#subacute neurotoxicity tests#سمیت سیستم عصبی تحت حاد#سمیت تحریک سیستم عصبی تحت حاد#مسمومیت عصبی تحت حاد#بیماری های سیستم عصبی تحت حاد#بررسی سمیت عصبی تحت حاد#اثرات سمیت عصبی تحت حاد#علائم سمیت عصبی تحت حاد#علایم سمیت عصبی تحت حاد#مسمومیت دستگاه عصبی تحت حاد#سمیت دستگاه عصبی تحت حاد#سمیت تحت حاد سیستم عصبی#سمیت تحت حاد دستگاه عصبی#سمیت تحت حاد عصبی#سمیت عصبی تحت حاد#sldj sdsjl uwfd jpj phn#sldj nsj’hi uwfd jpj phn#sldj uwfd jpj phn#sldj jpj phn uwfd#Hcl,k sldj uwfd#jsj sldj uwfd#بررسی سمیت سیستم عصبی

آزمون سمیت سیستم عصبی تحت حاد | Subacute Neurotoxicity

هدف از تست سمیت سیستم عصبی تحت حاد، ارزیابی پتانسیل سمیت عصبی لوازم و تجهیزات پزشکی (medical device)، در بازه ۲۸ روزه پس از تماس پیوسته (continuous dose) ماده آزمایشی و معمولا به صورت خوراکی است. آزمون سمیت عصبی تحت حاد، جهت ارزیابی سمیت محدوده وسیعی از محصولات پزشکی، دارو، آفت کش، سم و مواد شیمیایی صنعتی که احتمال اختلال دستگاه عصبی انسان بواسطه آن وجود دارد می باشد.

#subacute neurotoxicity tests#سمیت سیستم عصبی تحت حاد#سمیت تحریک سیستم عصبی تحت حاد#مسمومیت عصبی تحت حاد#بیماری های سیستم عصبی تحت حاد#بررسی سمیت عصبی تحت حاد#اثرات سمیت عصبی تحت حاد#علائم سمیت عصبی تحت حاد#علایم سمیت عصبی تحت حاد#مسمومیت دستگاه عصبی تحت حاد#سمیت دستگاه عصبی تحت حاد#سمیت تحت حاد سیستم عصبی

 روش کار

در مجموعه آزمایشگاه های سنجش و پایش کیاژن فارما، آزمون سمیت تحت حاد سیستم عصبی بر روی موش آزمایشگاهی نژاد سوری (NMRI) و یا رت آزمایشگاهی از طریق تجویز دهانی ماده با استفاده از لوله معدی (گاواژ) و یا ترکیب در آب و غذا انجام می شود.

نکته مهم: “جهت شناسایی دوز شروع آزمون، ابتدا آزمون سمیت عصبی حاد باید انجام شود“. 

• ۳ گروه اصلی با ۳ غلظت از ماده آزمایشی و در هر گروه ۱۰ سر موش سوری ۶ تا ۸ هفته با میانگین وزن ۲۰ تا ۳۰ گرم در نظر گرفته خواهد شد.
• جهت گروه کنترل، ۱۰ سر موش تحت تیمار با حلال/حامل قرار خواهند گرفت.
• حیوانات هر گروه علامت گذاری خواهند شد و ۵ روز هفته به مدت ۲۸ روز تحت تیمار با نمونه آزمایشی قرار خواهند گرفت.
• جهت بررسی برگشت پذیری و یا بروز تاخییری علایم سمیت، یک گروه اقماری (satellite group) همزمان با گروه های اصلی، تحت تیمار با بالاترین دوز آزمایه قرار خواهد گرفت.

