### Date : S ubj ect : UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , 

### D.C. 20460

July 22, 20 14 OFF I CE OF CHEMICAL SAFETY A ND POLLUTION PR E VE NTION



### H a lauxifcn-m eth y l. Occupational and Resident ial Exposure and Ri sk Assessment to Sup port the Registration of the New Active I ngredient on Wheat , Barley , and Triticale. P C Code: I 1750 I Deci s io n No.: 470169 Pe tition No
. : 2E8086 DP B a r c ode: 04161 29 Reg istrati o n No.: 62719

- AAE, AAG. AAN. AA R, AAU Reg ul ato r y Action: Section 3 R eg istra tion R isk Assessme nt T y p e: Ex posure Assessment T XR No.: NA Case N o.: A C AS No.: 94383 1-98-9 MRID No.: NA 

### F rom:

T hr o u g h:

To :

Introduction 40 C FR: New Active Ingredi en t Za id a Figueroa , Indu str ia l H ygie nist Ri s k As sess ment Branch II H ea lth Effec ts D i vision (7 509P ) Christi n a Swartz, Branch

# Chief**~** 

# A __, Risk As sess m ent Branch 11 

# J \._\ H ea lth Effects Division (7 509P ) and Matthew Crowley , ExpoSAC Reviewer

# t~ Matthew Lloyd. ExpoSAC Reviewer Exposure Science Advisory Committee ( xp oSAC) 

### I HED Maggie Rudic k/Kable Bo Davi s . PM Team 25 H e rbicid e Branch Registration Divi s ion (750 5P)

The R egistration Division ( RD ) reque s ted that the Health Effects Division ( I IED) co nduct an exposure and risk assessment for propo se d uses of th e new he rbicid e halauxifen-m e thyl to control annual broad leaf weeds in wheat , barl ey, and tritica le. There are no residential u ses proposed fo r halauxifen-methy l at thi s time ; th e refore , thi s ri sk assessment only addresses the p o tential occ upati o nal exposures associated with the propo se d uses. It is HED polic y to u se the best available data to a ssess exposure. Several so urces of generic data were used in this a ssess ment as s urr ogate data in the ab se nce of chemica l- spec ifi c data , including: th e Pesticide
Pa ge I of 17Hand lers Ex p os ure D a t ab a se Version 1.1 ( PH ED 1
. 1 ); a nd the Agricul tural Handl e r Expo s ure Task Force (A H ETF) database. Some of th ese data ar e propriet a ry, and s ubject to the d a ta protec tion prov i s ions of the Federal In sec ticid e, Fungicide
. and R ode nticid e Ac t ( FIFRA )
. Note: This m e morandum was r ev iewed b y th e Ex posure Sc ie n ce A d v i sory Co mmitte e (ExpoSA C ) o n May 

### I. 20 14
.

P age 2of 1 7

### Tab l e o f Contents 

### 1 .0 Exec uti ve Summar y . .......... .. ........ ...... ...... ...... ........ . ............................................ ..... ........ ... . 4 2.0 Ri s k Asse s sment Conclu s ions and Recommendations
........................................................ 6 2 .1 Summary of Risk Estimates
........ . . . .. .... . ... .. ....... .. .. . .......... .. .................. . ........... ... ...... ...... . 6 2.2 Label Recommendations from Occupational Assessment..
............................................. 6 2 .3 Label Recommendations from Residential Assessment
................................ ..... ......... .. .. 6 2.4 Data Deficiencies and Requirements
............... ... .......... .. ......... .. .......... . ........................... 6 3.0 I l azard Characteri zation
....................................................................................................... 6 4.0 Use Profile
..................................... .. ............ . .......................................... .. ......... .. . .. ......... .. . . 8 5.0 Residential Exposure and Ri sk Est im ates ..... ........ .. .......... .. .......... .. ......... ...... ........ .. .......... 10 6.0 Non-Occupational Spray Drift E xposure and Risk Estimates
..... .. ....................... .. ......... .. 10 7.0 No n-Oc cupation al Bystander Post-App li cation I nhalation Expos ure and Risk Estim ates 10 8.0 Occupational Exposure and Risk Estimates
...................................................................... l 0 8.1 Occupational Handler Exposure/Risk Estimates
....... .. . . ................. .. ............ .. . .. .. ........ ... 10 8.2 Occupatio nal Post-application Exposu re /Risk Estimates
.............................................. 15 8.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates
...................... 15 8.2.2 Occupational Po st-app li cation Dermal Expos ure/Ri sk Estimates
... . .......... . ......... .. 15 Appendix A. 

### Summar y of Occupational and Residential Non-cancer Algorithms
..................... 17

J>a gc 3 of 1 7

### 1.0 Exec uti ve S um mary 

### Halau xifen-meth y l is a new arylpicolinate post-emergence herbicide with proposed uses on cerea l gra in s to control a variety of annual broadleaf weeds s uch as common lambsquarters, redroot pigweed , cleavers, hen bit, wild buckwheat and mustards. The pesticidal mode of act ion is as a sy nthetic aux in. This new active ingredient (ai) is being reviewed by the Age ncy as part of a global joint review project with Canada [Pesticide Management Regulatory Agency (PMRA)] and Australia [Australian Pesticides and Veterinary Medicines Authority (A PVMA)J
. The proposed u ses are the first uses of halauxifen-mcthyl in the United States
. Halauxifen-methyl may be applied as a post-emergence broadcast spray through a variet y of application methods including ground and ae rial equipment at a maximum s ingle application rate of 0.009 l lb ai/A. This assessment addresses exposure and risk associated with the proposed end-use product fo r halauxifen-methyl when used as directed by occupational handlers. There is a potential for occupational exposure associated with handler activities (i.e. , mixing , loading , and applying). Post-application exposure is expected fo r workers re-entering treated areas. Ba sed on the proposed label s · use pattern/directions (e.g., 1-2 

