Document wg5L3NRNoqxRJgGm8nVaZ8ea6

V- P' S tudy Completed On May 20, 1991 I 1, Performing laboratory Haskell E. I. du Pont de Nemours arid Company laboratory for Toxicology and Industrial Medicine Elktdin Road, P. 0. Box 5 N e wark, Delaware 19714 Laribjo:ratory Project ID Haskell Lab oratory Report No. 333-91 !Page 1 of 12 i ( 3 Material Tested. Medical Research No.: Haskell No.: Haskell Test Code No.? Physical Form: Purity: Composition: GliNEBAL JNFOKMATIOH - iS-.-srie-- Du Pont HLA 333-91 Synonyms : Other Codes: CAS Registry No.: -2- Triftp I'Kfflit;*''** ;v'*-Mi `111fWs^ri^i '. -jj. :-i IMS'! :&t B?fSSSi .... Stability: -to t eterici .yap 'tg. he condition M ;' Sponsor: Near'<rs and Coapany pare Material Submitted By: Nemours and Company Deeup-vi ta-teir/N eVifJ-i,e^rsey Study Initiated - Completed: 4/19/91 - 5/20/l In-Life Phase Initiated - Completed: 4/23/91 - 4/26/91 Notebook: There are 12 pages in this report Distribution: I i "\ 3 I iV.-n*: WW Stability: Sponsor: Material Submitted By: v i e i l l e ; tp|y. X atera! yap mmmx4 i* he conditi5*of /* Nenr'*rs and Company yare Nemours and Company Study Initiated - Completed: In-Life Phase Initiated - Completed: 4/23/91 - 4/2/91 Notebook: There are 12 pages in this re|port Distribution: r -3- Eye Irritation Test Du Pont HUI 333-91 in Rabbits SUMMARY ras evaluated 9,:r acute eye irritation potential in 2 rabbits, The eyes o r T h e rabbits were examined on the day of treatment and on days 1, 2, and 3 following treatment The test material produced no irritation in either the washed or unvashei rabbit eye. Fluorescein tain examinations were negative for corneal in; ury, and bionicroscopic examinations revealed no corneal damage in either treiated eye. Under the conditions of his study] ras not an eye irritant. Work by: Study Director: CAbrL Carol Finlay Q Technician L p ^SoJ\yyr^\ John V. Sarver Technologist Approved by: Napgj C. Chromey, f f i . T h Manager Acute Toxicology Reviewed and Approved for Issue: John W. Sarver Study Director S /So/Cj ( Acknowledgement: Bryan W. Crossley also participated in the conduct of this study. JWS/lmr CO'spart -4- t\o' Oos n i s e * c *' f PPPMPI w m m g m n s r 5 Du Pont HLR 333-91 i QUALITY ASSURANCE DOCUMENTATION STUDY: H* 18,920 Eye Irritation Test with in Rabbits AUDITS: Items Audited Protocol, conduct Records, final report Audit Dates 4/23/91 5/14/91 SHORT-TERM AUDIT REPORT NUMBERi DATE FINDINGS REPORTED TO MANAGEMENT D STUDY DIRECTOR: 5/15/91 Reported by Quality Assurance Auditor Date CBl 5 Du Pont BLR 333-91 INTRODUCTION Hie purpose of tfrjp study as to evaluate ffce q$ute eye irritation potential o f B H ^ H p n young ladult rabbits. This study vas conducted according to tn^appTicable EPA Good Laboratory Practice Regulations. Areas of noncompliance are documented in the study records. No deviations existed that affected the validity of t:he study. MATERIALS AND METHODS A. Animal Husbandry I Tuung adult female Nev Zealand White rabbits vere received from Hare Marlaud, Hewitt, Nev Jersey^ The rabbits were housed singly in suspended, stainless steel,;vire-mesh cages. Each rabbit vas assigned a unique identification numbef vhich vas recorded on a card affixed to the cage. Purina Certified High Fiber Rabbit Chov #5325 and water vere available ad libitum. Rabbets vere quarantined, weighed and observed for general health for approximately 2 veeks. Animal rooms vere maintained on a timer-controlled, 12-hpur light/12-hour dark cycle. Environmental conditions of the rooms ver targeted for a temperature of 20CC 2C and relative humidity of 50Z 101. 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 2 female New Zealand White rabbits vere examined using illumination, magnification and fluorescein dye. These animals vere selected for this study as they showed no evidence of preexisting cornjeal or conjunctival injury or irritation and vere judged to be in good health. These rabbits weighed 2787 and 2947 grams, respectively, on the day of treatment. Approximately 0.01 mL o f l H ^ B H H v a s introduced into the lover conjunctival sac of each r a b l l m ^ ^ ^ ^ n t eye. The left eye of each rabbit vas not treated with the test material and served as a control. The treated and control eyes of 1 animal remained unwashed. Approximately 20 seconds after the test material vas administered, both eyes of the remaining rabbit vere rinsed! for approximately 1 minute with room temperature water. Each rabbit vas observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior vas noted. -6- ir.*.'l'W M ! l.Wjjj-*nigg.jg$ Ou t m t ' '>-f>`i* . . i-'m Appratirne . 