Document XzmEo7wz3NmyVyDEjM3x94yQK

AR226-3130 TRADE SECRET Study Title H-24119: Eye Irritation Test in Rabbits Laboratory Project ID: DuPont-3312 AUTHOR: Tracy A. Filliben STUDY COMPLETED ON: August 17,1999 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:I|BBJ SERVICE CODE NUMBER:! flB 1 company Sanitized. Does not contain TSCA CB1 Page 1 of 12 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. Reviewed by: ^WJ^^A^W^___________ Anne Marie Bathon, B.A. Senior Staff Scientist Hff'^-W Dafe PillibenDaS toned by Study DirectorN^g^Q. Qwt^f^________ Q fracy A. Associate Scientist 1^1'O^L^'tW k) Company Sanitized. DOBS not contain TSCA CBI ~~r- STUDY INFORMATION 9th Collective Nomenclature: Synonyms/Codes: j^i H-24119 Haskell Number: 24119 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 19, 1999 / (see report cover page) In-Life Initiated/Completed: July 20, 1999 / July 23, 1999 company Sanitized. Does not contain TSCA CBi! -3- STUDY PERSONNEL Study Director: Management: Primary Technician: Tracy A. Filliben Nancy C. Chromey, Ph.D. Tracy A. Pilliben Toxicology Report Preparation: Maryanne M. Wilfbrd, B.A. Laboratory Veterinarian: WandaL. West, D.V.M., A.C.L.A.M. company Sanitized. Does not contain TSCA CB1 .4- SUMMARY H-24119 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 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-24119 produced moderate conjunctiva! redness and slight chemosis in the treated unwashed rabbit eye. This eye was normal by 3 days after treatment. Slight chemosis and mild conjunctival redness were observed in the eye that was washed after treatment; all ocular irritation had resolved in this eye by 4 hours after instillation of the test substance. No clinical signs of toxicity or significant body weight losses were observed during the study. Under the conditions of this study, H-24119 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-24119 probably should not be classified as an irritant unless additional testing proves otherwise. Company Sanitized. Doss not contain TSCA CBf- -5- INTRODUCTION The purpose of this study was to evaluate the acute eye irritation potential ofH-24119 in young adult New Zealand White rabbits. MATERIALS AND METHODS A. Test Substance The test substance, H-24119, was supplied by the sponsor as The test substance was shaken to mix before each amount for do_s_in_g _wa_s_re_m_ov_e substance appeared to be stable under the conditions of the study. No evidence of 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 Mariand, 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 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 of 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 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 8 or 14 days. 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 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. Company Sanitized. Doas not contain TSCA CBl 6- H-241I9: Eye Irritation Test in Rabbits_________________________________DuPont-3312 C. 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 2603 or 3086 grams on the day of treatment. Approximately 0.01 mL ofH-24119 was introduced into the lower conjunctival sac of the right eye of 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-24119 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 (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. The rabbits were weighed on the day of treatment and at the last ocular evaluation. RESULTS AND DISCUSSION H-24119 produced moderate conjunctival redness and slight chemosis in the treated unwashed rabbit eye. This eye was normal by 3 days after treatment. Slight chemosis and mild conjunctival redness were observed in the eye that was washed after treatment; all ocular irritation had resolved in this eye by 4 hours after instillation of the test substance. No clinical signs of toxicity or significant body weight losses were observed during the study. Individual eye irritation scores are presented in Tables 2 and 3. CONCLUSIONS Under the conditions of this study, H-24119 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-24119 probably should not be classified as an irritant unless additional testing proves otherwise. -:' \ Company Sanitized. Does not contain TSCA CBI -7- H-24119: Eye Irritation Test in Rabbits_________________________________DuPont-3312 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 Font de Nemours and Company Records Management Center). D Company Sanitized. Doss not contain TSCA CBI -8- TABLES ^) Company Sanitized. Does nol contain TSCA CBI -9- TABLE 1 DRAIZE" SCALE FOR SCORING OCULAR LESIONS (1) Cornea (A) Opacity-degree of density (area most dense taken for reading) No opacity....................................................................................... 0 Scattered or diffuse area, details of iris clearly visible.................... 1 (Slight) Easily discernible translucent areas, details of iris slightly 2 (Mild) obscured.................................................................................... 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 2 (Severe) these)......................................................................................... (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels normal................................................................................ 0 Vessels definitely injected above normal........................................ 1 (Mild) More diffuse, deeper crimson red, individual vessels not easily discernible................................................................................. 2 (Moderate) Diffuse beefy red............................................................................. 3 (Severe) D Company Sanitized. Does no! contain TSCA CB1 -10- 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. -11- Company Sanitized. Does nol contain TSCA CB1 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE RABBIT EYE UNWASHED AFTER TREATMENT RABBIT NUMBER 33667 CORNEA Opacity IRIS Area CONJUNCTIVA Redness Chemosis Discharge 1 HOUR 0 0 0 2 0 0 4 HOURS 0 0 0 2 1 0 1 DAY 0 0 0 2 1 0 2 DAYS 3 DAYS 0 0 0 0 0 0 2 0 0 0 0 0 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE RABBIT EYE WASHED AFTER TREATMENT RABBIT NUMBER 33747 CORNEA Opacity IRIS Area CONJUNCTIVA Redness Chemosis Discharge 1 HOUR 0 0 0 1 1 0 4 . HOURS 0 0 0 0 0 0 1 DAY 0 0 0 0 0 0 2 DAYS 3 DAYS 0 0 0 0 0 0 0 0 0 0 0 0 -12- Company Sanitized. Does not contain TSCACB1