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AR226-3016 Study Titl Bye Irritation Test vith B-21095 in Rabbits Laboratory Project ID Baskell Laboratory Report No. 271-95 Author Carol Finlay Study Completed On April 20, 1995 Performing Laboratory Haskell E. I. du Laboratory Font de Neaours and Company for Toxicology and Industrial Elk ton Road, P. 0. Box 50 Nevark, Delaware 19714 Hedicine Hed i cal Research No. Company Sanitized. Does not contain TSCA CBI' Page i of 10 SSm?Srfkw':-tl'"~ ..ailaaBaseiU^ ^.^^ml^., Physical Fora; Coapogition; Transparent tan liquid H-21095 contains; Cont--iMtfttas gagiey; CASJIyjistry Hp.; Spongors Study InitiatOd - Coapletedi Zn Life Hbase Initiated - CoBpletedji None 30? Hone available DuPont Specialty Chemicals E. I. du Pont de Seaours and CoBpany Wiliiogton, Delaware 4/3/95 - 4/20/95 4/4/95 - 4/7/95 f&sg& Eye Irritation Tot vith g210*S ia iiafchitg sununr H-21095 was evaluated for acute eye irritatioa potential in. 2 rabbif* An aliquot of 0.01 L of the test sac of the right eye substance was instilled intoSfthe lover of each rabbit. Approxi--tly 20 seceadf corajunctival after instillation, the treated and control eyes of 1 rabbit ver vxhed. washed. Ittf The treated and control eyes of the renaining rabbit were not eyes of the rabbits vere ex&Rined on the day of treafent and on days 1, 2, and 3 following treafent. H-21095 produced aild conJunetival redness in the treated unvashed eye. Mild conjunctival rednesisn, sthliegheytecvhaesBhosdisa, ftaendr Mtroedaefraetne t.bloTohde-titnrgeeadted ey-- discharge vere observed of both rabbits vere norul by 4 hours after Instillation. No clinical l-CKi of toxicity ere observed during-the study. Under the conditions of this study, H-21095 was a aild, transient eye irritant. ork by: L ^A^^jilkl^ Oarer Finfay Toxicology Associate Reviewed b^y: /\- ^^MJH^ 0. ^'^JJJjUiAlUWU ^-y^uuLu traraeqyr'A. HriilllAbi " Jv Two--x^ictaoolol--guy Tjeifchh--nilciliain Reviewed and Approved for Issue: < ^ C lL>t<- .T^H ^ /t6^ Cf/slv .^tegMfetga^.^iaaiSi DuPont BU 271-95 IHTKOPOCnOII The purpose of this study was to evaluate the acute eye irritation potential of H-21095 in young adult rabbits. MATERIALS AND METHODS A. Aniaal Husbandry Young adult female HM;(NZV)fBR rabbits were received from Hare Marland, Hewitt, Nev Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which vas recorded on a card affixed to the cage. The last 3 digits of the identificatior number were written on the inside of each rabbit's ear vith a water insoluble marker. The rabbits were offered approximately 125 grans of Purina Certified High Fiber Rabbit Chow* #5325 daily during the study. Vater was available ad libitum. Haskell Laboratory has an animal health moritoring program. This program is monitored and administered by the Lafcoratory Veterinarian. Water sanples are periodically analyzed for total bacterial counts and for the presence of coll forms, lead, and other contaminants. Additipr.ally, samples from freshly washed cages and cage racks are periodically analyzed to assure adequate sanitation by the cagevashers. 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 vater in anounts 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 timercontrolled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20"C 1*C and relative lucidity of 50t IOX. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. S. Protocol On the day of treatment, the eyes of 2 female New Zealand White rabbits were examined using illwination, magnification, and fluorescein dye. Animals used on this study were free of pre-existing corneal or ^Panysa^^; * - '^^^rsCACSf DufORt KM 271-95 conjunctiva! injury or irritation end 2622 vr judged to be in good h--lth. th day of tr--t--aito The-- rabbits weighed 2269 or grau on to aliquot of 0.01 BL of H-21095 of eaeh right eye. vas The introduced into the lover left eye of each rabbit was not eonjunctival ac the teat substance and served aa a control. Approxi--tely both eyec of 1 treated with 20 seconds after the test substance vas 1 administered, with rooa teperature rabbit were The rinsed for approxiiately treated and control eyes ainute of the remaining rabbit vere not for approxiaately 30 to 60 seconds water. washed. Each rabbit vas observed abnoroal behavior vas noted. before being returned to its cage, and any of visible evidence to the contrary, the test substance the conditions of adainistration. In the abaence ^.as assured to be stable under Approxiaately 1 and 4 hours, and 1, exanined 2, and 3 days a;cer for evidence c? eye H-21095 vas iritrtion. administered, the rabbits were observation periods, eyes vere