### appl icati ons per season), short

- term ( 1 to 

### 30 days) and intennedi ate -term (I to 6 months ) are expec ted for handler s. Long-term exposures (greater than 6 months) are not anticip ated. There arc no regi s t e red or proposed res id ential u ses, or commercial/professional uses at residenti al sites associated with halauxifcn-meth y l at this time. Therefore , a quantitative residential exposure assessment is not required. Hazard Profile and Points of Departure (POD) Halau xifen -meth y l has low acute toxicit y v ia the oral and dermal routes; and no dermal or eye irritation (Tox icity Catego ry Ill 

### or IV for all categories). It is not a sk in se nsiti zer. HED has d eterm in ed that the toxicology database for ha lauxifcn-methyl is complete and adequate to assess occupational exposure. Halauxifen-methyl and its major metabolite, XDE -729 acid, s ho w s i gnificantly different toxicological profiles. For dermal exposure, external exposure is to the parent, but sy$temic internal expos ure is ex pected to be to the acid. A 28-day dermal toxicity stu dy on XDE-729 acid in rats did not result in systemic or dermal toxicity up to th e limit dose of 1.000 !Ti g/ kg/day. A dermal toxicity study was not conducted o n halauxifen-methyl. An adjus11nent of the No Observed Adverse Effect Level (NOAEL) / Lowe s t Observed Adverse Effect L eve l (LOAEL) indicated that toxicity i s on ly observed well above the limit dose tested ( 1 , 00P mg/kg/day). Therefore , no short- o r intermediate-term dem1al endpoin ts of concern we re identified. For short- and intermediate-term inhalation risk assess ment, a POD of 3 mg/kg/day**wa~** 

### selected from a 90 -da y rat oral study on halauxifen-methyl to protect for an increased Cyplal indu c tion aud the mol ecu lar initiating eve nt identifi ed for toxicity to the liv e r from halauxifon-methyl. S ince the NOAEL for inhalation risk assessment was chosen from an oral study, it was assumed that toxicity v i a th e inhalation route is equivalent lo oral toxicity. HE D determined that a s ubchronic inhalation s tudy i s not required; therefore , an additional dat abase uncertainty fac;tor (UF) is not required ( HASPO C, TXR #0056954).
Page 4or17The level of co n cern (LOC) for occupational inhalation ri sk assessments is a margin of exposure (MOE) of I 00, based on the combined interspecies ( 1 

### OX) and intraspecies 

### ( I OX) uncertainty factors. Halauxifen-meth y l is cons id ered n o t likely to be carcinogenic and , therefore, there is n o cancer risk associated with the proposed uses. Occupational Handler Exposure No chemical-specific handler exposure data were submit ted in support of this registration: therefore , H E D relied on surrogate data in accordance with standard policies. Default ass umption s estab l ished by the l IED Sc ience Advisory Counci 

### I for Exposure (Expo SAC) were used for parameters suc h as body weigh t and area t reated. Occupational assessments for halauxifen

- methyl a r e based on inhalation exposures o nl y. All occupa tional handler scenarios for the propo se d use s resulted in MO Es g r eate r than the LOC of 100 at baseline attire (i.e
.. long-sleeved sh irt and long pants , shoes plus socks) or engineering control for aeria l applications (enclosed cockp its), and therefore , are not of concern. The propo se d labels require app lic ators and other handlers to wear baseline attire and personal protective equipment (PPE; chemical-resistant gloves). No additional PPE will be needed on the propo se d lab e ls. Although a POD from an ora l study was u sed to assess handler inhalation risk. the calculated MO Es are all ;:::2,500, thus providing an ample margin to account for any uncertainties in the ro ut e-to-rou te ex trapo lation. Occupational Post-application Ex posure 

### Inhalation Based on the Agency's c urTent practices, a quantitative non-cance r occupational post-application inhalation exposure assessment is not being performed fo r halauxifen-methyl at this time. 

### If new policies or procedures are put into place, the Agency may revis it the need for a quantitative occupat ional post-app li cation inhalation exposure assessment fo r halauxifen-meth yl. 

### Dermal Occupat ional post-application ri sk est im ates for agr icul tu ral workers fo ll owing treatments to agricultural crops were not assessed. since no derma l endpoint of concern was identified. I lalauxifen-methy l is cla ss ified as Toxicity Catego ry IV via the dermal route and for skin irritation, and Toxicity Category Ill fo r eye irritation potential. 

### It is not a skin sensitizer. The r es tricted entry interva l (RE I ) of 1 2 h o urs li sted in the proposed labels i s adequate to protect agricultural workers from post-application exposures to h alaux i fen-methyl. Human Studies Review This risk assessment relies in part on data from studies in whic h adult human subjects we re intentionally exposed to a pestic i de or other che mical. These data, which include PH ED I
. I
Page 5 of 17database ; and th e AHETF database , a r c ( 1 ) subjec t to ethic s re v iew pursuant to 40 CFR 26, (2) have rece ived that rev iew, and (3) are co mpli a nt w ith ap pli cab le ethics requirements. Fo r ce rtain s tudies , th e ethi cs re v i ew may h ave i ncluded rev iew by th e H uman St udi es Review Board. D esc riptions of data sources, a s well as guidance on thei r u se . can be found at the Agency website'.


### 2
. 0 Ri s k Assess m e nt C on c lu s i o n s a nd Recommendations 2.1 S umma ry of Ri s k Es tim ates H ED h as id entified no occ upati o nal ri s k s of concern fo r th e proposed use s of h a laux i fen- m eth y l to co ntrol annua l broad leaf weeds in wheat, barley , a nd triti cale . 

