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AR226-2956 FOR DU POUT USE ONLY Du Pont HLR 214-91 Study T itle Eye Ir r it a t io n Test with in Rabbits Author John W. Server Study Completed On A p ril 26, 1991 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and In d u stria l Medicine Elkton Road, P. 0. Bex 50 Newark, Delaware 19714 . Laboratory Project ID Haskell Laboratory Report No. 214-91 Cpmpany Sanitized. Does not contain T SC A CBl Page 1 of 12 # SPHERAL FORMATION Du Pont HLR 214-91 Material Tested: Medical Research Ho.; Haskell Ho.: Haskell Test Code Ho.: Physical Porn; P u rit y : Composition: 18,790 M ilky-w hite *iquid Contaminants: Synonyms: Other Codes: S ta b ility : Sponsor: Material Submitted By: Study In itia te d - completed: In - L if e Phase In itia te d - Completed: Notebook : In the absence o f v is ib le evidence to the contrary, the te st material was assumed to be stable under the conditions of Du Pont Chemicals E. I . du Pont de Nemours and Company Wilmington, Delaware Du Pont Chemicals E. I. du Pont de Nemours and Company technical Lb, Chambers Works DeeDwater, New Jersey 2/8/91 - 4/26/91 3/5/91 - 3/8/91 2- - Sanitized. Dees noi contain TSCA B Du Pont HLR 214-91 GEMER. INFORMATION (COHT'D) There are 12 pages In th is report. D istrib u tio n : - 3- ed. Does no! contain t s c a c i , Eye Ir r it a t io n Test with Du Pont HLR 214-91 in Rabbits SUMMARY evaluated for acute eye ir r it a t io n potential in 2 rab b its. The eyes of the rabbits were examined on the day of treatment and on days 1. 2, and 3 follow ing treatment. The te st material produced m ild conjunctival redness in the unwashed rabbit eye. No Ir r it a t io n was observed in the eye washed a fte r treatment. Fluorescein sta in examinations were negative fo r corneal in ju ry, and biomioroscopie examinations revealed no corneal damage In e ith e r treated eye. The unwashed eye was normal by 4 hours afte r treatment. Under the conditions o f th is study, was a tran sie n t, mild eye ir r it a n t . Work by: Study Director: 7TL qaxt* - Jfc- M Carol Finlay Technician . 5, ohn W. Sarver Technologist Approved by: M 1- - NSntyD . Cnroiney, Pn.Dt) Manager Acute Toxicology Reviewed and ( \ fi Approved fo r Issue: ^ \ C UJ. ________ H / G ./ 'll John W. Sarver Study Director Acknowledgment: Bryan W. Crossley also participated in the conduct of t h is study. JW S:sfl:HLRf 146.4) - 4tCi>mpanj>SanF!7zotT. D o s s n o l contal,, T S C fl ^ Du Pont BLR 214-91 QUALITY ASSURANCE DOCUMENTATION STUDY: H# 18,790 Eye Irritation Test with n Rabbits AUDITS: Item Audited Conduct Protocol, Records, Report Audit Date 3/7/91 4/16,17/91 SHORT-TERM AUDIT REPORT NUMBER DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR: 4/17/91 Reported by: PY~V ju^'/yx . ' Melissa R. Moote Quality Assurance Auditor 4- < Date -5 K p ln p aty San itized . Does no! contain T Du Pont HLR 214-91 INTRODUCTION The p u r p o s ^ o ^ h is study was to evaluate the acute eye ir rig a tio n potential in young adult rabbits. This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of nonconpliance are documented in the study records. No deviations existed that s ig n ific a n tly affected the v a lid it y or' the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male New Zealand White rabbits were received from Hare Marland, Hewitt, New Jersey. The rabbits were housed sin g ly in suspended, s ta in le ss ste e l, wire-mesh cages. Each rabbit was assigned a unique id e n tific a tio n number which was recorded on a card affixed to the cage. Purina C e rtifie d High Fiber Rabbit Chow #5325 and water were a vailab le ad lib itu m . Rabbits were quarantined, weighed and observed for general health fo r approximately 2 weeks. Animal rooms were maintained on a tim er-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted fo r a temperature of 20C + 2C and re la tiv e humidity of 5 0 X ^ 1 0 % . Excursions outside these ranges were judged to have been of in su ffic ie n t magnitude and/or duration to have adversely affected the v a lid it y o f the study. B. Protocol