### EPA REGISTRAT ION DI VI S ION C OMPA NY NOTICE O F FILING FOR PESTI C ID E PET IT IO NS PUBLIS HED I N THE FEDERAL REG ISTER E PA Reg is tra tion Di vis i o n co ntact: Heath er 

### A. Garv ie, 

### (703) 308-0034



# ~ I

NST R UCT I ONS: P le a se utili ze t hi s o utlin e in pre par · in g t h e p es ticide pe t iti o n. In case s wher·e t h e o utlin e c le m e nt d oes not ap pl y, pl ease in se rt "NA -R emovc" and m a inta in th e outline. Pl ease do n ot c h a n ge t h e marg in s, f o nt, o r f ormat in yo ur p es ticide p e titi o n . S impl y r e pl ace t h e in s truction s that appear in green, i. e., 

## "I in se rt compan y nam e!," w ith the in fo rm atio n spec ifi c t o yo ur ac ti o n . 

### TEMPL A TE: ISK Bioscicnces Co rp ontti o n llnsc r ·t petition numh erl

1·1' \ ha
.... rL·cci\L'd a pvaicitk pL'Itlton ( ! in sert p e tition numbCI"I) fr()m IS K Bio s c i e nce s Co r · poration , 74 7 0 A uburn Road, S uite A, Co n co rd , O hi o, 44077, **tm>J1""in~.** pm"ill.llll l(l
....cl..liPn -10!\(d) ot' 

### the h:dcral l·ooJ. Drug. and Cosmetit; t\ct (I I I)(· \ ). 1 l l 1 S.( · **~·~<l.t(** d). to <llm:nd -10 ('I· R part l Xtl

**h~** C'\l<lhlishing a toli:rancc I'm tL idllL'" 111 th e h e rbicid e To lpy ralate , 1 -ll l -Ethy l
- 4 -13-(2- mctho xye thox y)-2- m e th y l
- .t - ( ml'lhyl s ulf o n y l) hen zoy ll- 11
-1
- p yntzo l-5-y ll oxy l(•th y l meth yl

**c~l** rhon a t e (CAS) , **in cludin~**  its metabo lite MT

- 2 1 53 , 111 ut 1111 tiH: I'll\\ 

### ,\gncullmal **rnmmoditic~** Co rn 

### "hiLh tncludc". 11rld 1.111'11. ·,\\L'l'l \.'lllll and f'\lpcorn. at 0.0 1 parts pL'r millton (ppml. IY.\ 

### h:t..; dl'IL'I'Iilllk'd th<tl thL· pctiti,H1 -:uJ't·uns 

### data lit' inlilf'lll<llion 

### n.:ttanJing the dements st:t lunll in ..;ccli(ltl

**~OX** !d\1.2) ,,, ll)f)l',\: hll\\'l'\l'l. U'·\ has not l'ully **e\·,llunt~d** the: <;ltJ'IiciLill.:y ol' tile "llhmith.:d

**d~1!.1** .11 thi-; time lll' \\ ilL'Lher tltl'

**d~tl<l** supports granting of the pditintl. .\ddititlnal dat:1 nl,l) hl'

**!1L'c~kd** 

### bc!'urL' 1-.P:\ ruks on tile pc:lititlll.
f>l<1111 lltdcthu/1.\111 The m e taboli s m of tolp y ntlatc a s \ Y

ell a s the nature of t h e r e s idue s in com ( maize) is adequate ly unders too d fo r the p urp ose s of thi s t o lerance. A metaboli s m s t ud y was co ndu c t ed with m a ize. T h e ma in metabolite o f tolp y ra latc was MT

- 2153 compris in g up to 8'Yt ) in immature har·vc s t s and up to .t' Yt, in matur e harvests a nd a number of minor metabo lites and bound re s idues. li e n ee, par·cnt tolpy ralate and t h e metabolite MT-2153 define t h e n. 's i duc of conccm .

. 111ult nnrl 111< I!Jtld. A pn1 c tical a nal ytica l m e thod for

**p~Ta atc**  and MT2 1 53 u s in g Liquid C h ro ma to g r ap hy-MS / MS i s a v ailab le for ana l ys is of a ll 

## APR 

## 1 4 2 0

152 plant matrice s . This method has b ee n confirmed through independent laboratory va li dation and is availab le for enfo r cement purpo ses.

