Document LJDaqajXKEjORyqEYmrbNwEwz

AR226-2941 FOR OU PONT USE ONLY Du Pont HLR 385-89 Study Title Eye Irritation Test withUUf 1n Rabbits Author Dolores E. Maiek Study Completed On July 31, 1989 Performing Laboratory E. I. du Pont (Se Nemours and Company, Inc. Haskell Laboratory for Toxicology and Industrial .Medicine Elkton Road, P, 0. Box 50 Newark, Del aware 19714 Laboratory Project ID Haskell Laboratory Report No. 385-89 Page 1 of 11 Company SanWzed. Does not contain TSCA CBI : GENERALINFORMATION Du Pont HLR 385-89 Material Tested: Medical Research No. Haskell No.; Physical Form; Puri ty: Composition: ^ 17,869 Milky liquid dispersion Synonyms: Other Code; Stability; The test material was assumed to be stable under the conditions of administration. Sponsor: Chemicals and.^igments Department E. I. du Pont de Nemours and Company, Wllinlngton, Delaware Inc. fteterial Submitted By; Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. In-Life Phase Initiated - Completed: 6/13/89 - 6/16/89 Notebook: There are 11 pages in this report. Distribution: D - 2- .Company Sanitized. Does not contain TSCA CB Du Pont HLR 385-89 Eye Irritation Test with HPD-7352A 1n Rabbits SUMMARY [was evaluated for acute eye Irritation potential In t young adult rabbits. Both rabbits were dosed with a single 0.01 mL aliquot of test material in 1 eye. In 1 rabbit the treated eye was washed after treatment. In the other rabbit the treated eye was not washed. The contralateral eye of each rabbit served as a control. Both eyes of each rabbit using illumination and magnification at 1 and 4 hours, and following treatment. Biom^croscopic and fluorescein stain also conducted on post-treatment days 1, 2 and 3. were examined 1, 2. and 3 days examinations were HHBHI produced mild conjunctival redness, slight chemosis and minimal blood-tinged discharge by 1 hour after treatment in 1 rabbit. Conjunctival redness only was observed in this animal at 4 hours. Similar ocular responses were observed in the second rabbit at 1 and 4 hours after treatment with the additioiti of moderate iritis and slight generalized opacity. Fluorescein stain and biomicroscopic examinations were neg i/e for cornea! injury in both treated eyes throughout the study. The treated eyes of both rabbits were normal by 1 day following study initiation. Under the conditions of this study imBB^ was a moderate eye irritant. Work by; ^^<-^ACar^ol[^Bpniay Technftian Study Director: _----_--_--_--_D^olWores^^E. -MaJievkU, P^ht.D^.______ Research Toxicologist Acute'and Developmental Toxicology Division Reviewed and Approved for Issue: DEM:a1r:MLR119.12 3 ^ ^ . ^ < Hl^f^ Dolores E. Maiek, Ph.D. Study Director ^Pany Sanitized. Doesno, .onf^ TSCA Cffi Du Font HLR 385-89 QUALITY ASSURANCEDOCUMENTATION AUDITS: Items Audijed Test System Identification and Bousing Audit Dates 6/13/89 Q J I B ^ SHORT-TERM AUDIT REPORT NUMBER: MANAGEMENTAND STUDY DIRECTOK: DATE FINDINGS REPORTED TO 6/13/89 Reported by: W^--j^. ^>-L William J. Lynam Quality Assurance Auditor 6/s//^ Date L - '\ w Company Sanitized. Does noi contam: TSCA CBl INTRODUCTION Ou Pont HLR 385-89 The purpose of this study was to evaluate the acute eye Irritation potential of Q------Bin young adult rabbits. This study was conducted according to the applicable ^PAGood Laboratory Practice Regulations. Areas of noncornpl^ance 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 female 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* 532<3 and water were available ad Mbitum. Rabbits were quarantined, weighed and observed for general heiTth for approximately 2 weeks. Animal rooms were maintained .-on a y.imer-cont rolled, 12-hour light/12-nour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C ^ 2C and relative humidity of 50% j_ 10%. Excursions outside these ranges'were judged to have been of inTufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On me day of study initiation, the eyes of 2 female rabbits were examined using illumination, magnification and fluorescein dye. These animals were selected for this study as they showed no evidence of preexisting cornea"! or conjunctiva! Injury or irritation and were judged to be in good health. These rabbits were approximately 14 weeks old and weighed 3067 "and 3086 grams, respectively, on the day of treatment. A 0.01 ml aliquot of^B|||^was introduced into the lower conjunctiva! sac of each right eye of 2 female rabbits. The left 