IR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 1 o f 7 --- - --- - -- - -- - --- - -- - -- - --- - - - --- - --- - -- - -- - --- - -- - -- - --- - - - --- - --- - --- EN V I R ONMEN TA L PR OTE C T I ON AG E N C Y Noti c e of F ili n g of a Pe sti c ide P e tition f or the Est a

blishm e nt of Tol er an ce s f or R e sidu e s of C hlo rantran i lip r ole in or on F ood C o mmoditi e s AGEN C Y: Envi r onm e nt a l P r ot ec tion Ag e n c y ( E P A )
. A C T I ON: Noti ce . Interregional Research Project Number 4 (I R
- 4) Pesticide Petition (PP#) 3E8170

--- - --- - -- - -- - --- - -- - -- - --- - - - --- - --- - -- - -- - --- - -- - -- - --- - - - --- - --- - --- S UMMA RY: This not i c e announ ce s the initi a l f iling of a p e sti c ide p e tition p r oposing the e st a

blishm e nt of tol eran ce s f or r e sidu e s of c hlo rantranilip r o le in or on f ood c ommoditi e s und e r the Fe d e ra l F ood, D ru g , and C osm e tic A c t ( F F D C A ) , a s am e nd e d b y the F ood Qu a li t y P r ot ec tion A c t of 1996 (F Q P A )
. FOR FURTHER INFORMATION CONTACT: L aura Nollen, (703) 305
- 7390, nollen.laura@epa.gov . Registration Division, (7505), Office of Pesticide Programs, Environmental Protection Agency , 1200 Penns yl vania Avenue, N.W., Washington, DC 20460. S U PP LEMEN TA RY I

N F O RMA T I O N: E P A h a s re c e iv e d a p e sti c ide p e t i tion #3E8170, p r oposing the e st a blishm e nt and/or am e n d m e nt of r e g ul ations f

or r e sidu e s of c e rt a in p e sti c ide c h e mi ca ls in or on onion, g reen, s ubgroup 3
- 07B; f ruit, stone, group 12
- 12, except cherry , chickasaw plum, and damson plum; papay a; passionfruit; nut, tree, group 14
- 12; and spice, subgroup 19B und e r s ec tion 408 ( d) of th e F e d e r a l F o od, D r u g , and C osm e tic A c t ( FF D C A ) , 21 U. S
. C
. 346a ( d )
. E P A h a s d e t er min e d th at this p e tition c ont a i n s d ata or in f o r m ation re g ar ding the e l e m e nts s e t f o rth in s ec tion 408 ( d ) ( 2 ) ; ho w e v er , E P A h a s not f ul l y e v a lu at e d the su ff

i c i e n c y of the submitt e d d ata at th is ti me or wh e th e r the d ata suppo rts gr anting of th e p e tition. Addition a l d ata m a y be n ee d e d b ef o r e E P A r ul e s on the p e tition. L ist of S ubj ec ts Envi r onm e nt a l P r ot ec ti o n, Agr i c ultura l C ommoditi e s, F ood Additiv e s, F e e d Additiv e s, P e sti c id e s and P e sts, R e po rting and Re c o r dk ee pi n g R e qui r e m e n ts. S umm ar y of P e tition A summ ar y of the p e sti c i de p e tition is g iv e n b e low. The p e tition e r p re p ar e d the summ ar yIR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 2 o f 7 of the p e tition.

PP# 3E8170 E P A h a s r ece iv e d a p e sti c ide p e tition , PP# 3E8170, f r om the I

nt erre g ion a l R e s earc h P r

oj ec t Nu mb e r 4 ( I

R
- 4 ) , I R
- 4 P r o

j ec t Hea d q

u ar t er s , 50 0 C o l l e g e Ro a d Ea s t , S uit e 2 0 1 W , P rin c eton , Ne w J er s e y , 08540 , p r oposin g , pur su ant to s ec tion 408 ( d) of the Fe d era l F ood, D r u g , and C osm e tic A c t ( F F D C A ) , 21 U. S
. C
. 346 a( d ) , to am e nd 40 C F R p art 180 to e st a blish tol eran ce s f

