Document zo1a9LewJq8OwYzQOJaazweLg

ANNEX I Classification of Plastics Plastics Class VI - 121 C With Teadit 24SH Classification of Plastics - Plastic Class VI -- 121 C (Systemic Injection Test-Intraperitoneal Administration) (Systemic Injection Test-Intravenous Administration) (Intracutancous Test) (Implantation Test) with Teadit 24SH Report BSL BIOSERVICE Project No.: 041502 Sponsor Teadit International Prodktions Gbi Roseneiner Si. 10 16330 Knfein Austria Tr edhI atsBene peosRdL SSV esorE sGrol BSL BIOSERVIGE Soc Crt 7L AsestetduC en m gl EE N/ TLC - Servonm MEE ar sanseor ReportBSL BIOSERVICE Project 041502 Copy of the GLP-certificate pose2027 e 2 o( RAEN BAYERISCHES LANDESAMT ARBEITPSlMoEsDsFIlUZRI0NA51RU3BMNEoDnIchTSaSnI-SCTCHaHlEoURnTH0ZE9,9I2T1S8T4E0CHNIK GLP(-gBemeastcihaeccionridginugngto/St1a9tbeAmbse.nt1 oCfheGmiLkPaliCeonmgepsloitas)nce c5TEoiar0nleEmSGiBLnIPCaS-ihIZtan0umsInipEgkaGakdltwooiarnorgnOdaLsusPe.rstGsrOuubbnaodwre:swdaisRczhheu:ng DacArzseoscroiasnisnemgaStnSoSoOfZrDcoomEniEfcoCartmeitnygewsiehlsGLsnPd B protoimicnung/tTacoisiety (1 protstandonTost site BL BioservicoBoShcviianngtsftrcaLsasbeoratorios GmbH menace se8g215o2t Planogyotardse) Prdfuna gen nacheKateR goren/iSveeas ofaEpxeports 3 Pif2uPnrgietnunsguemnus5t"uaSgoetnnoEtxiiggoioopugicinhuonsEgiogcnenishcnhsathtviooinrnevivno) 2WiibrcokbisolaomgeecntsSscpnaihsatntguapmnrtogutnogoenn Datum dep r In1s1po2h k0io2nD2ap 0t0e4of Inspection fDendr sderamnPro3f0ne0hen0gAGPLrPotUfsorEtvnaahvctiuorns: Gross toate FnTohiogsehTdorvenamha0ekPanEnPetGsLtCocoaomntrpeslsroecrsedtbso. SiHfnoocrdemsrLGP ersEor:gni GiatdnuosgnsgsoGn opoeeOsglrFa ePCrnAonSsaon SsnIPrNaeiGsy Jstosanoaolsttalaenelptosnaoey'psraai0laomsbcoctnoenes omminere sotgenvon Monchen, wa = J wRLi.otteerndor Gower4bed=iokior &E,RvTstOney) Yano Report BSL BIOSERVICE Project 041502 Contents COPY OF THE GLP CERTIFICATE PREFACE GPreonjeercatlStat Schedule Project Staff Signatures QUAGLuiIdeTlYineAs SSURANCE Archiving STATEMENT OF COMPLIANCE STATEMENT OF THE QUALITY ASSURANCE UNIT SUMMARY Conclusions INTRODUCTION MATERIALS AND METHODS CPhraerpaacrtaetriiosnatofitohneofTetshet TIetsetmIatnedmAdministration Procedure "Test Test Animals Animals - SInytsrtaecmuitcanIenojuesctTieosntTaesntd Implantation Test AExnpiemrailmeHnutsablanPdrroycedure for Systemic Injection Tests Experimental Experimental Procedure Procedure for for IImnptlraanctuatatnicoonuTsesTtest EVALUATION OF RESULTS EEvvaalluuaattiioonnooff RReesuslusoloffttthhsee SIytsrtaecmuitcanIcnojucstiToenstTests EvaluationofResultsof the Implantation Test DEVIATION FROM THE PROJECT PROTOCOL RESULTS AND DISCUSSION Conclusions DISTRIBUTION OF THE REPORT REFERENCES peses2o7 2 5 5 5 5 6 77 7 8 9 10 10 1 12 2 2 3 3 11 1 1 1166 16 " 19 20 2 21 2 Report BSL BOSERVICE Projet 041502 ANNEXT ANNEX IT ANNEX 111 pase so2r7 2 25 27 Report BS. BIOSERVICE Project 41502 pose sor Preface General Project Staff Schedule Sponsor: Study Monitor: Test Facility: BSL BIOSERVICEProject No. Test Item: Title: Teadit International Produktions GmbH Rosenheimer Sir. 10 A-6330 Kufstein Austria Mr Thomas Steffl BSL BIOSERVICE Scientific Laboratories GmbH Behringstrasse 6 82152 Plancgg Germany 041502 Teadit 24SH Classification of Plastics - Plastic Class VI -- 121C with Teadit 24SH Study Director: Deputy Study Director: Dr. Achim Albrecht Dr. Ingrid Haist Management: Dr. Wolfram Riedel Dr. Angela Lutterbach Quality Assurance Unit: ~~ Dipl. Biol. Uwe Hamann Dr. Margarete Hoechst Dr. Helga Kohn ArrivalofTest Item: Date of Project Protocol: StartofStudy