### 2.2 Label Recommendations from O cc upati onal Assess m e nt None. 

### 2.3 Label R eco mmend a ti o n s fr o m R es id e nti a l Assess m e nt No ne. 

### 2.4 Data Defi c i e nci es and Requirements No n e . 

### 3.0 Ha za rd C h a ra cterization Ac ute Toxicity Ha lauxife n-m ethyl ha s low acute toxicity v ia the ora l and dermal (Catego ry I V) routes. A n acute inhalati on s tud y was n o t conducted du e to probl e m s ge n era tin g a res pirabl e test a tm osp h e re. It i s minimall y irritating to the eye (Catego ry III ) , n o n-irritatin g to the s kin (Ca teg or y I V) , a nd i s n egati ve fo r sk in se n s iti zation.

Table 3.1. Ac u te T ox i city of Hal auxifen- meth y l (XDE-729 m eth y l ). G uidelin e No./S tud y T y pe MR ID Re s ult s Toxicity Cat e g or y 870. 11 00 /\cute ora l toxicity (rat) 485578 14 LD s o > 5000 mg/kg I V 870
. 12 00 Acute dermal toxicity (rat) 48557816 LD so > 5000 mg/kg I V

1 Imp ://www2. epa. gov/pe s t ic ide

-scicnce

-an d-as sess in g-pest ic ide-ri sk s / occupation a I-pesticide-handler-expo s ure-data a nd http :// www2. epa. gov/ pesticide- s cie nc e-and-asses s in g-o es t ic ide

-ri sk s /occupat io na I

- pe s t ic ide

- po s t-appI icat ionexpos urc

Page 6of 17870
. 1300 Acute inhalation toxicity (rat ) 48557818 Stud y not s ubmit1ed ba sed on 

### - inabi lity to genera t e le s t atm os phere
. 870
. 2400 Acute eye irritation (rabbit) 48557820 Mild eye irritant Ill 870
. 25 00 Acute dermal irritati o n (rabbit ) 4855 7822 1 ot a dermal irritant IV 870.2600 Skin sensit i zation (g uinea pig) 48557824 Nol a dermal s ensitizer NA 

### Toxicolog ica l PODs Used for Risk Assessment The toxicolo gy database for halauxifen-methyl i s comp l ete and adequate to assess the occupat ional exposures associated with the proposed use s. For dermal exposu re, external exposure is to the parent , but system ic internal exposure is expected to be to the acid. A 28-day dermal toxicity study on XDE-729 acid in rats did not result in sys temic or dermal toxicity up to the limit do se of 1 , 000 mg/kg/day. A 

### dermal toxicity study was not conducted on halauxifenmeth y l. Us ing ora l s tudie s on th e ac id with a dermal absorption factor for halauxifen-meth yl (24%) , toxicity was observed only at doses exceeding the limit dose. T here fo re , no short- or intermed i ate-term d e rmal endpoints of concern we re identified. A 90-day ora l rat s tudy was used to se lect th e dose and POD of 3 .0 mg/kg/day for s hort- and intermediate-term inhalati on risk assessment based on in creased Cyp 1 a I induction and to protect for the initial molecular event identifi ed for liver toxicity from halauxifen-methyl. The NOAEL of 10 mg/kg/day was based on the increased Cyp I 

### a I 

### indu ction effect. The effects at the LOAEL of 53 mg/kg/ day we re based on liver enlargement and hi s topathology. The se lected POD of 3.0 mg/kg/day i s considered conservat i ve and a protective endpoint for potential effects from 

### inhalation or oral (swallowi ng of non-resp irable particles) absorption. Furthermore , HED determined that a subc hronic inhalation study is not required; therefore. an add itional database uncertainty factor (UF) 

### is not required (HASPOC, TXR #0056954). There are no other uncertainty factors needed to account for missing data. Th erefore , the LOC for occupational inhalation ri sk assessments is a MOE of I 

### 00, based o n the combined interspecies ( 

### 1 OX) and intraspecies (1 

### OX) uncertainty factors. Halauxifen-methyl is considered not likel y to be carcinogenic: therefore , there is no cancer risk associated with the proposed uses. A 

### summary of the toxicolog ical doses and endpoints for halauxifen-methyl is provided in Tabl e 3.2.

Page 7of17T ab le 3.2. S umm ary o f Tox ico log ical Doses a nd E ndp o in ts for Ha la u xi f e n- methy l fo r Use in O cc up at io n al Hum a n H ealt h R is k Asses s me nts. Ex p os ure / P oi nt of U n certain ty Leve l of Co n ce r n fo r Ri s k St ud y a n d T ox icologica l E ff ect s Sce n a ri o D e p ar t ure Fac t or s A ss ess me nt Derma l Short

Term ( 1- 30 day s) and No ha1ard from dermal exposure wa s idcn1 ificd in th e available da1abasc: ther efo re. no risk is expected ln1 c rmcdia1e- from th is ex po s ure scenari o . Term ( 1- 6 months) 90

- day oral toxici ty in th e ra1 (halauxifenPOD = 3.0 me1hyl). Inhalation m g/

k

g/

day In creased hepatic Cyp l a I exp r essio n Shon-Te nn ( \- (molecular initiating event fo r toxicit y from 30 day s) a nd UFA = I Ox Occupational LO C /\ hR activation) \\as observed at 10 In termediate- ( Inh al at

ion U F11 = 1 0x fo r MOE= 100 m g/k g/day. term ( 1- 6 toxicity considered [Note: Study NOA EL= I 0 mg/kg/day months) equivalent to increased Cyp I a I induc ti on elTect. LOA EL oral tox i ci t

y.) based o n li ver e nl argeme nt a nd pathol ogy at 5 3 m l!f

k

g/da y. ] Cancer (oral. C las sificatio n : Not likely to be carcinogenic to hum ans at dose levels that do not induce Cyp Ia I express i on. The cRfD is considered protective of potential cancer effects in the absence of l ong-term de rmal. toxi ci ty data o n halau x ifcn-rncth y l becau se it protec ts for th e m o l

ec ular ini1i a1 in g event for liver to xic ity inhalation) from Ah R activa tion. Point of Depanure ( POD ) = /\ data point o r an estimated p oin l that is derived from ob erved dose -response data and used to mark th e beginnin g of ex trap o lation 10 de termine ri sk associated with lower envi ro nm entall y relevanl human exposures. OAEL
= no observed adve rse effec t le ve l. LO/\EL = lowe sl obse rved adve r se elTecl lt.:ve l. UF = un ce rt ainty fa c to r. UFA= ex trapolation from animal to human {i nters pecies). UF11 = potential variat i on in se ns itivity am ong me mb ers of the human population (intraspecics). MOE= marg in of exposure. LOC

- le vel of concern. eRfD = chronic reference dose
. 

