Document dYaadY8bYe6gy7rE10DEGZN9e

AR226-2989 Study Title Bye Irritation Tt with 8-20056 in Rabbif Author ^ohc 9. Sarvsr St^dy Co<iplf<l On Nay 4, 1993 PT^oCTJim Laboratory Baaifll I. E. 4u Font d NBour and Company Laboratory to^ Toxicology and Induatrlal Elkton Road, P. 0. Box 50 Nevark, Delaware 19714 Hadicim Laboratory Project ID Baakell Laboratory Report No. 309-93 Paye 1 of 11 rSaoWzg^ oggg DuPont HLR 309-93 COOP LABOKATOKT FIAC-TICI COMPLIANCE STATEMENT Thl etudy va conducted according to XPA TSCA Good Laboratory Practice Standttdi (40 CFR 792). Any ara of noneOMpUanc ar docu--nfd in the tudy reord. No dvltion xlfd that tfoefd the validity of th tody. Subaltfn I, I. du Pout d NMOun and Coap&ny SpoMori DuPwit Ch--lel ! Xi du Font d N--oun and Coapany ^snotconfafnTSCAes 2 - Substance Tested; Synonys/Codes; GENERAL INFORMATION DuPont HLR 309-93 Physical Fora; Coapositioni Sponsor; Study Initiated - Completed; In Life Phase Initiated - Completed; DuPont Ch--icals B. I* du Font de Neoours and Coapany VilRlngton, Delaware 3/22/93 - 5/4/93 3/23/93 - 3/26/93 eompany Sanitized. Does not contain TSCA W - 3 DuPont HLR 309-93 Bye Irritation Test vith H-20056 in Rabbits SUMMARY H-20056 was evaluated for acute aye Irritation potential in 2 rabbits. Approximately 0.01 L of the fat substance vaa instilled into the lover conjunctival sac of th 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 treafent and on days 1, 2, and 3 following treafent. H-20056 produced mild conjunctival redness and slight cheaosis in both treated rabbit ays and vas observed only at the 1 hour evaluation. Both treated eyea vere normal by 4 hours after treafent. Under the conditions of this study, H-20056 vaa a mild, transient eye irritant. ^AJCL^^^^^ c^d^t^V ffork by: ^JAjQjbLl CL (I Tracy A. Pilliben Toxicology Technician JVS/alv Reviewed and C\ C} \ ^s" tj. Approved for Issue; ^aJ^^ ^6J\^^______S/*{ /'O V. Sarver /jJohn ^/ Study Director Company Sanitized. Does not contain T;SGAgj DuPont HLR 309-93 QUALITY ASSURANCE DOCUMENTATION (H-20056) Dates of Inspection; Conduct - 3/23/93 Records, Report(s) - 4/30/93 Date(s) Findings Reported tot Study Director - 4/30/93 Management - 5/4/93 Reported by: Pflum4f<i /ft^ flt^L^M^ P^aeffChapman Quality Assurance Auditor ^Q Date eompanySanHized. Does not contain TSCA eg DuPont HLR 309-93 INTRODUCTION The purpose of this study vas to evaluate the acute eye irritation potential of H-20056 in young'adult rabbits. This study vas conducted according to the applicable E^AGood Laboratory Practice Standards. Areas of noncoapliance are documented ^n the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult Bale and female New Zealand White rabbits were received from Hare Harland, Hevitt* New Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit vas assigned a unique identification numoer vhich vas recorded on a card affixed to the cage. The rabbits vere offered approximately 125 grans of Purina Certified High Fiber Rabbit Chov* #5325 dally during the study. Water vas available ad libltua. Rabbits vere quarantined, veighed, 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 vere targeted for a temperature of 20C t 2C and relative tumidity of 50X i 10X. Excursions outside these ranges vere judged to have been 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 1 male and 1 female Nev Zealand White rabbits vere examined using illumination, magnification, and fluorescein dye. These animals vere selected for this study as they shoved no evidence of preexisting corneal or conjunctival injury or irritation and vere Judged to be in good health. These rabbits veighed 2907 and 3303 grams, respectively, on the day of treatment. Approximately 0.01 mL of H-20056 vas introduced into the lover conjunctival sac of each right eye. The left eye of each rabbit vas not treated with the test substance and served as a control. Approximately 20 seconds after the test substance vas administered, both eyes of 1 rabbit vere rinsed for approximately 1 minute with room temperature water. The treated and control