Endof Study: DateofReport: July 07,2004 July 08, 2004 July 18,2004 July 27, 2004 July 29,2004 R85,HOSE Prof 61502 Project StaffSignatures Study Director: Management: pacar? Dr. Aghim Albrecht Z2ol Ce aete:: 07 [4 22or Date: 79-July - dey Report BSL BOSERVICE Prec 041502 pose 7of27 Quality Assurance `This study was conducted to comply with Chemikaliengesetz ("Chemicals Act") of the Federal Republic of Germany, Appendix 1 10 19a as amended on May 08, 2001. Published May 14, 2001 in Bundesgesetzblatt 2001part Ino. 21, pp. 844- 854. OECD Principlesof Good Laboratory Practice (as revised in 1997); OECD Environmental Health and Safety Publications; Series on Principles of Good Laboratory Practice and Compliance Monitorin-g Number 1. Environment Directorate, Organisation for Economic Co-operation and Development, Paris 1998. `This study was assessed for compliance with the project protocol, the study plan and the study and/or Standard Operating Procedures of the test facility were periodically BSL BIOSERVICE. The inspected by the Quality Assurance Unit and the dates and phasesofthe inspections and audits are included in this report. These inspections and audits were carried out by the Quality Assurance Unit, personnel independentof the staff involved in the study. The final report of the study was audited. A Quality Assurance Statement, signed by the Quality Assurance, is included in this report. The test method is part of the BSL BIOSERVICE accreditation scope according to guideline 9038S/EWG, 17025 for testingof medical devices, 9342/EWG and DIN EN ISO/IEC Guidelines This study followed the procedures indicated by internationally accepted guidelines and recommendations: the following USP "Biological Reactivity Tests, in vivo - Classification of plastics" Archiving The following records will be stored in the scientific archives of BSL BIOSERVICE regulations: Scientific Laboratories GmbH according to the GLP A copy of the final report, the project protocol, the study plan anda d(dooccuummeennttaattiioonn offoralmls raaswwedlaltaasgeanenryatoetdherdunroitnegsotfhre acowndduactta,opfritnhteousttsudoyf instruments and computers) `concerning the project. and the correspondence with. the sponsor Iftest item is left over a sample will be stored according to the period fixed by the before tGhaLtP-tRiemgeu.lUantlieosnss.othSearmwpilseesagtrhaetedaruepounn,straebmlaeinmiangy be test disposed item will of be discarded three months after releaseofthe report, Statement of Compliance BSL BIOSERVICEProject No.: Test Item: Study Director: Title: 041502 Teadit 24SH Dr. Achim Albrecht Classification of Plastics - Plastic Class VI with Teadit 24SH This study performed in the test facility BSL BIOSERVICE Scientific Laboratories GmbH was conducted in compliance with Good Laboratory Practice Regulations: Chemikaliengesetz ("Chemicals Act") of the Federal Republic of Germany, Appendix 1 to 19a as amended on May 08, 2001, published May 14, 2001 "OECD Principles of Good Laboratory Practice", (as revised in 1997) Paris 1998. There were no circumstances that may have affected the quality or integrity of the study. Study Director: Dr. Achim Albrecht Jpece owe. rad2027... J ---- pesos? Statement of the Quality Assurance Unit BSL BIOSERVICE Scientific Laboratories GmbH Behringstr. 