1



# i

E P A R E G I S TR A TION DIVISION CO M PA N Y N O T ICE O F F I L I N G F OR
P E S TICIDE P ETI T IONS P UB L I S H E D IN THE F EDER A L RE G I S TER

E P A R e gist r a t ion Division c o n ta c t: [in s e r t n a m e a n d te lep h o n e nu m b e r w ith ar e a

c o d e ]

INST R UCTIO N

S : P le a se u tilize this o u tli n e in p re p a r i n g the p e sti c i d e p e ti t io n . In

c ases wh er e t h e o u tli n e e l e m e n t do e s n ot a pp ly, p lease i n s er t “ N A

- R e m ov e ” a n d

m ai n tain t h e o u tli n e
. P l e ase do n ot c h a n ge t h e m a r gi n s, f o n t, or f o r m a t in yo u r p e sti c i d e p e ti t io n
. S i m p ly r e p lace t h e i n st ru c ti o n s that ap p e ar in g ree n , i.e., “ [ i n s er t

c o m p a n y n a m e ] ,” w ith t h e i nf o r m a t ion s p ec i f

ic t o yo u r a c tion.

TEMPLATE:

[ Cla r iant Co r

po ra t i on, [ 4 000 Monroe Ro a d, Ch a r l ot t e , NC 2820 5 ]

EPA h a s r e c e ived a p e st i c ide p e t i t i on ( IN 10631 ) f rom [ Cla r iant Co r por a t i on (EPA C ompa n y Numb e r 83 4 0, 4000 Monroe Ro a d, Ch a rlotte, NC 2820 5 ]

r e qu e s t i n g , pursu a nt t o s e c t i on 408 ( d) of the Fe d er a l F ood, D r u g , a nd Cosmetic A c t (F F DCA ) , 21 U.S. C . 34 6 a (d ) , to am e nd 40 C F R p a rt 180 to establish an e x e mp t i on f r om
t he re qui r e ment of a to l e r a n c e f o r

[ C. I

. P i g ment R e d 112, ( CAS R N 653 5

- 46

- 2 ) also know n as 3

- h y d ro x y

- N

- ( 2

- met h y lphe n y l )

- 4

- [ 2

- (2,4, 5

- trichlo r oph e n y l ) di a z e n y l ]

- n a phthal e n e

- 2

- ca rbo x a m i d e ), a s a seed tr ea t m e nt pi g ment, not to e x cee d 1 0% w t / wt, und e r 40 C F R §180.920 pursu a nt t o S ec t i on 408 ( d ) (1) of the F e d e r a l F ood, D r u g , a nd Cosmetic A c t (F F DCA ) . Th e r e a r e

c u r r e n tl y no a p p rov e d non

- food uses or food u s e to l e r a n c e e x e mp t ions for C

. I

. P i g ment R e d 112 a s a p e st i c ide ine r t i n g r e dient. EPA h a s d e te r m i n e d that the p e t i t ion cont a ins data

or info r mation re g a rdi n g the e lem e nts se t fo r th i n se c t i on 408 ( d ) ( 2) of F D DCA; how e v e r, EPA h a s not ful l y e v a luat e d the su f fi c ien c y of the submi t ted d a ta a t t his t i m e or w h e ther the d a ta supports g r a nt i ng o f the p e t i t i on. Addit i on a l data m a y b e n ee d e d b e f o re E P A

r ules on the p e t i t i on.2

2

P r o p osed 40 C FR § 180

. 920 Tole r a n c e Ex e m p t i on a n d L i m ita t io n s

I n e rt I n g r e dient CAS R e g . No. L i m i t s
C

. I

. P i g m e nt R e d 112

6535

- 46

- 1 10% ( w t / wt) s ee d

tr ea t m e nt fo r mu l a t i on

A. R e sidue Che m is t ry

1

. Plant m e tabo l ism. [ Not a ppl i ca ble/Not re qu i r e d for the e stablishment of a to l e r a n c e e x e mp t ion for ine r t i ngr e dients.]

