Document 2j52QOoOgZZ41ndGpwg0jVwQN

AR226-2941 FOR D PONT USE ONLY Du Pont HLR 385-89 Study Title Eye Irritation Test with in Rabbits Author Dolores E. Malek Study Completed On July 31, 1989 Performing Laboratory E. I. du Pont de Nemours and Company, Inc. Haskell Laboratory for Toxicology and Industrial .Medic Elkton Road, P. 0. Box 50 laboratory Project ID Haskell Laboratory Report No. 385-89 Page 1 o f 11 _ Company Sanitized. Does not contain TSCA CBt Material Tested: Medical Research No.: Haskell No.: Physical Form: Composition: ^ Synonyms : Other Code: Stability: Sponsor: Material Submitted By: In-Life Phase Initiated - Completed: Notebook: GENERAL INFORMATION Du Pont HLR 385-89 17,869 Milky liquid dispersion The test material was assumed to be stable under the conditions of administration. Chemicals and/igments Department E. I. du Pont de Nemours and Company, Inc. Wilmington, Delaware Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Inc. Jackson Laboratory Deepwater, New Jersey 6/13/89 - 6/16/89 -i Company Sanitized. Does not contain TSCA CBf Du Pont HLR 385-89 Eve Irritation Test with MPD-7352A In Rabbits SUMMARY ________ was evaluated for acute eye Irritation potential In 2 . adult rabbits. Both rabbits were dosed with a single 0.01 ^ a l i q u o t o f t e s t material 1n 1 eve. In 1 rabbit the treated eye was washed after treatment. In the other rabbit the treated eye was not washed. The contralateral eye of each rabbitServed as a control. Both eyes of each rabbit were examined uslnq illumination and magnification at 1 and 4 hours, and 1, 2 J,,***!- following treatment. Blomicroscopic and fluorescein stain examinations were also conducted on post-treatment days 1, 2 and 3. produced mild conjunctival redness, slight chemosis and mlnima^lood-tlnged discharge by 1 hour after treatment 1" * TM bb1^* Conjunctival redness only was observed In ^ I s a n i m a l a t 4 hours. Simila ocular responses were observed in the second rabbit at 1 and 4 nours arrer treatment with the addltiort of moderate iritis and slight generalised iStv Fluorescein stain and blomicroscopic examinations were neg *e for eyes throughout the study. The treatea eyes of both rabbits were normal by 1 day following study initiation. Under the conditions of this study] irritant. 'was a moderate eye Work by: i fritti Carol ni ay Techn ian jkjLK Study Director: -------- Dolores E. Malek, Ph.u" Research Toxicologist Acute'and Developmental Toxicology Division Reviewed and Approved for Issue: DEM:alr:HLR119.12 ^ /s\ / g ^ Dolores E. Malek, pn.u. Study Director --- - 3Company Sanitized. Does not contain TSCA CB! Du Pont HLR 385-89 m u t TTY ASSURANCE DOCUMENTATION STUDY: 1 # 17,869 Eye Irritatio n Test vithj tin Rabbits AUDITS: Tfoins Audited Test System Identification and Bousing Audit Dates 6/13/89 s t u d y d i r e c t o r : 6/13/89 R eported byt ^ -- William J. Lynam Quality Assurance Auditor 6/sz/sf Date _L- Company Sanitized. Does noi contain TS CA CBI Ou Pont HLR 385-89 INTRODUCTION The purpose of this study was to evaluate the acute eye irritation ootential of ^ M i n young adult rabbits. This study was conducted according to t K p p l i c a b l e ^PA Good Laboratory Practice Regulations. Areas 5 ^ 2 c 2 p l ? i c e are documented In the study records. No deviations existed that significantly affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult female New Zealand White rabbits were received from Hare Marland Hewitt, New Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit ^ assigned a unique identification number which was recorded on a card affixed to the cage. Purina Certified High Fiber Rabbit Chow* #5325 and f available ad libitum. RUbbits were quarantined, weighed and ^ v e d for qeneral health for approximately 2 weeks. Animal rooms were maintained .on a i.imer-controlled, 12-hour light/12-hour dark cycle. L conditions of the rooms were targeted for a temperature of 20 C + 2 C and relative humidity of 50% + 10%. 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 i.ne day of study initiation, the eyes of 2 female rabbits were examined using illumination, magnification andhfluJr^ c ^ d^ : QIh animals were selected for this study as they showed no evidence of pilexlst" g cornJal or conjunctival injury or irritation and ere judged to be in good health. These rabbits ere approximately 14 * e k s old and weighed 3067 and 3086 grams, respectively, on the day of treatment. ' A 0 01 mL aliquot o f ^ M ^ ^ w a s introduced Into the lower conjunctival sac of each right eye of 2 female rabbits. The ^ eye 0 each rabbit was not treated with the test material and served as control! T h e < U S i b * treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the test administered, both eyes of the remaining rabbit were rinsed fo approximately 1 minute with water at room temperature. Each rabbit was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior was noted. - 5 Company Sanitized, Does not contain TSCA CBf Du Pont HLR 385-89 . jf t s n s ' "si* ^dSs