Document m12Y4a5mpvXjEqbOpGK0ZzE4

^;:^..!f^ AR226-2796 Haskell Laboratory Report No. 799-85 Hasken E* I. du Font de Nemours and Coapany Laboratory for Toxicology and Industrial P. 0. Box 50, Erkton Road Newark, Delaware 19714 Medicine Date Issued: February 12, 1986 Company Sanitized. Does not contain TSCA CB1 ___ _____nas evaluated for produced slight cornea! opacity frott 1 hou?througt 2 days in the unwashed eye,-4ilo-eye-iwUation -was-obsen gd-tn the washed-eye^throughout the study. Fluorescein examinations were negiittve at all Intervals. The unwashed eye was normal Within 3 days after trralBient. Under the conditions of this Study, slight eye Irritant. was a Work by: tAojLClAhQ^L^lcL ^f/^fS^ ----BeEwnna?cF------------ Technician Study Director: ^'^^f ' ^" John E. Henry Technologist ?-/t9f^ Approved by: t[ea^^f^tLfHQffacCy^^i a.fl. ^/f^ Section Supervisor. Acute Investigations Section JEH:smk:HLR21.5 - 2- Company Sanitized. Does not contain TSCA CBI HIX799-W .yv'-i.iS .^'-.'^wy RABBITS OF Because short-tera studies are niferoua and routine Is nature, representative etudiea fro chia teat cype are audited quarterly eo enaure the tadiea are deaigned ad conducted in coapliance ifch the Good Laboratory Practice Scandarda* : Reported by: ^ ^e.J^C. MX--U aeepphh C. HaBill ty Assurance Auditor 3 - Company Sanitized. Does not contain TSCA CBI Material Tested: Sponsor: Material Submitted By Chemicals and Pigments Department E I duPont de Neoours and Company Jackson Laboratory Deepwater, Mew Jersey Test Facility; E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine P. 0. Box 50, Elkton Road Newark, Delaware 19714 Study Initiated - Completed; 8/13/85 - 8/16/85 There are 12 pages in this report. Distribution: 4 company Sanitized. Does not contain TSCA CB1 ;""->'. ^^'^'^."W^I^B^ ''HLrwas- . " .':"..-' '..^; F.'i.;^W^^':. irritation potential lited according to the NBNU Areas of noncoipl lance latlons existed that significantly MATERIALS ANOmHOOS A. Animal Husbandry Young adult sale New Zealand White rabbits Mere received frca Buckshire Corporation, PerKasle, Pennsylvania. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique Identification nua&er urtilch MS recorded on a card affixed to the cage. Purlna Certified Rabbit ChW f5322 and water were available ad llbltum. Rabbits were quarantined, weighed and observed for general heZTth for approximately 2 weeks* Environmental conditions of the rooms were targeted for a teaperatime of 20*C * 2C and relative humidity of 50X + 10X. Any excursions outside these ranges were of brief duration and d1d~hot adversely affect the outcome of the study. B. Protocol On the day prior to study initiation, the eyes of 2 male New Zealand White rabbits weighing 3126 and 2764 grams were examined using fluorescein dye. Animals showing pre-existlhg cornea! or conjunctiva! injury or irritation were not used In this study. A 0.01 ml aliquot of flBU^HI^HBH^Mas introduced into the lower conjunctlval sac of theng^eyes of z male New Zealand White rabbits. The left eyes served as controls. The treated and control eye of one animal remained unwashed. Approximately 20 seconds after the test material was administered, both eyes of the remaining animal were rinsed for one minute with lukewarm tap water. Approximately 1 and 4 hours and 1, 2 and 3 days after treatment, the rabbits were examined for evidence of eye Irritation. At each observation the treated eyes were examined