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

### D.C. 20460

December 03, 20 1 5 OFFICE OF C HEMICAL SAFETY AND POLLUTION PREVENTION



### H y m e xazol: Occupational and R eside nti al Exposure Assessme nt for Seed Treatment Uses on Sugar Beets in Support of Registration Review.
P C Co d e: 129107 R eg i st r at io n Nos.: 348210-1 Petition No. : NA DP Barc ode: 0429298 Dec i s ion No.: 4°!Vc/I Regulatory Ac ti on: Section 3 Case No. : NA Ri s k Assess m ent T y p e: Occupational/ Residential Exposure Assessment TX R No. : NA CAS No
. : 10004

-44 -1 40 CF R: NA MRID No. : NA


### F rom:
Through:

To: Matthew Lloyd , CIH; Indu s trial Hygienist Risk Assessmen t Branch 

### V II 

### Health Effects Division (7509P) • -/ 

# oti.

Michael Metzger, Chief
.

# ~~ Risk Assessment Branch

# «'~**I (~B57)**  H ea lth Effects Divis ion (7509 P) and Kr i st in Rury, Biolog i st

# '{-.~ a/ 

# A11J

- Ge rad Thorton,

# Environme**nt al.** **;r ote~Specialist**  

# )JJ'fl\ Expos ure Science Advisory Committee (ExpoSAC) 

### I Jealth Effects Division (7509 P ) Ca itlin Newcamp , Chemica l Rev iew Manager 

### & Tom Moriarty, Team Leade r Ri s k Management and Im pleme ntati on Branch 

### I Pesticide Re- Eva luati o n Di vis io n (7508P) The Pesticide R eevaluation Division (PRO) requested that the H ealth Effects Division ( HED ) conduct an exposure and risk assessment for the existing registration of hymexa zo l. The only regi s te red u se of hymexazol is as a s u gar beet see d treatmen t and there i s only one act ively r egistered end-use product: EPA Re g . No. 482 10-1
. Because hymexazol i s on l y a commercial seed treatment , non-occupational exposure is not expected.

P age 1 of 17

### It is HED policy to use the best available data to assess exposure . Several sources of generic data were used in this assessment as surrogate data in th e absence of chemical-specific data , including P es ti cide Handler s Exposure Database Version 1.1 (P H E D 1
. 1) , and ExpoSAC Po li c ies 1 4/ 15. J 

### (SO P s for Seed Treatment);
. Some of these data a re proprietary , and subject to the data protection provisions of the Federa l In secticide, Fungicide , and Rodenticide Act ( FIFRA )

. 

### Note : This memora ndum was reviewed by the Exposu r e Science Advisory Committee (ExpoSAC) on October 1 5t h, 20 15
.

Page 2 of 17Tabl e of C onte nt s 1.0 Executive Summary
............................................................................................................. 4 2.0 Risk Assessment Conclus io n s and Recommendations
............ ............... ............................. 6 

### 2.1 Summary of Ri sk Estimates
............................................................................................. 

### 6 2.2 Labe l Recomm enda tions from Occupational Assessment..
............................................. 6 

### 3.0 Ha za rd C h aracter iza tion
... .. .................................................................................................. 

### 7 4.0 Use Profi le .. ....................... . .. .. ............................................................................ .. .. .. ........... 

### 9 

### 5.0 Residential Exposure and Risk Est im ates .......................................................................... 

### I 0 6.0 Non-Occupat ional Spray Drift Exposure and Ri sk Estimates
........................................... I 0 7. 0 R es id e ntial B yst and e r Po s t- A pplic a ti o n Inhalati o n Ex p os ur e ......... . .. ......... ............... 

### I 0 8

. 0 Occupational Exposure and Risk Estimates
. .. ......... ....... .................................. . .. . ............. I I 

### 8.1 Occupat io n al Hand l e r Exposure/R i s k Es tima tes . .. .............. .. .. .. .. .. ........... .... .... .. .. .. .. .. .... 

### 1 1 6.2 Occupationa l Po s t- app lication Exposure/ Risk E stimates .. . . . ... . ........ .. ..... . ........ .. .. . . . ... ... 

### 1 6 Appendix A. Summary of Occupational and Residential Non-ca n cer Algo rithm s ..... ............. ... 

### 17

Pa ge 3 of 1 7

### 1.0 Exec utive S ummary Hymexazol is the Internat ion a l Organization for Standardizat ion (ISO) common name for 

### 5- meth y lisoxazol-3-ol o r 5

- meth y l-1 ,2

- oxazol

- 3

- o l ( International Union of Pure and App li ed C hemistry , or IUPAC name). Hymexazol is a systemic fungicide for control of fo li ar a nd soilborne p lan t diseases. There is an existing r eg istrati o n on ly a s a seed treatment u se for sugar beets
. As a wettable powder int ended for comme rcia l see d tre at ment , th e maximum application rate is for s tandard pelletization , at the rat e of 45 

### t o 90 

### grams of TAC HI 

### GA RE N® 70 

### WP per unit o f I 00,000 

### see ds (approx. I 

### kilogram of raw sugar beet seed) . H ymexazol may be app li ed only u s ing comme rci al seed treatm e nt equipment. Based on the exist ing seed treatment registrati o n (suga r beet) , occupational handler is expected for the short- and interm ed iate-term for prim ary handlers treating seed, and for secondary handlers who plant the seed. According to the current product labelin g, App li cators and mixer / load e rs who handle h ymexazo l , s uch as at commerc i a l seed treatment fac iliti es, mu s t wear long-slee ved s hirt and long pant s, chem ica l-re s istant gloves made from any waterproof mat eri a l, s hoe s plus socks, protectiv e ey ewear , and in the absence of adequa te venti lation o r dust control systems, a nonpowered air purify in g respirator eq uipp ed w ith a R- 

### o r P

- series filter. Baggers and other pe rsons who handle treated seed, such as at commercial seed treatment faci liti es, must wear lo n g - sleeved s hirts and long pants , shoe s p lu s socks, and protective eyewear. Hazard Characterization Technical hy mexazo l s how s low acute tox icity by the oral, dermal, and inhalat ions routes of ex posure (Toxic ity Ca tegory llf ); 

### although it is a severe ocular irritant (Toxicity Catego ry I). Hymexazo l is class i fied as a Tox ic i ty Catego ry llI 

