Document g2qVk3YOm2VymBk2K2b8gRRaN

FOR PU PONT USE ONIY ^ AR226-2947 Ou Pont HLR 127-90 Eye IrrM^ WH^i n Rabbits Dolores I* Naiek CM^^lOn March 22, 1990 , pirforniln^ L a b o r a t o r y Haskell E. I. du Font de Nemours and Goi^pany, Inc. Laboratory for Toxicology and industrial Medicine Elkton Road, P. 0. Box 50 irk, Delaware 19714 Laboratory Project 10 Haskell Laboratory Report No. 127-90 page 1 of 11 Company Sanitized. Does not contain TSCA CBI GENERALINFORMATION Du Pont HLR 127-90 Material Tested: Medical Research Ho.; Haskelt No.: Haskell Test Code No.: Physical Form: Purl^: Composition: 18,267 Synonym; Stability: Sponsor: The test material was assumed to be stable under the conditions of administration. Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Inc. Ullmlngton, Delaware Material Submitted By: Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. Study Initiated - Completed; 2/15/90 - 3/22/90 In-Life Phase Initiated - Completed: 2/21/90 - 2/24/90 Notebook; There are 11 pages In this report. Distribution; 2 - Cofftpany Sanitized. Does no? contain TSCACBl Du Pont HLR 127-90 Eye irritation Test ^thfffflf^n Rabbits SUMMARY fBH"5 evaluated for acute eye Irritation potential In 2 rabbits. The eyes of the rabbits were evaluated on the day of treatment and on days 1, 2, and 3 following treatment. The test material produced no Irritation In the treated washed or unwashed eyes throughout the study. Huoresce+ft stalir examinations were negative for corneal Injury In both treated eyes throughout the study. L'-ider the conditions of this study,flflHH|was not an eye Irritant. ^^^ii^.M.n Mork '"' Technician Study Director: ______^s^W^E' vrlJlC Dolores E. Haiek, Ph.P.------------ \,, Research Toxicologlst Acute and Developmental Toxicology Division Reviewed and Approved for Issue: ^U^.^. /U*^ /^ -s /go Dolores E. Malek. Ph.D.------------ Study Director Acknowledgment: Cralg Ughtca'p also participated In the conduct of this study. DEM;a1r:HLR131.7 3 - Company Sanitized. Does not contain TSCA CBl Du Font HW 127-90 QUALITY ASSURANCEPOCUHEOTATXON v^^^m STUDY;: W 18,267 Bye Irritation Test with i AUDITS; Item Audited Audit Date In-life Observation: of Eye Irritation Protocol Evaluation Evaluation 2/22/90 2/22/90 Study Records and Final Report HLR 127-90 3/8,12/90 in Rabbits SHORT-TERM AUDIT REPORT (DUMBERi DATE FINDINGS REPORTED TO MANAG: STUDY DIRECTOR; 3/12/90 Reported by: HidL(jgl^Q.L)t^^ 'Deborah A. Vick Quality Assurance Auditor ^z-i ho Date company Sanitized. Does no? contain TSCA CBI Du Pont HLR 127-90 iwmmfm The purpose of this was: to evaluate the acute eye Irritation f^--Bin potential of j i|il|lHlt ra1>i>fts. This study was conducted ^^d according to the appllcal Ltwrat0)7 Practice Regulations. Areas of nbncompilance are ddooccu^ntedIn the tfudy N?ordsS No deviations existed that significantly affecttA the validity of the study. i mtERl^S AND NETHQPS 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 was assigned a unique Identification hunber which was recorded on a card affixed to the cage. Purlna Certified High Fiber Rabbit Chow* f5325 and water were available ad Hot turn. [Rabbits were quarantined, weighed and observed for general health for approximately 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour Hght/12-hoyr dark cycle. Environmental conditions of the roomi were targeted for a temperature of 2Q-C. ^ 2'C and relative humidity of 502 + 101. 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 prior to study Initiation, the eyes of 2 female New Zealand White rabbits were examined using Illumination, magnification, and fluorescein dye. these animals were selected for this study as they showed no evidence of ijireexisting cornea! or conjunctiva! Injury or Irritation and were judged to be In good health. The rabbits were approximately 15 weeks,old and weighed 2918 and 2722 grams, respectively. on the day of treatment. Approximately 0.01 conjunctiva! sac of ea The left eye of each r served as a control. unwashed. Approximate administered, both eye approximately 1 minute f mL of was Introduced Into the lower kh right eye of 2 female New Zealand White rabbits. tbbit was not treated with the test material and Fhe treated and control eyes of 1 animal remained y 20 seconds after the test material was ; of the remaining rabbit were rinsed for with water at room temperature. Company Sanitized. Does not conlamTSCA CB1 Du Pont HLR 127-90 Each rabbit was observed for approximately 30 to 60 seconds before being returned to Its cage and any abnormal behavior was noted. Approximately 1 and 4 hours, and 1, 2, and 3 days after--------was administered, the rabbles were examined for evidence of eye Irritation. At each of these observation periods, eyes were examined using Illumination and magnification and scored for ocular reactions using the Draize scale (presented'In Table 