Document QJYkZ3awqeGV6zM784ojE0874

li tS L E tC M w S C 0 H S IN P O S I O F F I C E B O X 7 54 S Ivi A D I S O U , W I 5 3 7 0 7 - 7 B 4 b ZtHQ- FINAL REPORT A R 'XSr-0363 Roger G. Perkins, PhD 3M Toxicology Services Building 220-2E-02 St. Paul, MN 55144-1000 HWI Number: 40200470 Study Title: Primary Eye Irritation/Corrosion Study of T-5898 in Rabbits (OECD Guidelines) \ A e p a -o t s 000811806O OOGllOGO i Signed: Steven' M. Glaza Study Director Acute Toxicology Date COJ> XCCj-j t ro Phon- 600-241-4471 F O R E >: P E i; $ j- f-/ A ! L P E L. J V E a V: 3 3 0 7 I! I N S M A I'J F r* > H 1L E V A R D, W A P 005766 HWI Number: 40200470 Sample: T-5898 Acute Toxicology Steven M. Glaza Study Director Manager Steven R. Sorenson Study Coordinator Patricia Padgham In-life Supervisor Rose M. Bridge Report Supervisor Page 2 KEY PERSONNEL Laboratory Animal Medicine Cindy J. Cary, DVM Dipl ornate, ACLAM Supervisor CONTENTS Key Personnel Objective Test Material Test System Procedures Summary of Results Discussion References Appendix - Raw Data Page 2 3 3 3 4 6 10 10 11 005767 HWI Number: 40200470 Sample: T-5898 Page 3 OBJECTIVE The objectiv of this study was to assess the relative level of irritation/ corrosion produced following a single exposure of a test material to one eye of albino rabbits.1 All procedures used in this study are in compliance with the Animal Welfare Act Regulations. In the opinion of the Sponsor and study director, the study did not unnecessarily duplicate any previous work. TEST MATERIAL Identification The test material was identified as T-5898 and described as a clear, lightyellow liquid. Purity and Stability The Sponsor assumes responsibility for purity and stability determinations (including under test conditions). Storage and Retention The test material was stored at room temperature. Any unused test material will be returned to the Sponsor after issuance of the final report according to Hazleton Wisconsin (HWI) Standard Operating Procedure (SOP). Safety Precautions The test material handling procedures were according to HWI SOPs and policies. TEST SYSTEM Test Animal Adult albino rabbits of the Hra:(NZW)SPF strain were procured from HRP, Inc. and maintained at the Hazleton Wisconsin facility at 3802 Packers Avenue, Madison, Wisconsin. Animal husbandry and housing at HWI comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals".2 The animals were individually housed in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds, Inc., and held for an acclimation period of at least 7 days. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. 005768 HWI Number: 40200470 Sample: T-5898 Page 4 Samples of the water are periodically analyzed by HWI. There were no known contaminants in the feed or water that would have interfered with or affected the results of the study. Three female acclimated animals, weighing from 2,628 to 2,722 g, were selected and maintained during the study in the same manner as for the acclimation period. If variations from the required temperature and humidity conditions existed, they were documented and considered to have had no adverse effect on the study outcome. The animals' eyes were examined on the day before test material administration using sodium fluorescein dye procedures. Only those animals with no sign of ocular injury or irritation were used. Animals were identified by animal number and corresponding ear tag. Justification for Soecies Selection Historically, the New Zealand White albino rabbit has been the animal of choice based on its large orbit and nonpigmented iris. PROCEDURES. Preparation of Test Material The test material was administered as received. The pH of the test material was determined to be 7.6. Treatment Each rabbit received 0.1 mL of the undiluted test material placed into the everted lower lid of the right eye, with the left eye serving as the untreated control. The upper and lower lids were gently held together for 1 second to prevent loss of material and then released. The eyes of the rabbits remained unflushed. Reason for Route of Administration Historically, the ocular route has been the route of choice based on the method of Draize.3 Observations The treated eyes were observed for ocular irritation at 1, 24, 48, 72, and 96 hours and Days 7 and 14 after treatment. Irritation was graded and scored according to the Draize technique. Sodium fluorescein examinations were used to aid in revealing possible corneal injury at 72 hours and Days 7 and 14. 