2. Anal y t i c al m e thod. [ Not a ppl i ca ble/Not re qui r e d for the e stablishment of a to l e r a n c e e x e mp t ion for ine r t i ngr e dients.]

3. M agni t ude of residues. [ Not a ppl i ca ble/Not re q uir e d for the e stablishment of a to l e r a n c e e x e mp t ion for ine r t i ngr e dients.]

B. T o x icological Prof

i le

1. A c ute to x icity. [ The f

ol l owing a c ute to x ici t y d a ta are available : O E CD 401 ( r a t ac ute o r a l) L

D 50 > 15, 0 00 m g /k g /d a y

. ( EPA I V , pra c t i ca l l y no n

- to x ic ) ; OECD 402 ( ra t a c ute d e rm a l ) L D 5 0 > 5000 m g / k g , EPA C a te g o r y II I ; OECD 404 ( r a bbit d e r m a l
i rr i t a t i on), n o n

- ir

r i t a t i n g ; OECD 405 ( ra bbit ac u t e e y e i r ritation) no n

- irr i t a t i n g ; OECD 429 ( mouse loc a l l y

mph node a ss a y ) non

- s e nsi t i z in g ; a nd O E CD 406 ( g uin e a p i g B u e hler Ass a y ) no n

- s e nsi t i z i n g

.

2. G e notoxi c ty. [ C

. I

. P i gment R e d did not disp la y mu t a g e n i c ac t i vi t y in t he following a s s a y s: AMES b ac te r ial ( O ECD 471) a s s a y with and w i t hout m e tabolic

ac t i v a t i on; C hinese h a ms t e r lung fib r oblast c e ll m i c ronu c leus test ( OECD 4 87, v e rsion 3) with and w i t hout m e tabolic ac t i v a t i on a nd n e g a t i v e a nd the m a m m a l i a n c e l l g e n e

mu t a t i on a ss a y ( OECD 4 76) w i t h a nd without met a bol i c ac t i v a t i on.]

3. R e produ c t i v e and d ev e lopm e ntal toxi c i t y

. [ In evaluating the potential for reproductive and developmental toxicity of C.I. Pigment Red 112 when used only as an inert ingredient in seed treatment formulations, Clariant requests that EPA should take into account both the relevant reproductive/develop mental toxicity endpoints in the OECD 407 28

- Day Rat Oral Toxicity Study in rats and its physicochemical properties, which make the possibility of foliar residues and dietary exposures to sensitive populations highly unlikely.

Although there were no reproductive or developmental toxicity studies available for C.I. Pigment Red 112, the OECD 407 28

- Day Rat Oral Toxicity Study in rats included relevant endpoints specific to reproductive toxicity including organ weights, gross patho logy and histopathology. The study demonstrated that there were no treatment

- related effects on the relative and absolute organ weight data for the testes or epididymides when compared to3

3

the vehicle control group mean. Gross pathology of the reproductiv e organs did not reveal
any treatment

- related effects in reproductive organs. Furthermore, histopathology of epididymides, prostate gland, seminal vesicles, testes, ovaries, vagina, cervix, and uterus of the high dose and vehicle control group animals dem onstrated no differences at doses up to 1000 mg/kg/bw/day. Additionally, as noted below, the DEREK modeling did not indicate any structural alerts for reproductive toxicity or endocrine

- related toxicity.

In evaluating reproductive and developmental toxicit y, EPA should also take into account that the physicochemical proprieties for C.I. Pigment 112 prevent the likelihood of potential foliar residues that could result in dietary exposures to the sensitive populations. EPA has previously applied a policy base d Pigment Red 1physicochemical based qualitative rationale in its FQPA evaluation of the potential reproductive and developmental toxicity
for another azo

- colorants when they are used only as inert ingredients in soil treatment pesticide formulations. tha t should be applicable in assessing the reproductive and developmental risk of C.I. Pigment Red 112 used an inert ingredient in seed treatment
formulations.