### Abso rption : No inhalatio n absorption data are available; th e refo re , tox ic ity b y the inhalation route is con s id ered to be equivalent to th e estimated toxicity by th e oral route of ex posure. 

### B ody Weight: Th e s tandard body weight for the general popul ation (80 kg) wa s u se d for a ll exposure sce nario s covered in thi s r isk assess me nt s inc e the endpoints selected were not d eve lopmental and / or fetal effects
. 

### 4. 0 Use Profil e Ha la ux ifen

- m ethy l products a r e intend e d to be u se d as post-eme rge nt he rbic ide s for the co ntrol of an nu al bro ad leaf wee ds such as c o mmon lambsquarters
. red ro o t pig weed. clea ve rs. henb it , wild buckwheat and mu s tard s in wheat , barley , a nd triti cale. A s umm ary o f th e u se directions i s pro vided in Tab le 4.1. Four agricultura l products are proposed for us e o n wheat , barley , and triticale : Gf-2685 , GF

2686, GF-2687 , and GF-2688. These e nd u se product s may be ap plied through a variety o f application method s includin g: ae rial a nd gro und equipment. These products a re not to b e applied usin g any t yp e of chemigation eq uipm e nt.

P

age 8 of 1 7

### GF-2685 (E PA Re g . No. 6271 9 -AAN) is fo rmulated a s a water di s per s ibl e gr anule ( WG) wh ich contains 10.4 % of th e ac tive ingredient halauxi fen -methyl. GF- 26 85 i s ge nerall y app lied 2 time s per grow in g seaso n at th e lower s in g le applicati o n rate o f 0
. 0045 lb ai / A. The re com mend ed max imum single app li cation rate is 0.0091 lb a i / A. GF-2686 (EPA Reg. No
. 62719-AAR) is formulated as a water dispersib le g ranul e and contains two ac tive in g re dient s (a i): halauxifen-methyl ( I 0.4% ai) and flora s ulan1(I0 % ai). GF

-2686 is generally applied 1 time per g row in g seaso n at th e max imum s in g le application rat e of 0.0049 lb ai / A. GF- 2687 (E PA Re g. No. 62719-AAE) is formulated as a water dispersible g ranul e an d contains two ac ti ve ingredients: halauxifen -methy l (20.94% ai) and florasulam (20% ai). G F-2687 is generally applied 1 time per grow ing season at th e maximum s in g le application rate of 0.0049 lb a i

/ A. GF- 268 8 (E PA Reg. No. 6271 9 -AAG) i s fo rmul a ted a s an e mul s ifi ab le concentrate (EC) a nd contains two act ive in g re dient s: halau x if e n-m e th y l (1
. 6 % a i) and fluroxypyr (34.9% ai )
. GF2688 is ge ne r a ll y applied 1 tim e per grow in g seaso n at th e maximum si ng le application rate of 0
. 0058 lb ai / A. B ased o n th e u se patterns (i.e., 1- 2 applications per seaso n) and re sis tan ce management practice s, th e durat ion of exposu r e for th e propo se d uses is ex pecte d to b e s hort-term ( 1 to 30 days) and intermed iate -t erm ( 1 to 6 m o nth s). Long -term ex p os ures (greater than 6 months) are not anticipat ed
. The PPE statement o n the proposed labe ls requ ires app li cato rs and o th er h and lers to wear: longs leeved s hirt a nd lon g pants, s hoes plus socks and chemical -r es ista nt gloves.
Tabl e 4.1. S ummar y o f se Di rection s for the Propo se d sc s of H alauxife n-mcthy l. Pr od u ct Method of App li cation Max. ll.ate N o. A ppl. Add itiona l C rop % A.I. Application Formu lati o n Equipment • R ates per se a so n per s ea so nt I nformati o n 0.009 1 lb 1-2 GF -2685 WG I 0
. 4% XDE

-729 ai /A 0.009 1 lb ail A (de pendin g on rate) Do not apply thi s 10.4 % XDE

-729: 0.0049 lb 1-2 product via GF-2686 WG I 0% Florasulam ai /A 0.0049 lb ai/ A (depending chem i gation sys tems. on rate) PHI = 60 days: REI = 13arley. PosH:rm:rgent: 1

- 2 12-hour Triticalc
. GF-2687 WG 20.9 % XDE

-729: A.:rial or 0.0049 lb 0.0049 lb ai /A (depending

Wheal 20 % Florasulam Ground boom ai /A on rate) Do not apply thi s 1.6°0 XDE

- 729: 0
. 0058 lb 1-2 product via GF-2688 EC 34.9% ai/A 0.0058 lb ai/ A (depend i ng chcmigation systems. Fluroxypyr on rate ) PHI - 60 day s: REI = 24 -hour

·j· The minimum proposed s pray vo lu me 1s 3 gal/A for aeria l apph ca1 1 0 11 s and 8 gal/ A fo r g r o und apphcat 1 011s.**~** Do not appl y halauxifcn

- meth y l mo r e than two g rowin g seas on s per year ( i .e., S prin g a nd/o r Fa ll ).

