Document 7Ozz4NJ0JyBMbwBZ7p87Z7v4R

Corning Hazleton Inc. P.O. Box 7545 Madison, WI 53707-7545 Deliveries: 3301 Kinsman Blvd., Madison, WI 53704 608.241.4471 608.241.7227 Fax flR a x o 3 C O R N IN G Hazleton Sponsor: 3M St. Paul, Minnesota FINAL REPORT Study Title: Primary Eye Irritation/Corrosion Study o f T-6684 in Rabbits (OECD Guidelines) A u th o r: Steven M. Glaza Study Completion Date: January 28, 1997 Performing Laboratory: Coming Hazleton Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704 Laboratory Project Identification: CHW 61101151 Page 1 o f 31 FEB - 3 1997 005 711 COMPLIANCE STATEMENT CHW 61101151 Primary Eye Irritation/Corrosion Study o f T-6684 in Rabbits (OECD Guidelines) This study was conducted in accordance with the Organisation for Economic Cooperation and Development Principles o f Good Laboratory Practice, C(81)30(Final). Acute Studies Coming Hazleton Inc. Date COS 712 2 QUALITY ASSURANCE STATEMENT CHW 61101151 This report has been reviewed by the Quality Assurance Unit o f Coming Hazleton Inc., in accordance with the Organisation for Ecomonic Cooperation and Development (OECD) Principles o f Good Laboratory Practice, C(81)30(Final). The following inspections were conducted and findings reported to the Study Director and management Date Inspection Dates Reported to From________ To______________ Phase____________ Study Director 12/03/96 12/03/96 Dose Preparation 12/03/96 01/23/97 01/23/97 Data/Report Review 01/23/97 Date Reported to Management 12/03/96 01/23/97 Representative, Quality Assurance Unit 3 / 2 f- f'? Date OOS 7X3 STUDY IDENTIFICATION CHW 61101151 Primary Eye Irritation/Corrosion Study o f T-6684 in Rabbits (OECD Guidelines) Test Material Sponsor Sponsor's Representative Study Director Study Location Study Timetable Study Initiation Date Experimental (In-life) Start Date In-life End Date Experimental Termination Date Study Completion Date T-6684 3M Toxicology Service Medical Department 3M Center, Bldg. 220-2E-02 P.O. Box 33220 St. Paul, MN 55133-3220 Roger G. Perkins, PhD 3M Toxicology Service Medical Department 3M Center, Bldg. 220-2E-02 P.O. Box 33220 St. Paul, M N 55133-3220 (612) 733-3222 Steven M. Glaza Coming Hazleton Inc. P.O. Box 7545 Madison, WI 53707-7545 (608) 241-7292 Coming Hazleton Inc. 3301 Kinsman Boulevard Madison, WI 53704 November 27, 1996 December 3, 1996 December 17, 1996 December 17, 1996 January 28, 1997 4 005714 Acute Studies Steven M. Glaza Study Director Manager Steven R. Sorenson Study Coordinator Jeffrey B. Hicks In-life Supervisor Rose M. Bridge Administrative Supervisor Toxicology Support Kathy Myers Manager Calvin L. H orton Supervisor KEY PERSONNEL Quality Assurance Sherry R. W. Petsel Manager CHW 61101151 Laboratory Animal M edicine Cindy J. Cary, DVM Diplomate, ACLAM Supervisor 5 0 0 5 715 CONTENTS CHW 61101151 COMPLIANCE STATEM ENT....................................................................................................2 QUALITY ASSURANCE STA TEM EN T................................................................................. 3 STUDY IDENTIFICATION........................................................................................................ 4 KEY PERSONNEL........................................................................................................................ 5 O BJECTIV E.................................................................................................................................. .8 TEST M ATERIAL..........................................................................................................................8 Identification................................................................................................................................ 8 Purity and Stability...................................................................................................................... 8 Storage and Retention................................................................................................................ 8 Safety Precautions...................................................................................................................... 8 TEST SY STEM .............................................................................................................................. 