50-35-1

• 常用中文名：沙利度胺
• 常用英文名：Thalidomide
• CAS号：50-35-1
• 分子式：C₁₃H₁₀N₂O₄
• 分子量：258.229
• 相关类别： 医药中间体 杂环化合物 吡啶类化合物 吡啶衍生物
• 发布时间：2018-09-05 11:02:01
• 更新时间：2024-01-02 16:42:30
• 沙利度胺在20世纪50年代作为镇静剂销售，具有明显的副作用。现在在多种疾病中作为免疫调节剂。可以用作镇静剂，对于各型麻风病反应如发热、结节红斑、神经痛、关节痛、淋巴结肿大等有一定疗效，对麻风无治疗作用。
• 沙利度胺是谷氨酸（α-邻苯二甲酰亚氨基 - 戊二酰亚胺）的合成衍生物，具有致畸，免疫调节，抗炎和抗血管生成特性。体外活性：沙利度胺选择性地抑制脂多糖和其他激动剂刺激人体单核细胞生产肿瘤坏死因子α。沙利度胺通过增强mRNA降解发挥其对肿瘤坏死因子α的抑制作用。沙利度胺通过诱导细胞凋亡和G1期生长停滞直接作用在MM细胞系以及抗美法仑，盐酸阿霉素和地塞米松的病人的MM细胞。体内活性：200 mg/kg 沙利度胺导致在兔子体内血管化角膜区的抑制，抑制率在三个实验中从30％到51％。

名称

• 中文名: 沙利度胺
• 英文名: 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione
• 中文别名: N-(2,6-二氧代-3-哌啶基)-邻苯二甲酰亚胺; N-(2,6-二氧-3-哌啶基)邻苯二甲酰亚胺; (±)-沙利度胺; 反应停
• 英文别名: EINECS 200-031-1; (±)-Thalidomide; Softenon; Thalomide; )-Thalidomide; 2-(2,6-dioxopipéridin-3-yl)-1H-isoindole-1,3(2H)-dione; Neurodyn; 2-(2,6-Dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione; Neosedyn; UNII:4Z8R6ORS6L; (±)-2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione; Neosydyn; 2-(2,6-Dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione; N-(2,6-Dioxo-3-piperidinyl)phthalimide; Talidomide [DCIT]; Contergan; 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-; 2-(2,6-Dioxopiperidin-3-yl)-1H-isoindol-1,3(2H)-dion; Thalidomide; MFCD00153873; Pomalidomide Impurity 9

物化性质

• 密度: 1.5±0.1 g/cm3
• 沸点: 509.7±43.0 °C at 760 mmHg
• 熔点: 269-271°C
• 分子式: C₁₃H₁₀N₂O₄
• 分子量: 258.229
• 闪点: 262.1±28.2 °C
• 精确质量: 258.064056
• PSA: 83.55000
• LogP: 0.54
• 外观性状: 白色固体
• 蒸汽压: 0.0±1.3 mmHg at 25°C
• 折射率: 1.646
• 储存条件:

  本品密封避光干燥保存。

• 稳定性: Stable. Combustible. Incompatible with strong oxidizing agents.
• 水溶解性: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 0.6 mg/mL | <0.1 g/100 mL at 22 ºC
• 分子结构:

  1、 摩尔折射率：62.35

  2、 摩尔体积（cm³/mol）：171.7

  3、 等张比容（90.2K）：496.5

  4、 表面张力（dyne/cm）：69.9

  5、 极化率（10-24cm3）：24.71

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:1

  3.氢键受体数量:4

  4.可旋转化学键数量:1

  5.互变异构体数量:8

  6.拓扑分子极性表面积83.6

  7.重原子数量:19

  8.表面电荷:0

  9.复杂度:449

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:1

  13.确定化学键立构中心数量:0

  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：淡黄色结晶性粉末，无臭，无味

  2. 密度（g/mL,25/4℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：269-271°C

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC, 5.2 kPa）：未确定

  7. 折射率：未确定

  8. 闪点（ºC）：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,25 ºC）：未确定

  12. 饱和蒸气压（kPa,60 ºC）：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：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：微溶于水(<0.1 g/100 mL at 22 ºC)、乙醇、丙酮中，不溶于乙醚、氯仿。45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 0.6mg/mL