Page 9of 1 7

### 5.0 Re s id e ntial Ex po s ur e a nd Risk Estimates There are n o regis t e red o r prop ose d res id en tial u ses a n d/o r commercial u ses at residential s ites of hal a uxifen-meth y l at thi s tim e . T he refore , a residential ex posure assessment is not require d. 

### 6.0 Non-Occupation a l S pray Drift Ex p os ure a nd Ri sk Estimates Sp ray drift i s a pote ntial so urc e of expo s ure to those nearby pe s ti c id e applications. This i s particularly the case with aerial application , but , to a lesse r extent, s pra y drift can also be a potential source of ex p os ure from the grou nd appli cati on me th ods (e.g
. . grou ndb oom) e mpl oyed fo r h alauxi fe n-m ethyl. The agency h as been wo rkin g w ith the Spray Drift Task Fo rce (a ta sk fo rce composed of various r eg is trant s which was d eve loped as a res ult of a D a t a Ca ll-In issued by E PA) , EPA Re g ional Offic es and Sta le Lead A ge nci es fo r pe s ticid e regulati o n and oth e r p arti es to de ve lop th e b est sp r ay dri f t ma n age ment p ract ic es (see th e agenc y's Spray Drift website for more information ). T he age n cy has also developed a pol icy o n h ow to approp riate ly co n s id e r s pray drift as a potential so urce of exposu re in ri sk assessme nt s fo r p esticides
. Th e potential for s pray drift will be quantit a tively evaluated for eac h p es ticid e durin g the R eg is trati o n Rev iew pro cess wh ich e n s ures that a ll u ses for th a t p esticid e wi ll b e con s id e re d concurre ntl y. The ap pro ac h is out lined in the r ev ised (20 1 2) Standard Operating Proc e dures for Residential Risk Assess m en t (S OP s) - R es id e ntial Exposure Assess m e nt Standard O p erat in g Proc e dures Addenda 1: Co n s id eration of S pray Ori 

### ft. T hi s do cu m e nt o utlin es th e quantific a ti o n o f indi rect non- occ upational ex posure to drift. 

### 7.0 No n-O cc upation a l Bystander Pos t- A pplica ti on Inhal at ion Expos ur e and Risk Estim at es V o lat ilization of pesticides may be a so urce o f post- app li cat ion inh a la tion exposure to individuals nearby pesticide app licati o n s. T he a gency soug ht expert adv ic e and input o n issu es related to vo lati li zati o n of pe s ti cides from its Federal In sec ticid e, Fun g ic id e, a nd R ode nti c id e Ac t Sc ie ntific Advi so ry Pan e l (SA P) in D ece mber 2009 , a nd rece ived th e SAP 's final re port on Marc h 2, 20 I 0 ( http: l/v vww .r eg ulation s . gov/# !docum e ntO e tail ; D = E PA- HQ-OPP- 2 009-0687- 0037). The agency h as eva lu a ted the SA P re p o rt a nd h as developed a Volatilization Screening Tool and a subseque nt Vo lati li zat io n Screeni n g Analysis ( http ://www .reg ul at ion s.gov/ # !doc ket D e t a il ; D = E PA- H Q -OPP- 20 14-02 19 ). Durin g Regi s tra ti o n R eview , th e agency wi ll utilize thi s anal ysis to dete rmin e i f data ( i. e., flu x s tudi es, route-spec ifi c inhal a ti o n toxicol og ical s tudi es) o r furth e r a n a lys is i s require d for halauxifen-methyl. 

### 8.0 Oc c upation a l Ex p os ur e and Risk Estimates 8.1 Occupational Handler Ex po s ur e/R isk Estim ates H E D u ses th e te rm h andl e rs to d esc rib e those individuals who are in vo lve d in th e pesticide app li cation proc ess. H ED b e lie ves that th e re are di s tinct job fun c ti o n s o r ta s k s re lated to appli ca tion s, and exposures ca n vary d e p e ndin g o n the spec ific s of each ta s k. J ob r e quire m e nt s (amou nt of chem ica l used in e ach app li catio n ), the kinds of equipme nt u sed, the target being

Page 10of 1 7treated, and th e level of protection used by a handler can cause exposure level s to di 

### ff er in a manner spec ifi c to each application event. Ba sed on the ant icip a ted use patterns and current labeling , as well as the types of equ ipment and techniques that can potentially be used , occupational handler exposure is expected from the proposed uses. Th e quantitative exposure/ risk assessment developed for occupational h and ler s is based o n the following sce nario s: Mixing/Loading Liquids for Aerial Application. Mixin g/Loading Liquids for Gro undboom Applicat io n , Applying Sprays with Aerial Eq uipment , Applying Sprays with Groundboom Equipment. and Flagging to s upport Aerial Applications. Occupational Handler Exposure Data and Assumptions A serie s of assumptions and exposure factors served as the basis fo r completing the occupational handler risk as se ssments. Each assumption and factor is detailed below on an individual basis. 

### Application Rat e : The maximum single application rates listed on proposed labels were used to assess handler ex po s ure sce narios (see Table 4.1). 

### Uni t Exposures: It is the policy of HED to use the be s t available data to assess handler exposure . Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, include PHED 1.1, the AHETF database, or other registrant-submitted occ up at ional exposure studies. Some of these data are proprietary (e.g., AHETF data) , and subject to the data protect ion provision s of FIFRA. The s tandard values reco mmend ed for use in predicting handl er exposure that are used in this assessment, known as " unit exposures., , are outlined in the ·'Occupational Pesticide Handler Unit Expos ure S urro gate R efere nce Table 2 " , which , along with additional information on HED policy on use of surrogate data, includin g descriptions of the various so urce s, can be found at the Agency website 3

. 

