### UN ITED ST ATES ENVIRONMENT AL PROT EC TIO N AGENCY WASHINGT ON , D. C. 20460
OFFICE OF C H EM I CA L SA F ETY AN D POLL UTION PREVENTION



### MEM ORA N DUM Date: S ubj ect: 22 -MAR- 2016 Ace quin ocy l
. Human H ealth Risk Assessment for the Propo sed Increase in the Permanent To lerance for Re s idues in / on Hop s. P C Co d e: 006329 DP No.: 0431305 Deci s io n No.: 50500 l R eg ist r a tion No.: NA P e titi o n No.: 5F8364 R eg ulat o r y Ac ti o n : Amend an Established Toleranc e Ri sk Assess m e n t Type: Single Chemical/Aggregate Case No.: 762 l T XR No.: NA CAS No.: 57960 -19- 7 MRID No.: NA 40 CF R : § 180.599

# =~~~---**---­** George F. Kramer, Ph.D ., Se nior

## mi**st ~**  

# fPt
Anwar Y. Dunbar , Ph.D., Ph armaco logitf::-t

## ~ 

# %::_. V Jam es S. Miller , Env ironm ental Scientist 

# r;;___} ) )**~** Ri sk Assessment Branch l (RA B I ) 

### FROM:

H ea lth Effec ts Division ( H ED) (7509 P) 

### THROUGH : C harle s W. Smi th III , Branch Ch ief C

# ~ RAB l / HED (7509 P) 

### TO : Andrew Ertman/Venu s Eagle, RM I Registration Division (RD) (7505P) T he HED of the Office of Pesticide P rograms (O PP) is charged wi th estimating the risk to human health from exposure to pe s ticides. The RD of OPP has reque s t ed that HED evaluate hazard and exposure data and conduct dietary , occupational / res i dential , and aggregate exposure assessment s . as needed , to estimate th e r is k to human health that will result from the registered uses of acequinocyl and the propo se d increase of the ex isting tolerance for residues inion hops from 4.0 ppm to 15.0 ppm. A summary of the estimated human health ri s ks resulting from the registered and proposed use s for acequinocyl are provid ed in this docum e nt. 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 prov ided by James Mi ll er (RAB I), and the drinking water exposur e assessment was provided by Michael Lowit of the Environmental Fate and Effects Di v i sion (E FED ). 

### NOT E : A human health risk scoping document for acequinoc y l to support Registration Review was completed on 27 -M AY-2015 by HED (Me mo , S. Le vy 

### er al., 0423850 )
. J n the present memo , dietary , existin g re s idential, and aggregate risks were re-evaluated based on the proposed increase of the exis tin g to l erance for r esidues in/on hop s . Page l of2 IAcequinocyl Human H ealth Risk Assessment 0431305 

### TABLE OF CONTENTS 1.0 EXECUTIVE SUMMARY
..................................................................................................... 3 2.0 HED Recom1nendations
.... ... ..................................................................................... . ......... 5 

### 2.1 Data Deficiencies/ Conditions of Registratio n ........................................................ 5 

### 2.2 Tolerance Considerations
............... . ... .. ................................................................... 5 3
. 0 Introduction
. .. .. . .. .. ... . ... ... . ....... ............................................................................................. 6 3. 1 C hem ical Ide ntity .............................. ....... ....... .. .. .. .. .............. . .. .. .. .... .. . .. . .. . .. . . .......... 6 3.2 Physical/C hemical Characteristics
. .. ... .... . ........... ................. ......... .......................... 6 3.3 P estic ide Use Pattern
............................................................................................... 7 3.4 Anticipated Exposure Path ways ............................................................................. 7 3.5 Consideration of Environm ental Justice
................................................................. 7 4
. 0 Hazard Characterizat ion and D ose R esponse Assessment
.................. ............................... 8 4. 1 Summary of Tox ico log ical Effects
......................................................................... 8 4.2 Safety Factor for Infants and C hildren (FQPA Safety Factor)
............................... 9 4.3 Toxicity Endpo int and POD Selections
......... ............. ............. ........ ................... .... 9 

### 5.0 D ietary Exposure and Risk Assessment
......... .. ................................................................ 

### 10 5. 1 Dietary Exposure/Risk P athway
........................................................................... 11 5
. 1

. 

### J Residue Profile
.......................... .. ... .. ......................................................... 11 5. l'.2 \Vater**~xpos ur** **e/Risk** Pathway
.. ................. ............. ........... ................ ...... 11

### 5.**~3** ·-

### Di**eta Ex.po~ure**  Analyses
....................................................................... 1 2 5.1.4

### l;**onic ,Oiet~**  Exposure Analysis
.......................................................... 

### 12 6.0 Residential (Non-Occupational) Exposure/Risk C haracterizat ion
...................... .... ......... 13 6. 1 Short-term Residential Handler Ri sk
.................................................................... 1 3 6.2 Short-term Residential Post-app lication Ri sk
....................................................... 14 6.3 Spray Dri ft
.......... ... .. .. .................. .. ... ... .. .. .................... .. . .. .. .. ................................ 1 5 6.4 Residential Bystander Po st-app lication Inhalation Expos ure ............................... 1 5 7 .0 Aggregate Exposure/ Risk Characterization
... . .................................................................. 15 7. I Ac ute Aggregate Risk
............................................................................... . ........... 15 7 .2 Short-Term Aggregate Risk
............... . .................................................................. 16 7 .3 Intermediate-Term Aggregate Risk
... .. ... .. ... .............. .. ...................... ..... ......... ..... 16 7.4 Long -T e1111 Aggregate Ri sk
....................................... . ....................... .................. . 

### J 6 7 .5 Cancer Ri sk
...... .. .. .. .............................................. ............. .................................... 16 8.0 Cumulati ve Ri sk Character izatio n/ Assessment
........................ .. ...................................... 1 6 9.0 Occupational Exposure/ Risk Pathway
... ..................... ............... ............. .......................... 17 A pp e ndix A: Toxicity Profile Tables
............................................ . ... . .......................................... 18 Append i x B: Greenhouse Ornamental Study S ummary .. .................... .. ................... . .. ......... ....... 2 1

Pa ge 2 of2 1Acequinoc v l Human H ealth R i s k Assessment 04 3 1305 

### 1.0 EXECUT I VE SUMMARY Acequinocyl [2-(acetylo xy) -3-dodecyl-1 ,4 -naphtha le nedion e)] is a quinoline-type miticide that is currently reg i s te red for th e u se in the U. S
. on a number of raw agricultural commodities (RACs) for the co ntrol of various p hyto phagou s mite spec ies . Ace quin ocy l i s also registe red for use in/on greenhouses , s h a d e houses, ornamental , floral , foliage , nursery crops , land scap e ornamentals in and around res id e nces , bu s in esses , public property , sc hool s , interiorscapes, and other n o n-production areas b y commercial applicators and ho meowners. Acequinocyl i s currently reg i s tered by Arysta LifeScienc e N o rth America Co rp orat ion as a 15 % so lubl e concentrate (SC) formulation. Arysta is requesting to increase the exi sti ng to lerance for resid ues of acequ i nocyl and its metabolite , 2-dodec yl

- 3- hydroxy -1 ,4-naphth oqui none , expressed as acequinocyl eq ui v alent s , in/on hop s from 4.0 ppm to 15.0 ppm. The purpose of th e amended toleranc e is to harm onize th e value with th e establ ished m ax imum res idu e li mit ( MRL) in the European U nion (EU)
. Th e dome st ic res idue data for ho p s we re previo u s ly s ubmitt e d and rev iewed und e r PP # 9E7598 (Mem o. S. Levy , 25

- AUG-20 10; 036910 0). 

### Ha zard Assessm ent: Th e toxicology datab ase is complete
. Fo r all s peci es, dur ation s and route s of exposure (oral and d e rm a l), the primary effects observed a re indicative of toxicity to the li ve r ( hepatoc y t e vac uolization , brown pigmente d cells and peri vasc ular inflammato 1 :y ce ll s in liver) and h ematopo ietic system ( he morrhage , increased clottin g factor times and in c rease d platelet coun t s). In the rat and rabb it developmental t ox ic ity studie s, there was n o evidence of increased quantit ati ve or qualitative feta l s u sce ptibilit y , w ith the materna l effec t s (cl ini ca l sig n s and gross necropsy findings) occurring at s imilar or lower doses than feta l re so rpti o n s . In the rat twogenerat io n reproductiv e t ox ic ity s tudy , off s prin g e ffects at th e mid- and high-d oses consisted of swo ll en body parts , protrudin g eyes, clini ca l s ig n s, dela ys in pupil development , a nd increase d mort a l ity occ urring mainly after w eanin g , howeve r these effects we re observed at the same doses as parental effects , and a clear NOAE L was established whic h is being u se d in end p oi nt s el ect ion . There were no effects on reprodu ct ive parameters. There was no evide nce of carcinogenicity , ge no tox ic ity , o r mutagenici ty. In an acute neu roto x icity st ud y , there were no effect s up to the limi t do se (2000 mg/kg). In a g uideline inununotox icit y s tudy , th e re were no effects up to the highest dose tested (45 m g/kg / day). Acequinocyl has low acute to x icity via th e o ral , dermal , a nd inh alati on routes (Toxicity Catego rie s Ill & IV ). No ocular or dermal irritation was noted. Aceq uin ocyl is not a dermal sens iti ze r. 