For example, the Pigment Red 48 is also a synthetic azo

- naphthalene di

- sodium salt
derivative tha t has been granted a tolerance exemption for use as an inert dye ingredient is
seed treatment formulation. Refer to the Inerts Tolerance Reassessment Petition (Attachment III; EPA, 2009). Specifically, as a result of the Pigment Red 48 EPISuite physicoch emical properties analysis, the Agency could determine that the Pigment Red 48 in seed treatments would not result in foliar residues. As such, the Agency rendered the following FQPA policy decision:

As stated on Page 8 of the February 10, 2008 Action Mem orandum “Inerts Reassessment Pigment Red, CAS Reg No. 3564

- 21

- 4) that, despite of no relevant reproductive toxicity and developmental toxicology data the following conclusions was reached:

“No significant health concerns were identified and so Pigment Red 48 was given a low concern for human health effects. ...There is little or no probability of exposure to Pigment Red 48 expected from its use as an inert ingredient in pesticide formulations, and therefore, risk concerns are not expected by the Agency.

Tak ing into consideration all available information on Pigment Red 48, it has been determined that there is reasonable certainty that no harm to any population subgroup will result from aggregate exposure to Pigment Red when considering dietary exposure and a ll other non

- occupational sources of pesticide exposure for which there is reliable information. Therefore, it is recommended that the exemption from the requirement of a tolerance established for residues of Pigment Red when used as a dye for seed treatme nt only can be considered reassessed as safe under section 408(q) of the FFDCA”4

4

In rendering this FQPA decision, EPA made note of the physicochemical properties of Pigment Red 48 and that there was little likelihood of foliar residues resulting from the us e of Pigment Red 48 as a seed treatment only.

As specified on page 5/8 in the EPA (2009) Tolerance Reassessment:

“Therefore, this estimated is based solely on estimated properties. Red Dye 48 is not expected to rapidly degrade in the environment; primar y degradation is expected to occur in the order of weeks and ultimate degradation (mineralization) on the order of months. The compound is classified as not readily biodegradable. Red Dye 48
has a low octanol

- water co

- efficient (Kow of

- 1.25), this not li kely to bioaccumulate in the environment. Red Dye 48 is soluble, non

- volatile and likely to be mobile. Leaching into ground water is expected because of low estimated soil partition coefficient. Potential to volatize from surface water is very low and atm ospheric degradation is expected to be fairly rapid”

Clariant is not bridging the physicochemical properties for C.I. Pigment Red 112 to Pigment Red 48, but rather is requesting that the Agency consider (along with the OECD
407 28

- Day Rat Oral Toxicity Stu dy data)the physicochemical properties of C.I. Pigment Red 112, the likelihood of foliar residues and how the potential of foliar residues may result in the evaluation of C.I. Pigment Red 112 reproductive and developmental effects. Clariant emphasizes tha t the use of C.I. Pigment Red 112 as an inert ingredient in seed treatments should result in less environmental risk than Pigment Red 48. Specifically, there is less likelihood of foliar residues because, unlike a dye, as a solid pigment the C.I. Pigment 112 pigment particles are less likely to diffuse into the soil from the seed treatment formulation. Additionally, EPA should take into account that in comparison to Pigment Red 48, C.I. Pigment Red 112, has a more extensive acute and repeat dose toxicolo gy database.

While EPISuite physicochemical properties indicate that both Pigment Red 48 and C.I. Pigment Red 112 may degrade slowly in the environment, and would not bioaccummulate and quickly degrade in air, C.I. Pigment Red 112, unlike Pigment Red 48, is not readily soluble in water and Koc calculations confirm that C.I. Pigment Red will, unlike Pigment Red 48, bind tightly to soil and sediment. Therefore, there is less likelihood that C.I. Pigment Red 112 may leach into ground or drinking water than P igment Red 48.

