Document rpaVm5D47E89MDG04L4y7N2LJ

HAZLEZON 3301 KINSMAN BLVD. Losopmemm &AOERC.A. W4-- P.O. BOX 7545 MADISON, WISCONSIN S3?07 Chemical & BloM*dical Sciences Division PHONE (OW 241-4471 TLX 703M MAZRAL MDS UD FINAL REPORT ROGER G. PERKINS MINNESOTA MINING & MANUFACTURING TOXICOLOGY SERUICES ST. PAUL, MN 55101 COMPANY SAMPLE: T-4101 PURCHASE ORDER NUMBER: T837389-410 753 SAMPLE NUMBER: SAMPLE ENTERED: REPORT PRINTED: 70905395 09/23/87 01/17/88 ENCLOSED: PRIMARY EYE IRRITATION/CORROSION (OECD GUIDELINES) 0 Key Personnel 0 Method Summary References Raw Data Appendix STUDY IN RABBITS SIGNED: STEVEN M. GLAZA STUDY DIRECTOR ACUTE TOXICOLOGY .........171t:@@ DATE ........ enh HAZLE%CN IANOMOMMOD AAOWRCA. *4-- Chemical& BiaMedicalSciencesDivision 3301KINSMAN BLVD. * P.O.BOX 7SO o MADISON, WISCONSIN 53707 - PHONE (M) 2414471 - TLX 70" MAZRAL MOS UD SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 2 KEY PERSONNEL Acute ToxLQD_L2" Steven M. Glaza Study Director Calvin L. Horton Group Leader Support Services Sharon L. Howery Report Coordinator Duality Assurance Debra Curley Arndt Manager lithorator-y-Animat Vaterina-' Cindy J. Cary, DUM Diplomat*, ACLAM HAZLE%CN L&ACPW%WNM &AOEPC.4W.r- 3=i KINSMAN OLVID. - P.O. BOX 7545 - MADISON, WISCONSlN-S3707 Chemical & BloMedical Sciences Division * PHONE (MI) 241.4471 - TLX 7039M HAZRAL MOS UD SAMPLE NUMBER: 70905395 SAMPLE: T-4101 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 Guidelines for Testing Chemicals. Test Material: T-4101 Physical Description: Purity and Stability: Storage and Retention: Safety Precautions: Clear yellow liquid Sponsor assume& responsibility for purity and stability determination&. The test material was stored at room Any unused material will be discarded temperature. according to HLA Standard Operating Procedure. Normal handling procedures were used according to HLA Standard Operating Procedure. Test Animal: Young adult rabbits of the Now Zealand White *train were procured, maintained individually in screen-bottom cages in temperatureto water Ad libitum and humidity-controlled quarters, provided accoalm and a measured amount of Puri-ma High Fiber Rabbit Chow, and hold 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 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 food or water which would have interfered with or affected the results of the study. Three acclimated animals, weighing from 2069 to 2146 9, were chosen at random for the test. The animals' eyes were xamined within 24 hours prior to test material administration using sodiuam 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 *or tag. Reason for Species Selection: The Now Zealand White albino rabbit is the animal of choice based upon its largo orbit and nonpigmented iris. Preparation and Administration of Test Material: received. The pH was determined to be 12.9. The sample 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 hold together for one second to prevent lose of material and then released. The eyes of the rabbits remained unflushed. IFIVal HAZLE%CN L-@@ chemical & SioMedicalSciences Division 3301KINSMAN BLVD- * P.O.BOX 7S4S - MADISON. WISCONSIN S3707- PHONE (am 2414471 o TLX 70" MAZRAL MDS Ut) SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 4 OECD EYE IRRITATION Reason for Route of Administration: based on the method of Draize. (CONTINUED) Historicallyp the route of choice Observations: The treated eyes were observed for ocular irritation at 1, 24) 48, and 72 hours after treatment. id in revealing At