**UNITED STATES**  **ENVIRONMENTAL PROTECTION**  **AGENCY WA** **SHINGTON,** 

### D.C. **20460** OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM Date: 2/12/2014 SUBJECT: Aminopyrali d . Human Health Assessment Seeping Document in Support of

Registration Review PC Code: 005 1 00 Decision No.: 482282 Petition No.: NA Risk Assessment Typ e : NA TXRN o . : NA MRIDN o . : NA DP Barcode: D414395 Registration No.: 6271 9 - 519 Regulatory Action: Registration Review Case No.: 7267 CAS No.: 150114 - 71 - 9 40 CFR: §180.610 FROM: Douglas Dotso n , Ph. D ., Chemist

Jaime D ' Agostino, Ph.D . , Toxicologist . - Za i d a Figueroa, Industrial Hygienist Risk Assessment Branch II He a lth Effects Division (7509P) Office of Pesticide Programs THROUGH: Christina Swartz, Branch Chief

Risk Assessment Branch II J e ss Rowland, Acting Associate Director Dana Vogel, Associate Director He a lth E f fects Division (7509P) Offi c · e of Pesticide Programs TO: Veronica Dutch, Chemical Review Manager

Pesticide Re - Evaluation Division (7508P) Office of Pesticide Programs Attached is the Health Effe c ts Division's (HED) human health risk assessment seeping document for aminopy

ralid to support registration review.Aminopy ralid Registr a

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### P a g e 2 o f 27 **Executive Summary**  The Health Effects Division Aminopy ralid Registration Review Team has evaluated th e database and the most recent human he a l th risk assessment for the herbicide aminopyralid. HED performe d this ev aluation in order to determine the scope of work necessary to support th e e s tabl i shed tolerances and e x i s t i n g registrations during registration r e view. The primary source of i n format ion for this evaluation was the most recent human health risk assessment (D359088, D. Dotson, et al, 10/22/2009 ). Aminopy ralid, 4 - amino - 3,6 - dichloro - 2 - pyridinecarboxylic a c i d , i s a sy ste m ic postemergence herbicide that belongs to the pyridine carboxylic acid class of herbicides. It is currently registered for use in rangeland, permanent grass pastures, non - cropland areas, natural areas, grazed areas in and around these sites, as well as on wheat and com. In addition, i t is registered for use on wildlife hab i

tat and i ndustri a

l vegetation management areas, inclu d ing right - of

- way for roads, railroads, and utility lines. Aminopy ralid provides sy stemic p o stemergence broadspectrum contr o l of a number of key no x i o u s and invasive annual, biennial, and perennial weed species, as well as agronomic broadleaf weeds. Aminopyralid can also provide r e sidual weed control against re - i n f

estations and can reduce the need for re - treatment depending on the rate applied and the target weeds. 

### It can be applied as a broadcast treatment by ground, aerial, and handheld equ ipme nt. The toxic o logy database for aminopy ralid is complete, and no ad d itional toxicity studies are required. HED's Hazard and Science Policy Council (HASPOC) determined that a subchronic inh a l ati on study in the rat is not required for aminopy ralid. The toxicology database for aminopy ralid includes studies with both the acid (XDE - 750) and triisopropanolammonium ( T IP A ) salt (GF - 871). An immunotoxicity study was submitted subsequent to the la s t risk assessment and has been reviewed by HED. The immunotoxicity study i s considered to be acceptable and has no impact on the overall hazard characterization, including doses and endpoints selected ( a lo n g with tra d i t ional uncertainty factors) for risk assessment. The toxicology studies with aminopyralid indicate that the main target organs in the rat and dog were the stomach, i l eum, and cecum f o llowi n g adm inistrat i on in subchronic and chronic studies. There is no evidence of neurotoxicity , carcinogenicity, or qualitative or quantitative susceptibility of the developing fetus or offspring, based on res u lts from the developmental, reprodu c ti ve, or carcinogenic toxicity studies. Therefore, based on the completeness of the databas e , the lack of suscepti b il i ty , the lack of neurotoxicity , and the conservative nature ofthe exposure assessment, HED previously recommended that the required 1 Ox Food Quality Protection Act (FQPA) Safety Factor be reduce d to 1 x. The residue chemistry database is adequate to support current registration review requirements. Adequate metabolism (crops, liv e stock, and rotational crops), storage s tability , magnitude of the residue, and processing data are available to support the registered uses. Adequate methods are available for enforcement of the currently established tolerances. The tolerance expression has been updated to include both coverage and compliance statements.Aminopy ralid Registr a

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### P a g e 3 o f 27 The diet ar y e x posure d atab a se is a d e qu ate to sup p o rt cur r ent re g is tr a

t i on requir e ments. The last risk a ssessment p r ovided c hr onic diet ar y e x posure e st i mat e s that ar e not of c on ce rn for a ll population sub groups ( D 35908 8 , D. D otson, e t a l, 10/22/2009). The g e n e r a l U. S . population and a ll sub groups use l e ss th an 1% of the c P A D . As p art of re g is tr at i on r e view, HED ant i c ipat e s p e r f o r m i n g r e vised diet ary e x posure an a l ys e s to refl ec t cur r ent A g e n c y pol ic y and potential l y upd ated drink i ng w at e r est i mat e s. The re sidenti a l e x posure d atab a se is compl e t e . D uring re g is tr a t i on r e vi e w , a r e vised r e sidenti a l e x posure a ssessment that includ e s pos t - a ppl i cat i o n incid e ntal o ra l e x posure to c hi l dre n (1 < 2 years old) pl a y

i n g on tr e ated r e c r e at i on a l s i tes might be re quir e d. This a ss e ss m e nt should inco r por a te r e c e nt l y up d ated H ea l th E f f ec ts Divis i on’s 2012 S t and ard O p er at i ng P roc e dur e s for R e sidenti a l P e st i c ide E x p osure Ass e ss m e nt. The Ag e n c y m i ght r e vis i t the n ee d for a qu ant i tative post - a

ppl i cat ion spr a y dri f

t e x posure a ssessment f

or am i no p y

r al id during re g is tr a t i on r e vi e w. Th e re is s u f

f i c ient info rmation av a i l a

ble to a sse s s oc cup at i on a l e x posure and risk f rom the re g is t e r e d u s e s. The p re vious o cc up at i on a l hand l e r a ssessment c ov e r e d the re le v ant e x pos u re s ce n arios and did not re s ult in risk estimat e s of c on ce rn. R e vised o cc up at i on a l handl e r a ssessments mi ght be r e q uir e d duri n g r e g is tr a t i on re view to i n c lude r e vised sur r o g ate unit e x posur e s for o cc u

p at i on a l handl e rs. An o cc up at i on a l qu ant i tative pos t - a p pl i cat i on a ssessment w a s not c ondu c ted p r e v i ous l y b e c a use a d e rm a l e ndpoint w a s not sel ec ted for am i no p y r al i d . Th e r e f o r e , a qu ant i tative o cc up at i on a l pos t - a ppl ic at i on a ssessment will not be n e c e ssar y duri n g r e g is tr a t i on re vi e w. **I n**  **t r**  **o du**  **c tion**  HED e v a luat e d the most rece nt hum an h ea l th risk a ssessment f or am i no p y

r a l i d in asso c iation with upd ates to its t o x ici t y, e x posur e , and u s a g e d atab a s e s to de t e rmine if s u f fi c ient d ata are av a i l a ble, and if furth e r upd ates ar e n ee d e d , to support r e g is tr a t i on r e v i e w. The most r ece nt human h ea l th risk a sses s ment w a s pe r f o r med in 2 009 wh e n HED e v a luat e d a re qu e st f o r a n e w use o n c o r

n ( D359088, D . Dotso n , e t al, 10/22/2009 ) . Tol e r a n c e s for am i no p y

r a l i d are e s t a

bl i shed i n 40 C F R §180 . 610. F or plan t commod i t i e s, the to l e r a n c e is e stablished in t e rms of f ree and c onju g at e d am i no p y r al i d. P l a nt commod i t y to l e r a n ce s r a n g e f r om 0. 0 4 ppm for wh eat gra in t o 50 ppm for gr a ss h a y . L i v e stock c omm odi t y to l e r a n ce s are e stablished in t e rms of am i no p y r a l i d on l y, and r a

n g e f r om 0. 0 3 ppm to 0.3 ppm. The stru c tur e , th e c h e m ic a l nam e s , and oth e r id e nt ifie r s can b e f ound in the c h e m i ca l i d e nt i t y table in Att ac hment 1. **Haza r**  **d I**  **d e**  **n ti**  **f**

**ica t**  **io n**  **/ T**  **oxicology** The h e rbi c i d a l m ode of a c t i on f o r am i no p y

r al i d is that of a plant gro wth r e gulato r . I t disrupts norm a l gro wth b y ac t i n g l i ke a c lass of plant gr o w th hormon e s known a s a u x ins. The c h e m i ca l moves s ystemi ca l l y thro u ghout the plant and d e regulat e s pl ant gro wth m e t abol i c p athw a ys a f f e c t i ng th e gro wth pr o c e ss of the p lant. This d i sruption of pl ant gr o wth p r o ce sses r e sul t s inAminopy ralid Registr a

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### P a g e 4 o f 27 c ontrol and d eath o f sus c e pt i ble pl ant spe c ies. T h e to x icolo g ic a l m ode of a c t i on in m amm a ls is unknown . The to x icology d atab a s e for am i no p y r al i d is comp lete and no a ddi t ional tox i c i t y stud i e s ar e r e quir e d. H E D ’ s H A S P OC d e te r m i n e d that a sub c hr onic inh a lation stu d y in the rat i s not r e quir e d f o r a m i no p y r al i d ( J . V anAlstine, T XR#00510 0 , 4/17 / 2013,). The to x icology d ata b a se for am i no p y

r al i d includ e s s tudies w i th both the ac id ( X DE - 750) and T IP A s a lt ( GF - 87 1 ). Unless othe r wise noted, the ac id f

o r m w a s used in the stu dies discuss e d in this s ec t i o n . An immunot o x ici t y stu d y w a s r e ce nt l y submi tted and h a s be en r e vi e w e d b y H E D ( M R ID 48364401 ) . The stu d y is a c c e p tabl e , and the r e sul t s show no e viden c e o f immunotox i c i t y. T h e se r e sul t s ar e c onsistent with the e x is t ing tox i c olo g i c a l dat a b a se whi c h do e s n ot i ndic ate th at the c h e m i ca l t ar g e ts the i mmune s ystem. Gi v e n the above info r mation, HED c on c ludes that this new i mmuno t o x ici t y stu d y h a s no impa c t on the ov e r al l h az ard c h ar ac t e ri z at i on, including doses and e ndpoint s sel ec ted ( a long wi th tr a di t ional un ce rt a i nt y f a c tors) f o r risk ass e s sment . The to x icology d atab a s e for am i no p y r al i d ind i cat e s that the sto m ac h, i l e um , and c e c um ar e tar g e ts for th i s ch e m ic a l. I n sub c hr onic studi e s in r a ts and d o g s, h y

p e rp l a sia of the mu c osal e pi th e l i um w a s obse r

v e d. I n a ddi t ion, h y

p e rtr op h y of the mu c osal e pi th e l i um w a s obse r v e d in the sub c hr onic d o g stu d y . F ol l owing c hr onic e x posure of r ats and d o g s, h y p e rtr op h y ( d o g ) and h y p e rpl a sia ( d o g and r a

t) of the mucos a l epitheli um w a s obse r v e d, a s w e ll a s c e c a l enl ar g e ment ( rat), thi c k e ni n g o f the sto m ac h mucosa ( d o g ) , sl i ght l y mpho i d h y

p e rpl a sia of the g a stric mu c o s a (dog ) , and c h ronic muco s a l i n f lammation (dog ) . No a dv e r s e e f f e c ts w e re obse r

v e d wh e n the T I P A s a lt w a s g iven to r ats for 13 w e e ks. No a dv e rse e f f e c ts w e re ob s e rv e d in sub c hr onic or c hr onic f ee di n g stud i e s in m ice e x posed to the ac i d fo r m . S to m ac h e f

f e c ts w e r e a l s o obse r

v e d in a d e v e lo p m e ntal to x ici t y stu d y in r a bbi t s. U lc e rs and e rosions w e r e se en in the g landul ar mu c osa o f th e sto m ac h in m ate r n a l an i mal s . Oth e r e f

f e c ts noted we re d e c r e a s e d b od y w e i ghts and incoo r di n ated g a i t . No d e v e lop me ntal e f f e c ts w e r e se en in f e tuses. I n anoth e r dev e lop m e ntal ra bbit stu d y with the T I