### fo r dem1al i rri tat ion and is not a dermal se nsiti ze r. For asses s ment of occupatio nal handler ex posures , a short

- and interm ed iate -term no observ e d adverse effect le ve l (NOAEL) o f 3 1 

### mg/ k g/day wa s selected for dermal and inha lation expo s ure assessment based o n an incre ase in post-implantation loss and a decrea se in litter s ize at th e lowest observed adverse effect le ve l (LOAEL) of 1 59 mg/ kg/day from a developmental study in rats . Since no dermal absorption data ar e ava il ab le and the physiochemical data cou ld not be u se d to estimate the d ermal absorption factor (DAF), toxicity via the d e rmal rout e was co n si dered to be equ i vale nt to tox icity by th e oral rou t e of ex pos ure (I 00% 

### demial a bsorpti o n). Since no inhalation data are available , toxicity by th e inhal at ion route i s co nsidered to be equivalent to toxicity by the ora l route of exposure. A lso, s in ce the POD se lected for dermal and inhalation exposures was ba sed on devel o pmental effects, the body weight appropriate for dennal and inhalation assessments is 69 kilograms. Per HED 's HASPOC Committee, the requirement for a subc hronic inhalation toxicity stud y was not waived (HASPOC; TXR 0057244). 

### In accordance with the Agency's 2005 

### Guide lin e fo r Carcinogen Risk Assessment, hymexazol is class ified as " Not 

### Likely to 

### be C arcino g enic to Humans. " The Agency has determined that the quantification of ri sk using a no n-linear approach ( i.e. , 

### RID ) i s protecti ve of carcin oge nicit y. Pa ge 4 of 17FQPA a nd U n ce rtainty Factors The leve l of concern (LOC) for all occupational sce narios i s an ARI of < 

### I ; Since th e t ox ic o log ic a l effec t s from th e d e rmal a nd inhalation studies are co mmon , these routes ar e combined fo r the purp oses of occu pati o n a l exposure assessment. There ar e no non-dietary n o noccupational ex posure sce nario s ant icip a ted for hymexazo l wher e the FQPA safety factor app li es. Residential Expos ure Th e ex i st in g use patt e rn does not resu lt in re s id ent ia l exposures , and th erefo re , th ere are n o exis tin g re siden ti a l uses re - eva lu a ted in this d ocu me nt. Occupational Handle r Exposure Based o n th e proposed u se p a tte rn , shor t- a nd inte rmedi a te- term durations of exposure are expected for occupationa l handl e r s. The es tim ates of expos ure t o pesticid e see d treatment handlers ( tre a tm e nt a nd planting) a re based upon Ex p oSAC P o li c ies 14 & 1 5 and a memorandum from th e Bi o log ic a l a nd Economic Analysis Di v i s ion (BEA D ), "Ac res Pl a nte d Pe r Day and Seed in g Rat es of Crop s Grown in the United Sta t es" 

### (J. Becker, M a rch 

### 201 1 ). The maximum s ingl e ap plicati o n rate fo r s ugar beet seed treatm e nt i s th e " s tandard pellet " s cen a ri o. A low e r application rate ("m inimum build up " sce nario ) i s also an option based on th e label , a lth ough it i s rare ly u sed in commercial seed treatment practice. Most " standard p e ll e t" ' occ up a tional h a ndler sce n a rio s are not of concern ( based on the Agg regat e Ri sk Ind ex [ARI] LO C of I ) with label- spec ified PPE. H oweve r , for the h a ndler mi x ing the we ttabl e powd e r , the use of eng in eeri n g controls ( i.e. , wate r so lubl e packets) i s required to reach acceptab le MO Es (an 

### ART > 1). Occupational Post

- app li cat io n Ex p os ur e The potential for derm a l po s t- app licati o n ex po s ures fo ll owing the plantin g of hym exaz ol-tr ea ted seeds i s unlikel y becau se no routine cultural pra c tices inv olve susta in ed leve ls of co nt act w ith treated seed after it has b een placed in the so il or o ther planting m ed ia. Commercial treatm e nt of seeds i s not within the sco pe of the W o rk e r Protec tion S ta ndard. H y m exazol i s n o t re g i s tered fo r non-commercial see d tr eatment a nd d oes not requir e W o rk e r pr o t ectio n Standard labeling. S imil a rl y , a post-application inhalation ex posure ass e ss m e nt is n o t required as exposure i s expected to be n eg li gib le. However, th e seed treatment handler assessme nt s provide quantitative inh a la tion exposure assessments fo r seed treat e rs a nd planter s, b o th of which h ave inhalation MOEs that we ll exceed the LO C and would b e protective of po s t- app licati o n inhalation expos ure scenanos. Hum a n Studies Revi ew This ri s k asse s sme nt re li es in part on data fr o m s tudi es in whic h adult hum an s ubj ects we re inte nti o nally exposed to a pe s ticide or o ther chemical. These data , which include Pe s ticid e H andl e r s Exposure D ata base Versio n I.I ( PH ED I.I ); ExpoSAC P o li cy 14 a nd 1 5. 1 (S OP s for
Pa ge 5 o f 1 7Seed Treatment); are ( I ) subject to eth ics review pursuant to 40 CF R 26, (2) ha ve received that rev iew, and (3) are co mpliant wi th applic a ble ethic s r equ ireme nt s . For ce1iain studies, the ethics review m ay have included revi ew by th e Human S tudies Review Bo ard. Descript io n s of data sources , as we ll as gu id ance o n their use, can be found at the Agency websi te 1 • 

### 2.0 Ri s k A ss es s ment Conclu s ion s a nd Recommendation s 2.1 S ummary of Ri s k Estimates The re s ult s of the occupational handler expos ure and risk assessment in dicate that at label specified PP E some " standard pellet" (i.e., maximum si n gle applicati on rate) scenarios represent risk estimates of concern . Where risk concerns ex i s t , the combined risk estim ates are driven by der m a l expos ur e. Wi th the label defined PPE , risk es t imates of co n cern were identified for th e fol lowin g "standard pellet" scenarios: • Mixer (we tt able powder)

- combined ARI of 0.22 • Mu ltip le Act iv it ies (w/ o g loves)

- comb in ed A RI of 0.87 Combined risk estimates for the wettable powder mixer scenari o remains of concern with the addition of double laye r dennal PPE (AR I of 0.23) and exceed the ARI LOC of 1 o nl y when e n g ine e rin g contro l s ( i .e., water so lubl e packe ts) are co n s id e red
. The mu lt ip le activ it ies (w/o g loves) scenario has a comb in ed ARI below I (0.87) because the dermal MOE i s 97. Th e addition of gloves to the scenario increases the dermal MOE to 3 10 and the ARI to 2.2 For occupat io nal post-app li cat ion exposures, because of the nature of the seed treatment uses , a quantitative assessment was not conducted as exposures are adequate ly addressed by WPS provisio n s. 