6, 82152 Planegg Germany BSL BIOSERVICE- Project No.: Test lems Study Director: Title: 041502 Teadit 245H Dr. Achim Albrecht ClassificationofPlastics - Plastic Class VI with Teadit 24SH "This report was audited by the Quality Assurance Unit and the conduct of this study was inspected on the following dates: QAU IPnhsapseesctoif-ons QaUsDapteecstoifoionnss || DtfahoteeeSSsotubfdRyeBDpiorrreetcsttotro Audit Project Protocol/ Study Plan: Experimental Phase Audit (Project Audit): Report Audit: July 09, 2004 July 20, 2004 August 09,2004 July 09, 2004 July 20, 2004 August 09,2004 `This report reflects the raw data. Member of the Quality Assurance Unit: cre FEEDS tr Date: 43:08: 2006 rrr Report BSL BOSERVICE Project 041502 pase 100s27 Summary In this study the test item was investigated according to USP Plastic Class VI ~ 121 C. The tests performed were the Systemic Injection Test (intraperitoneal and intravenous administration, respectively depending on the extraction vehicle used), the Itracutaneous and the Implantation Test 4 extracts of polyethylene the test glycol item (isotonic saline, 400, and vegetable 1 in 20 ethanol in isotonic oil) were investigated saline, in the Systemic Injection Test and the Intracutaneous Test. In the Implantation Test at least 4 strips/animal were investigated for the potentialof inducing local tissue effects. In the Systemic Injection Test no significant clinical signs were observed. "The average score in the Intracutaneous Reactivity Test was 0. In the Implantation Test no compound-related tissue reactions were found. Conclusions Considering the reported data the test item Teadit 24SH meets the requirementsofUSP Plastic Class VL. Repo BSL BOSERVICE Projet 1303 pase toy27 Introduction Six Plastic series of Classes are defined. in vivo tests for This classification is based on responses to a which extracts, materials, and routes of administration are specified. These tesis are directly related to the intended end-useof the plastic articles. the vehicles in preparations The with choiceof extractants which the plastics is are representative likely to be of in contact. In this project the test item was investigated according to USP Plastic Class VL uWsietohftehxetrexaccetpstitohnat,ofdtehpeenImdpilnagntoantitohneTheseta,t trheesipsrtoacnecdeuroefstahree mbaatseerdiaol,n atrhee prepared at oneof three standard temperatures: 50 C, 70 C and 121 C. The Systemic Injection Tests and the Intracutaneous Test are designed to determine the systemic animals to plastics and and local, respectively, other polymers by the biological responses single-dose injection of of specific extracts. `The the Implantation Test plastic and other is designed to polymers by evaluate the reactionofliving tissue to the implantation of the material into animal tissues. Report 85. BIOSERVICE Project 041502 pose 120727 Materials and Methods Characterisationof the Test Item The test item the sponsor. and the information concerning the test item were provided by Name: Batch No.: Nature of material: Sterile: Storage: Calculated surface: Melting temperature: Safety Precautions: Teadit 245H 5308 synthetic polymer no at room temperature 400 cm" per sample. 320- 340C Routine hygenic procedures wil be sufficient to assure personnel health and safety Additional specifications, concerning can be part of the Report and will the not test item, provided by the require an amendment to sponsor Project Protocol. Preparation ofthe Test Item and Administration Procedure "The test item was prepared in the following extraction vehicles: a) Isotonic Saline, NaCl 0.9%; (Lot 3451 A195, B. Braun Melsungen AG) Dose: 50 mL/kg intravenous - Systemic Injection Test Dose: 0.2 ml /animal - Intracutancous Test b) 1 in 20 solution of ethanol (Art. 159009, Lot K32152486 