Document QGo8j79jYR2RwOBdqZQk4N84

TRADE SECRET AR226-3077 Study Title H-22762: EYE IRRITATION TEST IN RABBITS LABORATORY PROJECT ID: HL-1997-00735 AUTHOR: Carol Fmlay, B.A. STUDY COMPLETED ON: August 8, 1997 PERFORMING LABORATORY: E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 WORK REQUEST NUMBERSrI^^^B")| Company SanRfzecf. (Toes-nof contain". TSIC'i&CCT1 Page 1 of 9 GENERAL INFORMATION Synonyms/Codes'---- H-22762 Haskell Number: 22762 Purity Known Impuritie| Physical Characteristics: Clear yellow liquid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: July 28, 1997 / (see report cover page) In-Life Initiated/Completed: July 29, 1997 / August 1, 1997 All study records, raw data, and the final report are retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain, 200 Todds Lane, Wilmington, Delaware 19802 (formerly known as the E. I. du Pont de Nemours and Company Records Management Center). Compel SanBteasL Boes not contain TSCACBt 2- SUMMARY H-22762 was evaluated for acute eye irritation potential in 2 New Zealand White 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 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. No clinical signs oftoxicity were observed. H-22762 produced moderate conjunctival redness and slight conjunctival chemosis in the treated unwashed and washed rabbit eyes. Additionally, minimal discharge was observed in the eye washed after treatment. The treated eyes of both rabbits were normal by 2 days after instillation. Under the conditions of this study, H-22762 was a moderate eye irritant. Compaq Sanifeed. Ds?ss not contain TSCA C88 3- SIGNATURES Reviewed and Approved for Issue: ^\/L f (LArri Carol Finlay, rfA. Toxicology Associate Study Director ^/^ STUDY PERSONNEL The following individuals were responsible for conduct of the study: Manager: Study Director: Nancy C. Chromey, Ph.D. Carol Finlay, B.A. Primary Technician: Assisting Personnel: Toxicology Report Preparation(s): M. Scott Karr, A.S. Barry A. Fritz Maryanne M. Wilford, B.A. The following individual was responsible for assessing the health status of the animals on study: Laboratory Veterinarian: Charles E. Cover, V.M.D. Company Sanded. Does not contain TSCA CBI 4- INTRODUCTION The purpose of this study was to evaluate the acute eye irritation potential ofH-22762 in young adult New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male HM:(NZW)BR New Zealand White rabbits were received from Hare Marland. 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 ofPurina 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 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 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/I 2-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of20C 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 prior to 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. The rabbits weighed 2515 or 2647 grams on the day of treatment. Approximately 0.01 mL ofH-22762 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. Company Sanitized. Does not contain TSCA CBI 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-22762 was administered, the rabbits were examined for evidence of eye irritation and for clinical signs oftoxicity. 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 oftoxicity were observed. H-22762 produced moderate conjunctival redness and slight conjunctival chemosis in the treated unwashed and washed rabbit eyes. Additionally, minimal discharge was observed in the eye washed after treatment. The treated eyes of both rabbits were normal by 2 days after instillation. Individual eye irritation scores are presented in Tables 2 and 3. CONCLUSION Under the conditions of this study, H-22762 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-22762 probably could be classified as "NON-IRRITANT" until further data is available. Company Sanitized. Does not contain TSCA CBI 6- TABLE 1 DRAIZE3 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............ 0 1 (Slight) 2 (Mild) Opalescent areas, no details of iris visible, size of pupil barely discernible................................................................................. 3 (Moderate) Opaque, iris invisible...................................................................... 4 (Severe) (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 quarters.......................... Greater than three quarters, up to whole area................................. 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values 0 Normal............................................................................................ Folds above normal, congestion, swelling, circumcomeal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive)............ 1 (Moderate) No reaction to light, hemorrhage, gross destruction (any or all of these)......................................................................................... 2 (Severe) (3) Conjunctiva (A) Redness (refers topalpebral and bulbar conjunctiva excluding cornea and iris) Vessels normal................................................................................ Vessels definitely injected above normal....................................... More diffuse, deeper crimson red, individual vessels not easily 0 1 (Mild) discernible................................................................................. 2 (Moderate) Diffuse beefy red............................................................................ 3 (Severe) Company Sanitized. Does not contain TSCACM 7- TABLE 1 (Continued) DRAIZE 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...... 0 1 (Slight) 2 (Mild) 3 (Moderate) 4(Severe) (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........................................... 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. Company Sanitized. Does not contain TSCA CBt 8- TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE RABBIT EYE UNWASHED AFTER TREATMENT RABBIT NUMBER 32049 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 HOUR 0 0 0 2 1 0 4 HOURS 0 0 0 2 1 0 1 DAY 0 0 0 1 0 0 2 DAYS 3 DAYS 0 0 0 0 0 0 0 0 0 0 0 0 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE RABBIT EYE WASHED AFTER TREATMENT RABBIT NUMBER 32050 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 HOUR 0 0 0 2 1 1 4 HOURS 0 0 0 2 1 1 1 DAY 0 0 0 1 0 0 2 DAYS 3 DAYS 0 0 0 0 0 0 0 0 0 0 0 0 Company San^. tfaes ^ ^^ ^^ ^ 9-