Additionally, as noted in Section VII, Potential Foliar Residues, we also ask EPA to take into account that the proposed amounts of C.I. Pigment 112 for seed treatment, not to exceed 10% wt/wt in the formulation, is low compared to the weig ht of the seeds that should be expected to be applied per acre. Following seed germination, it is also unlikely that any of the pigment would be taken up by the plant because C.I. Red Pigment 112 is expected to be tightly bound to soil.5

5

This is comparab le to the same rationale for Pigment Red 48 that was stated on Page 8 of the February 10, 2008 Action Memorandum “Inerts Reassessment Pigment Red, CAS Reg

No. 3564

- 21

- 4”:

“The amount applied to seeds is small compared to the weight of the seeds. By the ti me seeds germinate most of the dye will be absorbed by the soil and eventually degraded with little of the dye available for potential plant uptake.”

To summarize, Clariant requests that in consideration of the OECD 407 28

- Day Rat Oral Toxicity Study and the physicochemical properties for C.I. Pigment Red 112 that EPA can conclude that the use of Pigment Red 112 only as an inert ingredient in seed treatment formulations does not pose undue reproductive or developmental risk to sensitive populations. ]

5. Subchronic toxicity. [ The general systemic toxicity NOAEL from the OECD 407
28

- Day Rat Oral Toxicity Study in rats was 1000 mg/kg body weight/day.

6

. C h r on ic t o xic ity. [ T o x ico l o g i c a l s t udies of c h r onic dur a t i on a re not a v a i l a ble f or C

. I

. P i g m e nt R e d 112. B a s e d on the a v a i l a ble r e p ea ted dose testi n g in wh i c h the hi g h e st dose test e d, 1000 m g /k g bw/d a y p roduc e d no tr ea t men t

- r e lat e d e f f ec ts, a c h ronic
R e f e r e n c e Do s e ( Rf

D ) of 10 m g /k g bw/d a y c a n be d e riv e d b a s e d on the a p p l i ca t i on of

un ce rt a in t y f

ac tors f o r int e rsp ec i e s (10 X ) a nd in t r a

- spe c ies ( 1 0 X) dif f e r e n c e s. A De riv e d
No E f f e c t L e v e l ( D N E L ) ca n a lso be ca lcul a t e d. The D N E L q u a nt i fi e s the no e f f e c t

c on ce nt r a t i on f

o r hum a n e x posure b a s e d on the a p pl i ca t i on of un ce r t a in t y f ac tors f or in t e rsp ec ies dif

f e r e n ce s ( 5X ) , in t ra

- sp e c ies dif f e ren ce s (4 X ), a nd a f

a c tor f o r time

e x tr a polation (2 X ). A f

ac tor of 1 w a s ap p l i e d for r e maining in t e rs p ec ies di f f e r e n ce s, b eca use C

. I

. P i g ment R e d 112 is not l ike l y to b e c ome s y stemi c a l l y a v a i l a b le in re lev a nt

am oun t s bas e d on ECE T OC . T he r e sul t ing ove ra ll a ssessment f ac t o r is 40 ( 5 x 4 x 2) f

or

a D N E L of 25 m g /k g bw/d a y

. ]

7

. Animal m e tabo l ism. [ T h e re a re no publ ic a l l y a v a i l a ble m a m m a l i a n met a bol i sm data r e port e d f

o r C

. I

. P i g ment R e d 11 2 , but i t i s unlike l y that met a bol i sm would r e sult in t he p r odu c t i on of to x ic or ca r c inogenic met a bol i tes.] Cla r iant h a s p r opos e d the f ol l owi n g r a t i on a l e to add re ss t he p o tential a ni m a l m e tabolism i n humans.