生物活性

• 描述: Thalidomide 最初是一种镇静剂,能够抑制 ereblon (cullin-4 E3 泛素连接酶复合物 CUL4-RBX1-DDB1 的一部分),Kd 值约为 250 nM,具有免疫调节、抗炎、抗肿瘤作用。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> E1/E2/E3酶
  研究领域 >> 炎症/免疫
  研究领域 >> 癌症
• 靶点:

  Kd: ∼250 nM (CRL4CRBN)[1]

• 体外研究: 沙利度胺最初作为一种镇静剂被推广,具有免疫调节,抗炎和抗血管生成的癌症特性,并且靶向ereblon(CRBN),它是cullin-4 E3泛素连接酶复合物CUL4-RBX1-DDB1的一部分,其Kd为〜 250 nM [1]。沙利度胺(50μg/ mL)增强了依替替尼对PC9和A549细胞增殖的抗肿瘤活性,这种作用与细胞凋亡和细胞迁移有关。此外,沙利度胺和依替替尼抑制PC9细胞中的EGFR和VEGF-R2途径[3]。
• 体内研究: 沙利度胺(100mg/kg,口服)抑制胶原沉积,下调α-SMA和I型胶原蛋白的mRNA表达水平,并显着降低RILF小鼠中的促炎细胞因子。沙利度胺通过抑制ROS和下调依赖于Nrf2状态的TGF-β/ Smad通路来减轻RILF [2]。沙利度胺(200 mg/kg,po)联合icotinib在携带PC9细胞的裸鼠体内显示出协同的抗肿瘤作用,抑制肿瘤生长并促进肿瘤死亡[3]。
• 细胞实验: THP-1细胞，A549细胞和KYSE30细胞在补充有10％胎牛血清的RPMI-1640培养基中培养，并在5％CO 2和95％室内空气的气氛中维持在37℃。用单剂量的4Gy 6-MV X射线照射THP-1细胞，并在辐射后用或不用含有沙利度胺（0.2μmol/ mL）的培养基处理48小时。根据初步结果选择沙利度胺的浓度[2]。
• 动物实验: 小鼠[2]将总共24只WT C57BL / 6小鼠随机分成4组进行实验（每组n = 6）：对照组，照射组，与沙利度胺一起照射的组和仅沙利度胺组。基于初步结果，在实验中使用100mg / kg沙利度胺。将沙利度胺溶解在DMSO载体中。治疗组在第1天开始每隔一天通过管饲法接受200μL的指定剂量的沙利度胺，进行6次治疗。对照小鼠仅接受200μL含0.1％DMSO的盐水。照射后12周收获肺用于分析。将总共20只Nrf2 - / - 小鼠随机分成4组进行实验（每组n = 5）。 Nrf2 - / - 小鼠的实验程序与WT C57BL / 6小鼠相同。另外，将总共30只WT C57BL / 6小鼠随机分成5组用于随后的实验（每组n = 6）：对照组，照射组，与CDDO-Me和沙利度胺一起照射的组，与CDDO-Me一起照射的组和与沙利度胺一起照射的组。选择600ng和100mg / kg作为实验的CDDO-Me和沙利度胺的剂量。治疗组在第1天开始每隔一天通过管饲法接受200μL指定剂量的CDDO-Me或沙利度胺六次。对于CDDO-Me和沙利度胺的组合组，CDDO-Me在第1天开始每隔一天通过管饲法以200μL递送用于六次治疗。沙利度胺在第2天开始每隔一天灌胃200μL，进行6次治疗[2]。
• 参考文献:

  [1]. Fischer ES, et al. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature. 2014 Aug 7;512(7512):49-53.