### 2.2 Label Recommendation s from Occupational Assessme nt The occupationa l h and l er sce n ar ios associated with the "standard pell et " directions on the product labe l s ma y requ ire ri sk mitigation to address risk es tim ates of concern associated wi th label

- specified PPE and appli cat io n rates. Add iti ona ll y, the labe l specifies the use of " adequate ventilation or dust control systems" on the product lab el. HED recommends that additio n a l detail be a dded to ava il able prod u c t labe lin g t o de lin ea te w h e n re sp i ratory pro t ecti o n i s n ee ded for occupationa l handlers. The multiple activities (w/ o gloves) scenario is below an ARl of 1 (0.87) , although i t is because the dermal MOE (w / o gloves) is 97. The addition of gloves to the multiples activ iti es scenario in creases the AR Tto 2.2. Commercial treatment of seeds is not within the scope of the Worker Protection Standard. Hymexazol is not registered for non - commercial seed treatment and does not require Wo rker Pro tection Stan dard labe lin g.

1 hnp ://-.vww . cpa.gov / p es ticides/ sci e nc c / handler-cxposure-data.hrm l and http :// www .c p a .gov / pe s ti c ide s / s ci en ce / po sr-app- e xpo sur c -data

. html Page 6 of 17

### 3.0 

### Hazard Characterizati on H ymexazo l is a n oxazole fungicide that limit s fu n g i growth thro u g h inhibiti o n of RNA a nd DNA synthesis
. In mammal s, the adverse effects of h y mexazo l exposure were mo s t appar e nt with in utero exposu re. Developing rodents were the most s u scep tibl e popu la ti o n t o h ymexazo l tre atment, demonstrating increased se n s iti v ity at doses below that r equired to e li ci t m a tern a l toxici ty. O f th e adult a nimal s, d ogs were the m os t sensit ive to h y mexa zo l ex po s ure . Subchronic ora l exposure targeted the thyroid le adi n g to increased abso lut e a n d relative thyroid we i g ht accompa ni ed by minim a l in crease in ep ith e lial h eig ht and minim a l to mod erate th yro id ep ith el ial h yperp las ia. Neurological effects , decrease d brain wei g ht and cerebral len g th in m a les, w e re eq ui voca l and occur red aro und the limit dose. The respiratory syste m was unaffected in ora l or dermal ex p osu res and was minim a ll y tox i c in ac ut e inh a l at io n ex p os ures (Ca tego ry III )
. The immun e system was s imil ar ly unaff ec te d after ora l expo s ure up to the limit do se . Hymcxazol s h ows low ac ut e toxicity by the oral , d e rm a l , a nd inh a lation s routes of ex p osu re (T oxicity Catego ry III) , although it is a seve re oc u lar irrit a nt (Tox ic ity Category I )
. Hym exazo l i s classified as a Toxicity Category JV fo r derma l irrit a ti on and i s n o t ap pli cable for s kin se n s iti za tion. A s umm a r y of the ac ut e toxici ty fo r hymexazol i s provided in Tabl e 3. 1. 

### Table 3.1 Ac ute Toxicity Profile - H y m exazo l Guide lin e No. Study Type MRID( s) R es ults T oxic ity Ca tego ry 870
. 1100 Acute oral [rat] 42960008 LD so= Ill M = 1600 m g/k g F = 1 700 m g/k g B oth = 1 .7 g/ k

g 870
. 1100 Acute oral [mouse] LD so = 1700 m

g/ kg 870
. 1 200 Ac ut e de rm a l [rat] 42960009 LD so > 2000 Ill m g/kg 870.1300 Acut e inh alation [rat] 429600 1 0 L Cso > 0.65 m g/L Ill 4 ho ur, ae roso l, whole body 870.2400 Acute eye irritation [rabbit] 42960011 Severe ocu lar I irrit anr/Severe corn ea l opacity w / hyperaemic blood vesse ls 870 .2500 Ac ut e derma l irritation [rabbit] 4299730 1 N on-irritant I V 870.2600 Skin s ensitization [gu in ea pig] 42960012 Sensi tizing NI A ( Ma g nu ss onKli gma n maximization te st) For assessment of occupational h an dl e r ex po sures, a s h o rt - a nd int e rm ed iate -term no observe d adverse effect leve l (NOAEL) of 3 1 m g/kg/day was se l ected fo r dermal an d inhalation exposu r e assess m e nt based on a n increa se in po s t-implantation lo ss a nd a d ec rease in litt er s ize at th e

Pa ge 7 o f 1 7

### lowest obse rved adverse effect level (LOAE L ) of 1 59 mg/kg/ day from a developmental study in ra ts . A dennal abso rpti on s tud y was not submitted for hymexazo l ; th erefore , a conservative dermal absorp ti on factor of I 00% was used in lieu of an empi ricall y derived value. The p hys icochemical data and endpo int s from the g uid e line s tudi es could not be used to estimate the dermal abso rption factor (OAF). A c lea r LOAEL was not r epo rted fo r the dermal s tudy and cou ld not be compa red to LOAEL estab li s hed in th e o ral study. A I OOx UF (I Ox to account for interspecies extrapo lation and 1 

### Ox for intra s pecies variation) was ap pli ed to the NOAELs for derma l expos ures. In the ab se nce of a route spec i fic study , the offspring NOAE L from the two general reproduction s tud y was used for the s hort- ( 1- 30 da ys) and interm ediate-te rm ( l-6 

### months) inh a la tion ex posures. Absorpt io n from inhalation was assumed to be equivalent to an oral exposure. A 1 , 000x 

