59865-13-3

• 常用中文名：环孢霉素A
• 常用英文名：Cyclosporin A
• CAS号：59865-13-3
• 分子式：C₆₂H₁₁₁N₁₁O₁₂
• 分子量：1202.611
• 相关类别： 生物化工 抑制剂 免疫抑制剂
• 发布时间：2018-05-07 08:00:00
• 更新时间：2024-01-02 18:40:37
• Cyclosporin A 是一种免疫抑制剂,能与亲环素结合,抑制 calcineurin 活性的IC50 值为 7 nM。

名称

• 中文名: 环孢菌素
• 英文名: cyclosporin A
• 中文别名: 环胞霉素A; 环孢霉素A; 环孢素A
• 英文别名: ciclosporin A; sandimmun; Optimmune; cyclosporine A; Atopica; sandimmun neoral; s7481f1; Cyclosporin A; Neoplanta; MFCD00274558; Restasis; Sandimmun optoral; Neoral; Cipol N; ol27-400; EINECS 200-835-2; CyclosporineA

物化性质

• 密度: 1.0±0.1 g/cm3
• 沸点: 1293.8±65.0 °C at 760 mmHg
• 熔点: 148-151°C
• 分子式: C₆₂H₁₁₁N₁₁O₁₂
• 分子量: 1202.611
• 闪点: 736.3±34.3 °C
• 精确质量: 1201.841309
• PSA: 278.80000
• LogP: 3.35
• 外观性状: 从-15℃的丙酮得白色针状结晶，熔点148～151℃，[α]D20-244°(C=0.6，氯仿)。溶于甲醇、乙醇、丙酮、乙醚或氯仿，微溶于水及饱和碳氢化合物。急性毒性LD50小鼠，大鼠，兔子(mg/kg)：107，25，＞10静脉注射；2329，1480，＞1000口服。
• 蒸汽压: 0.0±0.6 mmHg at 25°C
• 折射率: 1.468
• 储存条件:

  2-8℃

• 稳定性:

  从-15℃的丙酮得白色针状结晶，熔点148～151℃，[α]_D²⁰-244°(C=0.6，氯仿)。溶于甲醇、乙醇、丙酮、乙醚或氯仿，微溶于水及饱和碳氢化合物。急性毒性LD₅₀小鼠，大鼠，兔子(mg/kg)：107，25，＞10静脉注射；2329，1480，＞1000口服。

• 水溶解性: ethanol: 30 mg/mL
• 计算化学:

  1、 疏水参数计算参考值（XlogP）：7.5

  2、 氢键供体数量：5

  3、 氢键受体数量：12

  4、 可旋转化学键数量：15

  5、 互变异构体数量：16

  6、 拓扑分子极性表面积（TPSA）：279

  7、 重原子数量：85

  8、 表面电荷：0

  9、 复杂度： 2330

  10、同位素原子数量：0

  11、确定原子立构中心数量：12

  12、不确定原子立构中心数量：0

  13、确定化学键立构中心数量：1

  14、不确定化学键立构中心数量：0

  15、共价键单元数量：1

• 更多:

  1. 性状：白色针状结晶，从－15℃的丙酮中得到。

  2. 密度（g/cm³ ，25 ºC）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：148-151

  5. 沸点（ºC）：未确定

  6. 沸点（ºC,5.2kPa）：未确定

  7. 折射率（°）：未确定

  8. 闪点（℉）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值（25℃）：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性(mg/mL)：溶于甲醇、乙醇、丙酮、乙醚或氯仿，微溶于水。

生物活性

• 描述: Cyclosporin A 是一种免疫抑制剂,能与亲环素结合,抑制 calcineurin 活性的IC50 值为 7 nM。
• 相关类别:
  信号通路 >> 其他 >> 其他
  研究领域 >> 炎症/免疫
• 靶点:

  IC50: 7 nM (calcineurin)

