15820401). 

(HED Review: Memo, M. Dow, 10-JUN-2003, 0 290655) 

This study was designed to collect data to evaluate DFR dissipation for the compound 

acequinocyl from Chrysanthemum foliage grown in a greenhouse at one site in 

California. Primary review of the study was conducted by Versar Inc., 13-DEC-2002. 

The secondary review was conducted by HED on June 10, 2003 (0290655). 

Kanemite1Y SC is a soluble concentrate that contains 15.0 % acequinocyl as the active 

ingredient. The study evaluated acequinocyl and its metabolite acequinocyl-OH. 

Kanemite® SC was applied with a backpack sprayer at 0.30 lb ai/A. Two applications 

were made with a 21 -day application interval. 

Study results indicate that DFR residues did not drop below the limit of quantification by 

35 days after treatment. The maximum average DFR value occurred immediately after 

the second application for both analytes (0.60 ± 0. 13 μg/cm2 for acequinocyl and 0.021 ± 

0.004 μg/cm2 for acequinocyl-OH). Assuming first-order kinetics, HEO modeled 

dissipation rates and estimated a half-life of 17.6 days for aceq uinocyl and acequinocylOH residues. 

It should be noted that the low R2 values obtained from the study data suggest either that 

the test product does not dissipate according to first-order kinetics, or that the data 

obtained is not accurate. For this reason, HED used the measured OFR value instead of 

the predicted value in the assessment of greenhouse cucumbers. so as not to 

underestimate post-application exposure risks. 

S umma ry o f DFR Values a nd R egression Ana lysis Results fo r T reated C hrysanthem ums in G reen houses 

with Aceq uinocyl (MRID# 454286-19). 

I nput/Paramcter Site: California 

Combi11erl Acel1uilloc11/ + Acetmi11oc)'/-OH 

Application Rate (lb ai/A)" 0.3 lb ai//\ Study Target Rate= 0.3 lb ai/A 

pray Volume (GPA) 40.7 and 39.5 gallons per acre. respectively for !St and 2 nd 

aoolieations 

Measured Average Day 0 Residue (u!!./cm1) 0.617 

Predicted Day 0 Residue ~1 j?/c ) b 0.346 

Slooe -0.0394 

I lalf-life (days) 17.6 

Rz 0.417 

a. rhc appltca11on was conducted us111g backpack sprayer equipment. 

b. Regressions are based on data collected after second application. 

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