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FOR DU PONT USE ONLY AR226-2947 Ou Font (HR 127*90 ' r'.-i Eye Irrititi .H : In Rabbits Autftpr Delores ! M alet On March 2 2 , 1990 prforninfi Laboratory E . I . du Porit de Nemours and Company, In c . H askell Laboratory fo r Toxicology and in d u stria l Medicine Elkton Road, P . 0 . Box SO Newark, Delaware 19714 Laboratory P ro je ct 10 Haskell Laboratory Report No. 127-90 Page 1 of 11 Company Sanitized. Does not contain TSCA CBI !GENERAL INFORMATION Ou Pont HLR 127-90 M aterial Tested: Medical Research Mo.; Haskell No.: H askell Test Code H o.: P hysical Form: P u rl5^: C om position: Synonym: S ta b ility : Sponsor: M aterial Submitted By: Study In itia te d - Completed: In -L1 fe Phase In itia te d - Completed: Notebook: There are 11 pages 1n th is D istrib u tio n : 18.267 The te s t m aterial was assumed to be stab le under the co nd itio ns o f ad m in istratio n . Chem icals and Pigments Department E . I . du Pont de Nemours and Company. In c . W ilm ington, Delaware Chem icals and Pigments Department E . I . du Pont de Nemours and Company, In c . Jackson Laboratory Deeowater. New Je rse y 2/15/90 - 3/22/90 2/21/90 - 2/24/90 -2 Coffipany Sanitized. Does not contain TSCACBl Eye Ir r ita tio n Test w ith] Du Pont HLR 127-90 Rabbits SUHHARY evaluated fo r acute eye Ir r it a t io n p o te n tia l In 2 ra b b its . The e y e ^ n & e ra b b its were evaluated on the day o f treatm ent and on days 1 . 2, and 3 follow ing treatm ent. The te st m aterial produced no Ir r it a t io n In the tre a te d washed o r unwashed eyes throughout: the study. F lu o re sc e d sta in examinatlo n s were negative fo r corneal In ju ry 1n both treated eyes throughout the stu d y. Lid e r the cond itions o f th is stu d y,] was not an eye ir r it a n t . "orkby! ttfitfrH. Haim T e c h n ic ia n Study D ire c to r: Dolores E . Maleic, Ph.D. , Research T o xico lo g ist Acute and Developmental Toxicology D iv isio n Reviewed and Approved fo r Issu e : 3 //*?> PO T Study D ire cto r Acknowledgment: C raig Lightcarp also p a rticip ated In the conduct o f th is stu d y . DEM:a lr : HLR131.7 - 3Company Sanitized. Does not contain TSC A CBl STUDY: Du Pont HI 127-90 QUALITY ASSURANCE d o c u m e n t a t i o n I i Bye Irritation Test with in Rabbits AUDITS: Item Audited Audit Date In-life Observation: Evaluation of Eye Irritation 2/22/90 Protocol Evaluation 2/22/90 Study Records and Final Report HLR 127-90 3/8,12/90 SHORT-TERM AUDIT REPORT lllUMBER: I DATE FINDINGS REPORTED TO MANAGE! ID STUDY DIRECTOR: 3/12/90 Reported by: ` ----Deborah A. Vick Quality Assurance Auditor Date - 4- Company Sanitized. Does no? contain TSC A CBI Du Pont HIR 127-90 The purpose o f t h is study was; to e vflu a te the aeute eye frotation p o tential o f oacfconordncinomg pt1o1anthcee aaprepfd1f$o1^Cit-MJf |iifn;|cptsbprAdaWwwiinowdt.Th.eUtshwttua'd. yfitJt,ryes'--c-JPo rrdJa2cs*,t. ic eNoRdeegvuilaattiioonnss. e xAisrteeads th at s ig n ific a n tly affected the v a lid it y o f the stud y. MATERIALS AMD METHODS A . Animal Husbandry Young sd u lt fM leH ew Zoolond White re b b lts r e received fro Here Marl and Hew itt Mew je rs e y . The ra b b its were housed sin g ly in sespendedlTteleless s 1 .1* w1rw s h ceges. Eech rb M t s unique id e n tific a tio n lumber which was recorded o n a c a rd to the caae. P urina C e rtifie d High F ib e r Rabbit Chow* #5325 and w ater were a v a ila b le ad llb ttu m . Rabbits were quarantined, weighed and observed fo r reneral h ealth fo r "approx1mately 2 weeks. Animal rooms were m aintained ot a tim e r-co n tro lle d ,jlZ -h o u r llg h tA Z -h o u r dorfc c^ l e . E w 1 ro n n ta l conditions o f the r o o n i r e targeted for e tw peratur. rela tiv e hum idity o f 50* + 10*. Excursions outside th ese ranges were Judged to have been o flin s u ffic le n t magnitude and/or duration to have adversely a ffe cte d th e ;v a lid ity o f the study. B. Protocol