P A s a l t , sev e r e inanit i on ( e x h a ust i on f r om l ac k of food), bo d y w e i ght l oss, de c re a s e d f e c a l out put, and incoo r dinat e d g a it w e re ob s e rv e d in m at e r

n a l animals. D e c r e a s e d fetal bo d y w e i ghts w e re o b s e rv e d at the n e x t hi gh e st do s e . No e f

f ec ts w e re noted in d e v e lop me ntal to x ici t y stud i e s in r at s with e i th e r the ac id or T I P A s a l t , or a r e p r o du c t i on stu d y in r ats. Th e r e fo r e , the r e w a s no e vi d e n c e of i n c re a s e d p r e and/or post - n atal qu ant i t at i ve and qu a l i tat i ve susc e pt i bi l i t y in the rat or r a b b i t . No s ystemic to x ic e f

f ec ts w e re ob s e rv e d in a 2 8 - d a y d e rm a l t o x ici t y stu d y i n r a t s ; how e v e r, d e rm a l t o x ici t y w a s ind ic ated b y sl i ght epid e rm a l h y p e rpl a sia in m a les. I

n an ac ute n e ur oto x ici t y stu d y in r ats, f

eca l so i l i ng in m a les and urine soil i ng in f e m a les w e re obs erv e d at the li m it dose. No a dv e r s e e f

f e c ts w e re obse r

v e d in a c hr onic n e ur oto x ici t y stu d y at the h i gh e st do s e test e d . Amino p y r a l i d is cl a ss i fi e d a s “n o t l ike l y to be c arcino g e nic to humans . ” N o inc r ea s e s in an y tum o r s w e re f

ound in car c inogeni c i t y stud i e s in r ats and mi ce . Amino p y r a l id w a s n e g at i ve in all mut a g e n i c i t y stud i e s, e xc e pt for an in vitro c h romosome a b e r r at i on a ss a y i n S p ra g

u e D awl e y r a ts. In th i s ass a y, the ac id fo r m induc e d c hr omo s ome a b e r r a t i ons, but on l y at c y

to t o x icAminopy ralid Registr a

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### P a g e 5 o f 27 c on ce ntr at i ons. Thus, the c last o g e nic r e sponse w a s indu ce d s e c ond ar y to t o x ici t y. An ac c e ptable r at m e tabolism s tu d y f or am i no p y

r a l i d is av a i l a

ble. B oth the ac id and T IP A s a lt of a m i no p y r a l i d h ave low ac ute to x ici t y ( T o x ici t y C at e g o r y IV ) via o ra l, de r mal, and inhal at i on r o utes of e x posur e . Both fo r ms ar e not i r

ri t at i n g to the skin and are not skin sensi t i z e rs. The ac id fo r m i s sev e r e l y ir

ri t at i ng to the e ye ( To x ici t y C ate g o r y I ) whi l e the T I P A s a lt is not i r

ri t at i ng to the e ye ( T o x ici t y C ate g o r y IV ) . In the most r ece nt risk a s s e ss m e nt, the re quir e d 1 0 x F QPA S a f e t y F a c tor w a s r e du c e d to 1 x b a s e d on: 1) the l a c k of i n c r e a s e d pr e - and pos t - n atal susc e pt i bi l i t y of r ats and ra bbi t s to in u te ro and/or post - n atal e x posure i n the d e v e lop m e ntal and r ep r odu c t i ve to x ici t y stud i e s; 2) the r e is no e viden c e o f n eur oto x ici t y in the d atab a s e ; and 3 ) t he risk ass e ss m e nt does n ot unde re st i mate e x posure b eca

use th e di e tary a ssessment is b a s e d on c onse r v at i ve a ssumpt i ons such a s to l e r a n c e lev e l r e sidues in foods an d upp e r - bound model e d e st i mat e s of re sidues in drinking w ate r . Th e se c o n c lus i ons are n o t e x p ec ted to c h an g e duri ng re g is tr a t i on r e vi e w. T he to x icolo g ic a l e ndpoint s and dos e s used in the most rece nt human h ea l th risk a ssessment are summari z e d in Atta c hment 3. The to x ici t y pro f i l e of am i no p y

r a l i d is s umm ari z e d in Att ac hment 4. Con c lus i ons for H az ard Id ent i fi cat i on/To x icology The to x ici t y d at a

b a se is c omp l e te f

or the pur po s e of r e g is tr a

t i on r e v i e w, an d is app r opri ate f o r a ssessment of potential c ar c in o g e nic, mut a g e nic, d e v e lop m e ntal, and r e p r o du c t i ve e f f ec t s . The F QPA S a f

e t y F a c tor wa s r e du ce d to 1 x b a s e d on a number of f a c to r s includ i ng the l a c k of susc e pt i bi l i t y in d e v e lo p ment a l and re p rodu c t i on stud i e s in r ats and r a bbi t s , the l ac k of e vi d e n c e for n e ur oto x ici t y, and the c onse r v at i ve a ssumpt i ons used in the e x posure a s s e ss m e nts. No n e w to x ici t y d ata are r e quir e d . Althou gh the c o n c lus i ons are not e x p ec ted to c h ang e , HED will c onsid e r the a

p p rop riat e n e ss of the e x is t ing e ndpo i nts bas e d on c ur r e nt po l ici e s and risk a ssessment methodolo g i e s during r e g is tr a t i on r e v i e w . **Di e**  **ta r** **y Ex p**  **os u**  **r e**  The re sidue c h e m i str y d atab a se is ad e qu ate to su p port c ur r ent r e g is tr a

t i on r e view re qu i r e ments ( D360100, D. D otson, 1 0 /2 2 /2009 ) . Ad e qu ate m e t a bol i sm ( c rops, livestoc k , and r o tational c rops ) , stor a ge stabili t y, ma gni tude of th e re sidu e , and p r o ce ss i n g d ata ar e av a i l a ble to support the r e g is t e r e d u s e s. Ad e qu ate m e thods ar e av a i lable f or e n f o rc e ment of th e c ur

r e nt l y e stablished to l e r a n ce s. No re sidue c h e m i stry d at a d e fi c i e n c i e s w e re c i t e d in the pr e vi o us risk a ssessment f or am i no p y r a l id . The pr e v i ous risk a ssessment st at e d that the p r opos e d la b e l for c o r

n should be mod i fi e d to sp ec i f

y that s p r a y or spot a

ppl i cat i ons m a y not be m a de a ft e r th e V6 gro wth s ta g e , and that f o r a ge m a y not be h arv e s t e d prior to the d e nt s t a ge of gr o wth. The r e g is tr a nt ad d e d these re strictions to the l ab e l. F or the 2009 risk a sses s ment , HED c ondu c ted a c hr onic diet ar y e x posure assessment for a ll c ur r ent l y re g is t e r e d food uses ( D369212, D. D ots o n, 10/22/2009). The a ss e ss m e nt w a s unr e fin e d and, the r e fo re , c onse r v at i ve. I t w a s ba s e d on the a ssumpt i on that am i no p y r a l i dAminopy ralid Registr a

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### P a g e 6 o f 27 re sidues ar e pr e s e nt at to l e r a n c e lev e ls i n a ll c omm odi t ies f or whi c h to l e r a

n ce s hav e b ee n e stablished, and that 10 0 % of those c rops are tr e at e d. D E EMTM V e rsion 7.81 d e f a ult proc e ss i ng f a c tors w e re a

ppl i e d to a l l pro ce ssed c omm odi t ies for whi c h th e y w e r e av a i l a ble. D rinki n g w at e r w a s inco r po r ated di r e c t l y int o the di e tary a ssessm e nt us i ng the e st i mat e d dri nking w at e r c on ce ntr at i on ( E D W C) f

or sur f a c e w ate r . T h e E D W C is a model e d sur f a c e w at e r r e sidue e st i mate p r ovided b y the Environm e ntal Fat e and E f f e c ts D iv i sion ( E F ED; D36192 6 , 7/24/2009, R. B aris ) . It w a s g e n e r a

t e d b y th e Tier 1 F QPA In d e x R e s e rvoir S c r e e ni n g Tool (F IR S T) Mod e l. The EDWC includ e s amino p y r a l i d on l y . It i s the on l y re sid u e of c o n ce rn i n drinking w ater f o r risk a ssessment. The c h r onic d i e tar y risk est i mat e s w e re not of c on c e rn f or the g e n e r a l U. S . population and a ll population sub groups. All subgro u ps use l e ss th an 1% of the c P A D . Duri n g re g is tr a t i on r e vi e w, HED will l i k e l y c ondu c t a n e w di e tar y e x posure and risk a ssessment if th e re are s i gnifi cant c h an g e s in the drink i ng w ater e st i mat e s . I f a n a ssessment is n ee d e d, H E D w i l l use the most c ur

r ent diet ar y e x posure model and food c onsumpt i on surv e y . Con c lus i ons for Di e tary E x posure No n e w d ata are n ee d e d to ass e ss po t e nt i a l d i e tar y e x posure and risk f or am i no p y

r a l i d . Ho we v e r, HED ant i c i p ates p e r f o rming a n e w di e t ar y e x posure a ssessment during re g is tr a t i on r e vie w . T h e most c ur

r en t drinking w at e r mod e ls will be used f or th i s ass e ss m ent. I

n a ddi t ion, the most c ur

r ent v e rsion of the di e tar y model will be use d , a lo n g with an y p otential c h an g e s in e ndpoint s and dos e s for r isk ass e ss m e nt. **R e**  **si d**  **e n**  **tial E**  **x p**  **os u**  **r e**  R e sidenti a l H andle r s B a s e d on th e c urr ent re g i ste re d use p atte rn, a m i n op y r a l i d is not applied b y homeo wn e rs to r e sidenti a l or r ec r eat i on a l settin g s; th e refo re , a re s i d e nt i a l handl e r e x posure a ssessment will not be n ee d e d for r e g is tr a

t i o n r e vie w . R e sidenti a l P os t - Applic a

t i on Amino p y r a l i d is appli e d b y c omme r c ial h and l e rs t o n atur a l r e c re at i on are a s (e . g ., wild l ife man a g e ment ar e a s, camp groun d s, tr a i l h ea ds an d tr a i l s) to c ontrol w ee ds. A s th e re is potential for short - te r

m e x posure of a dul t s and c hi l dre n f r o m ent e ring ar ea s p r e vious l y tr e ated w i th am i no p y r a l i d, r e sidenti a l pos t - a

ppl i cat i on e x posure s asso c iat e d with the use o f a m i no p y r al i d to c ontrol w ee ds on r e side n t i a l and re c r e at i on a l s i tes w e re a ssess e d in 2005 ( M. C ol l ante s , D305672 ) . R e sidenti a l p os t - a

ppl i cat i on d e rm a l and inh a lation e x posure a ssessments w e re not r e qui r e d b eca us e : 1 ) no de rm a l e n dpoint w a s sel ec ted, and 2) inhal at i on e x posure w a s e xp ec ted to be n e g l i g ib l e f

o r outdoor u s e s asso c iat e d with tr e ated rec r eat i on ar ea s. Risks r e sul t ing f rom h an d to - mouth tr ansf

e r, in c id e ntal in g e st i on of p e st i c i d e - tr e ated tur f gr a ss and s oil sc en arios w e re a ssess e d usi n g the H ED D ra ft S t and ar d Op e r at i ng P ro c e dur e s (SOPs) f or R e sidenti a l E x posure Ass e ss m e nts (12/18 / 97), a nd the Re v is i ons to the S t and ard O p e r at i ng P r o c e dur e s (SO P s) f o rAminopy ralid Registr a

