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AR226-2796 _ ' !i ' Haskell Laboratory Report No. 799-85 . I . du Po nt de Nemours and Company Haskell Laboratory fo r Toxicology and In d u s tria l Medicine P . 0 . Box 50; E lk to n Road Newark, Delaware 19 714 Date Issued: February 12 , 1986 Com pany Sanitized. Does not contain T S C A CB1 -y-S:-.<*r___ . , ,. ..__ * ; 305, was evaluated f o r acute eys~ i r r i t t ion potential in ;jfp e _______ . produced s lig h t corneal o p a c ity f r a i 1 hour th ro u g h 2 days in th e unwashed e y e . So eye i r r i t a t i o n was ' , .......................................................... Flu o re s c e in exam inations were neg ative a t a ll I n t e r v a ls . The unwashed eye was normal w ith in 3 days a f t e r tre a tm e n t. Under the conditions o f th is Study, s lig h t eye I r r it a n t . was a Work b v : r ^ - i j c C L s J ^ o3 if $ J ----------------- f e b o W r l H c f --------------------------------- Technician Study D ire c to r: t. John E . Henry T e c h n o lo g is t life Approved b y: Haneyy . chromey, R& . Section S u p e rvis o r, Acute In ve stig a tio n s Section JEH :sm k:H LR 21.5 - 2- Company Sanitized. Does not contain TSCA CBI Because short-tera studies are nuaerous and routine in nature, representative studies froa this test type are audited quarterly to ensure the studies are designed and conducted in conpliance with the Good Laboratory Practice Standards. : Reported by: " f l'oosseejffh C. Haul 11 Quality Assurance Auditor ^ d p zjk S e Date' }i1 - 3- Company Sanitized. Does not contain TSCA CBI Sponsor: ! C h a rle a !* and Pigments Department 1 . 1 . du P o n t d e Nemo u rs and Company W ilm in g to n , D e la w a r e ................................ M ateria! Subm itted By: Test F a c ility : Chemicals and Pigments Department E ,, I du P o n t de Nemours and Company Jackson la b o ra to ry ; D e e p w a te r, Net J e r s e y E . I du Pont de Nemours and Company Haskel1 La b o ra to ry fo r Toxicolog y and In d u s tria l Medicine P . 0 . Box 5 Q , E lk to n Road Newark, Delaware 19714 Study In itia te d - Completed; 8/13/85 - 8/16/85 There are 12 pages In th is re p o rt. D istrib u tio n : ! i - 4- Company Sanitized. Does not contain TSCA CBt " ! IT1* '' 'm m m - 'smepmtic- a p p lic a b le EPA Good Ubohaipfypi a re documented in t h r s tifl& rfi& o f a f f e c t e d th e v a l i d i t y o f th e sjtiudtw irrita tio n potential ^ ^W ^ycted according to the J ^ u t la iM iU Areas o f noncoapl lance jNd'l j ^ f a t i o n r e x i s t e d t h a t s i g n i f i c a t t l y m TERlALSAIffligm O O S A . Animal Husbandry ' . i' . Young a d u lt s a le New Zealand W hite ra b b its Mere received from BucksM re C o rp o ra tio n , P e rk a s ie , P e n n sylva n ia . The ra b b its Mere housed s in g ly in suspended, s ta in le s s s t e e l, wire-m esh cages. Each ra b b it was a ssign ed a u n iq u e i d e n t i f i c a t i o n nus&er w h ic h was recorded on a card a f f i x e d t o t h e c a g e . P u rin a C e r t i f i e d ;R a b b i t CbomP #5322 and w a te r were a v a ila b le ad lib itu m . R a b b its were q u a ra n tin e d , weighed and observed f o r general h e a lth fo r approxim ately 2 weeks. Environmental conditions o f th e rooms w ere ta rg e te d f o r a tem perature o f 2Q*C + 2C and r e la t iv e h