### Die tar y Expos ur e (Food + Drinking Water): A chronic agg r egate dietary (food + drinkin g w ater) e xpo s ure a nd risk assessme nt was cond ucted fo r acequinocy l using th e Di e tary Expo s ure Evaluati o n Mode l (D EEM-FC ID , Version 3. 1 6) whic h u ses 2003 -2008 food consumption data from the U.S
. Department of Ag riculture ' s (US DA 's) Nati o n a l Hea lth and N utriti o n E xam in at io n S u rvey , What We Eat in A merica, (NHANES/ WWE IA). Tol e ran ce -l eve l residues , DEEM ve r. 7.76 default processing factors , and 100 percent crop treated (%C T ) data were used in the c hro nic dietary assessment. An acute dietary assessment was not conducted for acequinocy l because an e ndp o int of conc e rn attributabl e to a s ingle do s e was n o t identified ; therefore , a n acute refere nce do se (aRID ) was not es tabli s he d
. A cancer dietary assessment was not conduc ted because acequinocy l was clas s ifi ed as no t like ly to be carc in ogen ic to human s . The chron ic di etary ri sk as s essment s ho ws that the chro ni c dietary risk es tima tes do not exceed HED ' s leve l of conce rn [(LOC); i.e. , < 100% of th e c hroni c population-adjusted d ose (c PAD )]. Page 3 of2 IAceguinocvl Human Health Ri s k Assessment 0431305 For the general U.S. population , the exposu re fo r food + drinking water utili zed 14% of the cPAD. The chronic dietary risk estimate fo r the highest expose d population subgroup, children 1- 2 years old, i s 60% of the cPAD
. 

### R esidential Exposure Assessment: The re are no proposed r es id e nti a l u ses assoc i ated with the cur re nt action; howeve r , there are ex isting re s idential uses that h ave been r eassessed in this document to refl ect revisions to H E D 's 2012 Residential SOPs 1 a long w i th policy changes for body-weight assumptions. A ll residential handler and post
- application MOEs we re > 100 and are not of concern to HED (see Tabl e 6.1. l ). 

### Aggregate Exposure Assessment: Acute and cancer aggregate-risk assessments were not performed because no appropria te endpoint was avail able to determin e the aRID for the general population o r a ny population s ubgroup , and acequ in ocyl i s class ified as "No t li kely to be Carci nogenic to Hum an s ," re s pectively. In termed iate- and lon g - term agg regate assessments were not performed s ince the use pattern is not expec te d to r es ult in r es id en ti a l handler or po st
application exposure of more than 30-day duration. A chronic aggregate exposure ri sk assessment was assessed by incorporating the drinking water directly into the dietary-exposure assessment. As the chronic dietary expos ure estimates are not of concern to HED for the general U.S. population or any population subgroup , the chronic aggrega te risk is no t of concern for these populations
. An aggregate risk assessme nt was performed fo r s hort-te rm aggregate exposure (food + drinking water + r es id e ntial exposure) because th ere are ex i s tin g residential u ses . S ho rt -term agg r egate expos ures and risk es tim ates were ca l cu lated for the general U.S. popu l at i on a nd females 1 3-49 years o ld (this s ub-populati o n is the highest exposed ad ult population a nd can be considered protective of the other adult populations groups). The aggregate MOEs are > 100 , therefore, they do not exceed HED ' s LOC. 

### Occ upational Expos ur e Assessm ent: As there are no proposed or requested c han ges in the acequinocy l label associate d w ith this action , a new occupational exposure assessment has not been performed. 

### Environmental Ju sti ce Cons id e rations: Pote ntial areas of e nvironmental ju s tice co nce rn s, to the extent possible , were considered in this hum an health risk assessment, in accordance with U.S. Executive Order 12898 , ·'Federal Actions to Add ress Env i ronmental Ju stice in Minority Populations and Low- Inc ome Populations
. " http: //www.archives.gov/ federal-register /executiveorders / pdf/12898.pdf. As a part of every pesticide ri sk assessment , OPP cons iders a large variety of consumer subgroups according to well-establ ished procedures. In line wi th OP P po l icy , HED estimates ri sks to po pul at ion s ub gro up s from pe sticide expos ures that are base d on patterns of that s ubgroup's food and water consump ti on, and activities in and around th e h o me that in vo lve pesticide use in a res iden t ial sett in g. Extensive data on food consumption patterns are compi led by the USDA under N HANES ! WWEIA and are used in pesticide risk assessments for all registered food u ses 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, special i zed subgroups and exposure assess ments 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 lAceguinocyl Human Health Risk Assessment 0431305 exposures based on home use of pest icide products and assoc iated risks for adult applicators and for toddlers, youths, and adult s entering or playing on treated areas post-application are evaluated. Furth e r considerat i o n s are currently in development as OPP has comm itted resourc es and expertise to the development of specialized sof tware and models that conside r exposure to bystanders and fann workers as well as life s ty le and traditional dietary patterns among specific su b gro ups. 

### 2.0 HE D Recomme nd atio n s There are no tox ic ological, residue chemistry, or occupational/residentia l exposure issues that would preclude increasing the existing tolerance for residues of the insecticide ace quinocyl in/on hops from 4.0 ppm to 15 ppm. 

### 2.1 D a t a D efi c i enci es/Co ndi t io n s of R eg is trati on No additional data arc required to support th e proposed actio n. 

### 2.2 To ler a n ce Cons i de r ati o n s 2.2. 1 E n fo r ceme n t A n a ly ti ca l Me th od There are adequate residue an a lytical method s fo r enfo rcing tolerances for acequ inoc yl re sidues of concern inion the reg iste red plant commoditi es . The se method s includ e two highperfonnance liquid chromatography method s with tandem mass - spectroscopy detection ( HPLC/MS/MS) for determining residues in/o n fruit and nut commodities (Mo rse 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 chro matograph y (GPC) and/or s ili ca-gel solid-p ha se extraction (SPE). 

### 2.2.2 Reco mm e nd e d To ler a n ces

Tab le 2.2.2. T o lera n ce S umm ary for Aceq uin ocy l
. 

# IPr opose d Tolerance 

# I Recommended 

# I Comments; Correct Commodity Commod ity (ppm) To lerance (ppm) Definitio n 40 CFR § 1 80.599(a) Hop , dried cones 

## I 15.0 

## I 15 

## I 2
. 2 .3 Revis io n s to Pe titi o n e d -Fo r T o le r a n ces HED is recommendin g a cha nge in the numerical expression of the hop , dried cones tolerance va lue in order to co nform to current HED policy on s ig nificant figure s . 

### 2.2.4 Intern ati o n a l H a rm oniza tion Residue definitions and MRLs for acequinocyl have not been established by Codex
. The U.S. and Canadian residue definitions are harmonized. There is currentl y no estab li shed Canadian MRL for acequ inocyl 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 l eve ls will be harmoni zed by this action. Page 5 of2 lAceguinocvl H uman Health Ri sk Assessment 0 431305


### 2.3 Lab e l Reco mm e nd a t io n s Th e re are n o p roposed o r requeste d c h anges in th e aceq uin o c yl labe l assoc ia t ed w i th thi s ac ti o n. 

### 3
. 0 In t rodu c ti o n Acequ inocy l is a quinoline-type miticide that is currently r egistered for the use to contro l various phytophagous mite species i n the U.S. on a number of RACs
. Tolerances are currently estab l ished under 40 CFR 

### § l 80.599(a) for the combined residues of acequi nocyl and its metabol i te , 2

- dodecyl-3-hydroxy

- 1,4-naphthoquinone , expressed as acequinocy l equ ivale nts , in/on a num be r of p la nt and li vestock commodit ies. Tole ra nces for pl ant commo di t ies range fro m 0.02 p p m (tree nuts a nd pistach ios) to 30 ppm (c i t ru s o il ), and to lera nces fo r l ives tock co mm o d iti es are es tab li shed at 0.02 ppm in the fa t a nd li ve r o f cattl e, goa t , ho rse, and s h ee p . 

