Document 0LjyB8VyomeV05YyMLBNgj50x

AR226-3047 Study Title Eye Irritation Test with H-21951 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 792-96 Author Tracy A. Filliben Study Completed On August 30,1996 Performing Laboratory Haskell E. I. du Font de Nemours and Company Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Page I of 12 Company Sanitized. Does not contain TSCA CBI Rye In-iialion Test with H-21951 in Rarbits Substance Tested: Synonyms/Codes: Haskell No.: Physical State: Composition: H-21951 Impurities: Punty: Submitter's Notebook No.: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington. Delaware 7/12/96-8/30/96 7/24/96 - 7/27/96 Company Sanitized. Does not contain TSCA CBl Eye irritation Test wilhH-21951 in Rabbits DuRnuHLR 792^6 -All raw-data and the final report wUl be stored m the aidiiyes of Had(^I^^ Toxicology and Industrial Medicine, E. L du Font de Nemours and Company, NewadE, Delaware or at Iron Mountain, 200 Todds, Lane, Wilnungtan. Delaware (formerly DuPont Records Management Center. -3- Company Sanitized. Does not contain TSCA CB1 ^L[MMAR^ H-21951 was evaluated lor acute eye irritation potential in 2 rabhiis. Approximately 0.01 mL of the lest substance was instilled into the lower conjunctival sac of the righl 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 (he day of treatment and on days I. 2. and 3 following treatment. H-21951 produced moderate conjunct! val redness and slight chemosis in both treated rabbit eyes. In addition, moderate discharge was observed in the treated unwashed rabbit eye. The treated washed and unwashed eyes were normal by 2 and 3 days, respectively. after instillation of the lest substance. No clinical signs of toxicity were observed during the study. Under the conditions of this study, H-21951 was a moderate eye irritant. 4 - Company Sanitized. Does not comaTn TSCA CB1 (-;ye lrril;iliii Tcsl willi H -'I1'.1'! in K.ihhils SIGNATURE PAGE. DuPimt HLR 792-Vh ^\ ' j*-! - \f.-dM^ Repon by: ^MJU/Q, Tracy A. Fillibcn Toxicology Associate by>'S^.(2_^^4^ Work /y Tracy A. Filliben - Toxicology Associate Reviewed and Approved for Issue: ..^S^dlJ^ Tracy A. Filliben Study Director Acknowledgement: Carol Finlay and Barry Fritz also participated in the conduct of this study. tt'/alw S Company Sanitized. Does not contain TSCA CBi t'.ye Iniliiliiiii >'csl mlh H-.'l^l in Kuhhils DuPonI HLK 792-9h INTRODUCTION The purpose ol' this study was to evaluate the acute eye imiaiion potential o(' H-21951 in young adult rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male HM:(NZW)fBR New Zealand While 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 of the identification number were written on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately i25 grams ofPurina Certified High Fiber Rabbit Chow:. #5325 daily during the study. Water was available ad I ihiturn. 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 roliforms, lead. and otnei contaminants. Additionally, samples from freshly washed cages and cage racks arc periodically analyzed to assure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed i.s 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 .imcr-controlled. 12-hour light/12-hour dark cycle. Environmental conditions of llie rooms were targeted for a temperature of 20"C 1"C and relative humidity of 50% W/<. Excursions outside these ranges were judged to have been of insuffiL-ien* magnitude and/or duration to have adversely affected the validity of the study. B. Prolocul On the day ol' trealmrn!. the eyes of 2 male New Zealand While rabbits were examined using illumination, magnification. and I'liiorcsccin dye. Animals used on this study Company Sanitized. Does not contain TSCA CB1 Hyc Irriiaiion Test with H-21951 in Rabbits____________________PuPont HLR 792-% ___werc.frce.of.pre-existing-comeal.or_conjunctivalJnjury_or-irTitalion-and-wcre-judgedtobe in good health. These rabbits weighed 2829 or 2893 grams on the day of treatment. Approximately 0.01 mL of H-21951 was introduced into the lower conjunctiva! 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 I rabbit were rinsed for approximately I 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-21951 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 H-21951 produced moderate conjunctiva! redness and slight chemosis in both treated rabbit eyes. In addition, moderate discharge was observed in the treated unwashed rabbit eye. The treated washed and unwashed eyes were normal by 2 and 3 days, respectively, after instillation of the test substance. No clinical signs of toxicity wen? observed during the study. Individual eye irritation .scores are presented in Tables 2 and 3. 7- Company Saniffzed. Does nof confam TSCA CBf Eye Imlaiion Tesi with H-21951 in Rabbits_______________DuPont HLR 792-96 CONCLUSION Under the conditions of this study, H-21951 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 publishedin the Official Journal of European Communities (EEC Directive 93/21. Annex VI), H-21951 probably could be classified as NON-IRRITANT until further data is available. 8Company Sanitized. Does not contain TSCA CBI TABLE 1 DRAKE 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 Greaqteurathratnetrhsre.e..q.u..a.r.te..rs.., .up..to..w.h.ole area .. (2) Iris (A) Values FNolodsrmaboavel.n.o.r.m..a.l,.c..o.n.g.e.s.t.io.n.,.s.w..elling, circum- comeal 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 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 CBI !-;yc Imiulion Test wilh H-21951 in Rabbits DuPoni HLR 792-96 -TABLE I (Gont'd) DRA1ZESCAU: 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 ^f the lids and hairs. and considerable area around [he eye ..... 0 I (Slight) 2 (Mild) 3 (Moderate) 4(Severe) 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. 10- Company Sanitized. Does not contain TSCA CBI Eye Irrilaliirn Test wilhH-21951 in R.ihhil.s DuRmi HLR 792-9h JABLE3_ EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 1 4 1 31052 Hour Hours Day Cornea Opacity 0 0 0 Area Iris 0 0 0 0 0 0 Conjunctiva Redness Chemosis Discharge 2 2 2 1 1 1 2 2 0 2 Days 0 0 0 3 Days 0 0 0 1 0 1 0 0 0 Compaq SanBteed. Does n.l oon,a(n TSM cA Kyc Iiriluliun Test wilh H-21951 in Rahhils DuPonI HLR 792-% -TABLE3-- EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Numbe. 31057 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge 1 4 i Hour Hours Day 0 0 0 0 0 0 0 0 0 2 1 1 1 0 0 0 0 0 2 Days 0 0 0 0 0 0 3 Days 0 0 0 0 0 0 Company Sanitized. Does not contain TSCA CBI