Document RpDJw2dV10ZmQM2dbeKB13zYB

1 AR226-2989 Study Title Bye Irritation] Test with H-20056 in Rabbits Author lohn V. Server Study Completed On May A, 1993 Parformlnx Laboratory E. I. du Pont da Neaours and Company Haskell Laboratory foil' Toxicology and Industrial Medicine Elktoi} Road, P. 0. Box SO Newark, Delaware 19714 Laboratory Project ID Haskell Laboratory Report No. 309-93 f a i l s ' Sanlll - , esnofconteJi,rscACB, Page 1 of 11 DuPont HLR 309-93 GOOD LABORATOET PBACTICB COMPLIANCE STATEHIHT Thin study vaa conductad according to BPA T8CA Good Laboratory Practice Standards (40 CPR 792). Any areas of noncoopliance are docunented in the study records. No deviations exiatod that affected the validity of the study. 8ubaitteri S. X. du Pont da Honours and Coap&ny Sponsort DuPont Chooicala B. I. du Pont do Neaours and Coapany Study Directors ^ . (a ) . John W. Sarver toxicologist i / M /1^ -2- Substance Tested: Synonyma/Codes; GENERAL INFORMATION DuPont HLR 309-93 Physical Fora: Compositioni Sponsor Study Initiated - Completed: In Life Phase Initiated - Completed: DuPont Cheaicals B. I. du Pont de Nemours and Company (filmington, Delavare 3/22/93 - 5/4/93 3/23/93 - 3/26/93 Company Sanitized Does not contain T SCA PH - 3- DuPont BLR 309-93 Bye Irritation Test with H-20056 tn Rabbits SUMH^RY H-20056 v u evaluated for acute eye Irritation potential In 2 rabbits. Approximately 0.01 aL of the test substance vas instilled into the lover conjunctival sac of the right eye of each rabbit. Approximately 20 seconds after instillation, the treated and control yes of 1 rabbit vere washed. The treated and control eyes of the remaining rabbit vere not vashed. The eyes of the rabbits vere examined on the day of treatment and on days 1, 2, and 3 folloving treatment. 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. Under the conditions of this study, H-20056 vas a mild, transient eye irritant. Work by: (I Tracy k. Fiiben Ttooxxiiccoollogy Technician Revieved and Approved for Issue: JVS/alv John V. Server Study Director S / H /`x'b Company Sanitized. Does not contain T S C A C if DuPont HLR 309-93 QUALITY ASSURANCE DOCUMENTATION (H-20056) Dates of Inspection: Conduct - 3/23/93 Records, Report(s) - 4/30/93 Date(s) Pindlngs Reported to: Study Director - 4/30/93 m Management - 5/4/93 Reported by: PA aeffChlaappmmaan Quality Assurance Auditor Date Company San itized. Does not contain TSCA C t -5- 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 B^A Good Laboratory Practice Standards. Areas of noncompliance 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 Nev Zealand Vhlte rabbits were received from Hare Norland, Hevitt* Nev Jersey. The rabbits vere housed singly in suspended, stainless steel, vire-mesh cages. Each rabbit vas assigned a unique identification number vhich vas recorded on a card affixed to the cage. The rabbits vere offered approximately 125 grams of Purina Certified High Piber Rabbit Chov* #5325 daily during the study. Water vas available ad libitum. Rabbits vere quarantined, velghed, and observed for general health for approximately 2 veeks. Animal rooms vere maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms vere targeted for a temperature of 20C 2C and relative humidity of 50X 10%. 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 velghed 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 vith 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 vith room temperature vater. The treated and control eyes of the remaining rabbit vere not vashed. Each rabbit vas 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 vas assumed to be stable tender the conditions of administration. -6 - Company Sanitized. Does not contain TSCA OBf DuPont HLR 309-93 Approximately 1 and 4 hours, and 1, 2, and 3 days after H-20056 vas administered, the rabbitjs 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 Dralze scale (presented in Table 1). Eyes vere also observed for any unusual responses toj treatment such as pannus, blistering of the conjunctiva, ulceration,; or other effects indicative of corrosive action. Control eyes vere not scared. These untreated eyes vere used for comparison and vere considered "normal'' relative to the treated eye. C. Records Retention All rav data and the final report vill be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, B. I. du Pont de Nemours and Company, pevark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. 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 mild, transient eye irritant. If these test scores are to be used for EBC/OBCD 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 "NON-IRRITANT" until further data is available. -7- Company Sanitized. Does not contain T SC C DuPont HLR 309-93 TABLE 1 PRAIZB* SCALE POR SCORING OCULAR LESIONS (1) 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 o b s c u r e d ......... .......... Opalescent aress, np details of iris visible, size of pupil bajrely discernible........... Opaque, iris Invisible ........................ 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) (B) Area of cornea involved One quarter (or leap) 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 whole area . . 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) - (2) Iris (A) Values Normal ....................................... Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (slugglph 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) Vessels normal ................................ 0 Vessels definitely injected above normal ....... 1 (Mild) More diffuse, deeper crimson red, individual vessels not easily discernible ............. 2 (Moderate) Diffuse beefy red . .......................... 3 (Severe) 8- - Company Sanitized ' Does not contain TSCA DuPont HLR 309-93 TABLE 1 (Cont'd) DEAXZB SCALE FOR SCORING OCULAR LESIONS (B) Chenosis No swelling .................................. Any swelling above noraal (includes nictitating aeabrane) . . . ............................. Obvious swelling with partial eversion of l i d s ......... ............................ Swelling with lids about half closed ........... Swelling with lids about half closed to conpletely c l o s e d ................. 0 1 (Slight) 2 (Hild) 3 (Moderate) 4 (Severe) (C) Discharge No discharge. . . . . . . ...................... Any anount different froa noraal (does not include saall aaounts observed in inner canthus of noraal aniaals) . ........................... Discharge with aolatening of the lids and hairs just adjacent to l i d s ......... ............ Discharge vith aoistening of the lids and hairs, and considerable Area around the eye ........ 0 1 (Mlniaal) 2 (Moderate) 3 (Copious) 1 Draize, J. B., "Deraal Toxicity." Appraisal of the Safety of Cheatcals in Poods, Drugs and Cosaetics. The Editorial Coaaittee of the Association of Food and Drug Officials ot the United States, Austin, Texas, 1959, pp. 46-59. -9- eom pan, Sanitized. Does no! com m t sot. 0=J 9 DuPont HLR 309-93 TABLE 2 EYE IRRITATION REACTIONS OBSERVED IN THE UNWASHED RABBIT BYE AFTER TRBATHBNT WITH H-200S6 Rabbit Nuabar 278S7 Cornea Opacity Area Iris Conjunctiva Redness Cheaosis Discharge ------- - I ---- ---- ;---- 1 --- J -- -- 3------ Hour Hours Day Days __ Days____ 0 0 00 0 0 0 00 0 0 0 00 0 1 0 00 0 1 0 00 0 0 0 00 0 Company Sanitized. Does not contain TSCA C - 10 I DuPont HLR 309-93 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN THE WASHED RABBIT BYE AFTER TREATMENT WITH H-20056 Rabbit Dunbar 27828 Cornea Opacity Area Iris Conjunctiva Redness Cheeosis Discharge ------------------1------- ------- ? ------- ------1----------- 2------- -- 3-----------Hour Hours Day Days Days 0 0 00 0 0 0 00 0 0 0 00 0 1 0 00 0 1 0 00 0 0 0 00 0 CD:Jgoffipaig Sanitised. Does not contain TSCA Wr - 11 - MW