eyes of the remaining rabbit vere not washed. Each rabbit was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior vas noted. In the absence of visible evidence to the contrary, the test substance was assumed to be stable vender the conditions of administration. Company Sam-feed. Does not contain TSCA CP? DuPont HLR 309-93 Approximately 1 and 4 hours, and 1, 2, and 3 days after H-20056 vas administered, the rabbitis vere examined for evidence of eye irritation. At each of these observation periods, eyes vere 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) treafent such as pannus, blistering of the conjunctiva, ulceration, or other effects indicative of corrosive action. Control eyes vere not scored. These untreated eyes were used for comparison and vere considered "normal" relative to the treated eye. C. Records Retention All raw data and the final report vill be stored in the archives of Baskell Laboratory for Toxicology and Industrial Medicine, B. I. du Font de Nemours and Company, Nevark, Oelavare or in the DuPont Records Management Center, Vllmlfigton, Oelavare. RESULTS H-20056 produced Mild conjunctival redness and slight chemosis in both treated rabbit eyes and vas observed only at the 1 hour evaluation. Both treated eyes vere normal by 4 hours after treatment. Individual eye Irritation scores are presented in Tables 2 and 3. CONCLUSION Under the conditions of this study, H-20056 vas a illd, transient 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 91/325, Annex VI), H-20056 probably could be classified as "MOM-IRRITANT" until further data is available. Company Sanitized. Does not contain TSCA&L DuPont HLR 309-93 TABLE 1 DRAIZE^ 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 les^) but not xero Greater than one quarter, but less 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 Folds above nomal, congestion, swelling, circiiB- ...................... 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, heaorrhage, 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) Vessels normal Vessels definitely injected above .................. More diffuse, deeper crimson red, . . . . . vessels not easily discernible ........................ Diffuse beefy red noraal individual 0 1 (Mild) 2 (Moderate) 3 (Severe) CompanySanity. Does not contain TSCA f DuPont HLR 309-93 TABLE 1 (Cont^d) DRAIZB SCALE FOR SCORING OCULAR LESIONS (B) CheBosis No svelling Any svelling above nonal (Includes nictitating ................... --brane) Obvious svelling vith partial eversion of ................... lids Svelling with lids about half closed . . . . . . . . . . . . . . . . . . . . . Svelling vith lids a)>out half closed to completely . . . . . . . closed .................... (C) Discharge ................... Ho discharge Any aaount different fco noroal (does not include SBall aaounta observed in inner canthus of nor--I aniBals) Discharge vith olstening of the lids and ................ just adjacent to lids Discharge vith aoistening of the lids and .................. and considerable are* around the eye hairs hairs, 0 1 (Slight) 2 (Mild) 3 (Hcderate) 4 (Severe) 0 1 (Hiniaal) 2 (Hoderate) 3 (Copious) 1 Draize, J. H., "Der--1 Toxiclty." Appraisal of the Safety of Cheaicals in Foods, Drugs and Cosaetics. The Editorial Co--lttee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. 9 - - Companysanifeed. Does not contain T^ TSCA CT I . DuPont HLR 309-93 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED BABBIT BYE AFTER TOBATMBff WITH H-20036 Rabbit Nubr 27857 Cornea Opacity Area Iris Conjunctiva Redneaa Ch--osis Discharge -I----------I----------I--------2----------3--- Hour Hoora Day Pay Day 0 0 0 00000000 1 1 0 0000 (Sompany Sanitized. Does not contain TSCA C': 10 DuPont HLR 309-93 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT EYE AFTER TREATMENT WITH H-20056 Rabbit Nurber 27828 Cornea Opacity Area Iris Conjunctiva Redness Cheaosis Discharge -I----------;----------^--------g----------5- Hour Hour* Day Days Daya 0 0 0 0 0 jgofflpangiSanifeed. Does not contain TSCA CEl 11 -