the 72-hour reading, sodium fluorescein was used to possible corneal injury. Irritation was gradad and scoraed according to the Draize technique. Animals were weighed just prior to test material administration. Pathology: At study discarded. Statistical Methods: statistical method termination Other than was performed. all animals average eye were outhanatized and irritation scores, no other Location of Raw Data and Final Report: The raw date and a copy of the final report will be retained in the archives of HLA. HAZLE%DN AAAEPC-A W@,C 3301 KINSMAN BLVD. * P-0. BOX 7546 - MADISON, WISCONSIN Chemical& elomedicalSciencesDivision S3707 - PHONE MM 2414471 . TLX "3$W HAZRAL MOS UD SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 5 OECD EYE IRRITATION SUMMARY (CONTINUED) Test Animal: Albino rabbits - Now Zealand White source: Hazleton Research Products, lnc.p Denver PA Date Animals Received: 10/20/87 Date Test Started: 11/06/87 Date Test Completed: 11/09/87 PRIMARY EYE IRRITATION OBSERUATION PERIOD 1 Hour: 24 Hours: 48 Hours: 72 Hours; SCORES* 3 Rabbit Mean 0.1 ml (Unwashed) 6.3 6.7 0.7 0.0 The 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. %7HAZLEZON LAMCX%WCPMS &AAMICA. Wr_ 3301 KINSMAN BLVD. - P.O. BOX 7545 - MADISON, WISCONSIN ChemicalA BloMedicalSciencesDivision 53707 0 PHONE (SM 241401 - TLX 70n" HAZFTAL MOS UD SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 6 OECD EYE IRRITATION Animal Number F20334 F20326 F20329 Observation Period 1 Hour 24 Hours 48 Hours 72 Hours 1 Hour 24 Hours 48 Hours 72 Hours 1 Hour 24 Hours 48 Hours 72 Hours (CONTINUED) Table 1 Individual Eye Irritation Scores Cornea A B 0 0 1 1 a a 0 0 0 0 1 1 0 0 0 0 0 a 0 0 0 0 0 0 Scare AXBXS a 5 0 0 a 5 0 0 0 0 0 0 Iris A a 0 a 0 0 1 0 0 0 Scare A X 93 0 0 0 0 a 0 a 0 5 a 0 0 Conjunctivae A 8 c 1 1 a 1 1 0 1 a 0 0 a 1 1 0 0 0 0 a 0 0 2 1 0 1 a 0 0 a 0 0 a 0 Score (A*B+C)2 4 4 2 0 4 4 0 0 6 2 0 0 Cornea A - Degree of opacity B - Area of involvement Conjunctivae A - Redness 8 - Chemosis C - Discharge Table 2 Sodium Fluorescein Examination Animal Number Observation Pro-initiation Period 72 Hours NEG - No stain POS - Positive F20334 F20326 F20329 retention stain retention NEG NEG NEG (area of cornea NEG NEG NEG involved). WHAZLEMON LAMOPARCMM &K4M4CA. WC 3301 KINSMAN BLVD. - P.O. BOX 7S45 - MADISON. WISCONSIN Chemical & SlaModical Sciences Division S3M7 - PHONE (SM 241-"Yl - TLX 7039M HAZRAL MOS UD SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 7 OECD EYE IRRITATION Comments: (CONTINUED) No pain response was elicited from any--animal following instillation of the test material. Corneal spithelial peeling was observed in two animals at 24 hours. References: 1. Organisation for Economic Cooperation and De"volopment's Guidelines for Testing of Chemicals, Section 405, Acute Eye Irritation/Corrosion.# 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 States, pp. 46-59 (1975). 3. OECD's Principles of Good Laboratory Practice, Annex 2, C(81)30 (Final). 4. NIH Publication No. 86-23 (Revised 1985). Personnel Signature Sh*@t Acute Toxicology MLA NO. Job Title BKky B*Ckwith Steve Beloungy Ken Bridges Pat Crary Sr. Lab. Animal AsSt. Uib. Animal AgSt. Sr. Lab. Animal Asst. Sr. Lab. Animal Asst. Shane Eith Shaw Frazier Steven N. GISZ& ftlly Hahn Kovin paw Iton Jeff Hicks Calvin Morton Sharon L. NowrY Gregory Johnson Paul Krebs Wayne Madison Lab Animal Asst. Lab Animal Asst. Group Leader Admin. Clerk Lab. Animal Asst. Sr. Lab. Animal Asst. Group Leader Administrative Asst. Lab. Animal Tech. Lab. Animal A22t. Section Swervisor Scott fteenneii Lab. Animal Tech. Shelley ftconmll Dawn Conant Dan Mavis Lak. Animal Tech. Sr. Lab Animal Asst. Lab. Ani*mal Asst. ltabinOlson Patricia Padom Joseph J. D@ Itichaelfttzka 30M Paulsm 36fw Poinow Dennis B. Steir.