Document jBMkvY9ER30R4R589zGB0gO29

AR226-3037 Study Title Eye Irritation Test with H-21460 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 82-96 Author Tracy A. Filliben Study Completed On February 26,1996 Performing Laboratory E. I. du Font de Nemours and Company Haskel! Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 ^- ^ _ ^j--n----HTj Page 1 of ! 1 ^"'P^y Sanitized. Does not contain TSCA CBI Substance Tested: Synonyms/Codes: Physical State: Composition: Contaminants: Purity: Submitter's Notebook No:: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: GENERAL INFORMATION DuPont HLR 82-96 DuPont Specialty Chemicals E. I. du Font de Nemours and Company Wilmington, Delaware 1/23/96 - 2/26/96 1/23/96 - 1/26/96 Company Sanitized. Does not contain TSCA CB8 ^. DuPont HLR 82-96 Eye Irritation Test with H-21460 in Rabbits SUMMARY H-21460 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-21460 produced moderate conjunctiva! redness and mild chemosis in the treated unwashed rabbit eye. Mild conjunctiva! redness was observed in the treated washed rabbit eye. The treated washed and unwashed rabbit eyes were normal by I and 2 days, respectively, following treatment. No clinical signs of toxicity were observed during the study. Under the conditions of this study, H-21460 was a moderate eye irritant. ICompany Sanitized. Does not contain TSCA CBI -3- S1GNATUP3PAGE DuPont HLR 82-96 Report by: L^yY^^^^'sQs^-^y- CLA'^^j^^^CO^^. oo^^^c'?^ (^myL. Williamson Secretary Work by: ^J^^f^ ^JJUlUUQf J T r a cTyraAcy. FAi. lFl ii lbl i beenn Toxicology Associate Reviewed and Approved for Issue: s. ^AZ^<^ ILUUJOf. />-^ ; 0Tracy A. Filliben Study Director 2 l2^l^ Acknowledgements: Bryan W. Crossley and M. Scott Karr also participated in the conduct of this study. 7F/alw Company Sanitized. Does not contain TSCA CB! -4- INTRODUCTION DuPont HLR 82-96 The purpose of this study was to evaluate the acute eye irritatk n potential of H-21460 in young adult rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult female HM:(NZW)fBR New Zealand White 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 125 grams of Purina 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 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, 12-hour light/12-hour dark Company Sanitized. Does not contain TSCA CBi DuPont HLR 82-96 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 b-xn of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day of treatment, the eyes of 2 female New Zealand White rabbits were examined using illumination, magnification, and fluorescein dye. Animals used on this study were free of pre-existing comeal or conjunctiva! injury or irritation and were judged to be in good health. These rabbits weighed 3221 or 3428 grams en the day of treatment. Approximately 0.01 mL of H-21460 was introduced into th<" 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 s'lbstance was administered, both eyes of 1 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 I and 4 hours, and 1,2, and 3 days after H-21460 was administered, the rabbits were examined for evidence of eye irritation and for clinical signs of toxicity. At each of ihese observation periods, eyes were examined using illumination and magnification and scored for ocular reactions according to the Draize scale (presented in Table I). 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. Company SamSized. Does not contain TSCA CBS DuPont HLR 82-96 C. Records Retention All raw data and the final report will be stored in the archives of Haskell Laboratory for To* Delawi 'ogy and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark, u- in the DuPont Records Management Center, Wilmington, Delaware. RESULTS H-21460 produced moderate conjunctival redness and mild chemosis in the treated unwashed rabbit eye. Mild conjunctival redness was observed in the treated washed rabbit eye. The treated washed and unwashed rabbit eyes were normal by I and 2 days, respectively, following treatment. No clinical signs of toxicity were observed during the study; however, one rabbit pawed its treated eye immediately after instillation of the test substance. Individual eye irritation scores are presented in Tables 2 and 3. CONCLUSION Under the conditions of this study, H-21460 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-21460 probably could be classified as "NON-IRRITANT" until further data is available. " 7 Company Sanitized. Does not contain TSCA CBI DuPont HLR 82-96 EYE IRRITATION TEST WITH H-21460 TABLE I DRAT7F.' 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..r.s., .up..to..w.h.ole area .. (2) Iris (A) Values Normal Folds above ........ normal, .c.o.n.g.e.s.t.io.n.,.s.w..elling, circum- corneal 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 ail of these)....... 0 1 (Slight) 2 (Mild) 3 (Moderate) 4(Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) 0 1 (Moderate) 2(Severe) -8- Company Sanitized. Does not contain TSCA CB8 DuPonf HLR 82-96 EYE IRRITATION TEST WITH H-21460 TABLE I (Confd) DRAEE SCALE FOR SCORING OCULAR LESIONS (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 ........ ................ (B) Chemosis No swelling Any swelling .ab.o.v.e. .n.o.rm..a.l .(i.n.c.lu.d.e.s. 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 (Mild) 2 (Moderate) 3 (Severe) 0 1 (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. -9- Company Sanitized. Does not contain TSCA CBI DuPont HLR 82-96 EYE IRRITATION TEST WITH H-21460 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT EYE Rabbit Number 4 1 30457 Hour Hours Day Cornea Opacity 0 0 0 Area 0 0 0 Iris 0 0 0 Conjunctiva Redness Chemosis Discharge 2 2 1 1 2 0 0 0 0 2 Days 0 0 0 3 Days 0 0 0 0 0 0 0 0 0 - 10- Company Sanitized. Does not contain TSCA CB! DuPont HLR 82-96 EYE IRRITATION TEST WITH H-2I460 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE Rabbit Number 30460 Cornea Opacity Area Iris Conjunctiva Redness Chemosi.s Discharge 1 Hour 0 0 0 4 Hours 0 0 0 1 0 0 0 0 1 Day 0 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 CBB