### 3. 1 C h em i c a l Id e n t i ty Tab le 3 .1. 1. N om e n cla t u r e o f T est Comp o un d and Me ta b oli tes . 0 

# «XCH,(CH,J,.CH , I OCOCH 3 Compoun d 0 Common name Acequinocy l Company experimental names TM-41301 or AKD-2023 I U PAC name 3

-dodecy l-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 product s/E P Kanemite® 15 SC ( 1.25 lb ai/gal; EPA Reg. No. 66330-38) Compound 0 

# «XCH,(CH,),.CH, I OH 0 Commo n name Acequinocyl-OH Company experimental name s RI I U PAC name 2-dodecyl-3-hydroxy-1.4-napthoquino n e CAS name 2-dodecyl-3-hydroxy-1.4-naphthalenedione CAS# 57960-31-3 

### 3.2 P h ys i ca l/C h e mi ca l C h a r acter is ti cs This info rm ation is provided in t h e human hea lth risk assessme nt scop i ng doc u me nt fo r acequinocyl to support Registration Review , completed on 27 -MA Y-2015 by H ED (Memo, S. Levy 

### et al. , D423850).

Page 6 of21Aceguinocyl Hum an H ealth Risk A ss e s sment 0431305 

### 3
. 3 P es ticid e Use P atte rn Kan e mite® 15 SC Miticide (E P A Reg. No. 66330-38) , a 1.25 lb/ ga l SC fo rmulation of ace quinoc y l is currently reg is te red for use on hops. Th e U.S
. and EU uses a re s ummar i zed in Tabl e 3.3.1.

T a bl e 3
. 3
. 1. S umm ar y o f Direc ti o n s for Use of Accq uin ocy l. Applic. Timing , Formulation Applic. Max
. No. Max. Seasonal PHI Us e Directions and Ty pe , and [EPA R eg . Rate Applic
. per Applic. Rate ( day s) Limi tations ' Equip. No.) (lb a i / A) Sea s on ( l b a i/ A) H

op s ( U.S. ) Postemergence , 1. 2 5 l b/gal Minimum spray volume foliar S C 0.3 2 0.6 7 of 100 gal/A; minimum G rou nd only [66330-38] R T l of21 days. H

o ps (EU) Postemergence , 1 .25 l b

/ gal folia r 0.67 I 0
. 67 21 Ground only S C
1 RTI = retreatment interval. 

### 3.4 Anticip a t e d Ex p os ure Pathw ays RD has requ es ted an assess ment of human hea lth ri s k to s upport th e proposed increase in the ex is tin g tolerance for res id ues of aceq uinocy l in / on hops. H umans may be ex p ose d to aceq uinoc y l in food and drinking water s ince acequinocyl may be applied direc t ly to growing cro p s , and application s m ay re su lt in acequinocyl reac hing s urf ace and gro und wa ter sources of drin ki ng water. The re are reg i s te red re s id e ntia l uses of aceq uinoc y l ; therefore , human ex p osure in residential o r non-occupational settings is a lso expected
. In an occupati ona l sett ing , applicato rs m ay be exposed w hile handlin g the pesticide prior to app li cation , as we ll as during applicatio n. T here is also a potential for post-application expos ure for wo rk ers re-entering treated fie ld s . Th is ri s k asses s ment co n s iders a ll of the afo re me n tion e d exposure pathways base d on the proposed i ncre ase d to le ran ce for residue s of ac eq uinoc y l and considers the ex is tin g registered u ses as we ll for the dietary and residential expos ure assessments. 

### 3.5 C on s id er ati o n o f E n v ironm ent a l Ju s ti ce Po te nti a l areas of env ironm e ntal justice concerns , to the extent possible , we re co n s id ered in thi s human health risk assessment, in accordance with U.S. Exec uti ve Order I 289 8 , " F ede ral Ac tion s t o Address Environme nta l Ju st i ce in Minority Popul at ions and Low-income Populations," ( http: //www . archive s . gov/ federal

- reg i s ter /exec ut ive - orders/ pdf/I 2898.pdf). As a part of every pesticide risk assess me nt , OPP cons ide rs a large va r ie ty of consumer s ub gro up s according to we ll- estab lished procedures. In line with OPP policy , H E D estimates risks to population subgro up s from p est ic id e expos ures that are based on patterns of t ha t subgrou p ' s food and wa te r consumpt ion , and act i vities in and around the home that involve pesticide u se in a residential setting. Exte n s ive data on food consumption patterns are co mpil ed by the USDA under the N H ANE S/WWE IA ; 2003-2008 and are u sed in pesticide risk assessments for all registered food uses of a pe s ticid e . Th ese data are analyzed and ca t ego ri zed by subgro up s based on age, season of th e yea r, ethnic gro up , and regio n of the country. Additionally, OPP is a b le to assess dietary P

age 7 of2 IAceguinocyl Human Health Ri s k Asses s ment 0431305 exposure to sma ll er. s pecialized subgroups and exposu re assessments are performed when conditi ons or circum s tances warrant. Whenever appropriate, non-dietary exposures based on home use of pesticide products and associated ri s ks for adult applicators and for toddlers , youths , and adults entering o r playing on treated areas postapplication are eva luated. Further considerations are cu rre ntly in dev e lopm e nt as OPP has commined r esou rces and expertise to the development of spec iali zed software and models that consider exposure to bystanders and farm workers as well as lif esty l e and traditional dietary patterns among spec ifi c subgro up s. 

### 4.0 Hazard C h a r acterization and Dose R espo n se Assess ment 4.1 Summary of Toxicological Effects The toxicological database is complete . In the 20 11 risk assessment (Memo, S
. Levy 

### e t al., 30- NOV

- 2011; D3895 I 9) , the following dat a gap s we r e identified: ( 1) an immunotoxicity study , (2) an acute neurotoxicity study, (3) a subchronic neurotoxicity study and (4) a subc hronic inhalation toxicity study. The Hazard Science and Policy Council (HASPOC) concluded , based on a weight -o f -e v idence approach, that the inhalation study was not requir ed at this time but the acute neurotoxicit y s tud y was required (TX R# 0056342). Since that tim e . acute neurotoxicit y and immunotoxicity s tudies were submitted and the results wer e in corporated into the current assessment. Based on the results from the acute ne urotoxicity stu d y , HASPOC determined that a subchronic neurotoxicity study is not required at thi s time (TXR # 0051465). Acequinocyl's absorption , metabolism , di str ibution , and excretion (ADME) are well characterized. Acequinocyl exhib its marginal abso rpti on into the plasma (l 3-16% for the 10 m g/ kg low dose and 8-9 % for the 500 mg/kg high dose) and relati ve ly rapid and comp lete exc reti on (24 hours for the low dose and 72 hours for the high dose ), primarily via the bile and feces ( 82.6%) in rat s. Acequinocyl undergoe s nearl y complete metaboli s m to hydrol ys is products and a glucuronide conjugate. There was no evide nce for selective tissue accumulation or sequestration. Across s pecie s, durations and routes of exposure (oral and dermal) , the prim ary effects in the acequinocyl ha zard database are indicativ e o f t oxic ity to the liver (hepatocyte vacuo li zation , brown pigmented cells and perivascular inflammatory cells in liver) and hematopoietic system (hemorrhage, increa sed clotting factor times and increased platelet counts). In an acute neurotoxicity study , there were no effect s up to the limit dose (2000 m g/ k g). In a guideline immunotoxicity study. th e r e were also no effects up to the highest do se t es t e d (45 mg/k g/day)
. In rats and rabbits , th ere was no evidence of in creased quant itati ve or qualitative fetal s usceptibility with clinical signs and gross necrop sy findings seen in maternal animals at s imil ar o r lo wer doses than those producing resorption s. In the rat two-generation reproductive toxicity study, offspring effects at the mid- and hi gh-doses consisted of swo ll en body parts , protruding eyes, clinica l s ig n s , delays in pupil de ve lopm ent , and increased mortality occur rin g ma inl y after wean in g , however these effects were observed at the same doses as parental effec t s, and a clear NOAE L was estab li s h e d which is being used in e ndpoint selection. Th e re were no effects on reproductive paramete rs. Th e re was no concern for ge notoxicity or muta ge nicity . There was no evidence of carcinogenic potential in either th e rat o r mouse carcinogenicit y s tudies , or in the genotoxicity and muta ge nicity studies indicating that acequinocyl is "not likel y" to be carc in ogenic to human s. Acequ inoc yl has low acute toxicity via the oral , dermal. and inhalation routes (Toxic ity Categories lIJ & IV ). No ocular or dermal irritation wa s n oted. Ace quinoc y l is not a derma l sensiti ze r. Page 8 of2 IAcequinocyl Human Health Risk Assessment 0 43 1305


### 4 .2 Sa fe ty Fa cto r for Infants a nd C hi ldren (F QP A Sa f ety Fac t o r ) HED 's RABI ri sk assessment team conclud e d that the Food Qualit y Protec tion Act (FQPA) Safety Factor (SF) may be reduced to l X for a ll ex posure scenario s . Th is reco mme ndat ion i s detai led in the 2011 ri sk assessment (Memo, S. Levy 

### e t al., 30

- NOV-20 I I ; 0389519). 

