Document Ex8NBeM7dqayym94wMV369QbL

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 Perfuming Laboratory Haskell E. I. du Pont de Ncmours and Company, Inc. 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 CBf 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; Sponsor: Material Submitted By; In-Life Phase Initiated - Completed: Notebook; There are 9 pages 1n this report Distribution: The test material was assumed to be stable under the conditions of administration. Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Wilmington, Delaware Inc. chemicals and Pigments Department E, !, d" Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. 11/16/88 - 11/19/88 ''\ - 2 - Company Sanitized. Does not contain TSCA C ;; Du Pont HLR 784-88 Eye Irritation Test In Rabbits of SUMMARY ___ was _________ evalu_a_te_d for acute eye Irritation pote_nt_ia_l _in__2_male rabbits, f gESlllXBBHBBBBBBfBpBBced no irritation in either the washed or uwaslred'ralrtilt--eye." ^l^rffSTcein^staln'anabTomlcroscopTc^^imTnafl negative for corneal Injury in bothtreatedeYe^hroughoutthestudy. Under eye irritant. Work by: Study Director; Carol'nnlTayn T--ec--h1n.i-cJi-aJn,- U IZ/'L/^ Reviewed and Approved for Issue: yjB:a1r:HLR!Q9.10 3 - Company Sanitized. Does not contain TSCA CBS Du Font HLR 784-88 QUALITY ASSURANCE DOCUMENTATION STUDY: 1--------^9 H# 17,503 Eye Irritation Test in Rabbits of AUDITS; Item Audited Records and final report Audit Date 12/12,19-21/88 1^9^ SHORT-TERM AUDIT REPORT NUMBER: DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR; 12-21-88 Reported by: ^^c^L, ^fiSp^ U. Stephen V. Records Quality Assurance Auditor '^-3^-ftfe Date 4 - - company Sanitized. Does not contain TSCA (.": INTRODUCTION Du Pont HLR 784-88 __iBBHBHBIIH^BHfe. jurpose of this study was to evaluate the eye irritation potential This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of noncompilance 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. The 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 libltum. Rabbits were quarantined, weighed and observed for .general health for approximately 2 weeks. Animal rooms were maintained on a timer-controned, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C ^_ 2C and relative humidity of 501 ^ 10%. 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 conjunctiva! injury or irritation were not used in this study. The rabbits weighed 3029 and 3405 grams on the day of treatment. introduced into the lower conjunctiva! 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 treatments the rabbits were examined for evidence of eye irritation. Company 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 Draizs scale (presented In 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, ulceratlon or other effects Indicative of corrosive action were also noted. Fluorescein dye was used to evaluate corneal ulceratlon and Irritation starting at the 1-day observation and at each subsequent observation. B1om1croscop1c 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, WHmington, Delaware. RESULTS AND CONCLUSIONS treated rabbit eye. negative for corneal Under the conditions not an eye irritant. ^produced no irritation in either _ Fluorescein stain and biomlcroscopic examinations were injury in both _treated_gYes_throu5hout the study. Uidffipdny Sanitized. Does not contain TSCA C8S Du Pont HLR 784-88 TABLE I DRAIZE1SCALE FOR SCORING OCULARLESIONS (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, 1r1s invisible ..................... (B) Area of cornea involved 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) One quarter (or less) but not zero Greater than one quarter, but less than half . . . . . ...... Greater than one half, but less than three quarters Greater than three quarters, up to whole area . . ............. ...... Score equals A x B x 5 Total Maximum = 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) 80 (2)" Iris (A) Values ...................... Normal Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction Is positive) . . . No reaction to light, hemorrhage, gross destruction (any or all of these) ....... Score equals A x 5 Total Maximum = 0 1 (Moderate) 2 (Severe) 10 (3) Conjunctiva (A) Redness (refers to paTpebral and bulbar conjunctiva excluding cornea and 1r1s) Vessels normal . . o vessels definitely injected above . . . . . . . . . . . . . . . More diffuse, deeper crimson red, . . . . . vessels not easily discernible ........................ Diffuse beefy red normal individual 0 1 (Mild) 2 (Moderate) 3 (Severe) impany Sanitized. Does not contain TSCA CBt 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 ................... lids Swelling with lids about half ..................... Swelling with lids about half . . . . . . . dosed evepsion of closed closed to completely .................... (C) Discharge ................... No discharge Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) Discharge with moistening of the lids and hairs ................ just adjacent to lids Discharge with moistening of the tids and hairs, . . . . . . . . . . . . . and considerable area around the eye . . . . . Score equals (A + B + C) x 2 Total Maximum = 1 (Slight) 2 (M11d) 3 (Moderate) 4 (Severe) 1 (Minimal) 2 (Moderate) 3 (Copious) 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- "^"""""-----------.inTSCACB Ou Pont HLR 784-88 TABLE II BIOMICROSCOPECLASSIFICATIONS OF CORNEAL INJURY (Blomic of Cornea) 0 No Injury; cornea within normal limits. Slight (1) = Epithelial changes visible only with biomlcroscope (may Include localized area of mild Injury). Mild (2) K Opacity visible with ophthalmoscope or light but Showing epithelial changes only with blomicroscope (may include localized area of moderate injury). Moderate (3) " Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes with blomicroscope (may include localized area of severe injury). Moderate to Severe (4) Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes and endothellal 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 endothe1ia1 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. Company Sanitized. Does not contain TSCA C8B