### UF ( 1 Ox to account fo r interspecies extrapolation and 1 Ox for intr aspec ies variation a long with a 1 

### Ox factor to acco unt for a missing inhalation s tud y) was applied to the NOAELs for inhalation expos ures. S ince no inh alation data are ava ilable , toxicity by the inhalation rout e i s co ns id ered to be eq ui va lent to t oxic ity by th e oral ro ut e of expos ure . Note: th e r equ iremen t fo r a s ubchronic inhalation toxicity study was not waived ( HASPOC , TXR 0057244). Th ere is a paucity of ev idence lin king hym exazo l t o a carcinogenic and mutage ni c mode of actio n. Rats and mice exposed to hymexa z ol at hi g h doses ( > 

### 500 mg/kg/day) fo r two years did not develop neopla s ti c tumors and no signs of mutagenicity we re reported in ge ne mutation , mouse ly mphoma , o r micronu cle us assays. In accordance with the Agency's 2005 Gu id eline for Carc i nogen Risk Assess ment , hymex azo l is cla ss ified as " Not Likely 

### to be Carci n ogenic to Human s. " 

### HED ha s applied th e tradition a l uncertainty factors o f I 

### OX for inte r-species extrapolation and I OX for intra - specie s var iabi lity. Exposure routes a re comb in ed because toxic effects are common between th e inhalat ion and dermal routes of exposure. A total agg regate d risk ind ex (A RI ) 

### was used s in ce the LOC va lues for derma l ex pos ure ( 100 ) 

### and inhalat ion expos ure (I 000) 

### a re diff e rent. A summary of the toxicological doses and en dp o int s for occupat ional and residentia l exposu re sce nario s is p r ovided in Table 3.2. Tab le 3.2
. Su mm a r y of T ox i co logica l Do ses an d Endpoints f o r H y me xazo l for Use in O cc u pationa l Human Hea lth Risk Assessments L eve l of Concern for Exposure/ Point of Uncert ain ty Risk Scenario Departure Factors Asse s smen t Study and Tox icological Effects De rm al UFA = !Ox 2- g cneratio n reproduction

- rat S hort
-and NOAEL = 3 1 Intermedi a t e - m g/

kg UFH = I Ox LO C = JOO LO A E

L = I59 m g/kg b as ed o n increase in Tenn post-impl a nt a ti o

n lo ss . d ec r ease in litt er s ize Inhalation UF"= !O x 2- gcnerati on n.:prod u cti on - rat S hort
- and NOAEL = 3J UF11 = 10 x Int ermedi ate - m g/kg UFoo= IOx LOC = 1 , 000 LO A EL = I59 m g/kg ba se d on incre ase in Tem1 post-impl a nt a ti o

n l

oss, d ec r e a

se in litt e r s iz e 

### Page 8 of 1 7Tabl e 3.2. S umma ry of To x ico logica l D oses a nd E ndp o in ts for Hy mexazo l fo r Use in O cc upational Hum a n H ea lth Ri s k Assess me nts Level of Concern for Exposure/ Point of Uncertainty Ri sk Scenario Departure Factors Assessment Study and Toxicological Effects Hymexazol is not carcinogenic in long term s tudies with rat s and mice and no t mutagenic in Ca ncer ( dermal the gene mutati o n , mouse l y mphoma , and micronucleus assays. In accordance with the and inhalation) Agency's 2005 Guideline for Ca rcinogen Ri s k Assessment, hymexazol is cla ss ified as "No t Likely to be Carc inoge nic to Humans''. Pomt of Departure ( POD ) =A data point or an estimated point that is derived from observed do se -re spo nse dat a and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOA EL = no observed adverse effect le vel. LOA EL = lowest observed adverse effect level. UF = uncertainty factor. UF A= extrapolation from animal to human (interspec ie s). UF11 = potential variation in se ns itivit y among members of the human popu lation ( intraspecic s). MOE = margin of exposure. LOC = level of concern. NI A = not app licabl e. 

### 4.0 Use P r ofile H ymexazol is a fung icide u sed in see d trea tment for con tro l of seed ling d iseases caused by Aphanomyces 

### spp. and Pythium 

### spp. in sugar beets. There are no exist in g registrations fo r agricultu ral or residential u se sites. Commercial seed treatm ent facilities may u se th e hym exazo l wettable powder (WP) form ul at io n in commercial seed treatment processing t o app ly hymexazol as either a s tand ard pellet or a minimum pellet build up. In 

### either case , hymexazol mu s t be used with an EPA approved dye that impart s an unnatural color to th e seed. Federa l Law requ ires that ba gs contain ing treated seeds sha ll be labeled with the fo l lowing information. " Thi s seed ha s be e n treated with Hymexazol fungicide. Do not us e for feed , food or o il purp oses . Store away from feeds and foodstuffs." Fo r App l ication as a standard p e ll et: 

### Apply as a comme r c ial seed trea tm e nt on p e ll eted suga r beet seeds at the r ate of 45 to 90 grams of TACH ! GAREN ® 70 WP per unit of I 00,000 seeds (approx. I kilogram of raw s ugar beet seed). Seed mu st be pelleted at a min im um weight to weight ratio of2: I pelleting mixtur e t o raw seed. Fo r App lic at ion as a minimum build-up 

### pe ll et: Apply as a commercia l see d treatment on minimum build-up pe l leted sugar beet seeds at the rate or20 to 30 grams ofTAC HI GAREN ® 70 WP per unit of I00 ,000 seeds (approx. I ki log ram of raw sugar beet see d)
. Seed mu st be pelleted at a minimum weight t o weight ratio of3 :10 pelleting mixture to raw seed. The ex i s ting lab el in g restri c ts use of hyme xazo l "on agricultural establ ishme nts in hopper-box , planter-box , slurry-box or other seed

- treatment appl ications at or immediately before planting. " Commercial seed treatment uses are registered for suga r beet, and the one wettable powder (W P ) fo rmulation ca n be applied using on ly commerc ia l see d treatm e nt eq ui pment. The existing use pattern is outlined below in Table 4 .1
. 

