Document NEdyL0pm4Ydbo4mJ9w5nb43VV

HAZLEZON LABORATORIES AAIERICA, INC. 3301 KINSMAN BLVD. P.O.BOX 7545 MADISON, WISCONSIN 53707 Chemical& B!oMedicalSciencesDivision PHONE (008)241-4471o TLX 703956HAZRAL MDS UD FINAL REPORT iPN@2 71 ROGER G. PERKINS MINNESOTA MINING & MANUFACTURING TnxICOLOGY SERUICES ST. PAUL., MN 55101 COMPANY SAMPLE: T-4102 PURCHASE ORDER NUMBER: T837389-410 754 SAMPLE NUMBER: 70905764 SAMPLE ENTERED: 09/25/87 REPORT PRINTED: 01/20/88 ENCLNSED: PRIMARY EYE IRRITATION/CORROSION (OECD GUIDELINES) Key Per5onnel Method Summary Reference5 Raw Data Appendix STUDY IN RABBITS STGNED: STEUEN STUDY ACUTE M. GLAZA DIRECTOR TOXICOLOGY DATE ........... HAZLETON L"9CXWX3RIr=S ANAERICA. INC. 3301 KINSMAN BLVD. o P.O.BOX 7545 MADISON, WISCONSIN 53707 Chemical& BioMedicaSlciencesDivision PHONE (608)241-4471o TLX 703956HAZRAL MDS UD SAMPLE NUMBER: 70905764 SAMPLE: T-4102 PAGE 2 KEY PERSONNEL Acute Toxicolog@2 Steven M. Glaza Stud@) Director Calvin L. Horton Group Leader Support Services Sharen Report L. Howery Coordinator Oualit@2 Assurance Debra Curley Manager Arndt Anatomical Patholoak.) Thomas E. Palmer, PhD Anatomical Pathologist Robert Senior Salava Section Supervisor Dennis Hoffman Group Leader Necropsy Anne Mosher Group Leader Pathology Data Laborator!2 Animal Veterinarian Cindy J. Cary., DVM Diplomate, ACLAM HAZLC%CN L"30RXVRIES ANERICA. INC. 3301 KINSMAN BLVD. 0 P.O.BOX 7545 MADISON, WISCONSIN 53707 Chemical& B!oMedicaSlciencesDivision PHONE (608)241-44710 TLX 703956HAZRAL MDS UD c,-;AMPLE NUMBER: SAMPL-E: T-4102 70905764 PAGE 3 OECD EYE IRRITATION Objective: To determine the level of ocular irritation produced following a single exposure of a test substance to one eye of albino rabbits according to the Organization for Economic Cooperation and Development's C,uidelines for Testing Chemicals. Test Material: T-4102 Physical Description: Purity and Stability: Storage and Retention: Safety Precautions: Dark amber liquid Sponsor a55ume5 responsibility for purity and stability determinations. The test material was stored at room Any unU5ed material will be discarded to HLA Standard Operating Procedure. Normal handling procedures were used to HLA Standard Operating Procedure. temperature. according accordino Test Animal: Young adult rabbits Of the New Zealand White strain were procured, maintained individually in 5creen-bottom cages in temperatureand humidity-controlled quarters, provided acC055 to water ad libitum and a measured amount of Purina High Fiber Rabbit Chow, and held for an acclimation period of at least 7 days. Animal husbandry and housing at HL.A comply with standards outlined in the "Guide for the Care and Use of Laboratory AniMal5". If variations from the prescribed environmental conditions eXi5ted., 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. Three acclimated animals., weighing from 2076 to 2155 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: The New Zealand White albino rabbit is the animal of choice based upon it5 large orbit and nonpigmented iris. Preparation and Administration of Test Material: received. The pH was determined to be 9.1. The 5aMple was dosed as Treatment: Each rabbit received 0.1 ml of the liquid test material placed into the everted lower lid of one eye, with the contralateral eye serving as the untreated control. The upper and lower lids were gently held tooether for one second to prevent loss of material and then released. The eyes of the rabbits remained unflushed. HAZLOTON L&aOR=MleS ANERICA, INC. Chemical& SloMedicaSlciencesDivision 3301 KINSMAN BLVD. 9 P.O.BOX 7545 . MADISON, WISCONSIN 63707 - PHONE (608)241-4471* TLX 703956HAZRAL MDS UD r;AMP[-E NLIMBER: 70905764 SAMPLE: T-4102 PAGE 4 OECD EYE IRRITATION (CONTINLJED) Reason for Route of Administration: based on the method of Draize. Historically, the route of