Merck) in Isotonic Saline, NaCl 0.9% Dose: 50 mL/kg intravenous - Systemic Injection Test Dose: 0.2 ml/animal - Intracutancous Test ) Polyethylene diluted "with Glycol 400 (Lot 452670/1, Fluka); 4.1 volumes of 09% NaCl in before order administration to obtain a c7.4oncvenotlruamteisonooffN2a0C0l mtgo /obmtLaiPnEaGcofnorceSnytsrtaetmioinc oIfnje1c2t0iomngT/emsLt,. aPnEdGwiftohr Intracutancous Test Dose: Dose: 10 g/kg intraperitoneal - Systemic Injection 0.2 mianimal - Intracutancous Test Test Report BSL BOSERVICE Projet 041302 pase 139727 d) Vegetable Oil - (Cotton Seed Oil, Lot 103K0064, Sigma Chemicals) Dose: 50 mL/kg intraperitoneal - Systemic Injection Test Dose: 0.2 ml/animal - Intracutancous Test The extraction was carried out according to USP. A ratio of 60 em? of sample to 20 mLof extraction medium was used. Extraction conditions: 121 + 2 C for 60 min. ) Implant strips at least 4 strips/animal (max 2 1 mm x 10 mm) - Implantation Test The implant stripes were processed by heating in an autoclave at 121 C for 20 minutes. Test Animals - Systemic Injection Test Albino mice, HsdWin: NMRI, female, 17 ~ 20 g at the commencement of the study 10 mice per test extract vehicle) group (5 treated with the extract and 5 treated with the `The animals were system (SPF). derived from a controlled full barrier maintained breeding Source: Harlan Winkelmann GmbH, D-33178 Borchen. According to Art. animals were bred 9.2, No.7 of the German for experimental purposcs. Act on Animal Welfare the Test Animals - Intracutaneous Test and Implantation Test New Zealand White Rabbits GmbH, D-33178 Borchen HsdIfNZW. Source: Harlan Winkelmann 4 (Intracut. Test) (weight >2.5 kg). rsp. 2 (Implantation) female animals/extract were used "The animals were system (SPF). derived from a controlled full barrier maintained breeding According to Art. animals were bred 9.2, No.7 of the German for experimental purposes. Act on Animal Welfare the Animal Husbandry ~ Semi-barrier inair conditioned rooms - Temperature: 18 +3 C for rabbits and 22 3 C for mice Report SL BIOSERVICE Project 01503 pase 14027 - Rel. humidity: 55 + 10% - Anificial light, sequence being 12 hours light, 12 hours dark - Air change: at least 10 x / hour - Free access 10 Altromin 2123 and Altromin 1324 maintenance diet for rabbits and mice, respectively, totally pathogene free-TPF - Free access to tap water (drinking mictobiol. controlled periodically) water, municipal residue control, - Rabbits: Housed in ABS - plastic rabbit cages, floor 4200 cm? ~ Mice: in Macrolon Type IV-cages on Altromin saw fiber bedding, max. `group size 5 animals - Certificates of food, water and bedding are filed at BSL Bioservice - Adequate acclimatization period Experimental Procedurefor Systemic Injection Tests Each of five mice was injected in a test group with the extract or the extract AvelhciochloelininthSeocdoinutrmolChglrooruipdse,wiVtehgeatdaobslee oOfil5)0amnLd/k1g0g(/fkogr S(foodriPuomlyCehtlhoyrliednee, Glycol 400). `The animals were injection, and then observed at least at immediately after injection, 24, 48 and 72 hours. again 4 hours after Experimental Procedurefor Intracutaneous Test On on the both day before the test, the fur was sidesofthe spinal columnover closely clipped on a sufficiently large the test animals area. back o`fTheeacrahbbaintismwaelraenidnjseicmtieldarwliytwhe0r.e2 imnLjeocfttedhweitexhtr0a.c2tsmLatoffivtehseiteexstroanctovneehiscildee at five posterior sites on the same sideofeach animal. sOibtsees,rviamtmieodnisatweelryeafreecroirndjeedctiaonndacnodm2p4arh,ed48toh