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### P a g e 7 o f 27 R e sidenti a l E x posure Ass e ss m e nt (Sci e n c e Adviso ry Coun c il f o r E x posure P ol ic y 12, R e vised Fe b r u ar y 22, 2001 ) . T h e re sul t s of the pos t - a ppl ic at i on r e sidenti a l e x posure a ssessment ind i cate no risks of c on c e r

n , with MOEs > 61,000 ( L OC = 100). A r e vised r e sidenti a l e x posure a ssessment that in c ludes pos t - a ppl i cat i on incid e ntal o ra l e x posure to c hi l dre n (1 < 2 ye ars o l d) pl a y i n g on tr eated r e cr eat i on a l s i tes mi ght be re quir e d und e r re g is tr a t i on r e vi e w. T his ass e ss m e nt should i n c o rpor a te r ece nt l y upd at e d p ro c e dur e s found in the H ea l th E f

f ec ts Divis i on’s 2012 S t and ard O p er at i ng P roc e dur e s for R e s i d e nt i a l P e st i c ide E x posure Ass e ss m e nt. In acc o rd a

n c e with the upd ated Part 158 data r e qu ir e ments (2007 ) , a tur f tr ansf e r r a ble r e sidue ( T TR) stu d y is r e quir e d f or a ll re sidenti a l or o cc u

p at i on a l tur f us e s ( e . g ., s o d f a rms, g olf c o urs e s, p arks, and r ec r eat i on a l ar ea s). Ho w e v e r, a TTR s t u d y is n o t r e qui r e d for am i no p y r al i d at this t i me b eca use p os t - a

ppl ic at i on incid e ntal o ra l e x posure ca l c ulat e d p r e viously ( D305672, M. Col l antes, 05/24/2005) re sul t e d in MOEs 10 ti m e s a s hi gh a s th e lev e l of c o n ce rn ( e . g ., an MOE> 1,000 c omp ar e d t o the L OC o f 100); the r e fo re , usi n g the d e f a ult re s idue transf

e r v alues should pr o vide an a d e qu ate m ar g in of s a f e t y f o r an y potential l y h i gh e r r e s i du e s se e n in a c h e m i ca l - s p ec ific T TR s tu d y . S p r a y D rift The A g e n c y h a s not c on s ide re d r e sidenti a l pos t - a p pl i cat i on inhal at i on e x p o sure f or am i no p y

r a l i d b eca use th e re are no re g i ste re d r e si d e nt i a l uses at th i s t i me. H ow e v e r, re s i d e nt i a l e x posur e s r e sul t ing f

rom o f f - si t e tr ansport (e . g ., spr a y dri f t o r vol at i l iz at i on) m i ght o cc ur a s a r e sult of a ppl i cat i ons of am i no p y

r a l i d. The A g e n c y is i n th e pro c e ss o f e v a l u at i ng th e se t y p e s of e x posur e s and m i ght, a s a ppro p ri ate, d e v e lop po l i c ies and p r o ce dur e s to i d e nt if y the n ee d for and, subsequ e nt l y, the wa y to i n c o rpo rat e these p os t - a ppl i cat i on e x posur e s int o the A g e n c y ’ s risk a ssessme nts. The A g e n c y m i ght c ondu c t a s p r a y drift ass e ss m e nt and e x am i ne the n ee d f o r a volati l i z at i on a ssessment for am i no p y r al i d duri n g r e g is tr at i on re vie w . Con c lus i ons for R e sidenti a l E x posure The re sidenti a l e x posure d atab a se is compl e t e . B a s e d on the c ur r ent r e g is te r e d us e s, a r e sidenti a l h andler e x posure a s s e ss m e nt will not be c ondu c ted during r e g is tr a t i on r e v ie w . Ho we v e r, the Ag e n c y m i ght c ondu c t a r e vised r e si d e nt i a l pos t - appl i cat i on a ssessment th at i n c ludes pos t a ppl i cat i on incid e ntal o r a l e x posure of c hi l dre n (1 < 2 ye ars ol d ) pl a y i n g on tr eated r ec r eat i on a l si t e s. This ass e ss m e nt should i n c o r por a te r e c e nt l y upd ated p r o c e dur e s foun d in the H ea l th E f f e c ts Divis i on’s 2012 S tand ard O p e r at i ng P r o c e dur e s f o r R e sidenti a l Pe st i c ide E x posure Ass e ss m e nt. **Agg re**  **ga t**  **e Risk**  **Ass e**  **s s**  **me n**  **t** The most rece nt a g greg at e risk a ssessment w a s p e r fo r med in c onjunction w i th the 2009 risk a ssessment. F or a g greg ate a ssessment, e x posure e st i mat e s r e sul t ing f rom f ood, dri n king w ate r , and r e sidenti a l uses are c omb i n e d. As no ac ute e n dpoint w a s identifi e d and can c e r risk i s not aAminopy ralid Registr a

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### P a g e 8 o f 27 c on ce rn for am i no p y

r a l i d, ac ute and can ce r a g greg ate risk ass e ss m e nts w e re not pe r fo r med. Th e re are r e sidenti a l uses f or am i no p y

r al i d on r ec r eat i o n a l s i tes (e . g ., c amp groun d s ). T he no n diet ar y sc en arios includ e d in the a ggre g at e a sses s ment c onsisted of incid e ntal o ra l e x posur e s ( e . g ., h and - to - mouth tr an sf e r of r e sidues, obj e c t - to - mouth, and in g e st i on of soi l ). T h e se s ce n arios are short - te r

m i n dur at i on and ar e a

ppl ic a ble to c hi l dre n on l y . T h e re are no no n - d i e tar y s ce n arios f

o r a m i no p y r al i d that are a

p p rop riate for a ssessing a dul t s, the re f or e , the a g gre g ate e x posure e st i mat e s for a d ul t s ar e e quival e nt t o the c hr onic di e t ar y ( food + w ate r) e st i mat e s . A short - te r m a g gre g ate risk a ssessment w a s p e r f o r m e d for v arious subgroups c omprised of c hi l dr e n less than 12 ye ars old ( i. e ., a ll inf ants <1 ye ar old, c hi l dre n 1 - 2, c hi l dr e n 3 - 5 , and c hi l dre n 6 - 1 2 ). The short - te r

m a ggreg ate risk est i mat e s w e re not o f c on c e rn. A g gre g ate M OEs ran g e d f r om 25,000 - 33,000, wh e r ea s t he L OC w a s 1,000. B a s e d on th e r e g is t e r e d and p r opos e d us e s, the r e are no r e sidenti a l s ce n arios that are l i k e l y to r e sult in i nte r

medi ate - t e rm e x posure ( 3 0 - 180 d a ys , c ont i nuous). Th erefo re , HED h a s not c ondu c ted an inte rm e diat e - te r m a ggre g at e risk as s e ss m e nt for am i no p y r al i d . Di e tar y ( fo o d + w ate r) c onsumpt i on is the on l y sour c e o f e x posure to amino p y r a l i d that is e x p ec ted to re sult in c hr onic e x posur e . Th e refo re , the lo n g - t e rm a g gre g at e e x po s ur e and risk e s t i mat e s ar e e quiva l e nt to the c hr onic di e t ar y e x posure and risk e st i mat e s discuss e d a bov e . T h e c hronic diet ar y risk e st i mat e s w e re not o f c o n ce rn f o r the g e n e r al U. S . population and a ll population sub groups. A ll sub groups use l e ss th an 1 % of the c P A D . Con c lus i ons for Aggr e g ate E xposure and R i sk A c ute, inte r

medi at e - te r

m , and can ce r a g greg ate ri s k a ssessments w e r e not pe r fo r med for am i no p y r a l id . The short - and lon g - te r m a g gre g ate risk e st i mat e s ar e not of c on ce rn to H ED f or an y o f the population sub groups for whi c h risk e st i mat e s w e r e g e n e r a ted. A t the t i me of re g is tr a t i on r e vi e w, HED will c ondu c t a n e w a g gr e g ate risk a s s e ss m e nt th a t will be b a s e d on r e sidenti a l e x posur e s esti m ated us i ng the up d ated r e sidenti a l S OP s , and will include an y potential upd ates to point s of d e p artur e or e x posur e e st i mat e s f r om food an d drinking w ate r . **Oc c**  **up a**  **t io**  **n al**  **E x**  **p o**  **s u**  **r e**  Amino p y r a l i d is r eg is te red for use in a v ari e t y of n on - c ropl and are a s and gr az e d are a s , a s w e ll a s on wh eat and c o r

n. It c an be a

ppl i e d a s a b ro a d c a st tr e atm e nt b y gr ound, a e ri a l , and h andh e ld e quip m e nt. The A g e n c y h a s det e rmin e d that th e re is a pote nt i a l for o cc u p at ional h andler and pos t - a ppl i cat i on e x posure s r e sul t ing f rom the re g is t e r e d us e s of am i no p y ra l i d. O cc up at i on a l H andle r s The pr e vious e x posure and risk a ssessments e v a l u ated a number o f oc c u p at i on a l handl e r s ce n arios that r e p re s e nt e d the m a jor am i no p y

r a l i d short - and int e rm e diat e - t e rm o cc u p at i on a l e x posur e s a ssoci ated w i th a ppl i cat i on e quip m e nt and f o r mu l at i on t y

p e . T he risk ass e ss m e nts ind i cated th at the r e are n o risks of c on c e rn a ssoc i ated w i th o cc u p at i on a l handl e r s c e n arios f o r wo r k e rs w eari n g b a s e l i ne c lo thing ( i.e., lo n g p ants, long sle e v e shirt, sho e s plus s o c k s ) .Aminopy ralid Registr a

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### P a g e 9 o f 27 HED will l i k e l y r ee v a l u ate the o cc u p at i on a l handl e r a ssessment f o r a m i no p y r a l i d to ad dr e ss upd ates to HE D ’s e x posure pol i c ies, spe c i fi ca l l y, r e vis i ons to the A g e n c y ’s s ce n ari o - s p ec ific sur r o g ate h an dler e x posure d ata and a ssumpt i ons for bo d y w e i ghts. O cc up at i on a l P os t - a

ppl ic at i on The pr e vious risk as s e ss m e nts ev a luat e d a numb e r of r ep r e s e ntative o cc u p at i on a l pos t a ppl i cat i on s ce n arios b a s e d on the r e g is t e r e d us e s. HED h a s det e rmin e d that the r e are potential d e rm a l e x posur e s of p e o ple e nte ri n g tr e ated sit e s ( e . g . , h ar v e ste r s) a ft e r p e st i c ide a

ppl i cat i on is c omp l e te. H ow e v e r, sin c e no d e rm a l endpoints w e re se l ec ted, a qu ant i tative pos t - a ppl i cat i on e x posure a ssessment f

or a gricultur a l wo r

k e rs w a s not c ondu c ted. In acc o rd a

n c e with the upd ated Part 158 data r e qu ir e ments (2007 ) , one o r more dis l od g e a ble f ol i ar re sidue ( D F R) stud i e s ar e r e quir e d wh e n a p e st i c ide h a s r e si d e nt i a l or o cc up at i on a l uses that c ould r e sult in pos t - appl i cat i on d e rm a l e x posur e . Ho w e v e r, a D F R stu d y is not r e qui r e d for am i no p y r a l i d at this t i m e b eca

use n o d e rm a l e nd

p oint s w e re sel e c ted, and t h e r e f o r e , a d e rm a l pos t - a ppl i cat i on e x posure a ssessment is not r e qui r e d. A f ter a ppl ic at i on of the p rodu c t , a gri c ul tur a l wo r k e rs c ould be e x posed to re si du e s f r om bo th the am i no p y r a l i d salt and the p ar ent a c id. Th e r e fo r e , the re strict e d e ntr y int e r v a l (RE I) f

or a gricultur a l o c c up at i on a l e x posure is bas e d on the ac ute to x ici t y of both am ino p y r al i d a c id te c hnic a l and the T IP A s a l t . Amino p y r al i d a c id i s cl a ss i fi e d a s To x ici t y C ate g o r y IV f o r a c ut e d e rm a l i r ri t at i on and leth a l i t y f

ol l owi n g ac ut e d e rmal e x posur e . Ho we v e r, und e r the r e quir e ments f

o r the W o rk e r Prot ec t i on S tand ard f or A gri c ul tura l P e st i c ides ( WPS ), am i no p y r a l i d is c lassifi e d a s To x ici t y C at e g o r y I in an ac ute to x ici t y e ye i rritation s tu d y . A cc o r di n g to W PS , a 4 8 - hour RE I is a ss i gn e d to c h e m i ca ls with a c ute To x ici t y C at e g o r y I c lassifi cat i ons. F urth e r

m o re , c h e m ic a ls cl a ss i fi e d a s To x ici t y C ate g o r y I f o r e ye ir ri t at i on r e quire the u s e of p r ot e c t ive e ye w ear. T h e refo re , HED re c omm e nds th at during r e g is tr a t i on re view the p rop er RE I b e includ e d on a ll r e g is t e re d master lab e l s and a ll the suppl e ment a l l a b e ls to ensur e that the RE I s ar e a d e qu ate to p r ote c t w o r k e rs f rom pos t - a

ppl ic at i on e x posur e s to am i no p y r a l i d. B a s e d on th e A g e n c y ’ s c ur r ent pr a c t i ce s, a qu ant i tative pos t - a ppl i cat i on inhal at i on e x posure a ssessment w a s not p e r f

o rm e d for am i no p y

r a l i d. Ho we v e r, i f n ew polici e s or p r o ce d ur e s are put into p l ace , the A g e n c y m i ght r e vis i t the n e e d for a qu ant i tative o cc up at i on a l pos t - a ppl i cat i on inhal at i on e x posure a ssessment f or am i no p y

r a l i d during r e g is tr a

t i on re vi e w. Con c lus i ons for O cc u

p at i on a l E x posure and R i sks Upd ated o c c up at i on a l h a ndler e x posure a ssessm e nts will l i k e l y be r e qui r e d und e r re g is tr at i on r e view b a s e d upon r e vis i ons to the A g e n c y ’s s c e n ari o - spe c i fic sur r o g ate h andler e x posure d ata and a ssumpt i ons for bo dy w e i ghts. No o cc u p at i on a l pos t - a

ppl i cat i on d e r

m a l e x posure a ssessment will be r e qui r e d und e r re g is tr a t i on r e v i e w ; how e v e r, the A g e n c y m i ght r e vis i t the n ee d for a qu ant i tative o c c up at i on a l pos t - a ppl i cat i on inhal at i on e x posure a ssessment . HED r e c omm e nds th at , duri n g r e g is tr a t i on re vi e w, the p rop er RE I be i n c luded on a ll r e g is t e r e d m a s t e rAminopy ralid Registr a