choice Ob-servations: The treated ekjes were observed for ocular irritation at 1.;24; 48, 72 and 96 hours, and at 7 and 14 days after treatment. At the 72-hour., 7- and 14-day readings, sodium fluorescein Was Used to aid in revealing possible corneal injury. Irritation was graded and scored according to the Draize technique. Animals were weights were or at death. weighed jU5t taken again prior to test material administration. at weekly intervals throughout the study Body period Pathology: At study termination surviving animals were euthanatized and discarded. The animal that died on study Wa5 subjected to a gr055 necrOp5y examination and abnormalities were recorded. the animal iiia5discarded and no tissues were saved. After necropsy, Statistical Methods: Other than average eye irritation 5cor85, statistical method W85 performed. no other 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. HAZLOTON LABCF%MnFqlr=S AKn=-RICA, INC. Chemical& BloMedicaSlciencesDivision 3301KINSMAN BLVD. o P.O.BOX 7646 o MADISON, WISCONSIN 53707 o PHONE (6082)41-44719 TLX 703956HAZRAL MDS UD c;AMPI.-E NLIMBFR: 709015764 SAMPLE: T-4102 OECD EYE IRRITATION (CONTINUED) SLIMMARY Test Animal: Albino rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 10/20/87 PAGE r? Date Test Started: 11/06/87 Date Test Completed: 11/20/87 PRIMARY EYE IRRITATION OBSERVATION PERIOD I Hour: 24 Hours: 48 Hours: 72 Hours: 96 Hours: 7 Days: 14 Days: SCORES* 3 Rabbit Mean 0.1 ml (Unwashed) 24.0 29.3 21.3 16.5** C3.5** 1.0** 0.0** The Primary Eye Irritation for all the animals divided observation period. Based on a two-animal mean. Score is the total eye irritation by the number of animals (3) at 5core each IFWII HAZLOTON LABORATORlr=S ANERicA, iNc, Chemica&lBioMedicalSciencesDivision 3301 KINSMAN BLVD. a P.O.BOX 7545 o MADISON, WISCONSIN 53707 0 PHONE (608)241-4471& TLX 703956HAZRAL MDS UD SAMPLE NUMBER: SAMPLE: T-4102 70905764 PAR-,E 6 OFCD EYE IRRITATION Animal Number F20347 F20333 F20344* Obserk)ation Period 1 Hour 24 Hours 48 Hours 72 Hours 96 Hours 7 Days 14 Days 1 Hour 24 Hours 48 Hours 72 Hours 96 Hours 7 Da ys 14 Days 1 Hour 24 Hours 48 Hours Individual (CONTINUED) Table 1 Eye Irritation Scores Cornea A 8 0 0 1 3 1 3 1 2 1 1 0 0 0 a Score Axexr;l 0 113 15 10 5 -0 0 Iris A 1 1 1 1 0 0 a Score A X 13 5 5 5 5 0 0 a Conjunctivae A B c 2 2 2 2 2 1 2 2 1 2 2 1 1 0 0 1 0 0 0 0 a 1 1 5 1 2 10 1 1 5 0 0 a 0 0 0 0 a 0 0 0 0 1 5 2 3 3 1 5 2 3 2 1 5 2 3 3 0 0 2 1 1 0 0 1 1 0 0 0 0 a a 0 0 0 0 0 1 2 10 1 2 10 0 0 0 1 5 2 3 2 1 5 2 3 2 0 0 2 1 1 Score (A+B+C)2 12 10 10 10 2 2 0 16 14 16 a 4 a 0 14 14 8 Co r n F-,,3 A = Degree of opacity 8 - Area of involvement Conjunctivae A = Redness B = Chemosi5 C = Discharge Sodium Table Fluorescein 2 Examination Animal Number Pro-initiation Observation Period '22 Hours 7 Days 14 Days F20347 F20333 F20344 NEG NEG NEC, POS (40%) NEG NEC, NEG NE(; NEG NEG = No stain retention Pnc=; Positik.,e stain retention (area of cornea inkpolved). Animal found dead at 72-hour ob5erkAation. \tw HAZLOZON --LABORmmRir=r. ANIERICA. Chemical& BioMedicalSciencesDivision 3301 KINSMAN BLVD. o P.O.BOX 7645 o MADISON, WISCONSIN 53707 o PHONE (608)241-4471o TLX 703956HAZRAL MDS UD SAMPLE NL-IMBER: 70901,5764 SAMPLE: T-4102 PAGE 7 OECD EYE IRRITATION (CONTINUED) Comments: A pain response (excessive Patling at the treated eye) was elicited from two animals immediately following instillation of the test material. Blanching of the conjunctivae 1.,IasSeen in all three animals at l@ 24@, and 48 hours', and in the remaining two animals at 72 hours. Petite hemorrhaging of the conjunctivae was seen in two animals at 48 hours. Corneal epithelial peeling Wa5 al.1 three animals at 24 hours, animal at 72 and 96 hours. exhibited by two animals at by two animals at 48 hours, 1 hour, by and by one Animal No. F20344 was found dead on Study Day 3. revealed no visible lesions. The gr055 necrDP51,) References: 1. Organi5ation for Economic Cooperation and Development'5 Guidelines for Testing of Chemicals, Secti.on 405, Acute Eye Irritation/CorrO5ion, adopted May 12, 1981. 