Document Ed2xMNj0q8RdKgwdBeLj7w9yx

AR226-3043 Study Title Eye Irritation Test with H-21987 in Rabbits Laboratory Project ID Haskel! Laboratory Report No. 606-96 Author Carol Finlay Study Completed On August 28.1996 Performing Laboratory E. L du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road. P. 0. Box 50 Newark, Delaware 19714 Page 1 of 12 .Company Sanitized. Does not contain TSCA CBI ,\e Iml.ition Ttf.sl with H-21W7 in R-ibblls GENERAL INFORMATION Substance Tested: Svnonvms: UuPuni HLR 606 96 Physical Form: Composition: Known Impurities: Purity: Structure: Submitter's Notebook No.: CAS Registry No.: Sponsor: Study InitigteJ - Completed: In Life Phase Initiated - Completed: DuPoni Specialty Chemicals E. I. du Font de Nemou;s and Company Wilmington, Delaware 8/5/96-8/28/96 8/6/96 -8/9/96 Ey Imt^ofi Tet wkfc H-21987 ia Rabbits PPtHLBife^<> GENERAL INFORMATION rONtfinued^ AIlniwdluidtheft^reponwUIbestoiedwUie^imQfHaal^Ld)0(oByf^ Toxico!(^a^Iiidbi^i^Medtoiae,E.I.duI^tdeNemoiini^ Delaware or at Iron Mountain. 200 Todds. Lane. WihwhiigtfflnD. dawue (fionaeriy DuPootRecoidsMciugenient Center). '.N! ',.':' ':j .3. Company Sanitized. Does not contain TSCA CE{ Eye Irritation Test with H-21987 in Rabbits HLR 606-96 ___________________DuPont SUMMARY H-21987 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 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-21987 produced mild conjunctiyal redness in the treated unwashed eye. Moderate iritis, moderate conjunctival redness, and slight conjunctiva! chemosis were observed in the eye washed after treatment. The treated unwashed eye was normal by 1 day, and the treated washed eye was normal by 3 days after instillation cfthe test substance. Under the conditions of this study, H-21987 was a moderate eye irritant. 4 . - Company Sanitized. Does not contain TSC.A CE Eye Irritation Test with H-21987 in Rabbits SIGNATURE PAGE DuPont HLR 606-96 Work by: ( lifl^ ^ih^fi. Carol Finlay 9 Toxicology Asssociate Reviewed and Approved for Issue: /L^ f Jh-ltX/i,, Carol Rnlay 0 f/WL Study Director Oral, Ocular, and Demial Toxicology Acknowledgement: Barry Fritz also participated in the conduct of this study. CF/Imp -5 Company Sanitized. Does not contain TSCA CBJ Eye Irritation Test with H-219S7 in Rabbits______________________DuPont HLR 606-96 INTRODUCTION The purpose of this study was to evaluate the acute eye irritation potential of H-21987 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 r'bbits 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. Haskeli Laboratory has an animal health monitoring program. This program is monitored and administered by in>; Laboratory Veterinarian. Water ssunples 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, 12hour light/12-hour dark cycle. Environmental conditions of the room; were targeted for a temperature of 20"C 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. -6- ipompany Sanitized. Does not contain TSCA CBl Eye Irritation Test with H-21987 in Rabbits______________________DuPont HLR 606-96 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 sh-dy were free of pre-existing comeal or conjunctival injury or irritation and were judged to be in good health. These rabbits weighed 3070 or 3405 grams on the day of treatment. Approximately 0.01 mL of H-21987 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. 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. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Approximately 1 and 4 hours, and 1,2. and 3 days after H-21987 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 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 of toxicity were observed during the study. H-21987 produced mild conjunctival redness in the treated unwashed eye. Moderate iritis, moderate conjunctival redness, and slight conjunctival chemosis were observed in the eye washed aiier treatment. The treated unwashed eye was normal by 1 day. and the treated washed eye was normal by 3 days after instillation of the test substance. Individual eye irritation scores are presented in Tables 2 and 3. 7" Company Sanitized. Does not contain TSCA CBI tiye Irritation Test with H-21987 in Rabbits______________________DuPont HLR 606-96 CONCLUSION Under the conditions of this study, H-21987 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-21987 probably could be Classified as "NON-IRRITANT' until further data is available. " ^P"^^"0'^""^ l:ye Imlation Test with H-219K7 in Rabbits DuPont HLR 606-96 TABLE DRA17.E 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 quarters................... Greater than three quarters, up to whole area .. (1) Iris (A) Values FNolodsrmaboavle.n..o.r.m.a.l.,.c.o.n..g.e.s.t.io.n.,..s.welling, circum- comeal injection (any or all of these or combination uf any thereof) iris still reacting ... to light (sluggish reaction is positive) No reaction to light, hemorrhage, gross destruction (any or all of these)....... (3j 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 1 (Moderate) 2 (Severe) 0 1 (Mild) 2 (Moderate) 3 (Severe) -9- Company Sanitized. Does not contain TSCA CBJ Eye Imtatitin Test with H-2I9K7 in Babbits DuPont HLR 606-% TABLE I (Cont'd) 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 .................... (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 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 1 (Minimal) 2 (Moderate) 3 (Copious) Draize.J. H., "Dermal Toxicily." Appraisal of the Safety ofCheiiicals 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. 10- ^MafnTsc Eye Irritation Test with H-21987 in Rabbits DuPont HLR 606-96 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 31071 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 Hour 0 0 0 4 Hours 0 0 0 1 1 0 0 0 0 1 Day 0 0 0 0 0 0 2 Days 0 0 0 3 Days 0 0 0 0 0 0 0 0 0 company Sanitized. Doss not contain TSCA CB6 Eye Irritation Test with H-^1987 in Rabbits DuPontHLR 606-96 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 31068 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 Hour 0 0 1 4 Hours 0 0 1 1 2 1 1 0 0 1 Day 0 0 0 1 0 0 2 Days 0 0 0 3 Days 0 0 0 1 0 0 0 0 0 - 12- Company Sanitized. Does not contain TSCACBH