Document MrGwmnJ3Xk5mx89YgjqKrbe9

FOR DU PONT USE ONLY AR226-2937 Du Pont HLR 784-88 . Study Title Eye Irritation Test In Rabbits of Author William J. Brock Study Completed On December 28, 1988 Performing Laboratory E. I. du Pont de Nemours and Company, Inc. iaskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark. Delaware 19714 Laboratory Project ID Haskell Laboratory Report No. 784-88 # Page 1 of 9 Company Sanitized. Does not contain TSCA CBS Material Tested: Medical Research No.: Haskell No.: Physical Form: Purity: Contaminants: GENERAL INFORMATION 17,503 White powder Du Pont HLR 784-88 Synonyms: Submitter's Notebook No.: Stability: The test material was assumed to be stable under the conditions of administration. Sponsor: Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Inc. Wilmington, Delaware Material Submitted By: Chemicals and Pigments Department E s I. du Pont de Nemours and Company, Inc. Jackson Laboratory Deepwater, New Jersey - In-Life Phase Initiated - Completed: 11/16/88 - 11/19/88 Notebook : There are 9 pages in this report. Distribution: 2- Company Sanitized, Does noi contain TSCA C v,` % Du Pont HLR 784-88 Eye Irritation Test 1n Rabbits of SUMMARY _____ ________________ _______ _ was evaluated for acute eye Irritation potential in 2 male rabbits. O d M S B B H B B S B B S H f f P B B c e d no Irritation in either the washed or unwashedrabblt eye. Flu^rescein staln and biomlcroscdp^ic exaininations were negative for corneal Injury in b o t h t r e a t e d e y e ^ h r o u g h o u t t h ^ t u d y . Under the conditions of this study, was not an eye Irritant. Work by: ri,iin Technician u Study Director: OJSMu U li. tst M1111'am^iT' Brock, Ph.D. Research Toxicologist Acute and Developmental Toxicology Division Reviewed and Approved for Issue: !2l2Sl WJB:alr:HLR109.10 \ P 3Company Sanitized. Does not contain TSCA CBI Du Pont BLR 704-88 QUALITY ASSURANCE DOCUMENTATION STUDY: H# 17,503 Eye Irritation Test in Rabbits of AUDITS: Item Audited Records and final report Audit Date 12/12,19-21/88 SHORT-TERM AUDIT REPORT NUMBER: ___ DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR: 12- 21-88 Reported by: Quality Assurance Auditor Date -4Company Sanitized. Does not contain TSCA C. Du Pont HLR 784-88 INTRODUCTION - ........ " iluate the eye irritation potential This study was conducted according actlce Regulations. Areas of noncompliance are documented in the study records. No deviations existed that significantly affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male New Zealand White rabbits were received from Hare Marland, Hewitt, New Jersey. Yhe rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which was recorded on a card affixed to the cage. Purina Certified High Fiber Rabbit Chow* #5325 and water were available ad libitum. Rabbits were quarantined, weighed and observed for general health for approximately 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C + 2C and relative humidity of 5 0 * ^ 1 0 * . Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day before study initiation, the eyes of 2 male New Zealand White rabbits were examined using fluorescein dye. Animals showing preexisting corneal or conjunctival injury or irritation were not used in this study. The rabbits weighed 3029 and 3405 grams on the day of treatment. A 0.01 g aliquot of was introduced into the lower conjunctival sac of the right eyes of 2 male New Zealand White rabbits. The left eyes served as controls. The treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the test material was administered, both eyes of the remaining animal were rinsed for 1 minute with lukewarm tap water. Approximately 1 and 4 hours and 1, 2 and 3 days after treatment, the rabbits were examined for evidence of eye irritation. -5Company Sanitized. Does not contain TSCA CB1 Du Pont HLR 784-88 At each observation the treated eyes were examined using Illumination and magnification and scored for ocular reactions using the Dralze scale (presented 1n Table I). The untreated eye of each animal was also examined and used for comparison. Any unusual effects, e.g., pannus, blistering of the conjunctiva, ulceration or other effects Indicative of corrosive action were also noted. Fluorescein dye was used to evaluate corneal ulceration and Irritation starting at the 1-day observation and at each subsequent observation. B1om1oroscopie examinations for corneal injury were conducted at the 1-day observation and each subsequent observation. Treated eyes were scored according to the system presented in