or re sidu e s of c hlo r antranilip r ol e , 3
- b r omo -N
- [ 4
- c hlo r o - 2
- m e th y

l
- 6
- [ ( m e th y

l amino )
- c ar

bo n y l ] ph e n y l ]
- 1
- ( 3
- c hlo r o - 2
- p y r idi n y l )
- 1 H
- p y r a z ol e - 5
- car

bo x a mide in o r on onion, gree n, sub gr oup 3
- 07B at 3 .0 ppm; fr uit, ston e , gr oup 12
- 12, e x ce pt c h er r y, c hi c k a s aw plum, and d amson plum at 4.0 ppm; p a p aya at 4.0 ppm; p a ssion fr uit at 4.0 ppm; nut, tree , gr oup 14
- 12 at 0.04 ppm; and spi ce sub gr oup 1 9 B at 40 ppm. C on c urre nt l y, IR
- 4 is re qu e sting removal of the f ollowing e x isting tim e - limit e d tol eran ce s: l ee k ; onion, gr e e n ; onion, W e l s h ; and sh a llots, fre sh l e av e s at 0.2 ppm .IR
- 4 is finally requesting remove of the f ollowing p er

m an e nt tol eran ce s: fr

uit, ston e , gr oup 12, e x ce pt c h er r y , c hi c k a s aw plum, and d amson plum at 4.0 ppm; m a y

h aw at 0.6 ppm; p a

p a ya and p a ssion fr

uit at 2.0 ppm; nut, tr ee , gr oup 14 at 0.04 ppm; pist ac hio a t 0.04 ppm and spi ce , su

b gr oup 19B at 14 ppm. E P A h a s d e t er min e d th at the p e tition c ont a ins d ata or in f o r m ation r e g ar ding the e l e m e nts s e t f o rth in s ec tion 408 ( d )( 2) of the FF D C A; how e v er , E P A h a s not f ul l y e v a lu at e d the su ff

i c i e n c y of the submitt e d d ata at this time or wh e th e r th e d ata suppo rt s gr anting of the p e tition. Addition a l d ata m a y be n ee d e d b ef o r e E P A r ul e s on the p e tition. A. R esidue C

h e mistry 1. Plant m e tabolism
. T h e m e t a b o l is m o f c hlo ra

nt ra ni l ip r o l e i s a d e qu a

t e ly und er s t oo d t o su

ppo r t th e p r opos e d ex emp tio n fr o m th e re q ui re m e nt o f t o l era

n ce s . S t udi e s i n a

ppl e , l ettu ce , ri ce , t om a

t o , a n d c o t to n wh e n t

re a t e d a t p r o p os e d l a

b e l ra t e s s h o we d n o s i g

ni f i c a nt m et a b o l i t e s . T h e o n ly si g

ni f i ca n t re s idu e i s th e p are nt c ompo u nd. 2. L i vesto c k Me tabolism
. The m e t a bolism of c hlo rantranilip r ole in r umin ants and poultr y is a d e qu at e l y un d er stood to suppo rt the e x e mption fr om the re qui re m e nt of tol eran ce s. L a c t ating g o at and l a y i n g h e n m e t a

bolism studi e s w er e c o n du c t e d. The g o at and h e n ra

pid l y e x c r e t e d > 9 3 % and > 98% of the dos e d ra di o l a b e l ed re sidu e s, re s p ec tiv e l y . The m e t a bolic p athw a y in poultr y and r umin ant ( g o at) anim a ls w a s c o n sist e nt. Th er e is no rea so n a

ble e x p ec t ation of trans fe r of f inite r e sidu e s of c hlo rantranilip r ole and its m e t a bolit e s to fat, m eat , milk, and e g g s. 3. Anal y ti c al m e thod
. S in c e c hlo rantranilip r ole and its m e t a bolic d e gra d at e s ar e not of to x i c olo g i ca l c on c er n, an a l y ti c a l m e thods ar e not a

