Document 50DNN8o6Dm0xqMXvXvvZLVNa4

AR226-3045 Study 1Mie Eye Irritation Test with H-219S3 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 Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. O. Box SO Newark, Delaware 19714 Page I of 12 Company Sanitized. Does not contain TSCA CBI Eve Irritation Test with H-21953 in Rabbits DuPont HLP 789-% Physical Form: Composition: Opaque tan to white liquid Contaminants: Purity: Submitter's Notebook N o.: CAS Registry N o .: Sponsor: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington. Delaware Company Sanitized. Does not contain TSCA CBI Study Initiated - Completed: In Life Phase in itia l Completed: 7/12/96 - 8/30/96 7/24/96 - 7/27/96 All raw data and the " ^ J S ii DuPont Records Management Center. ta T u ^ m d & r n p a n y . Newark. Lane, Wilraing.cn, DeLwara (fram ed, Company Sanitized. Does not contain TSCA CBI DuPont HLR 789% SUMMARY H-t i w was evaluated for acute eye irritation potential in 2 rabbits. Approximately 0 01 mL of the test substance was instilled into the lower conjunctival sac of the right eye Approximately 20 seconda after instillation. t o treated and control eyes 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 21953 produced moderate conjunctival redness and moderate iritis in both treated rabbit addition. Watering of the conjunctiva, mild chemosts, and coptous d lih a ra e were observed in the treated unwashed eye, and slight chemosis and moderate were o b ^ l e d 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 modrale eye irritant. Company Sanitized. Does not contain TSCA CBI i:yc -t.-q with H-2I9S3 inRabhitx SIGNATURE-PAGE DuPont HLR 7S9-96 .Report byK y /h " j ui 0 G 4R L M ^Tracy A. Filliben Toxicology Associate Work by s M' u f' ---------------- Tracy A. Filliben Toxicology Associate m Reviewed and Approved for Issue (J Tracy A. Filliben Study Director Acknowledgement: Carol Finlay and Barry Fritz also participated in the conduct of this study. TF/alw Company Sanitized. Does not contain TSCA CBI DuPont HLR 789-96 INTRODUCTION The purpose o f this study was to evaluate the acute eye irritation potential of H-21953 in young adult rabbits. MATERIALS AND METHODS Youne adult male HM:(NZW)fBR New Zealand White rabbits were received from Hare Mariand Hewill. New Jersey. The rabbits were housed singly in suspended. S l s s l whe-mesh cages. Each rabbi, was assigned a unique idenufuration number which was recorded on a card identification number were written on the inside of each rabbtt s ear wtth a a ...mii.hlp marker. The rabbits were offered appraunuttely 125 grams of Purina. C e r t f L High Fiber Rabbit Chow #5325 daily daring the study. Water was available ad libitum. Haskell Laboratory has an animal health monitoring program. This program is mmihoredand^administered by the Laboratory Vererinarian. Watt* ram p to are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, Snd other contaminants. Additionally, samples from freshly washed cages and cag racks are periodically analyzed to assure adequate sanitation b y thcage) ^ rSfe^ . from this program are maintained separately from study records. Animal feed certified by? th f manufacturer to meet specified nutritional requirements and to be free o f l list ofspecified contaminants. On the basis of these analyses, there is " evidence suggesting lh a t contaminants were present in the feed or water ,n amounts which may have interfered with the results of this study. Rabbits were quarantined, weighed, and observed for general heahhfor approximately 2 weeks. Animal rooms were maintained on a timer-controlled, dark cycle. Environmental conditions of the rooms were targeted for a `emperature of 7 0 r + lC and relative humidity of 50% 10%. Excursions outside these ranges " fu d g e d " h a s t e n of in su L ien , mugttitt.de attd/or duratiott to have adveisely effected the validity of the study. B. Protocol On the day of treatment, the eyes of 2 male New Zealand White - b b i ^ - re ^ ned using illumination, magnification, and fluorescein dye. Animals ^ ed (^ were free of pre-existing corneal or conjunctival injury or .rotation and were judged t Company Sanitized. Does not contain TSCA CBI be in good health. These rabbits weighed 2909 or 2984 grams on the day of treatment. Annroximatelv 0 01 mL of H -21953 was introduced into the lower conjunctival sac of ^ h T g h T e y e The left eye of each rabbit was not treated with die test substance and ! l e d ^ a contrel. Approximately 20 seconds after the test substance was administered both eyes of I rabbit were rinsed for approximately 1 minute with room S S S f J r . The treated and conhol eyes of the temaining rabbi, were no. washed Each rabbit was observed for approximately 30 to 60 seconds befo^ ,"8 returned to its cage, and any abnormal behavior was noted, n theabsence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions o f administration. Anoroximately 1 and 4 hours, and 1,2 . and 3 days after H-21953 was administered, tterabbits were examined for evidence of eye irritation and for clinical signs of toxicity At each of these observation periods, eyes were e ^ m m ^ u s in g illumination and magnification and scored for ocular reactions according to the DraiKScate Presented in Table 1). Eyes were also observed for any unusual responses to treatment such as pannus. blistering of the conjunctiva RESULTS h ?I953 oroduced moderate conjunctival redness and moderate iritis in both treated Company Sanitized. Does not contain TSCA CBI Eye Irritation Test with H-21953 in Rabbits CONCLUSION DuPont HLR 789-% 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 probably could be classified as NON-IRRITANT until further data is available. I -8- Company Sanitized. Does not contain TSCA CBI Irritation Test with H-21953 in Rabbits DuPont HLR 789-96 TABLEI PRAIZF1S r Al E 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 o b scu red ....................... 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 h a lf.. Greater than one half, but less than three q u arters........................................ Greater than three quarters, up to whole area . . (2) Iris (A) Values N o rm al.............................................. 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) . . . 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 norm al.................................... Vessels definitely injected above norm al......... More diffuse, deeper crimson red. individual vessels not easily discernible............... Diffuse beefy r e d ................................ 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) 0 1 (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 DuPont HLR 789-96 TABLE 1 (Cont'd) n e AI7F s rA I .F. FOR SCORING OCULAR LESIONS (B) Chemosis No sw e llin g ....................................... Any swelling above normal (includes nictitating m e m b ra n e )........... ............................ Obvious swelling with partial eversion of l i d s ............................................ Swelling with lids about half closed............. Swelling with lids about half closed to completely c lo s e d .......................................... (C) Discharge No discharge....................................... Any amount different from normal (does not include small amounts observed in inner canthus of normal anim als)................................ Discharge with moistening of the lids and hairs just adjacent to lid s .......................... Discharge with moistening of the lids and hairs, and considerable area around the e y e ......... 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Minimal) 2 (Moderate) 3 (Copious) Draize, J. H., "Dermal Toxicity." Appraisal ofthe Safety of Chemicals in Foods, Pm jlS and Cosmetics. The Editorial Committee of the Association o f Food and Drug Officials of the United States, Austin. Texas, 1959, pp. 46-59. - 10 Company Sanitized. Does not contain TSCA CBI Eye Irritation Tesi with H-2 l9S3jn_Rahhits DuPont HLR 789-% TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 3IOS8 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 Hour 4 Hours 00 00 11 22 l 2B 23 1 Day 0 0 1 2 I 0 2 Days 3 Days 00 00 00 I0 10 00 B = Blistering of the conjunctiva Company Sanitized. Does not contain TSCA CBI EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 31059 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 Hour 4 Hours 00 00 I1 22 Il 12 12 3 Day Days Days 000 000 ^ 10 o 0 2 10 10 0 000 Company Sanitized. Does not contain TSCA CBI