### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON

, D

. C

. 20460

O FFI C E OF C llEM I CA L SAFE T Y**A~D** POL L lIT I ON PR EVEN T I O N



### MEM O RAN D UM

D a t e : 27 -MA Y-20 1 5



### SU B JECT: Ace quin o c y l. Human He a lth Assess m ent Scoping D ocu m e nt in Support of Re gistration Re v i ew

.



### PC Co d e : 006329 

### D e ci s i o n N o .: 497220 

### Pe ti tio n No.: N I A D P 

### B a rcod e : D423850 

### R eg i s tr at i o n No.: N I A 

### R eg ul a t ory A cti o n: Re g i stratio n Review Sco pi ng D ocume n t 

### C a se No .: 7621 

### R i sk Assess m e nt Ty p e : N / A TXR No. : N I A 

### CAS No. : 57960 -1 9-7 40 

### C FR: § 18 0.599 

### MRID No

. : N I A



## Sara h J. 

## Levy
, Chemist 

# M n ti I /Ml./ /) 

# k

A nwa r 

### Y. Dunbar

, P h.D

., Pharm fog 

## t/ " '

# ~ ' 

## l/_ George F. Kramer
, Ph.D., Se ni or Che mi s t

## ;;?**~** ; 

# /J

Jam es S. Mi l l e r , E n vironmenta l H ea lth Scientis t

## /.·~**4 //Jvt.-~**  Ri sk Assessment Bran c h I (RAB I)

- 

### F RO M :

Health Effects Division ( H E D
, 7509 P ) 

# ///J**~** 

# A;Jf---

TH RO UGH : Thurs t on Morto n , Acting Branch C hi ef (

## 1 

# ,,,v-<Yj

RABl/HED (7509 P )



### T O: Dana Friedman

, Acting Team Leader / Cathryn Britt o n , Team Leader M a r ga r et H at h away, C h em i ca l R ev i ew Manager Pesticide Re-Evaluation Division ( PRD) (7508 P )

Attached i s H ED ' s human h eal th r i sk assessment scop in g do cu m e nt fo r acequinocyl to s upp ort Regi s tration Review.

Pa g e I of24

### Ace9uinocyl Registration R ev

i_

ew H

_ uman He alt h**Assess nt** **Sc~ing Document**  

## T a bl e of Cont e nt s
Exec uti ve Sun11nary

........................................................................................................................ 3 

### 1 .0 lntr o duction

............ . ...... . ........ . ......... .. .. ... ...... . ... ... ...... . ... ..... .. .. .. ..... ................ .. .. .... ... .... .. ......... 5 

### 2.0 Ha zard Characterization / Assessme nt

.............. . ............................. ... ..................... .. ..... .. .... .. ... 5 

### 3.0 Re sidue Chemistry

........................................................................................................ .. . ... .. ... 6 4.0 Di etary Exposure

.. .. .............. . .. . ........ .. ........... . . .. ........ .. ............................................................ 6 5.0 Residential Exposure

...................... .................... ... .......... . ....................................................... 7 6.0 Aggregate- Ri sk Assessment

.................................................................................................... 8 7 .0 Occupational Exposu r e

............................................................................... ... .... .. . .............. .. ... 8 8.0 Public Health and Pesticide Epidemiology Data

. .. ... .. ....... . ..................................................... 9 

### 9.0 Tolerance Assess m e nt a nd I nt e rnation a l H a rm on i zat i on

...................................................... 

### 10
I 

### 0.0 Env i ronmenta l Justice

................................................... ... ..... .. ......... ... .... ... .... .. ......... ..... .. .. .. 

### 10
11. 0 Cumulative

... ..................... ... .... ... ..... .. ... .. ...... . ........... .. .......... ... ........ ...... . .. ......... ..... .. ..... ... . .. l 0 

### 1 2 .0 I-lu1nanStudies

.............. . ... .. ..... .. ...... .. . . ... . ....... .. ........... .. .. ..... .... .... .. ..... .. .............................. 

### lO 

### 1 3.0 Risk Assessment Updates

, Dat a Deficiencies

, and L abel R evisions

................................... 

### 11
14.0 Reference s

............ . . .. .... ... ......... ... ......................... . ......................................... ..... .. . ........ . ..... 12 Attachment 

### 1: C h em ic al Id en tit y Table

. ..... .. ... .. .. ........ . .. .... . ............. . .... ...... .. .. .... .. .. 

### 14 Attachment 2: Acequinocyl Acute

, Subchronic

, Chron ic

, a nd Other Toxicity Profile

............... 

### 15 Attachment 3: Acequinocyl End p oint Selection Table (from 2011 Risk Assessment)

............... 18 Attachment 4: Summary of Re g ist ered Uses

... ... .. ... ..... .. ...... . ... . .......... ...... . .. ..... .. ....... . ..... . .......... 