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### P a g e 10 o f 27 lab e ls and a ll the suppl e ment a l l a b e ls to ensur e th at the RE I s are a d e qu ate to prote c t wo r k e rs f r om pos t - a

ppl i cat i on e xposur e s to amino p y r a l i d. **P ub**  **l i**  **c Heal**  **t h**  **a n**  **d P**  **e st**  **i c**  **i d**  **e E**  **p i**  **d e**  **m io**  **l ogy Da**  **t a**  F or th i s ev aluation, the A g e n c y c onsulted both the OPP I n c ident D ata S ys t e m ( IDS) and the C e nte r s for Dis e a se Control and P r e v e nt i on/N at i o n a l I nst i tut e f o r O c c up at i on a l S a f

e t y and H ea l th (CDC/

N I OSH) Se nt i n e l Ev e nt Not i fi cat i on S ystem for O cc u p at i on a l R is k - P e st i c ides (SENSOR) d a

tab a s e s for p e st i c i d e incid e nt data o n the ac t i ve i n gr e d i e nt am i no p y r al i d ( Memo, D415939, S . Re c o re , 11 / 1 2 /2013). T he pur p ose o f the d atab a s e sear c h w a s to i d e nt if y potential p att e rns in the f

r e qu e n c y and s e v e ri t y of the h ea l th e f f e c ts attribut e d to am i no p y r a l i d e x posur e . Am i no p y r a l i d is not i n c luded in the A gri c ul tura l H ea l th S tu d y ( AH S ) ; and the re fo r e, th at stu d y do e s not pro v ide in f

o r m at i on f o r this r e port. F or the M a in IDS, f

r om J anu ar y 1, 2008 to S e pt e mber 11, 2013, the r e w e r e 3 incid e nts r e port e d for sin g le c h e m ic a l on l y i n the d atab a s e . Th e r e w e re 11 a ddi t ional incid e nts re port e d invo l vi n g more than one c h e m i ca l. The incid e nts r e p o rt e d w e re c l a ss i fi e d a s mod e r a t e sev eri t y . O v e r al l , the r e are f

e w in c idents i n volv i ng am i no p y r al i d r e p o rted to IDS. In A g gre g ate ID S , f rom J anu ar y 1, 2008 to S e ptemb e r 11, 2013, the r e w e re 35 r ep o rt e d incid e nts invo l ving am i no p y r al i d . The S ENSO R - P e st i c ides d atab a se c ov e rs 11 stat e s f r om 199 8 - 2009, a l tho u gh r e porti n g v ari e s f r om s t ate to st at e . C a s e s of p e st i c id e - r e lat e d i l ln e sses are a s c e rt a ined f rom a v ari e t y of so ur c e s including re p o rts f

r om l o ca l P oison Control C e nter s, s t ate De p artme nt of L a bor w o r k e rs’ c ompens at i on c laims wh e n r eport e d b y p h ysici an s, r e ports f rom State D e p artme nts of Agri c ul ture , and p h ysic i an r eports to state D e p artments of Hea l th. A qu ery of S ENSO R P e st i c ides f

r om 1998 to 2009 r e v ea l e d that two ca s e s involv i ng am i no p y r al i d w e re r eport e d . B oth c a s e s involved mul t ip l e ac t i ve ingr e dients an d w e re low in s e v e ri t y . B a s e d on th e low f

r e qu e n c y and s e v e ri t y o f in c id e nt c a s e s r ep o rt e d in bo th IDS and S ENSO R P e st i c ides, the r e do e s not a pp ear to b e a c o n c e rn a

t th i s t i me th at would w ar rant furth e r investi g at i on. The A g e n c y will c ont i nue to m oni t or the in c ident info r mat i on and if a c o n ce rn is trig g e r e d, a ddi t ional an a l ys is will be includ e d in t he risk ass e ss m e nt. **Tole r**  **a n**  **c e**  **Ass e**  **s s**  **me n**  **t an**  **d I**  **n t**  **e r**  **n a**  **t io**  **n al**  **H a**  **r m**  **o n**  **iza t**  **ion** Tole ran c e s for r e sidues o f am i no p y r a l i d in or on a gri c ul tur a l commod i t i e s ar e e s t a bl i shed in 40C F R §180.610. F or p l ant commod i t i e s, the tol e r a n ce s are e stablished a s follows: “ T ole ran ce s are e s t a bl i shed for r e sidues of the h e rb i c ide am i n op y r a l i d, 4 - am i no - 3,6 - di c hloro - 2 - p y ridin e carbo x y

l i c ac id, including i t s metabolit e s and d e gr a d ates, in or on the c omm odi t ies in the t a ble b e low. Comp l ian c e with the to l e r an c e l e v e ls s p ec ified b e low is to be d e te r m i n e d b y me a suri n g on l y f

r e e and c onjugat e d am i no p y r al i d. ” F or ani m a l commod i t i e s, the tol e r a n ce s are e stablished a s follows: “ Tol e r a n c e s ar e e stablish e d for re sidues o f the h e rb icide am i no p y r a l i d, 4 - am i no - 3,6 - dichlo r o - 2 - p y

ridin ecarbo x y

l i c ac id, i n c lud i ng i t s metabolit e s and d e gra d at e s, in or onAminopy ralid Registr a

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### P a g e 11 o f 27 the c omm odi t ies in the table b e low. Comp l ian c e with the to l e r a n c e l e v e ls spe c ified b e low is to be d e te r m i n e d b y m e a sur ing on l y am i no p y r al id .” The Cod e x Ali m e ntarius C omm is s ion (Cod e x ) h a s e stablished max i mum r e sidue lim i ts ( M R L s) for am i no p y

r al i d on both plant and l i v e stock c o m mod i t i e s . The Cod e x re sidue d e finit i on is the s ame f or both t y p e s of c o mm odi t ies: am i no p y r a l i d and i t s co n

ju g at e s that can be h y

dr o l y z e d, e x p re ssed a s amino p y

r al i d. I n the ca s e s wh e r e the U.S. and Cod e x h ave e stablished M R L s f o r the s ame c omm odi t ies, the M R L s are not h armoni z e d. Cod e x h a s est a bl i s h e d M R L s f

o r c omm odi t ies th at do not h ave U.S. t ole ran c e s. Can a da h a s es t a bl i shed M RL s f

o r wh e at gr a in, wh eat br an, and s e v e r al l ivesto c k c omm odi t ies. The C an a dian r e sidue d e finit i ons and M R L s are a ll h armoni z e d with th ose o f the U.S. The h arm o ni z e d to l e r a n ce s include those for wh eat gr ain, wh eat br an, and l i v e stock c omm odi t ie s . C an a da d o e s not set M R L s in l ive s tock fee d i t e ms, s o the r e is no is s ue with harmon iz at i on f o r th e se c omm odi t ie s . The int e rn a t i on a l r e sidue lim i t status sh ee t c an be found in Att ac hment 6. During re g is tr a

t i on r e v i e w, H ED w i l l r e vis i t the to l e r a n c e s and h armoni z e them with the Cod e x M R L s, wh e n poss i ble. T he U.S. t ole ran c e s for s o me of the wh e at and liv e stock c omm odi t ies are sl i ght l y low e r th an the C od e x M RL s f o r the same c omm odi t ies. The U.S. could potential l y h armoni z e with C od e x b y maki n g sl i ght i n c re a s e s to the to l e r a n ce s for wh e at gr a in, h a y, and str aw. T he sam e is true f or the m eat and m e at b y

p rodu c ts of catt le, g o ats, hors e s, and sh e e p. **E n**  **viron m**  **e n**  **tal Justi c**  **e** P otential ar e a s of e nvir o nment a l j ust i c e c on c e rns, to the e x tent poss i ble, w e re c onsi d e r e d in the human - h ea l th risk a sses s ment, in a cc o r d an c e with U. S . E x ec ut i ve O r d e r 1 2 898, “Fe d e r al A c t i ons to Addre ss Environm e nt a l J u s t i c e in Minori t y P o p ulations and L o w - In c o m e P opulations,” (http://www.hss. e n e r g y . gov/nucl ears a f e t y /env/ g u i d an ce / j ust i ce /eo12898.p d f

) . The OPP t y pic a l l y c onsid e rs the h i gh e st po t e nt i a l e x posur e s f rom the l e g a l use o f a p e st i c ide wh e n c ondu c t i ng hum an - h e a l th risk a ssessments, in c lud i n g , but n ot l i m i t e d to, people who obt a in drink i ng w ater f

rom sour ce s near a gri c ul tura l ar e a s, the v ari a bi l i t y of d i e ts with i n the U . S ., and p e ople who m i ght b e e x posed wh e n h arv e st i n g c r o ps. S hould th e se hi gh e st e x posur e s ind i cate potential risks of c on c e r

n , OPP further r e fin e s the risk a ssessments to e nsur e that the risk e st i mat e s ar e b a s e d on th e b e st av a i l a ble i n fo r mat i on. **Cu m**  **u lative**  **Risk Ass**  **e s**  **s me**  **n ts**  Unlike oth e r p e st i c ides f

or whi c h EPA h a s follo w e d a c umu l at i ve risk a pp r o ac h b a s e d on a c omm on me c h anism of t o x ici t y, EPA h a s not m a de a c omm on me c h anism of to x ici t y f ind i n g a s to am i no p y

r al i d and an y other subs t an ce s , and am ino p y r al i d do e s not a

pp e ar to p r odu c e a to x ic met a bol i te p r odu ce d b y o ther subs t an ce s. F or the purp o s e s of this ac t i on, the re f o r e , EPA h a s not a ssum e d that am i no p y

r a l id h a s a c omm on me c h an ism of toxici t y with o th e r subs t an ce s. F o r info r mation r e g arding E P A ’ s e f f o rts to det e rmine whi c h c h e m ic a ls have a c omm on me c h anism of to x ici t y and to e v a luat e the c umu l at i ve e f f e c ts of su c h c h e m ic a ls, s e e th e pol ic y stat e ments r e le a s e d b y EPA’s O f

fi c e of P e st i c ide Programs c o n ce rni n g c omm on me c h anism d e te r m i n at i onsAminopy ralid Registr a

t i on Review Scoping Document



### P a g e 12 o f 27 and p r o ce d

ur e s f o r cumu lating e f

fe c ts fr o m subst an ce s found to h av e a c o m mon m ec h anism on EPA’s we bsi t e at htt

p: //www . e p a . g ov/

p e st i c ides/ c umu l at i v e / . **H u**  **m an**  **S tu**  **d ies**  The pr e vious am i no p y

r a l i d risk a ssessments r e l i e d in part on data f rom stu d ies in whi c h a dult human subje c ts w e r e inte nt i on a l l y e x posed to a pe st i c ide or other c h e m i ca l. S tud i e s such a s the P e st i c ide Handle r s E x posure D ata b a s e , Outdo o r R e sidenti a l E x posure T a sk F o r c e , and Agricultur a l H and l e r E x posure T a sk F o r c e h av e b e e n r e vie w e d b y the A g e n c y and f o un d , on the b a sis of a v a i l a ble e vide n c e , to h ave b ee n n e i th e r f und ament a l l y un e th i ca l n or si gnifi c ant l y d e fi c ient r e lative to st an d ards of e th ic a l r e s e ar c h c ondu c t pr e v a i l i n g wh e n t h e y w e r e c ondu c t e d. Th e re is no b ar

rier in E P A ’ s “ P rot ec t i on of Hum an S ubje c t s ” R e g u l at i on to r e l i an c e on th e se stud i e s. **Risk Ass**  **e ssm**  **e n**  **t U**  **pd a**  **te s, Da**  **t a D**  **e f**  **ici e**  **n c**  **ies, a**  **n d**  **La b**  **e l R**  **e vis**  **i o**  **n s**  No d ata d e f

i c ien c ies w e r e identifi e d for am i no p y r a l id . EPA ant i c ipat e s co n du c t i ng the f ol l owi n g risk a s s e ss m e nt updat e s duri n g r e g is tr at i on re vie w : To x icolog y :

 HED will c onsid e r the a p p r opri aten e ss o f the e x is ting e ndpoint s bas e d on c ur r ent po l ici e s and risk a ssessment meth odolo g ies. R e sidue Chemistry :
 Non e . Di e tar y E x posur e :

 R e vised diet ar y e x posure an a l ys e s m i ght b e re qui r e d to r e fl e c t upd ated di e t ar y e x posure models and upd ated dri n king w at e r e st i mat e s. O cc up at i on a l /R e sidenti a l E x posur e :

