Document qa92Ja8XNVggD8E03d0wge4LG

FOR DO FONT USE ONLY AR226-2970 Du Font HIS 809-91 Study Title Eye Irritation Test vithfif^lin Rabbits Author John W. Sarver Study Completed On February 13, 1992 Performing Laboratory Bsskell E. I. du Laboratory Font de Nemours and Company for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine Laboratory Project ID Haskell oratory Report No. 809-91 Page 1 of 12 ^ ^ iS1 Cott^ ^co^ ,es^ Substance Tested: Medical Research No.: Haskell Ho.? Haskell Test Code No.: Physical Form; Composition: GENERAL INFORMATION Du Font HLR 809-91 19,173 Slightly yellow liquid dispersion Purity; Synonym; Subtsitfcer's Notebook Ho. Stability: In the absence of visible evidence to the contrary, the test substance vas assumed to be stable under the conditions of administration. Sponsor? Du Font Chemicals E. I. du Font de Nemours and Company Vilmington, Delaware Substance Submitted By; Study Initiated - Completed; la-Life Phase Initiated - Completed; Uu Font Chemicals I. E. du Pont de Nemours and Company Chambers tforks Deepvater, Sew Jersey 11/15/91 - 2/13/92 11/19/91 - 11/22/91 Notebook; There are 12 pages in this report ^d.^^09^' 2 - Distributions Du Font BLR 809-91 Ejye Irritation Test with Du Font HLR 809-91 SUMMARY ^^----J^as evaluated for acute eye irritation potential in 2 rabbits. The eyes of the rabbits were examined on the day of treatment and on days 1, 2, and 3 following treatment. The test substance produced ffiild eonjunctival redness in the treated unwashed eye. Ho irritation was observed in the treated washed eye. Fluorescein stain examinations were negative for comeal injury, and bioaieroscopic eaaminations revealed no corneal damage in either treated The treated^ onwashed^ eysr TOST normal by~^a^s~foHowinif treatment. eye. Under the conditions of this study a mild eye irritant. work by; f //LO< ^UL^A^ Carol ^inlay Q Technician Study Director: ^-^fcs-^ Sa^^-\ f jJohn '-^ bO . 9. Sarver nT'e^c^h^n^oilo.g<ist Approved by; Uc^&VaRQan.Ccy^CA. ^C^hie^m^e_y_, P_h_.D_. Manager Acute Toxicology /JJohn Reviewed and F\ A "\ ^ Approved for Issue: ^BS^--^ i^>. <.Jfe|A^<^ V. Sarver '-/ Study Director ^3. /8'S/fa. Acknowledgment: Bryan V, Crossley also participated in the conduct of this study. JVS/lmr ,,^*T3C<-' Du Font HLR 809-91 QUALITY ASSURANCE DOCUMENTATION Pates, of. Ingpeetion; Conduct - 11/20/91 Records, Report(s) - 1/21/92 Findings reported to; Study Director - 1/24/92 Management - 2/11/92 Reported by: 0^^ ^fe^f 3f II ^ Janes Mackay ff- Quality Assurance Auditor ^//^ Date 5 - - -.iegrAain^30^ ^o^-a^^ ^ ffia-ntiUS8" n"asssO01-0 Du Font HL& 809-91 INTRODUCTION oJplf|in the purposeoftjris study was to evaluate the acute eye irritation potential young adult rabbits. This study vas conducted according to the applicable EPA Good laboratory Practice Regulations. Areas of aeneoapliaaee are documented in the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male and female New Zealand White rabbits were received from Hare Marland, Hewitt, Nev Jersey. The rabbits were housed singly in suspended, stainless steel, vire-aesh cages. Each rabbit vas assigned a unique identification number which was recorded on a card affixed to the cage. Purina Certified High Fiber Rabbit Chow* 15325 and water were available ad libitum. Rabbits vere 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 cycle. Environmental conditions of the rooms were targeted for a temperature of 20C 2C and relative humidity of 50% 10S. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol * On the day prior to treatment, the eyes of one female and one male New Zealand white rabbits were examined using illumination, magnification, and fluorescein dye. These animals were selected for this study as they showed no evidence of preexisting corneal or conjunctival injury or irritation and were judged to be in good health. These rabbits weighed 3608 and 3660 grams, respectively, on the day of treatment. Approximately 5.01 oL o|Hp|MMMb^sintroduced into the-lower eohjunctival sac of"each leneye.The right eye of each rabbit was net treated with the test substance and served as a control. The treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the test substance was administered, both eyes of the remaining rabbit were rinsed for approximately 1 minute with room temperature water. Each rabb' was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior was noted. .