9 Test A nim al.......................................................................... 9 H ousing.......................................................................... 9 Animal D ie t.......................................................... 9 Animal Selection......................................................................................................................... 9 Justification for Species Selection............................................................................................9 PROCEDURES............................................................................................................................. 10 Preparation o f Test Material.......................... 10 Treatm ent................................................................................................................................... 10 Reason for Route o f Administration.......................................................................................10 Observations.............................................................................................................................. 10 Term ination................................................................................................................................10 Statistical A nalyses.................................................................................................... 11 Location o f Raw Data, Records, and Final Report...............................................................11 RESULTS/DISCUSSION........................................................................................................... 11 SIGNATURE................................................................................................................................ 11 R E F E R E N C E S ............................................................................................................................... 12 6 005716 CHW 61101151 TABLE 1 Average Primary Eye Irritation S cores............................................................................ 13 2 Individual Eye Irritation Scores....................................................................................... .14 3 Sodium Fluorescein Examinations.................................................................... 4 Individual Body Weights ( g ) ............................................................................................. 18 A P P E N D IX ....................................................................................................................................19 Protocol T P 2072...................................................................................................................... 20 Protocol Amendment No. 1 ....................................................................................................31 18 7 005 717 OBJECTIVE CHW 61101151 The objective o f this study was to assess the relative level o f irritation/corrosion produced following a single exposure o f a test material to one eye o f albino rabbits.1 All procedures used in this study were in compliance with the Animal Welfare Act Regulations. In the opinion o f the Sponsor and study director, the study did not unnecessarily duplicate any previous work. All procedural times presented in this report fall within the acceptable ranges as specified in the Wisconsin facility o f Coming Hazleton Inc. (CHW) Standard Operating Procedure (SOP). TEST MATERIAL Identification The test material was identified as T-6684 and described as an off-white 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 o f the final report according to CHW SOP. Safety Precautions The test material handling procedures were according to CHW SOPs and policies. 8 00S718 TEST SYSTEM CHW 61101151 Test Animal Adult albino rabbits o f the Hra:(NZW)SPF strain were procured from HRP, Inc., Kalamazoo, Michigan on October 30, 1996. Housing After receipt, the animals were acclimated for a period o f at least 7 days. During acclimation and throughout the study, the animals were individually housed in stainless steel cages. Environmental controls for the animal room were set to maintain a temperature o f 19 to 23C, a relative humidity o f 50% 20%, and a 12-hour light/12-hour dark lighting cycle. In cases where variations from these conditions existed, they w ere documented and considered to have had no adverse effect on the study outcome. Animal Diet The animals were provided access to water ad libitum and a measured amount o f Laboratory Rabbit Diet HF #5326, PM I Feeds, Inc. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples o f the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results o f the study. Animal Selection Three healthy, acclimated male rabbits, weighing from 2,526 to 2,685 g and approximately 17 weeks o f age, were selected at random and identified by animal number and corresponding ear tag. The animals' eyes were examined on the day before test material administration using sodium fluorescein dye procedures. Only those animals with no sign o f ocular injury or irritation were used. Justification for Species Selection Historically, the New Zealand White albino rabbit has been the animal o f choice based on its large orbit and nonpigmented iris. 9 005719 PROCEDURES CHW 61101151 Preparation of Test Material The test material was administered as received. The pH of the test material was not able to be determined. Treatment Each rabbit received 0.1 mL o f the undiluted test material placed into the everted lower lid o f 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 o f material and then released. The eyes o f the rabbits remained unflushed immediately after treatment. Reason for Route of Administration Historically, the ocular route has been the route of choice based on the method o f Draize.2 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 using a penlight as the source o f illumination. Sodium fluorescein examinations were used to aid in revealing possible corneal injury at the observations conducted at 24 hours. Animals were weighed before test material administration and at weekly intervals throughout the study. Termination A t termination o f the in-life phase, all animals were euthanized and discarded. 10 COS 720 ________________________________________________________________________ Statistical Analyses N o statistical analyses were required by the protocol. CHW 61101151 Location of Raw Data, Records, and Final Report The raw data, records, and an original signed copy o f the final report will be retained in the archives o f CHW in accordance with CHW SOP. RESULTS/DISCUSSION Average primary eye irritation scores are in Table 1, with individual eye irritation scores in Table 2. Sodium fluorescein examinations and the individual body weights are in Tables 3 and 4, respectively. The test material, T-6684, when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal, iridal involvement in two animals, and slight to moderate conjunctival irritation in all three animals. All treated eyes had returned to a normal appearance by Day 14 after treatment. SIGNATURE Acute Studies V -L% A ~) Date 11 0 0 5 7 2 1 REFERENCES CHW 61101151 1. "Acute Eye Irritation/Corrosion, " Organisation for Economic Cooperation and Development Guidelines for Testing o f Chemicals, Section 405 (adopted M ay 12, 1981). 2. Draize, J. H., "Eye Mucosa," In: Appraisal o f the Safety o f Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, Association o f Food and Drug Officials o f the U .S.,pp. 49-50 (1959). 005722 12 Table 1 Average Primary Eye Irritation Scores Observation Period Average Score* 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 12.3 6.7 6.7 5.3 4.0 0.7 0.0 * The average primary eye irritation score is the total eye irritation score for all the animals divided by the number o f animals (3) at each observation period. CHW 61101151 005723 13 Table 2 Individual Eye Irritation Scores CHW 61101151 Animal Number Cornea AB Iris Conjunctivae Total C D E F Score* 1 Hour F612091 F61210" F612111 1 0 0 1 0 0 ll 2 l1 2 02 1 l d 18.0 1 l d 13.0 10 6.0 M ean 12.3 24 Hours F61209 F61210 F61211 0 0 0 0 0 0 0 2b 1 l d 8.0 0 2h 1 0 6.0 0 2 1 0 6.0 Mean 6.7 C o rn ea A - Degree o f opacity B -A re a o f involvement Iris C - Degree o f iridal irritation C o n ju n ctiv ae D - Redness E - Chemosis F - Discharge * Total score - (A x B x 5) + (C x 5) + [(D + E + F) x 2], b Blanching, d Purulent discharge, i Injected. t N o pain response after test material instillation, u Excessive pawing at the treated eye after test material instillation. 