Document EvoEwGv0yXkLpZnN7RgdjqeZN

.* K FOR DP PONT BSE PULT AR226-2970 Du Pont H M 809-91 Study Title Eye Irritation Test witt dn Rabbits Author John . Server Study Completed On February 13, 1992 Performing Laboratory E. I. d Pont de Nemours and Company __ Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Laboratory Project ID Haskell oratory Report No. 809-91 Page 1 of 12 Substance Tested: Hedical Research Ho.: Haskell No.: Haskell Test Code No.; Physical Form? Composition: GENERAL INFORMATION 19,173 Du Pont HLR 809-91 Purity: Synonym: Submitter's Notebook Ho.: Stability: In the absence of visible evidence to the contrary, the test substance vas assumed to be stable under the conditions of administration. Sponsor: Du Pont Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware Substance Submitted By: . I. du Pont de Nemours and Company Chambers Works Deepwater, New Jersey Study Initiated - Completed: 11/15/91 - 2/13/92 In-Life Phase Initiated - Completed: 11/19/91 - 11/22/91 Notebook: There are 12 pages in this report. -2- Bol contain TSCAC* j^e Irritation Test with Du Pont HLR 809-91 in Rabbits SUMMARY _ __ evaluated for acute eye irritation potential in 2 rabbits. The eyes of the rabbits vere examined on the day of treatment and on days 1, 2, and 3 following treatment. The test substance produced mild conjunctival redness in the treated unwashed eye. Ho Irritation vas observed in the treated vashed eye. Fluorescein stain examinations vere negative for corneal injury, and biomicroseopie examinations revealed no corneal damage in either treated eye. T h e t r e a t e d u n w a s h e d eye was normal by-S^dayr^fonsstf^ 'RsatBare. Under the conditions of this study, as a mild eye irritant. Work by: . . XLUkl-LAtv. Carol Finley Technician Study Director: John V. Sarver Technologist Approved by: yRaney C. Chiaramey, Ph.D. Manager Acute Toxicology Reviewed and Approved for Issue: John V. Sarver Study Director A /13/^3. Acknowledgment: Bryan W. Crossley also participated in the conduct of this study. JWS/lmr 4 jCompatvy T S C A cWl Du Pont BLR 809-91 QUALITY ASSURANCE DOCPMEHTATIQN Dates of Inspection: Conduct - 11/20/91 Records, Report(s) - 1/21/92 Findings reported to; Study Director - 1/24/92 Management - 2/11/92 Reported by: irPrnfc^ 'fot*/*, James Mackay II g Quality Assurance Auditor ik- Date Uos tainTSCA^CBt Du Pont BLR 809-91 INTRODUCTION The purpose of t&js study was to evaluate the acute eye irritation potential o f Q p H M p i n young adult rabbits. This study was conducted according to the applicable EPA Good laboratory Practice Regulations. Areas of noncompliance are documented in the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male and female New Zealand White rabbits were received from fore 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 id 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 50* 10Z. 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 prior to treatment, the eyes of one female and one male New Zealand White rabbits were examined using illumination, magnification, and fluorescein dye. Wiese animals were selected for this study as they showed no evidence of preexisting corneal or conjunctival injury or irritation and were judged to be in good health. Wiese rabbits weighed 3608 and 3660 grams, respectively, on the day of treatment. Approximately 0.01 m I o f p p B R ? a s introduced into the. lower conjunctival sac of each lefThye. The right eye of each rabbit was net treated with the test substance and served as a control. The treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the test substance was administered, both eyes of the remaining rabbit were rinsed for approximately 1 minute with room temperature water. Each rabb* was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior was noted. _6- noie01 ed.003 San&W c o m ? aOY fBl Du Pont HLR 809-91 Approximately 1 and 4 hours, and 1, 2, and 3 days a f t e i M H B H B n r a s administered, the rabbits ere examined for evidence of eyeWrritation. At each of these observation periods, eyes were examined using illumination and magnification and scored for ocular reactions according to the Draize scale (presented in Table 1). Eyes ere also observed for any nusiial 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 __ roduced mild conjunctival redness in the treated unwashed eye. No irritation was observed in the treated washed eye. Fluorescein stain examinations were negative for corneal injury, and biomicroscopic examinations revealed no corneal damage in either treated eye. The treated unwashed eye was normal by 3 days following treatment. Individual eye irritation scores are presented in Tables 3 and 4. CONCLUSION Under the conditions of this s t u d y , p H ^ H | w a s a mild eye irritant. 