 HED ant i c ipat e s c ondu c t ing re vi s e d o c c u p at i on a l e x posure a ssessments to r e fl e c t the use of the most rece nt h andl e r e x posure d ata and up d ated bo d y w e i ght s .  The A g e n c y m i ght c ond u c t a r e vised r e sidenti a l p o s t - a ppl i cat i on a ssessment that inco r por a tes r e c e nt l y up d ated p r o c e dur e s found in the H ea l th E f f ec ts Divis i on’s 2012 S tand ard O p e r at i ng P r oc e dur e s f o r R e sidenti a l Pe st i c ide E x posure Ass e ss m e nt.Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 13 o f 27 **R e**  **f ere**  **n ce**  **s Me**  **m oranda**  **R e**  **l e**  **v ant**  **t o**  **R eg**  **i s**  **t r**  **a ti**  **on R**  **e v**  **i e** **w A**  **uthor B**  **a r**  **code D**  **a t**  **e T**  **it l**  **e** D . D o t son D 359088 10 / 2 2 / 2009 A m i nop y r a l i d. Human He a lth Ri sk A s s e s s ment f o r th e Propo s ed U se on F i e l d C o rn ( P P #8F 7 455) J . V anAl s t i ne NA 4 / 7 / 2013 A m i nop y r a l i d: S ummary o f H a z ar d an d S c i en c e Po l i cy C ounc i l ( HA S POC ) M e e t i ng of M a r ch 28, 201 3 : R e c o mmendat i ons on th e R equ i re ment of a Sub c hr o ni c I nha l at i on S tudy D . D o t son D 360100 10 / 2 2 / 2009 A m i nop y r a l i d and Am

i no py r a li d Tri i so p r o p ano l ammo n i um ( T IP A ) Sa lt . R equ e st t o A dd U s es on Fi e l d C orn t o M il e s t o ne ® ( E P A Re g . N o. 62719 - 519 ) . Sum

mary of An a l y

ti c a l C he mi s try an d R e si d ue D at a D . D o t son D 369212 10 / 2 2 / 2009 A m i nop y r a l i d C hr o n i c A ggr e g at e D i e t ary ( Food and Dri nki ng Wat e r) Expo s ur e and Ri sk A s s e s s ment f or the S e c ti on 3 R e g i s tr at i on on F i e l d C o r n M. Co l l an

t es D 305672 5 / 2 4 / 2005 O ccup ati o n al and R e s i d enti al Exp o su r e Ri s k A s s e s s ment f

o r Pr o po s ed Us e s of Am

i nop yr a l i d Z . Fi g ue r oa D 370497 10 / 2 2 / 2009 A m i nop y r a l i d O cc u

pat i o nal Expo s ur e A s s e s s ment f o r the R e g i s tr at i on o f M i l e s t one H e r b i c i d e f o r U se on C o rn R . B ari s D 361926 7 / 2 4 / 2009 Ti e r I D ri n ki ng Wat er E x p o sur e A s s e s s ment f

o r th e S e c t i on 3 N ew U se of Tr i i so p r o p ano l ami ne Sa l t of Am i nop y r a li d o n Fi e l d C o rn and Fi e l d C o rn Gr o wn f

or E n s il a g e S. R eco r e D 415939 11 / 1 2 / 2013 A m i nop y r a l id : Ti er I R e vi ew of Human I nc i dent s



### A **t ta**  **c h**  **me n**  **ts** Atta c hment 1. Ch e m i ca l Id e nt i t y T a ble Atta c hment 2. To x icolo g y D ata R e quir e m e nts Atta c hment 3. Amino p y r al i d Endpoint S e le c t i on T a ble Atta c hment 4. To x ici t y P ro f

i l e T a ble Atta c hment 5. S umm ary of O cc u p at i on a l Us e s B a s e d on R e g is te r e d L a b e ls f or Amino p y

r a l i d Atta c hment 6. I

nte r n at i on a l R e sidue Li m it S tatusAminopy ralid Registr a

t i on Review Scoping Document



### P a g e 14 o f 27 **A t**  **ta c**  **h me**  **n t 1. Ch**  **e m**  **i c**  **al I d**  **e n**  **ti t** **y Ta b**  **le**

**A m** **inop y**  **r a**  **lid N**  **o m**  **e ncl**  **at ur**  **e** . Ch e mical s tr

u c t ur e N H 2 Cl O H C l N O C o mm o n n a m e Am i n o p y r alid C o m p a ny e xp e r i me ntal n a m e XD E - 750 I U P A C n a me 4 - a mi n o - 3 , 6 - d i c h l orop y r i d i n e - 2 - c arbo x y lic a c id C A S n a me 4 - a mi n o - 3 , 6 - d i c h l or o - 2 - p y r i d i n e c arbox y lic a c id C A S r e g i s tr y num

b er 150 1 1 4 - 71 - 9 Ch e mical s tr

u c t ur e N H 2 HO C H3 Cl H3 C



# . N OH C l N OH OH

O C H 3 C o mm o n n a m e Am i n o p y r ali d , trii s oprop an o la mmo n i um ( T I P A) s alt P C C od e 005 2 0 9 C o m p a ny e xp e r i me ntal n a m e XD E - 75 0 T I P A s alt I U P A C n a me 4 - a mi n o - 3 , 6 - d i c h l orop y r i d i n e - 2 - c arbox y lic a c id - (2R S, 2 ′ R S , 2 ′′ R S ) - 1 , 1 ′ , 1 ′′ - n itril o tri prop a n - 2 - o l (1 : 1 ) C A S n a me 4 - a mi n o - 3 , 6 - d i c h l orop y r i d i n e - 2 - c arbox y lic a c id c o m poun d wi t h 1 , 1 ′ , 1 ′′ - n itril o tri s [ 2 -prop an o l] (1 : 1 ) C A S r e g i s tr y num

b er 566 1 9 1 - 89 - 7 E n d - us e produ ct ( E P ) Milest o n e ® ( 2 lb a e / g al SL; E P A R e g . N o . 62 7 1 9 - 519)Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 15 o f 27 **A t**  **ta c**  **h me**  **n t 2. Toxicology Da**  **t a R**  **e qu**  **ir e**  **me n**  **ts** The re qui r e ments (40 C F R 158.340) f or am i no p y

r a l i d r e sidenti a l and o c c up at i on a l use ar e shown b e low. Use of the n e w guideline numb e rs do e s n ot i mp l y that the n e w ( 1 9 98) g uideline p r otocols w e r e use d . **T est**  **T e**  **c h**  **n ic**  **a l**  **Required S**  **at i**  **s f**  **ied** 870 . 1 10 0 A c ute O r al T o x ici t y ........................................................ 87 0 . 1 20 0 A c ute De r m al T o x ici t y ................................................... 870 . 1 30 0 A c ute Inh alati o n T o x ici t y ............................................... 870 . 2 40 0 P r i m

ar y E y e Irr itati o n ..................................................... 87 0 . 2 50 0 P r i m

ar y De r m al Irr itati o n ............................................... 870 . 2 60 0 De r m

al S e ns i t izati o n ...................................................... y es y es y es y es y es y es y es

y es y es y es y es y es 870 . 3 10 0 O r al S u

b c hron ic (rod e n t) ................................................ 870 . 3 15 0 O r al S u

b c hron ic ( n o n rod e n t) .......................................... 870 . 3 20 0 21 /2 8 - Day De r m al .......................................................... 870 . 3 25 0 90 - D a y De r m al ............................................................... 870 . 3 46 5 90 - D a y Inh alati o n ........................................................... y es y es no y es no y es

y es y es n o 1

- - - 870 . 3 700 a De v el o p m

e ntal T o x ici t y (rod e nt) ................................... 870 . 3 70 0 b De v el o p m

e ntal T o x ici t y ( n o nr od e nt) ............................. 870 . 3 80 0 R e produ cti o n .................................................................. y es y es y es y es

y es y es 870 . 4 100 a Chron ic T o x ici t y (r od e n t) ............................................... 870 . 4 10 0 b Chron ic T o x ici t y ( n o n rod e n t) ......................................... 870 . 4 200 a O n c o g e n ici t y (r at) ........................................................... 870 . 4 20 0 b O n c o g e n ici t y ( mo us e) .................................................... 870 . 4 30 0 Chron ic/ O n c o g e n ici t y .................................................... y es no y es y es y es y es

y es y es y es y es 870 . 5 10 0 M ut a g e n i c i t y

— G e n e M utat i o n - b a c te r ial ...................... 870 . 5 30 0 M ut a g e n i c i t y

— G e n e M utat i o n - m a mm ali a n ................. 870 . 5 37 5 M ut a g e n i c i t y

— Str u ct ur al Chr o mo s o mal Ab e rr ati o n s .... 870 . 5 39 5 M ut a g e n i c i t y — M a mm a lian E ry thro c y te M ic ro nu cl e u s . 870 . 5 55 0 M u ta g e n ic it y —U ns c h e du led D N A S y n t h es i s ................ 87 0 . 5 91 5 M uta g e n ic it y — I n Vivo Si s ter Chr o m atid E x c h an g e y es y es y es no no no y es

y es y es y es y es

-- 870 . 6 100 a A c ute Del a y ed Ne uro t o x . ( h e n) ...................................... 870 . 6 10 0 b 90 - D a y N e uro t o x ici t y ( h e n) ........................................... 870 . 6 200 a A c ute N e uro t o x . Sc r e e n i n g B a tte r y (r at) ........................ 870 . 6 20 0 b 9 0 Day N e uro t o x . Sc r e e n i n g B atte ry (r at) ...................... 870 . 6 30 0 De v el op . Ne ur o .............................................................. no no y es y es no - - -

- - - y es n o 2 870 . 7 48 5 Ge n e r al M e tabo li s m ....................................................... 870 . 7 60 0 De r m

al P e n etr ati o n ......................................................... y es no y es

y es 870 . 7 80 0 I mm

un o t o x ici t y ... ......... ... ...... ... ...... ... ... ... ......... y es y es 1 R e qu ir e m e nt f

u l f illed b y 21 / 2 8 d ay s tu d y . 2 R e qu ir e m e nt f

u l f illed b y c hr o n ic n e uro t o x ici t y s tu d y .Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 16 o f 27 **S u**  **m m**  **a ry**  **o f**  **T o**  **x ic**  **o l**  **og ic**  **a l**  **D o**  **s es**  **a nd**  **E n**  **d p**  **o in**  **t s**  **fo r**  **A m** **i n**  **o p**  **y r**  **a lid**  **fo r**  **Use in**  **Die ta**  **ry a**  **nd N**  **o n**  **- O**  **c c**  **u p**  **at i**  **o n**  **a l**  **H u**  **m a**  **n H**  **e a**  **lth Ri**  **s k**  **A ss**  **e ss**  **m e**  **nt s**  **. E**  **x p**  **o s**  **ure/ Scen**  **a rio**  **P o**  **int o**  **f**

**Dep a**  **r t**  **ure Unce**  **rta int**  **y /** 

**F Q**  **PA S**  **af**

**e t**  **y F**  **a c**  **to rs**  **R f** 

**D, PAD,**  **L e**  **v el**  **o f**  **C o**  **nce r**  **n fo**  **r Ri**  **s k**  **As s**  **e ss**  **m e**  **nt Study**  **a nd**  **T ox**  **ic o**  **l og**  **ic a**  **l Ef**  **f e**  **ct s** 
A c ute Dietar y ( Ge n e r al P op u lati o n , i n c l u d i n g I n f a nts a n d Ch i l dr en an d f e m ales 1 3 - 49) N / A N / A N / A A t o x ic e f f e c t attri b utab le to a s i n g le do s e w a s n o t se e n i n th e t ox ici t y d a tab ase; th e r e f or e, an a c ute e n dpo i nt h as n o t b e e n i d e nt i f ie d .
Chron ic Dietar y ( All P op u lati o ns ) N O AE L= 5 0

m g /kg/ d a y U F A= 10 x

UF H = 10 x FQ P A S F= 1 x Chron ic R f D

= 0 .5 mg/k g/ d a y c P AD

= 0 .5 mg/kg/ d a y Chron ic t o x ici t y/car c i n o g e n ic it y s tu d y i n

r ats ( XD E - 750) L O A E L= 50 0 mg /k g/ d a y b ased o n c e c a l e n lar g e m e nt, s l i gh t mu c o s al hy

p e rp las i a in m al e s an d s l i ghtl y d e cr e a s ed b o d y w e i g h ts I n ci d e ntal O r al S h or t - T e rm ( 1 - 3 0 d ay s ) I nte r me d iat e T e rm ( 1 - 6 mo nt hs ) N O AE L= 10 4

m g a e / kg/ d a y UF = 10 x

UF H = 10 x FQ P A S F= 1 x R eside ntial

L O C f o r MOE = 10 0 De v el o p me ntal r abb it s tu d y ( G F - 871)

L O A E L= 26 0 mg /kg/ d a y b ased o n s e v e r e i n a n iti o n ( e xh aus ti o n r es u lt i n g f

r o m la c k o f f

ood ) an d bod y w e i g ht l o ss , d e cr e a s ed f

e c al o ut p ut, a n d m ild i n c oord i n ated g a i t. De r m al S h ort T e rm ( 1 - 30 d ays ) I nte r me d iat e T e rm ( 1 - 6 mo nt hs ) N / A N / A N / A 28 - d ay d e r ma l t o x ici t y s t u d y i n r ats. No s ys t e mic t o x ici t y s e e n at th e l i mit do s e (1,0 0 0 mg/kg/ d a y

) ( XD E - 750) De r m al r i s k s ar e n o t o f c o n c e r n . I nh alat i o n S h or t - T e r m (1 - 3 0 d a y s ) I nte r me d iat e T e rm ( 1 - 6 mo nt hs ) N O AE L= 10 4

m g a e / kg/ d a y U F A= 10 x

UF H = 10 x FQ P A S F= 1 x R eside ntial

L O C f o r MOE = 10 0 De v el o p me ntal r abb it s tu d y ( G F - 871)

L O A E L= 26 0 mg /kg/ d a y b ased o n s e v e r e i n a n iti o n ( e xh aus ti o n r es u lt i n g f

r o m la c k o f f

ood ) an d bod y w e i g ht l o ss , d e cr e a s ed f

e c al o ut p ut, a n d m ild i n c oord i n ated g a i t. C an c e r (or al, d e rm al, i nh a lati o n) C la s s i f icati o n : “N o t l i k e l y to b e C ar ci n o g e n ic to H um a ns ” b ased o n th e ab s e n ce o f s i gn i f icant t umo r i n c r e a s es i n t wo a d e qu a te rod e nt c ar ci n o g e n i c i t y s tu d i es. 