ppli ca bl e .IR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 3 o f 7 4. M a gnitude of re si du e s. G r ee nhouse re sid u e tr i a ls w er e c ond

u c t e d with c hlo rantranilip r ole on the raw a gr i c ultura l c ommodi t y c u c umb e r s. Thre e MOR tr i a ls w er e c ondu c t e d. The lo cations of the f i e ld tr i a ls w er e s e l ec t e d to r e p re s e nt the r e g ions with most gr ee nhouse c u c umb e r p r o d u c tion. A f

oli ar b r o a d c a s t sp r a y of c hlo rantranilip r ole w a s a ppli e d at the rate of 0.1 lb a i/A/ a ppli cat i on. The c u c umb e r pl ants r ece i v e d two a ppli c ations t ar g e t e d at 1 d a y b ef o r e h ar v e s t ( 1
- d a y P H I) o f m atur e cr op. C on c urre nt r e c ov er i e s f r om c ontr ol s ampl e s f

o rti f i e d at 0.010 to 5.0 m g

/k g of c h l o rantranilip r ole r an g e d f r om 96 to 100 % . The m ax imu m re sidue l e v e l in c u c umb er s w a s 0.0738 ppm whi c h is b e low the c u rre nt l y e st a blish e d tol eran c e of 0 .5 ppm f or c u c u r bits. G ree nhou s e r e sidue tr i a ls w er e c ondu c t e d with c hlo rantr anilip r ole on t he r aw a gr i c ultura l c ommodi t y tom ato e s. F our M O R tri a ls w er e c ondu c t e d. The lo cations of the f

i e ld tr i a ls w er e s e l ec t e d to r e p re s e nt the r e g ions with most gr ee nhouse tom ato p r od

u c tion. A f

oli ar b r o a d ca st sp r a y of c hlo r antranilip r ole w a s a ppli e d at th e r ate o f 0 .1 lb a i/A/ a ppli cation. T he tom ato pl ants re c e i v e d two a ppli cations t ar g e t e d at 1 d a y b ef o r e h ar v e st ( 1
- d a y P H I ) of m atur e c r op. C on c urre nt r ec ov e r i e s f

r om c ontr ol s ampl e s f

o rt i f i e d at 0.010 to 5.0 m g

/k g of c hlo rantranilip r ole ran g e d fr om 98 to 10 2 %
. The m ax imum re sidue l e v e l in tom ato e s w a s 0.102 ppm whi c h is b e low the c ur r e nt l y e st a

blish e d tol eran c e of 1.4 ppm f or fr uiting v e g e t a

b l e s. F i e ld re sidue tr i a ls w er e c ondu c t e d with c hlo rantranilip r ole on the raw a gr i c ultura l c ommoditi e s c h e rr y , p a p a ya and l yc h ee . Two M OR tr i a ls w er e c ondu c t e d f

or e ac h c o m modi t y . A f oli ar b r o a d c a st sp r a y of c hlo r antran ilip r ole w a s a ppli e d at the ra

te of 0.1 lb a i/A/ a

ppli cati o n. The t e st pl ants rece iv e d two a ppli cations t ar g e t e d at 1, 3, 6
- 7, 9
- 10 and 13
- 15 d a y s b e f o r e h ar v e st of m atur e cr op. C on c ur

r e nt r ec ov e r i e s fr om c ontr ol s ampl e s f o rti f i e d at 0.010 to 5.0 m g