1). Eyes were also observed for any unusual responses to treatment such as pannus, blistering of the conjunctiva, ulceratlon or other effects Indicative of corrosive action. Blomlcroscopic and fluorescein stain examinations were also conducted at post-treatment days 1, ?, and 3. The eyes were scored according to the metnoa bTcrasslTrcattoB presented InTibTe2. Control eyes were not scored. These untreated eyes were used for comparison and were considered "normal" relative to the treated eye. C. Records Retention All raw data and the final report win be stored In the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Inc., Newark, Delaware or In the Du Pont Records Management Center, Wllmlngton, Delaware. RESULTS --------'produced no Irritation In either the washed or unwashed rabbit eyes throughout the study. Fluorescein stain examinations were negative for corneal Injury and biomicroscopic examinations revealed no corneal Injury In both treated eyes throughout the study. Individual eye irritation scores are presented in Tables 3 and 4. CONCLUSION Under the conditions of this study, ^--------was not an eye irritant. 6 - company Sanitized. Does not contain TSCA CBI Du Pont HLR 127-90 TABLE 1 pRAIZE1 SCALE FOR SCORING OCULARLESIONS (1) Cornea (A) Opacity-degree of density (area most dense taken for reading) No opacity Scattered or diffuse area, details of Iris ............... clearly visible Eas^lly dIscemlteTe transtvcent 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 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 . . 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Localized) 2 (Small) 3 (Moderate) 4 (Generalized) (2) Iris (A) Values Normal Folds above normal, congestion, swelling, circum- ...................... 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) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and fris) 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) Company Sanitized. Does no{ contain TSCA CBI Du Pont HLR 127-90 (B) Chemosis No swelling . Any swelling abov^ normi (Includes nictitating ............ ..... . membrane) Obvious swelling 4 With partial , , , . everslonof , . ,,,.., lids SenTng with T1d8 about half dosed .....?............ Swelling with Hdi about half closed to completely closed (0 Discharge No discharge Any amount diffe nt from normal (does not Include small amounts served In Inner canthus of normal animals)! Discharge with molistening of the lids and hairs .......... just adjacent tjo lids Discharge with molistening of the lids and hairs, . . . . . . . . . . . . and considerable area around the eye . . . . 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 1 (Minimal) 2 (Moderate) 3 (Copious) 1 Draize, J. H., "Dermal ToxSclty." Appraisal Of the Safety of Chemicals In Foods. Drugs and Cosmetjfcs. The EflltoriaT committee of tne Association of Food and Drug Officials of the United States, Austin. Texas, 1959, pp. 46-59. 8 Company Sanitized. Doos not contain TSCA CBt Du Font HLR W-90 T^glEa BIOmCROSCQPECtASSIFlCATIgNOSF CORHEAl INJURY (Biomic of Cornea)-------------- Injury; cornet within normal limits. Slight (1) ' Epithelial changes visible only with blonlcroscope Way Include localized area of mild Injury). Mild (2) (pacify visible with ephthalmoscope or light but showingepithelial changes only with Morolcroscope (nay Include localized area of moderate Injury). Moderate (3) Opacity visible with ophthalmoscope or light but Showingepithelial and stromal changes with b1omicroscope (may Include localized area of Severe Injury). Moderate to Severe (4) Opacity visible with ophthalmoscope or light but lowing epithelial and stromal changes and 6ndothe11a1 relucency with unremarkable swelling. [his type of Injury shows evidence of healing (reversible damage) within 14 days. Severe (5) s Opaqueness or opacity visible with ophthalmoscope <>r light but showing epithelial and stromal changes and endothellal relucency and swelling or Other distortion. This type of Injury does not Show evidence of healing (permanent damage) within 14 days. No blomicroscope evaluation performed. company SantHzed. Does not conlam TSCA CBl Du Font HLR 127-90 EYE IRRITATION REACTIONSOBSERVEDIN UNMASKEDRABBIT EYE AFTER TREATMENTMI""* Rabbit Number 24589 -T------------i----2------r- Hour Hours Day Days Days Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Blomic of Cornea Fluorescein examinations: 0 0 0000 0 0000 0 0 0 00000000000 Negative for cornea! Injury 10 company Sanitized. Does not contain TSCA CB1 Du Pont HLR 127.90 TI^I* EYE IRRITATION REACTIONSOBSWVEDIN THE HASHEDRABBIT EVE JUTER TfiEXH^IIT UI1 iMl,.^lTEffLl^lTOg1^^ Rabbit Nmnbr 24590 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Blond c of Cornea T T T -2- J2HL Hoars Day Days -fiSXi 0 Fluorescein examinations: Negative for corneal Injury 11 - ^mpany SanWzed. Does no? certain TSCA CB1