*r Michael TMsing Lab. Animl Asst. Tom Leader Lab. Animal Asst. Lab. Animal Asst. Sr. Lab.'Animal Asst. Lab. Animal Tech. Lab. Animal Tech. Lab. Animal Asst. Paul& a. vanvm Albert Olson Administrative Asst. ftnpower Jim Jirschole LTE Ben Haley Sr. Lab Animal Asst. Eileen M. McConnell Admin. Clerk Annette R. Turner Manpower SionatiLre li tA 16 Initials K AL cozr T> )(. "AS-1 fp6jc- ft @4b ,av, to 410) 41 Ck. 41 04 C,"o w CL- 10 c Zb "V al c co u CC, w. 6 a3..tco 0 TL :tz 27; .2 'a'1.6w 4c, 0 1. g 2 =I= c- ,up 0:; -D 0= a 20 30 3- 06 -0 00 -0 lp 0044O,C8 IV U 1 a4.1c1 -1I- tn at 16 31 iz a 0- 0 cg .0 c 602 6, 0r.c0 u c to oc-C vs 6.. @."L ft.."Z 6iJ .01 1.11 3 61 im I^ LOW w 40 vc ci c a ob its go = &cl a c- I cc c 'Z i '; #A. c ac a 6 AL 0 7Z cr.oa -c 31 1 7; C 4- .0 v C 'U, c 1,00 Group: I Test material: Test *ye:- Right MLA: PRIMARY EYE IRRITATION TEST OBSERVATIONS - 4jint IL41_Washed:k)Aseconds following instillationof test-material. the test eye was washed with_&&mL of lukewarm tap water for.&ZLseconds. 1--llnuwa shod Animal No. Location of corneal lesions Tail ----- Head Cornea - Opacity Area Iris Conjunctivae Redness Chowsis I Discharge Sodium fluorescein ox n I-tprv hcur 0 0 00 I Technician: )@gIIY9 Date: PiA Not applicable. A Petite h@ rrhaging. a Blanching. C Clear discharge. 0 ftruient discharge. E Hair loss around the eye. F Necrotic areas. G Unable to visualize due to severe swelling. N No reaction to light. I Injected. EYE IRRITATION SCORE: Calculated By: Verified SY: oat@ Oat* 11-9-;-49'7 J Corneal apithelial damage, pooling. K Corneal *pithelial damage, piling. L Corneal epithelia] 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: (00261/vmt) oat@: /.-7!g 7 MLA: -7(oqoc73q-,7 PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: I Test material: 44 1 Test eye: Riaht IL+L_Washed:k3Aseconds following instillation of testmaterial, the test eye was washed with_U&mL of lukftmrm tap water forl&_soconds. V-."Unwashed nhsL;.yA=t Parini4-e /@oa r4:@ AnimalNo.,LocationOf corneal lesions -t,.tql.e%iAj Tail H*ad b Cornea Opacity rea Iris 0 Conjunctiva* Redness Chowsis Discharce Sodium fl in exam AL4 AI,4 Technician: Date: u 11-7 A7 Not applicable. A Petits h@rrhaging. 5 Blanching. C Clear discharge. 0 Purulent discharge. E - Nair loss around the eye. F - Necrotic areas. G - Unable to visualize due to severe swelling. N - No reaction to light. I - InJ@ctod. EYE IRRITATION SCORE: Calculated By: Verified by: Date-u--l- /I Date J - Corneal apithelial damag*, pooling. K - Corneal *pithelial damge, piling. L - Corneal opithelial damgo, pitting. N - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positivestain retention. NEG - Negative stain retention. Reviewed by: (00261/vmt) Date: "LA: PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: Test Test eye! Right &ilnl IL@_washed:.&jPI.secondsfollowinginstillationof test-material, the test eye was washed with_U&ML of lukewarm tap water for.&a_soconds. -"'Um" shod Animal No. Location Of corneal lesions Tail ----- Head Cornea - opacity Area Iris Conjunctivae Redness Chowsis C) I Dischar 0 C) Sodiumfla&LtLLtienxam V14 Technician: Date: @s=@ I MA Not applicable. A Petits h@rrhaging. 5 Blanching. C Clear discharge. D Purulent discharge. E Nair loss around the eye. F Necrotic areas. 