### 20 Attac hm e nt 5 : Acequinocyl IRLS S he e t.

........... .. . . .... .. ... .. ...... . ........... . ........................................ 23

P age 2 of24Acequinocyl Registration Review Human Health Assessment Scoping Document

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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 (R ACs) 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, scho ols, 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 s ucculent s oybean v egetable; s ucculent s helled b eans; c owpea f orage;

c aneberry s ubgroup 13

- 07A; m elon s ubgroup 9A; c ucumber (greenhouse and field); c herry; l ow

g rowing b erry s ubgroup 13

- 07G; small fruit vine climbing

, except fuzzy kiwifruit

, subgroup 13

- 07F ; fruiting vegetables crop group 8 ( tomatoes & peppers); edible

- p odded beans; hops; o kra ; and tree nut crop group 14. Note that the cucumber and caneberry field trial data were a joint

review 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 Sa fety F actors for acequinocyl d uring R egistration R ev iew.

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 o n 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 (pri mary 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 un refined c hronic 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

- 201 1 ; D 389990 ). HED notes that the 201 1 chronic dietary assessment di d 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 fromAcequinocyl Registration Review Human Health Assessment Scoping Document

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Page 4 of 24 

### the Pesticide Root Zone Model/Exposure Analys is Modeling System (PRZM/EXAMS) model were used in the chronic dietary

- exposure database

. Furthermore, the 201 1 chronic dietary assessment did not utilize the latest dietary exposure model or consumption database. Since this dietary assessment, HED adopt ed 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 residenti al 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 chan ges for body

- weight assumption s ; an updated residenti al 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 Registrat ion 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 dietary

exposure 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 re gistered 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 occup ational 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

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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, flor al, 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 LifeSc ience 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 Cha racterization/Assessment

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

, the following data gaps were identifie d: (1) an immunotoxicity study, (2) an acute neurotoxicity study, (3) a subchronic neurotoxicity study and (4) a subchronic inhalation toxicity study. T he 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, H ASPOC 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, metabo lism, 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 (2 4 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 ac cumulation 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 perivascul ar 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 anim als 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, offsprin g 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 conc ern 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 hum ans. Acequinocyl has low acute toxicity via the oral, dermal, and inhalation routes (ToxicityAcequinocyl Registration Review Human Health Assessment Scoping Document

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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 Sa fety F actors for acequinocyl d uring R egistration R ev iew.

3.0 Residue Chemistry

Tolerances are currently established under 40 CFR §180.599(a) for the combined residues of
acequ inocyl 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 o il), 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 o n 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 is to be included as well. Adequate analytical enforcement methods are available. Additionally, adequate field trial, processing, and storage stability data are available. HED note s 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 sup port the current registrations. No additional data are required at this time.

4.0 Dietary Exposure

A c hronic dietary (food + drinking water) exposure and risk assessment w as conducted for the 201 1 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 co nducted 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 (a s residues were reduced in both grape juice (<0.02x) an d 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

- SEP

2011; 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 concer n to HED [i.e., <100% chronic population

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

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Page 7 of 24 

### utilizes 1 3% of the cPAD. The chronic dietary risk estimate for the highest reported exposed population subgroup, all children 1

- 2 year s old), is 55 % of the cPAD.

HED note s that the 201 1 chronic dietary assessment did not utilize the latest dietary exposure model or consumption database. Since this dietary assessment, HED adopted use of DEEM

FCID Version 3.16, which uses food consumption data from the USDA NHANES/WWEIA
survey from 2003 t hrough 2008. Furthermore, the asses sment did not incorporate ground water EDWCs modeled using PRZM

- GW or SWCC . The impacts of using th e s e model s 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 potenti al 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 th e 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 Residentia l 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 eva luated 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 Asses sment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification of indirect non

occupational exposure to drift.

In terms of volatilization, the agency has developed a Volatilization Screening Tool a nd a subsequent Volatilization Screening AnalysisAcequinocyl Registration Review Human Health Assessment Scoping Document

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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 analysi s, 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 ava ilable 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

- applica tion 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 informa tion provided on registered labels (e.g., two applications/season with a retreatment interval ( RTI ) of 14 and 21 days). The proposed pre

harvest intervals (PHIs) range from 1 to 7 days. The restricted entry interval ( REI ) specified on the label is 12 hou rs. 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 s hoes 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 mostAcequinocyl Registration Review Human Health Assessment Scoping Document

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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 a n 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 i nhalation 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 pos t

emergence as a foliar spray. Post

- application exposure is expected to be short

- and intermediate

term 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 handl er 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 Pesticid e Epidemiology Data

The Agency has reviewed the available incident data for acequinocyl (Memo, S. Recore and E. Evans
, 10

- FEB

- 201 5 ; D 425575 ) and concluded that because there were no incident cases reported f or 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

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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 Att achment 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 Low

Income Populations a



### . ” The OPP typically considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessmen ts, 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 risk s 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 mechani sm 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, theref ore, 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 su ch 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/.

