Document L2oXkpDDvrk5kLGkq5Xa1knz

Experiment No.: Conducted At: Dates Conducted: Conducted By: Acute Ocular Irritation Test with T-3608 in Albino Rabbits 0984ES0367 Pathology and Toxicology Riker Laboratories, Inc. St. Paul, ]Minnesota July 23, 1984 to July 30, 1984 Acute f okl-k, t ratory T*chnician Toxicology c?/:5/gL/ Datit DO O'Malley, s Senio-r"0ToxicologiSs- t Study Director Cl a4t dc:f K. L. 'Ebbons @r-Pe- Do Criffith-W. C. McCormick Summary The results of the acute ocular irritation test conducted from July 23, 1984 to July 30, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3608 is minimally irritating (10.3/110.0) to the eye of the female albino rabbit. Slight conjunctivitis was noted at the one hour evaluation and subsided by the three day evaluation. Neither corneal opacity nor iritis were noted during the seven day test period. Introduction The objective of this study was to determine the acute ocular irritation properties of T-3608 when instilled into the eye of female albino rabbits. This study was conducted for research and development purposes and is, therefore, not regulated by the Ptx>d and Drug Administrations'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 New Zealand breea were used to evaluate the ocular irritating properties of the test article. b modeled after that of Draize et alz--. 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 0 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 thp 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 I Eye Irritation Test - Albino Rabbits Treatment Procedure Test Article Number of Animals Evaluated Fbrm Administered T-3608 6 powder Quantity of Test Article Administered 0.1 gm Contact Period (seconds) Volume of Wash (tap water) unlimited none 5. Table 2 Eye irritation Test - Albino Rabbits scale of Weighted Scores for Grading the Severity of Ocular Lesions Ocular Tissues Conjunctiva 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 Opacity (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) Fmt not zeroo .1 Greater than one-quarter, but less than one-half. 2 Greater than one-half, but less than three-quarters. 3 Greater than thre"uarters, up to whole area. 4 Score equals A x B x 5 Total maximum - 80 Iris Values (A) Folds above normal, congestion, swelling, I circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggishreaction 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. Table 3 6. 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 Severely Irritating f Extremely Irritating Range 0.0 -,O.S >0.5 - 2.5 >2.5 - 15.0 >15.0 - 25.0 >25.0 - 50.0 >50.0 80.0 >80.0 - 110.0 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. .I Tb maintain this rating, all scores by 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 sieven day mean score is < 20 but7-< 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 buC-< 60% of the animals show 'icores < 30, then no animal among thosi showin4,-Bcores > 30 can exceed a score of 60 if rating is to be maintained; otherwise, raise rating one level. Tissue Lrxamination Period 4BI141 Cornea(D-A) iris Conjunctiva (RSD) I Hour Total 0 0 8(2-2-0) a Cornea(D-A) Iris Conjunctiva (RSD). I Day Total 0 0 6(2-1-0) 6 Cornea(D-A) iris Conjunctiva (RSD) 2 Days Total 0 0 4(1-1-0) 4 Cornea(D-A) 3 Days 0 iris 0 Conjunctiva 0 (RSD) Total 0 Cornea(D-A) 7 Days 0 iris 0 Conjunctiva 0 (RSD) Total .0 Table 4 Eye Irritation Test - Albino Rabbits with T-3608 4DII44 RESULTS 4BI136 ANIMAL NUMBERS 4BI139 0 0 10(2-2-1) 0 0 12(3-2-1) 0 0 14(3-2-2) 10 12 14 0 0 4(2-0-0) 4 0 0 2(1-0-0) 0 0 8(2-2-0) 8 0 0 2(1-0-0) 0 0 8(2-1-1) 8 0 0 4(1-1-0) 2 2 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4DII42 0 0 8(2-1-1) 8 0 0 4(2-0-0) 4 0 0 0 0 0 0 0 0 0 0 0 0 Keyt Cornea: D-Density A-Area Conjunctiva: R-Redness S-swelling 0-nischarqe APPEMIX I PROTOCOL FUker Experiment No.: 09SA-EM367 TEST: A=Ae Ocular IrritatiToenst SPONSOR: 3M Commercial Chemicals CONDUCTED BY: Safety EvaluaflonLaboratory,Riker Laboratories,Inc.,St Paul,Minnesota TEST ARTICLE: T-36o8 CONTROL ARTICLE: ?41A - PROPOSED STARTING/COMPLETION DATE OF TEST: L TEST SYSTEM: Female Now Zealand White Abrio Rabbits SOURCE: 6r--@ ILX@@ Pa.- Division OBJECTIVE: METHOD: The objectiveofthistestwillbe todetermine the irritatipoontentiaolfthe testarticlteo theoculartissues (cornea,irisand conjunctivao)f 6 alb@inorabbits.Rabbits were selectedas the testsystem fortheirsensitivitoyirritanthsi,storicaulse, ease ofhandlingand generalavaiialyillty. The animals willbe housed in standard wire-mesh cages in temperatureand humiditycontrolled rooms with foodl and water offeredad libitum.Each animal willbe assigned a numbered ear tag which willcorrespondto a card affixetdo ft outsideof the cage.The testarticlweillbe instillbefdt the conjunctivaslac ofthe righteye at a dose of 0 -1 g withthe contralateraelye ofeach animal servingas a control.At I hours and 1, 2. 3 arin 7 days (additionaslcoringintervalmsay be added to furthercharacterizfetm ocularreactions)f,t tissueswill be examirod and graded for irritatiaonnd injuryacoordingto a standardscoringsystem of Dralze et &/t!.Aftercompletionof the test,the scores willbe analyzed,and a descriptiveeye irritatiroanting assigned to the testarticleE.ye examinationsmay be carriedout withthe aid of sodium fluorescein. Ifdeemed necessary by the study directorw,ashed eye proceduresentailinag 5 and 30 second contactperiodwitha _ 5 liter wash over -% 5 minute periodWillbe conductedusing 3 animals per procedure.Allraw data generated by the study directoarnd the finalreportwillbe storedinthe Riker LaboratoriesA'rchive,St.Paul,Minnesota. 1 Purina RabbitChow, Ralston-PurinaS,t.Louis,ML-Lwuri Draise:AppraisaloftheSafetyofChemicals inFoods, Drugs, and C@@efics (1965) Published by the EditoriaClommittee of The Associationof Food and 'Di@gOfficials ofthe United States. *nsor FoM 19171-7-A-PWO batk S;tu* Director 9. APPENDIX 11 Principal Participating Personnel Involved in the Study Name Function G. E. Hart Sr. Laboratory Technician Acute Toxicology X. D. O'Malley, SS Senior Toxicologist Study Director X. L. Ebbens, BS supervisor Toxicology Testing G. C. Pecore Supervisor Animal Laboratory 10. APPENDIX III Ccmposition Characteristics This study is not regulated by the Good Laborat=y Practice Act of 1978 and therefore information partaining to composition characteristics is not applicable for inclusion in this study. APPENDIX IV ouality Assurance Statement This study is not officially 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 laboratory does adhere to the general principles of this regulation. The C=Wliance Audit department does inspect different significant phases for studies underway in the Acute Toxicology Laboratory on a recurring cycle, and the facilities are examined on a three month 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.