u m id ity o f 50X _+ 1 0 X . A n y e x c u rs io n s o u ts id e the?e ranges were o f b r i e f d u ra tio n and d id""lo t a d v e rs e ly a ffe c t th e outcome o f th e s tu d y . B . Protocol On th e d a y p r i o r t o s tu d y i n i t i a t i o n , th e eyes o f 2 male New Ze ala n d W hite r a b b its w eighing 3126 and 2764 grams were examined using flu o re s c e in d y e . Anim als showing p r e -e x is tin g corneal o r c o n ju n c tiva l In ju ry o r I r r i t a t i o n were not used In th is stu d y. A 0 .0 1 ml a liq u o t o f was In tro d u c e d in f o th e low e r c o n ju n c tiv a l sac o f t h e r i g n t eyes o r 2 male New Ze a la n d W hite r a b b its . The l e f t eyes served as c o n tro ls . The tre a te d and co n tro l eye o f one anim al remained unwashed. Ap proxim ate ly 20 seconds a f t e r th e te s t m a te ria l was a d m in iste re d , both eyes o f the remaining animal were rinsed fo r one m inute w ith lukewarm ta p w a te r. Ap p ro xim a te ly 1 and 4 hours and 1 , 2 and 3 days a fte r tre a tm e n t, th e ra b b its were examined fo r evidence o f eye I r r i t a t i o n . A t each ob se rva tio n th e tre a te d eyes were examined using an ophthalmoscope and scored f o r o e u la r re actio n s using th e D ra ize scale (presented in Tab le I ) . The u n tre ate d eye was a lso examined and used f o r com parison. Any unusual e ffe c ts , e .g ., panhus, b lis te rin g o f the c o n ju n ctiva , ulceration or; other e ffe c ts indicative o f corrosive action 5 Company Sanitized. Does not contain TSCA CBI  ' '`i "'.: 1 *' / ? . ,-/i -, t ' ' M. t oy' / . -.1 R wer a lso noted. M o b Iv a te corneal and Ir r ita tio n and a t e id h : observation^ A -- - p p p w i ^ o f ***** H f m u "f m "yi-y S t.jfi'--s C . Test M aterial Physical Fo ra : P u rity: S,';. Com position: Synonyms: Other Codes: CAS R e g is try N o .: S ta b ility: The) t e s t m a te ria l was assumed t o be s ta b le under the conditions o f adm inistratio n. 0 . Records Retention A l l raw d ata and th e f i n a l re p o rt w ill be s to re d In th e a rc h ive s o f H a ske ll La b o ra to ry f o r T o x ic o lo g y and In d u s tria l M e d ic in e , E . I . du Pont de Nemours and Company, Newajrk, Delaware o r in th e Du Pont H a ll o f Records, W ilm ington, Delaware. ; RESULTS I ^ H ^ B H H ^ m m i H l p r b d u c e d slig h t cornal opacity fo r 1 hour t h r o u g ^ ^ W ^ f l ^ n ^ i n w a s h e d e y e . No o th e r eye I r r i t a t i o n was presen t throughout the s tu d y . Fluoroescein examinations were negative a t a ll in te r v a ls and both eyes appeared; normal by day 3 . In d ivid u a l eye I r r i t a t i o n scores are presented in Tables I I I and IV . CONCLUSION Under the conditions o f th is study, s lig h t eye Ir r ita n t. - 6- v;: Company Sanitized. Does not contain T S C A CB1 ( 1 ) Cornea : (A ) Opacity-degree o f density ^ ^ aken fo r read ing ) Ho o p jK 'lt y - S c a tte re d o r d if f u s e afepi> d e ta ils iif early vis ib le . , E a s i l y d is c e r n ib le t r a fts lo c M t a ^ s f>d f t ^ | s o f i r i s s l i g h t l y 0 1 Opalescent areas, no d ^ i l s o f f r f s y $ iifle s ize o f p u p il b are ly discernible i . . . . > . . . , . . . . . - . OpstjUBt i r i s i n v i s i b l e * - . 