### A **t ta**  **c h**  **me n**  **t 3. E ndp**  **o i**  **n t Sel**  **ec tion**  **T a**  **b les**  **Su m**  **m a**  **r y of**  **Toxicological Dos e**  **s a n**  **d E**  **n d**  **p oi**  **n t**  **s f**  **or Use**  **in H**  **u m**  **an Risk**  **Ass e**  **ssm e**  **n ts** 

A

P o i nt o f De p art

ur e = A d ata po i nt o r an est i m ated po i nt th a t is d e r i v ed f r o m ob s e rv ed do s e - r es po ns e d ata an d us ed to m ar k th e b e g i nn i n g o f e xtrap o lati o n to d ete rmi n e r i s k as s o ciat e d wi th l o w er e nv ir onm e nt al l y r ele v a nt hum a n e xpo sur es. N O A E L = n o ob s e rv ed a dv e r s e e f f e c t l e v el. LO A E L = l o w est ob s e rv ed a dv e r s e e f f e c t le v el. UF = un c erta i nt y f

a c t or . U F A = e xtrapo lati o n f r o m a n i ma l to hum an ( i nte r s p e ci e s ) . U F H = po te ntial v ar iati o n i n s e n s it i v i t y a m o n g m e m

b e r s o f th e hum an pop u lati o n ( i ntras p e c ies). FQ P A SF = F Q P A S a f e t y Fact or . P AD = pop u lati o n a d

j us ted do s e ( a = a c ute, c = c hro n ic ) . R f D = r e f e r e n ce do s e. N/A = n o t app li c ab le. A e = a c id e qu i v al e nt. XD E - 7 5 0 = a c id f orm o f a mi n o p y

r ali d . G F - 87 1 = trii s oprop an o la m m on i u m s a lt o f a mi n o p y r ali d .Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 17 o f 27 **S u**  **m m**  **a ry**  **o f**  **T o**  **x ic**  **o l**  **og ic**  **a l**  **D o**  **s es**  **a nd**  **E n**  **d p**  **o in**  **t s**  **fo r**  **A m** **i n**  **o p**  **y r**  **a lid**  **fo r**  **Use in**  **O c**  **c u**  **p at**  **i o**  **n a**  **l H**  **u m**  **a n**  **H e**  **a lth**  **Ri s**  **k A**  **ss e**  **ss m**  **e nt**  **s .**  **E x**  **p o**  **s ure/**  **Scen a**  **rio P**  **o int**  **o f** 

**Dep a**  **r t**  **ure Unce**  **rta int**  **y /** 

**F Q**  **PA S**  **af**

**e t**  **y F**  **a c**  **to rs**  **R f** 

**D, PAD,**  **L e**  **v el**  **o f**  **C o**  **nce r**  **n fo**  **r Ri**  **s k**  **As s**  **e ss**  **m e**  **nt Study**  **a nd**  **T ox**  **ic o**  **l og**  **ic a**  **l Ef**  **f e**  **ct s** 

De r m al S h ort T e rm ( 1 - 30 d ays ) I nte r me d iat e T e rm ( 1 - 6 mo nt hs ) N / A N / A N / A 28 - d ay d e r ma l t o x ici t y s t u d y i n r ats. No s ys t e mic t o x ici t y s e e n at th e l i mit do s e (1,0 0 0 mg /kg/ d a y) ( XD E - 750) De r m al r i s k s ar e n o t o f c o n c e r n . I nh alat i o n S h or t - T e r m (1 - 3 0 d a y s ) I nte r me d iat e T e rm ( 1 - 6 mo nt hs ) N O AE L= 10 4

m g a e / kg/ d a y U F A= 10 x

UF H = 10 x Oc c u

p ati o n al L O C f o r MOE = 10 0 De v el o p me ntal r abb it s tu d y ( GF - 871)

L O A E L= 26 0 mg /kg/ d a y b ased o n s e v e r e i n a n iti o n ( e xh aus ti o n r es u lt i n g f

r o m la c k o f f

ood ) an d bod y w e i g ht l o ss , d e cr e a s ed f

e c al o ut p ut, a n d m ild i n c oord i n ated g a i t. C an c e r (or al, d e rm al, i nh a lati o n) C la s s i f icati o n : “N o t l i k e l y to b e C ar ci n o g e n ic to H um a ns ” b ased o n th e ab s e n ce o f s i gn i f icant t umo r i n c r e a s es i n t wo a d e qu a te rod e nt c ar ci n o g e n i c i t y s tu d i es. P o i nt o f De p art

ur e = A d ata po i nt o r an est i m ated po i nt th a t is d e r i v ed f r o m ob s e rv ed do s e - r es po ns e d ata an d us ed to m ar k th e b e g i nn i n g o f e xtr apo lati o n to d ete rmi n e r i s k as s o ciat e d wi th l o w er e nv ir onm e nt al l y r ele v a nt hum a n e xpo sur es. L O A E L = l o w est ob s e rv ed a dv e r s e e f f e c t le v el. UF = un c erta i nt y f a c t or . U F A = e xtrapo lati o n f r o m an i m al to huma n ( i nte r s p e c ie s ) . U F H = po te ntial v ar iati o n i n s e n s itivi t y a m on g m e m b e r s o f th e hu ma n pop u lati o n ( i ntras p e c ies). P AD = pop u lat i o n a d j us ted do s e ( a = a c ute, c = c hro n ic ) . R f D = r e f e r e n ce do s e. ) . F Q P A SF = FQ P A S a f

e t y Fact o r . MOE = m a r g i n o f e xpo sur e. LOC = l e v el o f c o n c e rn . N/ A = n o t app licab le. A e = a c id e qu i v al e nt. XD E - 75 0 = a c id f orm o f a mi n o p y

r ali d . G F - 87 1 = trii s oprop an o la mm on i um s a lt o f a mi n o p y r ali d .Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 18 o f 27 **A t**  **ta c**  **h me**  **n t 4. Toxici**  **t y**  **P r**  **o f**  **i l**  **e s**  **Acu t**  **e T**  **o x**  **ici t**  **y Pr**  **of**

**ile -**  **A m** **i n**  **o p**  **y r**  **a lid**  **T e**  **c h**  **n ic**  **a l**  **( XD**  **E -**  **750) .**  **G u**  **i deli**  **n e**  **N o**  **. Study**  **T y**  **pe M**  **RID(s) Resu**  **l t**  **s T**  **o x**  **ici t**  **y C**  **at e**  **go ry**  870 . 1 10 0 A c ute or a l - r at 462 3 56 0 3 LD 50 = > 500 0 mg/ k g/ b w (bo th s e x es) IV 870 . 1 20 0 A c ute d e r ma l - r abb it 462 3 56 0 5 LD 50 = > 500 0 mg/ k g/ b w (bo th s e x es) IV 870 . 1 30 0 A c ute i nh al a ti o n - r at 462 3 56 0 7 L C 50 = > 5 .5 mg/ L (bo th s e x es) IV 870 . 2 40 0 A c ute e ye irr itat i o n - r abb it 462 3 56 0 9 C orn e a l op a c i t y i n 1 /3 unr e s o l v ed throug h d a y 3 5 I 870 . 2 50 0 A c ute d e r mal irr itati o n - r abb it 462 3 56 1 1 n on - irr ita nt IV 870 . 2 60 0 S ki n s e ns i tizati o n - g u i n ea p i g 462 3 56 1 3 N o t a s e ns i tizer N / A **Acu t**  **e T**  **o x**  **ici t**  **y Pr**  **of**

**ile -**  **A m** **i n**  **o p**  **y r**  **a lid**  **T ri**  **i s**  **o pr**  **o p**  **a n**  **o l**  **a m**  **m o**  **n i**  **u m**  **S a**  **lt (**  **G F**  **- 871)**  **. G**  **u i**  **deli n**  **e N**  **o .**  **Study T**  **y pe**  **M RID(s)**  **Resu l**  **t s**  **T o**  **x ici**  **t y**  **C at**  **e go**  **ry** 870 . 1 10 0 A c ute or a l - r at 462 3 56 0 4 LD 50 = > 500 0 mg/ k g/ b w (bo th s e x es) IV 870 . 1 20 0 A c ute d e r ma l - r abb it 462 3 56 0 6 LD 50 = > 500 0 mg/ k g/ b w (bo th s e x es) IV 870 . 1 30 0 A c ute i nh al a ti o n - r at 462 3 56 0 8 L C 50 = > 5 . 7 9 mg/ L (bo th s e x e s ) IV 870 . 2 40 0 A c ute e ye irr itat i o n - r abb it 462 3 56 1 0 No po s iti v e s i g n s o f c orn e a l op a c ity , irit i s o r c o n

j un ct i v it i s ob s e rv ed IV
870 . 2 50 0 A c ute d e r mal irr itati o n - r abb it 462 3 56 1 2 Sl i g ht e r y th e m a ob s e rv ed at 2 4 h o ur s a n d 7 2 h o ur s , r es o l v i n g b y s t u d y d a y 7 IV
870 . 2 60 0 S ki n s e ns i tizati o n - g u i n ea p i g 462 3 56 1 4 N o t a s e ns i tizer N / AAminopy ralid Registr a

t i on Review Scoping Document



### P a g e 19 o f 27 **S u**  **bchr o**  **n ic,**  **Chr o**  **ni c**  **, a**  **nd O**  **t her**  **T o**  **x ici**  **t y**  **Pr of**  **ile G** **D L**  **N Study**  **T y**  **pe D**  **o s**  **e L**  **e v**  **els M**  **RID Resu**  **l t**  **s** 870 . 3 10 0 2001 - 1 3 W EEK

FE E D IN G - RAT ( XD E 750 ) w i t h 4 w e e k r e co v e r y p e r i o d m g /kg/ d a y =

0 , 10 , 1 0 0 , 5 00 , 10 0 0 A c c e p tab le/ G u i d el i n e 462 3 56 2 1 N O AEL ( m g /k g / d a y) : M =500 , F= 1 00 0 L O A E L ( mg / k g / d a y) : M =100 0 b ased o n hy p e rp las i a o f t h e mu c o s al e p ith e l i um o f t h e ile um an d c e c um . F= n o t d ete r mi n ed 870 . 3 10 0 2004 - 1 3 W EEK

FE E D IN G - RAT ( G F 871 ) ‡ XD E - 75 0 T I P A* m g / k g / d a y= 0 , 1 9 2 , 5 00 , 10 0 0 ¶ A C I D EQU I V A L E NT

( a e ) m g a e / kg / d a y = 0 , 1 00 , 26 0 , 5 2 0 A c c e p tab le/ G u i d el i n e 462 3 56 2 2 N O AEL ( m g /k g / d a y) : 520 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed

870 . 3 10 0 2001 - 1 3 W EEK

FE E D I N G - M OUSE ( XD E - 750) m g /kg/ d a y =

0 , 10 , 1 0 0 , 5 00 , 10 0 0 A c c e p tab le/ G u i d el i n e 462 3 56 1 8 N O AEL ( m g /k g / d a y) : 1000 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed 870 . 3 15 0 2002 - 1 3 W EEK