“ The to x icokin e t i c pro f

i l e of a subs t a n c e c ompri s e s i t s abso rpt i on in t o the bo d y , i t s distribu t ion i n the bo d y , i t s metabolism in t he bo d y a nd i t s

e x c r e t i on f

r om t he bo d y

. T a king in t o a cc ount t he p h y sico c h e m i ca l

p r op e rties a nd the to x icolo g i c a l t e st r e sul t s, qu a l i tative e st i mat e s for these

a spe c ts m a y be d e du c e d f or P i g ment R e d 112.6

6 Abso r p tio n : A p re r e qui s i t e f or a r e lev a nt abs o rption is that the subs t a n c e

ca n be dis s olved in e i t h e r a qu e ous ( e

. g ., g a stroin t e st i n a l fluid, blood plasm a , sw ea t) o r lipophil i c (e

. g ., l i popr o teins, lip i d memb ra n e s, tri g l y c e rid e s) m e d i a or in both. P i g ment R e d 112 c a n be c onsid e r e d inso l uble b eca use it has a n e x tr e me l y low solubi l i t y in w a t e r a nd n

o c tanol. Th e r e fo r e , it is un l ike l y that P i g ment R e d 112 b ec omes

s y stemi ca l l y bioa v a i l a ble a ft e r o r a l, de r m a l or inh a lation e x posur e . The

r e sul t s of ac ute o r a l t o x ici t y , ac u t e d e rm a l t o x ici t y a nd r e p e a ted o r a l

to x ici t y stud i e s also g i v e v a luable ind i ca t i ons with re g a rd to a bsor p t i on of the t e st s ubst a n ce

. B a s e d on the ac u t e or a l t o x ici t y a nd the 2 8

- d a y o r a l

to x ici t y stud i e s, which d i d not r e v ea l a n y s y stemic e f f e c ts t h a t would ind i ca te th a t t he pi g m e nt had e nte r e d the bo d y , no ind i ca t i ons of si g nifi ca nt a bsorption v i a the g a str o in t e st i n a l t r a c t h a s to be a ssu m e d.

P i g ment R e d 112 do e s n ot have p a rticul a r skin or e y e ir r i t a t i n g or skin

s e nsi t i z ing pro pe rties th a t would i mp l y a d e rm a l a bsorptive pot e nt i a l. I n the unlike l y e v e nt of e x posure to a e rosoli z e d p i gment in r e spir a ble f o rm, the substan c e is conside r e d l i k e l y to be h a ve l i ke a n ine r t dus t . Th e r e f o r e , the d e posited pi g ment p a rticl e s will mos t l y b e c l e a r e d f rom the lung v i a the mu c o c i l l i a r y tr a nspo r t. As the pi g ment will not d i sso l ve in t he lung

sur fac tant, the on l y w a y t he pi g m e nt ca n e n t e r the bo d y is v i a ph a g o c y tos i s of pi g ment p a rticl e s b y lu n g ma c ro p h a g e s follow e d b y

m i g r a t i on of the m ac rop h a g e s in t o the inte r st i t i um and into t he dr a in i ng l y mph nodes. H o w e v e r, t he in t e rn a l dose d e l i v e red via this me c h a nism

ca n be c onsid e r e d n e g l i g i ble.

Distribution : The 28

- day oral repeated dose toxicity study did not indicate any relevant histopathological changes in any of the investigated organs. This may indicate that either the pigment does not affect special organs as targets, i.e., is non

toxic, or is not distributed within the body in significant amounts. As indicted above, the physico

- chemical parameters of the pigment support the conclusion that the pigment is not absorbed into the body and thus does not become systemically available. There were also no other signs of deposition of the pigment in any organ including excretory organs, like the kidney, indicating that even exposure to high doses of the pigment does not lead to bioaccumulation in special compartments of the body.