### Page 9 of 17Tab l e 4 .1. S ummar y o f P ro p ose d C omm e r c ia l See d Tr e a t m e nt Uses o f Hy m exazo l Fo r mu l:llion Use Direction s an d !EPA Reg. No.I Crop Max Applkation Rat cb Limitat ions Trade Na me• 

### • 90g/ 1 00.000 seeds 

# . Seed mu s t be 70% TACHIGAREN® 70 pelleted at a WP Sugar beet 90 g produc t I kg seed 0
.056 lb ai/lb seed minimum 148210-1] Standard pe ll et weight to weight ratio of 2 : I pelleting mixture t o raw seed
. 

# . 30g/l 00.000 seeds 

### • Seed mu s t be 70% TACH lGAREN® 70 Sugar beet pelleted at a minimum WP Minimum build up 30 g product I kg seed 0
.02 1 lb ai/lb seed weight to [-1821 0 -11 pellet weight ratio of 3 : 1

0 pelleting mixture t o raw seed • Fomrnlation codes: WP = wettable powder. b As registered rates are given as "mass ai per seed", a seed count( # see ds per pound) is neede d to convert to " mass

ai per pound seed" for th e purposes of estimating exposure. Ba sed o n the BEAD m emo "Acres Pl anted Per Day and Seeding Rates of Crops Grown in th e United States" (J. Becker , March 2011), the followi ng seed count convers ions were used to convert lb ai / seed r ates into lb ai/lb seed: sugar beet

- 40,000 seeds per pound. 

### 5
. 0 R es id e ntia l Ex p os ure a nd Ri s k Es tim ates The ex i s ting see d treatment u se of h ymexazol are not expected to re s ult in residentia l (nonoccupational n on -diet a ry ) exposures. Therefore , no quantitative assess m ent has been completed for handlers o r post-application sce nari os. As there are no residential use s assessed, there i s no resid e ntia l contribution to the aggregate r i sk assessment. 

### 6 .0 No n - O cc up a ti o n a l S pr ay Drift Ex p os ure a nd Ri s k Estim a t es Spray drift i s a potential sou rc e of exposure to those ne arby pesticide applications. Where appropriate, the potential for spray drift will b e quantitatively evaluated for each pesticide during the R eg i stration Rev iew proce ss wh ich e nsu r es that a ll u ses for that pesticide w ill be considered co n cur rently. 

## r n the case of h ymexazo l , the on ly registered use si te is commercial seed treatment. Planting p elle ted seed treated with hymexazol is not anticipated to result in spray drift. 7 .0 

### Res id e nti a l B ys t a nd e r P os t -A pp li ca ti o n I nh a l ati o n Ex p os u r e Volatilization of pe stic ide s may be a source of post-application inhalation exposure t o indi v iduals nearby pe s ticide app l ication s . The agency sought expe r t advice and input on i ss ues relat ed to volatilization of pesticides from its Federal I n sect ic ide , Fungicide , and R o denticid e Act Scientific Adv i so ry Panel (SAP) in D ecember 2009, and rece ived the SAP 's final report o n March 2, 2010 ( http ://www.epa.gov/ scipoly/ SAP/ meeting s/20 09/1 20 109meeti ng . html)
. Th e agency has evaluated the SAP r e port and has dev e loped a Volatilization Screen i n g Tool and a Page 10 of 17

### subsequent Vo latili zatio n Screening Analysis ( http :/ / www.regulations.gov/ # !docketDeta il ;D=E PA-HQ-OPP-2014-0 2 1 9). During Registration Rev iew , th e agency will utilize this analysis to determine if data (i
. e. , flux studies, route-specific inhalation toxicological studies) or further analysis is required for hymexazo l. 8.0 Occ up ati o n a l Ex p os u re a nd Ri s k Es t i m a t es 8. 1 Occ up ati o n a l Handl e r Ex p os ur e/ Ri s k Es tim a t es 

### HED uses the term handlers to describe those individuals who are involved in the pesticide app lication process. HED be li eves that there are distinct job functions o r tasks r e lated to applicat ions and exposures can va ry depending on the specifics of each task. Job requirements (a mount of chemical used in each application), the kinds of equ ipment used , the target being treated, and the leve l of protective gear or controls used by a handler can ca use exposu re leve ls to differ in a manner speci fic to each application event. Based on the existing seed treatment registration (sugar beet) , occupati ona l handl er exposure is ex pected. Occupational seed tr eatment handlers may experience short- and interm ediate-t e rm exposure to hymexazol while performing seed treatment activities in comme rci a l sett ing s. In addition , occupationa l handler s may experience shor t- and int ermediate-term exposure while planting hymexazol-treated seeds (for the purpo ses of seed treatment ri sk assessment, plant i ng treated seeds are ref e rred to as 's econdary handl ers'). Treating Seed ( Prim ary Handler) Potential occupational exposure scena r ios from the use of hyme xazo l as a commercial seed treatment include: mixing, loadi ng, app ly in g wettable powder formulations ; bagging treated seed ; sew ing bags ; and multiple act i v ities. Typically , for large - scale commercial seed treatments , workers perform only those spec ific individual tasks li s t ed above; however , it is assumed that workers a lso ma y perform multiple activities throughout the da y. As a re s ult a " multiple activities " scenario (i.e. where one worke r performs all see d treatment ta s ks such as loading/applying , sewing, bagging , cleaning, calibration, repair , forklift driver, etc.) was addressed. Planting Treated Seed (Secondary Handler) Potential occupat ional exposure sce nario s from the use of hym exazol as a co mmerci al seed treatm e nt include planting tr eate d seed (seco ndary handler). P lanting treated seed consists of the farme r purchasin g bags of treated seed , placing the seed in the hopper and applying seed to fields. The quantitative exposure/risk assessment developed for occupational handlers i s based on the follow in g sce narios:

• Mixer

- wettable powd er s lurry • Mixing/loadin g/applying wettable powders; Page 11 of 1 7• Bagging treated seeds; • Sewing bags with treated seeds; • Multiple (commercial) seed treatment act ivities; and, • Planting treated seeds. Occupational Handler Exposure Data and Assumpt ions Applicators and mixe r/loaders who handle hymexazol , such as commercial seed tr eatment facilities, must wear long-sleeved shirt and lon g pants, che mical-r esis tant gloves made from a n y waterproof materi a l , s ho es plus socks, protective eyewear, and in the absence of adequate ventilation or dust control systems, a non-powered air purifying respirator equipped with a Ror P- series filter. Baggers and othe r persons who handle treated seed, s u c h as commercial seed treatment facilities, must wear the same protection as app licator s and mixer / loaders minus the chemical resi sta nt gloves. A ser ies of assumptions a nd exposure factors served as the basis for comp leting the occupational handl er risk assessments. Each assumption and factor is deta il ed below on an indi v idual basis. 

