Document a1J64nmqQn54qjK7VV9q47bVb

Experiment No.: Conducted At: Dates Conducted: Conducted By: Reviewed By: Acute ocular Irritation Test with T-3493 in Albino Rabbits 0884EB0008 Safety Evaluation Laboratory Piker Laboratories, Inc. St. Paul, Minnesota January 3, 1984 to January 10, 1984 LA@. L^@@ D. M. Markoe, Jr., BS Toxicologist Study Director V14/?4- Date K.I:@. O'Malley, BS Senior Toxicologist Acute Toxicology Date dc: M. T. Case K. L. Ebbens W. C. McCormick summary The results of the acute ocular irritation test conducted from January 3, 1984 to January 10, 1984 at Riker Laboratories$ Inc., St. Paul, .F Minnesota indicate that T-3493 is minimally irritating (2.0/110.0) to the eye of the female albino rabbit. Minimal conjunctivitis was noted at the one hour evaluation and subsided by the two day evaluation. Corneal opacity and iritis were not produced during the study. Introduction The objective of this study was to determine the acute ocular irritation properties of T-3493 when instilled into the eye of female albino rabbits. This study is not regulcated by the Food and Drug Administration's Good Laboratory Practice Regulation of 1978, although the standard operating procedures of this laboratory adhere to the general principles of this regulation. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 2. Method and Results Young albino rabbits of the tiew Zealand breecp- were used to evaluate the ocular irritating properties of the test article. b modeled after that of Draize et al-;--. The test method was The test article was instilled into the conjunctival sac of the right eye of each rabbit according to the treatment procedure presented in Table 1 with the left eye of each animal serving as a control. At each scoring interval, the cornea, iris and palpebral conjunctiva were examined and graded for irritation and injury according to a standard scoring system b . The maximum possible score at any one examination and scoring period 110 points, which indicates maximal irritation and damage to all three ocular tissues (cornea, iris, conjunctiva) while a score of zero indicates no irritation (Table 2). in this scoring system, special emphasis is placed upon irritation or damage to the cornea, while less emphasis is placed upon damage to the iris and conjunctiva. After completion of the test, the scores were analyzed, and a descriptive eye irritation rating was assigned to the test article. The criteria used for assignment of the descriptive rating were the frequency, the extent and the persistence of irritation or damage which occurred to the three ocular tissues (Table 3). The individual results are presented in Table 4. a Hazleton Dutchland, Inc., Denver, PA Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1965). 3. The rating is arrived at by selecting the maximum mean irritation score at one hour, one, two or three days after instillation. if the rate of dissipation of injury does not meet the requirements defined for the descriptive rating appropriate for a particular numerical score, the descriptive rating is raised by one or more levels. The rating system is presented in Table 3. The protocol, principal personnel involved in the study, composition characteristics and Quality Assurance statement are contained in Appendices I IV. Table 1 Eye Irritation Test - Albino Rabbits Treatment Procedure Test Article Number of Animals Evaluated Ebrm Administered Quantity of Test Article Administered Contact Period (seconds) Volume of wash (tap water) Eva Pos Admi T-3493 6 paste 0.1 gm unlimited none 1 Hot and 5. Table 2 Eye Irritation Test - Albino Rabbits Ocular Tissues Conjunctiva Scale of Weighted Scores for Grading the Severity of ocular Lesions Description Redness (A) Redness (refers to palpebral conjunctiva only). Vessels definitely injected above normal. More diffuse, deeper crimson red, individual vessels not easily discernible. Diffuse beefy red. Chemosis (B) Any swelling above normal (included nictitating membrane). obvious swelling with partial eversion of -the lids. Swelling with lids about half-closed. * Swelling with lids about half-closed to completely closed. Discharge (C) Any amount different from normal (Does not include small amount observed in inner canthus of normal animals). Discharge with moistening of the lids and hairs just adjacent to the lids. Discharge with moistening of the lids and hairs and considerable area around eye. Score (A + B + C) x 2 Total maximum = 20 Draize Grade 1 2 3 1 2 3 4 1 2 3 Cornea Op city (A) Opacity - Degree of density (area which is most dense is taken for reading). Scattered or diffuse area, details of iris clearly visible. 1 Easily discernible translucent areas, details of 2 iris slightly obscured. Opalescent areas, no details of iris visible, size of 3 pupil barely discernible. opaque, iris invisible. 4 Area of Cornea Involved (B) One quarter (or less) but not zero. 1 Greater than one-quarter, but less than one-half. 2 Greater than one-half, but less than three-quarters. 3 Greater than three-quarters, up to whole area. 4 Score equals A x B x 5 Total maximum = 80 Iris Values (A) Fblds above normal, congestion, swelling, 1 circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive). No reaction to light, hemorrhage, gross 2 destruction (any or all of these). Score equals A x 5 Total maximum = 10 Note: The maximum total score is the sum of all scores obtained for the cornea, iris and conjunctiva. 