exaalned using according Ailtluemacinhaotifontheansde ag(npirfeicsaentitoend ainnd Tsacbolered1).for Eoyecsulawerereaaclstioonosbserved for to the Draize scale any unuuual responses to treatment such as pannus, blistering of the indicative of corrosive action. conjunctiva, ulceration, or other effects the rabbits were exaained for clinical signs of toxieity at Additionally, each observation period. A Henastix* reagent strip vas used to detect of 1 rabbit. Control eyes occult blood in discharge from the treated eye These untreated eyes vere used for conparison and vere were not scored. considered "normal" relative to the treated eye. C. Records Retention All raw data and the final report and will be stored in the archives of Industrial Medicine, E. I. du Font HdeasHkoenlol uLrsabaonrdatoCroympfaonry, TNoexwicaorklo., gyDelaware OK in the DuPont Records Management Center, Wiloington, Delaware. RESULTS H-21095 produced aild eonjunctival redness in the treated unwashed and moderate blood-tinged eye. Mild conjunctiva! redness, observed in slight cheaosis, the eye washed after tre&fent. The treated eyes dooiffscbthooaxthrigeeriatywbbewrietesrewoebresenrvoerdaadl ubrying4 hthoeursstuadfyte. r Iinndsitviildlautaiol ney. e Nirorictalitnioicnal ssciogrness are presented in Tables 2 and 3. Does not conSam TSCfi. 5 - ou COREE 0 SS HE OF Durst MERHCISECC comcuuston was 1 z BE PelUndertthee ttnconditionsof thisote study, K-110%5v-as il, cransieiw biff |RHE If these test scores are to be used for EBC/OECD classification, according to the guide to the labeling of dangerous substancesJubiishnd in 7 - i i available, 4 i Ht-h2e1O0f9f5icpiraolbaJboluyrncaoluldof bEeurcolpaesssnifCieodmsuasnit"iNeOsN-I(REREICTADNiTr"ectuinvteil 93f/u2r1t,heArndnaetxaVIi)s, | |i : | i i | + F: 4i Sa,pg ey, od nlasaa ag 6 ! ` +H eB Gb el cudiibn] Oufowt BJl ETE IRRITATION TEST VITfl B-21095 TABU 1 Mma* SCALE you SCORING OCULAR LESIOHS (1) Cornea (A) Opacity-degree of density (area ost dense taken for reading) Ho opacity Scattered or diffuse area, details of iris .................... clearly visible Easily discernible translucent areas, details of ................ iris slightly obscured Opalescent areas, no deiails of iris visible, ............ size of pupil barely discernible Opaque, iris invisible ..................... (9) 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 vhole area . . 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (SBall) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values Norcal Folds above nornal, congestion, swelling, circua- ...................... 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) Rednecs (refers to palpebral and bulbar conjunctiva excluding cornea and it is) Vesseic noraal Q Vessel* definitely Injected above noreal 1 (Mild) .................. Here diffuse, deeper criason red, individual . . . . . vessels nut easily discernible 2 (Moderate) ........................ Diffuse beefy red 3 (Severe) t lDoesrfofes^^^ 7 - Dufoat BLR 271-95 EYE IRRITATION TEST CTTH S-21095 TABLE 1 (Cont'd) DRAIZE SCALE FOR SCaSSIB OCULAR LBSIOBS (B) Chcmosis No svelling Any svelling abo-'e normal (includes nictitating ................... aeBbrane} Obvious svelling vith partial eversion of ................... lids Svelling vith lids about half closed ..................... Swelling vith lids about half closed to completely . . . . . . . closed .................... (C) Discharge No discharge Any amount different from normal (does not include . . . . . . . . . . . . . . . . . . . snail aaounts observed in inner c^nthu'. of normal animals) Discharge vith moistening of the lids and ................ just adjacent to lids Discharge vith moistening of the lids and . . . . . . . . .......... and considerable area around the eye hairs hairs, 1 (Slight) 2 (Mild) 3 (Moderate) A (Severe) 0 1 (Miniul) 2 (Moderate) 3 (Copious) 1 Draize, J. H., "Deraal Toxicity." Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial Co--it tee of the Association of Pood and Drug Officials of the united States, Austin, Texas, 1959,.pp. 46-59. ^^^^.Does^ eonfafoTSCAGW 8 - DuPcnt LX 271-95 EYE IRKITATIOM TEST VITB H-21095 TABLg 2 EYE IIUlITATIOti REACTIONS OBSERVED IN TBE UNWASBBD RABBIT ETE Rabbit Nunber" 30019 Cornea Opacity Area Iris Conjunctiva Redness Cheaoiis Discharge "i----------5- Hour Hours 1----------g------------3- Day Days Pays 0 0 0 0 Wzetf. 9 - Rabbit Nurber 30020 Cornea Opacity Area 1 4 1 i S Hour Hours Day Days Om 0 0 0 0 0 0 0 0 0 C Iris Conjunctiva Redness Cheaosis Discharge 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 2H+ 0 0 0 0 H* - Heaastix* evaluation positive for blood