On the day of treatment, the eyes of 2 male New Zealand White rabbits were examined u sing illum ination, m agnification and fluorescein dye. These animals were selected for th is study as they showed no evidence of p re -e xistin g corneal or conjunctival in ju ry or ir r it a t io n and were judged to be in good health. These rab b its weighed 3028 and 2879 grams, respectively, on the day of treatment. Approximately 0.01 mL f f l H | j ^ B B was introduced into the lower conjunctival sac o f each ra b b it 's rig h t eye. The le f t eye of each rabbit was not treated with the test material and served as a control. The treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the te s t material was administered, both eyes of the remaining rabbit were rinsed fo r approximately 1 minute with room temperature water. Each rabbit was observed for approximately 30 to 60 seconds before being returned to i t s cage and any abnormal behavior was noted. 6 - Sanitized. Does noi contain TSCA c m Du Pont HLR 214-91 Approximately 1 and 4 hours, and 1, 2, and 3 days after was administered, the rabbits were examined fo r evidence of eye ir r it a t io n . A t each o f these observation periods, eyes were examined u sing illu m in atio n and magnification and scored fo r ocular reactions using the Draize scale {Table 1 ). Eyes were also observed for any unusual responses to treatment such as pannus, b lis t e rin g of the conjunctiva, ulceration or other effects indicative of corrosive action. Biomicroscopic and fluorescein sta in examinations were also conducted at post-treatment days 1, 2, and 3. The eyes were scored according to the method of c la s s if ic a t io n presented in Table 2. Control eyes were not scored. These untreated eyes were used fo r comparison and were considered "normal" re lative to the treated eye. C. Records, Retention A ll raw data and the final report w ill be stored in the archives of Haskell Laboratory fo r Toxicology and In d u stria l Medicine, E. I. du Pont de Nemours and Company, Newark, Delaware or in the Du Pont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS _______ produced mild conjunctival redness in the unwashed ra b b it eye. No ir r it a t i o n was observed in the eye washed afte r treatment. Fluorescein sta in examinations were negative fo r corneal in ju ry, and biom icroscopic examinations revealed no corneal damage in either treated eye. The unwashed eye was normal by 4 hours a fte r treatment. Individual eye ir r it a t io n scores are presented in Tables 3 and 4. Under the con d itio ns of th is study,) ir rit a n t. was a tran sie n t, m ild eye - 7- : contain TSCACB* K*:Sariv -.{feed. 'Poes 0 # Du Pont HLR 214-91 TABLE 1 DRAIZE1 SCALE FOR SCORING OCULAR LESIONS (1) Cornea (A) Opacity-degree of density (area most dense taken for reading) No o p a c i t y ........................................................ Scattered or diffuse area, d etails of i r i s c le a rly v is ib le ............................................ Easily discernible translucent areas, details of i r i s sl ig h tly o b s c u r e d ................................ Opalescent areas, no d e ta ils o f i r i s v is ib le , siz e of pupil barely d isce rn ib le .................. Opaque, i r i s in v is ib le ....................................... 0 1 (Slight) 2 (Mfld) 3 (Moderate) 4 (Severe) (B) Area o f cornea involved One quarter (or le s s) but not z e r o ..................... Greater than one quarter, but le s s than h a lf . . . Greater than one h alf, but le s s than three quarters ....................................................... Greater than three quarters, up to whole area . . 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) Iris (A) Values Normal ...................................... ..................... Folds above normal, congestion, sw e llin g, circum- corneal in jectio n (any or a ll of these or combination of any thereof) i r i s s t i l l reacting to lig h t (sluggish reaction is positive) . . . No reaction to lig h t , nemorrhage, gross destruction (any or a ll o f these) .................. 