• 体外研究: 环孢菌素A能够与T细胞中的亲环蛋白结合[1]。环孢菌素A通过形成亲环蛋白-环孢菌素A复合物来抑制神经钙蛋白[2]。环孢菌素A对钙调神经磷酸酶具有抑制作用,IC50为7 nM [3]。环孢菌素A抑制NF-AT的核转位[4]。环孢菌素A通过阻止MTP打开显示对线粒体的影响,IC50为39 nM [5]。
• 体内研究: 环孢菌素A具有免疫抑制活性,并且在小鼠,大鼠和豚鼠中通过肠胃外和口服给药具有活性[6]。环孢菌素A可用于器官移植以防止排斥反应[7]。
• 激酶实验: 与纯化酶的反应混合物含有100 nM钙调神经磷酸酶，100 nM钙调蛋白和5μM32P标记的磷酸肽，在60μL（总体积）的含有20 mM Tris（pH 8），100 mM NaCl，6 mM MgCl 2,0.5的分析缓冲液中mM二硫苏糖醇，每毫升0.1mg牛血清白蛋白，和0.1mM CaCl 2或5mM EGTA。与细胞裂解物的反应混合物含有20μL未稀释的裂解物，5μM32P标记的磷酸肽和40μL测定缓冲液。反应混合物含有50μM肽412或413和/或500nM冈田酸，磷酸酶1和2A的特异性抑制剂; 500nM冈田酸足以抑制Ca2 +非依赖性磷酸酶，而较高浓度也部分抑制Ca2 +依赖性磷酸酶活性。在30℃下15分钟后，通过加入0.5mL含有5％三氯乙酸的100mM磷酸钾缓冲液（pH7.0）终止反应。通过Dowex阳离子交换色谱法分离游离无机磷酸盐，并如所述通过闪烁计数进行定量。
• 细胞实验: 免疫抑制剂以比细胞处理所需浓度高1000倍的浓度溶解在乙醇中。将细胞（106）悬浮于微量离心管中的1mL完全培养基中;加入1μL乙醇或环孢菌素A的乙醇溶液，并将细胞在37℃下孵育1小时。将细胞在冰上用1mL PBS洗涤两次，并在含有50mM Tris（pH 7.5）的50μL低渗缓冲液中裂解; 0.1mM EGTA; 1 mM EDTA; 0.5mM二硫苏糖醇;每毫升50μg苯甲基磺酰氟，50μg大豆胰蛋白酶抑制剂，5μg亮肽素和5μg抑肽酶。将裂解物在液氮中进行三个循环的冷冻，然后在30℃下解冻，然后在4℃下以12,000×g离心10分钟。
• 动物实验: 在第0天腹膜内用0 5mL免疫大鼠，小鼠静脉内用0 2mL 10％洗过的绵羊红细胞（SE）悬浮液免疫。为了引起二次反应，在初次免疫后8-11周，用静脉内注射0-2mL的25％洗涤的SE（107个细胞）对小鼠进行加强免疫。对于长期治疗，动物在13周内每天在食物中平均接受45mg / kg环孢菌素A.在杀死前5天对这些大鼠进行免疫。
• 参考文献:

  [1]. Handschumacher RE, et al. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544-7.

  [2]. Liu J, et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807-15.

  [3]. Fruman DA, et al. Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3686-90.

  [4]. Flanagan WM, et al. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991 Aug 29;352(6338):803-7.

  [5]. Nicolli A, et al. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996 Jan 26;271(4):2185-92.

  [6]. Borel JF, et al. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017-25.

  [7]. Williams, R, et al. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet, 1994, 344(8920), 423-428.