Met a b ol i s m : S ince the d is s olu t ion of the subs t a n c e in c e l l ular f lu i d or

ce l l ular memb ra n e s is a p r e r e quis i te f o r its m e tab o l i sm, i t i s u n l i k e l y that the insoluble pi g me n t be c omes a c ce ss i ble f o r met a bol iz ing s y stems i n

r e lev a nt amounts. The resul t s of the mu t a g e nici t y tests provide use f ul ind i ca t i ons for qu a l i tative c onsid e r a t i on of the m e tabolic fa te of P i g ment R e d 112. I

n t h e mu ta g e n i c i t y tests, t he p i g ment p r ov e d to be no n

- to x ic

a nd nonmu t a g e nic in the a bsen c e a s w e ll a s in t he p re s e n c e of a n

e x o g e nous m e t a bol iz ing s y stem, indic a t i n g that the pi g ment is not7

7 c onv e rt e d in t o to x ic or g e noto x ic m e taboli t e s. Th i s co nc lus i on is a lso support e d b y t h e la c k of a n y mor p holo g i c a l and h is t op a tho l o g ic a l c h a n g e s of o r g a ns involved in x e nobio t ic m e tabolism, su c h a s the l i v e r, in the

r e p ea t e d dose to x ici t y stu d y

.

Ex cre tio n : The a v a i l a ble d a ta indic a te th a t P i g m e nt R e d 112 is not

a bsorb e d in t o the bo d y

. In line with t his con c lus i on, the 2 8

- d a y o r a l

r e p ea t e d dose to x ici t y stu d y did not ind i ca te mo rp holo g ic a l or his t op a tho l o g ic a l e f

f e c ts of the pi g ment on o r g a ns invo l v e d in e x c r e t i on of c h e m i ca ls f

rom the b o d y , such a s the kidn e y

. T h e re w a s no indic a t i on that the substan c e w a s p r e s e nt i n the u r ine. Mo r e o v e r, f rom the r e p e a ted

o ra l t o x ici t y stud i e s, it c a n be c on c luded t h a t, a ft e r or a l e x posur e , the pi g ment is e x c r e ted u n c h a ng e d via the f a e ce s.

7. Me tabo l i t e toxi c olog y

. [ No Da ta]

8. Endo c rine disrupt i o n

. [ C. I

. P i g ment R e d 112 d o e s not b e long to a c lass of

c h e m i ca ls known or sus p ec ted of h a ving a dv e rse e f fec ts on the e st r o g e n r e c e ptor or

e ndo c rine s y stem.]

C. Aggr e gate Ex

posure

1

. Di e tary ex

posure

. [ W hi l e no spe c i fic r e sidue info r mation is a v a i l a b l e for C

. I

. P i g m e nt R e d 1 1 2

, on the b a sis of the p r opos e d to l e r a n c e e x e mp t ion a nd the p h y sic a l

c h e m i ca l p r o p e rti e s a n a l y si s , it is not l i k e l y that dietary exposures could result f r o m the

use of C

. I

. P i g ment R e d 112 a s p e st i c ide ine r t ingr e die n ts only in s ee d tr ea t m e nt
fo r mu l a t i ons und e r 40 C F R §180.920 a t c on ce nt r a t i ons not to e x cee d 1 0 %

. T h e s ee d

t r ea t m e nt fo r mu l a t i ons c o ntaining C

. I

. P i g ment R e d 112 will b e a ppl i e d dir e c t l y to the

s ee ds a nd if r e l e a s e d in t o the e nvironme n t, the pigment will bind t i g ht l y to soil a nd

s e di m e nt a nd not be soluble in w a te r

. Un d e r the s e c ondi t ions, C.I. Pigment 112
would not be t a k e n up b y t h e g e rmin a t e d s ee dl i n g s a nd tr a nsl o ca t e d with i n the plant

v a s c ular s y stem to r e sult in c rop r e sidues a nd diet a r y e x posur e s.

A dietary risk assessment s undertaken to confirm that potentially

, if foliar residues should result from seed treatment use, that C.I. Pigment Red 112 does not pose undue dietary risk to US general and sensitive populations.