005769 HWI Number: 40200470 Sample: T-5898 Page 5 Animals were weighed just before test material administration and at weekly intervals throughout the study. Termination At termination of the experimental phase, all animals were designated to be euthanized and discarded. Statistical Analyses No statistical analyses were required by the protocol. Location of Raw Data. Records, and Final Report The raw data, records, and a copy of the final report will be retained in the archives of HWI in accordance with HWI SOP. 00S770 HWI Number: 40200470 Sample: T-5898 Page 6 SUMMARY OF RESULTS Test Animal: Albino Rabbits - Hra:(NZW)SPF Source: HRP, Inc., Kalamazoo, MI Date Animals Received: 02/17/94 Experimental Start Date: 02/24/94 Experimental Termination Date: 03/10/94 Average Primary Eye Irritation Scores* Observation Period Average Score 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 24.3 26.7 15.0 10.3 7.3 4.3 0.0 * The average primary eye irritation score is the total eye irritation score for all the animals divided by the number of animals (3) at each observation period. 005771 HWI Number: 40200470 Sample: T-5898 Page 7 Animal Number F49828u F49829t F49795u Table 1 Individual Eye Irritation Scores Cornea AB Iris C Con.iunctivae DEF 1 Hour 1 1 l1 2 2 2C 1 2 l1 2b 3 2C 1 1 l1 2b 2 2C Mean Total Score* 22.0 29.0 22.0 24.3 24 Hours F49828 1 1 l1 2b 2 Ie 20.0 F49829 1 3 l1 2b 3 t 34.0 F49795 1 1 l1 2b 3 3C 26.0 Mean 26.7 F49828 0 0 F49829 1J 2 F49795 lj 1 48 Hours 01 l1 2b l1 2 0 2 1 Mean 0 2C 0 2.0 27.0 16.0 15.0 Cornea Iris Coniunctivae A - Degree of opacity B - Area of involvement C - Degree of iridai irritation D - Redness E - Chemosis F - Discharge * Total score = (A x B x 5) + (C x 5) + [(D + E + F) x 2], b Blanching, c Clear discharge, d Purulent discharge, i Injected. j Corneal epithelial peeling. t No pain response after test material instillation, u Excessive pawing at the treated eye after test material instillation. 005772 HWI Number: 40200470 Sample: T-5898 Page 8 Animal Number F49828 F49829 F49795 Table 1 (Continued) Individual Eye Irritation Scores Cornea AB Iris C D 72 Hours Con.iunctivae EF 000 10 0 1 1 l1 2b 1 Ie 1J 1 0 210 Mean Total Score* 2.0 18.0 11.0 10.3 96 Hours F49828 0 0 0 F49829 1 1 0 F49795 1 1 0 0 0 0 0.0 2 1 0 11.0 .2 1 0 11.0 Mean 7.3 F49828 0 0 F49829 0 0 F49795 l3 1 Cornea A - Degree of opacity B - Area of involvement Dav 7 0 00 0 10 0 21 Mean Iris C - Degree of iridai irritation * Total score = (A x B x 5) + (C x 5) + [(D + E + F) x 2]. b Blanching, c Clear discharge, i Injected. j Corneal epithelial peeling. 0 0.0 0 2.0 0 11.0 4.3 Conjunctivae D - Redness E - Chemosis F - Discharge 005773 HWI Number: 40200470 Sample: T-5898 Page 9 Animal Number F49828 F49829 F49795 Table 1 (Continued) Individual Eye Irritation Scores Cornea AB Iris C D Day 14 Con.iunctivae EF 000 000 000 000 000 000 Mean Total Score* 0.0 0.0 0.0 0.0 Cornea A - Degree of opacity B - Area of involvement Iris C - Degree of iridai irritation * Total score = (A x B x 5) + (C x 5) + [(D + E + F) x 2]. Con.iunctivae D - Redness E - Chemosis F - Discharge Table 2 Sodium Fluorescein Examination Animal Observation Period Number Sex Preinitiation 72 Hour Dav 7 Dav 14 F49828 F49829 F49795 F F F NEG NEG NEG NEG NEG NEG NEG NEG NEG POS (5%) POS (5%) NEG NEG Negative stain retention. POS Positive stain retention (area of cornea involved). 005774 HWI Number: 40200470 Sample: T-5898 Page 10 DISCUSSION The test material, T-5898, when evaluated for its primary eye irritation potential in rabbits, produced corneal and iridal involvement and moderate to severe conjunctival irritation. All treated eyes had returned to a normal appearance by Day 14 after treatment. REFERENCES 1. "Acute Eye Irritation/Corrosion," Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 405 (adopted May 12, 1981). 