Table II. C. Records Retention All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Inc., Newark, Delaware or in the Du Pont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS __ produced no irritation in either treated rabbit eye. Fluorescein stain and blomlcroscopic examinations were negative for corneal injury 1n both t r e a t e ^ e v e ^ t h r o u g h o u t t h ^ s t u d j ^ ^ Under the conditions of this study, was not an eye irritant. -6uompany Sanitized. Does not contain T SC A C B i Du Pont HLR 784-88 TABLE I DRAIZE1 SCALE FOR SCORING OCULAR LESIONS (1) Cornea (A) Opacity-degree of density (area most dense taken for reading) No opacity ..................................... Scattered or diffuse area, details of 1r1s clearly visible..................... Easily discernible translucent areas, details of Iris slightly obscured . . . . . .......... Opalescent areas, no details of 1r1s visible, size of pupil barely discernible . . . . . . Opaque, Iris invisible ........ . ............ 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) (B) Area of cornea involved One quarter (or less) but not z e r o .............. Greater than one quarter, but less than half . . . 1 (Localized) (Small) Greater than one half, but less than three quarters ...................................... Greater than three quarters, up to whole area . . 3 (Moderate) 4 (Generalized) Score equals A x B x 5 Total Maximum = 80 2( )" Iris (A) Values Normal ........................... : Folds above normal, congestion, swelling, circum- 0 corneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) . . . 1 (Moderate) No reaction to light, hemorrhage, gross w destruction (any or all of these) (Severe) Score equals A x 5 Total Maximum = 10 (3) Conjunctiva .. (A) Redness (refers to paTpebral and bulbar conjunctiva excluding cornea and iris) Vessels normal .............. . . . . . ........ Vessels definitely injected above normal ........ 0 1 (Mild) More diffuse, deeper crimson red, individual vessels not easily discernible .............. Diffuse beefy red ............................... 2 (Moderate) 3 (Severe) -7'impany Sanitized. Does not contain TSCA CBf Du Pont HLR 784-88 TABLE I (Cont'd) DRAIZE SCALE FOR SCORING OCULAR LESIONS (B) Chemosis No swelling ............................ Any swelling above normal (Includes nictitating membrane) . . . . ................... .. Obvious swelling with partial eversion of .............................................. Swelling with H d s about half c l o s e d ............ Swelling with H d s about half closed to completely closed ...................................... 0 1 (Slight) 2 (Mild) 3 (Moderate) * (Severe) (C) Discharge No discharge................. 0 Any amount different from normal (does not Include small amounts observed 1n Inner canthus of normal animals) .............................. 1 (Minimal) Discharge with moistening of the lids and hairs just adjacent to lids . . . . . ............... 2 (Moderate) Discharge with moistening of the H d s and hairs, and considerable area around the e y e ........ 3 (Copious) Score equals (A + B + C) x 2 Total Maximum = 20 The maximum total score is the sum of all scores obtained for the cornea, iris and conjunctiva. Total maximum score possible = 110. ^ Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial Committee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. . - -8 pany Sanitized. Does not contain T S C A C B I Du Pont HLR 784-88 TABLE II BIOMICROSCOPE CLASSIFICATIONS OF CORNEAL INJURY (B1om1c of Cornea) 0 * No Injury; cornea within normal limits. Slight (1) = Epithelial changes visible only with biomicroscope (may include localized area of mild Injury). Mild (2) - Opacity visible with ophthalmoscope or light but Showing epithelial changes only with biomicroscope (may Include localized area of moderate injury). Moderate (3) =* Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes with biomicroscope (may Include localized area of severe Injury). Moderate to Severe (4) = Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes and endothelial relucency with unremarkable swelling. This type of Injury shows evidence of healing (reversible damage) within 14 days. Severe (5) > Opaqueness or opacity visible with ophthalmoscope or light but showing epithelial and stromal changes and endothelial relucency and swelling or other distortion. This type of injury does not show evidence of healing (permanent damage) within 14 days. No biomicroscope evaluation performed. -9Company Sanitized. Does not contain TSCA CBS