#Hcl,k svxhkchdd#Hcl,k svxhk chdd#Hcl,k j,l,vchdd#Hcl,k jl,vchdd#Hcl,k j,l,v chdd#آزمایش سرطان#آزمایشات سرطان زایی#آزمایشات تومورزایی

آزمون سرطان زایی | Carcinogenicity

هدف از آزمون سرطانزایی (cacinogenicity test)، ارزیابی موارد زیر پس از تماس پیوسته (continuous dose) و طولانی مدت (۲۴ ماهه) محدوده وسیعی از محصولات پزشکی، آرایشی و بهداشتی، دارو، آفت کش، سم و مواد شیمیایی صنعتی با بدن حیوانات آزمایشگاهی است:

• شناسایی خصوصیات سرطانزایی نمونه آزمایشی که منجر به افزایش شیوع و یا کاهش زمان بروز نئوپلاسم ها می شود
• شناسای اندام های هدف ماده آزمایشی
• شناسایی زمان بروز نیوپلاسم ها
• ارتباط دوز – پاسخ

#آزمون سرطان زایی#آزمون سرطانزایی#آزمون تومورزایی#آزمون تومور زایی#آزمون سرطان‌زایی#carcinogenicity tests#تست سرطانزایی#تست سرطان زایی#تست تومورزایی#تست تومور زایی

در مجموعه آزمایشگاه های سنجش و پایش کیاژن فارما، تست سرطان زایی بر روی موش آزمایشگاهی نژاد سوری (NMRI) و یا رت آزمایشگاهی و معمولا بصورت خوراکی و یا کاشت انجام می شود.

روش تجویز بستگی به هدف آزمون و خصوصیات فیزیکی و شیمیایی و توکسیکوکینتیک ماده دارد، با این حال جهت رعایت اخلاق کار با حیوانات آزمایشگاهی (ethics) و براساس نظر دامپزشک بخش حیوانی کیاژن فارما، روش تجویز خوراکی از طریق ترکیب ماده آزمایشی با رژیم غذایی یا آب آشامیدنی و یا از طریق کاشت نمونه در بافت هدف، روش ارجع می باشد. سایر روش ها فقط در مواردی استفاده خواهد شد که الزامات قانونی آن را توجیه کند.

• ۳ گروه اصلی با ۳ غلظت از ماده آزمایشی و در هر گروه 100 سر موش سوری 4 تا 6 هفته با میانگین وزن ۲۰ گرم در نظر گرفته خواهد شد.
• جهت گروه کنترل، 100 سر موش تحت تیمار با حلال/حامل قرار خواهند گرفت.
• حیوانات هر گروه علامت گذاری خواهند شد و 7 روز هفته به مدت 24 ماه تحت تیمار با نمونه آزمایشی قرار خواهند گرفت.
• جهت بررسی برگشت پذیری و یا بروز تاخییری علایم سمیت،  همزمان با گروه های اصلی یک گروه اقماری (satellite group) تحت تیمار با بالاترین دوز آزمایه قرار خواهد گرفت.

در بخش حیوانی کیاژن فارما، جهت حصول نتایج آماری دقیق، در برخی موارد تعداد غیر یکسانی از حیوانات (تقسیم افتراقی) در گروه های تیمار در نظر گرفته می شود، مثلا بیش از 100 حیوان در گروه های دز پایین و تعداد کمتری از حیوانات در گروه های دز بالا تا پتانسیل تومورزایی در دزهای پایین بهتر تخمین زده شود. چنین مواردی در طرح آماری و برگه نتایج تست ذکر خواهد شد.

#آزمون سرطان زایی#آزمون سرطانزایی#آزمون تومورزایی#آزمون تومور زایی#آزمون سرطان‌زایی#carcinogenicity tests#تست سرطانزایی#تست سرطان زایی#تست تومورزایی#تست تومور زایی

مشاهدات ماکروسکوپی و میکروسکوپی | Gross Necropsy and Histopathology

در پایان آزمون و یا در نقطه پایانی انسانی (humane endpoints)، کلیه حیوانات بر اساس موازین اخلاقی، معدوم سازی و کالبدگشایی شده و بافت های داخلی شامل کبد، معده، کلیه ها، غدد فوق کلیوی، اپیدیدیم، بیضه ها، پروستات، تیموس، طحال، مغز، ریه، قلب و باتوجه خاص به بافت های هدف آزمون از نظر وجود تومور مورد ارزیابی دقیق ماکروسکوپی (gross necropsy) قرار خواهند گرفت. در صورت مشاهده تومور، بافت مربوطه به همراه غدد لمفاوی ناحیه، مورد ارزیابی میکروسکوپی (histopathology) قرار گرفته و پاتولوژیست به دقت بین هایپرپلازی (Hyperplasia)، دیسپلازی (Dysplasia) و نئوپلازی (Neoplasia) تمایز قائل شده و تومورها را به شکل خوش خیم (Benign) یا بدخیم (Malignant) و یا اولیه (Primary) یا متاستاتیک (Metastatic) طبقه بندی خواهد کرد.