### A re a Treated: The input s for area treated were based on information in ExpoSAC Polic y 9.1 a nd include:1 ,2 00 acres for aerial applications to high acreage crops, 350 acres for flaggers to s upport aerial applications to high acreage crops, a nd 200 acres for groundboom applications to high ac reage crops. 

### Exposure Duration: HED classifies exposures from I to 30 days as short-term and exposures 30 da ys to s ix months as intermediate

- term. Exposure duration i s dete rmin e d by many thin gs, in clud in g the exposed population , the use s ite, the pest pressure triggering th e use of the pesticide. and the cultural practices surrounding that u se site. For most agricu ltural uses , it i s

2 Available: http: //www2.epa.gov/ si tes/production/ filc s/2015-09/ documents/handler-cxposurc-table-2015.pdf 3 Available: http ://www2.epa.gov/ pes ticide- sc ience-and-a ssess ing-pesticide-ri s ks/ occuP.ational-pesticide-handlerexposure-data Pagellofl7reasonable to be li eve th at occupationa l handlers w ill not app ly the sa m e c he mic a l ever y day for more than a one-month tim e frame; however, th e re may be large agribusinesses and/o r co mm e r c i

a l applicators who ap pl y a produ c t over a period of weeks (e
. g., co mpl e tin g multiple applications fo r multiple clie n ts w i thin a region). No data o n the number of exposure days per year was provided. Based o n th e proposed labe ls ' use panern/directions (e.g
. , 1-2 app li cat io n s per season), short

- term 

### (I to 30 days ) and intermedi ate -term (l to 6 month s) are expecte d for h a ndler s. Lon g- t e rm expos ures (g reater than 6 months) are not anticipated. 

### Mitigation /

Personal Protective Equ i pment: Es tim ates of d erma l and inhalation expos ure were calculated for various levels of PPE. Resu lt s are pre se nted fo r ..ba se line ,' ' de fin ed as a single laye r of clothing co n s is tin g of a lon g s leeve d s hi11 , lo ng p a nt s, s h oes plu s soc ks , no protec ti ve g lo ves, and no respirato r. as well as base lin e with various le ve ls of 

### PPE as necessary (e.g
.. g loves , res pirator, etc). The halauxifen-methyl produ ct lab e ls direct mixer s, loade rs, applicators and o th e r handl ers to wea r: lo n g - s leeve d s hirt a nd long pant s, s ho es p lu s soc ks, and c he mi ca lres istant g loves. Occu p at io n a l H a ndl er Non

- Cancer Exposure and Ri sk Estimate Equations The a l go rithm s used to esti m ate non-cancer expos ures and doses fo r occ upational handler s can be found in Appendix A. Sum m ary of O ccupational Handler Non

- Cancer Exposur e and Ri sk Es tim ates Tab l e 8.1 presents th e es timated s hort- a nd inte rm e di a t e- t e rm inhalati o n ri s k estim ates fo r occupational handlers. All occupational h andler scenarios for the proposed uses resulted in inhalation risk es timates that are g reate r than the LO C of I 00 ( i. e. , not of conce rn ) at so m e leve l of risk mitigation ( i.e. , base lin e attire w ith no r espirato r ; eng in eer in g control fo r ae ri a l applicati ons - enclosed cockp it s). Th e lowest inhalation MOE identified for handlers conductin g mixer/loader act iviti es with WDG for ae ri a l app li cati ons was 2,5 00. No a ddition a l 

### PPE reco mm e ndations are needed on the proposed label s. The Age ncy matches quantitative occupational exposure assessment with appropr iate characterizati on of exposure pote nti al. While HED presents quantitative ri sk estimates for human fl agge rs w here ap propri a t e, agricultura l aviation ha s changed dram a ticall y over th e pa st two decades. According the 20 12 ati onal Agricu l tu ral Aviatio n Assoc iatio n (NAAA) s urvey of th e ir m embers hip , the u se of GPS for swath gu idan ce in agricultural av iati o n h as grown s t ead il y from the mid 1990's. Ove r the same time period , the use of hum an naggers for ae ri a l pe s ti c id e applications ha s decrea se d steadily**from ~**  1 5% in the late l 990's to only I % in the most recent (20 12) NAAA s urvey . The Agency will continue to monit o r a ll ava ilabl e infonn at ion so urce s to best assess and characterize th e exposure potential for hum a n flag ge rs in agricu ltura l ae ri a l ap plicati o n s. H E D ha s no data to assess exposures to pilot s using open cockpits. The o nl y dat a ava il able are fo r e xp os ures of p il ots in enclosed c ockpit s. Therefore , risks to pilots are assesse d u s in g the

Page 1 2 of 1 7eng in eerin g control (enc losed cockpits) and baseline att ire (long-sleeve shirt, long pants , s hoes. and socks); per the Agency's Worker Protection Standard stipulations for engineering controls
. pilots are not required to wear protecti ve gloves for the duration of the application. With thi s leve l of protection
. there are no risk estimates of concern for applicators.