3 f (8) Area o f cornea involved (hie q u a r t e r f o r le s s ) put n o t z e r o . # ................................................... G r e a te r th a n one q u a r t e r , b u t le s s th a n h a l f ................................................... 1 2 G r e a te r th a n one h a l f ,' but le s s th a n t h r e e q u a r t e r s ........................... 3 G rea ter than th re e q u a rte rs , up t o whole area 4 Score equals A x B x S : T o ta l Maximum * 80 (2) Iris ; (A ) Values ! Normal .................................................................................................................................................... . . 0 Folds above norm al, congestion, s w e llin g , circumcorneal In je c tio n (any o r a ll o f these o r com bination o f any th e re o f) i r i s s t i l l reacting! to lig h t (sluggish reaction Is p o s itiv e ) No re a c tio n to l i g h t , hem orrhage, gross d e s tru c tio n (any o r a ll o f t h e s e ) .......................... ...... . ..................................... ............................................................... 2 Score equals A x 5 ; T o ta l Maximum * 10 (3) Conjunctiva : (A ) Redness (re fe rs to palpebral and b u lb ar conjunctiva excluding cornea and i r i s ) V e sse ls normal . . . . ...................................................................................................................... Vessels d e f i n i t e l y in je c te d above normal . . .................................................. More d i f f u s e , deeper crimson re d , in d iv id u a l vessels not e a s i l y d i s c e r n i b l e .............................. D if f u s e b e e fy red . * . . . . . . . ............................................................................ (B ) Chemosis No s w e llin g Any s w e llin g above noifmal (in c lu d e s n i c t i t a t i n g membrane) . . O b viou s s w e llin g w i t h i p a r t i a l e v e rs io n o f l i d s .......................... . . . S w e llin g w ith li d s abdut h a l f closed . ............................................................... Sw elling w ith lid s about h a lf closed to com pletely closed . . 0 1 2 3 0 1 2 3 4 - 7- Company Sanitized. Does not contain TSCA CBI (C) Discharge Ito d is c h a rg e , . . -, . . Any amount dfffiepew t; | d o p # s n a il am ounts observed in in n e r canthus i f f norm al a n im als ) o ! ;S<j- 2 'S'- , and co n sid e rable area abound th e eye . * . . . . . . . . . . 3 Score equals ( A B + C) x 2 Total Haxlmun - 2D fI The maximum t o t a l scorie is th e sum o f a l l sco res o b ta in e d f o r th e c o rn e a , 1 r 1 s and c o n ju n c tiv a . T o ta l maximum sc o re p o s s ib le = 1 1 0 . 1 D r a lz e , J . H . , "Dermal T o x i c i t y ." Ap p raisal o f th e S a fe ty o f Chemicals in Fo o d s. Drugs and Cosm etics.. The E d it o r ia l com mittee o f th e A s s o c ia tio n o f Food and Drug O f f ic ia l s o f th e U nited S ta te s , A u s tin , T e x a s , 19 5 9 , p p . 46-59. 