005724 14 Table 2 (Continued) Individual Eye Irritation Scores CHW 61101151 Animal Cornea Iris Conjunctivae Total Number A B C D E F Score* 48 Hours F61209 F61210 F61211 0 0 0 0 0 0 0 2b 1 l d 8.0 02 10 6.0 0 2 1 0 6.0 Mean 6.7 72 Hours F61209 F61210 F61211 0 0 0 0 0 0 0 2 1 l d 8.0 0 1 1 0 4.0 0 1 1 0 4.0 Mean 5.3 Cornea A - Degree o f opacity B - Area o f involvement Iris C - Degree o f iridal irritation Conjunctivae D -R edness E - Chemosis F - Discharge * Total score = (A x B x 5) + (C x 5) + [(D + E + F) x 2], b Blanching, d Purulent discharge. t os 725 15 Table 2 (Continued) Individual Eye Irritation Scores CHW 61101151 Animal Cornea Iris Conjunctivae Total Number A B C D E F Score* 96 Hours F61209 F61210 F61211 0 0 0 0 0 0 0 1 1 0 4.0 0 1 1 0 4.0 0 1 1 0 4.0 Mean 4.0 Day 7 F61209 F61210 F61211 0 0 0 0 0 0 0 1 0 0 2.0 0 0 0 0 0.0 0 0 0 0 0.0 Mean 0.7 C o rn ea A - Degree o f opacity B - Area of involvement Iris C - Degree o f iridal irritation C o njunctivae D - Redness E - Chemosis F - Discharge * Total score = (A x B x 5) + (C x 5) + [(D + E + F) x 2], 005726 16 Table 2 (Continued) Individual Eye Irritation Scores CHW 61101151 Animal Number Cornea AB Iris Conjunctivae Total C D E F Score* D ay 14 F61209 F61210 F61211 0 0 0 0 0 0 0 0 0 0 0.0 0 0 00 0.0 0 0 00 0.0 Mean 0.0 Cornea A - Degree o f opacity B - Area o f involvement Iris C - Degree o f iridal irritation Conjunctivae D - Redness E - Chemosis F - Discharge * Total score = (A x B x 5) + (C x 5) + [(D + E + F) x 2], 17 Table 3 Sodium Fluorescein Examinations Animal Observation Period Number Preinitiation 24 Hour F61209 NEG NEG F61210 NEG NEG F61211 NEG NEG NEG Negative stain retention. CHW 61101151 Table 4 Individual Body Weights (g) Animal Number F61209 F61210 F61211 Sex M M M Initial 2,685 2,526 2,632 J>EL__________ 7 14 2,802 2,684 2,814 2,900 2,796 2,992 18 6 0 5 7 2 8 APPENDIX Protocol TP2072 Protocol Amendment No. 1 CHW 61101151 19 0 0 5 7 2 9 CHW 61101151 Sample Submittal Form This form Is to bo used when submitting sam ples tor routine acute testing. Special testing needs can be easily arranged by contacting the Acute Studies Department at (608) 241-7292. CHW Study No. Enclose with samples and send to: Com ing Hazleton Inc. 3301 Kinsman Boulevard Madison, W isconsin 53704 Submitted bv: Q > CZ, /v f Date Sam ple Sent: l / " t * f r *> Com pany:__________________________________________________ Number of Reports Required: 3 Full G LP Compliance: Yos ____ FDA(21CFR58) __ _ EPA (FIFRA-- 40 CFR 160) ____ MAFF ------- No -------- E P A (T SC A -- <0 C F R 792) - X - O E C O ------- M O H W Sam ple N am e :. fry t - & c k c r - 6 6 e 4_______________ Physical Description: _______ _____________________ ______________________________________ Special Handling PrecautiorHs: O~ ~ J O *7 - 7 $ & 7 ~ V, Test material purity and stability information (including under test conditions) on file with Sp o n so r Y e s ___ No Test mixture analysis for concentration/homogenelty/stability to be conducted: ___ Yes* ____ by Sponsor ___ by CHW Sa m p le D isp o sa l: ,, Return to Sp o n so r at following address: -- N o P - K o ~ t i _______________ itv9CDu 6la 5 . 3 - J S - q 2 - 5s~<yy-/oo' ------- Dispose of according to C H W S O P s Sam ple Storage Requirements: Room temperature _____ Refrigerated _____O ther_______________________________ * At additional cost to Sponsor (CH W will contact Sponsor a s to these additional charges). Tests Acute Oral Toxicity in Rats ----- TP8084 Up and down LD50 procedure ----- TP3206 F H SA screen; 5M -5F at 5.0 g/kg ----- Conduct defined study if death occurs at 5.0 g/kg ____TP3013 E P A screen; 5M -5F at 5.0 g/kg . . ----- Conduct defined study If death occurs at 5.0 g/kg _ X _ T P 2 0 6 9 O E C D screen; 5M -5F at 5.0 g/kg ----- Conduct defined study if death occurs at 5.0 g/kg Special instructions: Acute Derm al Toxicity in Rabbits ----- TP3207 F H SA screen; 5M -5F at 2.0 g/kg ----- TP 3016 E P A screen: SM -SF at 2.0 g/kg ----- Conduct defined study if death occurs at 2.0 g/kg ----- TP2070 O E C D screen; 5M -5F at 2.0 g/kg ----- Conduct defined study if death occurs at 2.0 g/kg Special instructions:. ^ V .1 7 - -- frJ L j ---------------- i For CH W U se Only IProtocol Issue Date: Study Director: t - Wiiite copy-- C H W VVrZ-~tAV> ---- \ Yellow copy-- Submitter Prim ary Skin Irritation ____TP3208 FH SA : 6 rabbits-1 abraded, 1 Intact site/rabblt __ TP3014 EPA ; 6 rabbits-1 Intact slte/rabbit - X T P 2 0 7 1 O EC D ; 3 rabbits-1 intact site/rabblt ____TP4206 D O T corrosivity; 6 rabbits-1 intact site/rabblt ____TP7145 Phototoxicity; 6 rabbHs-2 Intact sltes/rabbit (one site with U VA exposure) Special