Document dYrwy3Q8vDLKbQZ3eLMBNB5Bb

AR226-3045 Study! Pie Eye Irritation Test with H-21953 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 789-96 Author Tracy A. Filliben Study Completed On August 30, 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 I of 12 Company Sanitized. Does not contain TSCA CBI Suhslancc Tested: Synonyms: GENERAL INFORMATION Physical Form: Composition: Opaque tan to white 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-21)53 in Rabbits DuPontHLR-W^. Study Initiated - Completed: 7/12/96-8/30/96 In Life Phase Initiated - Completed: 7/24/96-7/27/96 All data and the final report will be stored in the archives of Haskell Laboratory for raw Medicine. E. I. du Font de Nemours and Company. Newark. TDoexlaicwoalroegyoraantdIrIonnduMstoruianltain, 200 Todds, Lane, Wilmington, Delaware (formerly DuPont Records Management Center. -3- Company Sanitized. Does not contain TSCA CBI hyc Imluimn Test with H-21953 in Rahbits SUMMARY DuPunlHLR 789-96 H-21953 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 I 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-21953 produced moderate conjunctiva! redness and moderate iritis in both treated rabbit eyes. In addition, blistering of the conjunctiva, mild chemosis, and copious discharge were observed in the treated unwashed eye, and slight chemosis and moderate 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. Under the conditions of this study, H-21953 was a moderate eye irritant. -4- Company Sanitized. Does not contain TSCA CBI DuPunt HLR 7X9-96 b^^Wx0^Tracy Report Q. ^KjUljk^. A. Filliben Toxicology Associate ^KiUdH^ (JTracy Work hy\ UCLLUQ. A. Filliben Toxicology Associate ^AUuH^- Reviewed and Approved for Issue^^^(jU^ . Tracy A. Filliben Study Director ^W ^ Acknowledgement: study. Carol Finlay and Barry Frilz also participatedin the conduct of this TF/alw - sCompany Sanitized. Does not contain TSCA CBI Eye Irriimion Test with H-21')53 in Rabhils__________ INTRODUCTION DuPom HLR 789-96 ___ The purpose of this study was to evaluate the acute eye irritation potential of H-21953 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 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 of Purina Certified High Fiber Rabbit Chow #5325 daily during the study. Water was available ad libitum. Haskel! 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 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, 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 were free of pre-existing comeal or conjunctival injury or Irritation and were judged to h- Company Sanitized. Does not contain TSCA CBI Eye Imialion Test with H 21953 in Rabbits___________________PuPoni HLR 789-96 be in good health. treatment. These rabbits weighed 2909 or 2984 grams on the day of Approximately 0.01 mL of H-21953 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 tost 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 the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Approximately I and 4 hours, and 1.2, and 3 days after H-21953 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. Contio! eyes were not scored. These untreated eyes were used for comparison and were ccn-.iilc^d "normal" relative to the treated eye. H-21953 produced moderate conjunctiva! redness and moderate iritis in both treated rabbit eyes. In addition, blistering of the conjunctiva, mild chemosis, and copious discharge were observed in the treated unwashed eye, and slight chemos's and moderate 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- Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21953 in Rabbits CONCLUSION DuPonlHLR 789-96 Under the conditions of this study, H-21953 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 published in the Official Journal of European Communities (EEC Directive 93/21, Annex VI), H-21953 probablycould be classified as NON-IRRITANT until further data is available. -K- Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21953 in Rabhils DuPonlHLR 789-96 TAgLE\ DRAIZE 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 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 involved One quarter (or 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 NFolodsrmaboavel.n.o.r.m..a.l,.c..o.n.g.e.s.t.io.n.,..s.w.elling, circum- corneal injection (any or all of these or combination of any thereof) iris still reacting No rtoealcigtihotn(stolulgigghisth, hreemacotirorhnaigsep, ogsroitsivse) ... 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 I (Moderate) 2(Severe) 0 1 (Mild) 2 (Moderate) 3(Severe) -9- Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21953 in Rabbits DuPOnlHLR 789-96 TABLE I (Confd) DRAKE SCALE FOR SCORING OCULAR LESIONS (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 .................... (Q 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 ..... 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 Officials of the United States, Austin. Texas, 1959, pp. 46-59. -1( Company Sanitized. Does not contain TSCA CBI Eye lirHalion Test wilh H-21953 in Rahhitii DuPoni HLR 789-96 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 1 4 1 31058 Hour Hours Day Cornea Opacity 0 0 0 Area 0 0 0 Iris 1 1 1 Conjunctiva Redness 2 2 2 Chemosis 1 2B 1 Discharge 2 3 0 2 Days 0 0 0 3 Days 0 0 0 1 0 1 0 0 0 B = Blistering of the conjunctiva Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21953 in Rabbits DuPuntHLR 789-96 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 1 4 1 31059 Hour Hours Day Cornea Opacity 0 0 0 Area Iris 0 0 0 1 1 0 Conjunctiva Redness Chemosis Discharge 2 2 2 1 1 1 1 2 0 2 Days 0 0 0 3 Days 0 0 0 1 0 0 0 0 0 -12Company Sanitized. Does not contain TSCA CBI