Document EZEjr58pVm4RkBkd4xg2V56b

HAZLETON LAEC)RATORIES AMERC.A. rlC. 3301 KINSMAN BLVD., P.O. BOX 7545 MADISON, Wl 53707 USA FINAL REPORT Karen Armstrong 3M Toxicology Services Building 220-2E-02 St. Paul, MN 55144-1000 Sample: T-4416 V%eC E ILl 1,!,AR5 1990 3 iN@. c0 1 HLA Number: 91201741 Enclosed: Primary Eye Irritation/CorrosionStudy in Rabbits (OECD Guidelines) o Key Personnel o Methodology o Summary of Results o References o Raw Data Appendix Signed: Ste@len M. Glaza Study Director Acute Toxicology PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD Date a CXDF"ww"(3L&borakxv't cowoony HAZLETON LAEOPMTOPW-S AWERICA. r,,C- i3Ol KINSLAAN BLVE),,P.O. BOX 7545 MADISON. Wi S3707 USA HLA Number: 91201741 Sample: T-4416 Acute Toxicology Steven M. Glaza Study Director Section Supervisor Steven R. Sorenson Study Coordinator Patricia Padgham Group Leader Sharen L. Howery Report Coordinator Page 2 KEY PERSONNEL Ouality Assurance Deborah L. Keller Manager Laboratory Animal Veterinarian Cindy J. Cary, DVM Diplomate, ACLAM PHONE (608)241-4471 FACSIMILE (608)241-7227 TELEX TLX 703956 HAZRAL MDS UD LaboraWV Se,@som Co.*" HAZLETON LABC)RATORES AMERCA. fY--. 3301KINSMANBLVD.P,.O.BOX 7W MADISON.Wl S3707USA HLA Number: 91201741 Sample: T-4416 Page 3 METHODOLOGY Objective: To assess the relative level of ocular irritation/corrosion produced following a single exposure of a test substance to one eye of albino rabbits according to the Organisation for Economic Cooperation and Development's Guidelines for Testing Chemicals. Test Material: T-4416 Physical Description: Purity and Stability: Storage and Retention: Safety Precautions: Clear colorless liquid Sponsor assumes responsibility for purity and stability determinations (including under test conditions). The test material was stored at room temperature. Any unused material will be returned to Sponsor according to HLA Standard Operating Procedure. Normal handling procedures were used according to HLA Standard Operating Procedure. Test Animal: Adult albino rabbits, Hra:(NZW)SPF, were procured, maintained individually in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of High Fiber Rabbit ChowO 5326, Purina Mili-s,--Inc-.a,nd held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals". 2 If variations from the prescribed environmental conditions existed, they were documented and considered to have no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study. One male and two female acclimated animals, weighing from 2148 to 2500 g, were chosen at random for the test. The animals' eyes were examined within 24 hours prior to test material administration using sodium fluorescein dye procedures. Only those animals with no sign of ocular injury or irritation were used. Test animals were identified by animal number and corresponding ear tag. Reason for Species Selection: Historically, the New Zealand White albino rabbit is the animal of choice based upon its large orbit and nonpigmented iris. Preparation and Administration of Test Material: The sample was dosed as received. The pH was determined to be 9.9. PHONE (6082)41-4471 FACSIMILE (608)241-7227 TELEX TLX 703956 HAZRAL MDS UD 0 C)OPP4W40 Labor*Wy Swvc" Com"ny HAZLETON LABC)RATOFIES AKAERC.A@ rjC. 3301 KINSMAN BLVD., P.O. BOX 7545 MADISON, Wi S3707 USA HLA Number: 91201741 Sample: T-4416 Page 4 Treatment: Each rabbit received 0.1 mL of the test material placed into the everted lower lid of one eye, with the contralateraleye 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: Historicall@,the ocular route is the route of choice based on the method of Draize. Observations: The treated eyes were observed for ocular irritationat 1, 24, 48, 72 and 96 hours, and Days 7, 14 and 21 after treatment. At the 24- and 72-hour, and 7-, 14- and 21-day readings, sodium fluorescein was used to aid in revealing possible corneal injury. Irritationwas graded and scored according to the Draize technique. Animals were weighed just prior to test material administrationand at weekly intervals throughout the study. Termination: At terminationof the experimentalphase, all animals were euthanatized and discarded. StatisticalMethods: No statisticalmethod was performed. Location of Raw Data and Final Report: The raw data and a copy of the final report will be retained in the archives of HLA. PHONE (608)241-4471 FACSIMILE (608)241-7227 TELEX TLX 703956 HAZRAL MDS UD a C)Oopdrao Labmwo v s@ ca"nny HAZLEMON LABORATORII---S ATAERCA.TC- 3301KINSMAN BLVD.,P.O.BOX 7545 MADISON, Wi S3707 USA HLA Number: 91201741 Sample: T-4416 Page 5 SUMMARY OF RESULTS Test Animal: Albino Rabbits - Hra:(NZW)SPF Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 12/19/89 StartDate (In-life):01/10/90 End Date (In-Life): 01/31/90 Average Primary Eye IrritationScores* Observation Period Average -Score I Hour 41.0 24 Hour 49.0 48 Hour 36.0 72 Hour 38.3 96 Hour 34.3 Day 7 16.0 Day 14 6.0 Day 21 0.0 The averageprimaryeye irritationscore is the total eye irritation score for all the animalsdividedby the numberof animals (3) at each observationperiod. PHONE (608)241-4471 FACSIMILE (608)241-7227 TELEX TLX 703956 HAZRAL MDS UD s C)ORNW40 Laborawvse,.Nmc..,Pw HAZLETON LABOFMTORESANIERCAfl-K--. 3301 KINSMAN BLVD.,P.O.BOX 7545 MADISON, Wl S3707 USA HLA Number: 91201741 Sample: T-4416 Page 6 Animal Number F31165 F31127 F31194 Observation Period 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 I Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 I Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 Table 1 IndividualEye IrritationScores Cornea AB Score AXBX5 Iris A Score AX5 14 20 1 5 14 20 1 5 13 15 1 5 14 20 1 5 13 15 1 5 21 10 0 0 00 0 0 0 00 0 0 0 14 20 1 5 14 20 1 5 14 20 1 5 14 20 1 5 14 20 1 5 11 5 1 5 11 5 1 5 00 0 0 0 Conjunctivae AB C 23 3 33 3 32 2 32 2 32 1 21 0 10 0 00 0 23 3 33 3 32 1 32 2 32 2 21 0 21 0 00 0 Score (A+B+C)2 16 18 14 14 12 6 2 0 16 18 12 14 14 6 6 0 14 20 1 24 40 1 14 20 1 14 20 1 13 15 1 12 10 0 00 0 0 00 0 0 5 23 3 16 5 33 2 16 5 32 1 12 5 32 1 12 5 32 1 12 0 21 0 6 0 00 0 0 0 00 0 0 Cornea A - Degree of opacity B - Area of involvement Conjunctivae A - Redness B - Chemosis C - Discharge PHONE (608)241-4471 FACSIMILE (608)241-7227 TELEX TLX 703956 HAZRAL MDS UD 8 OCOW4W40 LabooNaW S@ Com"ny HAZLEZON LABORATORF-S AK-IEFACAt,,C. 3301 KINSMAN BLVD., P.O.BOX 7S45 MADISON, wi S3707 USA HLA Number: 91201741 Sample: T-4416 Page 7 Animal Number F31165 F31127 F31194 Table 2 Sodium Fluorescein Examination Observation Period Pre-initiation 24 Hour 72 Hour DaY 7 Day 14 NEG POS (80%) POS (55%) POS (157.) NEG NEG POS (100%) POS (80%) POS (5%) POS (5%) NEG POS (75%) POS (8(r/.) NEG NEG