On the day p rio r to study In it ia t io n , the eyes o f 2 female New Zealand White ra b b its were examined using as they and flu o re sce in dye. These anim als were selected fo r th is study as tney showed no evidence o f p re e x is tin g c r neal r co n ju n ctiva l in jiu ry o ir r it a t io n and were judged to be in good h e a lth . The ra b b its were S t a t e l y " . k s ' i ld and weighed 2918 and 2722 grams, re sp e c tiv e ly . on the day o f treatm ent. . Approxim ately 0.01 co n ju n ctival sac o f ea The le f t eye o f each r served as a c o n tro l, unwashed. Approximate mL o f f l H B i w a s Introduced in to the lower :h rig h t eye o f 2 female New Zealand White ra b b its ib b it was not treated w ith the te s t m aterial and The treated and control eyes o f 1 animal remained ly 20 seconds a fte r the te s t m aterial was , adm inistered, both eye ^ o f the remaining ra b b it were rin sed fo r approxim ately 1 minute w ith water a t room tem perature. -5- Company Sanitized. Does not containTSCA CB1 Du Pont HLR 127-90 Each ra b b it was observed fo r approxim ately 30 to 60 seconds before being returned to t t s edge and any abnormal behavior was noted. Approximately 1 and 4 hours, and 1 , 2 , and 3 days adm inistered, the rab b its were examined fo r evidence o f eye Ir r it a t io n . At each of these observation p erio d s, eyes were exam ined sing Illu m in a tio n and m agnification and scored fo r o cu lar TM Dralze sca le (presented 1n Table 1 ). Eyes were. * J s i!Jr I J dth2r * ny unusual responses to treatment such as pannus, b lis te rin g of tne co n ju n ctiva , u lceratio n or other e ffe c ts In d ic a tiv e o f eorroslw e a c tio n . Blom icroscoplc and flu o rescein sta in exam inations were a lso conducted a t post-treatm ent days 1 , 2 , and 3 . The eyes were scored according to the method o fc la s s lflc a t io r t presented in Table 2 .... Control eyes were not scored. These untreated eyes were used fo r comparison and were considered "normal" re la tiv e to the treated eye. C . Records Retention A ll raw data and the fin a l report w ill be stored in the arch ive s o f Haskell Laboratory fo r Toxicology and In d u stria l E: k Jco rd s de Nemours and Company, In c ., Newark, Delaware o r In the Du Pont Records Management Center, Wilmington, Delaware. RESULTS f lB M lp r o d u c e d no Ir r it a t io n 1n e ith e r the washed or unwashed eves throughout the study. Fluorescein sta in exam inations were negative fo r corneal In ju ry and blom icroscoplc e x a m f f o n s ^ J J a t io n scores are both treated eyes throughout the study. In d ivid u al eye Ir r it a t io n scores are presented in Tables 3 and 4 . CONCLUSION Under the conditions of th is study, was not an eye ir r it a n t . - 6Company Sanitized. Does not contain TSCA CBI Du Pont HLR 127-90 ' TABLE 1 PRAIZE* qCALE F0R SCORING OCULAR LESIONS * 4` (1 ) *y_degree o f density (area most dense taken fo r reading) .................... , Scattered^or d l f f i s i art.' d e t a il o f ' l r l j ^ EasITy d isce rn ib le translucent are as, d e ta ils o f i r i s s lig h tly obscured . . ; * * * Opalescent areas, no d eta ils o f I r is v is ib le , s iz e o f pupil barely d isce rn ib le .............................. Opaque, I r i s In v is ib le .................................................. 1 (S lig h t) 2 (MUd) 3 (Moderate) 4 (Severe) (B) Area o f cornea involved 1 (Lo calized ) One q u arter (o r le s s ) but not zero * * ' , ; * ' * G reater than one q u arter, but le s s than h a lf . 2 (Sm all) G reater than one h a lf, but le s s than three ^ ^ ^ 3 (Moderate) G re a te r'th a n ' three *q u arters, up to whole area . . 4 (Generalized) (2) Iris (A) Values NFooirmdsal above *normal, congestion, sw e llin g , clrcum - 0 corneal In je c tio n (any or a ll o f these combination o f any th ereo f) I r i s J ^ a c t 9 1 (Moderate) to lig h t (slu g g ish reaction Is P s**1ve) * * * No re a ctio n to lig h t , hemorrhage, gross d estru ctio n (any or a ll o f th ese) .............................. 