  [2]. Bian C, et al. Thalidomide (THD) alleviates radiation induced lung fibrosis (RILF) via down-regulation of TGF-β/Smad3 signaling pathway in an Nrf2-dependent manner. Free Radic Biol Med. 2018 Dec;129:446-453.

  [3]. Sun X, et al. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling. Med Sci Monit. 2018 May 15;24:3193-3203.

MSDS

(+/-)-沙利度胺 模块1. 化学品 产品名称： (±)-Thalidomide 5.3 模块2. 危险性概述 GHS分类 　物理性危害未分类 　健康危害 急性毒性（经口） 第3级 急性毒性（经皮） 第4级 生殖毒性 第2级 　环境危害未分类 GHS标签元素 　图标或危害标志 　信号词危险 　危险描述吞咽会中毒。 皮肤接触有害 怀疑会损害生育能力或胎儿 　防范说明 [预防]使用前获取特定手册。 处理前必须阅读并理解所有安全措施。 使用本产品时切勿吃东西，喝水或吸烟。 处理后要彻底清洗双手。 穿戴防护手套/护目镜/防护面具。 [急救措施] 食入：立即呼叫解毒中心/医生。 皮肤接触：用大量肥皂和水轻轻洗。 被污染的衣物清洗后方可重新使用。 如接触到或相关接触：求医/就诊。 [储存]存放处须加锁。 [废弃处置] 根据当地政府规定把物品/容器交与工业废弃处理机构。 (+/-)-沙利度胺 模块3. 成分/组成信息 单一物质/混和物单一物质 化学名(中文名)： (+/-)-沙利度胺 百分比： >98.0%(HPLC)(N) CAS编码： 50-35-1 俗名： N-(2,6-Dioxo-3-piperidinyl)phthalimide 分子式： C13H10N2O4 模块4. 急救措施 吸入： 将受害者移到新鲜空气处，保持呼吸通畅，休息。求医/就诊。 皮肤接触： 立即去除/脱掉所有被污染的衣物。用大量肥皂和水轻轻洗。 求医/就诊。 眼睛接触：用水小心清洗几分钟。如果方便，易操作，摘除隐形眼镜。 求医/就诊。 食入： 立即呼叫解毒中心/医生。漱口。 紧急救助者的防护：救援者需要穿戴个人防护用品，比如橡胶手套和气密性护目镜。 模块5. 消防措施 合适的灭火剂：干粉，泡沫，雾状水，二氧化碳 特殊危险性：小心，燃烧或高温下可能分解产生毒烟。 特定方法：从上风处灭火，根据周围环境选择合适的灭火方法。 非相关人员应该撤离至安全地方。 周围一旦着火：如果安全，移去可移动容器。 消防员的特殊防护用具：灭火时，一定要穿戴个人防护用品。 模块6. 泄漏应急处理 个人防护措施，防护用具， 使用特殊的个人防护用品（针对有毒颗粒的P3过滤式空气呼吸器）。远离溢出物/泄露 紧急措施：处并处在上风处。 泄露区应该用安全带等圈起来，控制非相关人员进入。 环保措施：防止进入下水道。 控制和清洗的方法和材料：清扫收集粉尘，封入密闭容器。注意切勿分散。附着物或收集物应该立即根据合适的 法律法规处置。 模块7. 操作处置与储存 处理 技术措施：在通风良好处进行处理。穿戴合适的防护用具。防止粉尘扩散。处理后彻底清洗双手 和脸。 注意事项：如果可能，使用封闭系统。