### Expo s ure Duration Treatment of the proposed seeds is expected to r es ult in s h o rt- and interm ediate -te rm exposu re. However, since the same dermal and inh a lation endpoints were selected for short

- and intermediate-term exposure durations , and the assessment is protective of both exposure durations. According to a survey by the Agricultura l Handlers Exposure Task Force (AHETF, 20 I 0) com commercial facilities operate 240 days per year (50 1 h percentile; range 150 to 270 days) , canola commerc ial faci liti es operate 180 days per year (50 111 percentile: range 90 to 2 10 days) and 39% of soybean i s treated downstream for a duration of 49 days (50 111 percentile; range 4 to 150 days), while soybean comme r c i a l facilities operate 210 days per year (50 1h percenti le; range I to 270 days). No information is available on sugar beet seed treatment. While these durations would be considered to potentially exceed the typical intermediate-term duration used in H ED's occupationa l assessments, HED had no information to indicate that the same chemical is u sed consecutively for a long-term duration. Therefore, chronic occupational handler exposure for seed treatment was not assessed. 

### Application Rate Refer to the proposed use pattern table in Section 4.0. Tab le 6.1.1 s how s the risk estimates for the maximum s ingle application rate (i.e., the "s tandard pellet"). The standard pellet rate that is assessed is protective of the lower application rate (i.e., minimum buildup) identified in Section 4.0. 

### Unit Exposures

P age 12of17It is the policy of HED to use the best available data to assess handler exposure. Che mi calspec ific data for assessing exposure durin g commercial seed treatment and seed planting were not s ubmitt ed to the Agency in su pp or t of this Registration Review action. Unit expos ures are der i ved from: 1) 

### mixing /loading well

### able powders

- Septe mber 20 I 5 Occupational P es ticide Handler Unit Expos ure S urrogat e Referenc e Tab le (M/ L wettab le powders) 2) 

### all other occupational handle r scenarios

- ExpoSAC P o lic y 14: SOPs for Seed Treatment (May 1 , 2003), which are based on data for open mixing/loading/ application systems. 

### Amount Handled HED is currently in the process of re v i si ng ExpoSAC Polic y 1 5: Amount of Seed Treated o r Planted pe r Day (Marc h 2, 2004) in effo rt s to update the dai ly amoun t of see d treated in comme rcial seed treatment facilities. With the in creas ing demand for hybridized treated seeds, the re have bee n modifications not only in the seed treatment equ i pment , but in the market shares of new and currently registered pesticide products. HED und ersta nd s that due to th e high cost of producing hybr id seeds, direct seed ing i s done in a prec i se manner wh ich requir es lower volumes of seed per acre. H owever, thi s does not pro v id e a direct correlation to the amount of seed which is treated in the commercial seed treatment facilities. The amount of seed handled (for both pr imary / treater and secondary/ planter handlers) is ba se d on HED ExpoSAC Policy 15 , HED ExpoSAC Policy S OP 15.1 , and the BEAD memo: " Acres Planted Per Day and Seed in g Rates of Crops Grown in the Uni ted States. " In some cases, the amou nt of see d p lan ted per day i s a conserva tive calculation based on a low amount of seeds per pound and a high amount of seeds planted per ac re (e.g
. , for s ugar beet s: 435 ,600 seeds/ acre -;- 40,000 seeds/lb 

## * 80 acres planted per day = 870 lbs seed). The amount of seed t r eated per day at a commerc ial fac i lity i s s ummari ze d below for sugar beets.

Amo u nt o f Seed Crop /Seed Treated p e r D ay So u rce (lb)B ExpoSAC Policy 15. l Sugar beet 3 ,000 ( " General infonnation from a small number of facilities (exac t number not reported) that film-coat small seeded vegetables was collected by the AH ETF (20 10 ). ")

• Estimates are based on s hort-term / intermediate-term durations. The amount of seed planted per day is su mmari zed b e low for eac h crop. Amo unt of Seed C rop/Seed Pl a n ted per D ay So u rec/ Calcu l atio n (lb) 435,600 seeds/ acre + 40,000 seed s/lb • 80 acres planted / da y Sugar beet 870 • 435 , 600 seeds/ acre: Table I 0, BEAD m e mo • 40,000 seeds/lb: Tab le B-1 , BEAD m e m o • 80 acres planted per day: ExpoSAC Policy 15
Page 13 of 17

### Mitigation /Personal Prot ec ti ve Equipment: 

### To reflect th e r eg istered registrati o n , estimates o f dermal and inh ala tion exposure we re calculated for " baseli ne"

- defined as a sing le layer of clothing consisti ng of a long s leeved shirt, long pants, shoes plus socks, no chemical -res istant gloves , and no respirator. Additional dermal and inhalation exposure est im a te s were calculated where potential risk concerns were identifi ed
. For exa mple , the mi xe r sce n ario for co mmercial seed tr eatm en t was al so eva lu ated with double laye r denn al PPE plus c hemical -resis t ant gloves. Occupational Handler Non-Cancer Exposure and Ri sk Estimate Equatio n s The algorithms used to estimate non-cancer exposure and dose fo r occupational handlers can be found in Append ix A. Combining Exposures/ Risk Estimates Exposure routes are combined because toxic effec ts are common between the i nhalation and dernrnl routes of exposure. A 

### total aggrega ted risk ind ex (AR I) was used since th e LOC values for dermal exposure (I 00) 

### and inhalation exposure ( 1000) 

### are d i fferen t. The target ARI is 1; 

### therefore , ARls of le ss th an I 

### a re risk estimates of concern. The aggregate ri sk ind ex (A RI ) was calculated as follows.
A ggregat e Ri s k Ind e x ( ARI )= /.:,- [ (D e rmal LOC + D e rmal lv!OE ) + (/nha/ati o 11 LOC .:,- fnhalati o n J\1/0£ )) 

### Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates Occup at io na l handler risk es tim ates are prese nt e d below in Table 8
. 1. l
. 