tahnedr7e2agheonutrscoanfttreorlinijnejcetcitoino.n Experimental Procedurefor Implantation Test On the dayofthe spinal column test, the furof the animals was clipped on both sidesof the oAtnloeansets4idsetroifpsothfethsepinteestofietaecmhwoefre2imrpablbainttse,d2i.n5tototh5e epamrafvrerotmebtrhael mmiudslcilnee and parallel to the spinal column, andabout2.5 cm apart from cach other, In Repu BSL BOSERVICE Project 041502 pase 1527 the same manner 2 sips of USP Negative Control Plastic RS (Promochem GmbH, Lot F1) were implanted in the opposite muscleofcach animal. `The animals were kept for a period of not less than 120 hours and were sacrificed at the end of the observation period by administering an overdose of an anesthetic agent. The areaofthe tissue surrounding the center portion of cach implant strip was examined macroscopically. por BSL BIOSERVICE Project 041302 pose lor Evaluation of Results EvaluationofResultsof the Systemic Injection Tests Ifduring the observation period noneof the animals treated with the extract ofthe test item animals treated showsa significantly greater biological reactivity than with the extraction vehicle, the material meets the the requirementsofthe test. If two or more mice die, or if abnomal behavior such as convulsions or prostration occurs in two or 2 g oceures in three or more more mice, mice, orif the a body weight loss greater test item does not meet than the requirementsofthe test. If any animals treated biological reactivity, and with the not more test than item showed only one animal showed slight signs of gross symptoms ofbiological test-mice. reactivity or dies, the test will be repeated using groups of 10 Evaluationof Resultsof the Intracutancous Test Tissue reaction for erythema and oedema are graded according to the classification system given in table 1. Report BSL BOSERVICE Projet 041502 pose 170127 Table 1 Classificationsystem for intracutaneous reactions Erythema and Eschar Formation No erythema 0 Very slight erythema (barely perceptible) 1 Well-defined erythema 2 Moderate to severe erythema 3 Severe erythema (beef-redness) to slight eschar formation 4 (injuries in depth) Edemaformation No edema 0 Very slight edema (barely perceptible) 1 Slight edema (edges of area well-defined by definite raising) 2 Moderate edema (raised approx. mm) 3 Severe edema (raised more than Imm and extending beyond the 4 areaof exposure) `The average erythema and oedema scores for the extract of the test item and extract vehicle are determined at every scoring interval for each rabbit. After the 72 hour scoring, all erythema scores plus oedema scores are totalled separately for cach extract and extract vehicle. Eachof the totals is divided by 12 (2 animals x 3 scoring periods x 2 scoring categories) to determine the overall mean score for each extract versus cach corresponding extract vehicle. `The requirements of the test are metif the difference between the test item extract and the extract vehicle mean score is 1.0 or less. Ifat any observation period the average reaction to the test item extract is questionably greater than the average reaction to the extract vehicle, the test will be repeated using 3 rabbits. Evaluationof Resultsof the Implantation Test The test item and the control implant sites are observed for hemorrhage, necrosis, discolorations, and infections, and the observations are recorded. The encapsulation, if present are measured by recording the width of the capsule (from the peripheryofthe space occupied by the implant control