/k g of c hlo rantranilip r ole r an g e d f r om 97 to 123 %
. I

n c h e rr y s ampl e s, the tot al re sidu e s of c hlo r antranil i p r ole r an g e d fr om 0.151 to 0.192 ppm in s ampl e s t ak e n at 1 d ay P H I , 0.135 to 0.162 ppm in s a mpl e s t ak en at 3 d ay s P H I , 0.105 to 0.120 ppm in s ampl e s t ak e n at 6 d a y s P H I , 0.132 to 0
. 151 ppm in s ampl e s t ak e n at 10 d a y s P H I and 0.0994 to 0.129 ppm in s ampl e s t ak e n at 15 d a y s P H I
. I n l y c h e e s ampl e s, the tot a l re sid

u e s of c hlo rantranilip r ole ran g e d fr om 0.402 to 0.500 ppm in s ampl e s t ak e n at 1 d ay P H I , 0.306 to 0.442 ppm in s ampl e s t ak e n a t 3 d ay s P H I , 0.363 to 0.386 ppm in s ampl e s t ak e n at 6 d a ys P H I , 0.239 to 0.3 1 3 ppm in s ampl e s t ak e n at 9 d ay

s P H I and 0.308 to 0.337 ppm in s ampl e s t ak e n at 13 d a y s P H I
. In p a

p a ya s ampl e s, the tot a l re sidu e s of c hlo rantranilip r ole ran g e d fr om 0.284 to 0.292 ppm in s ampl e s t ak e n at 1 d a y P H I , 0.204 to 0.224 ppm in s ampl e s t ak e n at 3 d a y s P H I , 0.1 9 6 to 0.211 ppm in s amp l e s t ak e n at 7 d a ys P H I , 0 .164 to 0.196 ppm in s ampl e s t ak e n at 10 d a ys P H I and 0.137 to 0.142 ppm in s ampl e s t ak e n at 14 d a ys P H I
. F i e ld re sidue tr i a ls w er e c ondu c t e d with c hlo rantranilip r ole on the raw a gr i c ultura l c ommoditi e s onions and dill. F ive MOR tr i a ls w er e c ondu c t e d with onions and two MOR tr i a ls w er e c ond u c t e d with dill. The lo cations of th e f i e ldIR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 4 o f 7 tr i a ls w e r e s e l e c t e d to r e p re s e nt the r e g ions with most onion and spi c e p r o du c tion. A f oli ar b r o a d c a st sp r a y of c hlo rantranilip r ole w a s a ppli e d at the rate of 0.1 lb a i/A/ a ppli cation. The onion and dill cr ops rece iv e d two a ppli cations t ar g e t e d at 1 d a y b ef o r e h ar v e st ( 1
- d a y P H I ) of m atur e cr o p . C on c urre nt r e c ov er i e s fr om c ontr ol s ampl e s f

o rti f i e d at 0.010 to 5.0 m g

/kg of c hlo rantranilip r ole r an g e d fr om 81 to 117 %
. The tot a l r e sidu e s of c hl o rantranil i p r ole ran g e d f r om 0.371 to 1.50 ppm in fre sh gr e e n on i on s ampl e s t ak e n at 1 d a y P H I
. The tot a l r e sidu e s of c hlo rantranilip r ole ran g e d fr om 0.900 to 11.1 p p m in dr i e d gree n onion s ampl e s t ak e n at 1 d ay P H I
. The tot a l re sidu e s of c hlo rant ranilip r ole ra

n g e d fr om 15.4 to 24.3 ppm in dill s ee d s a

mpl e s t ak e n at 1 d a y P H I
. Num er ous re sidue studi e s h ave b ee n c ond u c t e d on m an y cr ops in the Unit e d S t at e s and g lob a l l y b y th e r e g istrant and b y oth e r o r g ani z ations su c h a s the I R
- 4 P r oj ec t. The r e l e v ant U
. S
. and f o re i gn r e sidue s tu d y r e po rts r e qui re d to s uppo rt use of c hlo rantr anilip r ole and e x isting tol eran c e s in the Unit e d S t at e s h a ve b ee n submitt e d to E P A and re vi e w e d a s p art of p r ior r e g istr ation ac tions f or this ac tive in gre d i e nt. B. T ox i c ologi c al Profile

1. A c ute to x i c i t y . B a s e d on E P A cr it e r i a , c hlo r antranilip r ole is c l a ssi f i e d a s f ollows f or To x i c i t y C at e g o r i e s: **G u**  **i d**  **e l**  **i ne**  **Ti t**  **le Re**  **s u**  **l ts**  **C a**  **te go**  **r y**  870.1 1 00 870.1 2 00 870.1 3 00 870.2 4 00 870.2 5 00 870.2 6 00 Ac ut e Ora l To x i c i ty