### 4 .3 Toxici ty E ndp oint a nd POD S election s Table 4.3.1 provides the tox ic olog ical do ses and endpoints used in this risk assessme nt. No changes w ere mad e from the prev ious risk assessment.

Ta b le 4 .3. 1. S umm a r y o f T oxico logic a l D oses a nd E nd po int s for Acequin ocy l fo r Use in Di e t a r y, O cc up a ti o n a l , a nd R es id e nt ia l E xp os u r e Ri s k Assess m e n t s. 1 Exposure/ POD Uncertai nty/FQPA Sf's RID. PAD. LOC Study and Toxicolog i ca l Effec t s Scenario Acute Dietary An endpoint of concern (effect) (Ge neral attributab l e to a sing l e 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. C hronic Dietary NOAEL = 2.7 UFA= IOX ePAD = eRID = 0.027 18-monih carcinogenicity study in (All Populations) m g/kg/day UFu = IOX mg/kg/day mice: FQPASF = I X LOA EL= 7.0 mg/kg/day based on clinical chemist r y and microscopic non-neoplas tic lesions (b rown pigmented cells and perivascu lar innammatory cells in liver). Short -term ( 1-30 NOAEL = 60 UFA= IOX LOC (reside ntial )= Developmental toxicity study in days) incidental mg/k g/day UF11= ! OX MOE < 100 rabbits: oral Maternal LOAEL = 120 mg/kg/day based on clinical signs ( hcmaturia, reduced fecal outpuL body-weigh t loss. and reduced food consump ti on) and gross necrop sy findings (pa l e lung s and li ver. hemorrhaging uterus. nuid in the cecum. fur in the stomach
. blood stained vaginal opening. blood-stained urinary bladder content s/ urine). Int ermediate

- NOAEL = 16 UFA= IOX LOC (residential)= Subchronic toxicity in mice: tcrn1 mg/kg/day UFH= I OX MOE < IOO LOAEL = 81 mg/kg/day based on { 1-6 months) hcpatocy1c vacuol ization. incidental oral Short

- ( 1-30 Dermal NOAEL UFA= !OX LOC (occupationa l / 28-day dennal study in rats; days) and = 200 m g/kg/day UFH = IOX residential)= LOA EL = I 000 mg/kg/day based Int e rm ediate

- MOE < 100 on increased cloning factor time s . term ( 1-6 months) Dermal Short

- term ( 1-30 Oral OAEL = UFA= I OX LOC (occupational / Deve l opmental toxicity study in days) Inhalation 60 mg/k g/day UFH = IOX residential) = rabbits: MOE < IOO Maternal LOAEL = 120 (inhalation mg/kg/day based on clinical signs absorption rate= {hcmaturia. reduced fecal ou tpuL 100%) body-weight lo ss. and reduced food consumption) and gross necrop sy findings (pale lun gs and liver. hemorrhaging uterus, nu id in Page 9 of2 IAceguinocvl Human Health Risk Assessment 0431305 T ab l e 4.3. 1. S umm ary of T oxico l og ica l D oses a n d E nd poi n ts fo r Acequin ocy l for Use in Di et a ry, Occ uo a t io o a l , a nd R esidentia l Exoos u re Ri s k Asscss m e n ts.1 Exposure/ POD Unccrtainty / FQPA SFs RID. PAD. LOC S t udy and Toxicological Effa:ts Scenario the cecu m. fur in the s tomach. blood sta ined vaginal opening. blood- s tai ned urinary bladder con t ents/urine). Intermediate

- Ora l NOA EL = UFA= IOX LOC (occupational/ Subchronic toxicity in mice: ( 1-6 months) 16 m g/

k

g/day UF11 = IOX residential)= LOA EL= 8 1 mg/k g/day based on Term Inhalation MOE < 1 00 hepatocyte vacuolization. (inhalation absorption rate = 100%) Cancer (oral. dermal. inhalation) C l assilication: ··Not likely to be Ca rcin ogenic to Human s :· 1 Point of departure (POD) = A data point o r an esti m ated point that is derived fr om observed dose-response data and used to mark the beginning of extrapolation to determine ri s k associated with lower e nvi r o nm en tall y relevant hum an expos ures. UF = un cer taint y factor, UFA= extrapolation from anima l to human ( interspecies), U1711 = potentia l var i a tion in sensitiv it y amo ng members of th e human population (i ntraspec ie s). FQPA SF = FQPA Safety Factor, NOAEL = no-observed-adverse- effect leve l. LOAEL = l owest-observed

- adverse-effect l evel. Rfl) = r efere nce dose (a= acute. c = chronic). PAD = population

- adjusted do se. MOE = margin of exposure. LOC = level of concern . N I A = not applicable. 4. 3 .1 Recommend a ti o n for C ombinin g R o ut es o f E xpo s ur es for Ri s k Assess m e nt Ba se d upon the u se of th e same oral studies and e ndp o ints , short

- term incid e ntal oral exposures ca n be combined w ith s hort-term inhalation exposu r es and intermed ia t e-term incidental oral expos ures can be combined with i ntermed iate-te rm inl1alation exposu res. As d ifferent effects were see n i n t he route - s p ec ific dermal study compared to the effects see n in t he oral studies used to se lect the oral and inhalation points of d epa rture, s hort- and i nterm ed iate -t e rm dermal expos ures should not be co mbined with incid e ntal oral or inhalation ex po su re s . 5 .0 Diet a ry E xpo s ure a nd Ri s k Assess m e nt Please refer to the following documents for detailed considerations of the material summarized in th i s section:

• PP# 5F8364. Acequinocyl. Petition for In creas in g th e P e rmanent Tol e ranc e for R esid ue s in/on Hop s. Summary of Analytical Chemi stry and R es idu e Data. G. Kramer, 22-MAR-2016; 0427588. • PP# 5F8364. Acequinocyl. Chronic Aggregate Die ta ry (Food + Drinking Water) Exposure and Ri sk Assessme nt for the Proposed In crease in th e Permanent Tolerance for R esidues in / on Hops. G. Kramer, 22 -MAR- 2016; D43 I306. • Acequinocyl: Drinking Water Assessment to Support Proposed New IR-4 Uses (Succu lent Soybean Vegetable , Low Growing Berry, Small Fruit Vine Climbing

- Except Fu zzy Kiwifruit. Succule nt Shelled Beans , Cowpea Forage, Ca neberry , Melon, Cucumbe r. and Cherry ). M. Lowit e t al., 07-SEP -2011 ; D389520. A rysta L i feScience is re questing to increase th e ex ist ing to leranc e for res idue s of the insecticide acequinocyl, 2-(acety l oxy)-3-dodecyl-1,4-naphthalenedione, and it s metabolite , 2-dodecyl-3- hy droxy-1 ,4 -naphthoquin one, expressed as acequinocyl equival ents in/on hops from 4.0 ppm to 15.0 ppm. The purpose of the amended tol e ran ce is to harmonize the va lu e with the established MRL in the EU. The domestic residu e data for hops were pre v iousl y submit ted and review ed und e r PP#9E759 8 (Me mo. S. Levy, 25-AUG-2010: 0369100).