7- - Do Pont HLR 809-91 TABLE 1 ppaTgRi SCALE FOR SCORING OCULAR LESIONS (A) Opacity-degree of density (area most dense taken for reading) No o p a c i t y ....................... ........... Scattered or diffuse area, details of iris clearly visible .......... * Easily discernible translucent areas, details of iris slightly obscured . . . * * * Ooalescent areas, no details of iris visible, size of pupil barely d i s c e r n i b l e .......... * Opaque, iris invisible ........................... 0 1 (Slight) 2 (Mild) 3- (Moderate ) 4 (Severe) (B) Area of cornea involved Ono quarter (or less) but not z e r o ............ .. Greater than one quarter, but less than half * Greater than one half, but less than three q u a r t e r s ....................... * ............ Greater than three quarters, up to whole area . - 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values N o r m a l ............. Folds above normal, congestion, swelling, circura- corneal 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) ............ 0 1 (Moderate) 2 (Severe) (3) Conjunctiva ,, (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels n o r m a l .......................* .......... Vessels definitely injected above normal . . . . . 0 1 (Mild) More diffuse, deeper crimson red, individual vessels not easily d i s c e r n i b l e ............... Diffuse beefy red ............................... 2 (Moderate) 3 (Severe) C o m p a q SOt" -8 on*** t5Ostl0iiC v-r Du Pont HLR 809-91 TABLE 1 (Cont'd) lRATTR SCALE FOR SCORING OCULAR LESIONS (B) Chemosis No swelling ......................... ........... Any swelling above normal (includes nictitating m e m b r a n e ) .......... .......... ................ Obvious swelling with partial eversion of l i d s .............. .......................... Swelling with lids about half closed ............ Swelling with lids about half closed to completely 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) (C) Discharge No discharge . . . . .......... . . . . . . . . . Any amount different from normal (does not include email amounts observed in inner canthus of normal animals) . . Discharge with moistening of the lids and hairs just adjacent to l i d s ......................... Discharge with moistening of the lids and hairs, and considerable area around the e y e ........ 1 (Minimal) 2 (Moderate) _ 3 (Copious) i 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- .Does files'tain I ; jJ i Du Pont BLR 809-91 TABLE 2 BIOMICROSCOPE CLASSIFICATIONS OF CORNEAL INJURY 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 shoving epithelial changes only with biomicroscope (may include localized area of moderate injury). Moderate (3) - Opacity visible with ophthalmoscope or light but shoving epithelial and stromal changes with biomicroscope (may include localized area of severe injury). Moderate to Severe (4) = Opacity visible with ophthalmoscope or light but shoving 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 shoving 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. Du Pont HLR 809-91 TABLE 3 Ell IRRITATION REACTIONS OBSERVED IN TOE UNVASHBD RABBIT, EIE AFTER TREATMENT WITH Rabbit Number 26667 Cornea Opacity _Area Iris Conjunctiva Redness Chemosis Discharge Biomioroscopie Examination of Cornea 1 4 12 3 Hour Hours Day Days Days 0 0 00 0 o 0 00 0 0 0 00 0 1 1 11 0 0 0 00 0 0 0 00 0 - - 00 0 Fluorescein examinations: negative for corneal injury on days 1-3. - 11 - ss1 ote t)oes r*- Du Pont HLR 809-91 TABLE 4 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBITEYE.AFTERJgtBATMENT WITH Babbit Number 26583 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Biomioroscopie Examination of Cornea ------------ j2 3 Hour Hours Day Pays Pays 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 00 0 Fluorescein examinations: negative for corneal injury on days 1-3. 1 r - 12 -