FE E D IN G - D OG ( XD E 750) %= 0 , 0 . 1 5 , 0 . 75 , 3 .0

§ pp m = 0 , 150 0 , 7 5 00 , 30 0 0 0 m g /kg/ d a y = M: 0 , 55 , 2 8 2 , 1 07 0 F: 0 , 53 , 232 , 9 2 9 A c c e p tab le/ G u i d el i n e 462 3 56 2 3 N O AEL ( m g /k g / d a y) : M =282 , F= 2 3 2 L O A E L ( mg / k g / d a y) : M =1070 , F= 92 9 b ased o n s t o m a c h h i s t op ath o l og y ( s li g h t d i f f us e hy p e rp las i a a n d hy p e rtr op h y o f th e mu c o s al e p ith e l i u m ) .Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 20 o f 27 870 . 3 20 0 2002 - 2 8 D A Y D E RM A L RAT ( XD E - 750) m g /kg/ d a y = 0 , 1 0 0 , 5 00 , 10 0 0 A c c e p tab le/ G u i d el i n e 462 3 56 2 6 S ys t e mic: N O A E L ( mg / k g / d a y) : 1000 L O A E L : ( mg/ kg/ d a y

) n o t d ete rm i n ed De r m al: N O A E L ( mg / k g / d a y) : M =100 , F= 1 00 0 L O A E L ( mg / k g / d a y) : M =500 , b ased o n h i s t op ath o l o g ical c h an g es ( s li ght ep i d e r m al h yp e rp las i a ) . F= n o t d ete r mi n ed 870 . 3 70 0 200 1 -

D E V E L O P M E N T AL T OX - RA T ( XD E - 750) m g /kg/ d a y = 0 , 1 0 0 , 3 00 , 10 0 0 A c c e p tab le/ G u i d el i n e 462 3 56 2 9 M ate rn al: N O A E L ( m g/ k g/ d a y ) : 100 0 L O A E L ( mg/ kg / d a y

) : n o t d ete rm i n ed De v el o p me ntal: N O A E L ( m g/ k g/ d a y ) : 100 0 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed 870 . 3 70 0 200 4 -

D E V E L O P M E N T AL T OX - RA T ( GF - 871) ‡ XD E - 75 0 T I P A* m g / k g / d a y= 0 , 2 0 0 , 5 00 , 10 0 0 ¶ A C I D EQU I V A L E NT

( a e ) m g a e / k g / d a y= 0 , 1 0 4 , 2 60 , 52 0 A c c e p tab le/ G u i d el i n e 462 3 56 3 1 M ate rn al: N O A E L ( m g/ k g/ d a y ) : 52 0 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed De v el o p me ntal: N O A E L ( m g/ k g/ d a y ) : 52 0 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed 870 . 3 70 0 200 2 -

D E V E L O P M E N T AL T OX - RABBI T ( XD E - 750) m g /kg/ d a y = 0 , 25 , 1 0 0 , 2 5 0 (p h ase 1) m g /kg/ d a y = 0 , 5 0 0 , 7 5 0 (p h ase 2 ) A c c e p tab le/ G u i d el i n e 462 3 56 3 0 M ate rn al: N O A E L ( m g/ k g/ d a y ) : 25 0 L O A E L ( mg/ k g/ d a y

) : 50 0 b ased o n d e cr e a s e in bod y w e i g ht ( GD 7 - 10) , d e cr e a s ed f

oo d c o ns u m p ti o n , i n c oord i n ated g ait (23 /2 6 ) , an d u lce r s an d e ro s i o n s o f th e s t o m a c h . De v el o p me ntal: N O A E L ( m g/ k g/ d a y ) : 50 0 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n edAminopy ralid Registr a

t i on Review Scoping Document



### P a g e 21 o f 27 870 . 3 70 0 200 4 -

D E V E L O P M E N T AL T OX - RABBI T ( G F - 871) ‡ XD E - 75 0 T I P A* m g / k g / d a y= 0 , 2 0 0 , 5 00 , 10 0 0 ¶ A C I D EQU I V A L E NT

( a e ) m g a e / k g / d a y= 0 , 1 0 4 , 2 60 , 52 0 A c c e p tab le/ G u i d el i n e 462 3 56 3 2 M ate rn al: N O A E L ( m g/ k g/ d a y ) : 10 4 L O A E L ( mg/ k g/ d a y

) : 26 0 b ased o n s e v e r e i n a n iti o n an d bod y w e i g ht l o ss , d e cr e a s ed f

e c al o u tp u t, an d mild i n c oord i n ated g ait. De v el o p me ntal: N O A E L ( m g/ k g/ d a y ) : 26 0 L O A E L ( mg/ k g/ d a y

) : 52 0 b ased o n d e cr e a s ed f

etal bod y w e i gh t s . 870 . 3 80 0 2003 - 2 - G E N ERA T I ON

RE P R OD U C T I O N - RA T ( XD E - 750) m g /kg/ d a y = 0 , 50 , 2 5 0 , 1 00 0 A c c e p tab le/ G u i d el i n e 462 3 56 3 5 P ar e ntal: N O A EL ( m g / k g / d a y) : 100 0 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed R e produ cti v e: N O A EL ( m g /k g / d a y) : 1000 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed O f f s pr i n g : N O A EL ( m g / k g / d a y) : 1000 L O A E L ( mg/ k g/ d a y

) : n o t d ete rm i n ed 870 . 4 10 0 2003 - 1 Y E AR FE E D I N G DOGS ( XD E - 750) % =0 , 0 . 0 3 , 0 . 30 , 3 .0

§ pp m = 0 , 300 , 30 0 0 , 30 0 0 0 m g /kg/ d a y = M: 0 , 10 , 99 , 9 6 7 F: 0 , 9 , 9 3 , 1 03 8 A c c e p tab le/ G u i d el i n e 462 3 56 2 7 N O AEL ( m g /k g / d a y) : M =99 , F= 9 3 L O A E L ( mg / k g / d a y) : M =967 , F= 1 03 8 b ased o n th ic k e n i n g o f s t o m a c h mu c o s a ( f e mal e s ) , an d s t o m a c h h i s t op ath o l og y i n all an i m als ( s l i ght d if

f us e hy p e rp las i a a n d hy p e rtr ophy o f th e mu c o s al e p ith e l i u m , s li g h t l y m p h o id h y p e rp las i a o f th e g a s tric mu c o s a an d v e r y s li g ht

/ s l i g ht c h ro n ic mu c o s al i n f

l a m m ati o n ) . 870 . 4 20 0 2003 - 1 8 MO N T H

C A R C I NOG E N I C I T Y M I C E ( XD E - 750) m g /kg/ d a y = 0 , 50 , 2 5 0 , 1 00 0 A c c e p tab le/ G u i d el i n e 462 3 56 2 8 N O AEL ( m g /k g / d a y) : M =100 0 L O A E L ( mg / k g / d a y) : n o t d ete r mi n e d .Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 22 o f 27 870 . 4 30 0 2004 - 2 Y E A R

T OX I C I T Y/ C A R C I NOG E N I C I T Y RA T ( XD E - 750) m g /kg/ d a y = 0 , 50 , 5 0 0 , 1 00 0 A c c e p tab le/ G u i d el i n e 462 3 56 1 5 N O AEL ( mg / k g / d a y) : 5 0 L O A E L ( mg/ k g/ d a y

) : 50 0 b ased o n c e c a l e n lar g e m e nt, s l i g h t mu c o s al h yp e rp las i a ( m ales) an d s l i g h t l y d e cr e a s ed b o d y w e i g h t s . 870 . 5 1 0 0 2004 - B A C T E R I AL

REV ER SE MU T A T I ON AS S A Y ( XD E - 750) 0 , 1 0 0 , 3 33 , 10 0 0 , 3 30 0 o r 5 0 0 0 μ g /p late ( Sa l m o n e ll a - E s c h e r i c h ia c o li) in th e pr ese n ce a n d ab s e n ce o f m etab o lic a c ti v ati o n ( + S 9) . A c c e p tab le/ G u i d el i n e 462 3 56 3 6 Ne g at i v e

870 . 5 10 0 2004 - B A C T E R I AL

REV ER SE MU T A T I ON AS S A Y ( G F - 871) XDE T I P A *

33 , 1 00 , 333 , 1 0 00 , 33 3 0 , 500 0 μ g /p late ( Sa l m o n e ll a - E s c h e r i c h ia c o li) in th e pr ese n ce a n d ab s e n ce o f m etab o lic a c ti v ati o n ( + S 9) . A c c e p tab le/ G u i d el i n e 462 3 56 3 7 Ne g at i v e

870 . 5 30 0 2004 - I N V I T R O

M AM M A L I AN C E LL G ENE MU T AT I ON T E S T 0 , 31 , 63 , 1 2 5 , 2 50 , 500 , 1000 , 1 5 00 , 20 7 0 μ g / m L (1 s t a ss a y ) ; 250 , 500 , 1000 , 2 0 00 , 40 0 0 μ g / m L (2 n d as s a y

) , bo th in th e pr ese n ce an d ab s e n ce o f m etab o lic a c ti v a ti o n ( + S 9) . A c c e p tab le/ G u i d el i n e 462 3 58 0 1 Ne g at i v e

870 . 5 30 0 2004 - I N V I T R O

M AM M A L I AN C E LL G ENE MU T AT I ON T E S T ( GF - 871) XDE T I P A *

250 , 500 , 1 0 00 , 20 0 0 , 400 0 μ g/mL i n th e pr ese n ce an d ab s e n ce o f m etab o lic a c ti v a ti o n ( + S 9) . A c c e p tab le/ G u i d el i n e 462 3 58 0 4 Ne g at i v eAminopy ralid Registr a

t i on Review Scoping Document



### P a g e 23 o f 27 870 . 5 37 5 2002 - I N V I T R O

M AM M A L I AN C E LL C H R OMOSOME AB E RRAT I ON T E S T ( XD E - 750) 0 , 32 , 65 , 1 2 9 , 2 59 , 518 ,

1035 , 2 0 7 0 μ g/ m

L w i th an d with o ut m e tabo lic a c ti v ati o n (1 s t a ss a y ) ; 0 , 125 , 250 , 5 0 0 , 7 50 , 10 0 0 , 1400 , 1 7 00 , 20 7 0 μ g / mL wi t h o ut m etab o lic a c ti v ati o n an d 0 , 62 . 5 , 125 , 500 , 1 0 0 0 o r 2 07 0 μ g/ mL wi th m etab o lic a c ti v ati o n (2 n d as s a y

) ; 400 , 600 , 8 0 0 , 1 000 , 1200 , 1 4 00 , 16 0 0 , 1 700 , 1800 , 2 0 7 0 μ g/ m L wi t h o ut m etab o lic a c ti v ati o n (3r d as s a y) . A c c e p tab le/ G u i d el i n e 462 3 58 0 2 XDE i n du c e d c hr o mo s o me ab e rr ati on s , b ut o n l y at c y t o t o x ic c o n c e ntrati o ns ; t h e clast o g e n ic r es po ns e w a s i n du c e d s e co n d ar y to t o x ici t y .