,**/u~nitude 1~/**  

### n.: ., id!f(:s. Co rn trials were conducted at 28 s ite s in the USA and Canada on field corn (20), s weet corn (S) a n d po p corn (3)
. One app lication at the target rate of 0.089 lb a. i./A (100 g a i / h a) wa s made to the treated p l ots . The total a pplicati on r ate rang e d f r om 0.070 to 0.093 lb a . i./A (7 8- 104 g a.i./ha)
. No re s idue s above the LOQ were found in s amp l es with PH l 's of 20 day s or longer. Proce ss in g sam ple s t r ·catcd at a 5X rate had no detected re s idues e i the r in the cor·n g nlin or the pro cesse d fract i o n s . /J 7 nxiw/op,icul**l'n~ji/e** I.
. ·/cut e toxicitv. Re s ult s fr o m a battery of acute toxic i ty st ud i es place techn ica l To l pyralate i n Toxicity Categot·y II I for o r a l 

### LO su a nd d e rma l LD:-o , and Category IV for inha l ation LCso, derma l i rri tat i on, and eye i rritat i o n . Technica l To lp y r a l ate was not a dermal sensitizer. In an acute ne u rotoxicity st udy , Tolp yr alate was adm i n is tered ora ll y to groups of rat s 

### at oral do ses up to 2000 m g/ kg , with no ev idence of neurotoxicity o r · neu r ·o hi s topatho l og ica l c h ang e. Co n se quently, 2000 mgll<g wa s cons idered to be the NOEL. 2. ( ;cnotoxicity
. The ge no tox ic potential of To lp yndate ha s be en assessed a s n egative by several 

### in vitro and 

### in vivo mutagen i city studies. Tolpyra l ate d i d n ot e li cit a gcnotoxic r esponse in any o f the st udie s conducte d
. 

### :1. l<eproduuin· and dcn:loJmJel?lal toxicil)'. Res u lt s from a two-generatio n s t u dy indicate that Tolpyn1latc is not a reproductive toxicant. T h e N OEL for r eproductive performance wa s > I 000 ppm , t h e hig h est do s e te s ted (equiva l ent to >54.9 and >8 1.8 m g/kg/d a y, respec ti ve ly for P male s and female s and > 63.3 a n d >9 0.2 mg/ kg/ day for 

### Fl ma les and female s)
. The no observed-adverse-effect le ve l (NOAEL) for sys temic effects i n par·enta l r·at s is S ppm (0.27 0/0 .4 1 0 mg/ l<g bw/ day male/ female ). Results from deve lopmenta l s tudie s in rat s and rabbits provided no in d ication of t e rato genic effects for fetu s es of either s pecie s and n o evidence of developm e ntal effects in the ab se nce of rnatcma l tox i c ity. For t h e rat teratology st ud y, do ses up to 5 00 m g/l< g bwt / day were adm ini s te r ed betwee n Days 

### 6 and 

### 19 of gestati on. The NOEL for materna l tox i city and developm e nta l to xicity was 

### 10 m g/l \.g bwt /day for materna l rats and t h e i r fe t u ses. Tolpy r alate tec h n ica l wa s not terato ge nic to ntt s . For t h e rabb i t terato logy s tud y, do ses up to 500 m g/l ig hwt / day were adm ini ste re d between lhy s 6 and 27 of gestation. T h e NOEL fo r mate m a l toxicity and deve l opmental tox icit y wa s 5**mg lq~**  bwt/day and that of 500 rng/ kg/ da y is the e ffect l evel fo r · both of mat e rna l r abbits and their fetu ses . To l pyra l ate3 technical was not

**tcrat o~c**  **ni c**  to rahbits . 4 **.\uh<·hmn~<·** tuxlcil.t S ubchr·onic (9 0-day) feed in g s tud ies wer·e conducted in rats, mice and do g s . Dose s ev a lu a t ed in t h e rat ( r ep e ate d do se, ora l) s tudy were 

### 0, 5, 20, 2000 and 20000 ppm. T h e NOAEL wa s 

### 5 ppm in ma les (equi va lent to 0.323

**g/Jq~** bwt /da y ) and 

### 2 0 ppm fo r· fema les (equiva le nt to 

### 1.5 8 mg/ kg bwt/day). E ff ec ts o n t he liver 

### and eye were obscr'Vcd for both sexes . D oses eva lu ated in 

### mice ( r e p ea ted do se, oral) s tudy were 0 , 50 , 500, 2000 and 7 00 0 ppm. T he NOAF.L wa s 500 ppm in m 1 lles (equiva lent to 70.8 m g/ kg/ d<ty) and 2000 pp m 

