Document dQyjMaXqEBbyY9ebY0ZdOydZB

primary Skin Irritation Test with T-3371 in Albino Rabbits Experiment No.: Conducted At: 0883EB0079 Safety Evaluation Laboratory Riker Laboratories, Inc. St. Paul, Minnesota i)ates Conducted: conducted By. JUL'9e_)-O'18_.1'39O83 LOS 0 March 1, 1983 to March 17* 1983 io.L.., D. M. MiiLrkoe,Jr., BS Toxicologist Study Director 70 Da e Reviewed By: K. D. O'Malley, BS Senior Toxicologist Acute Toxicology I)ate dc: M. T. Case K. L. Ebbens F. D. Griffith W. C. McCormick summary The results of the ICAO skin irritation test conducted from March 1, 1983 to March 17,1983 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3371 produced irreversible tissue damage to the skin of female albino rabbits following a four hour, a one hour, and a three minute contact period. moderate arythema and edema, as well as, chemical burn, eschar and necrosis were produced following all three contact periods. An endpoint, as required by ICAO, was not achieved due to the extreme irritation following each contact period. Introduction The objective of this study was to determine the ICAO skin irritation pot@ntial of T-3371 to the skin of female albino rabbits. This study is not regulated 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. #4ethod and Results Young albino rabbits of the New Zealand a breecf- were used in the evaluation of the primary skin irritating properties of the test article. b The test procedure was modeled after that of Draize et al!;-. One day prior to the application of the test article, the hair was clipped from the back and flanks of each rabbit and two test sites selected lateral to the midline of the back approximately ten centimeters apart. The test article (0.5 g) was applied to each of the test sites on each rabbit and immediately covered with two-inch square gauze-patches. The patches, which were placed directly over the test sites, were secured with gauze wrap. The trunk of each animal was then wrapped with impervious plastic sheetingc- which held the patches in position during either a four d hour, one hour or three minute exposure period. At the end of the exposure period, the plastic wrappings, patches, and e all residual test article were removecl;--.One, 24 and 48 hours after removal of the test article, the test sites were examined for irreversible damage and scored separately for erythema and edema on a graded scale of 0 4 (Table I). The length of the exposure period is reduced until an endpoint of no irreversible damage is reached, if possible. The results are presented in Tables 2-4. The protocol, principal personnel involved in the study, composition characteristics and gua3.ity Assurance statement are contained in Appendices I - IV. a Hazleton Zb-Oraize: Dutchland, Inc., Denver, PA Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1965). -ElO x 12 x .002 Extra Clear polyethylene sleeves, PFC Industries, Inc.# Wheeling, Illinois. d @--Three animals per exposure group. .!The test article was removed with water. 3. Table 1 Scoring Criteria for Skin Reactions Reaction Description Score Erythema Edema Barely perceptible I (Edges of area not defined Pale red in color and area definable 2 Definite red in color and area well 3 defined. Beet or crimson red in color 4 Barely perceptible 1 (Edges of area not defined) Area definable but not raised more 2 than I mm. Area well defined and raised 3 approximately I mm. Area raised more than 1 mm. 4 maxi-um Primary Irritation Score 4. Table 2 Primary Skin Irritation Test - Albino Rabbits with T-3371 (four hour contact) Animal Number 3B358 3B350 3B353 Irritation Scores for Right intact Skin Sites After Removal Tm diately ER ED 24 Hours ER ED 48 Hours ER ED 2E 4 2 EC 3 2 EN 2 2E 4 2 EC 3 2 EN 2 2 4 2 EC 3 2 ENX 2 Animal Number 3B358 3B350 3B3$3 Irritation Scores for Left Intact Skin Sites After Removal immediately ER ED 24 Hours ER ED 48 Hours ER ED 2E 4 2 EC 3 2 EN 3 2E 4 2 4 2 EC 3 2 EC 3 2 EN 2 2 ENX 3 Key: C - Chemical burn E - Eschar N - Necrosis X - Epithelial sloughing ED - Edema ER - Erythema Animal Number 3B349 3B384 3B355 5. Table 3 Primary Skin Irritation Test - Albino Rabbits with T-3371 (one hour contact) Irritation Scores for Right Intact Skin Sites After Removal Immediately ER ED 24 Hours ER ED 48 Hours ER ED 1 2 1 1 2C 3 2C 2 2 EN 3 2 EN 2 1 2 2C 2 2 EN 2 Animal Number 3B349 3B384 3B355 Irritation Scores for Left Intact Skin Sites After Removal Immediately ER ED 1 2 1 1 1 2 24 Hours ER ED 2C 3 2C 2 2C 2 48 Hours ER ED 2 EN 2 2 XE 2 2 N)X 2 Key: C - Chemical burn E - Eschar N - Necrosis X - Epithelial sloughing ED - Edema ER - Erythema Animal Number 3B397 3B395 3B394 6. Table 4 Primary Skin Irritation Text hlhino Rabbits with T-3371 (three minute contact) Irritation Scores for Right Intact Skin Sites After Removal immediately ER ED 24 Hours ER ED 48 Hours ER ED 2B 1 2 NOX 2 2 NOX 2 2B 1 2 NO 2 2 NO 2 2B 1 2 NOX 2 2 NOX 2 Animal Number 3B397 3B395 3B394 Irritation Scores for Left Intact Skin Sites After Removal Immediately ER ED 24 Hours ER ED 48 Hours ER ED 2B 1 2B 1 2 NOX 2 2 NO 2 2 NOX 2 2 NO 2 2B 1 2 NO 2 2 NO 2 Key: B - Blancing X - Epithelial 0 - Eschar N - Necrosis ED - Edema ER - Erythema sloughing AppEND3:X I PROTOCOL Rker ExperimeNnot.: TEST: Acute primarySkin irritatiToenst SPONSOR: 3M Cormei-cialChemicals CONDUCTED BY: SafetyEvaluationLaboratory,RikerLaboratoriesI,nc.,SL Paul,Minnesota TEST ARTICLE: l'-'?