Pa ge 13 of 17Table 8. 1. S h ort- a nd Int erm ed iat e-Te rm Occupationa l Hand l e r Ex p osure and Ri s k Es timate s for ll ala u xife n - m ct h y l. Ex posure Sce n a ri o Miti ga t ion Inhal a ti o n Un it App lication R a t e ' Arca Treated d Inh a l ation Level • Exposure b Do s e• (μgl ib ai) (mg/ kg/ da y)**1** ixe r / L oader Mixin g/Load in g WDG for Ba se lin e 8
. 96 0.009 1 lb a i / A 1 .200 A 0.00 1 220 Aer ial 0.00..19 lb ai /A 0.000659 Mixin g/Loadi ng WD G for B asdine 8
. 96 0.009 1 lb ai/ /\ 200 A 0.00020 ..t Gro undb oo m 0.00..19 l b ai/ /\ 0
. 000 11 0 Mixing/l
. oading Liquids Baseline 0
. 2 1 9 0.0058 lb ai / A 1 .200 A 0.0000 1 9 fo r Aer ia l Mixing/Loading Liquid s Bas eline 0
. 219 0.0058 lb a i/ A 200A 0
. 000003 1 8 for Grounclboom Applicator Applying Sprays for En g ineering 0.00-19 0.009 1 lb ai/ A 1.200 A 0
. 00000067 Aer i al App lication con trol (enc l o s ed 0.0049 l b a i / A 0.00000036 cockpit s ) 0
. 0058 lb a il/\ 0.000000..t3 App l y in g S pr ays for B ase li ne 0.34 0.009 1 lb ai / A 200 /\ 0.00000774 Grou nclb oom Application 0
. 00..!9 lb ai l/\ 0.00000 ..t 16 0.0058 lb ai/ A 0.00000493 Flaggcr Applying Sprays for B a s eli ne 0
. 35 0.009 1 lb ai / A 350 /\ 0
. 0000 1 39 Aerial App lication 0
. 00 ..1 9 l b ai /A 0
. 0000075 0.0058 lb ai/ A 0.00000889

.. a . M 111 ga 11 o n l evel : baseline (lon g -sleeve d s hirt and lo ng**panl .**  s hoes plu s soc k s) or c11g 111 cc nn g co ntro l (c nckisc d cockpits ) lo r ac rrnl appli cati o ns . b
. Unit Exposures based o n Al I ET F / PHED
. c . Appl ica ti on Rate s based on pro p osed use o n labels
. d
. Ex p os ure Scie nce Advisory Co un c il P o li cy No
. 9
. 1
. c . Inhalation Dose ( mg/kg/day)

- Dail y Un it e xposure (1 1 g/l b ai) x App lica tio n Rate (lb ai / acrc) x Ar ca Treated I Body Weight (80 k g)
. f
. Inhalati o n ,.,!O E I I ED ( 3 .0 mg/kg/ da y)/ Inhalati o n Daily D os e ( mg/ k g/day). L OC I00.

P age 14 of 17 I nhalation**~IOE'**

2.500 ..t.600 1 5.000 27.000 160.000
9..t0.000

..t.500.000 8. 300 .000 7.000.000 390.000 720.000 6 1

0.000

220.000 400.000 3..t0.00 0

### 8.2 Occ up a ti o n a l Post-a ppli cati on Ex p os ure/Ris k Estimat es HED uses the term post-application to describe expos ures that occur when individuals are present in an env ironm ent that has been previously treated wi th a pesticide (also referred to as re entry exposure). Such exposures may occ ur when workers e nter previously treated area s to perform job functions. includin g act ivities related to crop production , suc h as scou tin g for pests or harvesting. Pos t- app li cat ion ex po s ure levels vary over tim e and depend on such things as th e type of activity. the nature of the crop or target that was treated, the type of pesticide application , and the chemical ' s degradation properties. [n add ition, the timing of pesticide applicat ions, relative to harvest activities. can greatly reduce the potential for post
- application exposure. 

### 8
. 2. 1 Occ u pati o n a l Pos t-a ppli ca ti o n Inh a l a ti o n Ex p os ure/R i s k Estim ates There are multiple potential sources of post-application inhalation exposure to individuals performing post-application activities in prev i ously treated fields. These potential so urce s include volati li zation of p esticides and resuspension of dusts and/o r particulates that conta in pesticides. The agency so ug ht ex pert advice and i nput o n i ss ues related to volatilization of pesticides from its Federal Insecticide , Fungicide, and Rodenticide Act Scientific Advisory Panel (SA P) in December 2009 , and received th e SAP ' s fina l report on March 2, 20 I 0 (http: //www.regu lati o n s . gov/# ! documentOetail;D = EP A-HQ-0PP- 2009-0687-003 7). The agency ha s evaluate d the SAP report and ha s dev e loped a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http :// www.regulations.gov /#!docketDetail : D = E PA-HQ

- OPP

-2014

- 0219)
. During Re g is trati on Review , th e agency will utilize this analysis to determine if data (i.e
. , flux studies, route-specific inh a lat io n toxicological s tudie s) o r further analysis is req uired for h a lauxife n-m ethy l. ln add iti o n , the Agency i s co ntinuin g to evaluate the available post-application inh a lation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts , the Agency will continue to identify the need fo r and, s ub seque ntl y, th e way to in corpo r ate occupationa l post-application inhalation exposure into th e age nc y's ri sk assessmen t s. Although a quantitative occupational post-application inhalation exposure assessment was not performed, an inhalation ex po s ure assessment was p e r fo rm ed for occ up a tion al/comme r c ia l handlers. Handl e r exposure resu ltin g from appli cati on of pesticides outdoo r s is likely to result in hi g he r ex po s ure than post-application expos ure . Therefo re , it is expected that these handl er inhalation exposure estimates would be protective of most occupat i o nal post-application inh a lati o n exposure scena ri os. 

### 8. 2 .2 Oc cup a tion a l P os t -app li ca ti o n D erm a l E xp os ure/ Ri s k Es tim a t es Quantitative occ upational post-app l ication r isk estimates for agr i cul tural workers following treatments to agricul tural c rops were not assessed, since no dermal endpoint was identified. 