### for femal es (equiva le n t 

### to 33 1 m g/l<g/day). C'e ntr·il o hular h epatoce ll ular hy pertro ph y was H treatment-related c han ge 

### for t h e 2000 ppm group for ma les and 7 000 ppm g r o up for· female s . Do s e s evaluated in t h e d og s t u d y we r e 0 , 20 0, 2000 and 20000 ppm. T h e NO A E L wa s 2000 ppm for mal es (6 4.61 m gll<g bw/day) a nd 2000 ppm fo r fe m a les ( 65. 33 m g/k g bw /d ay). 

### ). ( '/zmnit· wridL.t An 1 8- m o n t h o n cogen ic ity s t ud y wa s conducted in m ice wit h di et ar y com·entration s of 0 , 7 0, 7 00 a nd 7 000 ppm. T h e r e Wil S no evidence of ca r c ino ge ni c i ty. A 1-y car c hroni c tox ic ity s tud y wa s condu c ted in rats w it h d ieta r y conccntn1tion s 

### of 0 , 5, 20, 2000 , and I0000 (M) o r 2 0000 (F) ppm t ec hn ical To lpyra lat c. T h e sys temic N OAEL wa s co n s id ered t o b e 20 ppm (ma les, 0.925 m g/ l<g bw/da y; female s, .J.18 mg/l q?, bw/da y). A 2-ycar c hroni c toxicit y/c arc in ogen icit y s tud y was conducted in rats with dietary co n cc ntn1tio n s of 0 , 5, 20,2000 an d 10000 ppm t ec hnica l To lp ynllat e. The n o-o b se r -ved

- advers e-effect lev e l (NOAEL) for toxicity wa s d e t e r m in e d to be 2 0 ppm fo r · m ale s (0.765 m g/l <gl day) and 2 0 ppm for fema le s ( 1.0 1 m g/ l <g bw/da y). T h ere was n o ev idence of carcino geni c ity. A 52-w ed< c hro ni c toxic it y s tud y was conducted in do gs w ith d ietary conccntt·ation s of 0, 100, 1000 and 10,000 ppm. T h e N OA E L wa s 1000 pp m ( male s, 28 .1 3 mg/ l<g bw/da y; fema les, 28 A6 

### m g

l l

<g bw/ d ay)
. (, .·lmmfll llil'tctl•oliwl The m et aboli s m of To lpy r a late in rats, go ats and layin g h e n s arc a d e quate l y undcr· s t ood. To lp yra h1tc is rapi d ly excreted ma in ly v ia the f eces. The m ajor ity of exc r e t e d material wa s u n c h a n ge d To lp y nl l ate , w it h scv(• t ·a l min or metabolit es pres ent in f e ce s, bil e, urine and t iss ue s . T h er ·e 1 u·e n o s ign ifica n t q ualitative diff ere n ces h c tw(.·e n r at and n rminant m et abolic pathways. 7. \!duho/itc
**~rn·icoloi..!,J.** No to x ico lo g ica lly s ignificant m e tabo lit es were detect e d in p l ant or a nim a l m e taboli s m s tudi es . The r es idue o f co nc e rn f o r tolerance se ttin g purpo ses i s the pare nt co mp o und nnd th e maj o r p la nt m e tab o lite, MT-2 15 3. C on s equently, there is n o a dditi o n a l co nc c r · n f o r to x icity of metabolite s .4

X. 