P

age l0 of2 1Acequinocvl Human Health Ri sk Assessment 0431 305 

### 5.1 Dietary Exposure / Ri s k Pathwa y 5 .1. l Residue Pro fil e The nature of acequinocyl residues in apples , oranges , and eggplants is understood based on the previously s ubmitted and reviewed m etabo li sm stud ies. In the se crops , the metabolism of acequinocy l involve s th e loss of the acetyloxy moiety to form 2 -d odecyl-3-hydroxy -1 ,4

- naphthoquinone (ace quinocyl-OH), the opening of the quinone ring to form AKM- 18 , and the s ub seq uent degradation of the qui none ring to yie ld polar metabolites that degrade to phthal ic acid. These data are considered sufficient for th e curre ntly register ed crops . For purposes of ri sk assessment and the tolerance expression, HED ha s determined that the re s idues of concern in the currently registered crops include parent and acequinocyl

- OH (Memo , S. L evy, 07-JAN

- 2004; DP # 297872)
. There are no livestock feedst uff s associated w ith hops. Therefore , no livestock metabolism dat a, enforceme nt method s, sto rage stab ili ty data , or feeding st udi es are required to support this pet ition. The U.S. tolerance (4.0 ppm) is based on three hop fie ld trials conducted in North American Free Trade Agreement (NAFTA) Growing Zone 11 ( ID , OR , WA) during the 2005 grow ing season. Each trial consisted of one untreated and one treated plot. At each site , a 1.25 lb/ gal SC fonnu lation of acequ in ocy l was app li ed to hop s as two directed foliar app li catio n s during cone development at rates of 0.288 -0. 330 lb ai / A/ app li catio n , with a 19- to 28 day retreatment interval (RT I), for a total rate of0.588-0 .641 lb ai / A (

- IX ). Total residues ofacequi nocy l and acequinocy l-OH were 1.32-2.83 ppm in/on dried hop cones . The German re s idue data (2X U.S. s in g le app li cation rate; IX U.S. seasonal application rate , longer preharvest interval ( PHl ) , parent o nl y) s how that the U.S. tolerance level is likel y se t at too low of a level. H ED notes that analysis of the U .S. da ta wi th the Organization for Econo mic Co-operation and Development (OEC D ) MRL Calculator would have result ed in a recommended tol e rance of 7.0 ppm. Harmonization of the U.S. tolerance level with the MRL of 15 ppm is thus recommended. There is currently no estab li s hed Canad ian MRL for acequinocy l i n/on hops. 

### 5.1.2 Water Ex po s ur e/R isk Pathway The drinking water resid u es us ed in the dietary risk assessment were provided by EFED (M. Lowit , 07

- SEP-2011: 0389520) and incorp orat ed directly into this dietary assessment. As there a re no proposed or reques t ed changes in the acequi nocyl label associated with this action , a new drinking water assessment has not been perfo rmed. Water residue s were incorporated directly into DEEM-FCID und e r th e food categories
..water, direct, all sources " and ·'water, indirect , all sou rces . "
Tab le 5.1.2.1. R eco mm e nded E OWC s of Aceouinoc v l Derived from the Pre v iou s Uses. ED WC s from Surface Water Sources ( ug/L) 1 • 2 Drinking water Proposed Approach I Approach 2 source (model) Use/ ccnario 3 (assume no accquinocyl degradation) (comb ined acequinocvl and RI ) l-in-10· I -in- I0

- yea r 30

- year l-in-1 0

- I-in- I0

-year 30-ycar year acute chronic mean year acute chronic mean Surface water 6.69 6.69 6.69 0.42 0.26 ( PRZ M/ EXAMS) C herry/ MI c herry (25.89 )4 ( 17 .84)4 ( I 0.19)4 5.59 S urface water Small fruit (vine 6.69 6.69 6
. 69 4.22 0 .38 0.27 (P RZM/EXAMS) c limbin g, except fuzzy (23. 1 2)4 ( 15.34)4 (9.57) 4 Page 11 of2 IAceguinocvl Human Health Risk A ssessment 043130 5 kiwifrnit. I 3-07F) y gra pe S urface water Cranberry/ Provi s ional 3.8 15 1.36 5 (Provisional 4.24 3.75


### -- 

## -- Cra nberry Model ) Cra nberry Model Grou n dwater A 1 1propo s ed uses 3.6 x 10· 3 s 3.6 x 1 0

-

3 :::3 .6 x 1 0- 3 3.6 x 10 ·3 s 3.6 x 10- 1 s 3.6 x 10

- 3 (SC I GROW) 1 Bolded values are the recommended ED WCs by EFED. ! A default PCA of 0.87 wa s applied. 3 Maximum of two app li cations o f0.3 lb ai/A for all propo sed uses.**~** EDWC (shown in parenthe ses) exceeds the solubility limit o f acequinocyl (6 .69 μg/ L at 20 ° C): thc.Tcfo re. the recommended EDWC i s 6.69 ppb.**~** B ase d on a one-year s imul a tion: 1-10-y ear calculation i s not applicable. S in ce the s urfa ce wate r E DWC s are hi ghe r than th e grou ndwate r E DW C , H E D selecte d th e s urface water val ue fo r u sc in the chronic dietary assess ment. Th e EDWC derived v ia A ppro ac h # 1 represent s the uppe r-bound value (6.69 ppb ) while that de rived via Approach #2 represe nt s the lowe r-bound valu e ( 1.36 ppb). The 6.69 ppb va lue was used in this dietary assessment as th i s va lu e ass ures a co n servati ve assessment. 

### 5 .1.3 Di et ary Ex p os ur e An a lyses A n acute diet ary assessment was not conducted for aceq uino cy l because an endpo int of concern att ributabl e to a s in gle dose was not identified ; therefore , an aRID was not es tab l i s h ed and an acute dietary assessment is not necessary . A cancer dietary assessment was not conducted b eca u se acequinocy l was cl ass ified as not lik e l y to be carci nogen ic to human s. An acequinocyl c h ro ni c dietary expos ure assessment was condu cted using DEE M-FCID , Ve rsion 3 .1 6 , w hi ch incorporates 2003

- 2008 consumption data from USDA · s N H ANES / WWEIA. The data are based on the reported consumpt ion of more than 20,000 ind ividual s over two non-consecutive survey days. Foods "as consumed " (i
. e., apple pie) are linked to E P A-defined food commo diti es (i.e
.. app les, peeled fru it

- cooked; fresh o r N/ S; baked ; o r wheat flour

- cooked; fres h or N/ S , baked) using publicly available recipe trans lation files developed jointl y by USDA/ARS and E P A. Fo r c hronic ex posure assess me nt , consumption dat a are averaged for the e ntire U
. S. popu lation a nd w ithin popu lation s ub gro up s , but fo r acute ex p os ure assessment a re re ta in ed as indi v idu al cons umption eve nt s . B ased on analysis of the 2003

- 2008 NHANES / WWEIA consumption data , wh ich took in to acco unt dietary patterns and s urvey respondents , H ED concluded that it is mo st approp riate to report ri sk fo r the following populatio n subgroups: th e general U .S. population , a ll infants (< I- yea r old). children 1

- 2 years o ld. c hildren 3

- 5 years old , c hildren 6

- 12 years old , youth 1 3

- 1 9 years o ld
. adults 20

-49 years o ld , fem al es 13-49 yea rs o ld , and adult s 50-99 years o l d. 

### 5. 1. 4 C hron i c Di et ary E xpo s u re Ana lys is The DEEM

- FCID an a lys is estimates the dietary exposur e of th e U.S. population and var ious popu lat io n subgroups. The c hron i c dietary exposure assessme nt (us in g tolerance level residues and 1 00% CT information for a ll registered and proposed uses) was conducted for the ge nera l U
. S. po pul at io n and vario u s p opu l ation subgroups. DEEM ver. 7.81 default processing factors were used with the exception of those fo r grape juice and raisins. As re s idues were red u ced in both grape juice ( < 0.02X) and raisin (O. l 5X) , se parate tolerances are not required fo r th ese commo diti es. The D EEM ver. 7.81 d efault proces s in g factors for juice and ra is in were se t to l as conce ntration was show n not to occur (Memo, S. Levy , 05-SEP-2007; DP# : 342 805 ). D r i nk in g Pa ge l 2of2 1Aceguinoc y l Human Health Ri s k A s sessm ent 043130 5 water wa s incorporated directly into the dietary assessment using the chronic concentration for surface water ge nerated 

### by the PRZM/EXAMS model. The highest chronic surface water va lu e (i.e., most conserva tive) of 6.69 ppb was u sed for this assessment. This asse s sment concludes that the chronic dietary exposure es timates are not of concern to H E D for the gen e ral U.S. population (14% c P AD) and all population subgroups. The most highly exposed population subgroup is children 1-2 years old at 60% of the c PAD
. The use of anticipated residues (ARs) , emp irical processing factors, and %CT data would refi n e further HED' s expos ure and risk est imates; however , refinement is not n eeded at thi s tim e .