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 tast material was administered, both eyes of the remaining rabbit were rinsed for approximately 1 minute with water at room temperature. Each rabbit was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior was noted. Company Sanitized. Does no; contain TSCA CBf Du Pont HLR 385-89 Approximately 1 and; 4 hours, and 1, 2 and 3 days after--------y was administered, the rabblks were examined for evidence of eye Irritation. At each of these observation periods eyes were examined using Illumination and magn location and scored for ocular reactions using the Draize scale (presented In 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. Hemastix* reagent stripis were used to detect occult blood in discharge from the eye. B1om1crojscopic 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, Inc., Newark, Delaware or in the Du Pont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS ^UBi^produced mild conjunctival redness, slight chemosis and minimal blood-tinged discharge by l| hour after treatment in 1 rabbit. Conjunctiva! redness'only was observed in this animal at 4 hours. Similar ocular responses were observed in the second rabbit at 1 and 4 hours after treatment with the addition of moderate iritis and slight generalized opacity. Fluorescein stain and biomicroscopic examinations were negative for corneal injury in both treated eyes throughout the study. The treated eyes of both rabbits were normal by 1 day after study initiation. Individual eye irritation scores are presented in Tables 3 and 4. Under the conditions of this study ,1f^was moderate eye irritant. CompanySanitized. Does net .orrt^ T?CA CB. Du Pont HLR 385-89 TABLE 1 DRAIZE1SCALE 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 iris ................ clearly visible Easily discernible translucent areas, details of ................ iris slightly obscured Opalescent areas, no details of iris visible, ............ size of pupil barely discernible Opaque, iris invisible ..................... (B) Area of cornea i involved 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 . . 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values Normal Folds above normal, congestion, swelling, circum- ...................... corneal injection (any or alt 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 a11 of these) 0 1 (Moderate) 2 (Severed (3) Conjunctiva (A) Redness (refers to palpebral and bufbar 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 (Mild) 2 (Moderate) 3 (Severe) ;:Ampany san'l'^ed ^no^conlain TSCACBi Du Pont HLR 385-89 TABLE 1 (Cont'd) DRAIZE SCALEFOR SCORING OCULARLESIONS (B) Chemosis No swelling Any swelling above normal . . . . . . . . . . . . . . . . . . . membrane) (includes nictitating Obvious swelling with partial eversion of ................... lids Swelling with lids about half closed . . . . . . . . . . . . . . . . . . . . . Swelling with lids about half closed to completely . . . . . . . dosed .................... (C) Discharge ................... No discharge Any amount differeat 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) Oraize, J. H., "Dermal ToxScity." 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 - ''""""""""^"-"''"".^rsCACB, Du Pont HLR 385-89 TABLE 2 BIOMICROSCdPECLASSIFICATIONS OF CORNEAL INJURY --------------(Momk 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 swan ing. 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. company Sanitized. Does not contain TSCACBE Ou Pont HLR 385-89 ' TABLE 3 EYE IRRITATION UNWASHEDRABBIT EYE ^ REACTIONS OBSERVEDI AFTER TREATMENTMITH Rabbit Number 23931 Cornea Opacity Area 1 hr 4 hr 0 1 0 4 1 day 0 0 2 days 0 0 3 days 0 0 Iris 1 1 0 0 0 Conjunctiva Redness Chemosis Discharge 1 1 0 0 0 1 1 0 0 0 0 0 0 0 0 Biomic of Cornea Fluorescein examinations: 0 0 0 Negative for corneal injury at all observation periods. 10 Company Sanitized. Does not contain TSCA CB( Du Pont HLR 385-89 TABLE 4 EYE IRRITATION REACTIONS OBISERVED II< THE WAS1tED RABBIT EYE AFTER TREATHE;NT HITH^ Rabbit Number 23932 Cornea Opacity Area 1 hr 4 hr 1 day 2 days 3 days 0 0 0 0 0 0 0 0 0 0 Iris 0 0 0 0 0 Conjunctiva Redness Chemosis Discharge 1 1 0 0 0 1 0 0 0 0 KH+) 0 0 0 0 B 0 0 0 Biomic of Cornea F^uo^escein"'exaIIn"nat^'or<s: Negative for cornea! injury at all observation periods. H+ = Hemastix* evaluation was positive for blood. ^ 11 - Company Sanitized. Does not contain TSCA CBi