Day 21 NEG NEG NEG NEG - No stain retention POS - Positive stain retention (area of cornea involved) Comments: A pain response (excessivepawing of the treated eye) was elicited in all three animals followinginstillationof the test material. Blanching of the conjunctivaewas observed in all three animals at 1, 24, 48, 72 and 96 hours, and Day 7. Petite hemorrhaging of the conjunctivae was observed in two animals at 24 hours. Corneal epithelial peeling was seen in all three animals at 24, 48, 72 and 96 hours, in two animals at Day 7, and in one animal at Day 14. REFERENCES 1. "Acute Eye Irritation/Corrosion," Organisation for Economic Cooperation and Development's Guide7ines for Testing of Chemicals, Section 405 (adopted May 12, 1981). 2. NIH PublicationNo. 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 Officialsof the U.S., pp. 49-50 (1975). PHONE (608)241-4471 FACSIMILE(608)241-7227 TELEX TI.X703956HAZRAL MDS UD a OC)RNW40 Labor&Wy Sorw%M Cefflpwq IILA: PERSOtIlIEL SIGIIATURE SIIEET ACUTE TOXICOLOGY flame Jot)Title Signature Initials Becky Beck@-iitti Lab Animal Technician Ann Bursavi Sr. Clerk Anthony Cass Lab Animal Assistant Cindy J. Cary, DVI,LLab Animal Veterinarian n Co--a,,t@-C-Lc ukk@U@ \.CaAL,,, Kari Gassen Steven 1-1G.laza Sr. Lab Animal Assistant Section Supervisor L; ykr Ben llaley Sr. Lab Animal Assistant Jeff Ilicks Lab Animal Technician .77-7/ SliarenL. lio@-jery flesearciAissistant JiniJirscliele Lab Animal Assistant l,laynIe-ladison Senior Section Supervisor A= Bud f-icdonald St-.Lab Aiiini,A3s1sistant (/,Jot 7 Eileen I-IcConnell AdiiiiiiisLi-atCilveerk lienryI-likula Lab AiiiniaAlssistatit Albert Oleson Si-.Lab AiiiiiiAaslsistant Patricia Padgliani Group Leader 12ffI( Jane Poliiow Lab Animal Technician Steven R..Sorenson Study Coordinator Zt.-. Da%-inTliieding Annette R. Turner C,lei-k Sr. Clerk ILI /-/,L,)VL (09/11/89) L-i ti c V 21 c) ci c - 0 LiC) L-1 j 0 .@l ci Li LJ - -1 ZI 0 Cl 0 0 L/)L'i vc m 'I c EI 0 c: 0 1-3 ti ci :7 Cd c :3 ki L- r- c '0 L) c@'. L) clC'l ci 13 .> )L L L, IJ L- L) el c Cl L% 'XI Cd 'tl @z @o 13 tt ci 0 ri.11 13 u 0 C) c 0 Cu1,< a0 D.C ci- z) Lj r-) tnLn CD ni :3 w Cl L- 2j 4) a 'V @j -3 Li el c Li C3-7-a, EL) c@ I.- m &A L3 -0 ra m o- C) Li Ll > @3 4@ In 4-1 tn c: Gi 0 'Su41 LA (%j rt3 r3 ra CLJ 0) u 4-@ ra a) :St. L) cu E: 0 -J C', > Ll al r,4 L3 C) : c w C 0 -C C. cu C) c 11 L Cr LA. c 0 ci "i L ci L C-L, jci L 11 Cl c IC,7 'C@ U Cr :x 'E tJ 12 c L '. @t C. ru u of 13 C:) 'r11 ty, CD 0 u C, -1 > U-1 L Ij E.3 IILA: qtaol-I-Lu- PRIMARY EYE IRRITATIot4 TEST OBSERVATIONS Group: Test material: Test eye: Right 4 LAIi- _z,pLWastied:ag4seconds following instillation of test material, the test eye was washed witti-LLOA-MoLf lukewarm tap water forlij@L_Seconds. __,,,-Unwashed 0 servattorl---Ppriod: Animal No. Location of corneal lesions Ta 11 ----- flead Cornea - Opacity C/D a-) Iici L( Area Iris (.onjunctivae Redness Chemosis C- Discharge ,Sodium fluorescein exam Technician: Date: riA Not applicable. A Petite hemorrhaging. B Blanching. C - Clear discharge. D - Purulent discharge. E - liairloss around the eye. F - Necrotic areas. .G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. 