using an ophthalmoscope and scored for ocular reactions using the Oralze scale (presented In Table I). The untreated eye was also examined and used for comparison. Any unusual effects, e.g., panhus* blistering of the conjunctiva, ulceration or' other effects indicative of corrosive action Company Sanitized. Does not contain TSCA CBI All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Font de Nemours and Company, Newark, Delaware or In the Du Pent Hall of Records, Wilmington, Oelawarje. RESULTS ^----^----I^HlUUprbduced slight corneaI opacity for 1 hour througn^W^^nmeunwashed eye. No other eye Irritation was present throughout the study. Fluoroescein examinations were negative at all Intervals and both eyes appeared; normal by day 3. Individual eye Irritation scores are presented in Tables III and IV* CONCLUSION Under the conditions of this study, slight eye Irritant. was a 6 - Company Sanitized. Does not contain TSCA CB1 ^^::.-^N^ (1) Cornea :'^ . ..'... ...^^.' (A) Opacity-degree of dens ty (^en,.jHist^^laiiK^akenfor reading) Unjok ojmp^ajacjtAit--y -.^:- "' " ^1''-^1 :-.--7; /r^ ''-''- ^.r-^:- .'^.("'i-'*--?';;'' '. ;. A:^':..;' ..i^^.^'s,1:.:., .' v A ^iirti deWs Scattered or diffuse a "e^ of early visible . . 1 Easily discernible traislucent areas, details of iris s1tght.1y .^..'.^i^^'^':^ Obscured -.. ,. 2 d^lls^ ...... Opalescent arws, no Crts yj|il<^tB. size of pupil barely discernible , . . . . 3 . . . . . . . . . . . . . ,'. Opaque,-trts 4nv4&WI<i. . .".'".''".-'": . . C . . . . . . . . (8) Area of cornea involved (tee quarter (or less) but not zero 1 Greater than one quarter, but less than half 2 ; . , . . . . . . . . . . Greater than one half.^ but less than three quarters 3 . . . . . . . . . Greater than three quarters, up to whole area 4 . . . . . Score equals A x B x 5 Total Maximum 80 ........ , (2) Iris ! (A) Values .......................... Normal Folds above normal, congestion, swell ing circumcorneal 0 Injection (any or all of these or cortblnatlon of any thereof) Iris still reacting to light (sluggish reaction is positive) . . . . . . . . . . . . . . . . . . . . . . . . . No reaction to light, hemorrhage, gross destruction (any or all of these) 2 Score equals A x 5 ' Total Kaxfnua 10 (3) Conjunctiva : (A) Redness (refers to paTpebral and bulbar conjunctiva excluding cornea and Iris) Vessels normal 0 Vessels definitely Injected above normal 1 . . . . . . . . . . . . . . . . . . . . . . . . More diffuse, deeper crimson red. Individual vessels not ........... easily discernible a 2 Diffuse beefy red 3 ......... .......... (B) Chemosis ...................... No swelling . 0 . . . Any swelling above normal (includes nictitating membrane) . . 1 ..................... Obvious swelling w1th:part1al eversion of lids 2 Swelling with lids about half closed 3 . . . . . ................ Swelling with lids about half closed to completely closed . . 4 7 - Company Sanitized. Does not contain TSCA CBI '-. ''."w '' 'y^:\'w,fK':^'w*s^, (C) Discharge ^ fto .. d1sch?r9?'..'.-..': "y?:;-*-'.<. ./.; :5^ita-,;' Any arount different f^noraaHdoes not include snail a-ounts observed in fnner canthus of niirBial animals) 1 Discharge with rolsten|lngof the 114s and ia1rs just . . , adfac'ent t<^^:T(ds ^rfi'',!'''*^*''^^*":* .<^:(;i;'^ 2 . 