^---""' COWP^5 6_ Du Font HLR 809-91 ApproxiBately 1 and 4 hours, and 1, 2, and 3 days aftex adninistered, the rabbits were examined for evidence of eye At each of these observation periods, eyes were examined using illuainatloii and magnification and scored for ocular reactions according to the Draize scale (presented in Table 1). Syes were also observed for any unusual responses to treatment such as pannus, blistering of the conjunctiva, ulceration, or other effects indicative of corrosive action. Biofflicroscopic and fluorescein stain examinations were also conducted at post-treataent days 1, 2, and 3. The eyes were scored according to the ethod of classification presented in Table 2. Control eyes were not scored. These untreated eyes were used for comparison and were considered "nonaal" relative to the treated eye. C. Records Retention All raw data and the final report will be stored in the archives of I. Haskell Laboratory for Toxicology and Industrial Medicine, B. du Font de Neffiours and Company, Newark, Delaware or in the Du Font Records Management Center, tfilmington, Delaware. RESULTS produced mild conjunctival redness in the treated unwashed eye. irritation vas observed in the treated washed eye. Fluorescein stain examinations vere negative for corneal injury, and biomicroscopic examinations revealed no corneal damage in either treated eye. The treated unwashed eye vas normal by 3 days following treatment. Individual eye irritation scores are presented in Tables 3 and 4. CONCLUSION Under the conditions of this study yiUBHr215 a mild eye irritant. ^w^'"1^"85"8' 7 - Du Font HLK 809-91 TABLE 1 BBAIZEt 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, ao details of iris visible, . . . . . . . . . . . . size of pupil Barely dTscenffBle ....... Opaque, iris invisible .............. (B) Area of cornea involved . . . . . . . . OGnreeaqteurartthearn(oonreleqsusa)rtbeur,t nboutt zleesros than half . .' . Greater than one half, but less than three quarters ............. ...... Greater than three quarters, up to whole area . . 0 1 (Slight) 2 (Mild) 3 ^Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values Normal i Folds above normal, congestion, swelling, 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 all of these) 0 1 (Moderate) 2 (Severe) (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) 0 vessels normal Vessels definitely injected above normal 1 (Mild) ....................... More diffuse, deeper crimson red, individual vessels not easily discernible 2 (Moderate) 3 (Severe) ........................ Diffuse beefy red ^ t ^ ^ 5 Compa^9 ^K'-.* /^-', notc^" 8 - Du Font HLR 809-91 TABU 1 fCont'd) DR&IZE SCALE FOR SCORING OCULAR LESIONS (B) Chemosis No swelling Any swelling above normal (includes nictitating ................... membrane) Obvious swelling with partial aversion 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 eoistening 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) 1 Draize, J. H. "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial Committee of the Association of Pood and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. ^SKiSltoTSS^ -----^.^^atpoe3fto r-i -viStl'KPiV l3*" 9 - Du Font HLR 809-91 TABLE 2 BIOMZGROSCOPE CLASSIFICATIONS OF CORKEAL INJURY 0 No injury; cornea within normal limits. Slight (1) = Epithelial changes visible only with biomlcroscope (nay include localized area of mild injury). Mild (2) = Opacity visible with ophthalmoscope or light but shoving epithelial changes only vith biondcroscope (may include localized area of moderate injury). Moderate (3) Opacity visible with ophthalmoscope or light but shoving epithelial and stromal changes vith biomicroscope (may Include localized area of severe injury). Moderate to Severe (4) Opacity visible vith ophthalmoscope or light but shoving epithelial and stromal changes and endothelial rslucency vith unremarkable swelling. This type of injury shovs evidence of healing (reversible damage) vithin 14 days. Severe (5) = Opaqueness or opacity visible vith ophthalmoscope or light but shoving epithelial and stromal changes and endothelial relucency and swelling or other distortion. This type of injury does not shov evidence of healing (permanent damage) vithin 14 days. No biomicroscope evaluation performed. ^--T^a?^ "''"' '6,.;' " - 10 - ;^^--("s.'" ''.9,yv.' ^ Du Font HLR 809-91 TABLE 3 EYE IRRITATION BEACTIONS OBSERVED IN THE {IHirASBBD KABBIT, En! AFTEB-.TKEATMEKT VITH Rabbit HuBber 26667 Cornea Opacity .. Area Iris Conjunctiva Redness Cheaosis Discharge Bioaicroscopic Examination of Cornea 1 Hour 0 0 0 4 Hours 0 0 0 1 Day 0 0 0 2 Days 0 0 0 3 Days 0 0 0 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Fluorescein examinations: negative for corneal injury on days 1-3. ^ ^r-o'tl: g6ie<SD- o5 tioic^a' Sgw CoWp^ 11 - Du Font HLR 809-91 TABLE 4 EYE IBBITATION REACTIONS OBS13WED IN THE BASHED RABBIT EYE a y " A FTEILIREATOEMT TCTH Babbit Number 26583 Cornea Opacity Area Iris Conjunctiva Redness Cheoosis Discharge Biomicroseopic Examination of Cornea --^-- 1 Hour Sours 0 0 0 0 0 0 ^ Day -Dagys gDays 0 0 0 0 0 0 . 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Fluorescein examinations: negative for eorneal injury on days 1-3. ^^s 12