همچنین تعدادی از حیوانات از هر گروه، در فواصل تعیین شده بر اساس صلاحدید مدیر فنی آزمون، جهت شناسایی تومور و کسب اطلاعات درباره پیشرفت تغییرات نئوپلاستیک (neoplastic)، بر اساس موازین اخلاقی معدوم و کالبد شکافی خواهند شد.

#آزمون سرطان زایی#آزمون سرطانزایی#آزمون تومورزایی#آزمون تومور زایی#آزمون سرطان‌زایی#carcinogenicity tests#تست سرطانزایی#تست سرطان زایی#تست تومورزایی#تست تومور زایی

مشاهدات بالینی | Clinical Observation

در طول آزمون علایم بالینی ناشی از تومور یا تیمار با ماده آزمایشی به دقت بررسی و در صورت مشاهده ثبت خواهد شد.

کلیه حیوانات تحت آزمون، به صورت ماهیانه تا پایان آزمون، وزن کشی و میزان مصرف آب و غذا ثبت خواهد شد.

#آزمون سرطان زایی#آزمون سرطانزایی#آزمون تومورزایی#آزمون تومور زایی#آزمون سرطان‌زایی#carcinogenicity tests#تست سرطانزایی#تست سرطان زایی#تست تومورزایی#تست تومور زایی

استاندارد های زیست سازگاری | References

ISO 10993-1: Biological Evaluation of Medical Devices – Evaluation and testing within a risk management process.

ISO 10993-2: Biological Evaluation of Medical Devices – Animal welfare requirements.

ISO 10993-3: Biological Evaluation of Medical Devices – Tests for genotoxicity, carcinogenicity and reproductive toxicity.

ISO 10993-4: Biological Evaluation of Medical Devices – Selection of tests for interactions with blood.

ISO 10993-5: Biological Evaluation of Medical Devices – Tests for in vitro cytotoxicity.

ISO 10993-6: Biological Evaluation of Medical Devices – Tests for local effects after implantation.

ISO 10993-7: Biological Evaluation of Medical Devices – Ethylene oxide sterilization residuals.

ISO 10993-8: Biological Evaluation of Medical Devices – Selection and qualification of reference materials for biological tests.

ISO 10993-9: Biological Evaluation of Medical Devices – Framework for identification and quantification of potential degradation products.

ISO 10993-10: Biological Evaluation of Medical Devices – Tests for skin sensitization.

ISO 10993-11: Biological Evaluation of Medical Devices – Tests for systemic toxicity.

ISO 10993-12: Biological Evaluation of Medical Devices – Sample preparation and reference materials.

ISO 10993-13: Biological Evaluation of Medical Devices – Identification and quantification of degradation products from polymeric medical devices.

ISO 10993-14: Biological Evaluation of Medical Devices – Identification and quantification of degradation products from ceramics.

ISO 10993-15: Biological Evaluation of Medical Devices – Identification and quantification of degradation products from metals and alloys.

ISO 10993-16: Biological Evaluation of Medical Devices – Toxicokinetic study design for degradation products and leachables.

ISO 10993-17: Biological Evaluation of Medical Devices – Toxicological risk assessment of medical device constituents.

ISO 10993-18: Biological Evaluation of Medical Devices – Chemical characterization of medical device materials within a risk management process.

ISO 10993-19: Biological Evaluation of Medical Devices – Physico-chemical, morphological and topographical characterization of materials.

ISO 10993-20: Biological Evaluation of Medical Devices – Principles and methods for immunotoxicology testing of medical devices.

ISO 10993-22: Biological Evaluation of Medical Devices – Guidance on nanomaterials.

ISO 10993-23: Biological Evaluation of Medical Devices – Tests for irritation.

OECD Test No. 401: Guidelines for the Testing of Chemicals – Acute Oral Toxicity.

OECD Test No. 402: Guidelines for the Testing of Chemicals – Acute Dermal Toxicity.

OECD Test No. 403: Guidelines for the Testing of Chemicals – Acute Inhalation Toxicity.

OECD Test No. 404: Guidelines for the Testing of Chemicals – Acute Dermal Irritation/Corrosion.

OECD Test No. 405: Guidelines for the Testing of Chemicals – Acute Eye Irritation/Corrosion.

OECD Test No. 406: Guidelines for the Testing of Chemicals – Skin Sensitisation.

OECD Test No. 407: Guidelines for the Testing of Chemicals – Repeated Dose 28-day Oral Toxicity Study in Rodents.