### Th e occ up at io na l handler ri sk est im ates are prese nt ed fo r the " stand a rd pellet " app lic at io n scenario (the hi gher appl ication rate). The results of the occupational handler exposure a nd ri sk assessme nt indicate that short- and interm ed iate -term combined derma l and inh a lati o n risk estimates exceed H ED's LOC in some cases. Where ri s k concerns ex ist, the combined ri sk estimates are dr iven by de rm a l expos ure , and with the label defined PPE , ri sk es timat es of concern were id ent ifi ed for the following "standard pellet " scenarios: • Mixe r ( wettab le powder)

- combined ARI of 0.22 

### • Multiple Acti vities (w / o gloves)

- combined ARI of 0 .87 

### Overall , derma l MO Es range fr om 97 

### to 1,800 

### fo r see d treate rs (L OC 

## = I 00). The mu ltiple act iv iti es (w/ o gloves) sce n ari o has a combined AR I below 1 

### (0.87) 

### because the dermal MOE is 97. 

### Inhalation MOEs range from 300 to 70 , 000 

### for see d tr eaters (LOC 

### = 1 , 000). 

### Combined risk estimates for the wettable powder mixer exceed the ARI LOC of I 

### only when engineering controls (i.e., water solub l e packets) are considered
.

P

age 14 of 1 7Table 8.1.1 S umm a r y of S hort- and Int er me di ate- Term Hand le r Exposure s a nd Risks fo r H y me xazo l See d Treatment Max U nit Expo s ure 2 Amount Ab s orbed Do se Applicati o f See d MOE 5 See d T y pe on R a te 1 (mg / lb ai) Treated 3 (mg/ kg/da y) 4 Total ARl 6 ls u ga rb ee t) l b ai/lb l b D e rm a l Jnhal. s eed D erm a l I n ha I. s ee d/ da y Dermal lnhal. (LOC= (LOC= 100) 1,000) Mixe r - W etta bl e P ow d er (single layer, g loves , n o r e s pirator) S ta nda rd 0.056 0
. 1 70 0
. 04 3 4 3, 000 0.4 1 0.1 04 76 300 0.22

Pe ll et Mixer

- Wettable Powder (do ub le l aye r , g loves , PFS r e s pi rato r ) S t andard 0.056 0.130 0.0434 3,000 0.3 1 0 .1 04 100 300 0. 2 3

Pe ll e t Mi xe r - Wettable Powd e r ( d o u bl e la ye r , g l oves , no r es pirat o r ) S t a ndard 0.056 0. 1 30 0.00868 3,000 0.31 0.021 1 00 1500 0
. 6

Pellet Mixer

- Wettab le Powder (wate r solu bl e packets, n o r es pirator) S t a nda r d 0.056 0.0 0 98 0. 0 002 3, 000 0 .023 0.001 1 3 00 54 , 000 1 0.S Pe ll e t 4 LOADER/APPLICATOR (single laye r , g love s 7 ) Standard 0.056 0.023 0.0003 .t 3,000 0.055 0.001 560 38,000 4.9

Pellet SE W E R (si n g le layer, no g loves) S t and a rd 0.056 0.0062 0.00023 3,000 0.0 173 0.0006 2, 10 0 56,000 1 5.3

Pe ll et BAGGER**(s in~l** **e** l aye r , no glov es ) Standard 0.056 0.009 1 0.000 1 6 3,000 0.02532 0.00045 1,400 8 1 ,000 I 1.9

pe ll e t M U L TrPLE ACTIV I TIE S (co mbi n a tion of load e r /app l icator w ithout g loves '+ no covera ll s, sewer without glove s , s tacker wi th o ut g l oves) Standard 0.056 0.134 0.00 1 6 3,000 0.320 0.0038 97 8. 100 0.8 7

pellet M U LTrPLE ACTIVITIES (co mbin at io n of l oa d er / a pplic ato r with g loves 7 + no covera ll s, sewer with g loves, stac ker w i t h !! loves) S t andard 0.056 0.042 0.0 01 6 3,000 0. 1 00 0.0038 3 10 8, 100 2.2

pellet I Applica1ion Rates based on existing label uses fo r hymcxazol (sec Table 4
. 1 )
. 2 Uni t Expos ures from HED Exposure Science Advisory Counci l Po l icy 14
. 3 1 I ED default for lb see d lrcmed per day from HED Expo s ure Science Advisory Co un ci l I nte rim Policy 15
. 1 an d t

he 13EAD me m o**"Ac s**  Planted Per Day and Seed in g Raic s of Crops Gro wn in lh e U nit ed S ta t es" (J. Bec k e r. Marc h 20 11 ). 4 Daily Absorbed Dose (mg/kg/day)= dai l y u nit exposure (mg/lb ai) >< ap pl ication rate (lb ai/lb seed) >< amoun t tr eated ( l b seed/ day ) >< Absorp1io11 ( 100% fo r dem1al, 100% fo r inhalat ion) + body wcigh1 (69 kg adult female for derma l exposure due t o sex -specific t ox icity ; 5 MOE = NOAE L (dcm1al = 31 mg/kg/day for shon- and intermediate

-term exposure: inhalation= 31 mg/kg/day for shon- and intcrrnediatc-tcm1)

... Absorbed Dose (mg/kg/day)
. LOC = I00
. 6 ARI "' Aggregate Risk Index = I + [ ( Demial LOC + Dc n nal MOE)+ ( I nh alation LOC + Inhalation MOE)]
. 7 Avai lable data r eprese n t s wo r ke r s wcar in l! chc m ical-res is 1 m11 gloves a n d other label- r e prese nt ed P PE
.

Table 8.1.2. S umm ary of Seco ndary H a ndler (P la nt e r ) Ex po s ure a nd Ri s k Esti mat es for H y mc xazo l (Sing l e L ave r , Gloves during L oa ding On l y )
.