Instructions:___________________________________ Prim ary Eye Irritation ____TP 6360 Low-volume procedure; 6 rabbits unwashed ____TP3209 FH SA ; 6 rabbits unwashed TP2012 1978 EPA ; 6 rabbits unwashed, 3 w ashed ____TP3015 1982 EPA; 6 rabbits unwashed _ ^ C jP 2 0 7 2 O EC D ; 3 rabbits unwashed ___ 3 rabbits w ashed at 4 seconds ----- 3 rabbits w ashed at 30 seconds Special instructions:_________________________________ Guinea P ig Sensitization ___ TP2017 E P A M agnusson-Kligm an maximization ___ TP6164.EC O EC D /EC M agnussun-Kligm an maximization ___ TP2008 Buehler sensitization ___ TP6289 Photoallergenic contact dermatitis (Armstrong) Special instructions:____________________ i------------------------- 005 730 20 CHW 61101151 HAZLETON WISCONSIN POST O FFICI SOX 7S4S MADISON. W ISCONSIN 53707-7545 C O R N I N G laboratory Services Company S p on s o r: 3M St. Paul, Minnesota PROTOCOL TP2072 Study Title: Primary Eye Irritatlon/Corrosion Study in Rabbits (OECD Guidelines) Elk: June 1, 1993 Performing Laboratory: Hazleton Wisconsin, Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704 Laboratory Project Identification: HWI C.llailS-1 21 0 0 5 7 3 1 CHW 61101151 TP207Z Page Z STUDY IDENTIFICATION Primary Eye Irritation/Corrosion Study in Rabbits (OECD Guidelines) HWI No. Test Material Sponsor Sponsor's Representative Study Director Study Location Proposed Study Timetable Experimental Start Date Experimental Termination Final Report Date Date Crtlaft&l (See sample submittal form) 3M Toxicology Services 220-2E-02 3M Center St. Paul, MN 55144 John L. Butenhoff, PhD 3M Toxicology Services Z20-2E-02 3M Center St. Paul, MN 55144 (612) 733-1962 Steven M. Glaza Hazleton Wisconsin, Inc. P.0. Box 7545 Madison, WI 53707-7545 (608) 241-7292 Hazleton Wisconsin, Inc. Building No. 3 3802 Packers Avenue Madison, WI 53704 Week of >< Week of Week of 2. -3-^1 005732 22 CHW 61101151 TP2072 Page 3 f. Study Primary Eye Irrltatlon/Corrosion Study 1n Rabbits (OECD Guidelines) 2. Purpose To assess the relative level of irritation/corroslon produced following a single exposure of a test material to one eye of albino rabbits 3. Regulatory Compliance This study will be conducted 1n accordance with the following Good Laboratory Practice Regulatlons/Standards/Guidelines: [ ] Conduct as a Nonregulated Study [ ] 21 CFR 58 (FDA) [ ) 40 CFR 160 (EPA-FIFRA) [ ] 40 CFR 792 (EPA-TSCA) txtC(81)30 (Final) (OECD) [ ] Notification No. 3850, August 10, 1984 (Japanese MAFF) [ ] Notification No. 313, March 31, 1982, and as amended by Notification No. 870, October 5, 1988 (Japanese KOHW) All procedures in this protocol are in compliance with the Animal Welfare Act Regulations. In the opinion of the Sponsor and study director, the study does not unnecessarily duplicate any previous work. 4. Quality Assurance For regulated studies, the protocol, study conduct, and the final report will be audited by the Quality Assurance Unit in accordance with Hazleton Wisconsin (HWI) Standard Operating Procedures (SOPs) and policies. 5. Test Material A. Identification (See sample submittal form) B. Physical Description (See sample submittal form) C. Purity and Stability The Sponsor assumes responsibility for purity and stability determinations (including under test conditions). Samples of test material/vehicle mixture(s) (if applicable) for concentration, solubility, homogeneity, and stability analyses will be taken before administration if requested by the Sponsor. These samples (if taken) will be sent to the Sponsor after experimental termination for possible analysis. 0S733 23 CHW 61101151 TPZ072 Page 4 D. Storage (See sample submittal form) E. Reserve Samples Studies of less than 4 weeks in experimental duration will not have reserve samples retained. Reserve sample(s) of each batch/lot of test material will be taken if this study Is more than 4 weeks in experimental duration. The test material reserve sample will be stored at HWI in a freezer set to maintain a temperature of below 0*C for 10 years per HWI SOP. The Sponsor will be contacted after 10 years for disposition in accordance with the appropriate regulatory Good Laboratory Practices. F. Retention Any unused test material will be discarded after issuance of the final report, unless directed otherwise by the Sponsor. G. Safety Precautions As required by HWI SOPs and policies 6. Experimental Design A. Animals (1) Species Rabbit (2) Strain/Source Hra:(NZW)SPF/Hazleton Research Products, Inc. (3) Aoe at Initiation Adult (4) Weight at Initiation 2.0 to 3.5 kg (5) Number and Sex 3 of any sex per group (6) Identification Individual numbered ear tag 00S734 24 CHW 61101151 TP2072 Page 5 (7) It o band ry (a) Housing Individually, In screen-bottom stainless steel cages (heavy gauge). (b) ffiM A measured amount of High Fiber Rabbit Chow #5326 (Purina Mills, Inc.). The food Is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. (c) M e r Ad libitum from an automatic system. Samples of the water are analyzed by HWI for total dissolved solids, hardness, and specified microbiological content and for selected elements, heavy metals, organophosphates and chlorinated hydrocarbons. (d) Contaminants There are no known contaminants 1n the food or water that would interfere with this study. (e) Environment Environmental controls for the animal room will be set to maintain a temperature of 19 to 23*C, a relative humidity of 50% 20%, and a 12-hour light/12-hour dark cycle. (f) Acclimation At least 7 days (8) Selection of Test Animals Based on health and body weight according to HWI SOPs. An adequate number of extra animals will be purchased so that no animal in obviously poor health is placed on test. The rabbits' eyes will be examined using sodium fluorescein dye procedures on the day before test material administration. Only animals with no sign of corneal injury or eye abnormalities will be used. (9) Justification for Species Selection Historically, the New Zealand White albino rabbit has been the animal of choice based upon its large orbit and nonpigmented iris. *05735 25 CHW 61101151 TP2072 Page 6 B. Dose Administration (1) Dose Administration Before administration of liquid test materials, the pH of the material will be determined (1f possible). Each rabbit will receive 0.1 mL of undiluted liquid test material or the weight equivalent of 0.1 ml of solid test material (not to exceed 0.1 g). If necessary, solid test materials will be finely ground Into a dust or powder. The test material will be placed Into the everted lower lid of the rabbit's eye. The upper and lower lids will then be gently held together for 1 second before releasing to prevent loss of material. If the test material is an aerosol, the test eye will be held open and the test material administered In a single burst of about 1 second from a distance of approximately 10 cm directly 1n front of the eye. The eyes of the Group 1 rabbits will remain unflushed for approximately 24 hours following Instillation of the test material. After 24 hours, a washout may be used If considered appropriate. If specified by the Sponsor, the treated eyes of two other groups of animals (three animals/group) will be washed with lukewarm tap water for approximately 30 seconds beginning approximately 4 and 30 seconds, respectively, after instillation of the test material. The volume and velocity of the flow should not cause Injury. The right eye of each animal will be treated with the test material and the left eye will serve as the untreated control. (2) Reason for Route of Administration Historically, the ocular route has been the route of choice based on the method of Draize. C. Observation of Animals (1) Reading of Ocular Irritation The treated eyes of all animals will be examined for ocular irritation at approximately 1, 24, 48, and 72 hours after treatment. If no irritation or injury is present at 72 hours, the group will be terminated. If irritation is present at 72 hours, additional observations may be made at 96 hours and at 7, 14, and 21 days. If at any of these time points there is no irritation, the group will be terminated. If injury is still present at 21 days, additional observations may be requested by the Sponsor. After recording the 24-hour observations, sodium fluorescein may be used to aid in revealing possible corneal injury. 005736 26 CHW 61101151 TP2072 Page 7 Irritation will be graded and scored using the Dralze technique (Attachment 1). All eye abnormalities will be recorded. All animals that have a damaged eye producing undue stress or discomfort will be brought to the attention of the study director or designee according to HWI policy. (2) Body Weights Before test material administration and weekly thereafter (when applicable). D. Pathology Any animals dying during the study will be subjected to an abbreviated gross necropsy examination and all abnormalities will be recorded. After necropsy, the animals will be discarded and no tissues will be saved. At termination of the experimental phase, surviving animals will be designated to be sacrificed and discarded. E. Statistical Analyses No statistical analyses are required. 