OECD Test No. 408: Guidelines for the Testing of Chemicals – Repeated Dose 90-Day Oral Toxicity Study in Rodents.

OECD Test No. 409: Guidelines for the Testing of Chemicals – Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents.

OECD Test No. 410: Guidelines for the Testing of Chemicals – Repeated Dose Dermal Toxicity: 21/28-day Study.

OECD Test No. 411: Guidelines for the Testing of Chemicals – Subchronic Dermal Toxicity: 90-day Study.

OECD Test No. 412: Guidelines for the Testing of Chemicals – Subacute Inhalation Toxicity: 28-Day Study.

OECD Test No. 413: Guidelines for the Testing of Chemicals – Subchronic Inhalation Toxicity: 90-day Study.

OECD Test No. 414: Guidelines for the Testing of Chemicals – Prenatal Developmental Toxicity Study.

OECD Test No. 415: Guidelines for the Testing of Chemicals – One-Generation Reproduction Toxicity Study.

OECD Test No. 416: Guidelines for the Testing of Chemicals – Two-Generation Reproduction Toxicity.

OECD Test No. 417: Guidelines for the Testing of Chemicals – Toxicokinetics.

OECD Test No. 418: Guidelines for the Testing of Chemicals – Delayed Neurotoxicity of Organophosphorus Substances Following Acute Exposure.

OECD Test No. 419: Guidelines for the Testing of Chemicals – Delayed Neurotoxicity of Organophosphorus Substances: 28-day Repeated Dose Study.

OECD Test No. 420: Guidelines for the Testing of Chemicals – Acute Oral Toxicity – Fixed Dose Procedure.

OECD Test No. 421: Guidelines for the Testing of Chemicals – Reproduction/Developmental Toxicity Screening Test.

OECD Test No. 422: Guidelines for the Testing of Chemicals – Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.

OECD Test No. 423: Guidelines for the Testing of Chemicals – Acute Oral toxicity – Acute Toxic Class Method.

OECD Test No. 424: Guidelines for the Testing of Chemicals – Neurotoxicity Study in Rodents.

OECD Test No. 425: Guidelines for the Testing of Chemicals – Acute Oral Toxicity: Up-and-Down Procedure.

OECD Test No. 426: Guidelines for the Testing of Chemicals – Developmental Neurotoxicity Study.

OECD Test No. 427: Guidelines for the Testing of Chemicals – Skin Absorption: In Vivo Method.

OECD Test No. 428: Guidelines for the Testing of Chemicals – Skin Absorption: In Vitro Method.

OECD Test No. 429: Guidelines for the Testing of Chemicals – Skin Sensitisation.

OECD Test No. 430: Guidelines for the Testing of Chemicals – In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER).

OECD Test No. 431: Guidelines for the Testing of Chemicals – In vitro skin corrosion: reconstructed human epidermis (RHE) test method.

OECD Test No. 432: Guidelines for the Testing of Chemicals – In Vitro 3T3 NRU Phototoxicity Test.

OECD Test No. 433: Guidelines for the Testing of Chemicals – Acute Inhalation Toxicity: Fixed Concentration Procedure.

OECD Test No. 434: Guidelines for the Testing of Chemicals – Acute Dermal Toxicity – Fixed Dose Procedure.

OECD Test No. 435: Guidelines for the Testing of Chemicals – In Vitro Membrane Barrier Test Method for Skin Corrosion.

OECD Test No. 436: Guidelines for the Testing of Chemicals – Acute Inhalation Toxicity – Acute Toxic Class Method.

OECD Test No. 437: Guidelines for the Testing of Chemicals – Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage.

OECD Test No. 438: Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage.

OECD Test No. 439: Guidelines for the Testing of Chemicals – In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method.

OECD Test No. 440: Guidelines for the Testing of Chemicals – Uterotrophic Bioassay in Rodents.

OECD Test No. 441: Guidelines for the Testing of Chemicals – Hershberger Bioassay in Rats.

OECD Test No. 442A: Guidelines for the Testing of Chemicals – Skin Sensitization – Local Lymph Node Assay: DA.

OECD Test No. 442B: Guidelines for the Testing of Chemicals – Skin Sensitization – Local Lymph Node Assay: BrdU-ELISA or –FCM.

OECD Test No. 442C: Guidelines for the Testing of Chemicals – In Chemico Skin Sensitisation – Assays addressing the Adverse Outcome Pathway key event on covalent binding to proteins.

OECD Test No. 442D: Guidelines for the Testing of Chemicals – In Vitro Skin Sensitisation – ARE-Nrf2 Luciferase Test Method.

OECD Test No. 442E: Guidelines for the Testing of Chemicals – 442E: In Vitro Skin Sensitisation – In Vitro Skin Sensitisation assays addressing the Key Event on activation of dendritic cells on the Adverse Outcome Pathway for Skin Sensitisation.