EPA assesses potential dietary exposures to i nert ingredients used in agricultural pesticide formulations using a screening

- level model referred to as “I

- DEEM,” in which the “I” stands for inerts and “DEEM” is the dietary exposure evaluation model that is used by EPA to assess dietary exposures to ac tive ingredients in pesticide products. EPA’s Inert Ingredients Assessment Branch and residue chemists in the Health Effects Division of the Office of Pesticide Programs jointly developed I

- DEEM. The model, as developed by EPA, uses crop

- specific residue data (i.e., maximum tolerances) for 57 active ingredients as surrogates for potential inert ingredient residue levels. I

- DEEM estimates that inert ingredients are used on all crops, and that 100 percent of all crops are assumed to be8

8

“treated” with th e inert ingredient(s). I

- DEEM also assumes that the inert is present at a concentration of 50% in all the pesticide formulations. In addition, EPA includes potential residues of 100 ppb in water for potential drinking water exposures. Using these

assump tions, and including the 10% cap for use in seed treatments, the chronic dietary exposure is estimated to be 0.040 mg/kg/d for the general U.S. population and 0.144 mg/kg/d for children 1

- 2 years of age (i.e., the most highly exposed subpopulatio n]

.

Cal culation of Chronic Reference Dose

[The no

- observable

- adverse

- effect

- level (NOAEL) for C.I. Pigment Red 112 may be assigned as 1000 mg/kg/day.

The chronic reference dose (cRfD) is therefore 10 mg/kg/day.

 cRfD = 1000 mg/kg body weight/day / 100

 cRfD/cPAD = 10 mg/kg/day

The data and use pattern of low level soil application as a seed treatment support that the FQPA safety factor for C.I. Pigment Red 112 should be reduced from 10X to 1X. Therefore, only the 10X factors for intra

- and inter

- spe cies variability should be included in calculating the chronic reference dose (cRfD) and the chronic population adjusted dose (cPAD).

The dietary (food plus drinking water) exposures for C.I. Red Pigment 112 are expressed as a percentage of the proposed cPAD are summarized in Table 3. Chronic Safety Assessment,
% cPAD for the general U.S. population and children 1

- 2 years old, the subpopulation with the highest potential exposures. Based on I

- DEEM screening level calculations for , the chronic dietary e xposures are estimated to be 0.40% of the cPAD for the general U.S. population and 1.44% of the cPAD for children 1

- 2 years old. These data demonstrate that
the I

- DEEM screening

- level chronic dietary (food and drinking water) exposures are below
the cPAD and are therefore below EPA’s established level of concern for all U.S. subpopulations.

On the basis of the proposed chronic NOEL (1000 mg/kg/day derived from the OECD 407 compliant 28

- day oral repeated dose toxicity study) and comparison of I

- DEEM exposure estimates, Clariant contends that there is sufficient basis for EPA to grant a tolerance exemption for the 180.920 seed treatment uses at the maximum level of 10% in formulated products. ]

i. Food. [ The c h r onic di e ta r y e x posur e s esti m a ted using the c on s e rv a t i ve I

DE E M s c r e e ni n g le v e l m od e l ( f o od a nd d r ink i ng w a te r ) a r e w e ll b e low 100% o f the

c P A D

, a nd a re th e r e f

o re b e low the lev e l of c o n c e rn f o r a ll U.S. subpopulation s .]9

9 i i

. Drin k ing wate r

. [ D r i n king w a t e r is includ e d in the I

- DE E M

e x posure a ssessment a nd b a s e d on a nt i c ipat e d c on c e ntr a t i o n s e x p ec ted to be

n e g l i g ib l e.]

2. Non

- dietary ex

posure

. None

D. Cumulative Eff

ec ts

[ It has not been d e te r m i n e d that C

. I

. P i g m e nt R e d 112 h a s a c om m on

me c h a nism of to x ici t y with o t h e r subst a n ce s .]