01 scharge Mitt) iMl^tenjiiiiiof the 1ids and ^hal rs, and considerable area arlound the eye . * . Score equals (A'T8~+ C)' x p Total Kaxiima 20 The maximum total scone is the suo of all scores obtained for the cornea. Iris and conjunctiva. Total fflaximum score possible = 110. Ora1ze J. H.. "Dennal Toxiclty," Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial ConniH tee of the Association of Food and Drug ornciais of the United States., Austin, Texas. 1959, pp. 46-59. Company Sanitized. Does not contain TSCA CB1 HLf) 799-85 BIOMICROSCOPECLASSIFICATIONS OF CORNEALINJURY ----------------(gSic-pgfopnea)---------- 0 s No Injury; cornea within normal limits. Slight (1) Epithelial changes visible only with blomicroscopc (nay; Include localized area of mild Injury). Mild (2) a Opacity visible with ophthalnoscope or light but showing epithelial changes only with bioiaicroscope (may Include localized area of moderate injury). Moderate (3) = Opacity visible with ophthalmoscope or light but showing epithelial and stromal changes with biom'tcroscope (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 swell ing. This type of injury shows evidence of healing (reversible damage) within 14 days. Severe (5) = Opaqueness or opacity visible with ophthaloioscope or light but showing epithelial and stromal changes and endotheT^laT relucency and swelling or other distortion. This type of Injury does not show; evidence of heaTIng (permanent damage) within 14 days, No biomicroscope evaluation performed. 9 Company Sanitized. Does not conlam TSCA CB1 < Mild (2) Opacity visible with opht ha Imoscope or light but shpwing epithelial changes only with bioaicroscope (may include localized area of moderate injury), Moderate (3) - Opacity visible ith ophthalmoscope or light but Sh<^ng epHhelial and stromal changes with bfttmfcroscope (ay include localized area of severe Ift^ury).- Moderate to Severe (4) " Opacity visible with ophthalmoscope or light but shdrtng epUhelia.l and stromal changes and enqothelial relucency MJth unreaarkable SMelling. This type of i'n.ihiry shows evidence of healing (reversible damage} within 14 days. Severe (5) Opaqueness or opacity visible with ophthalnoscope or'light but showing epithelial and stromal changes and endothelial relucency and swelling or otter distortion. This type of injury does not shew evidence of heal ing (permanent damage) within 14 days. - No ;bioinicroscope evaluation performed. - 9- .'.a^A nnoe nnt contain TSCA CB1 Fft^^W^-g^^ ^ ^ r ^ ^ ^ f l : .^.;''.;aife,%;^% .; '.'." '..s^'s-'^-"- . ^ ^ r g ^ : ,..;.....'. ,-.A--'.;.ft ''^s'^T?-"1^' ^^IS^t^' HLR 799*85 ! TMI.6 III eve UNHASHEPRABBIT ^ i uinATgj EYE AFTER EXPOSURET- kabbit 'Number 19230 Cornea Opacity Area 1 Hour --T Hours 1 1 4 4 INTtC .':. 1 Day 1 4 -T- 2 Days Oays 1 0 1 0 IMS 0 0 0 0 0 Conjunctiva Redness Chemosis Discharge 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Biocic of cornea Fluorescein Stain Examinations: negative at all intervals. 10 - Comoanv Saniiorf n^a *---,-. ---- _- ^/^wis^ ?p^^'!R:?K^-;^^i^^ '.^'^"' 'k. ' HLR 799-85 ;' - w.s.E^s^m^^^^. ^.: ^WWm OjE^ MASHE& RABBIT.EXE '- ; i ;.; pwfls^^daaaaBa gEACTK^BBSaED 1 .:' ' ":: ^^^ '^'it'-i: '^';^:",-' I ABTOI !" ' 1- "'""'^"W----ii^i^^^^^^^^^^ 3- Rabbit Nu^er ----'------I------W"----,1 - ,,. ^ ,,, 19231 Hour Hours , Day Days Oays Cornea Opacity Area 0 0 0 0 0 -0 0- 0 -0 0 Iris Conjunctiva Redness Chemosis Discharge 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Biomfc of cornea Fluorescein Stain Examinations: negative at all intervals. 11 - Company SanK.zed. Does not contain TSCA CB1