2. NIH Publication No. 86-23 (revised 1985). 3. Draize, J. H., "Eye Mucosa," In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, Association of Food and Drug Officials of the U.S., pp. 49-50 (1959). 00S77S HWI Number: 40200470 Sample: T-5898 APPENDIX Raw Data Page 11 005776 PERSONNEL SIGNATURE SHEET ACUTE TOXICOLOGY hwi: ^ O Z O O h t T a Name Job Title Signature Rose M. Bridge Report Supervisor Anthony Cass Lab Animal Technician Cindy J. Cary, DVM Lab Animal Veterinarian Donna J. Clemons, DVM, MS Lab Animal Veterinarian John A. Disch Lab Animal Caretaker Charles W. Fritz Lab Animal Technician K a n Garfoot Lab Animal Technician Steven M. Glaza Manager Sts, Kevin Grossman Lab Animal Caretaker Jeff Hicks Lab Animal Technician Sharen L. Howery Research Assistant Wayne A. Madison Supervisor O0ly*L //? . Doug McConnell Lab Animal Technician Eileen McConnell Bud McDonald Staff Assistant Study Coordinator & < d PV\o?7at Albert Oleson Lab Animal Caretaker AQ Patricia Padgham In-life Supervisor - Steven R. Sorenson Study Coordinator Annette R. Turner Staff Assistant JtL. Tamra L. Walker Staff Assistant Lana M. Weeden dtefAcr M. Itither Staff Assistant ^LiaSH. U UnrGrtalP^M hr /J. D ^lL - k L VrAo \ W \ m A Gxv^Aate r ~ ~ ^XJl 1. (G2/10-06-93) 005777 HWI Mo.: A 4 2 Q C y - j n n TEST MATERIAL ADMINISTRATION RECORD Test Material: -r- -Sgff_____________________________________________ Physical Description: L J G J - l r ' \j^JLL.CM j l j G>LU A ___________ pH Result: 7-k>_____ with Corning pH Meter No. 05510 pH was determined on: undiluted material / .A dilution of v % v a /m a U - Unable to determine pH due to m o __________________________ _______ Storage conditions of test material: ______ Approximately 5 mTnDtw-banftJ:est material instillation 2 drops of 0.5% proparacaine HC1 (Qphthaine Lot ___ were placed on the corneal surface o f ______ eye(s) of each rabbit. Tech. l______ L Group fcjQ Dose:Q. I mL/ /vJAg f/On mL equivalent) Time: From To i s :q % ^ Unflushed fcjQ Flushed: k )& seconds after test material Instillation, the test eye of each animal was flushed with r J A _ mL of lukewarm tap water for k J A seconds / minutes. Time: From M A To /OA lX Dose was administered using a 1-mL disposable syringe. t jQ Dose was administered using a m A - uL glass syringe. JdDose was weighed into and administered using a weighing paper. jNJkDose was placed directly on the corneal surface of the right eye. The eyelids were released Immediately without forced blinking or manipulation. ^ Dose was placed into the everted lower lid of the right eye. The upper and lower lids were gently held together for one second and then released. M Q Other: n J A __________________________________________________ - Dosing Techn1cian/Date: ^ a c / ______ Time of 1-hour scores: k -.a q Technician/Date: Q r / ______ NA Not applicable. error a c (E8/12-09-92) Final data review by/Date: *77/ / 005778 __ HW I No.: *-402jQC>l-4-in> BODY WEIGHT / TREATMENT EFFECT RECORD Test Material: "7~- - S _____________________________________ Species/Source Strain/Location: Rabbit/Hra:(NZW1SPF/MI Date Animals Received: 12. - -C13 Initiated in Room Number: I ANnuimmbaelr PUQftZFS \ Group n !b. >f Sex Time:IniStFi*al PaiFnolRleoswpionngse Animal BodyWeights (g) I Dosing Initiation Day7 Day 14 Day21 | O (Of-jC-n* L |0 |3tod 1 m 12_ ks 3 1 9 9 9tSO j> -Q0> > 3b2X 9l\to Technician Date Scale Used |Cm ac ^23 Jira * _________ A O * Sodium fluorescein examination. "t* NEG Negative. POS Positive. NA Not applicable. V Vocalization. E Excessive pawing of treated eye. N None. <xc 9-9H cSUrtHfoS cxv ac 3-3 s l , otvi 2 - n - q q - . IG=\ x-2-S-Rs-^ On the day of treatment, all animals were weighed and appeared normal before test material administration. Technician/Date: a c Surviving animals were designated for sacrifice and discard. Technician/Date: k'-ry A 3 - m (E2/12-09-92) Final data review by/Date: / 3 - 1 1~ 005779 Hwi n o .: `-tozcyrLjnn PRINARY EYE IRRITATION OBSERVATIONS Test Material : Group: hJc\ "T- 5 S ----------------------------------------------- Test eye: Rioht Observation Period: 1 IgAur- Animal Number f"> j Location of Corneal QO ooLesions Q fv a Q"7Q5 \ tornea Iris Opacity . Area \1 \ l __ 2 ____ 1 l1 I1 Redness tonjuncnvae .... Chemosls 3 A 3 3 2 Discharge 3C Qc Sodium Fluorescein exam /VJA f j A Technician: Q-C Date: ________ Eye Irritation Score: oN-3_________ Calculated by/Date: a c / a-Q v-W _ Verified by/Date: ,7 / ( NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E Hair loss around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. 