Document oeL3r95KDDMaQy022Zg475Q6w

AR226-2956 FOR Oil POUT USE ONLY Du Pont HLR 214-91 Study Title Eye Irritation Test with^^^^ln Rabbits Author John W. Server Study Completed On April 26, 1991 Performing Laboratory Haskell E. I. du Pont de Nemours and Company Laboratory for Toxicology and Industrial Elk ton Road, P. 0. Bex 50 Newark, Delaware 19714 Medicine Laboratory Project ID Haskell Laboratory Report No. 214-91 Company Sanitized. Does not contain TSCA CBI Page 1 of 12 ) Material Tested: Medical Research No.: Haskell Ho.: Haskell Test Code No. Physical Form; Purity: Composition: GENERAL INFORMATION Du Pont HLR 214-91 18,790 Milky-white liquid Contaminants: Synonyms: Other Codes: Stability: Material Submitted By: Study initiated - uompleted: In-Life Phase Initiated - Completed: Notebook: In the absence of visible evidence to the contrary, the test material was assumed to be stable under the conditions of administration. Du Pont Chemicals E. I. <lu Pont de Nemours and Company Milroington, Del ware Du Pont Chemicals E. I. du Pont de Nemours and Company technical Lab, Chambers Works Deepwater, New Jersey 2/8/91 - 4/26/91 3/5/91 - 3/8/91 -- SO_a^H^.Sanltu-a'd. Dees not contain TSCA -w, - 2 Du Pont HLR 214-91 GENERALINFORMATION (CONT'D) There are 12 pages In this report. Distribution: h - 3 - ^^^C^^ Du Font HLR 214-91 Eye Irritation Test withj^^^^B in Rabbits SUMMARY fl^Bkwas evaluated for acute eye Irritation potential in 2 rabbits.The eyes of the rabbits were examined on the day of treatment and on days 1, 2. and 3 following treatment. The test material produced mild conjunctiva! redness in the unwashed rabbit eye. No irritation was observed in the eye washed after treatment. Fluorescein stain examinations were negative for cornea! injury, and bioiBicroscopic examinations revealed no cornea! damage in either treated eye. The unwashed eye was normal by 4 hours after treatment. Under the conditions of this study,fB----R was a transient, mild eye irritant. Work by: CaCvarTol^F-Jin^l.aHy^(\. T-e-c1-h--n"i-c-"ia~n- W Study Director: \^JJoh-n QftAAr-O^ W. Sarver Technologist Approved by: fj &^^ <\ Cj------h--DOr^ N&hcyC. Chromey, Ph. Manager Acute Toxicology Reviewed and Approved for Issue: ^ i^. ^GAArS^_____^ /otG./"T< John K. Sarver Study Director Acknowledgment: Bryan W. Crossley also participated in the conduct of this study. JWS;sfl:HLR(146.4) companSyanded. Does not contain TSCA CB Du Font HLR 214-91 QUALITT ASSURANCE DOCUHENTATIOK STUDT: H 18,790 Eye Irritation Test with] in Rabbits AUDITS: Item Audited Conduct Protocol, Records, Report Audit Pate 3/7/91 4/16,17/91 SHORT-TERM AUDIT REPORT NUKBEK:^^|9 DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR: 4/17/91 Reported by: fT), ^y^ <. (Y}r-r^ ' Melissa R. Hoore Quality Assurance Auditor H-^-QI Date 5 - - fePa/S.n,,^. noes no, ^ ^A CBI INTRODUCTION Du Pont HLR 214-91 The purpose of this study was to evaluate the acute eye irri-'-stion potential of^JHHH^ 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 significantly affected the validity 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 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 l?5325 and water were available ad libitum. Rabbits were quarantined, weighed and observed for general heaTth 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 ^ 2-C and relative humidity of 50% ^ 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 of treatment, the eyes of 2 male New Zealand White rabbits were examined using illumination, magnification and fluorescein dye. These animals were selected for this study as they showed no evidence of pre-existing corneal or conjunctival injury or Irritation and were judged to be in good health. These rabbits weighed 3028 and 2879 grams, respectively, on the day of treatment. Approximately 0.01 mL of----IBBB'*'85 introduced into the lower conjunctiva! sac of each rabbit's right eye. The left eye of each rabbit was not treated yith the test material and served as a control. The treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the test material was administered, both eyes of the remaining rabbit were rinsed for approximately 1 minute with room temperature rfater. Each rabbit was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior was noted. ^nip^Sanfflzed.DoesnolconlalnTSCAeW 6 . Du Font HLR 214-91 Approximately 1 and 4 hours, and 1, 2, and 3 days after 1 was administered, the rabbits were examined for evidence of eye irritation. At each of these observation periods, eyes were exanined using illumination and magnification and scored for ocular reactions using the Draize scale (Table 1). Eyes were also observed for any unusual responses to treatment such as pannus, blistering of the conjunctiva, ulceration or other effects indicative of corrosive action. Biomicroscopic and fluorescein stain examinations were also conducted at post-treatment days 1, 2, and 3. The eyes were scored according to the method of classification presented in Table 2. Control eyes were not scored. These untreated eyes were used for comparison and were considered "normal" relative to the treated eye. 