6. Table 3 Eye Irritation Test - Albino Rabbits Classification of Test Materials Based on Eye Irritation Properties Rating Non-Irritating Practically Non-Irritating Minimally Irritating Mildly Irritating Moderately Irritating Range 0.0 0.5 >0.5 2.5 >2.5 15.0 >15.0 25.0 >25.0 50.0 Severely Irritating >50.0 80.0 Extremely Irritating >80.0 - 11010 Definition To maintain this rating, all scores by the one day reading must be zero; otherwise, increase rating one level. To maintain this rating, all scores by the one day reading must be zero; otherwise, increase rating one level. To maintain this rating, all scores by the three day reading must be zero; otherwise, increase.rating one level. To maintain this rating, all scores ]@y-the seven day reading must be zero; otherwise, increase rating one level. To maintain this rating, scores by seven days must be < 10 for 60% or more of the animals. Also, mean seven day score must be < 20. If seven day mean score is < 20 bu@-< 60% of animals show scores < 10, then no animal among those showing scores > 10 can exceed a score of 30 if rating is to be maintained; otherwise, raise rating one level. To maintain this rating, scores by seven days must be < 30 for 60% or more of the animals. Also, mean seven day score must be < 40. If seven day mean score is < 40 but < 60% of the animals show scores < 30, then no animal among those showing scores > 30 can exceed a score of 60 if rating is to be maintained; otherwise, raise rating one level. TABLE 4 EYE IRRITATION TEST - ALBINO RABBITS with T-3493 RESULTS Examination ANI14AL NUt4BERS Tissue Period 3B2058 --3B2061 3B2064 3B2067 3B2057 31 Cornea(D-A) I Hour 0 0 0 0 0 0 Iris 0 0 0 0 0 .0 Conjunctiva 2(1-0-0) 4(2-0-0) 4i2-0-0) 2(1-0-0) 0 0 (RSD) Total 2 4 4 2 0 0 cornea(D-A) I Day 0. 0 0 0 0 0 Iris 0 0 0 0 0 Conjunctiva 0 2(1-0-0) 0 0 0 0 (RSD) To I,a'- 0 2 0 0 0 0 ;ornea(D-A) 2 Days 0 0 0 0 0 0 Iris 0 0 0 0 0 0 6onjunctiva 0 0 0 0 0 0 (RSD) Total 0 0 0 0 0 0 Cornea(D-A) 3 Days 0 0 0 0 0 0 Iris 0 0 0 0 0 0 Conjunctiva 0 0 0 0 0 (RSD) To.al 0 0 0 0 0 0 Cornea(D-A) 7 Days 0 0 0 0 0 0 Iris 0 0 0 0 0 0 Conjunctiva 0 0 0 0 0 0 (RSD) To",-ai 0 0 - 0 0 0 0=- Y,ey: Cornea: D--Density Conjunctiva: R=Redners 1,t RikerExperiment No.: APPENDIX I. PROTOCOL TEST: Acute Ocular IrritatiToenst SPONSOR: 3M CONDUCTED BY: SafetyEvaluationLaboratory,Riker Laboratories,Inc.,St.Paul,Minnesota TESTARTICLE:CONTROL ARTICLE: PROPOSED STARTING/CPMPLETION DATE OF TEST: TEST SYSTEM: Female New Zealand White AlbinoRabbits SOURCE: Division OBJECTIVE: METHOD: The objectiveofthistestwillbe to determinethe irritatipoontentiaolfthetestarticlteothe oculartissues (comea, idsand conjunctivao)f albinorabbitsR.abbits were selectedas the testsystem fortheirsensitivityoirritanthsi,storicaulse,ease ofhandlingand generalavailability. The animals willbe housed In standardwire-mesh cages In temperatureand humiditycontrolled rooms withfood-aand water offeredad libitum.Each animal willbe assigned a numbered ear tag which willcorrespondto a card affixedto the outsideofthe cage.The testarticlweillbe instilliendto theconjunctiva@lac ofthe righteye ata dose of servingas a control.At ,withthe contr.a1l.at.e,r-.a.el!y.e.g..feach animal hours and @ days (additionaslcoringintervalmsay be added tofurthercharacterizethe ocularreactions)t,he tissueswill be examined and graded for irdtatioannd injuryaccordingto a standardscoringsystem of Draize et alb.Aftercompletionof the test,the scores willbe analyzed,and a descriptiveye irritatiroanting assigned to the testarticleE.ye examinationsmay be carriedout withthe aid of sodium fluorescein. Ifdeemed necessary by the study directorw,ashed e Iprocedures entailinag 5 and 30 second contactperiodwitha wash over a r t periodwillbe conducted using 3 animals per procedure.Allraw data generated by the study directorand the finalreportwillbe storedinthe Riker LaboratoriesA'rchive,St.Paul,Minnesota. 2 Pudna RabbitChow, Ralston-Pudna,St.Louis,Missouri Draise:Appraisalofthe SafetyofChemicals inFoods, Drugs,and Cosmetics (1965) Publishedby the EditoriaClommittee of The Associationof Food and Drug Officials ofthe UnitedStates. Sponsor Fenn 19171.7-A-PWO Date--' Study Director Date 9. APPENDIX II Principal Participating Personnel involved in the Study Name D. ft. Markoe, Jr., BS K. L. Ebbens, BS K. D. O'Malley, BS G. C. Pecore Function Toxicologist S4@,udyDirector Supervisor Toxicology Testing Senior Toxicologist Acute Toxicology Supervisor Animal Laboratory 10. APPENDIX III Composition Characteristics This study is not regulated by the Good Laboratory Practice Act of i 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. APPENDIX IV .Ouality Assurance Statement This study is not officialli regulated by the Good Laboratory Practice Regulation of 1978, and therefore a statement signed and prepared by the Compliance Audit department is not applicable. The standard operating procedures of this laborato--y.does adhere to the general principles of this regulation. The Compliance Audit department does inspect different significant phases-for studies undex-%..-iany the Acute Toxicology Laboratory on a recurring cycle, and the fac,-lities are examined on a three -tonth schedule. in addition a select number of Research & Development studies are routinely picked at random from the Archives by the Compliance Audit department for review.