0 Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: 005780 HW I No.: ^ 2 r j Q ^ 7 Q Test Material: Group: hJf PRIMARY EYE IRRITATION OBSERVATIONS "7~- _________________________________________ _____ Test eye: Right Animal Number Location of Corneal Lesions Observation Period: 2J-4 Q@Q05Oo\QP>2> iK 2 a i-TQS tornea Opacity .... Area Iris Redness vOnJUnCv1VaG Chemosis Discharge Sodium Fluorescein exam 1 _ _ _ ! ____ 13 1* 2-& 11. Ie - 2 J> --- kJC * / I )* 3 3e iOa Technician: Date: 1C Eye Irritation Score: Z u > .i Calculated bv/Date: / X-XS-QU' Verified bv/Date: J& S / NA Not applicable. A Petite hemorrhaging. B B1anching. C Clear discharge. D Purulent discharge. E Hair loss around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. J Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. H Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: ^ 005781 -- Test Material: Group: r^\ HWI No.: J-/Q PRIMARY EYE IRRITATION OBSERVATIONS ~7~- S & Q Q ______________________________________________ _ Test eye: Right. Observation Period: _____ Y IP a 4>*,x> NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E Hair loss around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. J Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: 005782 1^ HWI Mo.: * - / T > 2 y - f 7Q PRIMARY EYE IRRITATION OBSERVATIONS Test Material: Group: hJc\ T - 5 8 Q 8 _________________________________________ _____ Test eye: Riaht Observation Period: ______7 ? A/ov/z. Animal Number f i f Location of Corneal Ow)QC5opLesions Q & 2 & iP 2 Q \ uornea Opacity Area o o SKg // // Iris /* o Redness conjunctivae / J* J Chemosis o / A Discharge /* o Sodium Fluorescein exam A/&? A/'a A r S * Z Technician: _______.7 ? / Date: _______ Eye Irritation Score: . __ _____ Calculated by/Date: *77/ / Verified by/Date: n r / 'k-s-Hy NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E Hair loss around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. J Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: 005783 -- HWI No.: - ^ 2 / Y V - / - 7 Q PRIMARY EYE IRRITATION OBSERVATIONS Test Material: Group: hJc\ "T"- -55& Q Q > ___________________________________________________ Test eye: Rioht Observation Period: Q i s i-jn u Animal Number Location of Corneal Lesions PPOpooQ&Z& QPOQ Q-lQs \ uornea Opacity O 11 Area I 1 Iris o o o Redness conjunctivae Chemosis <o o 211 Discharge oo Sodium Fluorescein exam aJ A Technician: Date: 2 - - 2 J & - 9 t- L _ Eye Irritation Score: 7.3 Calculated bv/Date: //- / 2 .-2A - * W _ Verified by/Date: __ r\c 7 ^ - 3 - ^ _____ NA Not applicable. A Petite hemorrhaging. B B1anching. C Clear discharge. D Purulent discharge. E Hair loss around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. J Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: c x c / 3 -/>-^7 005784 HWI No.: PRIMARY EYE IRRITATION OBSERVATIONS Test Material: Group: hJd\ PQP>__________________________________________ _ Test eye: Right Observation Period: -? Animal Number Location of Corneal Lesions OoOQOOQ?