MSDS

Cyclosporin A Revision number: 5 SAFETY DATA SHEET Section1. IDENTIFICATION Product name:Cyclosporin A Revision number:5 Section2. HAZARDS IDENTIFICATION GHS classification PHYSICAL HAZARDSNot classified HEALTH HAZARDS Acute toxicity (Oral)Category 4 Category 1A Carcinogenicity Reproductive toxicityCategory 1B Reproductive toxicity (Effects on or via lactation) Additional category for effects on or via lactation ENVIRONMENTAL HAZARDSNot classified GHS label elements, including precautionary statements Pictograms or hazard symbols Signal wordDanger Hazard statementsHarmful if swallowed May cause cancer May damage fertility or the unborn child May cause harm to breast-fed children Precautionary statements: Obtain special instructions before use. [Prevention] Do not handle until all safety precautions have been read and understood. Do not breathe dust/fume/gas/mist/vapours/spray. Avoid contact during pregnancy/while nursing. Do not eat, drink or smoke when using this product. Wash hands thoroughly after handling. Use personal protective equipment as required. [Response]IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. Rinse mouth. IF exposed or concerned: Get medical advice/attention. [Storage]Store locked up. [Disposal]Dispose of contents/container through a waste management company authorized by the local government. Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substance Substance/mixture: Cyclosporin A Section3. COMPOSITION/INFORMATION ON INGREDIENTS Components:Cyclosporin A Percent:>97.0%(LC)(N) CAS Number:59865-13-3 Synonyms:Cyclosporin Chemical Formula:C62H111N11O12 Section4. FIRST AID MEASURES Inhalation:Remove victim to fresh air and keep at rest in a position comfortable for breathing. Get medical advice/attention. Skin contact:Remove/Take off immediately all contaminated clothing. Gently wash with plenty of soap and water. Get medical advice/attention. Eye contact:Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Get medical advice/attention. Ingestion:Get medical advice/attention.Rinse mouth. Protection of first-aiders:A rescuer should wear personal protective equipment, such as rubber gloves and air- tight goggles. Section5. FIRE-FIGHTING MEASURES Suitable extinguishingDry chemical, foam, water spray, carbon dioxide. media: Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to from the chemical:generate poisonous fume. Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing method according to the surrounding situation is used. Uninvolved persons should evacuate to a safe place. In case of fire in the surroundings: Remove movable containers if safe to do so. Special protectiveWhen extinguishing fire, be sure to wear personal protective equipment. equipment for firefighters: Section6. ACCIDENTAL RELEASE MEASURES Use extra personal protective equipment (P3 filter respirator for toxic particles). Keep Personal precautions, protective equipment and people away from and upwind of spill/leak. Entry to non-involved personnel should emergency procedures: be controlled around the leakage area by roping off, etc. Environmental precautions: Prevent product from entering drains. Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it. containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with up: appropriate laws and regulations. Section7. HANDLING AND STORAGE Precautions for safe handling Technical measures:Handling is performed in a well ventilated place. Wear suitable protective equipment. Prevent dispersion of dust. Wash hands and face thoroughly after handling. Use a closed system if possible. Use a local exhaust if dust or aerosol will be generated. Advice on safe handling: Avoid all contact! Conditions for safe storage, including any incompatibilities Storage conditions:Keep container tightly closed. Store in a refrigerator. Store locked up. Store away from incompatible materials such as oxidizing agents. Heat-sensitive Comply with laws. Packaging material: Section8. EXPOSURE CONTROLS / PERSONAL PROTECTION Engineering controls:Install a closed system or local exhaust. Also install safety shower and eye bath. Cyclosporin A Section8. EXPOSURE CONTROLS / PERSONAL PROTECTION Personal protective equipment Respiratory protection: Dust respirator, self-contained breathing apparatus(SCBA), supplied air respirator, etc. Use respirators approved under appropriate government standards and follow local and national regulations. Hand protection:Impervious gloves. Safety goggles. A face-shield, if the situation requires. Eye protection: Skin and body protection: Impervious protective clothing. Protective boots, if the situation requires. Section9. PHYSICAL AND CHEMICAL PROPERTIES Physical state (20°C):Solid Crystal- Powder Form: Colour:White - Almost white No data available Odour: pH: No data available Melting point/freezing point:151°C Boiling point/range:No data available Flash point:No data available Flammability or explosive limits: Lower:No data available Upper:No data available Relative density:No data available Solubility(ies): [Water]No data available [Other solvents] Very soluble:Methanol, Ether, Acetone, Ethanol Soluble:Chloroform Log Pow:2.92 Section10. STABILITY AND REACTIVITY Chemical stability:Stable under proper conditions. Possibility of hazardous No special reactivity has been reported. reactions: Incompatible materials: Oxidizing agents Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx) products: Section11. TOXICOLOGICAL INFORMATION Acute Toxicity:orl-rat LD50:1480 mg/kg ipr-rat LD50:147 mg/kg scu-rat LD50:286 mg/kg ivn-rat LD50:24 mg/kg Skin corrosion/irritation: No data available Serious eyeNo data available damage/irritation: Germ cell mutagenicity: sce-hmn-lym 1 mg/L oms-hmn-lym 50 mg/L Carcinogenicity:orl-man TDLo:259 mg/kg/2W-C IARC =Group 1 (Carcinogenic to humans) NTP =a (Known to be carcinogens) No data available Reproductive toxicity: RTECS Number:GZ4120000 Section12. ECOLOGICAL INFORMATION Ecotoxicity: Fish:No data available Crustacea:No data available Cyclosporin A Section12. ECOLOGICAL INFORMATION Algae:No data available Persistence / degradability: No data available BioaccumulativeNo data available potential(BCF): Mobility in soil 2.92 Log Pow: Soil adsorption (Koc):No data available No data available Henry's Law constant(PaM3/mol): Section13. DISPOSAL CONSIDERATIONS Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all federal, state and local regulations when disposing of the substance. Section14. TRANSPORT INFORMATION Does not correspond to the classification standard of the United Nations Hazards Class: UN-No:Not listed Section15. REGULATORY INFORMATION Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002 and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport, loading and unloading were prescribed. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

