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AR226-3043 Study Title Eye Irritation Test with H-2I987 in Rabbits Laboratory Project ID Haskel! Laboratory Report No. 606-96 Author Carol Finlay Study Completed On August 28, 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 CEI L \e Irritation Tost with H-219X7 in Rabbits Substance Tested: Svnonvms: GENERAL INFORMATION DuPont HLR 606 96 Physical Form: Composition: Known Impurities: Purity: Structure: Tan liquid dispersion Submitter's Notebook No.: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase initiated - Completed: DuPont Specialty Chemicals E. I. du Pont de Nemouis and Company Wilmington, Delaware 8/5/96 - 8/28/96 8/6/96 -8/9/96 PENERAI NFCTlMAHQ!(Copticwgd) AU raw Toxicology and Indtoitrial Medicine, E. I. DuPont Records Management Center). I ;! m ' r; ;3 Eye Irritation Test with H-21987 in Rabbits DuPont HLR 606-96 SUMMARY H-21987 was evaluated for acute eye irritation potential in 2 rabbits. Approximately 0.01 mL of the test substance was instilled into the lower conjunctival sac of the right eye of each rabbit. Approximately 20 seconds after instillation, the treated and control eyes o f 1 rabbit were washed. The treated and control eyes of 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-21987 produced mild conjunctival redness in the treated unwashed eye. Moderate iritis, moderate conjunctival redness, and slight conjunctival chemosis were observed in the eye wasted after treatment. The treated unwashed eye was normal by 1 day, and the treated washed eye was normal by 3 days after instillation c f the test substance. Under the conditions of this study, H-21987 was a moderate eye irritant. -4 - Company Sanitized. Does not contain TSGA CE Eye Irritation Test with H-21987 in Rabbits SIGNATURE PAGE DuPont HLR 606-96 Work by: ________ C tLAAii, L Jl L A ul Carol Finlay 1 Toxicology Asssociate Reviewed and Approved for Issue: ________ ( l/LcK, 'nC M l/lu f/tS/^L Carol Finlay Q Study Director Oral, Ocular, and Dermal Toxicology Acknowledgement: Barry' Fritz also participated in the conduct of this study. CF/lmp -5- Company Sanitized. Does not contain TSCA Cflf tye Irritation Test with H-21987 tn Rabbits INTRODUCTION DuPont HLR 606-96 The purpose of this study was to evaluate the acute eye irritation potential of H-21987 in young adult rabbits. MATERIALS AND METHODS A. Animal Husbandr, Young adult male HM:(NZW)fBR New Zealand White rabbits were received from Hare Marland, Hewitt, New Jersey. The r ?bbits 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. 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 125 grams o f Purina Certified High Fiber Rabbit Chow #5325 daily during the study. Water was available ad libitum. Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by ine Laboratory Veterinarian. Water 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 of 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, 12hour light/12-hour dark cycle. Environmental conditions of the rootm were targeted for a temperature of 20C 1C 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. -6- ompany Sanitized. Does not contain TSCA CBL Hye Irritation Test with H-21987 in Rabbits DuPont HLR 606-96 B. Protocol On the day of treatment, the eyes of 2 male New Zealand White rabbits were examined using illumination, magnification, and fluorescein dye. Animals used on this study were free of pre-existing comeal or conjunctival injury or irritation and were judged to be in good health. These rabbits weighed 3070 or 3405 grams on the day of treatment. Approximately 0.01 mL of H-21987 was introduced into the lower conjunctival sac of each right eye. The left eye of each rabbit was not treated with the test substance 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 tire 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 and 4 hours, and 1,2, and 3 days after H-21987 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 illumination 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 of the conjunctiva, ulceration, or other effects indicative of corrosive action. Control eyes were not scored. These untreated eyes were used for comparison and were considered "normal" relative to the treated eye. RESULTS No clinical signs of toxicity were observed during the study. H-21987 produced mild conjunctival redness in the treated unwashed eye. Moderate iritis, moderate conjunctival redness, and slight conjunctival chemosis were observed in the eye washed aiter treatment. The treated unwashed eye was normal by 1 day, and the treated washed eye was normal by 3 days after instillation of the test substance. Individual eye irritation scores are presented in Tables 2 and 3. -7 - Company Sanitized. Does not contain TSCA CB1 tiye Irritation Test with H-21987 in Rabbits CONCLUSION DuPont HLR 606-96 Under the conditions of this study, H-21987 was a moderate eye irritant. If these test scores aie to be used for EEC/OECD classification, according to the guide to the labeling of dangerous substances published in the Official Journal o f European Communities (EEC Directive 93/21, Annex VI), H-21987 probably could be classified as "NON-IRRITANT' until further data is available. - K- Sanfeed.Dae not ontaln T3CCB* otnpany Hye irritation Test with H-21987 in Rabbits DuPont HLR 606-96 TABLE 1 DR AI7IF-1SCALE FOR SCORING OCULAR LESIONS ( l ) 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 o f cornea involved One quarter (or less) but not zero ............... 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 .. (7) Iris (A) Values N orm al........................................... Folds above normal, congestion, swelling, circum 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)............. (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels norm al................................... Vessels definitely injected above norm al........ More diffuse, deeper crimson red, individual vessels not easily discernible............... Diffuse beefy r e d ............................... 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) 0 1 (Moderate) 2 (Severe) 0 1 (Mild) 2 (Moderate) 3 (Severe) -9- Company Sanitized. Does not contain TSCA CBI Eye Imiaiitin Test with H-21987 in Babbils DuPont HLR 606-96 TABLE 1 (Cont'd) ORA17.F. S C A l E FOR SCORING OCULAR LESIONS (B) Chemosis No sw elling ..................................... Any swelling above normal (includes nictitating m e m b ra 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 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 animals)............................... Discharge with moistening of the lids and hairs just adjacent to lid s......................... Discharge with moistening of the lids and hairs, and considerable area around the e y e ........ 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 1 (Minimal) 2 (Moderate) 3 (Copious) 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 Officiais of the United States, Austin, Texas, 1959, pp. 46-59.1 10 1. Does CBS Eye Irritation Test with H-2I987 in Rabbits DuPont HLR 606-96 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 31071 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 Hour 4 Hours 00 00 00 11 00 00 1 Day 0 0 0 0 0 0 2 Days 3 Days 00 00 00 00 00 00 il Company Sanitized. Does not contain TSCA CBf Eye Irritation Test with H-219K7jr^Rabbits^ DuPont HLR 606-96 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 31068 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge l Hour 4 Hours 12 D ay... Days 0000 0000 I 1' 0 0 12 I 1 10 000 1 0 0 3 Days 0 0 0 0 0 01 12 Company Sanitized. Does not contain TSCACBJ