and Repu BSL BOSERVICE Project 041502 pose 180727 material to periphery of the capsule) rounded to the nearest 0.1 mm. The encapsulation are scored according to Table 2. The differences are calculated between average scores for the sample and control sites. The requirements of the tests are metifthe difference did not exceed 1.0, or ifthe difference between the test item and control mean scored for more than onc of the four implant sites does not exceed 1 for any implanted animal. Table 2 Evaluation of Encapsulation in the Implantation Test EvaluationofEncapsulation in the Implantation Test Capsule Width Score None 0 p10 0.5 mm 1 0.6- 1.0mm 2 L1-20mm 3 Greater than 2.0 mm 4 Report BSL BOSERVICE Projet 041502 Deviation from the Project Protocol `There was no deviation from the project protocol. pase 190727 Repu BSL BIOSERVICE Prec 041302 pase 200727 Results and Discussion In this study the test item was investigated according to USP Plastic Class VI 121 C. The tests performed were the Systemic Injection Test (intraperitoneal and intravenous administration, respectively depending on the extraction vehicle used), the Intracutaneous and the Implantation Test. 4 extractsof the test item (isotonic saline, 1 in 20 ethanol in isotonic saline, polyethylene glycol 400, and vegetable oil) were investigated in the Systemic Injection Test and the Intracutaneous Test. In the Implantation test at least 4 strips/animal were investigated for the potential to induce local tissue effects. In the Systemic Injection Test no significant clinical signs and no significant changes in the weight development of the animals were obtained (Results see Annex 110 this study) `The average score in the Intracutancous Reactivity Test was 0 as compared to the injection sites of the reagent controls (Results see Annex II to this study) In the Implantation Test no compound-related tissue reactions were found (Results see Annex Ill to this study) Conclusions. Considering the reported data the test item Teadit 24SH meets the requirements of USP Plastic Class VI Report BSL BOSERVICE Project 041502 Distribution of the Report Sponsor Study Director 1x (original) 1x (copy) pase 21027 Report BSL BOSERVICE Proje 041502 pose 220127 References Duaize, LH. (1965) Appraisal ofthe Safetyof Chemicals in: Foods, Drugs and Cosmetics - Dermal Toxicity pp. 49-52 Assoc.ofFood and Drug Officialof the United States, Topeka, Kansas Draize, 1H. (1955) Dermal Toxicity pp. 46-59 Associationof Food and Drug Officioaftlhes U.S. Washington D.C. prt SL BOSERVICE Pj 01307 seg Annex I Table 3: A0n.i9ni%alanwdeiNgahtCslo0f.t9he% systemic toxicity Ethanol test with extraction vehicles NaCl Euraction vehicle Group Animal number Animal weight at the beginning of Animal weight ai the endof the Weight gain (2) the study 9) study (0) NaCl Testitem group 1 2 2 21 3 2 4 2 s 2 2% +2 2 +2 25 +3 2 +2 2 2 NaCl Control group 6 2 2 + 7 2 2 +3 s 20 2 + 9 2 2 + -- ere 10 -- 2 m-- 2 pete +3ee NaCl/ Testitem group 1 zn 2 +2 Basan) 2 2 25 +3 3 2 u + 4 2 2% -- ree -- 5 20ee -- eD zn re+3, NaCl/ Ethanol Control group 6 , 19 % 2 +3 " i 3 2 9 21 ee -------- 10 e13 2% 3 zn +2 ie2eel+ s eon B51 BOSIRICE rjc 1302 poe seog37 Tabled: APonliymeatlhylweenieghGtlsycoofl 4t0he0 asnydstCeomtitcontsoexeidciOyiltest with extraction velicles vehicle umber the beginning of the endofthe gain () the study (g) study (0) PEG400 Test item group 1 21 2 2 3 21 4 2 s 2 23 +2 2 + 2 + 2 + 2 +2 PEG 400 Control group 6 20 7 21 5 19 9 21 10 20 2 2 2 +2 21 +2 2 +2 23 +3 Cottonseed Test item group 1 20 ol 2 20 3 20 4 1" 5 20 2 +2 2 +2 2 +2 19 +2 2 +2 Cottonseed Control group 6 19 oi 7 20 8 20 9 19 10 20 21 +2 2 +2 2 + 21 +2 2 +2 RepoBrSt BIOSERVICE Projc 041302 pose 250127 Annex Il Table 5: Results Intracutaneous Reactivity in the Rabbit - Extracts NaCl and NaClEthanol T-- H-- B-------- rr ------------------------------ 558o Postinjectionem 24 hjoeucrtsioanfier 48ihnojuecrtsioanfier $5 4 fothema Ocdema Enthema Ocdema Erythema Ocdema 72 ihnojuerctsiaofnter Enthema Ocdema L RL RL RL RL RL RL RL R ~ 10 2.