Document jKkKDqYvY8eLZdnO05d7vO3Q

AR226-3051 < Study Title Eye Irritation Test with H-21946 in Rabbits laboratory Project ID Haskell Laboratory Report No. 788-96 Author Tracy A. Filliben Study Completed On September 4,1996 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. O. Box 50 Newark, Delaware 19714 Page I of 12 Company Sanitized. Does not contain TSCA CB1 Eye Irritation Tesi with H-21946 in Rabbits DuPont HLR 788-96 Substance Tested: Synonyms: GENERAL INFORMATION Physical Form: Composition: Light beige, ooaque liquid Contaminants: Purity: Submitter's Notebook No.: CAS Registry No.: Sponsor: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-2I 946 in Rabbits DuPont HLR 788-96 Study Initiated - Completed: In Life Phase Initiated - Completed: 7/12/96-9/4/96 7/24/96 - 7/27/96 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 at Iron Mountain, 200 Todds Lane, Wilmington, Delaware (formerly DuPont Records Management Center. -3 - Company Sanitized. Does not contain TSCA CBl Eye Irritation Test with H-21946 in Rabbits SUMMARY DuPont HLR 788-96 H-21946 was evaluated for acute eye irritation potential in 2 rabbits. Approximately 0.01 mL o f the test substance was instilled into the lower conjunctival sac of the right eye o f each rabbit. Approximately 20 seconds after instillation, the treated and control eyes of 1 rabbit were washed. The treated and control eyes o f the remaining rabbit were not washed. The eyes of the rabbits were examined on the day of treatment and on days 1, 2, and 3 following treatment. H-21946 produced mild conjunctival redness in the treated unwashed rabbit eye. M oderate conjunctival redness, slight chemosis, and minimal discharge were observed in the eye washed after treatment. Both treated eyes were normal by 3 days after instillation o f the test substance. No clinical signs of toxicity were observed during the study. Under the conditions of this study, H-21946 was a moderate eye irritant. -4 - 'Ompany Sanitized. Does not contain TSCA CBi Eye Irritation Test with H-21946 in Rabbits SIGNATURE PAGE DuPont HLR 788-96 Report by: JAJLLLL Q. U Tracy A. Filliben . Toxicology Associate Work to 'C S u u n Q . 0 Tracy A. Filliben Toxicology Associate Reviewed and Approved for Issue: Tracy A. Filliben Study Director j j% Acknowledgment: Carol Finlay and Barry Fritz also participated in the conduct o f this study. TF/alw -5 - Company Sanitized. Does not contain TSCACB1 Eye Irritation Test with H-21946 in Rabbits DuPont HLR 788-96 INTRODUCTION The purpose of this study was to evaluate the acute eye irritation potential of H-21946 in young adult rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male HM:(NZW)fBR 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 c^ge. The last 3 digits of the identification number were written on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 123 grains o f Purina Certified High Fiber Rabbit Chow #5325 daily during the study. W ater was available ad libitum. Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratoiy Veterinarian. W ater samples are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to assure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed is certified by the manufacturer to meet specified nutritional requirements and to be free o f a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or water in amounts which may have interfered with the results of this study. 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 1C and relative humidity of 50% 10%. Excursions outside these ranges were judged to have been o f insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day o f treatment, the eyes of 2 male New Zealand White rabbits were examined using illumination, magnification, and fluorescein dye. Animals used on this study -6 - CompanySaniteed. Doesnoi conialotsca cbi Eye Irritation Test with H-21946 in Rabbits DuPont HLR 788-96 w erefree o f pre-existing corneal or conjunctival injury or irritation and werejudged to be in good health. These rabbits weighed 2507 or 2702 grams on the day of treatment. Approximately 0.01 mL of H-21946 was introduced into the lower conjunctiva] sac o f each right eye. The left eye of each rabbit was not treated with the test siihstanry and served as a control. Approximately 20 seconds after the test substance was administered, both eyes of 1 rabbit were rinsed for approximately 1 minute with room temperature water. The treated and control eyes of the remaining rabbit were not washed. Each rabbit was observed for approximately 30 to 60 seconds before being returned to its cage, and any abnormal behavior was noted. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions o f administration. Approximately 1 and4 hours, and 1,2, a id 3 days after H-21946 was administered, the rabbits were examined for evidence of eye irritation and for clinical signs of toxicity. At each of these observation periods, eyes were examined using ilhimmarinn and magnification and scored for ocular reactions according to the Draize scale (presented in Table 1). Eyes were also observed for any unusual responses to treatment such as pannus, blistering o f the conjunctiva, ulceration, or other effects indicative o f corrosive action. Control eyes were not scored. These untreated eyes were used for comparison and were considered "normal" relative to the treated eye. RESULTS H-21946 produced mild conjunctival redness in the treated unwashed rabbit eye. Moderate conjunctival redness, slight chemosis, and minimal discharge were observed in the eye washed after treatment. Both treated eyes were normal by 3 days after instillation of the test substance. No clinical signs of toxicity were observed during the study. Individual eye irritation scores are presented in Tables 2 and 3. -7 - Sompany Sanitized. Does not contain TSCA CBS Eye Irritation Test w ith H-21946 in Rabbits CONCLUSION DuPont HLR 788-96 Under the conditions o f this study, H-21946 was a moderate eye irritant. If these test scores are to be used for EEC/OECD classification, according to die guide to the labeling of dangerous substances published in the Official Journal of European Communities (EEC Directive 93/21, Annex VI), H-21946 probably could be classified as NON-IRRITANT until further data is available. -8Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21946 in Rabbits DuPont HLR 788-96 _________________________________TA B LE!_______________________________ nPA lTF.1SCALE FOR SCORING OCULAR LESIONS (1) Cornea (A) Opacity-degree o f density (area most dense taken for reading) No opacity...................... 0 Scattered or diffuse area, details of irk clearly v isible........................ Easily discernible translucent areas, details of iris slightly obscured....................................... Opalescent areas, no details of iris visible, size of pupil barely discernible .. -- . Opaque, iris invisible........... 4 (B) Area o f cornea involved One quarter (of less) but not z ero ............... Greater than one quarter, but less than half. . . Greater than one half, but less than three q u a rte rs ..................... 3 Greater than three quarters, up to whole area . . (2) Iris (A) Values N orm al............................................ Folds above normal, congestion, swelling, circumcomeal injection (any or all of these or combination o f any thereof) iris still reacting to light (sluggish reaction is positive) . . . No reaction to light, hemorrhage, gross destruction (any or all o f these)............ (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels norm al................................... Vessels definitely injected above normal. . . . . More diffuse, deeper crimson red, individual vessels not easily discernible.............. Diffuse beefy r e d ............................. * (Slight) 2 (Mild) 3 (M oderate) (Severe) 1 (Localized) 2 (Small) (M oderate) 4 (Generalized) 1 (M oderate) 2 (Severe) 0 I (Mild) 2 (Moderate) 3 (Severe) -9 - Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21946 in Rabbits DuPont HLR 788-96 ----------------------- TABLE 1 (Cont'd)_______________ DUAIZE SCALE FOR SCORING OCULAR LESIONS (B) Chemosis No sw e llin g .................... Any swelling above normal (includes nictitating m em brane)...................................... Obvious swelling with partial eversion of l i d s .......................................... Swelling with lids about half closed............ Swelling with lids about half closed to completely c lo s e d ........................................ (C) Discharge No discharge...................................... Any amount different from normal (does not include small amounts observed in inner canthus of normal anim als)............................... Discharge with moistening o f the lids and hairs just adjacent to lid s.......................... Discharge with moistening o f the lids and hairs, and considerable area around the e y e ......... 0 1 (Slight) 2 (MM) 3 (Moderate) 4 (Severe) * (Minimal) 2 (Moderate) 3 (Copious) ' Draize, J. H., "Dermal Toxicity." Appraisal o f the Safety of Chemicals m Foods, Dregs and Cosmetics. The Editorial Committee of the Association o f Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. -10Company Sanitized. Does not contain TSCA CB! j Eye Irritation Test with H-21946 in Rabbits DuPont HLR 788-96 ------------------------------TABLE-2---------------------------- EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 31183 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 14 Hour Hours 00 00 00 11 00 00 1 Day 0 0 0 1 0 0 2 Days 3 Days 00 00 00 10 00 00 - ii Company Sanitized. Does not contain TSCA CBS Eye Irritation Test with H-21946 in Rabbits DuPont HLR 788-% TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 31185 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge I4 Hour Hours 00 00 00 22 11 01 1 Day 0 0 0 2 0 0 2 Days 3 Days 00 00 00 10 00 00 - 12- Cpmpany Sanitized. Dees not contain TSC CBt