E. Safety D e ter

m ina t ion

1. U.S. populat i on. [ B a s e d on the c onse r v a t i ve e x posure e st i mat e s, the r e is a

r e a sona b l e c e rt a in t y t h a t no ha r m wi l l r e sult to t he U.S. popu l a t i on f r om t he

a ggre g a t e e x posure to C

. I

. P i g ment R e d 112 used a t 10% c o n ce ntr a t i on in se e d

t r ea t m e nt only fo r mu l a t i ons with ch r onic di e ta r y e x posure e st i m a ted to be 0.04

m g /k g /d a y (0.4 0 %

. P A D ) f or the g e n e r a l U S populatio n

.
There are no proposed uses for Pigment Red 112 that would result in residential exposures to the US Population. ]

2. Infants and childr e n

. [ The F F DCA S ec t i on 408 re quir e s an a ddi t ional

t e n f old ma r g in o f s a f

e t y for the p rot ec t i on of inf a nts and c hi l d re n in c a se of t h r e sh o ld

e f fe c ts t o acc ount f

o r p re n a tal a nd postn a tal to x ici t y , a nd a n inad e qu a te to x ic it y d a t a b a s e

. W h e re a n a d e q u a te a nd r e l i a ble d a tab a se is a v a i l a ble a nd the r e is a l a c k of

e vide n c e f

or inc r ea s e d susc e pt i bi l i t y , t h e F QPA s a f e t y f a c tor m a y b e re d u ce d or

r e moved. B a s e d on a v a i l a ble in f o r mation d i s c ussed h e r e in, Cla ra in t

, I n c

. believes the
F QPA s a f e t y fa c tor should be reduced to 1X

. for the r e a sons des c rib e d below . T he

c R f D is th er e fo r e e quival e nt t o the c h r onic population adjust e d dose (c P A D ).]

 An e v a luation of sus c e pt i bi l i t y a nd un c e rt a in t y is s u e s asso c iat e d with the use to C

. I

. P i g m e nt R e d 112 us e d a t 10% c o n ce nt r a t i on in s ee d tr e a t m e nt fo r mu la t i ons

r e sul t e d in I

- DE E M est i mat e d c h r onic di e t a r y e x posur e s to child re n 1

- 2 y ea rs of

a ge ( the pot e nt i a l l y most e x posed population of 0.144 m g /k g /d a y ( 1.44% P A D ).

 C.I. Pigment 112 has a sc i e nt i fi ca l l y sound m a m m a l ian to x icology d a t a b a se t h a t includ e s a c ute, su b c h r on i c , a nd g e noto x ici t y d a ta. Th e se test d a ta, did not in dicate d e v e lop m e nta l

, re p r odu c t i ve , n e u r o l o g i c a l e ndpoin t s or g e no t o x ic

e f f e c ts.

 DEREK modeling also did not provide structural alerts for reproductive or developmental toxicity.

 P h y sico c h e m i ca l / e nviro n ment a l prop e rties analysis ind i ca te s th a t c r op r e sidues

, that may r e sul t in d i e ta r y e x posu r e s to s e nsi t ive pop u lations

, a re unl i k e l y wh e n C

. I

. P i g ment R e d 112 is used only as a n inert ingredient in se e d tr ea t m e nt f o rmul a t i on a t con ce nt r a t i ons not to e x cee d 10% wt/wt.10

10  C

. I

. P i g m e nt R e d 112 d o e s not b e long to a c lass o f c h e m i ca ls known o r su s p ec ted of h a ving adv e rse e f

f e c ts on the e str o g e n re ce pt o r or e ndo c ri n e s y s t e m.]

F. I nternational T

oleran ce s

[ Th e re a r e no known int e rn a t i on a l t ole ra n c e s for C

. I

. P i g ment R e d 11 2 .]