Ac ut e Der

m a l T o xi c ity A c ute Inh a l ation To x i c i t

y P rim ar y E y e Irrit a tion P r im ar y D er

m a l I rr it ati o n S kin S ens i t i z a

tio n LD 50 : > 5,00 0 m g /k g ( R a t) LD 50 : > 5,00 0 m g

/k g ( R a t) L C 50: > 5.1 m g

/ L ( R at) Mild i rr it a

tion ( R a bbit) No i rr it ation ( R a

bbit) Not a s e nsiti z e r ( Mouse L L N A) C a

t e g o r y I V C a t e g o r y I V C a t e g o r y I V C a t e g o r y I V C a t e g o r y I V

--------------- F o r mul at e d p r odu c ts ar e a s e qu a l l y no n - to x ic f ollowing a c ute e x posur e s a s is t ec hni ca l c hlo r antranilip r ol e . The ac ut e inh a l ation to x i c i t y f or the susp e ns i on c on ce ntr ate f o r mul ation c ould not be d e t er min e d a bove the m ax imum p rac ti ca l l y att a in a b l e atmosph er ic a er osol c on c e ntration of 2 m g / L
. Th er e w a s no e vid e n c e of n e ur oto x i c i t y in rats f ollowing a si n g le limit dose of 2,0 00 m g /k g 2
. Ge notox i c t

y . C hlo r a ntra nil ip r ol e h a s sho w

n n o g e not o xi c ac ti v ity i n th e f o l lo w ing li s t e d i n v i tro a

n d i n vi v o t e sts :IR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 5 o f 7 − B ac t eri a l re v er s e m

ut a tio n

− I n v i t ro m a mm a li a n g e n e mut a

tio n ( C H O /HG P RT )

− I n v i t ro c hr o mo s om a l a

b erra tio n ( hum a n l y mpho c y t e s )

− I n v i v o mous e mi cro nu c l eus 3
. Re p rodu c ti v e an d d

eve lop me n t

a l tox i c it y . I n d e v e lo p m e nt a

l t o x i c i ty s t

udi e s i n ra t s a n d ra bbi t s , c hlo ra

nt ra ni l ip r o l e e xhi b it e d n o effec t s o n a ny p ara m e t e r i n p re gn a

nt fe m a l e s o r th e i r o ff

sp rin g a t l e v e l s u p t o a n d in c ludin g th e m a

x i m u m t e st e d dos e o f 1 , 0 0 0 m g /k g b w /d a y . N o rep r odu ctiv e t o xi c i ty wa s obs er v e d in a t w o - g e n era

tio n re p r odu cti o n s tudy w it h c hlo ra nt ra ni l ip r o l e i n ra

t s . N o a dv er s e effec t s wer e obs er v e d o n re p r o du c t i on , fer t i l i t y, sp er m p ara m e t er s , e st

r o u s c y c l e , litt e r s i z e , pu

p s u r viv a l a n d d e v e lo p m e nt a

l l a ndm ar k s u p t o th e m a xi m u m t e s t e d do s e o f 2 0 ,00 0 p p m i n th e di e t
. T h er e wer e n o a d v er s e h i st o lo g i c a

l f ind in g s indi c a

tiv e o f rep r

odu c tiv e t o xi c i t y . T h er e wa s a sli ght re du c tio n i n t h e F 1 pu p (but no t F 2 pup ) w e i g

ht du rin g l ac t a tio n a t th e h i g h e s t dos e l e v e l ( m ea

n m a t er n a l i n t a k e du ring l ac t a t i o n e qu a l t o 3 ,11 8 m g

/k g b w /d a y ) ; thi s wa s a

tt ri b ut e d , i n p ar

t , t o w e i g ht lo s s i n one d e h y d ra t e d d a m du rin g l ac t a tio n w hi c h h a d a l i t

