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AR226-3138 DuPont-3615 TRADE SECRET Study Title H-24256: Eye Irritation Test in Rabbits Laboratory Project ID: DuPont-3615 Author: Deborah A. Vick, A.A.S. Study Completed on: December 9,1999 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 19714-0050 Work Request Number: Service Code Number: Com pany Sanitized. Does not contain T S C A CB1 Page 1 of 12 H-24256: Eye Irritation Test in Rabbits DuPont-3615 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. Reviewed by: Carol Finlay, B.A. Associate Scientist m -'V , , . m-? Date Issued by Study Director: ____________ Deborah A. Vick, A.A.S. Associate Scientist Q 9 ~ Qg<L- Date 9 Com pany Sanitized. Does not contain T S C A CBt -2- H-24256: Eye Irritation Test in Rabbits STUDY INFORMATION DuPont-3615 Haskell Number: 24256 MSDS Reference Number CAS Registry Number:! Submitter's Notebook Numbertsl^j Composition:^ Known Impurities: ll Physical Characteristics: 1 Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: November 15,1999 / (see report cover page) In-Life Initiated/Completed: November 16,1999 / November 19,1999 Com pany Sanitized. Does not contain T S C A CBi -3 - H-24256: Eye Irritation Test in Rabbits STUDY PERSONNEL Study Director: Deborah A. Vick, A.A.S. Management: Nancy C. Chromey, Ph.D. Primary Technician: Deborah A. Vick, A.A.S. Toxicology Report Preparation: Maryanne M. Wilford, B.A. Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-3615 Com pany Sanitized. Does not contain T S C A C B r H-24256: Eye Irritation Test in Rabbits DuPont-3615 SUMMARY H-24256 was evaluated for acute eye irritation potential in 2 young adult New Zealand White rabbits. Approximately 0.01 mL of the test substance was instilled into the lower conjunctival sac o f 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 o f the rabbits were examined on the day o f treatment and on days 1, 2, and 3 following treatment. The test substance produced no ocular irritation in the treated eye of both rabbits during the study. No clinical signs of toxicity or body weight losses occurred during the study. Under the conditions o f this study, H-24256 was not an eye irritant. Com pany Sanitized. Does not contain T S C A C BI -5 - H-24256: Eye Irritation Test in Rabbits DuPont-3615 INTRODUCTION The purpose o f this study was to evaluate the acute eye irritation potential o f H-24256 in young adult New Zealand White rabbits. MATERIALS AND METHODS A. Test Substance The test substance, H-24256, was supplied by the sponsor as The test substance appeared to be stable under the conditions instability, such as a change in color or physical state, was observed. B. Animal Husbandry Young adult 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 o f 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 PMI Nutrition International, Inc. Certified High Fiber Rabbit LabDiet 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 o f coliforms, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to ensure 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 o f 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 o f this study. Rabbits were quarantined, weighed, and observed for general health for 11 days. 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 o f 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 o f the study. C om pany SanifzecT. Does n of contain T S C A C B f -6 - H-24256: Eye Irritation Test in Rabbits DuPont-3615 C. Protocol On the day of treatment, the eyes o f 2 male New Zealand White rabbits were examined using illumination, magnification, and fluorescein dye. Animals used on this study were free o f pre existing corneal or conjunctival injury or irritation and were judged to be in good health. The rabbits weighed 2799 or 3018 grams on the day of treatment. Approximately 0.01 mL o f H-24256 was introduced into the lower conjunctival sac of the right eye o f each rabbit. 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 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. Approximately 1 and 4 hours, and 1, 2, and 3 days after H-24256 was administered, the rabbits were examined for evidence o f eye irritation and for clinical signs o f toxicity. At each o f these observation periods, eyes were examined using illumination and magnification and scored for ocular reactions according to the Draize Scale (Table 1). Eyes were also observed for any unusual responses to treatment such as pannus, blistering of 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. The rabbits were weighed on the day o f treatment and at the last ocular evaluation. RESULTS AND DISCUSSION The test substance produced no ocular irritation in the treated eye o f both rabbits during the study. No clinical signs o f toxicity or body weight losses occurred during the study. Individual eye irritation scores are presented in Tables 2 