@71 CONTROL ARTICLS: PROPOSED STARTINGICOMPLETION DATE OF TEST: c/E3 TEST SYSTEM: Female Now ZealandWhiteAbno Rabbits SOURCE: PAr 7. Division OBJECTIVE: To determinethe irritatipontentiaolf the tW articlteo the skinof animals.Rabbitswere selectedas the testsystem due to theirhistoricuasle, sensitivittoyirritantesa,se of handlingand generalavailability. METHOD: The animalswillbe housed instandardwire-meshcages intemperatureand humiditycontrollerdooms withfoociaa-nd water offeredad Mbitum.Each animalwillbe assigned a numbered ear tag,which will correspondtoa card affixetdotheoutsideofthecage.PriortotheapplicatioonfthetestarticlMee, hair willbe clippedfrom theback and flanksofeach animaland --- 2 testedes selectedlateral tothemidlireoftheback approximateltyencentimeteraspart. 0 ofthe - 2 site$willbe abraded by making fouroodeffnalincisionst,wo perpendiculatro theothertwo,whilethe othertestsite(sw)ill remain intaclThe testarticle intacstite(so)n each animalt,boverewdith willbe appliedto abraded and -au,-e and securedwith The trunkofeach animalwillthenbe wrapped withimperviousplastischeetingwhich willo6dude ft testarticldeuringthe I day exposurepedod*rw.bmjr,&-44WAwilktter removalofft testarbcle. V* intacatnd abradedtestsiteswilble examined and scoredseparatelfyororythemaand edema on a graded scaleof 0 to4. The averageirritatipornoduced willbe evaluatedby addingthe mean soores foreqftma and edema oftheintactestsitese'ro@o"4nd4&+eumVogHemova@of thetestarticleS.iFno -48dy,*IG-4V4MtM-%ClDMS- l@, p itisgma apd-edefn 4NUUm-added. These Awe valueswillbe totaledand dividedby.@W& toobtainthemean primaryirritationndexand then assigned a descriptivperimaryskinirritatriaotningas folk)ws: t 4.71,.Ue tf,rff..-tC,@^ r nc. n 1.5 Mean PrimaryIrritatiSocnore 0 0.1-0.5 0.6- 1.5 1.6-3.0 3.1-5.0 5.1-6.5 6.6-8.0 DescriptivReating Non-inftting MSilniigmhatllllyryIrrirtiatbartiigngFEB MildlyIrritating Moderatelylrritabng SeverelyIrritating Extremelylrrttagti 2 11983 Sponsor The ratingfora testarticlmeay be increasedifthe reactioncaused isbeyond eryftma arW edema and aredeemed to be of importanceintheinterpretatioofntheresultsA.JIraw data generatedby the studydirectoarnd thefinarleportwillbe storedinft RikerLaboratoriesA'rchive,St.Paul,Minnesota. one si;ht; one hr. appl.-*Lcat4?-nodn,sirlit4 hr. apr;lic--.tioi. PurinaRabbitChow, RaistonPurinaCo.,St.Louis,Missouri Draize:AppraisaloftheSafetyofChemicalsinFood,Drugsand Cosmetics(1965) Publishedby theEditoriCaolmmitteeofft Associatioonf Food and Drug Officiaolfsft UnitedStates Rezd cach site ul)onrei.ov,-o,fl test substmce ard 1 and 3 ..Vs. 'Date_Y StudyDirector Oka Fam 19171-124@-PWO R:Lker Experiment ,4o. 0883EB0079 APPENDIX I (concluded) Deviations and/or AmandMafttS to-PrctocO-l in addition to theifour hour and one hour contact applications an additional application of three minute contact with three animals will be dosed, study Director 3/3/8 3 Date 2. Due to a delay in report processing the proposed completion date should be Amended to 6/83. Study Director 6/30/83 Date 3. Study Director Date 4. Study Director Date S. Study Director Date 9. APPMMIX 11 Principal Participating P@rsonnal Involved in the Stud Name D. m. markoe, Jr., RS K. L. Ebbens* BS Y,. D. O'Malley, BS G. C. pecore Flunction Toxicologist Study Director supervisor Toxicology Testing senior Toxicologist Acute Toxicology Supervisor Animal Laboratory APPENDIX III Composition Characteristics This study is not regulated by the Good laboratory Practice Art of 1978 and therefor* information pertaining to composition characteristics is not applicable for inclusion in this study. APPENDIX IV Quality 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 Compliance Audit dftpartment does inspect different significant phases !or studies underway in the Acute Toxicology Laboratory on a recurring cycle, and the facilities are examined on a three month schedul@. in addition a select number of Research & Development studies are routinely picked at random from the Archives by the Compliance Audit department for review.