3 days afterW P B M j vs*, adninisieped, idence of. p y ? . At (eaj^i. # j e ... illumination i#j |e exaoined f|[nfV;.:;!^1,;v ". ocular reactions ap to the Bpgfze res vere also observed for any unusual re, ius, blistering of tile conjunctiva, r 5_itive of corrosiveaction. Biomicroscoplc and Ions vere also conducted at post-treatment method of classification'-: |e scored according to the s Control eyes were not scored. These untreated and vere considered "normal11 rel* iw to the' * M H U t - All rav data and the final report will be stored in the archives of ft.ell Laboratory for Ti'CXi oology and Xndiuistrial Medicine, E. I. du Pont de Nemours and Company, j($evaric, Delaware or in the Du Pont Records Management Center, Vi Imitigton, Delaware. RESULTS ^ _______ p r o d u c e d no irr itation in either treated rabbit eye. Fluorescein's tain examinationn^s vere negative for corneal injury, and biomicroscopic examinations revealed no corneal damage in either treated eye. Individual eye irritation see res are presented in Tables 3 and 4. CONCLUSION Under the conditions of tlhis study, 3Ivas not an eye irritant. '\ J I! ' ' v` .:; ZlriM Du Pont BUI 333-91 TABLE 1 DRAIZE* SGA FQR SCORIKG BCHLAB LESIONS (1) Cornea i ... (A) Opacity-degree of density (area Bost dense taken for reading) No opacity . . . . T ............... - * * * Scattered or diffuse area, details of iris clearly visible i . . . * Easily discernible translucent areas, details of iris slightly obscured . . . . Opalescent areas n 6 details of iris visible, size of pupil barely discernible . . . . Opaque, iris invisible (B) Area of cornea involved One quarter (or les$) 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 (Slight) 2 (Hild) 3 (Moderate) A (Severe) 1 (Localized) 2 (Small) 3 (Moderate) A (Generalized) V (2) Iris (A) Values N o r m a l .............................. Folds above normal, congestion, swelling, circum- corneal injection (any or all of these or combination of aijy thereof) iris still reacting to light (sluggish reaction is positive) . . 1 (Moderate) No reaction to light, hemorrhage, gross destruction (any or all of these) . ........... 2 (Severe) (3) Conjunctiva . .. (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea:and iris) Vessels normal ......... Vessels definitely injected above normal ......... !? l l"110* More diffuse, deeper crimson red, individual vessels not easily discernible . . ........... Diffuse beefy red * ........... ................... 2 (Moderate) (Severe) 3 )) 8- - Somp'SnySanKff*i-e3o. CB1 eoniS5n T S C A (B) Chemosis No svelili^ sveliiog *iW''W ^ W S W M . Swelling with lids #$$ut '** ;4**'' closed . . (C) Discharge No discharge . . . ...... , ..... Any amount different iirom normal '(dp^ji small amounts bhseirved in inner csntl normal animals) . . , . . |SiA * * ` * Discharge with moistening of the lids'a b d h a i r s just adjacent to libs Discharge with moistening of the lids iand h a i r s , and considerable area around the eye 1 (Minimal) 2 (Moderate) 3 (Copious) m & 1 Draize, J. H., "Dermal Toxicity:y," Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics The Editorial Committee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. -9- % Du Pont HLR 333-91 V T ^ j g ;2 , .... BIOMICROSCOPE LASBXFIC&TIONSOF UffilNBiL INJURY No injury cornea within normal limits Slight (1) Epithelial changes visible only with biomicroscope (miiy include localized area of mild injury) Mild (2) - Opacity visible with ophthalmoscope or light but shaving epithelial changes only with biomicroscope (may include localized area of moderate injury). D 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. Thjs type of injury shows evidence of healing (reversible damage) within 14 days. Severe (5) = Opaqueness or opacity visible with ophthalmoscope or light but shoving epithelial and stromal changes and endothelial relucency and svelling or other distortion. This type of injury does not shdv evidence of healing (permanent damage) within 1 4 'days. No biomicroscope evaluation performed. Tscft r** V - 10 - Compaq Rabbit Number 26289 Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Biomicroscopic Examination of Cornea 0 0 0 0 0 0 0 00 0 0 00 0 0 00 0 0 00 0 0 00 0 0 00 0 00 0 Fluorescein examinations: negative for corneal injury at all observation periods. nlSCAOBi contai Cornea Opacity Area Iris Conjunctiva Redness Chemosis Discharge Biomicroscopic Examination of Cornea o: 0 0 0 6 0 0 Ml' 0 'M 0 0, o 0 'fV :: 1 00 00 00 0 0 0 0 0 0 G 00 0 0 0 0 0 0 0 if 1. Fluorescein examinations: ns tive for corneal at all observation :S periods ih- s % : 7 i H 1 :i - 12 WiastViSeA^ yvi-? tjv;-- : T' i ? 5