and 3. CONCLUSIONS Under the conditions o f this study, H-24256 was not an 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 o f European Communities (EEC Directive 93/21, Annex VI), H-24256 probably should not be classified as an irritant unless additional testing proves otherwise. Com pany Sanitized. Does noi contain T S C A C B f -7 - H-24256: Eye Irritation Test in Rabbits DuPont-3615 RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware (formerly known as the E. I. du Pont de Nemours and Company Records Management Center). Com pany Sanitized. Does not contain T S C A CB1 -8 - H-24256: Eye Irritation Test in Rabbits DuPont-3615 TABLES Com pany Sanitized. Does not contain T S C A CBS -9 - H-24256: Eye Irritation Test in Rabbits DuPont-3615 TABLE 1 DRAIZE3 SCALE FOR SCORING OCULAR LESIONS (1) Cornea (A) Opacity-degree o f density (area most dense taken fo r reading) No opacity.......................................................................................... 0 Scattered or diffuse area, details o f iris clearly visible................... 1 (Slight) Easily discernible translucent areas, details o f iris slightly obscured....................................................................................... 2 (Mild) Opalescent areas, no details of iris visible, size o f pupil barely discernible.................................................................................... 3 (Moderate) Opaque, iris invisible......................................................................... 4 (Severe) (B) Area o f cornea involved One quarter (or less) but not zero..................................................... 1 (Localized) Greater than one quarter, but less than half..................................... 2 (Small) Greater than one half, but less than three quarters.......................... 3 (Moderate) Greater than three quarters, up to whole area.................................. 4 (Generalized) (2) Iris (A) Values Normal................................................................................................ 0 Folds above normal, congestion, swelling, circumcomeal injection (any or all o f these or combination o f any thereof) iris still reacting to light (sluggish reaction is positive)............ 1 (Moderate) No reaction to light, hemorrhage, gross destruction (any or all o f these)............................................................................................. 2 (Severe) (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels normal................................................... 0 Vessels definitely injected above norm al........................................ 1 (Mild) More diffuse, deeper crimson red, individual vessels not easily discernible.................................................................................... 2 (Moderate) Diffuse beefy re d ............................................................................... 3 (Severe) Com pany Sanitized. Does not contain T S C A C B ! -10- H-24256: Eye Irritation Test in Rabbits DuPont-3615 TABLE 1 (Continued) DRAIZE SCALE FOR SCORING OCULAR LESIONS (B) Chemosis No swelling........................................................................................ 0 Any swelling above normal (includes nictitating membrane)....... 1 (Slight) Obvious swelling with partial eversion of lids................................ 2 (Mild) Swelling with lids about half closed................................................ 3 (Moderate) Swelling with lids about half closed to completely closed............. 4 (Severe) (C) Discharge No discharge...................................................................................... 0 Any amount different from normal (does not include small amounts observed in inner canthus o f normal animals)........... 1 (Minimal) Discharge with moistening o f the lids and hairs just adjacent to lid s ................................................................................................ 2 (Moderate) Discharge with moistening of the lids and hairs, and considerable area around the eye............................................... 3 (Copious) a 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. Com pany Sanitized. Does not contain T S C A CBI - li - H-24256: Eye Irritation Test in Rabbits DuPont-3615 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE RABBIT EYE UNWASHED AFTER TREATMENT RABBIT NUMBER 33883 CORNEA Opacity Area IRIS CONJUNCTIVA Redness Chemosis Discharge 1 HOUR 0 0 0 0 0 0 4 HOURS 0 0 0 0 0 0 1 DAY 0 0 0 0 0 0 23 DAYS DAYS 00 00 00 00 00 00 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE RABBIT EYE WASHED AFTER TREATMENT RABBIT NUMBER 33884 CORNEA Opacity Area IRIS CONJUNCTIVA Redness Chemosis Discharge 1 HOUR 0 0 0 0 0 0 4 HOURS 0 0 0 0 0 0 1 DAY 0 0 0 0 0 0 23 DAYS DAYS 00 00 00 00 00 00 Com pany Sanitized. Does not contain T S C A C B I - 12-