2. Draize J.H.., "Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics - Dermal Toxicity",, Association of Food and Drug Officials of the United Statesy pp. 46-59 (1975). 3. 40 CFR 792. 4. NTH Pijblication No. 86-23 (Revised 1985). Personnel Signature Sheet Acute Toxicology NLA No. Name Job Title Becky Beckwith Sr. Lab.,Animl Asst. Steve Beloungy Lab. Animal Asst. Ken Bridges Pat Crary Sr. Lab. Animal Asst. Sr. Lab. Animal Asst. Shane Eith Lab Animal Asst. Shawn Frazier Lab Animal Asst. Steven M. Glaza Group Leader Molly Mhn Admin. Clerk Kevin Hamilton Lab. Animal Asst. Jeff Hicks Sr. Lab. Animal Asst. Calvin Norton Group Leader Sharen L. Nowery AdministrativeAsst. Gregory Johnson Lab. Animal Tech. Paul Krebs Lab. Animal Asst. Wayne Madison Section Supervisor Scott McConnell Lab. Animal Tech. Shelley McConnell Lab. Animal Tech. Dawn Conant Sr. Lab. Animl'Asst. Don *Avis Lab. Animal Asst. Robin Olson Lab. Animal Asst. Patricia Padghm Joseph J. Daun TOM L"der Lab. Animal Asst. Michael Patzka Lab. Animal Asst. John Paulson Sr. Lab; Animal Asst. Jane Polnow Lab. Animal Tech. Dennis S. Stainer Lab. Animal Tech. Michael Thesing Lab. Animal Asst. Paula G. Vangen AdministrativeAsst. Albert Olson Manpower Jim Jirschele LTE Ben Haley Sr. Lab Animal Asst. Eileen M. McConnell Admin. Clerk Annette R. Turner @lanpower. Sianature d4l wa. GOAOM @L--- A? -Uikt Initials s t, t-AL t61wc. @4"c) ri ;tr- BODY WEIGHT/o@,aE RECORD liLA: Study title: Primary Eye Irritation Test materia F'-T-- io Physical descr pt on: i@Asv_. pH result: with Hanna lieterNo. 689U Dose: MTI-- icA-mT-equiva lent) -_,,,4ois--e@-fiikw-3iaAt gniL--@@sliposabslyeringe/.riAAIeach dose individually drawn up with a I)S@-ijWLam Uton Syringe Date animals received: Species/strain: Rabbi ea an Source: Hazleton Research Products liic Room t4o:____M Review of folder preparation by: Pain Response Initial Following Animal No. Group Sex SF* Dosing_ Fa (>34-1 I- L@- FQ03,-15 4 IL%gc. Animal Body Weights (g) Initiation Day 7 Day 14 Day 21 All animals appea just prior to dos Technician:--L& @ 1 21qf %"1 @ Sodiufmluo NEG- Negative. Pos - Positive. INA - Not applica U - Unable to d V - Vocalizatio E - Excessive p N - None Dosed direc The eyelids imwdliately blinking or Technician Date Scale Used 15019 /,1 15611 Surviving animals designated for sacrifice and discard. Technician Dosed in th ol The upper a gently held second. I Time of dosing: Technician Time of first s Teclinician:__.,tt- Date Reviewedby:_ Date:. (00261/vmt) HLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test material: -r -44Ina Test eye: Right _LffiWashed:w)Aseconds following instillation of test-material, the test eye was washed with_h).e_mLof lukewarm tap water fork)A seconds. 4-1@'Unwashed Animal No. Locationof corneallesions Qj)sLarvati*nitP@riodi hour Tail ----- Head Cornea - Opacity Area Iris Conjunctivae Redness Chemosis 3 Oischarce Sodium fluorescein exam )3A L K)A Technician: Date: EYE IRRITATION SCORE: Z4, C) Calculated By: Date Verified By: trI Date 13-5@-7 NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulent discharge. E - Hair loss around the eye. F - Necrotic areas. G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pi-tting. N - 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: , fy (00261/vmt) Date: HLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test material: Test eye: Right Ie),Z -Lffiwashed:QA seconds following instillation of test-material, the test eye was washed with_L8_mL of lukewarm tap water foriJA seconds. 