3 C- zL t)k EYE IRRITATION SCORE:-x4ir) calculated BY' Verified By:. K-4- Date 1-_14-c4n ff2, Date '1211117) i - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by: Date: ICZ9 fiLA:- Iao Il_ql_ PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:_ I Test material: I-- 14tAi Test eye :_2j-qht- -zLeLWastiedt:jq seconds following Instillation of test material, ttie test eye was washed with_bLoi_mLof lukewarm tap water tortip@ seconds. __ie-Unwa shed Animal No. Location of corneal lesions Tail fiead Cornea - Opacity Area o.servatin Perioda-) 1 IC4 t4 J@-5--7) 2 L* Iris (,.onjunctivae Redness Ctiemos i s C Discharge Sodium fluorescein examPOI@0&7. Technician: Date: 1 -11-90 NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E liairloss around the eye. F Necrotic areas. .G Unable to visualize due to severe swelling. H No reaction to light. I Injected. poli--wI,?nOI7 pt),S EYE IRRITATION S C 0 R E Calculated By: Verified By: ap@ C) Date IDate J - Corneal K - Corneal L - Corneal epithelial damage, peeling. epithelial damage, piling. epithelial damage, pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. 4L%CA4 C IILP,.nC.)Aj ep_4C@A 1&7 Reviewe(i by: Date-- fiLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test material: T- iL- Test eye: Right ,If@%Wast)edp:jc@seconds following Instillation of test material, the test eye was washed with 4o@mL of lukewarm tap water torp;@k seconds. __L.,Unwashed 0 servatl-cr@--Ppriod- P, "ris Animal t4o. Location of corneal lesions Tai I ----- lipad I (Is IIa-) Iict Cornea - Opacity Area Iris (,.onjunctivae Redness Ctiemos Is ,2 Discharge Sodium fluorescein exam AI,4 Technician: Da te NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D.- Purulent discharge. E - liairloss around the eye. F - Necrotic areas. .G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. 7 A117- EYE IRRITALION SCORE: Calculated By: Verified By: x:77 Diate D a te -qL) ./z3f9tN J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. M - Hypopyon. t4- Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by: Date:_,-' liLA:qlnr)l-lql PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:- I Test material: - 'r-(4q I Test eye: Right _ZLL,LWaslied:jp,seconds following Instillation of test material, ttie Lest eye was washed witt)-ta mL of lukewarm tap water torp4;@,seconds. _h,,-Unwa s lied Animal No. Location of corneal lesions n servatic Ppriod- Ll Tai 1 ----- Head Cornea - Opacity Area I r Is (.onjunctivae Redness Cliemosis Dlscharqe 1.2- -2 -2c- S od ium f Iu o re sc e In e m 53-,@ Technician: Date: NA Not applicable. A Petite hemorrhaging. B Blanching. C - Clear discharge. 0 - Purulent discharge. E - liair loss around the eye. F - Necrotic areas. .G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. EYE IRRITALION SCORE: Calculated By: Verified By: DD ate -iLj-- Ci ate 214 i - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal eplthelial damage, pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by:- Date: liLA: PRIMARY EYE IRRITATIOli TEST OBSERVATIONS Group: Test mateF'7a]-T'Test eye: Right tAq'L- -,LtWastied:pjpkseconds following Instillation of test material, the test eye was washed with-ELI@L--MoLf lukewarm tap water tortl;k seconds. __,,-Unwashed ;ervallnj Ppriod- Animal No. Location of corneal lesions TaII - -- -- Ilead Cornea - opacity Area iris C:onjunctivae Redness Chemosis Discharge Sodium fluorescein exam &J Pt- Technician: Date: NA - Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. 