T a bl e 5.1.4.1. S umma ry of Dietar y (Food + Drinkin g Water) Expo s ur e an d Risk for Aceq uino cyl. Chro nic Dietary 1 Population Subg roup Di etary Exposure % cPAD (mg/k g/day) U.S. Population (total) 0.0037 11 14 All Infants ( < I year old) 0.006769 25 Chi ldren 1-2 yea r s o ld 0.016168 60 Childr e n 3- 5 years old 0.011083 41 Childr e n 6-12 years old 0.005226 19 Youth 13-19 years old 0.002605 10 Adults 20-49 years old 0.002758 10 Adult s 50 + years old 0.002615 10 Femal es 1 3 -49 y ears old 0.002624 10 1 Ch ro ni c d i e tary e ndpo int of0.027 mg/kg/day applie s to th e ge ne ral U
. S
. popu la uo n and a ll populau o n subg ro up s . T he va lue s fo r th e hi g h es t ex p ose d p o pul ati on a re bo ldcd. 

### 6.0 Residentia l (Non-Occupational) Ex po s ure/Risk C haracterization There are no proposed residential uses associated w ith the current act ion; however , there are existing re s idential uses that have been reas s essed in this document to reflect revisions to H ED 's 2012 Residential S0Ps 2 along with policy changes for body weight assumptions. The revision of residential exposures will impact the human health aggregate ri sk assessment for acequinocyl. The algorithms used to es tim ate exposure a nd dose for residential handl e r s can be found in the 2 012 R eside ntial SOPs. 

### 6.1 Sho rt-t erm R esident ial Handler Risk Acequinocyl is currently registered for use on l andscape ornan1entals in and around residences , businesses , public property , sc hools , interiorscapes, and other non-production areas by commercial app licators and h omeowners. Short- term residential handler dermal and inhalation exposure from applying acequinocyl to trees and ornamenta l s 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 ilable: lill.P.: // www .epa.gov / pesticides /scicncc/rcsidential-exposure-sop. htm I Pa ge 13 of21Aceguinocy l Human H ealth Ri s k Assessment 0431305 Table 6.1.1. S ummar y o f Re s id e ntia l H andle r Ex p os ur e and Ri s k
. Application Unit Exposure Amount Re sidential Residential Scenario Rate llandled Handler Dose ( l

b ai/ gal) (mg/lb ai) (gals) (mg/kl!,/day) Handler MOE Mix e r / Loader /Appl ieator

- Dermal : De rm al: Liquid Fonnu l ati on with Dermal: 63 0.0049 41.000 0.00125 5 Manually-pres s urized Inhalation: 0.0 18 Inhalation: Inh alation: Hand wand 0.00000 1 4 43.000.000 Dermal: Dermal: Mix er/Loader / Appl ieator

- Dermal: 58 0.0 1 20.000 Liquid Fonnulation with 0.0012 5 11 Ho se - End Sprayer Inhalati on: 0.00 14 Inhalation : Inhalation: 0.00000024 250.000.000

Dermal: Dermal: Mixer /Loader /Applicator

- Dermal: 1 30 0.0 1 20.000 Liquid Formulation with 0.00 1 25 5 Backpack Inh alation: 0. 14 Inh alation : Inhalation : 0.0000 11 5.500.000 Dermal : Dermal: Mixer / Loader /Applicator

- Dermal: 58 0.0045 44.000 Liquid Fonnulation with 0.00 1 25 5 Sprinkler Can Inhalation: 0.00 14 Inhalation: Inhalation: 0.000000 11 550.000
. 000 

### 6.2 Short-term Re s idential Post-application Ri s k Short-ter m post-app li cat io n dermal exposure is anticipate d for th e registered res identi a l u ses; however , a quantitativ e post-application assessment has not been previou s l y cond ucted. Consis tent with th e 20 12 Res ide ntial SOPs , HED assesse d residential po s t-application expo su re from contacting trees a nd o rnamental s previously tre a ted with acequinocyl for thi s action. C he mical- spec ific dislodgeable-foliar re s idu e (OFR) data are available for aceq uinocy l for c hrysan themum s in gree nh o u ses (MRID 45428619) and the se DFR data we r e used in the po s tapplication dermal expos ur e assessment. B ased o n an analysis of the chrysanthemum data, the R2 value is low (0.4 1 7) , indi cat in g t hat the te s t product may not di ss ip ate accord in g to first-order kinetics in greenho u ses; therefore, the m eas ure d DFR valu e was u sed so as to not underestimate ri s k. In addition , th e DFR va lu e was adjusted to re flect the maximum app li catio n allowed on the label (0. 1 25 lb a i/ A) as compared to th e application rate used in the DFR s tud y ( 0.3 lb a i/A)
. Th e m eas ure d average D ay - 0 residue from the study was 0.617 ug/cm 2 or 0.257 u g/c m 2 once adjusted for application rate. Appendix B provides a s unun ary of the study. A ll MOEs were > 100 a nd are not of concern to H ED (see Table 6.2.1).
Tab l e 6.2.1. S umm ary o f Re s identi a l P ost-a ppli catio n Exposu r e a nd R isk. Trans f er /\b so r bcd Derma l Scenario Lifcstage DFRt Coefficie nt Ex po sure Dermal MOE (ug/cm2 ) (em 2 /h r ) Time (hr) Dose (rounded) ( mj.!/kg, day) Po st-appli cation Adult 8400 2.2 0.059 3.400 Gardens 6 < 11 yrs 4 600 I. I 0.04 1 4.90 0 0.257 Post-application Adult 1.700 I 0.005 37.000 Trees 6 < 11 yrs 930 0.5 0.004 54.000

Pa ge 14 of2 IAceguinocyl Human Health Ri sk Assessment 0431305 

### 6.3 S pray Drift Spray drift is a potential so urce of exposure to tho se nearby pesticide applications. This is particularly the case with ae rial application, but , to a lesser extent, spray drift can also be a potential source of exposure from t he ground app li cation methods (e.g., gro und boom and a irblast) emp loyed for aceq uinocyl. The Agency ha s been working with th e Spray Drift Ta s k Force (a task force composed of various registrant s which was developed a s a resu lt of a D ata Call-In issued by E P A), E PA Regional Offices and State Lead Agencie s for pesticide regulation and other parties to d eve l o p the best spray drift management practice s (see the Agency's Spray Drift websi te for more information). 3 The Agency has also develop e d a po li cy on how to appropriately consider s pray drift as a potential so urce of exposure in ri sk assessments for pe s ticides. The pote ntial for spray drift will be quantitatively evaluated for each pesticide during the 

### Reg istration Rev iew process, whi ch ensures that all uses for that pesticide w ill be considered conc urrently. The approach i s outlin e d in the rev ised (2012) 

### Standard Operating Procedures For Residential Risk Assessment (S OP s)

- Resid e ntial Exposure Assessm e nt Standard Operating Procedures Addenda 1 : Cons ideration o/Spray Dr(ft. This document outlines the quantification of indirect non-occupational exposure to drift. 

### 6.4 Re s identi a l Bystander Po s t-appli cation Inh a l a tion Ex po s ur e Volatilization of pe s ticides may be a source of post-application inhalation exposure to individuals nearby pe s ticid e applications
. The Agency sought expert advice and input o n issues related to volatilization of pesticides from its F ede ral In secticide , Fungicide , and Rodenticide Act ( FIFRA) Scientific Adv iso ry P anel (SAP) in D ecember 2009, and received th e SAP's final report on March 2, 20 l 0 ( http: ! / arch ive .epa.g ov/ sc ipoly / sap / meeting s/ web / pdf / 1203 09meetingmi nut es .pdf). The Agency h as evaluated the SAP r epo rt and has de ve loped a Volatilization Screening Tool and a su b sequent Volatilization Sc re e ning Anal ys i s ( http: // www.regu lations.gov /# !docketDetail ; D = EPA-HQ-O PP-201 4-02 I 9). During Registration Review , the Agency will uti l ize this analysis to detem1ine if data (i.e., flux s tudies , route-specific inhalation toxicological s tudies) or further ana lys is is required for acequinocyl. 

### 7. 0 Aggregate Ex po s ure/Risk Characterization In accordance with the FQPA , HED must consider and aggregate (add) p es ticide exposures and risks from three major so urces: food , drinkin g wate r. and residential exposures. In an aggregate a ssess ment , exposures from relevant sources are add e d together and compa red to quantitative estimates of hazard , o r the ri sks themselve s can be aggregated. When aggregating exposures and ri s ks from various so urc es, HED considers both th e route and duration of exposu re. 

### 7. 1 Acute Agg re ga te Risk An endpoint of concern was not identified to quantify acute -dietar y ri s k to the gene ral popu lation or to any population s ub gro up. Since an acute haza rd does not exist , an acute aggregate assess ment was not p erfo rmed.