如果粉尘或浮质产生，使用局部排气。 操作处置注意事项：避免所有部位的接触！ 贮存 储存条件：保持容器密闭。存放于凉爽、阴暗处。 存放处须加锁。 远离不相容的材料比如氧化剂存放。 包装材料：依据法律。 模块8. 接触控制和个体防护 工程控制：尽可能安装封闭体系或局部排风系统。同时安装淋浴器和洗眼器。 个人防护用品 　呼吸系统防护： 防尘面具，自携式呼吸器（SCBA），供气呼吸器等。使用通过政府标准的呼吸器。依 据当地和政府法规。 (+/-)-沙利度胺 模块8. 接触控制和个体防护 　手部防护：防渗手套。 　眼睛防护：护目镜。如果情况需要，佩戴面具。 　皮肤和身体防护：防渗防护服。如果情况需要，穿戴防护靴。 模块9. 理化特性 固体 外形（20°C）： 外观： 晶体-粉末 颜色： 白色-极淡的黄色 气味：无资料 pH:无数据资料 熔点： 276°C 沸点/沸程无资料 闪点：无资料 爆炸特性 　爆炸下限：无资料 　爆炸上限：无资料 密度：无资料 溶解度： [水] 不溶于(60mg/L, 25°C) [其他溶剂] 易溶于： 二甲基甲酰胺, 吡啶, 二氧六环 极微溶于： 甲醇, 丙酮, 乙醇, 乙酸乙酯, 冰乙酸 不溶于： 醚, 苯, 氯仿 log水分配系数 = 3.09 模块10. 稳定性和反应性 化学稳定性：一般情况下稳定。 危险反应的可能性：未报道特殊反应性。 须避免接触的物质氧化剂 危险的分解产物: 一氧化碳, 二氧化碳, 氮氧化物 (NOx) 模块11. 毒理学信息 急性毒性： orl-rat LD50:113 mg/kg skn-rat LD50:1550 mg/kg ipr-rat LD50:>6 g/kg 对皮肤腐蚀或刺激：无资料 对眼睛严重损害或刺激：无资料 生殖细胞变异原性： cyt-hmn-lym 1 mg/L mmo-omi 10 g/L (-S9) 致癌性： scu-mus TDLo:34 g/kg/57W-I IARC =无资料 NTP =无资料 生殖毒性： orl-wmn TDLo:16 mg/kg(28-35D preg) orl-rat TDLo:28 g/kg(3D male/3D pre-22D preg) ipr-rat TDLo:1200 mg/kg(9-11D preg) ivn-rat TDLo:45 mg/kg(12D preg) RTECS 号码: TI4375000 模块12. 生态学信息 生态毒性： (+/-)-沙利度胺 模块12. 生态学信息 鱼类：无资料 甲壳类：无资料 藻类：无资料 残留性 / 降解性：无资料 潜在生物累积 （BCF):无资料 土壤中移动性 　log水分配系数： 3.09 　土壤吸收系数 （Koc）：无资料 　亨利定律无资料 constant(PaM3/mol): 模块13. 废弃处置 如果可能，回收处理。请咨询当地管理部门。建议在可燃溶剂中溶解混合，在装有后燃和洗涤装置的化学焚烧炉中 焚烧。废弃处置时请遵守国家、地区和当地的所有法规。 模块14. 运输信息 联合国分类： 第1项 毒害品。 UN编号： 2811 正式运输名称： 有毒固体, 有机物, 不另作详细说明 包装等级： III 模块15. 法规信息 《危险化学品安全管理条例》（2002年1月26日国务院发布，2011年2月16日修订）: 针对危险化学品的安全使用、 生产、储存、运输、装卸等方面均作了相应的规定。 模块16 - 其他信息 N/A