0 1 (Moderate) 2 (Severe) (3) Conjunctiva (A) Redness (re fe rs to palpebral and bulbar conjunctiva excluding cornea and i r i s ) Vessels normal .................................................. 0 V essels d e fin ite ly injected above n o rm a l............ 1 (M ild) More d iffu se , deeper crimson red, in d ivid u al v e sse ls not e a s ily d isce rn ib le ..................... 2 (Moderate) D iffu se beefy red ............................................ 3 (Severe) 8- - Com pany Sanitized. Does not contain T SC A CBt Du Pont HLR 214-91 TABLE 1 (Cont'd) DRAIZE SCALE FOR SCORINE OCULAR LESIONS (B) Cheoosis No s w e l l i n g .................................................... Any sw elling above normal (includes n ic tita tin g membrane).................................................... Obvious sw elling with p artial eversion of l i d s .......................................................... Sw elling with li d s about h a lf closed .................. Sweljjng__with lid s about h a lf closed to completely c l o s e d ............................ 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Sevre) (C) Discharge No d is c h a r g e ..................................................... Any amount d iffe re n t from normal (does not include small amounts observed in inner canthus of normal a n im a ls ) ............................................ Discharge with moistening o f the li d s and h a irs ju s t adjacent to lid s ................................... Discharge with moistening o f the l i d s and h a irs, and considerable area around the eye ............ 0 l (Minimal) 2 (Moderate) 3 (Copious) Draize, J. H., "Dermal T o x ic ity ." Appraisal o f the Safety of Chemicals in Foods, Drugs and Cosmetics. The E d ito ria l Committee of the Association of food and Drug O f f ic ia ls of the United States, Austin, Texas, 1959, pp. 46-59. Ou Pont HLR 214-91 TABLE 2 BIOMICROSCOPE CLASSIFICATIONS OF CORNEAL INJURY O = No In ju ry; cornea within normal lim it s. S lig h t (1) - Epithelial changes v isib le only with biomicroscope (may include localize d area of mild in ju ry ). M ild (2) = Opacity v is ib le with ophthalmoscope or lig h t but showing e p ith e lia l changes only with biomicroscope (may include lo c a liz e d area of moderate in ju ry ). Moderate (3) = Opacity v is ib le with ophthalmoscope or lig h t but showing e p ith e lia l and stromal changes with biomicroscope (may include localized area o f severe in ju ry). Moderate to Severe (4) = Opacity v is ib le with ophthalmoscope or li g h t but showing e p ith e lia l and stromal changes and endothelial relucency with unremarkable sw e llin g. T his type o f in ju ry shows evidence of healing (re ve rsib le damage) w ithin 14 days. Severe (5) = Opaqueness or opacity v is ib le with ophthalmoscope or lig h t but showing e p ith e lia l and stromal changes and endothelial relucency and sw e llin g or other d isto rtio n . This type o f injury does not show evidence of healing (permanent damage) w ithin 14 days. = No biomicroscope evaluation performed. - 10 C o m p a n y S a n W * a . O w V ,''a',' ' r S C ' Du Pont HLR 214-91 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE 'UNWASHED RABBIT EYE AFTER TREATMENT WITH Rabbit Number 25879 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Biomicroscopic Examination of Cornea *1 -------------3 Il Hour Hours Day Pays 0 OOO 0 0 00 0 0 00 T~ Pays 0 0 0 1 0 ooo 0 0 00 0 0 0 ooo - -0 Fluorescein examinations: Negative for corneal in ju ry at a ll observation . periods. ! Du Pont HLR 214-91 TABLE 4 EYE IRRITATION REACTIONS OBSERVED IB THE HASHED RABBIT EYE AFTER TREATMENT WITH Rabbit Number 25875 ---------- I -------------y -- Hour Hours Cornea Opaci ty Area 00 00 Iris 0 0 Conjunctiva Redness Chemosis Di scharge 00 00 00 Biomicroscopic Examination of Cornea 1' -- 1------ -----3---------Day Days Days 00 00 00 0 0 0 00 00 00 U 0 0 00 u Fluorescein examinations: Negative for corneal injury at a ll observation periods. i - 12 - ^nipanjr SanifizecJ. Does o! contain t$ca