### l.ndocrine 

### di,ru;1titm. The s ubmitt e d s t udi es includ e ev aluation o f the p otentia l e ff ects o n r ep roducti o n a nd d eve lopment and an eva lua t i o n o f t h e patholo gy of t h e endoc r in e o r ga n s fo ll ow in g s hort or l o n g-term ex p os ure . T he data demon s trate no trea tm e nt
- re l ate d e f fects on the e ndocrine syste m. () fmnullwloxicity. Fo ur-wee k immun o toxi c it y s tudie s were co ndu cte d in fema l e mic e. There was no effect on t h e immun e sys tem at an y d ose tes ted. T h e NOE L wa s g t·eater- than 5 , 500 ppm

**(~**
**I** , 002 mg/ k g

**hwt**

**a~ ).** 
I
. J>ietar.l (''(fJ/1\'/Jrc. Ex po s un.' a ss l· ss m c n ts were co ndu c t e d t o eva luate the p ote ntial ri s l < du e to di etary e xpo s ure of th e U.S. popu l at ion to re s idu es of Tolpyra l at e. Fo r acut e dietary ex po s ure, an Ac ut e Ref e t

·cnc e Do se ( aRf"D) is no t identi f ied for To lp y ralate s ince th e r e w as no ev iden ce o f ini t ia l acute effec t s in t h e acute oral or s h ort-temt t ox i city s tud ies, o t · the developm e ntal toxic it y s tudi es in rat s and rabb it s . There w ere no e ff ects s een in t he acute neurotox i c i ty s tud y at t h e limi t do s e level of 2 000 m g/ l<g/ day. No ini tial acute e ffect s we r e s ee n in the 9 0

- day n e ut · otoxi c it y st ud y . For d11·onic di e tary e xpo s ure , th e c hroni c r eference dose ( cJHD ) is 0.002 70 m g/k g b wt / day, ba se d on the NOAEL from the ra t 2-ye: n r e pro ducti H tox icit y s tudy (0.270 mg/ k g bwt/day) a nd div i d in g b y a n un certai nt y fac t or of 100. T h e c hro nic p opu l ation adju s ted do se (c P A D) is also 0.002 70 m g/ k g

**bwt**
**/c l:.t~** 

**'** s ince th e FQPA

**afe~**

**·** fa cto r is a n t i cipat e d to be I for Tol p y r a l ate. 

### i. l-oud T ie r · 1 ch r o ni c di etary ex p os ure a n a lyses wu e co n d u cted fo r Tolpyralatc in / on corn (field, s weet a nd popcorn) to det·c nnine th e ex p o s ure co ntributi on of thi s commo di ty to t h e diet a nd to a s ce r tai n the c hronic ri s l <. p oten tial. The ex po s ure esti m ate s w e re ba se d on t h e p t ·opo se d to l e ran ce leve l re s idu es, average proce ss ing fa c tors and a ma r ket s h: u ·e of 100 °/., crop tt·c atcd a s a conservative a ss umption. The co n s u mption data were from the US D A's N ationa l Health and N u triti o n Exam in ati on S urvey/ W h at W e Ea t in A m e rica N II ANES / WWEIA di eta r y s urv ey cond uct e d in 2005-20 10 (2

**d<~ y**  food co n s umpti o n data) u s ing the Dietar y Exp os ut ·e Evf -tluat ion Mod ul e ( D EEM-FCI D) s oftware, ve r s io n 4. 02/10.00. U s in g all o f the wors t ca se ex p o s ure sce n ario s li s ted above , the T i er 1 c hron ic di e ta r ·y expos ure esti mat es re s ult e d in an est imate d ex p os ure for t h e ge n era l U.S. popu l at i on of 0.000152 

### m g/ l< g bwt / day. Thi s e xpo s ure cor r es pond s to 

### 5.6' Yo o f the c P A D. The hi g he s t ex p os ure es timate calcu la ted was for th e s u b g r · oup A ll I nf ants. T his cx p os ut ·c wa s d ete rmin e d to be 

### 0.000551 mg/ l ig bwt / d ay 

### (20.-t'Yo of the cPAD). The c hronic di etat ·y ex po s ut·c ana lys i s is s umma r ized in t h e tab le below.

## s

P o pul ation Expos u re E st imate % ofcPAO Su b g roup (mg/ l <g body wi/da y) U.S. Population 

### 0.000152 5.6 A ll Infan ts( < I yea r o ld ) 

### 0.000551 20.4 C hildre n (1-2 years old) 

### 0.00022 1 8. 2 C hi l dr·en 

### (3 -5 yea r s o l d ) 

### 0.000 187 6.9 Ch i ldren ( 6-12 ye ars o l d) 

### 0.000 139 5. 1

Yo uth (13- 1

### 9 year s old) 

### 0.000114 4.2 Fe mal es ( 1 3-49 ye ars o ld ) 

### 0
. 000 149 5.5 Ad ul t s (20-49 ye ars old) 

### 0
.000 141 5.2

A du l t s ( 50 + rears o ld ) 