Seed M ax Un i t Ex po s ureb Amount Ab s orbed Do se App l ication of Seed MOE • Tota l ARI' T y pe Rate ' (m g/l b a i ) P l ante d ( m g / kg/da y ) d


### Page 15 o f 17P e r Da y e lb Der ma l l nba l
. lb ai/lb see d D e rmal l n h a l
. seelfl <lay Derma l In h a l
. (LOC = ( L OC = 1 00) 1 , 0 00) S tand a rd 0.056 0 .25 0. 00 34 87 1 0
. 1 74 0.0 0 24 1 80 1 3,000 1. 6

Pe ll et a A ppli c au o n Rate s based on p roposed label use s for h y mc xa/ o l (s ee Table 4
. 1 )
. b U ni t Expos ure s fro m 111 !0 E xposure Science Advisory Co u ncil P o licy 1 4 : S tan dard Ope r a 1

i n g P r oced ures fo r Seed T r eatm e n t Avai lable data r cprc sc nl s wo r ke r s wea ri n g c h c 111i ca l· rc s is 1 a nt g l ove s . U nit ex pos ures r c prcse n1 i n g w o rker s with o ul chc111i ca l

-r cs is 1an1 g l oves we r e ca l culat e d b y in c re as in g ex pos ure t o 1h e h a nd s -o nl y po rti o n o f 1h c t o ta l d e rmal e xp os ure m eas urc m c ni ass umin g c hemi cal-res is ta nt g l oves prov ide 90 % p r

o 1

cc 1

io n ( i.e
. , d iv idin g n o n- g l ove d h an d ex po s ure s by 0
. 1 ). th e s t a ndard prol cc tio n fac 1 o r ass um p tion fo r c h emica l-rc s is 1an1 g l o ves . c 1 IE

D dcfa ul l for lb s eed p l a 111 cd per day fo r s u g ar bee ls fro m H E D Expos ure S c ie n ce Advi so ry Co un c il lnl er i m P o li cy 1 5 and th e B EAD m

e m

o ··Ac re s Pl a 111 c d Per Day and Seedin g Ra1es o f Cr o ps G r o 11n in the U niled S 1a1es · · (J
. B e cker , Marc h 2 0 1 1)
. d Dail y A b so rbed Dose ( m g/kg/ day)= dai l y uni l expos ure ( m g/

lb ai ) >< applica 1 io n r:ue ( lb a i/l b s eed )**~** am ou nl trealcd ( l b s eed/day ) x A

bsorp 1 ion ( 1 00% fo r de mial , 1 00 % f o r i nh ala 1i o n ) + bo dy wei gh! (69 k g)
. e MOE = NOAEL (d erm al = 3 1 m g/kg/ da y fo r s h o rt- and in1 c rm cdi a1 c -1 e rn1 ex p os ure : inhalali o n = 3 1 m g/kg/ da y fo r s h o rt - an d i

n1 c nn c di a1c1 c rm) + A bsorb ed D os e ( m g/k g/day)
. LO C = 1 00
. f A RI = A ggre gale Ri sk I ndex = I + [ ( Der m

al L OC + Der m al MO E)+ ( lnh ala1 ion L OC + lnh alali on MO E) ]
. 

### 6.2 Occ u pationa l Po s t
- app li cation Exposu r e / Risk Estimates 

### H

E D u se s th e te rm post-appli cati o n to de sc ribe expo s ur es that occur when indi v idu a ls are prese nt in an e nv ironment th a t has b een prev io usl y tre ated w ith a pes ti c ide ( al so refe rred to as r e e ntr y exposure)
. S uch expo s ures may o ccur when work e r s enter prev iously treat e d areas to perform j ob functions , including ac ti vities related to crop production , suc h as scou tin g fo r p es ts or harvesting. Th e p o t e ntial fo r d e rma l and inhalation pos t-applicati o n e xposure s fo ll o win g th e plantin g of hym exazol -tr eated seeds is unlike ly becau se no rout in e cu ltural practices in vo lve susta in ed le ve ls of contact with treated seed afte r it has been p lac e d in th e so il o r other plant ing media. Co mm ercial tr eatm e nt of see d s is not w ithin the scop e o f th e Worker Protecti on S tandard. Hy mex azo l is no t reg is tere d fo r no n-comm erc ial se ed treatment and d oes not r equi re Worke r Protec ti o n Stand ard labelin g .
A 

### pos t-applic ati o n inhalati o n ex posure a ssess m e nt is no t required as e xposure is ex p ecte d to be n eg li g ible. Seed tr eatment a sses sment s pro v ide quantitative inhalati o n e xposure a s s e ssment s for see d treaters and secondary handlers (i
. e. , planters). It 

### is expected that these exposure estima t es would be protecti ve of any p otential low-l e ve l post-application inhal a tion expo s ure that could re s ult from th ese ty pe s of a ppli ca tio ns.

Page 1 6 of 17Ap p e ndi x A. S umm a ry o f Oc c up at io n a l a nd Res i de nti a l N on- ca n cer A l gori t h ms Occupational Non-cancer Handler Algorithms Potential daily exposures for occupational hand lers are calculated using the following formulas:

where: E UE AR A 

## = E = UE *AR* A 

### * 0.001 mg l ug

exposure (mg ai/day) , unit exposure ( μg ai/l b ai) , maximum application rate acco r d ing to proposed labe l (e.g., lb ai / seed or lb ai / lb seed) , and area treated or amount handled (e.g., lb seed / day ,# seed/day)
. The daily doses are calculated using the following fo rmula:

where : ADD 

### E AF 

### BW = 

### ADD = E*AF 

### BW

average da i ly dose absorbed in a given scenario (mg ai/kg/ day) , exposure (mg ai /day) , absorption factor (dermal and/ o r inhalation), and body weight (kg). 

### Margin of E

xpo s ure: Non-cancer risk est imates for each app lication hand l er scenario are calculated using a Margin of Exposure (MOE), w hi ch is a ratio of the toxicolog ical endpo int to the dai ly dose of concern. The daily demrnl and inhalation dose received by occupati ona l hand lers are compared to the appropriate POD ( i .e . , NOAEL) to assess the risk to occupational handlers for each exposure route . All MOE va lues are calculated using the following formu la:

where: MOE 

## = POD 

## = ADD 

### POD MOE = - ADD
margin of exposure : value used by HED to represent risk estimates (un it less), point of departure (mg/kg/day), and average daily dose absorbed in a g iven scenario (mg ai / kg/ day). The Aggregate Risk I ndex (AR I) formula (that comb ines dermal and inhalation doses with difference tox i cological Le ve l s of Concern (LOCs) is located in Sect ion 

### 8. 1
. Page 1 7of 17