سمیت تحت حاد دستگاه عصبی#سمیت تحت حاد عصبی#سمیت عصبی تحت حاد#sldj sdsjl uwfd jpj phn#sldj nsj’hi uwfd jpj phn#sldj uwfd jpj phn#sldj jpj phn uwfd#Hcl,k sldj uwfd#jsj sldj uwfd#بررسی سمیت سیستم عصبی

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 مورد ارزیابی دقیق ماکروسکوپی (gross necropsy) قرار خوتهند گرفت. همچنین در صورت لزوم چند بافت از موارد زیر، بر اساس نظر مدیر فنی و آسیب شناس (pathologist) آزمون و با توجه خاص به حالت عروقی سیستم عصبی و محل های با ساختار رشته ای و سلولی در سیستم عصبی مرکزی و محیطی مورد ارزیابی دقیق میکروسکوپی (histopathology) قرار خواهند گرفت. براساس نظر پاتولوژیست آزمایشگاه، این نواحی معمولا پیش از سایر نواحی تحت تاثیر مواد سمی قرار می گیرند، بنابراین نواحی مناسب جهت بررسی سمیت عصبی هستند. اگر در بررسی هیستوپاتولوژی هرگونه نشانه ای از تغییرات یا ضایعات بافتی مشاهده شد، یک بررسی ثانویه بر روی تمام نقاط سیستم عصبی انجام خواهد شد.

• بخش قدامی مغز (Forebrain)
• هیپوکامپوس (Hippocampus)
• مغز میانی (mesencephalon)
• مخچه (Cerebellum)
• پل مغزی (Medulla/pons)
• پیاز مغز (medulla oblongata)
• چشم با عصب بینایی (Optic nerve) و شبکیه (retina)
• طناب نخاعی (Spinal cord) در گره های کمر و گردن (cervical and lumbar swellings)
• گره های ریشه پشتی (dorsal root ganglia)
• رشته های ریشه پشتی و شکمی (dorsal and ventral root fibres)
• عصب سیاتیک (proximal sciatic nerve)
• عصب ساق و شاخه های ماهیچه ای عصب ساق پا (proximal tibial nerve)
• بخش هایی از عصب محیطی (peripheral nerve sections)
• طناب نخاعی (spinal cord)
• ماهیچه های اسکلتی (skeletal muscle) خصوصا ماهیچه ساق پا (calf muscle)

#subacute neurotoxicity tests#سمیت سیستم عصبی تحت حاد#سمیت تحریک سیستم عصبی تحت حاد#مسمومیت عصبی تحت حاد#بیماری های سیستم عصبی تحت حاد#بررسی سمیت عصبی تحت حاد#اثرات سمیت عصبی تحت حاد#علائم سمیت عصبی تحت حاد#علایم سمیت عصبی تحت حاد#مسمومیت دستگاه عصبی تحت حاد#سمیت دستگاه عصبی تحت حاد#سمیت تحت حاد سیستم عصبی#سمیت تحت حاد دستگاه عصبی

علائم بالینی | Clinical Observation

در طول تست علائم بالینی ناشی از بیماری یا تیمار با نمونه آزمایشی به دقت بررسی و در صورت مشاهده ثبت خواهد شد.

مشاهدات، وزن کشی و میزان مصرف آب و غذای حیوانات تحت تست، به صورت هفتگی و تا پایان آزمون، با توجه خاص به هفته اول آزمون، انجام و ثبت خواهد شد.

#سمیت تحت حاد عصبی#سمیت عصبی تحت حاد#sldj sdsjl uwfd jpj phn#sldj nsj’hi uwfd jpj phn#sldj uwfd jpj phn#sldj jpj phn uwfd#Hcl,k sldj uwfd#jsj sldj uwfd#بررسی سمیت سیستم عصبی

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.

#subacute neurotoxicity tests#سمیت سیستم عصبی تحت حاد#سمیت تحریک سیستم عصبی تحت حاد#مسمومیت عصبی تحت حاد#بیماری های سیستم عصبی تحت حاد#بررسی سمیت عصبی تحت حاد#اثرات سمیت عصبی تحت حاد#علائم سمیت عصبی تحت حاد#علایم سمیت عصبی تحت حاد#مسمومیت دستگاه عصبی تحت حاد#سمیت دستگاه عصبی تحت حاد#سمیت تحت حاد سیستم عصبی#سمیت تحت حاد دستگاه عصبی#سمیت تحت حاد عصبی#سمیت عصبی تحت حاد#sldj sdsjl uwfd jpj phn#sldj nsj’hi uwfd jpj phn#sldj uwfd jpj phn#sldj jpj phn uwfd#Hcl,k sldj uwfd#jsj sldj uwfd#