毒理学数据: 小鼠，大鼠，兔子静脉注射LD50(mg/kg):107、25、＞10;经口：2329、1480、＞1000。 生态学数据: 对水是稍微危害的，若无政府许可，勿将材料排入周围环境。 CHEMICAL IDENTIFICATION RTECS NUMBER : GZ4120000 CHEMICAL NAME : Cyclosporin A CAS REGISTRY NUMBER : 59865-13-3 LAST UPDATED : 199801 DATA ITEMS CITED : 35 MOLECULAR FORMULA : C62-H111-N11-O12 MOLECULAR WEIGHT : 1202.84 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 1911 mg/kg/91W-I TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - coma Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 62500 ug/kg/5D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes Nutritional and Gross Metabolic - body temperature increase TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 20 mg/kg/2D-I TOXIC EFFECTS : Behavioral - headache Vascular - acute arterial occlusion Lungs, Thorax, or Respiration - cyanosis TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 12 mg/kg TOXIC EFFECTS : Vascular - BP elevation not characterized in autonomic section Endocrine - antidiuresis TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 30 mg/kg/4D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1480 mg/kg TOXIC EFFECTS : Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 147 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 286 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 24 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2329 mg/kg TOXIC EFFECTS : Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 96 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 10 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 140 mg/kg/14D-I TOXIC EFFECTS : Endocrine - changes in spleen weight Blood - changes in spleen TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 350 mg/kg/7D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - multiple enzyme effects TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 800 mg/kg/10D-I TOXIC EFFECTS : Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 420 mg/kg/28D-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Musculoskeletal - other changes TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 700 mg/kg/28D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes in urine composition TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 210 mg/kg/14D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - renal function tests depressed Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1200 mg/kg/40D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Metabolism (Intermediary) - amino acids (including renal excretion) Biochemical - Metabolism (Intermediary) - Plasma proteins not involving coagulation TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 140 mg/kg/7D-I TOXIC EFFECTS : Vascular - BP elevation not characterized in autonomic section Vascular - regional or general arteriolar or venous dilation TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 60 mg/kg/3D-I TOXIC EFFECTS : Vascular - BP elevation not characterized in autonomic section Vascular - structural changes in vessels Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 259 mg/kg/2W-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 166 mg/kg SEX/DURATION : male 45 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - other effects on male Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 420 mg/kg SEX/DURATION : male 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 560 mg/kg SEX/DURATION : male 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - other effects on male TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 90 mg/kg SEX/DURATION : female 6-8 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 50 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 210 mg/kg SEX/DURATION : female 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Fertility - other measures of fertility MUTATION DATA TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 1 mg/L REFERENCE : IGAYAY Igaku No Ayumi. Progress in Medicine. (Ishiyaku Shuppan K.K., 1-7-10, Honkomagom, Bunkyo-ku, Tokyo, Japan) V.1- 1946- Volume(issue)/page/year: 134,403,1985 *** REVIEWS *** IARC Cancer Review:Human Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990 IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990 IARC Cancer Review:Group 1 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990

安全

• 符号: GHS07, GHS08
• 信号词: Danger
• 危害声明: H302-H350-H360
• 警示性声明: P201-P301 + P312 + P330-P308 + P313
• 个人防护装备: Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
• 危害码 (欧洲): T:Toxic
• 风险声明 (欧洲): R45;R60;R22
• 安全声明 (欧洲): 53-45-36/37-24/25-22
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: GZ4120000
• 海关编码: 2941909000

上下游产品

上游产品  0
下游产品  2
59865-15-5 121584-52-9

制备

1.以多孢木霉菌(Tolypocladium inflatum Cams)为生产菌株。75L罐内装50L种子培养基，接种5×10⁹个孢子，Ph=5.4—4.3，培养72h，得到一级种子液。750L发酵罐内装500L发酵培养基，种入上述一级种子液，培养6天，得二级种子液。4500L发酵罐内装3000L发酵培养基，发酵12天，得到环孢素发酵毒。往发酵液中加人等体积的乙酸乙酯提取，分出有机层，减压蒸发，得粗品。融化处理，可得环孢素和环孢菌素C组分，其中环孢素的产量约为150～200mg/L环孢菌素C约为50～100mg/L。

2.以多孢木霉菌为生产菌株。先制备环孢素发酵液。向发酵液中加入乙酸乙酯提取，分出有机层，减压蒸发，得粗品。经纯化处理可得。

海关

海关编码	2941909000