3 Available: http ://www 2
.e pa . gov/ red ucing

- pesticide

- drif1 Pa ge l 5of2 1Acequinocyl Human Health Ri s k A sse ss ment 0431305 

### 7. 2 S hort-T e rm Agg r egat e Ri s k Short-term aggregate risk is made up of d ietary and non - dietary sources of exposure . Si n ce aceq uin ocyl h as a residential use o n o rn amen tals , adu lt resident ia l hand le r exposure i s ex p ected. Short-term aggregate r i sk i s mad e u p of average die tary exposures fro m food and drinking wa ter sou rces , and de rma l a n d inha lat io n res ide n tial exposu r es . Derma l post-app li cation residentia l exposures were not inc luded in the short-term aggregate as d ifferent 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 Tie r 1 (unrefined) chron ic dietary exposure assessment (see Table 5.1.4.1 ). Residential exposure estimates are conservative estimates du e to th e stan dard ass u mptio n s that we re b uil t in to the calculations. Resident ia l expos ure estim ates we r e take n from Tab le 

### 6.1.1. The short

- te rm agg regate ri s k calc u lat io n s are shown in Table 7
. 2
. 1 and are not of concern to HED.

Ta b le 7. 2
. 1. S h o r t- T erm APore1rn t e Ri s k Calc ul a ti o ns. Dietary Re s id ential Inhalation Aggregate Expo s ure Aggregat e Population Exposure Ex pos ure ( mg/kg/ day) MOE3 ( mg/kg/day)' ( mg/kg/da y)2 Adults 20-49 years old 0.002758 0.000011 0
. 00275869 22 ,000 1 From Table 5.1.4.1. 2 Re s ident i al expo sure from Tab le 6.1. 1 ··Mixer/Loader /Applicator

- Liquid Fonnulat i on with 13ackpack"' scenario. 3 Aggregate MOE = s hort-term oral NOAEL (60 m g/

k

g/day ) + agg reg ate exposu r e. 

### 7
. 3 Interm e diate- Term Ag gregate Ri s k l ntem1ediate-tenn aggregate risk was not calculated since the use pattern i s not expected to result in residential handler or post-application expo s ure of more than 30-day duration. 

### 7.4 Lon g -Term A gg re ga t e Ri s k Chronic ( long- te r m) agg r egate ri sk i s m ade u p o nl y of dietary sour ces; th e refore, the chronic exposure estimates provided in the chron ic d ie t ary exposure a n a l ysis (see Tab le 5. I .4. 1 ) represents chronic aggregate exposure. 

### 7. 5 Cancer Ri s k Aggregate cancer risk was not calculated because acequi n ocy l is not con s idered to be a carc inogen. 

### 8
. 0 C umul ative Ri s k C hara cteri z ation / Ass ess ment Un li ke oth er pesticides for wh i ch EPA has followed a cumulative risk approach based on a common mechanism of toxicity , E PA has not made a common mechan i sm of toxicity find i ng as to acequinocyl and an y othe r substances and ace quinocy l does not appear to prod u ce a toxic metabolite produced by other substances. For the purposes of this to lerance action , therefore , EPA has not assumed tha t acequinocyl has a common mechanism of toxiciry with other substances. Fo r info rmation regarding E P A ' s effort s to determ ine which chemicals h ave a common mechanism of toxic ity and to eva luate the c u m ul ati ve effects of suc h che m icals, see th e Pag e 16 of 2 IAcequinocy l Human Health Ri sk Assessment 0431305 policy statements re l eased by EPA's Offic e of Pesticide Programs concerning common mech anism determinations and procedures for cumulating effects from substances found to have a common mechanism on E P A ' s webs ite ( http: //www.epa.gov/ pesticide

- sc i e nce-and-as sess ingpesticide-risks /cumulative-assess ment-ri sk -pe stic ide s)
. 

### 9.0 Occupational Expos ure/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.



### L i st of Appendices: Append i x A. T oxicity Profile Tab le s 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 of21Aceguinocy l Human Health R i s k Assessment D43 1 305 

### A ppendix A: Tox i city Profil e Tab l es . T a b l e A-l. Acut e To x ici ty o f A ce quinoc y l.

Guide l ine S t ud y T y p e MRJD #(s) Re s u lt s To x icity Category No. 870.1 1 00 Acute Ora l (rat) 4543 5011 LD so > 5000 m g/kg I V

(8 1-1) 870.1 2 00 Acute Dermal 45435 01 2 LD so > 2000 m g/kg Ill

(8 1 -2) 870. 1 300 Acute Inha l ation 454350 1 3 LC so > 0.84 m g/L Ill

(81-3) 870.2400 Primary Eye Irritation 45435014 No t an eye irritant IV

(8 1-4 ) 870.2500 Prim ary Skin Irritation 454350 1 5 No t a d e rmal irritant IV

(8 1 -5 ) 87. 2600 Dermal Sensitization 45435016 Not a derm a l se n siti ze r N I A ( 8 1

- 6) T a bl e A -2. To x ic ity Pr o fil e fo r A ce qui n oc y l. Guideline No. ;

Study Type MRlD (year); Doses ; C lass ification Re s ult s 870
. 3 1 00 45673701 ( 1995): NOAEL ( M /F) = 1 612 1 mg/k g/day: LO AE L (M/F) = 81 / I 00 mg/ kg/day based on 90 -D ay Oral Toxicity 0, I00. 500. 1000 ppm hepatocy te vacuo lization. Rodents-MO USE M: 0. 1 6. 81. 15 1 mg/k g/da y F: 0
. 2 1
. I 00. 23 1 mg/kg/day Acceptab l e/ G u i de l in e 870.3100 4553 1904 ( 1998): NOAEL (M / F) = 30.4 / 32.2 mg/kg/ day: LOAEL (M/F) = 11 9.5/129.2 mg/k g/day 90-Day Oral Toxicity 0. I00
. 400. 1600. 3200 ppm: based on increased prothrombin tim es in Rodents-RAT M:. 7.6. 30.4, 119.5, 252
. 7 mg/kg/ day ma l es and increased ac ti vated partial F: 0. 8.3
. 32.2 , 1 29.2
. 286.0 mg/kg/day thromboplastin times in both sexes . Accep t able/ G uid el in e 870.3150 45531905 ( 1995): NOAEL (M/ F) = 40 1 40 mg/k g/day: LOAEL (M/F) = 1 60/160 mg/kg/day based on 90 -Day Ora l Toxic i ty 0
. 40, 16 0 , 640. I 000 mg/k g/day decreased body-weight gai ns and reduced Nonrodcnts -D OG food cfticiencics in ma l es and fo r female Acceptab l e/G uideline beagle dogs based on increased plate le t cou nts. 870.3200 4553 1906 ( 1999): Sys t emic NOAEL = 200 mg/kg/day: LOA EL = 1000 mg/kg/day based o n 28 -D ay Dermal Tox i cit

y - 0. 40. 200, I000 mg/kg/day increased dolling factor times (i ncr eased RAT prothrombin time. increase d ac ti vated partial Acceptable/ Guide lin e prothromboplastin time. in creased fibrin ogcn levels). Derma l NOAEL = 10 00 mg/k g/ day: LOA EL = not es tabl is hed. 870.3700a 4553 1908. 45651706 ( 1 995); M aterna l NOAEL = 1 50 mg/kg/day : LOAEL = 500 m g/kg/day based on s i g ns of Prenatal D evelopmental in 0. 50, 1 50. 500. 750 mg/kg/day internal hemo rrh age and increased in c id e nce Rodents - R AT of clinica l signs (pa l e eyes. pi loercction , red Acceptable /Guidc lin e vagina l discharge). Developmental NOAEL = 500 mg/kg/day mg/kg/ day: LOA E L = 750 mg/kg/day based o n in creased re so rptions.

