Document N4qEN715g6BLJzaEmQGmgvob

PV*V"!^gS^^''"^3'S^W-"'^ ^AR226-2988 Study Title Sye Irritation test irith H-19913 in Rabbits Author John V. Sarver Study Coapleted On Hareh 10. 1993 Performing Laboratory Haskell I. E. du Font de MeBiours and Company Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 197U Medicine Medical Research M Ho Laboratory Project ID Haskell Laboratory Report Ho. 865-92 Page 1 of 12 pQEMpangSanitized. Does not contain TSCA CBS Du Pont SI& 885-92 COOP MORATORY FEACTKS COKPLIAKCS STATEMENT This study was conducted according -to'SBk'TSCA'Sood Laboratory Practice Standards (40 CER 792). Any areas of noncompliaace are documented in the ststdy records. Ko deviatioas existed that effected the validity of the study. Subaitterf 5. I. du Pont de Kemours and Company Sponsor: Du Pont Cheaicals S. I. du Pont de Nemours and Comparey Study /jJohn Pireetori^p^ (^. ^CL^r^_____3 W. Sarver \_} Toxicologist /So/^^ 2 - .Gpmpati^ Sanitized. Does not contain TSCA C51 Testeds s Du Font HLR 885-92 ; ^^SSlMS1 Paries Subtter''s Notebook No.; 39.5Z ^^wmmfmwwWinu^ None available for this polymeric product GENERAL INFORMATION (OQNT^D.) CAS gesigtry Ho. (Cont'd.); Du Font BI& 885-92 SpOHSOCi Study Initiated - Coapletedi la Life Phase Initiated - Coapleteds Du Posit Chemicals I. E. du Font d Bfeaiours and Coaspany VilBington, Etelaware 12/14/92 - 3/10/93 12/15/92 - 12/18/92 A - - OffSKpsm^.Switeed. Do@ "oi oniaa TSCA CBI. Du Font BLR 885-92 Eye Irritation Test vith B-19913 in Rabbits SUMMARY B-19913 vas evaluated for acute eye irritation potential in 2 rabbits. Approxiaately 0.01 BL of the test substance vas instilled into the lower conjunctival 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 ressining rabbit were not washed. The eyes of the rabbits were examined on the day of treatment and on days 1, 2, and 3 folloving treatment. H-19S13 produced ooderate eonjunctival redness in both treated E-abbit eyes* The treated washed and unwashed eyes were normal by 2 and 3 cEays, respectively, following treatment. Under the conditions of this study, B-19913 vas a moderate eye irritant. Work bv! ^liU^ ^3^tCJ 63. (/ Tracy A. Filliben Toxicology Technician JVS/ler /^fJohn Reviewed and ( \ f] \ Approved for Issw^-JQl^^ ^Q. .^ Qo/l^g^_____3 V. Sarver Study Director /io /^ 5 - Gsm^aay. Sanitized. Does noi wwm 'i 6CA CBl DuPont HLR 885-92 QUALITY ASSURARCE DOCUMENTATION (H-19913) Dates of ZnspeetSont Conduct - Oeeeaber 15, 1993 Records, Report(s) - February 25, 1993 March 1, 2, 1993 Date(s) Findings Reported to: Study Director - Kerch 2, 1993 Management - March 4, 1993 Reported by: y ^M^S. 7%^/ Linda S. MauzyV Quality Assurance Auditor - w Date 6 - -CompanySanitized. Does not contain TSCA CBI INTRODUCTION Du Font HLR 885-92 The purpose of this study was to evaluate the acute eye irritation potential of H-19913 in young adult rabbits. This study was conducted according to the applicable EPA Good Laboratory Practice Standards. Areas of noncoBpliance are documented in the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Anieial Husoandry Young adult Bale New Zealand Phite rabbits were received from Hare Karland, Hevitt,. Kev Jersey. The rabbits were housed singly in suspended, stainless steel, vire-mesh cages. Each rabbit v&s assigned a unique identification number which was recorded on a card affixed to the cage. The rabbits vere offered 125 grass of Purina Certified Sigh Fiber Babbie Chow 15325 daily during the study. Water v&s available ad libitua. Rabbits were quarantined, weighed, and observed for general health for approxinately 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooas were targeted for a temperature of 20C 2C and relative huidity of 50% 10X. 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 of treatment, the eyes of 2 male New Zealand White rabbits vere 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 3185 or 2737 grams on the day of treafent. Approximately 0.01 mL of H-19913 was introduced into the 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 eft 1 rabbit vere rinsed for approximately 1 minute with room temperatLEre water. The treated and control eyes of the remaining rabbit weres "ot washed. Each rabbit was observed for approximately 30 to 60 seca*^5 before being returned to its cage and any abnormal behavior was noted. In the absence of visible evidence to the contrary, the test subs tance was assumed to be stable under the conditions of administration. ^firopan^ .Sanitized. Does