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, Newark, Delaware or in the Du Pont Records Management Center, Wilmington, Delaware. RESULTS AMD CONCLUSIONS ^fBB^f produced mild conjunctival redness in the unwashed rabbit eye. No irritation was observed in the eye washed after treatment. Fluorescein stain examinations were negative for corneal injury, and biomicroscopic examinations revealed no cornea! damage in either treated eye. The unwashed eye was normal by 4 hours after treatment. irritation scores are presented in Tables 3 and 4. Individual eye UJJU| Under the conditions of this study, irritant. was a tr'a^s^'e^t, mild eye - 7 - y^^.^"-^'80"" JD 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) Mo opacity Scattered or diffuse area, details of iris .................... clearly visible Easily discernible translucent areas, details of . . . . . . . . . . . . . . . . trissTi-ghtTy-otscured Opalescent areas, no details of iris visible, . . . . . . . . . . . . size of pupil barely discernible Opaque, iris invisible ..................... (B) Area of cornea involved One quarter (or less) but not zero Greater than one quarter, but less than half . . . . . ...... Greater than one haK, but less than three quarters ............. ...... Greater than three quarters, up to whole area . . 0 1 (Slight) 2 (Mtid) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values Normal Folds above normal, cungesliun, swelling, circum- ...................... corneal injection (any or all of these or combination of any thereof) ins still reacting to light (sluggish reaction is positive) . . . No reaction to light, nemorrhage, gross . . . . . . . destruction (any or all of these) 0 1 (Moderate) 2 (Severe) (3) Conjunctiva (A) Redness (refers to palpebrai and bulbar conjunctiva excluding cornea and iris) Vessels normal Vessels definitely injected above .................. More diffuse, deeper crimson red, . . . . . vessels not easily discernible ........................ Diffuse beefy red normal individual 0 1 (Kild) 2 (Moderate) 3 (Severe) 8 .'FjDffipanSyanitized. Does not contain TSCAC^ - S) Du Pont HLR 214-91 TABLE 1 (Cont'd) DRAIZE SCALE FOR SCORING OCULAR LESIONS (B) Cherosis No swelling Any swelling above normal (Includes nictitating . . . . . . . . . . . . . . . . . . . membrane) Obvious swelling with partial everslon of ................... lids Swelling with lids about half closed ..................... SweT.Ltng.jfith lids about half closed to completely . . . . . . . closed .................... (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 ................ just adjacent to lids Discharge with moistening of the lids and .................. and considerable area around the eye hairs hairs, 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 1 (Minimal) 2 (Moderate) 3 (Copious) 1 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. 9 - ,^ T=-^--^-----, , - .^- - a j - n i S ^ Q --.-';'^;'l"u/ rt^-a^8^^ ^^.--...- D Du Font HLR 214-91 TABLE 2 BIOMICROSCOPE CLASSIFICATION.; OF CORHEAL INJURY No Injury; cornea within normal limits. Slight (1) = Epithelial changes visible only with biomicroscope (nay 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 bioniicroscope (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 bionicroscope evaluation performed. 10 - company ^ ^ s ^ ^ Du Font HLR 214-91 TABLE 3 ElfE IRRiTATIOH REACTIOMS OBSERVED IN THE 'UWASHED RABBIT EYE AFTER.TREATHEHT WITH Rabbit Number 25879 Cornea Opacity Area Ins Conjunctiva Redness Chemosis Discharge Bionncroscopic Examination of Cornea 1 4 1 2 3 Hour Hours Day Days Days 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Fluorescein examinations: Negative for cornea! injury at a11 observation periods. D ...... :...,,-.-. -y.j l;s.'& i%?.c-sfi'ai''i '<SC/ Du Pont HLR 214-91 TABLE 4 EYE IRRITATION REACTIONS OBSERVED IS THE WASHED RABBIT EYE AFTERJREATHEHT WITH Rabbit Number Z5875 1 4 1 t 3 Hour Hours Day Days Days Cemea Opacity Area Iris Conjunctiva Redness ChemoEis Discharge 0 0 0 - 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Biomicroscopic Examination of Cornea Fluorescein examinations: Negative for corneal injury at all observation periods. 12 - 'HompanSyanHize-d. Does Rot eontatn rscA W1