w^bbse* SSSacSr ^S5Sr.5S5E#^ ar- S tie e y e ? Biomicr&oplc and flUoresce1 r staln e * a m n at(ons ere also conducted at post-treatment days 1, 2 and 3. The eyes were scoreo accordino to the method! of classification presented in Table 2. Control tlll tlrl TM t " ored. these entreated eyes ere used for comparison and J r * considered "normal"' relative to the treated eye Records Retention All raw data and the final report will be.s ^ . ir? the archives of dLHieaasetkNreeslimlo1urlLsaabbooanrrdaattooCrroyympafTnooyrr,T'ooIxxniict.c-,ouloNmiegLwya-rakni,,d DnIenlidaauwwstaarrrieealoorrMemindictmihenee,D^u E.PonIt. dRuecoProdnts Manaaement Center, Wilmington, Delaware. FSIIITS AND CONCLUSIONS -- -- ^ p r o d u c e d mild conjunctival redness, slight ' J f " j"!!" ' lood-tinged discharge by 1 hour after . t w i t in 1 rabbn. ^njunetlval issr-iiszjxsspi njury in both treated eyes throughout the study. The treated eyes or do abbits were normal by 1 day after study initiation. Individual eye rritation scores are presented in Tables 3 and 4. Under the conditions of this study. Pwas moderate eye irritant. - 6- . Company Sanitized. Does net aanissn TSCA CBS Ou Pont HLR 385-89 TABLE 1 DRAIZE1 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 .......................... 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) (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 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 (sluggish reaction is positive) . . . No reaction to light, hemorrhage, gross destruction (any or all of t h e s e ) .......... .. 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 normal ........ 0 1 (Mild) More diffuse, deeper crimson red, individual vessels not easily discernible .............. Diffuse beefy red .............................. 2 (Moderate) 3 (Severe) - 7Company Sanitized. Dees not contain TSCA CBl Du Pont HLR 385-89 TABLE 1 (Cont'tf) nRAIZE SCAjlE FOR SCORING OCULAR LESIONS (B) Chemosis No swelling Any swelling above normal (includes nictitating membrane)........ * * * * *.* * * Obvious swelling with partial eversion of l i d s ................ .. * : : ............ Swelling with lids about half c osed . . . Swelling with lids about half closed to completely closed ...................................... 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) (C) Discharge Anydamount9different from normal (does not include small amounts observed in inner canthus of normal animals).......... ** Discharge with moistening of the lids and nairs just adjacent to lids * Discharge with moistening of the lids and hairs, and considerable area around the eye ........ 0 1 (Minimal) 2 (Moderate) 3 (Copious) n 1 h "Dermal Toxicity." Appraisal of the Safety of Chemicals ?:arnnH,J*nn^s and R e t i e s / The M i t o H a l Committee oi the AssocTition of Food and Drug Officials o7 the United States, Austin. Texas, 19 . PP- 46-59. - 8Company Sanitized. Does not contain TSCACBI Du Pont HLR 385-89 TABLE 2 BIOMICROSCdPE CLASSIFICATIONS OF CORNEAL INJURY 1 (Biomic of Cornea) 0 = No injury; cornea within normal limits. Slight (1) = Epithelial changes visible only with biomicroscope (may include localized area of mild injury). Mild (2) = Opacity visible with ophthalmoscope or light but showing epithelial changes only with biomicroscope (may include localized area of moderate injury). Moderate (3) = Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes with biomicroscope (may include localized area of severe injury). Moderate to Severe (4) = Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes and endothelial relucency with unremarkable swelling. This type of injury shows evidence of healing (reversible damage) within 14 days. Severe (5) = Opaqueness or opacity visible with ophthalmoscope or light but showing epithelial and stromal ' changes and endothelial relucency and swelling or other distortion. This type of injury does not show evidence of healing (permanent damage) within 14 days. - = No biomicroscope evaluation performed. -9- Company Sanitized. Does not contain TSCACBI Du Pont HLR 385-89 TABLE 3 EYE IRRITATION REACTIONS OBSERVED IN UNWASHED RABBIT EYE AFTER TREATMENT WITH Rabbit Number 23931 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Biomlc of Cornea 1 hr 4 hr 1 day 2 days 3 days 01 0 0 04 0 0 0 0 11 0 0 0 11 0 0 11 0 0 00 0 0 - - 0 0 0 0 0 0 Fluorescein examinations: Negative for corneal injury at all observation periods. - 10 Company Sanitized. Does not contain TSCA CBi Du Pont HLR 385-89 TABLE 4 EYE IRRITATION REACTIONS OBSERVED IN THE ! WASHED RABBIT EYE AFTER TREATMENT WITH) ~ Rabbit Number 23932____________ __________ 1 hr Cornea Opacity Area 0 0 4 hr 0 0 1 day 0 0 ,, 2 days _ 0 0 .. 3 days _ 0 0 Iris 00 0 0 0 Conjunctiva Redness Chemosis Discharge Biomic of Cornea _ 11 0 u 10 0 0 1(H+) 0 0 0 -- 00 ,, u 0 0 0 FIuorescein-examinatiors: Negative for corneal injury at all observation periods, H+ = Hemastix* evaluation was positive for blood 11 - Company Sanitized. Does not contain TSCA CBI as