not contain TSCA CBi Du Font BLR 885-92 ApprosiBately 1 and 4 hours, and 1, 2, and 3 days after B-19913 vas adaiaistered, the rabbits were exacined for evidence of eye irritation. At each of these observation periods, eyes were exaained using illuaination and Damnification and scored for ocular reactions according to the Draise scale (presented in Table 1). Eyes vere also observed for any unusual responses to treatsent such as pannus, blistering of the conjunctiva, ulcesation, or other effects indicative of corrosive action. Control eyes vere not scored. These untreated eyes vere used for cottparison and were considered "noraal" relative to the treated eye. C. Records Retention I. All raw data and the final report idll be stored in the archives of Basket! laboratory for Toxicology-and Industrial Medicine, E. du Pont de Seassacs and Company, Newark, Delaware or in the Du Pont Records Management Center, Vilffiington, Delaware. RESULTS H-1991? produced moderate conjunctival redness in both treated rabbit eyes. The t "eated washed and unwashed eyes vere normal by 2 and 3 days, respectively, following treatment. Individual eye irritation scores are presented in Tables 2 and 3. CONCLUSION ^^hes^-^i ^cc'^ <t^ Under the conditions of this study, H-19913 was a moderate eye irritant* ,. .. to hi- ^wfL ^Dr ^&.c-{oe'W> c/A^^iffi.^ ^Base<Lon the repponaoe obgruad-4-tSiis study, ssri' according to the guide to the labeling of dangerous substances published in the Officia^Journal of European CoiuBunities (EEC Directive 837467, Annex VI), H-19913 probably could be classified as a "NON-IRRITAKT" until further data is available. ^u^ 8 - .Company Sanitised. Ooe not centam TSCA CBI Du Font HLR 885-92 TABLE 1 PRAIZEl SCALE FOR SCORING OCULAR LESIONS Cornea (A) Opacity-degree of density (area aost dense taken for reading) No opacity Scattered or diffuse area, details of iris ................... clearly visible ........................ .. Easily discernible translucent areas, details of iris slightly obscured e 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 G r quar eater t er th s an .t .hr .ee . .qu .ar .... ters, up .t .o .wh o l e . . .are a . 0 1 (Slight) 2 (!ild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) Iris (A) Values ...................... Noraal Folds above norsal, congestion, swelling, circuia- eorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) . . . . . . . . . . No reaction to light, henorrhage, gross destruction (any or all of these) 0 1 (Moderate) 2 (Severe) 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 normal individual 0 1 (Mild) 2 (Hod^^te) 3 (Severe) .ampanv Sanitized. 0o@ 1191 GOs'Hen 't CA CBS Du Font HLR 885-92 TABLE 1 (Cont'd) ORftZZB SCALE FOR SCORING OCULAR LESIONS (B) Cheoosis No swelling Aay swelling above noraal (includes nictitating ................... exbrane) Obvious swelling with partial eversion of ................... lids Swelling with lids about half closed . . . . . . . . . . . . . . . . . . . . . Spelling with lids about half closed to completely . . . . . . . closed .................... (C) Discharge ................... N0 discharge lay axount different froa noraal (does not include Sflull aiROunts observed in inner canthus of Booal anicals) Discharge with aoistening of the lids and ................ Just adjacent to lids Discharge with moistening of the lids and .................. and considerable area around the eye hairs hairs, 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 1 (Mi.nioal) 2 (Moderate) 3 (Copious) t Qraize, J. H. "Denaal Toxicity." Appraisal of the Safety of Cheatieals in Poods i, Prugs and Cosateties. The Editorial Committee of the Association of Food and Drug Officials of the United States, Austin, Texas; 1959, pp. 46-59. - 10 - |5aEiBpsnr.Sanitized. Does not contain TSCA CBB -- . ,.,- ~wy>.tS%)iy^5S^S-Si^S^,SSW'-ial?r - - Ou Font ELR 885-92 TABLE 2 ... .;'. BIZ ZBRITJOZOR REACTIONS OBSERVED IN THE UWgASHEP BABBIT SYB AFTER TREATHBKT gITB H-19913 Rabbit lhasber 27590 Ceroea Opacity Area Iris Conjunctiva fiswssss Gbeuaslsi Discharge T------r Hour Sours D1ay 2Pays 3___Days 0 0 0 0 0 0 - 11 - mpaii^ Sanitized. Does not contain T5CA CB1 Du Font Hl& 885-92 TABt83 EYE IEEITATION REACTIONS OBSERVED IN THE gASHEP BABBIT EYE AFTBR TSE&THEiCT VITS B-19913 Babbie Muaiber 27595 Consea Opeeity Area Iris Cwijunctiva BedBess Cheaosis Discharge 1Bottc 4Bours 1nr 2Days 3 Pays 0 0 0 0 1 0 0 0 0 0 12 - - S.inpffliX.SanStKed, Dee? net conNn TSCA CBI