t e r w it h s o m e o f th e lo we s t pu

p we i g ht s . T h e sli g ht c h a n g e i n pu p we i g ht wa s w itho u

t su b s e qu e nt effec t s s in c e ov era l l bo dy we i g ht , we i g ht g a i n an d d ev e lo p m e nt i n F 1 r a t s fe d 20, 0 0 0 pp m wer e s i m i l a r t o c ont r o l a n i m a l s . 4
. Sub chro n i c t

o x i c i t y . S ub c hr o ni c ( 90
- d ay

) fee d in g st

udi e s wer e c on d

u c t e d w i t h ra t s , mi c e a n d do g s . N o a dv er s e effec t s wer e obs er v e d a t th e hi g h e s t di e t ar

y c on ce nt ra tion s t e st e d o f 20,00 0 pp m in ra t s ( 1 , 18 8 m g

/k g b w /d a y f o r m a l e s a

n d 1 ,52 6 m g

/k g b w /d a y f o r fe m a l e s ) , 7, 0 0 0 pp m in mi c e ( 1 , 13 5 m g

/k g b w /d ay f o r m a l e s a

n d 1 ,53 9 m g

/kg b w /d a y f o r fe m a l e s ) a

n d 4 0 ,00 0 pp m i n do g s ( 1,1 6 3 m g

/k g b w /d a y f o r m a l e s a

n d 1, 2 2 0 m g

/k g b w /d ay f o r fe m a l e s ). Chlo r a nt ra nilop rol e sho w e d n o e v id e n c e o f immu n ot o xi c ity i n 28
- d a y fee din g studi e s i n ra t s o r mi c e an d n o e vid en c e o f n eu r ot o xi c i ty i n a 90
- d a y f

e e din g stu dy i n ra

t s a t di e t a ry c on ce nt ra tion s g rea t e r th a n th e l i m i t d o s e o f 1 ,00 0 m g /k g b w /d a y . A 28
- d a y d er

m a l t o x i c i ty study i n ra

t s wa s c ondu c t e d a

t dos e s o f 1 0 0 , 3 0 0 a

n d 1,0 0 0 m g /k g b w /d a y . T h e N O A EL f

o r m a l e an d fe m a l e ra

t s wa s 30 0 m g

/k g b w /d ay b a s e d on re du c ti o n s i n b o dy we i g

ht g a i n an d f

o o d eff i c i e n c y a t 1, 0 0 0 m g

/k g b w /d a y . N o a dv er s e t ar g e t o r g a

n effec t s wer e obs er

v e d in a ny sub c hr oni c t o xi c i ty study . 5. C hronic tox i c it

y . Chlo r a nt ra nil i p r ol e wa s n o t carc ino g e ni c i n e i t h e r a 2
- y ea r stu dy i n ra

t s o r a n 18
- mont h s tu dy i n mi ce . Th e NOA EL f o r c hr oni c t o xi c ity i n th e 18
- m o nt h m ous e s tu dy wa s 1,20 0 p p m ( 15 8 m g

/k g b w /d ay i n m a l e s ) a

n d wa s b a s e d o n e osi n oph i li c f o c i acc omp a

ni ed by h ep a to ce llul a r h y p er t r o p hy a n d in crea s e d l i v e r w e i g

ht
. I n ra ts , th er e wer e n o a d

v er s e effec t s o n a

ny in
- l i f e p ara m e t e r in e i th e r m a l e s o r fe m a l e s a dm ini s t ere d c hlo ra nt r a ni l ip r o l e u

p t o a n d in c lu din g a m axim u m di et a r y c on ce nt ra tio n o f 20 , 00 0 p p m f

o r 2 y ear s ( 80 5 a

n d 1 ,07 6 m g

/k g b w /d a y , re sp ec tiv e l y

)
. I n a on e - y ea r fee din g study i n do g s , th e NOA EL w a s th e hi g h e s t dos e t e s t e d , 40,0 0 0IR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 6 o f 7 pp m ( 1 ,16 4 a