2 (Severe) (5 ) m ^ S e d il (re fe rs to palpebral and bu lb ar co n ju nctiva excluding cornea and I r i s ) V essels n o rm a l.............................. * * * . * ..................... V essels d e fin ite ly In jected above " } * * * More d iffu s e , deeper crimson re d , In d ivid u al v e s se ls not e a s ily d isc e rn ib le ................................... D iffu se beefy red ........................................................................... 1 (M ild) 2 (Moderate) 3 (Severe) - 7- Company Sanitized. Does not contain TSCA CBI %if Du Pont HLR 127-90 DRAME SKALE FOR LESIONS (B) Chemosls I No sw ellin g . . . . * , *: Any sw ellin g above normal (In clu d e s n ic tita tin g membrane) . . t ........................ V* > ............................ Obvious sw ellin g With p a rtia l eversion of lid s | ................................... ...................................... swelling with lid s about half c lo s e d ................. Sw elling w ith lid $ about h a lf closed to com pletely c lo s e d ........................................ 0 1 (S lig h t) 2 (M ild) 3 (Moderate) 4 (Severe) (C) Discharge No discharge . . J ................... ........................................... .... Any amount d iffe re n t from normal (does not include sm all amounts observed In Inner canthus o f normal a n im a ls)!............................. .... ....................................... Discharge w ith moistening o f the lid s and h a irs ju s t adjacent to lid s . . . . . . . . . . . . . Discharge w ith moistening o f the lid s and h a irs , and considerably area around the eye .................... 0 1 (M inim al) 2 (Moderate) 3 (Copious) 1 D raize, J . H ., "Dermal T o x ic ity ." Appraisal o f the S afe ty o f Chem ical! in Foods. Drugs and Cosm etics. The E d ito ria l Committee o f the A sso ciatio n o f Pood and Drug O ffic ia ls 'o f the United S ta te s, A u stin , Te xas, 1959, pp. 46-59. 8Company Sanitized. Does not contain TSCA CBI TABLE 2 Du Pont HLR 127-90 l|o in ju ry ; corne w ith in normal lim it s . S lig h t (1 ) - E p ith e lia l changes v ls lb le only wUh blOTlcroscope 9 (pay Include lo ca lize d area of m ild in ju r y ;. M ild (2 ) bpaclty v is ib le with ophthalmoscope or lig h t but showing e p ith e lia l changes only " 1** P p a y Include lo ca lize d area of moderate In ju r y ). Moderate (3 ) * dnad tv v is ib le w ith ophthalmoscope or lig h t but S K in g e p ith e lia l and%tromal changes w ith biomicroscope (may Include lo c a lize d area of Jevere In ju ry ). Moderate to Severe (4) (toadtv v is ib le w ith ophthalmoscope o r lig h t but e o lth e lla l and stromal changes and endothelial relucency w ith unremarkable Th is type o f In ju ry shows evidence of healing (re v e rsib le damage) w ith in 14 days. Severe (5 ) - e i 1t h ll 1a l ' , ng [ r Show evidence o f healing (permanent damage) w ith in 1A Have. . = No biomicroscope evaluation performed. - 9- Company Sanitized. Does not contain TSCA CB l I II I Du Pont HLR 127-90 i TABLE 3 EYE IRRITATICI REACTIONS OBSERVED IJJ UNWASHED RABBIT EYE AFTER TREATMENT WI~ Cornea O p acity Area Ir is C o n ju n c tiv a Redness Chemosis Discharge Blomlc o f Cornea 0 0 0 00 0 00 0 0 00 0 0 0 0 00 0 00 0 00 00 Flu o rescein exam inations: Negative fo r corneal in ju ry 0 0 0 0 0 0 0 - 10 Company Sanitized. Does not contain T S C A CB! TABLEA EYE IRRITIflON REACTIONS 0] WASHED RABBIT EYE AFTER TR Du Pont HLR 127*90 IN THE Rabbit Humbe* 24590 Cornea O p acity Area Ir is C o n ju n c tiv a Redness Chemosis Discharge Biomic o f Cornea " ----- 1------ j ------ 1 1i '-- I-- -- 2----- ---- 3--------- Hour Hours Day ....m i _______ j0 0 0 0 0 _ u 00 u 0 0 0 00 0 0 0 0 0 0 0 __ uu 00 00 ,, u 0 0 - 00 0 Flu o rescein exam inations: Negative fo r corneal in ju ry 11 ->mpany Sanitized. Does noi conialo T S C A CB1