### 0.000 146 5.4

It ca n b e co ncluded 

### t h at lo n g-tcrn1 di e tar y expo s ure 

### to To l py ral ate throu g h r es idue s on a ll commod itie s s hould not be of ca u se fo r concern.

-, 

### it 

### I

**1ri11~in'..!** ,, 11/t'l' Using 

### P' l RST , 

### SC IGROW and 

### PRZM-GW m ode ls, estimates o f To lt w ra late r es idue s in s urfa ce an d oro und water were

• 1:> ca l cula t ed. T h e hi g h es t EEC v alu e of 0.0068-J m g/ L wa s u se d a s input into the Dli: EM / FC ID m o d e l for drinkin g water (direct and indir ect s ou r ces)
. 

### \r•n-.lict,o:\· c.\fi0\1/IT
. Ba se d o n t h e proposed u ses for To l pyralat c 

### on the cro p s

n oted ab ove, non - occupati ona l expos ure of Tolpyralate wo uld not b e ex p ected 

### t o th e g<.· n c 1 ·al p opu l ati o n . The o nl y ant icip a t ed ex po s ure r o u te for th e US po p u lation is v ia the diet ( f oo d and wa t er o nl y)
. Therefore , re s id e nti a l l'i s k assessme nt s f or th e in c id e n ta l oral, d er mal , and inhalat ion ex po s ure rout

### cs arc 

### no t 1 ·eq 

### u i J 'cd
. Occ upation a l po s t -a ppli ca tion ex po s ure is p o ss ib le . For de rm a l s ho• ·t
- ten n ex p os ure, n o tox ic it y

**w~• s**  fou n d at 1000 m g/ l<g in a 28 -da y rat d e rmal tox icit y s tudy. T hc : r c fo r c, i n th e :th s<.· n ce of an y ha zard identifi e d for dermal ex p os ure, a d e nnal po s t-app li ca ti on r is l< assess ment wa s n o t con du cte d
. P ote n tial inh alation cxpos u1 ·e wa s not co n s id ered s in ce it is neg li gib le wh e n a ss e ss in g 1 ·c-c ntry ri s k s . O cc upati onal ex p os ure for mixing/ lo ad in g and app ly in g

**To p~Talate**  wa s co n s idered. Potentia l expos ure wa s considered n eg li g ible s inc e MOE s we 1 · e g r cate1· than 1 , 000 fo r a ll c al c u . l atio n s . I 1 1 tlillll!tllil'c' F!!<'t'J\ E P A ha s not mad e a co mmon mechani s m of toxicit _y findin g a s to To lp y ralat c and any o th c 1 · s uh s t<n1ce s, and To lp yralatc doc s n ot appear to produce a toxic m eta b o lit e6 

### [H·odu c cd b y o th e r s ub s tan c e s . Fo r th e purp o ses o f t hi s to le r a n ce ac ti o n , th e r e f o r e, E P A ha s not a s s um ed tha t Tolpy r a la t e ha s a co mm o n m e c h a ni s m o f tox ic it y wi t h oth er s ub s tanC l' S
.
I. I·.\ I)()PIIIatiuJI 

### lla s c d o n th e co mpl et e n es s and rcliahili t) · of the tox ic ity d a ta and th e co n s e r v a tive ex p o s u re a ss es s m e nts, th ere is a re a s on a bl e cel'ta in ty t hat no h a rm w ill re s ul t fro m th e agg r ega t e ex po s ure o f r e s idu es o f T o lp y r a la t c. 2. lnlunl.\ and children. 

### B a se d o n th e co mpl ete n ess and r e li a bili ty o f th e tox ic it y da t a a nd th e co n s u v ati vc expo s ure a ss ess ments, th e re i s a r ·ea so n a bl e ce r ta int y th a t n o harm will r ·cs ult to infants and childre n fro m th e a gg r ega t e e x p o s ure o f r es idu es ofTo lpy ralatc . 

### F lntanutiuno/ Ji,fert/1/(,' 

### Pres e ntl y, th e t · c ar ·c n o C od ex m ax imum r e s idue le v els ( M R L s) es t abli s h e d for r e s id u e s o f To lp yn1latc o n a ny cro p .