0 Purulent discharge. E - liairloss around the eye. F - Necrotic areas. @G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. AB C- &A AiA EYE IRRITAIION SCORE: N4 Calculated By: Verified By: Date L.-I!i-cKi Date i Corneal epithelial damage, peeling. K Corneal epithelial damage, piling. L Corneal epithelial damage, pitting. M Hypopyon. N Corneal neovascularization. P Pannus. R Unable to visualize due to severe opacity. S Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Revieweti by: rL3 Date: Ao IILA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:_ I Test material: (444 Test eye: Right _jl!@LWastiedj:piseconds following instillation of test material, the test eye was washed with_&O,_mL of lukewarm tap water toriji@_seconds. __L,-Unwashed 0 @ervation Pprind- --I Aniinal No. Location of corneal lesions Tail ----- liead Cornea Opacity Area Iris C'.onjunctivae Redness Cliemos is Discharge Sodium fluorescein examico" Technician: Date: NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E liairloss around the eye. F Necrotic areas. :G Unable to visualize due to severe swelling. H No reaction to light. I Injected. EYE IRRITATION SCORE: Calculated By: E, Date Verified By: 7n7 Date iA -cio a J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewe(i by: Date- 2@- PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test material: T'- c4tA iL. Test eye: Right _zl,tLWastiedp:jckseconds following instillation of test material, the test eye was washed witti_&i)_mLof lukewarm tap water torIL2@_seconds. __L@,Unwashed 0-servattan Pprind: IL( Animal No. cl Location of corneal lesions Tail ----- fiead Cornea - Opacity n Area Iris r) C) ('.onjunctivae Redness C) Cliemos is Discharge C) Sodium fluorescein exam Technician: Date: NA - Not applicable. A - Petite hemorrhaging. 8 - Blanching. C - Clear discharge. 0 - Purulent discharge. E - liairloss around the eye. F - Necrotic areas. .G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. EYE IRRITATION SCORE: Calculated By: Verified By:_ 4p,_ Date @1214@91, l@=1 Date i J - Corneal epithelial damage, peeling. K - Corneal epittielialdamage, piling. L - Corneal epithelial damage, pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by: Date: liLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:- I Test material: 'r- 44141L- Test eye: Right _SpL_Washed: Ickseconds following Instillation of test material, the test eye was washed with 4;hmL of lukewarm tap water torILi@_seconds. ,Unwashed 0 @prvatic i) PF?riod: Animal No. Location of corneal lesions Tail ----- Ilead Cornea - Opacity 0 Area 0 Iris 0 (,.onjunctivae Redness Chemosis n Discharge 0 Sodium fluorescein exam @j Technician: l@n I Date: NA A BCDEF'.G - HI- Not applicable. Petite hemorrhaging. Blanching. Clear discharge. Purulent discharge. liairloss around the eye. Necrotic areas. Unable to visualize due to severe swelling. No reaction to light. Injected. 0 EYE IRRITALION SCORE: Calculated By: Verified By: Date i 0a te JKLMNPR- SPOS NEG Corneal epithelial damage, peeling. Corneal epithelial damage, piling. Corneal epithelial damage, pitting. Hypopyon. Corneal neovascularization. Pannus. Unable to visualize due to severe opacity. Granulation scar tissue. - Positive stain retention. - Negative stain retention. Reviewed by: ,-,.-, I 1 11 Date: 2--qL-9@@