8- - j I Company Sanitized. Does not contain TSCA CBI | TABLE I I '' .. --1< . . BIOMICROSCOPE C L l ft ^ E f O t t & W S O F CORMEAL INJURY (Bfoptc or cornea) - 0 = No 1in ju ry; cornea w ith in nonnal l i m i t s . i. S lig h t ( 1 ) E p ith e lia l changes v is ib le only 1th biom icroscope (may; In c lu d e lo c a liz e d area o f m ild I n j u r y ) * M ild (2) = O pacity v is ib le w ith ophthalmoscope o r lig h t but showing e p ith e lia l changes o n ly w ith biom icroscope (may In clu d e lo c a liz e d area o f d e r a te i n j u r y ) . Moderate (3) = O pacity v is ib le w ith ophthalmoscope o r lig h t b u t showing e p it h e lia l and strom al changes w ith biom icroscope (may In c lu d e lo c a liz e d area o f severe in ju r y ). Moderate to Severe (4) = O pacity v is ib le w ith ophthalmoscope o r lig h t but showing e p ith e lia l and strom al changes and endothelial relucency t1th unremarkable s w e llin g . T h is typ e o f i n j u r y shows e vid e n c e o f healing (re v e rs ib le damage) w ith in 14 d ays. Severe (5) = Opaqueness o r o p a c ity v is ib le w ith ophthalmoscope o r lig h t but showing e p ith e lia l and strom al changes and e n d o th e lia l relucency and sw ellin g o r oth er d is to rtio n . Th is type o f in ju ry does not show; evid e n ce o f h e a lin g (perm anent damage) w it h in 14 days. - No biom icroscope e v a lu a tio n p erform ed. - 9Company Sanitized. Does not contain TSCA CB1 ff:*'- - ,'ls a |e i^ ^ B j normal l i m i t s . Slig ht ( l) E p ith e lia l changes a r t i c l e o n ly w ith biom icroscope (m fy include lo c a lize # area o f m ild In ju r y ). M ild (2 ) O p a c ity v is ib le w ith ophthalmoscope o r lig h t b ut shewing e p ith e lia l changes o n ly w ith biom icroscope (may in c lu d e fo c a liz e d area o f m oderate i n j u r y ) . Moderate (3) O p a c ity v is ib le w ith ophthalmoscope o r lig h t b u t Showing e p it h e lia l and strom al changes w ith bipmfcroscojjte (may in c lu d e lo c a lize d area o f seyere in ju ry ).- Moderate to Severe (4) O p a city v is ib le w ith ophthalmoscope o r lig h t but showing (E p ith e lia l and strom al changes and e n d oth elia l relucency w ith unremarkable s w e llin g . T h is typ e o f in ju r y shows evidence o f h ealing (r v e rs ib le damage) w ith in 14 d ays. I '' 1. Severe (5) Opaqueness o r o p a c ity v is ib le w ith ophthalmoscope o r jlig h t b u t showing e p ith e lia l and strom al changes and e n d o th e lia l relucency and sw elling o r ^ }e r E s c o r t io n . This type o f in ju ry does not show evidence o f h e a lin g (permanent damage) w ith in 14 jd a y $ . . * No-biom icroscope e va lu a tio n perform ed. I - 9- __ r.__ nnoe nnt rontain TSCA CBl y.w'vl;. !, T L E i h EV E U tR IT A T I M m #'* UNWASHED R A B B IT E r e A F T E R E X P O S U R T T f l IH THE H L * 799-85 Rabbit Number 19230 Cornea O p a c ity Area Iris -- n-- ------ r -------- ------- 2--------- *" T ~ " 3 Hour Hours W ., Days Days 11 44 1 10 4 10 00 000 C o n ju n c tiv a Redness Chemosis Olscharge B io n ic of com ea 0 0 0 '- 0 000 0 000 0 000 - - - - Fluorescein Stain Exam inations: negative a t a ll in te rva ls fi - 10 - Coirmanv Sanificar! n/ia HmI *. _. - I fru sti? -fi", > ?:>;.''}'"f .: .'- `'z. / . - ; i :_ rRRI|TIOH E A C ^ l I ' " MASHED RABBIT E I E A FTER E tP O S tg g T n . ; . : ', / - /. - .. i r HLR 799-85 Rabbit Number 19231 Cornea O p a c ity Area Iris C o n ju n c tiv a Redness Chemosis 0 1scharge Biomic o f cornea " 1 --------!--------~ 4 T 1 -- -- 2-- Hour Hours Day Days 3 Days 00 00n _o o_ Q 0 0 00 000 00 o n Au 0 0 o o nu 0 0 000 -' -' - - - Fluorescein Stain Exam inations: negative at a ll in te rv a ls . I 11 - Company Sanitized. Does noi contain TSCA CBI