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3.0 4.0 0 0 0.0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 --S$----0 --0----0em0m 0--0--0--0--0e0e0 0i0 0 0 0 10 2.0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 0 0 00 00 0 0 0 0 0 0 0 0 "3.0 40 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 S$ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 m BConHtrolmmm------------------ IEo Postinjectionem 24 hours afer injection 48hows ater injection 72 hours afier injection e 55 Syte em Ocdenar Folens Ous dema Bythena t Octowa Erie homa Odom L RL RL RL RL RL RL RLR ~ 1.0 2.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 00 00 0 0 0 0 00 00 3.0 4.0 0 0 0 0 0 0 0 0 00 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ee 5eS e0 e0 0 ep0 0p0 p 0 0ee0A 0 0 ern0 0re0ee0 e0 1.0.0 0 2.0 0.0 0 0 0 0 0 0 00 00 0 0 0 0 00 00 00 00 00 00 "3.0 40 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 r 5S 0 0 0we0 e0t0 0 n 0 0 0 ee0ee0 0 e 0 e 0 e0 L= left; NaCl R =right; NaCl/Ethanol Overall Mean Score: NaCl Test: 0 NaCl Control: 0 NaClEthanol Test: 0 NaCl/Ethanol Control: 0 Control-Corrected: 0 0 Report BIOSERVICE rjc 0412 pose 26087 Table 6: Results Intracutaneous Reactivity in the Rabbit - Extracts PEG 400 and Cotton Seed Oil -- ee ---- TRo Postinjectionen 2 S 13 bothena Oclema iMnhjoewctsiaofnir 48inhjoeucrtsioafnter 72ihnojewcstiaofnier Enhema Ocdema Erythema Ocdema Erythema Ocdema L RL RL RL RL RLZRTLERTLER 1 00 00000000000000 - 2 000 0000000000000 43 .0000 00 00 00 00 00 00 00 00 00 00 00 00 00 00 $s 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 2 0000000000000000 +3 00 00000000000000 54 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 Control 33 o Postinjectionem 2i4nhjoeucrtsioanffer 48inhjoeucrtsioanfter 72nheocwtsiofnier $5 4 otena Odena Enthema Ocema Erythema Odea Erthema Ocdema L RL RL RL RLRLURTLRTLR 1.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 w 2 0000000000000000 3 00 00000000000000 4 00 00000000 000000 $ 0000000000 000000 21 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 +3 0000000000000000 4 0000000000000000 $ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 L = left; PEG R = right; CottonSced Overall Mean Score: PEG Test: 0 CottonSeedTest 0 PEG Control: 0 CottonSeed Test Control: 0 Control-Corrected: 0 0 Fagot 05. BIOSERMICE Project 081502 poser Annex ITT Table 7a: Test Item Animal No. Inplant Sites Tissue Reaction Hemorrhage Necrosis Discoloration Infection Results Implantation - Tissue Reactions 1 2 12 3 4 12 3 4 mm mom mom mom mm wp wp mp wm om wm om mw wm mw mm wp mom wm mp wm mp mp mp mp mp mp mp Control Animal No. Inplant Sites 1 4 2 Tissue Reaction Haemorrhage Necrosis Discoloration Infection np = not present; mw mw mw w mw w w w Table 7b: Results Inplantation-Encapsulation Animal No. 1 Test tem Implant Sites 12 3 4 Capsule Width Score Average Difference 0000 0 0 2 1 2 w wp mw mp mp mw mp mw mw Control 12 [I 0 0 Animal No. 2 Implant Sites Capsule Width Score Average Difference Test lien 23 a 000 0 0 0 Control 12 (I) 0 0