>2> Q - 7Q 5 \ LOrnGa Opacity Area c> o 3-S% o1 o1 Iris o oO Redness wOnjuncviVoG Chemosis o 0 1a o1 Discharge O o n Sodium Fluorescein exam MEG- Pos s-% \ Technician: Or Date: ________3 - 3 "T t Eye Irritation Score: Calculated by/Date: Verified by/Date: S.3_________ c ic / 3-3 ^ /3-^.q<-f NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E Hair loss"around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. J Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: -9^-- 00578S HWI No. J - j c Z L C & O n a PRIMARY EYE IRRITATION OBSERVATIONS Test Material: Group: frJt) '1~- *5 B Q Q Test eye: Rioht Animal Number Location of Corneal Lesions Observation Period: ^ /<-f OOOQO0f'j f. NQ - 7 Q 5 Lornoa Opacity Area Iris Redness uonjuncc1 vae Chemosis Discharge Sodium Fluorescein exam o o O o o ___Q ____ o o o /vlcbi o o o o o Technician: Date: Eye Irritation Score: o.o Calculated bv/Date: Verified bv/Date: a c /3-n-^H NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E Hair loss around the eye. F Possible necrotic areas. G Unable to visualize due to severe conjunctival swelling. H No reaction to light. I Injected. J Corneal epithelial peeling. K Corneal epithelial pitting. L Corneal edema. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe corneal opacity. S Granulation scar tissue. POS Positive stain retention. NEG Negative stain retention. (E3/07-15-92) Final data review by/Date: CXc /3--H-RH 005786 HWI No.: ^ O O ^ - 7 < Q SCALE FOR SCORING OCULAR LESIONS (DRAIZE TECHNIQUE) (1) Cornea (A) Opacity - Degree of density (area most dense taken for reading) No opacity.................................................................................... 0 Scattered or diffuse area, details of Iris clearly visible................................. 1 * Easily discernible translucent areas, details of iris slightly obscured................... 2* Opalescent areas, no details of Iris visible, size of pupil barely discernible............3* Opaque, iris invisible........ ...............................................................4* (B) Area of Cornea Involved One-quarter (or less), but notzero.......................................................... 1 Greater than one-quarter, but less than half..... ................. ........................ 2 Greater than half, but less than three-quarters............................................. 3 Greater than three-quarters up to whole area................................................ 4 A x B x 5 Total Maximum * 80 (2) M s (A) Values Normal........................................................................................ 0 Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris 1s still reacting to light (sluggish reaction is positive) ..................................................................................... 1* No reaction to light, hemorrhage, gross destruction (any or all of these)................. 2* Ax5 Total Maximum * 10 (3) Conjunctivae (A) Redness (refers to palpebral and bulbar conjunctivas excluding cornea and iris) Vessels normal................................................................................0 Vessels definitely Injected above normal.................................................... 1 More diffuse, deeper crimson red, individual vessels not easily discernible.............. .2* Diffuse beefy red.............................................................................3* (B) Chemosis No swelling................................................................................... 0 Any swelling above normal (includes nictitatingmembrane)................................... 1 Obvious swelling with partial eversion of the lids.......................................... 2* Swelling with lids about half closed......................................................... 3* Swelling with lids about half closed to completely closed.................. ................ 4* (C) Discharge No discharge...................... ............................................................0 Any amount different from normal (does not Include small amounts observed in Inner canthus of normal animals)................................................................... 1 Discharge with moistening of the lids and hairs just adjacent to the lids................. 2 Discharge with moistening of the lids and hairs, and considerable area around the eye.....3 Score (A + B + C) x 2 Total Maximum = 20 The total score for the eye is the sum of all scores obtained for the cornea, iris, and conjunctivae. * Indicates a positive effect. (FHSA Interpretation) (E4/01-06-91) 005787