4.1--@unwashed Animal No. Location of corneal lesions Tail ----- Head Cornea - Opacity Area Iris Conjunctivae Redness Chemosis Discharge Sodium fluorescein examiAJA Technician: Date: NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulentdischarge. E Hair loss around the eye. F Necrotic areas. G Unable to visualizedue to severe swelling. H No reactionto light. I Injected. L%LLy"i Parind- AOUr'@-> _;r A to AIA AiA I EYE IRRITATION SCIDRE, CalculatedBy: VerifiedBy: Dat: Bat J - Cornealepithelialdamage, peeling. K - Cornealepithelialdamage, piling. L - Cornealepithelialdamage,pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unableto visualizedue to severe opacity. S - Granulationscar tissue. POS - Positivestainretention. NEG - Negativestain retention. Reviewed by: 12f (00261/vmt) Date.- HLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test materi a 1 14 Test eye: Right _,uawashed:O%'@seconds following instillation of test-material, the test eye was washed with_Llfi_mLof lukewarm tap water fo.rPJAseconds. 4@-@unwashed Animal No. Location of corneal lesions QjiservatiniiP@rind! hour Tail ----- Head Cornea - Opacity Area Iris Conjunctivae Redness Chemosis 2ischarge Sodium fluorescein examievA, 41Pr i A)P Technician: Date: EYE IRRITATION SCORE, Calculated By: Verified By..- Dat: LiOat it NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. 0 Purulent discharge. E Hair loss around the eye. F Necrotic areas. G Unable to visualize due to severe swelling. H No reaction to light. I Injected. J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. N - 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: ro (00261/vmt) Date: HLA: Group: Test material: Test eye: Right PRIMARY EYE IRRITATION TEST OBSERVATIONS 44 -Lfiwashed:k)A seconds following instillation of test-material, the test eye was washed with_Lla_mL of lukewarm tap water forQA seconds. L.-@Unwashed Animal No. Location of corneal lesions i P@rind.-7P-hours .6Lks3 Tail ----- Head Cornea - Opacity Area Ai C) Iris (3 Conjunctivae Redness Chemosis Discharge -D I Sod ium f1uorescei n exam -@b6 4t'j kioq I Technician: Date: EYE IRRITATION SCORE: Calculated By: Verified By: I (Z-iql)vM*t Mrt*40) Ettae H-%-M Date //-/3-97 NA Not applicable. A Petite hemorrha(jing. B Blanching. C Clear discharge. 0 Purulent discharge. E Hair loss around the eye. F Necrotic areas. G Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. J - Corneal epithelial damage, peeling. K - Co,rneal epithelial damage, piling. L - Co rneal 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: (00261/vmt) Date: HLA: -@nIgns?@n PRIMARY EYE IRRITATIONTEST OBSERVATIONS Group: Test material: Test eye: Right -LWashed:OA seconds following instillation of test-material, the test eye was washed with_L)fi_mLof lukewarm tap water fork)A seconds. 1--@unwashed Animal No. Location of corneal lesions Tail ----- Head Cornea - Opacity Area Iris Conjunctivae Redness Chemosis Discharge Sodium fluorescein exami Pt Technician: /Y,-? IA b4- Date: //-/0-?7 NA Not applicable. A Petite hemorrhaging. B Blanching. C Clear discharge. D Purulentdischarge. E Hair loss around the eye. F Necrotic areas. G Unable to visualizedue to severe swelling. H No reactionto light. I Injected. USUA=I PL-rind-q(ohoucr-, 11 1 1 EYE IRRITATION SCORE: :!5- Calculated By: Date VerifiedBy:. ----IY7- Date /I-13-q7 J - Corneal epithelialdamage, peeling. K - Corneal epithelialdamage, piling. L - Corneal epithelialdamage, pitting. N - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualizedue to severe opacity. S - Granulationscar tissue. POS - Positivestainretention. NEG - Negativestain retention. Reviewed by: (00261/vmt) Date: HLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test material: Test eye: Right -Ltwashed:LA seconds following instillationof test-material, the test eye was washed with_QfLmL of lukewarm tap water fork)A seconds. @6@'Unwashed rolbserv i P@riod: --'I@aAJ Animal No. Location of corneal lesions Tail ----- Head Cornea - Opacity Area Iris Conjunctivae Redness Chemosis 0 uischarge Sodium fluorescein -TM amam a& Technician: Date: NA Not applicable. A Petite hemorrhaging. 