870 . 5 37 5 2004 - I N V I T R O

M AM M A L I AN C E LL C H R OMOSOME AB E RRAT I ON T E S T ( GF - 871) XDE T I P A *

1000 , 2 0 00 , 40 0 0 μ g / m L wi t h a n d w ith o u t m etab o lic a c ti v a ti o n ( + S 9) ; 0 , 5 00 , 10 0 0 , 2 00 0 μ g/ mL wi th o ut m etab o lic a c ti v ati o n . A c c e p tab le/ G u i d el i n e 462 3 58 0 3 Ne g at i v e

870 . 5 39 5 2002 - M A M M A L I AN

E RY T H R O C Y T E M I CR O N U C L E U S T E S T ( XD E - 750) mg/ k g/ d a y = 0 , 500 , 100 0 o r 20 0 0 A c c e p tab le/ G u i d el i n e 462 3 58 0 5 Ne g at i v e

870 . 5 39 5 2004 - M A M M A L I AN

E RY T H R O C Y T E M I CR O N U C L E U S T E S T ( GF - 871) m g /kg/ d a y = 0 , 500 , 1000 , o r 20 0 0 A c c e p tab le/ G u i d el i n e 462 3 58 0 6 Ne g at i v e

870 . 6 20 0 2001 - A C U T E

N E U R O T OX I C I T Y - RA T ( XD E - 750) m g /kg/ d a y = 0 , 5 0 0 , 1 000 , 2 0 0 0 A c c e p tab le/ G u i d el i n e 462 3 56 1 6 N O AEL ( mg / k g / d a y) : 1000 L O A E L ( mg / k g / d a y) : 2000 b ased o n f

e c al s o il i n g i n m ales a n d ur i n e s o il i n g i n f e m ales. 870 . 6 20 0 2003 - C H R ON I C

N E U R O T OX I C I T Y - RA T ( XD E - 750) mg/ k g/ d a y = 0 , 5 , 50 , 500 , 1 0 0 0 A c c e p tab le/ G u i d el i n e 462 3 56 1 7 N O AEL ( mg / k g / d a y) : 1000 L O A E L ( mg / k g / d a y) : n o t d ete rm i n edAminopy ralid Registr a

t i on Review Scoping Document



### P a g e 24 o f 27 870 . 7 48 5 2004 - M E T A B O L I SM

AN D P H A R M A C O K I N E T I C S RAT ( XD E - 750) m g /kg/ d a y = L o w do s e: 5 0 Hi g h do s e: 100 0 R e p e ated l o w do s e: 5 0 ( un lab elle d ) f o r 1 4 d ay s , 5 0 ( lab elle d ) o n d a y 1 5 A c c e p tab le/ G u i d el i n e 462 3 58 0 7 R e co v e r y a f ter 16 8 h r s : 96 % in l o w do s e ( ur i n e 50 %, f e c e s - 43 %, ti s s u e s 0 . 1 %, c a g e w a s h 3 %), 95 % in h i g h do s e ( ur i n e - 41 %, f

e c e s - 43 %, ti s s u e s - 1 %, c a g e w a s h 10 %), an d 95 % in th e r e p e ated l o w do s e ( ur i n e 59 %, f e c e s - 33 %, t i s s u e s 0 . 1 %, c a g e w a s h - 3 %). XDE - 75 0 r e pr ese n ted > 96 % o f a d mi n i s te r ed do s e ( AD) in ur i n e a n d 100 % AD in f

e c es. T h r ee unkn o w n c o m p o n e nt s ( > 4 %) f o un d i n ur i n e w e r e also f oun d in do s e f o r mu lati on s . 870 . 7 80 0 201 0 -

I M M UNO T OX I C I T Y RAT ( XD E - 750) m g /kg/ d a y = 0 o r 103 8 A c c e p tab le/ G u i d el i n e 483 6 44 0 1 S ys t e mic N O A E L ( mg / k g / d a y) : N o t d ete r mi n ed L O A E L ( mg / k g / d a y) : 103 8 b ased o n i n c r e a s ed c e c um s ize I mm un o t o x ici t y N O A E L ( mg / k g / d a y) : 1038 L O A E L ( mg / k g / d a y) : N o t d ete r mi n ed

N o n Gu i d el i n e XD E - 750 ,

T r ii s o p rop an o la m m o n i u m

s alt, Di ss o ciati o n an d M e tabo li s m i n M a le Fi s c h er 34 4 R ats m g / k g / d a y= 5 0 o r 9 6 462 3 58 3 3 14 C - XD E - 75 0 an d 14C XD E - 75 0 - T I P A , wh en a dm i n i s te r ed or al l y to r ats, we r e b i o e qu i v a le n t in te r m s o f ab s orp ti o n , d i s tri b uti o n , m etab o li s m , an d e x c r eti o n o f t h e a mi n o - d i c h l or o - p ic o li n ate porti o n o f th e m o lec u le ( s ) .Aminopy ralid Registr a

t i on Review Scoping Document



### P a g e 25 o f 27 **A t**  **ta c**  **h me**  **n t 5.**  **Su m**  **m a**  **r y of**  **Oc c**  **up a**  **t io**  **n al Us**  **e s**  **Based on R**  **e gist**  **ere d**  **La b**  **e ls**  **f or**  **A m**  **i n**  **o p**  **y r**  **al i**  **d S**  **u mm**  **a ry**  **o f**  **O ccu**  **p a**  **ti o**  **n a** **l U**  **s e**  **s B**  **a s**  **e d on**  **R eg**  **i s**  **t e**  **r e**  **d L**  **abe l**  **s f**  **or A**  **mi n**  **opyr a**  **l i**  **d. E**  **PA Re**  **g .**  **N o**  **. Re**  **g i**  **s t**  **r at**  **i o**  **n N**  **a m**  **e F**  **o r**  **m ula**  **t i**  **o n**  **% a**  **i o**  **r a**  **e Use**  **site** 627 1 8 - 518 Am i n o p y r alid T e c hn ical L i qu id

95 . 3 % W h e at ( i n c l u d i n g durum ) , p e rm a n e nt gr ass p as tur e s , r a n g el a n d , f al l o w c rop lan d , c o ns e rv ati o n r ese rv e ar e a s, i n du s trial s it e s , r i g ht s - of

- w a y , n on irr i g ati o n d it c h b ank s , wil d l i f e /n at ur al ar e a s, gr a z ed ar e a s 627 1 9 - 519 Milest o n e E m u l s i f iab le C o n c e ntrate 21 . 1 % W h e at ( i n c l u d i n g durum ) , c orn , r ang el a n d , p e r ma n e nt gr a s s p a s t ur es ( i n cl u d i n g gr a s s es gr o w

n f o r h a y ) , c o ns e rv ati o n r ese rv e ar e a s, n o n c rop lan d i n dus trial s ite s , r i ghts - o fw a y , n o n - irr i g ati o n d it c h b a nk s , wil d l i f e /n at ur al ar e a s, gr a z ed ar e a s 627 1 9 - 525 C lean w av e E m u l s i f iab le C o n c e ntrate 1 . 92 % W h e at ( i n c l u d i n g durum) 627 1 9 - 537 Milest o n e VM E m u l s i f iab le C o n c e ntrate 21 . 1 % N o n - c rop lan d ar e a s i n dus trial s ite s , r i ghts - of - w a y , n on - irr i g ati o n d itch b anks , wi l d li f

e /n atur al ar e as , g r a z ed ar e a s 627 1 9 - 572 Milest o n e VM P l u s ( alte rn ate

n a me C ap s t o n e ) E m u l s i f iab le C o n c e ntrate 1 . 1 5 % R an g el a n d , p e rma n e nt gr a s s p ast ur es, c o ns e rv ati o n r ese rv e ar e a s , f or est s , n on - c rop lan d ar e a s i n du s trial s ite s , r i ght s - o f

- w a y , f e n c er o w s , n o n irr i g a ti o n, d itch b a nk s , wil d l i f e /n atur al ar e a s , gr a z ed ar e a s F L 07000 3 C lean w av e E m u l s i f iab le C o n c e ntrate 1 . 92 % G r as s , f or a g e, h a y , p as t ur esAminopy ralid Registr a

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### P a g e 26 o f 27 **A t**  **ta c**  **h me**  **n t 6. I**  **n t**  **e r**  **n a**  **tional R**  **e si**  **du e**  **Li m**  **it Sta t**  **u s** 



### A m in o p y ra li d ( 0 0 510 0 ; 1 1 - 8 - 2 0 1 3 ) **S u**  **m m**  **a ry**  **o f**  **US a**  **nd I**  **nt e**  **rn a**  **t i**  **o n**  **a l**  **T o**  **ler a**  **nces a**  **nd M**  **a x**  **i m**  **u m**  **R e**  **s id**  **u e**  **L i**  **m i**  **t s**  **.** Resid u e Defi n itio n : US C an a d a M e x ic o 1 C od e x 2 4 0 C FR 180 . 6 1 0 ( a) (1 ) P lant s : F r ee an d c o n

j u g ated Am i n o p y r alid (4 - a m i n o - 3 , 6 - d ic h l or o - 2 - p y r i d i n e c arbox ylic a c i d ) P lant s : 4 - a m i n o - 3 , 6 - d ic h l or o - 2 - p y r i d i n e c arbox ylic a c id ( f r ee an d c o n j ug ate d ) a m i n o p y r alid an d its c o n j ug ates th at c a n b e hydro l ys e d , e xpr es s ed as a m i n o p y r ali d .

C o mm odity T o lera n ce ( pp m) /Maxim u m R esid

u e Limit ( m g /k g ) US C an a d a M e x ic o 1 C od e x 2 C orn , f iel d , f or a g e 0 . 3 0 C orn , f iel d , gr a i n 0 . 2 0 C orn , f iel d , s t o v er 0 . 2 0 3 f odd er ( dry

) o f c er e a l gr ai n s ) G r ai n , as p irated f

r a c ti on s 0 .2 G r as s , f or a g e 25 G r as s , h a y 50 7 0 h a y o r f odd er ( dry

) o f gr as s e s W h e at, br an 0 .1 0 .1 0 .3 w h e at br an , un

pro c e ss ed W h e at, f or a g e 2 .0 W h e at, gr ain 0 . 0 4 0 . 0 4 0 .1 W h e at, h a y 4 .0 3 f odd er ( dry

) o f c er e a l gr ai n s ) W h e at, s tr a w 0 . 2 5 0 .3 s tr a w o f c er e a l gr a i n s US [4 0 C FR §180 . 6 1 0( a ) (2) ] C an a d a M e x ic o 1 C od e x 2 L i v esto c k : Ami n o p y

r a l id L i v esto c k : 4 - a m i n o 3 , 6 - d ic h l or o - 2 - p y r i d i n e c arbo x ylic a c id S a m e as abo v e

C o mm odity T o lera n ce ( pp m) /Maxim u m R esid

u e Limit ( mg /k g ) US C an a d a M e x ic o 1 C od e x 2 C attle, f a t 0 . 0 2 0 . 0 2 C attle, ki dn e y 0 .3 0 .3 1 C attle, m e at 0 . 0 2 0 . 0 2 0 .1 m e at ( f r o m m a mm als o th er th a n mar i n e m a mm a l s ) C attle, m e at b y

produ cts, e x c ep t ki dn e y 0 . 0 2 0 . 0 2 0 . 0 5 e d i b le o ff al m a mm a lian ( e x c ep t ki d n e y) G o at, f at 0 . 0 2 0 . 0 2 G o at, ki dn e y 0 .3 0 .3 1 G o at, m e a t 0 . 0 2 0 . 0 2 0 .1 m e at ( f r o m m a mm als o th er th a n mar i n e m a mm a l s )Aminopy ralid Registr a

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### P a g e 27 o f 27 **S u**  **m m**  **a ry**  **o f**  **US a**  **nd I**  **nt e**  **rn a**  **t i**  **o n**  **a l**  **T o**  **ler a**  **nces a**  **nd M**  **a x**  **i m**  **u m**  **R e**  **s id**  **u e**  **L i**  **m i**  **t s**  **.** Resid u e Defi n itio n : US C an a d a M e x ic o 1 C od e x 2 G o at, m e a t b y produ cts, e x c ep t ki dn e y 0 . 0 2 0 . 0 2 0 . 0 5 e d i b le o ff al m a mm a lian ( e x c ep t ki d n e y) H or s e, f at 0 . 0 2 0 . 0 2 H or s e, ki dn e y 0 .3 0 .3 H or s e, m e at 0 . 0 2 0 . 0 2 0 .1 m e at ( f r o m m a mm als o th er th a n mar i n e m a mm a l s ) H or s e, m e at b y produ cts, e x c ep t ki dn e y 0 . 0 2 0 . 0 2 0 . 05 e d ib le o ff al ma mm ali a n ( e x c ep t ki dn e y) Milk 0 . 0 3 0 . 0 3 S h e ep , f at 0 . 0 2 0 . 0 2 S h e ep , ki d n e y 0 .3 0 .3 1 S h e ep , me at 0 . 0 2 0 . 0 2 0 .1 m e at ( f r o m m a mm als o th er th a n mar i n e m a mm a l s ) S h e ep , me at b y

produ cts, e x c ep t ki dn e y 0 . 0 2 0 . 0 2 0 . 0 5 e d i b le o ff al m a mm a lian ( e x c ep t ki d n e y) MRLs Wi t

h N o US Equ iv a le n t B ar ley 0 .1 E g g s 0 . 0 1 ( * ) Ki dn e y o f p i g s 1 Oats 0 .1 P o u ltry m e at 0 . 0 1 ( * ) P o u ltry , e d i b le of

f al o f 0 . 0 1 ( * ) Str a w o f c er e a l gr ai n s 0 .3 T r iticale 0 .1 C o m p lete d : : M. Ne g u s s ie; 08 /29 / 1 3 1 M e x ico a dop ts US t o le r an c e s an d/ o r C od ex M R L s f o r its e xport p urpo s es. 2 * = ab s e nt at th e l i mit o f qu a ntitati o n ; P o = po s th arv est tr e a t m e nt, s u ch as tr e at m e nt o f s t or ed gr ai ns . P o P = pro c e ss ed po s th a rv est tr e ated c o mm od i t y , su c h as pro c e ss i n g o f tre ated s t or ed w h e at. ( f at) = to b e m

e a s ur ed o n th e f at por ti o n o f th e s a m

p le. M RL s i n d icat e d as propo s ed h av e n o t b e e n f i n aliz e d b y th e C C P R an d th e C A C .