Document 2jkqpVG10bvL7GkKQRZ94OGBb

AR226-3051 Study Title Eye Irritation Test with H-21946 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 788-96 Author Tracy A. Rlliben Study Completed On September 4,1996 Performing Laboratory E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Page lofl2 Company Sanitized. Does not contain TSCA CBI 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 Font de Nemours and Company Wilmington, Delaware -2. Company Sanitized. Does not contain TSCA CB1 Eye Irritation Test with H-2:946 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 Font de Nemours and Company. Newark, Delaware or at Iron Mountain, 200 Todds Lane. Wilmington. Delaware (formerly DuPont Records Management Center. 3Company Sanitized. Does not contain TSCA CBt Eye tmuuion Test with H-21946 in Rabbits SUMMARY- DuPontHLR 788-96 H-21946 was evaluated for acute eye irritation potential in 2 rabbits. Approximately 0.01 mL of the test substance was instilled into the lower conjunctiva! sac of the right eye of each rabbit. Approximately 20 seconds after instillation, the treated and control eyes of 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-21946 produced mild conjunctiva! redness in the treated unwashed rabbit eye. Moderate conjunctiva! redness, slight chemosi^ and minimal discharge were observed in the eye washed after treatment. Both treated eye- ere normal by 3 days after instillation of 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 CompanySanitized. Does not contain TSCA CBI Eye Irritation Test with H-21946 in Rabbits____________________DuPont HLR 788-96 SIGNATUREPAGE ^K^Mt^ Report by: ^A^LUiOi. 0 Tracy A. Filliben . Toxicology Associate Work by:^tq/<3. CflfJLLu^ 0TracyTArac.yFAiU. Fiiblliebenn Toxicology Associate ft Reviewed and Approved for ^ue:^jSg^/ 0- ^JilW^ dTracy A. Filliben Study Director ^ IJ-1% Acknowledgment: Carol Finlay and Barry Fritz also participated in the conduct of this study. TF/alw 5Company Sanitized. Does not contain TSCACBS 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 cige. 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 grains of 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 the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence ofcoliforms, 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, 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 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. Animals used on this study -6- CompanySaniteed. Does not contain TSCA CB| Eye Irritation Test with H-21946 in Rabbits DuPPnt HLR 788-96 were'fre^ofpre-existiffgicorneal or conjunctiva! injury or irritation and were judged 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 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 I 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 me absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Approximately 1 and 4 hours, and 1,2, and 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 illumination and magnification and scored for ocular reactions according to the Draize scale (presented in Table I). 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 H-21946 produced mild conjunctiva! redness in the treated unwashed rabbit eye. Moderate conjunctiva! 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 signsof toxicity were observed during the study. Individual eye irritation scores are presented in Tables 2 and 3. 7eompany Sanitized. Does not contain TSCA CBB Eye Irritation Test with H-21946 in Rabbits CONCLUSION, DuPontHLR 788-96 Under the conditions of this study, H-21946 was a moderate eye irritant. If these test scores are to be used for EEC/OECD classification, according to the guide to the labeling of dangerous substances publishedin 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 Tesi with H-21946 in Rabbits DuPontHLR 788-96 TABLE 1 DRAKE SCALE 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 irL 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 involved One quarter (of less) but not zero........ Greater than one quarter, but less than half... Greater than one half, but less than three Greaqteurathratnetrhsre.e..q.u..a.r.te..rs.., .up.t.o..w.h.ole area .. (2) Iris (A) Values NFolodsramboavel.n.o.r.m..a.l,.c.o..n.g.e.s.ti.o.n.,.s.w..elling, circum- comeal 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 normal.................. Vessels definitely injected above normal..... More diffuse, deeper crimson red, individual vessels not easily discernible ........ Diffuse beefy red ................ 0 1 (Slight) 2 (Mild) 3 (Moderate) 4(Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) 0 ((Moderate) 2 (Severe) 0 1 (Mild) 2 (Moderate) 3(Severe) -9- eompany Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21946 in Rabbits -TABLE l(Confd) DRAIZE SCALE FOR SCORING OWL (B) Chemosis ................... No swelling Any swelling above normal (includes nictitating membrane)................... Obvious swelling with partial eversion of ..................... lids Swelling with lids about half closed....... Swelling with 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 hairs just adjacent to lids............. Discharge with moistening of the lids and hairs, and considerable area around the eye ..... DuPonlHLR 788-96 0 1 (Slight) 2(MUd) 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 Officials of the United States, Austin, Texas, 1959, pp. 46-59. 10- CompanySanitized. Does not contain TSCA CB1 Eye Irritation Test with H-21946 in Rabbits DuPoni HLR 788.96 -TABLE2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 1 4 1 31183 Hour Hours Day Cornea Opacity Area Iris 0 0 0 0 0 0 0 0 0 Conjunctiva Redness 1 1 1 Chemosis Discharge 0 0 0 0 0 0 2 Days 0 0 0 3 Days 0 0 0 1 0 0 0 0 0 1) - Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-2I946 in Rabbits DuPonlHLR 788.96 TABLE3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 31185 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 Hour 4 Hours 0 0 0 0 0 0 2 2 1 1 0 1 1 Day 0 0 0 2 0 0 2 Days 0 0 0 3 Days 0 0 0 1 0 0 0 0 0 12- Company SanRTzed. Dees ftet contain tSCA CBt