8 Blanching. C Clear discharge. 0 Purulent discharge. E - Hair loss around the eye. F - Necrotic areas. G - Unable to visualize due to severe swelling. H - No reaction to light. I - Injected. 0 o o C) o oix I / EYE IRRITATION SC@ORE: Calculated By: verified By: Date /1-13-2 Date J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, pi.ling. L - Corneal epithelial damage, pitting. M - Hypopyon. N - Corneal neavascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by: (00261/vmt) Date: HLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test material: ICQ Test eye: Right _.Ltwashed:OA seconds following instillation of test-material, the test eye was washed with_L)ja_mLof lukewarm tap water fork)4A seconds. il@6nwashed ()hsarvatiniL_Epriod! 4 Animal No. Locationof corneallesions Tail Head Cornea - Opacity Area 0 Iris Conjunctivae Redness Chemosis Discharge Sodium fluorescein exam L Technician:Date: EYE IRRITATION SCORE: 0.0 Calculated BY: Date VerifiedBy: @V? Date--12 - NA Not applicable. A Petite hemorrhaging. 8 Blanching. C Clear discharge. 0 Purulentdischarge. E Hair loss around the eye. F Necroticareas. G Unable to visualizedue to severe swelling. H No reactionto light. I Injected. J - Corneal epithelialdamage,peeling. K - Corneal epithelialdamage,piling. L - Corneal epithelialdamage,pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualizedue to severe opacity. S - Granulationscar tissue. POS - Positivestainretention. NEG - Negativestain retention. oi@,il Reviewed by: (nnp;i/vmt) Date: HLA: SCALE FOR SCORING OCULAR LESIONS (DRAIZEI TECHNIQUE) (1)Lornea (A) Upacity - degree of density (area most dense taken for reading) No opacit 0 Scattered or diffusearea, details of iris clearlyvisible 1* Easily ciscernibletranslucentareas, details of iris slightlyobscurid 2* Opalescentareas, no details of iris visible, size of pupil barely discernible 3* Opaque, iris invisible 4* (b) Area of cornea involved One qu-a-rt-e-r-l7eosrs), but not zero I Greater thiinone-quarter, but less than half 2 Greater trianhalf, but less than three-quarters 3 Greater tnan three-quarters,up to whole drea 4 Ax 6 x5 Total maximum 80 (e) Iris (A) Values Norina7- 0 Folds above normal, congestion,swelling, circumcorneal injection(any or all of thtse-or 1* combinationof any thereof) iris still reactingto light (sluggishreaction is positive No reaction to light,hL4,iorrnageg,ross destruction (any or-all of these) 2* Ax5 Total maximum = 10 (3)Conjunctivae (A) Redness (refersto palpebral and bulbar conjunctivaeexcluding cornea and iris) - VesseTs- no-rmai 0 Vessels definitely injected above normal I More diffuse, deeper crimson red, individual vessels not easily discerni5le 2* Diffuse beefy red 3* (ii) Chenosis No swell@ing- 0 Any swellin above normal (includes nictitating membrane) 1 2* Ouvious swellingwith partial eversion of lids Swelling with lids about half closed 3* Sweiliny with lias about half closed to completely closed 4* (C) Uischarge No discharge 0 Any amount differen; from normal (does not include small amounts observed in inner 1 cantnus of normal animals) UISCharge witn iaoisteningof the lids ano hairs just adjacent to lids 2 uiscnarge with twistening of the lids and hairs, and considerable area-a-r-o-un-d--t-Fe-eye 3 Score (A + 8 + C) x 2 Total maximum - 20 'rhetotal score for the eye is the sun,of all scores obtained for the cornea iris, and conjunctivae. Indicatespositiveeffect, (FHSA Interpretation) uraize, J. H., "Appraisalof the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity", Association of Food and Drug Officialsof the United States, pp. 46-59 (1975). (00261/vmt)