Document G5Xqwaan3rV41g1kB7KN4kzex

AR226-3037 Study Tille 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 Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. O. Box 50 Newark, Delaware 19714 rage 1 of 11 Company Sanitized. Does not contain TSCA CBI Substance Tested: Svnonvms/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 Pont de Nemours and Company Wilmington, Delaware 1/23/96 - 2/26/96 1/23/96- 1/26/96 Company Sanitized. Does not contain TSC CB1 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 o f the test substance was instilled into the lower conjunctival sac of the right eye o f 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 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. Under the conditions of this study, H-21460 was a moderate eye irritant. .Company Sanitized. Does not contain TSCA CB1 -3- S1GNATUP1 PAGE DuPont HLR 82-96 Report by: (& ny L. Williamson Secretary d. Tracy A. Filliben Toxicology Associate kastjj Q.Reviewed and Approved for Issue: . Tracy A. Filliben Study Director 2 z&qc Acknowledgements: Bryan W. Crossley and M. Scott Karr also participated in the conduct o f this study. TF/alw Company Sanitized. Does not contain TSC CBI -4 - INTRODUCTION DuPont HLR 82-96 The purpose o f 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 o f a list o f 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 -5Company Sanitized. Does not contain TSCA CBI DuPont HLR 82-96 cycle. Environmental conditions of the rooms were targeted for a temperature of 20C |C and relative humidity o f 50% 10%. Excursions outside these ranges were judged to have boen o f insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day o f 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 conjunctival injuiy or irritation and were judged to be in good health. These rabbits weighed 3221 or 3428 grams cn the day o f treatment. Approximately 0.01 mL of H-21460 was introduced into tlv 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 o f 1 rabbit were rinsed for approximately I minute with room temperature water. The treated and control eyes o f 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-21460 was administered, the rabbits were examined for evidence of eye irritation and for clinical signs o f toxicity. At each o f 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 o f 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. -6- Company Sanitized. Does not contain TSC CBI DuPont HLR 82-96 C. Records Retention All raw data and the final report will be stored in the archives o f Haskell Laboratory for To* 'ogy and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark, Delaw, 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 o f 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 TABLE1 DRAIZE1 SCALE FOR SCORING OCULAR LESIONS (1) Cornea (A) Opacity-degree of density (area most dense taken for reading) No o p a c ity .......................................... 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 o f pupil barely discernible............. Opaque, iris invisible............................ (B) Area of cornea involved One quarter (or less) but not z e ro ............... Greater than one quarter, but less than half. . . Greater than one half, but less than three q u arte rs......................................... Greater than three quarters, up to whole area . . (2) Iris (A) Values N o rm al............................................... Folds above normal, congestion, swelling, circumcorneal 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 o f these)............. 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized)2 0 1 (Moderate) 2 (Severe) - 8 - Company Sanitized. Does not contain TSC CBS DuPont HLR 82-96 EYE IRRITATION TEST WITH H-2I460 TABLE I CCont'dY PRAIZE SCALE FOR SCORING OCULAR .ESTONS (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels no rm al..................... Vessels definitely injected above normal......... More diffuse, deeper crimson red, individual vessels not easily discernible............... Diffuse beefy r e d ................. . ............ (B) Chemosis No s w e llin g ........................................ Any swelling above normal (includes nictitating membrane) ....................................... Obvious swelling with partial eversion of H<JS ............................................ Swelling with lids about half closed............. Swelling with lids about half closed to completely c *ose<* ......... ................................ (C) Discharge No disch arg e........................................ Any amount different from normal (does not include small amounts observed in inner canthus o f 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 ___ _ 0 j (Mild) 2 (Moderate) 3 (Severe) 0 I (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 1 (Minimal) 2 (Moderate) 3 (Copious) Cosmetics. The Editorial Committee of the Association o f 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 1 4 1 2 3 30457 Hour Hours Day Days Days Cornea Opacity 00 00 0 Area 0 0 0 0 0 Iris 0 0 0 0 0 Conjunctiva Redness 22 I00 Chemosis I 200 0 Discharge 0000 0 - 10 - Company Sanitized. Does not contain TSCA CBI DuPont HLR 82-96 EYE IRRITATION TEST WITH H-21460 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE 1 Rabbit Number 30460 Cornea 1 Hour 4 Hours I Day 2 Days 3 Days Opacity Area Iris 00000 00 000 0000 0 Conjunctiva Redness Chemosis Discharge ! 1000 0000 0 00 00 0 - Il - Company Sanitized. Does not contain TSCA CBS