n d 1 ,23 3 m g

/kg /d a y i n m a l e s a

n d fe m a l e s , re sp e ctiv e l y

)
. 6. Rat m e tabolism
. T h e a bso r p tio n o f [ 14 C ]
- c hlo ra

nt ra ni l ip ro l e i n ra

t s wa s ra pi d w i t h p ea k c on ce nt

ra ti o n s o cc u rrin g a t 5
- 1 2 h ou

r s af t e r s in g l e dos e a d

m in i stra tio n . T issu e d i st

r ib u tio n o f th e a

bso r b e d dos e wa s ex t e n siv e a

n d i n di ca t e d lo w p o t e nti a l f

o r acc u m ul a tio n . E x cr etio n was sub s t a nti a ll y c ompl e t e by 48
- 7 2 h ou r s a f t e r d o sin g ( > 90 %)
. F ol l o w in g 1 4 d a y

s o f o ra l a d

m in i st r a tio n 1 4 C re s idu e s wer e rea d i ly e lim in a t e d fr o m th e pl a sm a a

n d tissu e s an d c on f

i r m e d mi nim a

l p o t e nti a l f o r acc um ul a tion
. T h e p ro f

i l e o f m e t a b o l i t e s in u

ri n e a n d f ece s indi c a

t e d ex t ens i v e m e t a

b o li s m c o n si s t e nt w it

h th a t obs er v e d f o r th e sin g l e dos e s tudy . 7. Me tabolite tox i c olog

y . D u e t o th e e xt

re m e l y lo w toxi c i ty o f th e p are nt c o mpou nd a n d th e ex t e n siv e m e t a

bol i s m obs er

v e d i n m a

mm a li a n s y st e ms , c hlo ra

nt r a ni l ip r o le m e t a b o l i t e s ar e no t ex p ec t e d t o re s ul t in a ny s i g ni f i ca nt t o xi c ity . T oxi c olog y studi e s c ondu c t e d w i t

h m et a b o li t e s su ppo r t t hi s c o n c lu s io n . 8. Endo c rine disruption
. N o a dv er s e effec t s wer e obs er v e d o n a ny e ndo crin e tis s u e i n s ho r t - a n d l on g - t er

m s t udi e s i n r a

ts , mi c e a n d d og s . C. Aggr e gate E x posure 1. Di e tary ex

posure - - i. Food
. B e c a use an e nd

p oint attr ibut a

ble to a si n gle dose w a s not id e nti f

i e d, the d i e t ar y e x posur e a s s e ssm e nt c onsid ere d on l y c hr on i c e x posure . C hr onic di e t ar y e x posur e a s s e ssm e nts w e r e c ondu c t e d usi n g the D i e t ar y E x posur e Ev a lu ation Mod e l ( DE E M
- F C IDTM, V er sion 2. 0 3) whi c h us e s f ood c o n sumption d ata fr om the U. S
. D e p artm e nt of A gr i c ultur e’ s C ontinuing S ur v e ys of F o od I

nt ak e s b y Individu a ls ( CSF I I ) fr om 1994
- 1996 and 1998. T he c hr on i c di e t ar y e x posur e a s s e ssm e nt w a s c ondu c t e d usi n g a c hr onic re f ere n c e dose of 1.58 m g /kg bw/d a y b a s e d on the NOA E L e st a

blish e d in the 18
- month stu d y in mi ce . Du P ont h a s c o n du c t e d c hr onic a ss e ssm e nts whi c h a ssume th at 100% of a ll cr ops
– in c luding those not l a b e l e d
- ar e treat e d with c hlo rantrani l ip r ole and th at a ll cr ops c ont a in re sidu e s at tol er an c e l e v e l or at re sidue l e v e ls e qu a l to tol eran c e l e v e ls f o r s imil ar cr ops. I

n p art i c ul ar a ll l e a f

y v e g e t a bl e s, in c ludi n g l ea v e s of r oot and tub e r v e g e t a bl e s and l ea f