### Dislodgeable Foliar Residue (DFR): In accordance w ith 40CFR 158, DFR data are required fo r all occupatio n al (e.g. , crop , nursery , g reenhouse use si t es) uses th at could result in postapplication exposure to foliage. In the abse nce of chem ical -spec ific DFR data, EPA u ses default
Page 1 5of17values. The 

### 2012 Standard Operating Procedures fo r Residen tial Pesticide Exposure Assessm e nt includes an a naly s i s of a number of D FR s tudi es , which resulted in th e se lecti o n of a r ev ised default values for the fraction of the app licati on rate availab l e for tr ansfer after a fo liar a pplicati o n (F A R). These values are based o n an analysis of 19 DFR studi es. Sin ce that time , th e Agricultura l R e - e ntry Task Force ha s s ubmitte d information (M RID 49299201) that correc ts an application rat e e ITor m a de in th e ori g inal submission of "ARF039

- Determination of D e rmal and Inh alation Ex posure to Re e ntry Workers During Chrysanthemum Pinching in a Greenhouse" (EPA MRID 4534450 I). As a result , the range of F AR values was r ev ised from 2%

- 89 % to 2%

- 47%. Jn the data, a la rge range of tran sferab ility is observed and thi s va riability can p oten tiall y be attributable to many factors s uch as ac tive ingredi e nt ; formulation; field conditions in the s tudi es ; weather co nditi o ns (e
. g. , humidity) ; o r man y o ther difficult to quantify factors. A lthou gh w itn esse d across multipl e che mic a ls, thi s ran ge in F A R va lu es is not ex p ecte d w hen considering DFR data for a single ch e mical. At thi s time , th e ARTF s ubmi ss ion did not alte r the se lecti o n o f 25% as the reasonab le , hi g h-end default va lu e. B ecau se DFR data are not ava ilabl e for halauxifen-methyl , EPA i s u s ing the default value of 25%. A lth o ugh th e re ma y be a s mall degree of uncert a inty in the u se of the default DFR va lu e for halauxifen-m e thyl (i.e. , there is a sma ll chance th at the F A R va lu e may exceed th e applicable default val ue ), it is like ly that the health-protective aspect s of EPA's occupatio n a l po s t-application assessment methodology will m o re than compensate for thi s potential un certainty. For example , when assess in g residential and occupational post-applicati o n exposure to gardens and ornamentals, E PA as s umes th e fo ll owing: exposures occur to ze ro-da y (i .e. , day of application) residues every day of the assessed ex po s ure durati o n ( i. e .. E P A ass um es that n o dis sipation o r degradation occ urs , it doesn ' t rain, etc) ; individuals perform the same post-application activities perform e d in the tra n sfer coef fi c ie nt study da y afte r d ay (e.g
. , weeding, harve s ting , pruning , e tc. ); a nd indi vidua ls e ngage in thes e post-applicati o n activities for a high-end am o unt of time eve ry d ay ( represe nted b y data r e flectin g time s pent ga rd ening based on survey dat a)
. Given the con se r vati sms discu sse d above and the potential compounding nature of these co n servati s ms , E PA is ab le to rely up o n the ca lculated exposure estimates w ith confidence that expos ure i s not being undere stimated. S ince n o dermal endpoint of concern was id e ntified fo r ri s k assess ment , a DFR s tudy i s not requested for halauxifen-methyl at thi s time. In this in s tan ce , it is unlikel y that DFR data wo uld be ne e d e d to further re fine expos ur e assess m ents or would add apprec iably to our overall under s tandin g of the availabi lity of dislodgeable foliar pesticide res idu es for h a lauxifen-methyl. Thi s deci s ion of n o t requ es tin g a DFR s tudy mi g ht nee d to be recon s idered i f th e re i s a change in u se p a tte rn s o r toxi co log ical e ndp o int s for halauxi f e n-methyl. Restrict e d E ntr y Interval (REI) H a lau xife n-meth y l i s classified as To xic ity Category IV v ia the d e rm a l route and for skin irritation a nd Toxicity Catego ry Ill fo r eye irritation potential. 

### It i s not a skin sen s iti zer. U nd er 40 CFR 156.208 (c) (2) ( iii ) , a i ' s cla ss ified as Ac ute III or IV for acute d e rmal , eye irritati o n and primary skin irritation are assigned a I 2 -hour REI. Therefore , the [I 56 s ubpart 

## Kl Worker Protecti o n Statement inte rim RE I of 1 2 hour s is adequate to protect agricultural workers from p ost
- application exposures to halauxifon-me th y l. T hi s is th e REI li ste d on the prop osed lab e ls , and is considere d protective of post-applicati o n exposure.

P ag e l6 of l 7

### A pp e ndix A. S umm ary of O ccupati o n al and Re s id e nti al No n-c a nc e r Algorithms Occupat iona l Non-cancer Handl e r Algorithms Potential dail y exposures for occu p at io n a l handler s are calculated using the following fo rmul as:

where: E U E 

## A

R A 

## = 

## = E = U E *AR *A 

## * 0.001 mg/ ug

exposure ( m g ai / day) , unit exposure ( μg ai / l b ai) , max imum a ppli cation rate acco rdi ng to propos ed labe ls ( lb ai / A), and area treated (e.g
.. A/da y)
. The daily do ses are calcu la ted u s in g the fo ll ow in g formu la :

where: ADD E 

## = AF 

### BW 

## = A DD = E*AF BW

average dail y do se abs o rbed in a g i ve n sce n ario ( m g a i / kg/day) , exposure ( mg a i /day) , ab so rpti on fac tor ( inh a la tion ). and bod y weight (kg). 

### Ma r gin of Exposure: Non-cancer ri sk estim ates fo r each app lic ation handler scen a ri o are calcul ate d u s ing a MO E , which i s a ratio of the tox ico log ica l endpoint to the daily dose of concern. The daily inhalation dose received by occupational handlers is compared l o the a ppro p riate POD ( i. e., NOAEL) to as sess the risk to occupational handl e r s fo r each ex po s ure route. A ll MOE va lues a re calculated using the fo ll owi n g formula:

·w h ere: MOE 

## = POD 

## = A DD 

### POD MOE = - 

### ADD

marg in of ex po s ure: va l ue u se d b y I J E D to represe nt ri sk es tim a tes ( unitlc ss)
. point of departure (mg/kg/day) , and average daily do se absorbed in a g i ve n sce nari o ( mg ai / kg/day).

Pa ge 17of 17