Pa ge 18 of2 1Aceguinocyl Huma n H ealth Ri s k Assessme nt Table A-2
. To xi city Profil e for Acequ in oc y l. Guideline No.;

Study Type 870.3700b Prena t a l Developmenta l in Non rodents

- RABBIT

870.3800 Two

- Generation Reproduction and Fer tilit yRA T

870.4100b C hronic Toxicit)-DOG
870.4300 Chronic/ Carc inogen icityMOUSE

870.4300 Chronic/ Carcinogenicity

- RAT

870.5100 Ge ne Mutation

870.5300 Gene Mutation MRID (year); Do ses; C lassifica tion -15531907 , 45651705 ( 1995 ): 0. 30. 60. 120 m g/kg/day Accep table/ G uid el in e

4553 1 909 ( 199 7): 0. I00. 800. 1 500 ppm: M: 0. 7.3. 58.9 , 1 11.2 mg/k g/day F: 0. 8.7. 69.2. 1 33.5 mg/k g/ day Acceptable / Guideline

4553 1 910 ( 1 996): 0. 5. 20
. 80
. 320 mg/ kg/day Acceptable/Guidelin e 45531911 ( 1994 ): 0. 20. 50
. 150. 500 ppm : M: 0. 2.7
. 7.0, 20.3. 66.0 m g/

kg/day F: 0. 3.5. 8 .7. 26
. 3. 86
. 00 mg/k g/day Acceptable/Guideline -155319 1 2 ( 1 997): 0. 50. 200. 8 00. 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/k g/ day Acceptable/Guideline 45435 1 0 I ( 1998): 1 9.5, 39 .1 , 78.1. 1 56. 3 1 3. 625. 1250. 2500 or 5000 μg/p l ate in the presence and absence of mammalian metabolic activation (S9 -mi x) and additionally at 9. 77 μg/ plate withou t S9

- mix. Acceptable/Guideline -15435102 ( 1998 ): 5- 7 doses rangin g from I 0-320 p g/ mL Acceptab l e / Guideline Page 19 of2 I 0 431305

Re s ults Maternal NOAEL = 60 mg/kg/day; LOAEL
= 120 mg/kg/ day based on treatment-relat ed c li nical s ig n s l eading t o premature sacrifice (hc ma turia, reduced feca l o utpuL body weight lo ss. and reduced food co n sumption) and gross necrop sy findings (pa le lungs and liver. hemorrhaging uterus, tluid in the cecum. fur in the s tomach. blood stained vaginal opening. blood-stained urinary bladder contcnLSlu rinc , and hair loss). Developmental NOA EL= 60 mg/kg/day ; LOAEL = 12 0 mg/ kg/day based upon increased number of complete resorptions. Parental NOAEL (M / F): 7.3 / 8.7 mg/ kg/ day : L OAEL (M / F) = 58.9/ 69.2 based o n increased i ncidences of hemorrhagic effec ts in F1 mal es. Offspring OAEL (MJF): 7.3 / 8.7 mg/k g/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. Reprod u ctive NOA EL (M / F): 124/ 1 36 m

g/kg/day: LOA EL ( M / F) = not established. NOAEL (M/F) = 80 1 80 mg/kg/day. LOA EL (NVF) = 320 / 320 mg/kg/day based on premature sac rifice (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 clinica l chemis try and microscopic nonneoplastic lesion s (brown pigmented cell s a nd periva sc ular i nnammatory 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 ev idence of induced mutant colonie s over background.

There was no clear evidence ofbiologicallysignifican t induction of mutant colonies over background.Acequinocvl Human Health Ri sk Assessmen t 04 31305 T a bl e A-2. T ox ic it y Pr o fil e fo r Accquinoc y l. Guideline No.;

Stud y T y p e MRJD (year); Do ses; C l ass ification Re s ults 870.5375 45435 1 03 ( 1998 ): The re was no ev id ence of chromosome aberratio n s indu ce d over backg round. C hromosome Abe rration 0. 1 50, 300, 600. or 1200 μ g/ m I, for 24 o r 48 h o ur s w ith out metabo lic act iva ti o n (S9 -mix ) a nd to concen tration s of 0. 4 8 1
. 963. 1 92 5 o r 3850 μg/ mL (highest concentra ti on is equivalent to 1 0 mM ) for 6 hours with S9

- mlX. Acceptable / Guideline 870.5395 45435104 ( 1993 ): There was no s tati s tically sig nific ant in crease in th e frequency ofm icronucl ea tcd Mammalian Ery thro cy te 0. 1250. 2 50 0
. o r 50 00 mg/kg body weight pol yc hr oma ti c ery throcy tes in mou se bone Micronucleu s Te s t in marro w at any d ose o r harve s t tim e. MI CE Acceotab l e / Guid e lin e 870.7485 45435105. 45531913 ( 1997): Acequinocy l exh ibit s marg inal absorption. re l ati vely rapid a nd com plete excretion M e tabo li s m-RAT S in gle ora l doses of 1 0 or 500 mg/kg (phe n yl primarily via th e bi l e and feces. and label ) or 1 0 mg/kg (dodccyl label). and 14- undergoes ne arly complete metabolism to day repeated 1 0 mg/kg dose ( phen yl label). hydro l ys i s products and a glucuronide conjugate. There was no evidence for Acceptable/Guideline se lective t issue accumulation o r sequestration of 2023 (acequ in ocy l ) o r it s m etabol it es in rat s. 8 70.7600 45435 1 06(2000): Perce nt of do se abso rb e d decreased with exposure co ncentration indicating t hat Dermal Penetration-RAT 0. 0.001. 0.01. 0
. 1
. 1 .0 mg/ cm2 sa turati o n of a b sorp tion at/or about th e hi g h dose. Ab so rpti o n at 168 ho urs was 12.2 3%. Acceptab l e/Guide lin e 1 9.75%. and 14
. 77% for the 0 .1 , 0.0 I
. and 0.00 I mg/cm 2 dose groups. resoectivel v.

Page 2 0 of2 IAceguinocvl Human Health Ri s k A ss e ss ment 04 31305 

### A pp e ndix B: G r ee nh ouse Orn a m ent a l S tud y S umm ary . Dissipation of Dislodge ab/e Foliar R es idues of A cequinocy/ and its Metabolite Following Applica tion of Kanemit e SC 

### to Ch r ysan th em um in th e Greenhouse 

### ( MRJD No.: -15820401). (HE D R ev iew : Memo , M. Dow , 1 0-JUN- 20 0 3 , 0 290655) This stud y was des ig ned to collect data to eva luate DFR dissipation for the compound aceq uinocyl from Chrysanthemum fo li age grown in a gree nh o u se at one si te in Cal i forn ia . Primary review of the study was co ndu cted by Versar Inc. , 1 3-DEC

- 2002. The secondar y re v iew was conducted by HED on June 10 , 2003 ( 0290655). Kanemite 1Y SC is a so lubl e co nce ntrat e that co nta in s 15.0 

### % acequ in ocyl as the active ingredient. Th e s tud y eva luate d acequinocyl a nd its metabo lite acequinocyl

- OH. Kanemite ® SC was applied w i th a backpack s prayer at 0
. 30 lb ai / A. Two applications were made with a 21 -day app li cation inte r val. Study results indi cate that DFR residues did not drop below the limit of quantification by 35 days after treatme nt. T he maximum average DFR valu e occurred immediately after the second app li cati on fo r both anal y tes (0.60 ± 0. 1 3 μg/cm 2 for acequinocy l and 0.021 ± 0.004 μg / cm 2 for acequinocy l-OH ). Assuming first-order kinetics , HEO modeled dissipation rates and estimated a half-life of 17 .6 days for aceq uin ocyl and acequinocylOH residues. It s hould be n oted that the low R 2 va lu es ob ta ined from th e stud y data sugges t either that the test product does not d i ssipate according to first-order kinetics , o r that th e data obtained i s n ot accurate . For this reason , HED used the measured OFR va lu e instead of the predicted value in the assess m ent of greenhouse cucum be rs. s o a s not to underestimate po s t-application exposure ri s ks.
S umm a r y o f DF R Va lu es a n d R eg r ess ion A n a lys is R esu lt s fo r T reate d C hr ys an th e m ums in G r ee n ho u ses wit h Ace q u in ocy l ( MRID# 4542 8 6- 1 9). Inpu t/ Param c ter S ite : C alif o rnia Combi11erl Acel1uilloc1 1 / + Acetmi11oc)'/
- OH Appli cation Rate ( lb ai/ A)" 0.3 lb a i //\ S tud y T arget Rat e= 0.3 lb a i / A pray Vo lume ( GP A) 4 0.7 and 39.5 ga llon s per ac re . res p ec ti ve l y fo r ! St and 2 nd aoo li ea t io n s Me as ur e d A verage D ay 0 Res i d ue ( u !!./c m1 ) 0.6 17 Pr

e dicted Day 0 Re s idu e**~1 j?/c** **)** b 0.3 4 6 S l

o o e - 0.0394 I l a lf-life (days) 17
. 6 R

z 0.4 17 a. rhc app ltca 11 on was c o nducted u s 111 g backpack s prayer equ i pment. b
. Re g r ess ion s are based o n data co ll ec t e d after second app li cati o n.

Page21 of2 1