6 Unable to visualize due to severe swelling. m - No reactionto light. - InJ@Ctod. C) I 4j EYE IRRITATION SCORE: Calculated By: Verified By:. Date Date i3-9- J - Corneal opith*lial damge. pooling. K - Corneal opithelial dam"e, piling. L - Corneal opithelial damage, pitting. P - Hypopyon. N - Corneal neavascularization. P - Pannus. R - Unable to visualize duo to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by: ty" (00261/vmt) at@: 12 - MLA: PRI14ARY EYE IRRITATION TEST OBSERVATIONS Group: Test material:---I:-Lil6i Test eye: Right 11@_Wash*d:&LO1_seconds following instillation of test-material, the test eye was washed with_&Ia_mL of luke"rm tap water for.&a_soconds. k-I"Unwashod ObSLCXLU&t Porind- -72 @eyir'c@ Animal No Location ;f corneal lesions Tail ----- Head Cornea - Opacity Area Iris Conjunctiva* -Redness 0 C) Chowsis C) Discharoo Sodium fluorescein exam 0 1 kl#A I Technician: Date: ii-q-T7 MA Not applicable. A Petite h@ rrhaging. 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. N No reaction to light. I Injected. EYE IRRITATION SCORE: Calculated By: 4A Verified By: ng C).C) - oDaat:. I t -1-2--,k7- J - Corneal spithelial damgo. pooling. K - Corneal epithelia] damage, piling. L - Corneal apithelial damage, pitting. N - Hypopyon. k - Corn*&] neovascularization. P - Pannus. R - Unable to visualize du* to severe opacity. S - Granulation sear tissue. POS - Positive stain retention. REG - Negative stain retention. Reviewed by: (00261/vmt) Date: 1.2-53-S7 MLA: SCALE FOR SCOR@NGOCULAR LESIONS (DRAIZE TECHNIQUE) (1)Lorne& iA) UPSCit - degree Of 44MSitY (Area most dOnSO t&ktn for reading) no Opacity , 0 Scattered or diffuse area. detaiTs--o-Vi-rcilsearly visib-F* 1. Easilyatscarnioletranslucentareas, details of iris slightlyobscured 2. Opalescentareas. no details of Iris visible,size of pupiI barely alcornible Opaque. iris invisible 3* 4* (6) Area of cornea Involved On@ 4u&rter (or lessto.u-t not zero 6reater than one-quarter. but less tnan nalf I tireat*rthan half. but less than tnro*-qw rs 2 (irvatertnan thr"uarters. up to wnole&;:f 14 A xdx 5 Total maximum - 80 i,e)Iris (A) Values morm7- Fo)as awwo normal, congestion, swelli 0 i injoctfbk (any or all of se@or combinationof any t m.oo ) iris stililreactingto light (sluggishreaction is positive reactionto light,mwrrnap. gross truction(any or ail of- 2* A x5 ToUl maximum - 10 (3)Conjunctivas (A) madness (refersto palpabraland bulber Conjwlctivaeouluding Cormu and iris) vess@Tas-or= 1 0 Vessels definitely inj*cted above ramul I More diffuse, d@Wr Crimean red. individualves" Is not easily discernible Diffuse bwy red 2* 3* (0) cnomsis N o seeT =no- Any swellin moove nornT-(i"Cju"s nicziu ng @ans) ouvious s ling with partial @versionat l'idIs swelling with lips about hall .U*qm 2* $wol)inv with lips &Dmt half CIO ad to Completely Closed 341* tc) Uis 6 no dischar=", Any amount diftwent from nw"-F-Td"s- not lnc]UGG SMII amounts Observed 0 cantnusof norm) animals) Inin;;ir- I Uulissccnnaarr"gewwiittnh ihdooiissttaennii"ngooff tthhee lliidessaanmd M;iMrrss .jaunsdt acdojnascieanmtabtloelaircetas-around the-0)0= 23 $care (A + I + C) x 2 Total mxi@ - 20 The total scwe for the eye Is the am of all scaresobtainedfor the cornea.iris. and cunjunctivas. Indicatespositive affect. (FNSA Interpretation) Uraizd.J. *.. -Appraisalof the Safety of Chemicals in Foods. Drugs aft Cosmetics - Ommi Toxicity*.Associationof Food and Orug Officialsof the United States, pp. 46-59 (1975). (DO261/vm)