7. Egeort A final report including those items listed below will be submitted: Description of the test material Description of the test system Procedures Dates of experimental Initiation and termination Summary table showing the Irritation data at each observation period Any special observations that were recorded 8. Location of Raw Data. Records, and Final Report Original data, or copies thereof, will be available at HWI to facilitate auditing the study during its progress and before acceptance of the final report. When the final report is completed, all original paper data, including those items listed below will be retained in the archives of HWI according to HWI SOP. Protocol and protocol amendments Dose preparation records In-life records Body weights Dose administration Observations Anatomical pathology records (if applicable) Study correspondence Final report (original signed copy) 005737 27 CHW 61101151 TP2072 Page 6 The following supporting records will be retained at HWI but will not be archived with the study data. Animal receipt/accllmatlon records Water analysis records Animal room temperature and humidity records Refrigerator ana freezer temperature records Instrument calibration and maintenance records 0 S 738 28 CHW 61101151 TP2072 Page 9 \ V PROTOCOL APPROVAL John L. Butenhoff, PhD Sponsor's Representative 3M Steven M. G l a Study Director Acute Toxicology Hazleton Wisconsin, za Inc. 0 _____l ? d w A S . Sif/si. Representative Quality Assurance Unit Hazleton Wisconsin, Inc. (TP2072.3M) ___ q & t- te t Date7 f f Date ____________ (<///<2. ^ Date 005739 29 CHW 61101151 TP2072 Page 10 Attachment 1 SCALE FOA SCORING OCULAR LESIONS (BRAIZE TECHNIQUE) (1) Cornea (A) Opacity Degree of density (area aunt dense taken for reading) No opacity............................................................. Scattered or diffuse area, details of Iris ctaarly 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 lest), but not zero..................................................... 1 Greater than one-quarter, but less than half............................................ 2 Greater than half, but less than three-quarters......................................... 3 Greater than three-quarters tf> to ahole area........................................... 4 A z I x $ Total Kaxlatis BO (2) M i (A) Values Normal........................... ........................................................ 0 Folds above normal, congestion, swelling, clrcuncomeal Injection (any or all of these or combination of any thereof) Iris Is still reacting to light (sluggish reaction Is positive) ......................... 1* No reaction to light, hemorrhage, gross destruction (any or all of these)...............2* A x5 Total Haxiaua 10 (3) ConJunctivae (A) Redness (refers to palpebral and bulbar ConJunctivae excluding cornea and Iris) Vessels normal.......................................... Vessels definitely injected abovenormal................................................ 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 (includesnictitating membrane)..... .......................... t 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 anoint different from normal (does not include small amounts observed in inner c a m hus 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 8 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) 0 0 005740 30 CHW 61101151 CHW No. ( W / Q / / S 7 PROTOCOL AMENDMENTS Amendment No. I Effective N o v J g M g g / t - 1. ISTC. Portion of Protocol Being Modified: Applicable sections of the protocol. Reason for Modification: To identify the location where the study will be conducted and to reflect a company name change from Hazleton Wisconsin, Inc. (HWI) to Corning Hazleton Inc. fCHWl. replace wherever applicable the following changes Modification: _____________ Corning Hazleton Inc. (CHW1_______________________________ 3301 Kinsman Boulevard. ____________________________ Madison. WI 53704________________________________________ (G21/01-07-91 ) Study Director Approval: v\--nAV> 005741 31