OECD Test No. 443: Guidelines for the Testing of Chemicals – Extended One-Generation Reproductive Toxicity Study.

OECD Test No. 451: Guidelines for the Testing of Chemicals – Carcinogenicity Studies.

OECD Test No. 452: Guidelines for the Testing of Chemicals – Chronic Toxicity Studies.

OECD Test No. 453: Guidelines for the Testing of Chemicals – Combined Chronic Toxicity/Carcinogenicity Studies.

OECD Test No. 455: Guidelines for the Testing of Chemicals – Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and Antagonists.

OECD Test No. 456: Guidelines for the Testing of Chemicals – H295R Steroidogenesis Assay.

OECD Test No. 457: Guidelines for the Testing of Chemicals – BG1Luc Estrogen Receptor Transactivation Test Method for Identifying Estrogen Receptor Agonists and Antagonists.

OECD Test No. 458: Guidelines for the Testing of Chemicals – Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of Chemicals.

OECD Test No. 460: Guidelines for the Testing of Chemicals – Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants.

OECD Test No. 471: Guidelines for the Testing of Chemicals – Bacterial Reverse Mutation Test.

OECD Test No. 473: Guidelines for the Testing of Chemicals – In Vitro Mammalian Chromosomal Aberration Test.

OECD Test No. 474: Guidelines for the Testing of Chemicals – Mammalian Erythrocyte Micronucleus Test.

OECD Test No. 475: Guidelines for the Testing of Chemicals – Mammalian Bone Marrow Chromosomal Aberration Test.

OECD Test No. 476: Guidelines for the Testing of Chemicals – In Vitro Mammalian Cell Gene Mutation Tests using the Hprt and xprt genes.

OECD Test No. 477: Guidelines for the Testing of Chemicals – Genetic Toxicology: Sex-Linked Recessive Lethal Test in Drosophila melanogaster.

OECD Test No. 478: Guidelines for the Testing of Chemicals – Rodent Dominant Lethal Test.

OECD Test No. 479: Guidelines for the Testing of Chemicals – Genetic Toxicology: In vitro Sister Chromatid Exchange Assay in Mammalian Cells.

OECD Test No. 480: Guidelines for the Testing of Chemicals – Genetic Toxicology: Saccharomyces cerevisiae, Gene Mutation Assay.

OECD Test No. 481: Guidelines for the Testing of Chemicals – Genetic Toxicology: Saacharomyces cerevisiae, Miotic Recombination Assay.

OECD Test No. 482: Guidelines for the Testing of Chemicals – Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells in vitro.

OECD Test No. 483: Guidelines for the Testing of Chemicals – Mammalian Spermatogonial Chromosomal Aberration Test.

OECD Test No. 484: Guidelines for the Testing of Chemicals – Genetic Toxicology: Mouse Spot Test.

OECD Test No. 485: Guidelines for the Testing of Chemicals – Genetic toxicology, Mouse Heritable Translocation Assay.

OECD Test No. 486: Guidelines for the Testing of Chemicals – Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo.

OECD Test No. 487: Guidelines for the Testing of Chemicals – In Vitro Mammalian Cell Micronucleus Test.

OECD Test No. 488: Guidelines for the Testing of Chemicals – Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays.

OECD Test No. 489: Guidelines for the Testing of Chemicals – In Vivo Mammalian Alkaline Comet Assay.

OECD Test No. 490: Guidelines for the Testing of Chemicals – In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene.

OECD Test No. 491: Guidelines for the Testing of Chemicals – Short Time Exposure In Vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage.

OECD Test No. 492: Guidelines for the Testing of Chemicals – Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage.

OECD Test No. 493: Guidelines for the Testing of Chemicals – Performance-Based Test Guideline for Human Recombinant Estrogen Receptor (hrER) In Vitro Assays to Detect Chemicals with ER Binding Affinity.

OECD Test No. 494: Guidelines for the Testing of Chemicals – Vitrigel-Eye Irritancy Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage.

OECD Test No. 495: Guidelines for the Testing of Chemicals – Ros (Reactive Oxygen Species) Assay for Photoreactivity.

OECD Test No. 496: Guidelines for the Testing of Chemicals – In vitro Macromolecular Test Method for Identifying Chemicals Inducing Serious Eye Damage and Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage.

OECD Test No. 497: Guidelines for the Testing of Chemicals – Defined Approaches on Skin Sensitisation.

OECD Test No. 498: Guidelines for the Testing of Chemicals – In vitro Phototoxicity – Reconstructed Human Epidermis Phototoxicity test method.

OECD Test No. 19: Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation. Environmental Health and Safety Monograph Series on Testing and Assessment.

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