1 2

. 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/complia nce/environmentaljustice/resources/policy/exec_order_12898.pdfAcequinocyl Registration Review Human Health Assessment Scoping Document

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Page 11 of 24 

### any of them was either fundamentally unethical or significantly deficient rela tive 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 continu ed reliance on these studies.

1 3 .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 volati lization 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

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Page 12 of 24 

### 1 4 .0 References

Memor anda 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

- JAN

2008 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 D 380302 25

- AUG

- 2010 Acequinocyl ; Response to the Health Effects Division (HED) Review of 25

- JUN

- 2008 (M emoranda, 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 Edible

Podded 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 Climbi ng, 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 Fuz zy 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

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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) R DI: RAB1 ( 1 8

- FEB

- 20 1 5 ) , D. Vogel ( 27

- FEB

- 20 1 5 ) S. Levy :S1095 3 :PY

- S:(703)305

- 07 83 :7509P:RAB1Acequinocyl Registration Review Human Health Assessment Scoping Document

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Page 14 of 24 

### Attachment 1: Chemical Identity Table

.

Table A .1. Test Compound Nomenclature Acequinocyl

. Compound

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

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

- APR

2004, D298191; MRID 45854501 pH 5.19 (2% suspension in 0.1% NaCl) 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 (pK a ) No acid or base properties between pH 2 and pH 12 Octanol/water partition coefficient Log(K OW ) 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

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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 LD 50 >5000 mg/kg IV

870.1200 (81

- 2) Acute Dermal 45435012 LD 50 >2000 mg/kg III

870.1300 (81

- 3) Acute Inhalation 45435013 LC 50 >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. 870.37 00a 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

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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 findin gs (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 increas ed 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 develo pment 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 non

neoplastic 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 ove r background.Acequinocyl Registration Review Human Health Assessment Scoping Document

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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 biologically

significant 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/k g/ 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 hy drolysis 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 i mmunotoxicity 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

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Page 18 of 24 

### Attachment 3: Acequinocyl Endpoint Selection Table (from 201 1 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 UF A = 10 X

UF H =10 X 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 pigment ed cells and perivascular inflammatory cells in liver).

Short

- term (1

- 30 days) incidental oral NOAEL = 60

mg/kg/day UF A = 10 X

UF H =10 X 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

- s tained urinary bladder contents/urine).

Intermediate

- term (1

- 6 months) incidental oral NOAEL = 16

mg/kg/day UF A = 10 X

UF H = 10 X LOC (residential) =

MOE <100 Subchronic toxicity in mice;

LOAEL = 81 mg/kg/day based on hepatocyte vacuolization.

Short

- (1

- 30 days) and Intermediate

term (1

- 6 months) Dermal Dermal

NOAEL = 200 mg/kg/day UF A = 10 X

UF H = 10 X 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%) UF A = 10 X

UF H = 10 X 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).

Int ermediate

- (1

- 6 months) Term Inhalation Oral NOAEL

= 16 mg/kg/day (inhalation absorption rate=100%) UF A = 10 X

UF H = 10 X 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 d eparture (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 humanAcequinocyl Registration Review Human Health Assessment Scoping Document

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Page 19 of 24 exposures. UF = uncertainty factor, UF A = extrapolation from animal to human (interspecies), UF H = 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

- eff ect level, RfD = reference dose (a = acute, c = chronic), PAD = population

- adjusted dose (c = chronic), MOE = margin of exposure, LOC = level of concern, N/A = n ot a pplicable

.
Table C.2. Summary of Toxicological Doses and Endpoints for Acequinocyl for Us e 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 Intermediate

term (1

- 6 months) Dermal Dermal

NOAEL = 200 mg/kg/day UF A = 10 X

UF H =10 X 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%) UF A = 10 X

UF H = 10 X 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 l iver, 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%) UF A = 10 X

UF H = 10 X 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 d eparture (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, UF A = extrapolation from animal to human (interspecies), UF H = 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 = n ot a pplicable

.Acequinocyl Registration Review Human Health Assessment Scoping Document

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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

Limitations 1

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

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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

Limitations 1

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, Hone ydew 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 0.1 2 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, Bl ack Walnut, and English Walnut) and PistachiosAcequinocyl Registration Review Human Health Assessment Scoping Document

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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

Limitations 1

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. 1 3 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

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Page 23 of 24 

### Attachment 5: Acequinocyl IRLS Sheet.

Table E .1. Summary of U.S. Tolerances and International MRLs. U.S. Canada Mexico 1 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 Res idue Limit (mg/kg) Commodity U.S. Canada Mexico 1 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 0.15Acequinocyl Registration Review Human Health Assessment Scoping Document

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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 nu ts, 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, roselle s, 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.