y v e g e t a bl e s in c luding b ra ssi c a v e g e t a

bl e s, ar e a ssum e d to h ave re si d u e s of 15 p arts p e r million. All oth e r hum an f oods ( in c luding pl ant and anim a l c ommoditi e s) ar e a ssum e d to h ave re sidu e s of 2 p arts p e r million. Th e se a ssumptions re sult in c ons er v a tiv e , h ea lth
- p r ot ec tive e stim at e s o f e x posur e whi ch ar e w e ll b e low the A g e n c y ’ s l e v e l o f c o n cer n ( 100% of the c P AD )
. The m ax imum e stim ate is l e ss th an 11% of the c P AD f o r a ll pop u l ation sub gr oups. ii. Drin k ing w ate r . A dr inking w at e r a ss e ssm e nt f or c hlo rantr anilip r ol e , c ondu c t e d b a s e d on PR Z M/EXAMS ( P e sti c ide R oot Z one Mod e l/E x posur e An a l y sis Mod e ling S yst e m ) , w a s us e d to c a l c ul ate the s urfa c e w at e r e stim at e d dr inking w at erIR
- 4 C h l o r a ntr an i l i p r o l e

P a g e 7 o f 7 c on ce ntr ations ( ED WC s) and th e S c r ee ni n g C on ce ntration in G r ound W at e r ( S C I
G R O W ) mod e l w a s us e d to ca l c ul ate the gr o u ndw at e r ED WC
. The E D WC s do n o t e x cee d the A g e n c y ’ s l e v e l of c on c er n. 2. N on - di e tary e

x posur e . R e sid e nti a l e x posu r e ( non - o c c up ation a l, no n - di e t ar y e x posur e to c onsum er s ) w a s c on s er v ativ e l y a ss e ss e d f

or d er m a l p ost - a

ppli cation e x posur e (c hildre n and a dults ) , and f or c hildre n the o ra l e x posure s via h and
- to - mouth, obj ec t - to - mouth, and in c id e nt a l in g e stion of soil w er e a lso a ss e s s e d. T he m ar g ins of e x posur e ( MOE) gr eat l y e x cee d the 100
- f old MOE re qui re d f

or th e se r out e s and fr om the c ombin e d c hild

re n ’ s i n c id e nt a l o ra l i n g e stion. Th eref o re , r e sid e nti a l non - di e t ar y e x posur e is not a c on cer

n . D. C umulati v e Eff

ec ts It is not n ece s s ar y at this time to c onsid e r c umul ative ef f ec ts b e ca use th e r e is no indi cation th at t o x ic eff

e c ts of c hlo rantr anilip r ole h ave a c ommon m ec h a n ism with those of an y oth e r c h e mi ca l c o mpounds. E. Saf e ty D e te rmination 1. U.S. population
. B a s e d on r isk a ss e ssm e nts p erf o r m e d usi n g wo r st - ca se e x posur e a ssumptions t

h er e is a r ea son a

b l e c e rt a int y th at no h ar m will re sult to the g e n era l popul ation fr om the a g gr e g ate e x posur e to c hlo rantr anilip r ol e . No a ddition a l s afe t y f a c to r s ar e w ar

r ant e d. 2. I nfants and c hildr e n . B a s e d on the r isk a ss e s s m e nts p erf o r m e d usi n g w o r st - ca s e e x posur e a ssumptions th er e is a rea so n a ble c ert a i nt y th at no h ar

m will re s ult to the in fants and c hildre n fr om the a g gr e g ate e x posur e to c h lo rantranilip r ol e . No a d dition a l s afe t y fac to r s ar e w ar

r ant e d. F. I nte rnational T

ole ran ces Num er ous c hl o rantrani l ip r ole M R L s h ave b ee n e st a blish e d or ar e e x p ec t e d to be e st a blish e d suppo r

ti n g r e g istr ations in 92 c oun t r i e s. C od e x M R L s h ave a lso b e e n e st a blish e d f or c hlo r ant

r anilip r ole on num er ous c r ops.