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : TI4375000 CHEMICAL NAME : Phthalimide, N-(2,6-dioxo-3-piperidyl)- CAS REGISTRY NUMBER : 50-35-1 BEILSTEIN REFERENCE NO. : 0030233 LAST UPDATED : 199706 DATA ITEMS CITED : 85 MOLECULAR FORMULA : C13-H10-N2-O4 MOLECULAR WEIGHT : 258.25 WISWESSER LINE NOTATION : T56 BVNVJ C- DT6VMVTJ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 113 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 : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1550 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 : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >6 gm/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 : 2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 800 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 - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >1538 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 - rabbit DOSE/DURATION : 21500 mg/kg/43W-I TOXIC EFFECTS : Peripheral Nerve and Sensation - recording from afferent nerve TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 34 gm/kg/57W-I TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Tumorigenic - tumors at site of application Lungs, Thorax, or Respiration - tumors TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2 mg/kg SEX/DURATION : female 30 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 17500 ug/kg SEX/DURATION : female 1-5 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2 mg/kg SEX/DURATION : female 29 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 16 mg/kg SEX/DURATION : female 28-35 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 560 mg/kg SEX/DURATION : male 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 500 mg/kg SEX/DURATION : female 10-14 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 500 mg/kg SEX/DURATION : female 7-11 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1050 mg/kg SEX/DURATION : female 1-21 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 28 gm/kg SEX/DURATION : male 3 day(s) pre-mating female 3 day(s) pre-mating - 22 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - urogenital system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 200 mg/kg SEX/DURATION : female 15 day(s) pre-mating TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 1200 mg/kg SEX/DURATION : female 9-11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 22 mg/kg SEX/DURATION : female 6-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 45 mg/kg SEX/DURATION : female 10 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 Reproductive - Specific Developmental Abnormalities - eye/ear TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 15 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 45 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 1700 mg/kg SEX/DURATION : female 6-22 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 750 mg/kg SEX/DURATION : female 2-7 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 600 mg/kg SEX/DURATION : female 1-7 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 400 mg/kg SEX/DURATION : female 12-15 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - parturition Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 155 mg/kg SEX/DURATION : female 7-11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 124 mg/kg SEX/DURATION : female 7-10 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - abortion Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 25 mg/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 25 mg/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 100 mg/kg SEX/DURATION : female 13 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - other effects to embryo TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 2 gm/kg SEX/DURATION : female 11-12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - other developmental abnormalities TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 390 mg/kg SEX/DURATION : female 8-20 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 - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 2 gm/kg SEX/DURATION : female 20-24 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 250 mg/kg SEX/DURATION : female 20-24 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 10 mg/kg SEX/DURATION : female 28 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 60 mg/kg SEX/DURATION : female 24-26 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 330 mg/kg SEX/DURATION : female 1-33 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 110 mg/kg SEX/DURATION : female 10-20 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 360 mg/kg SEX/DURATION : female 15-17 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - abortion Reproductive - Specific Developmental Abnormalities - homeostasis TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 150 mg/kg SEX/DURATION : female 7 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 450 mg/kg SEX/DURATION : female 7-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - urogenital system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 450 mg/kg SEX/DURATION : female 7-9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 400 mg/kg SEX/DURATION : female 7-16 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - other developmental abnormalities Reproductive - Effects on Newborn - biochemical and metabolic TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 833 mg/kg SEX/DURATION : female 6-11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - gastrointestinal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 125 mg/kg SEX/DURATION : female 8-12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 1500 mg/kg SEX/DURATION : female 6-20 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - other developmental abnormalities Reproductive - Specific Developmental Abnormalities - body wall TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 1700 mg/kg SEX/DURATION : female 1-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 1800 mg/kg SEX/DURATION : female 3-20 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 1200 mg/kg SEX/DURATION : female 1-20 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 750 mg/kg SEX/DURATION : female 6-10 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 12500 ug/kg SEX/DURATION : female 8-12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 10 mg/kg SEX/DURATION : female 7 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 900 mg/kg SEX/DURATION : female 7-12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - gastrointestinal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 1050 mg/kg SEX/DURATION : female 7-13 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 500 mg/kg SEX/DURATION : female 7 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 550 mg/kg SEX/DURATION : female 12-33 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 300 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1500 mg/kg SEX/DURATION : female 8-12 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1800 mg/kg SEX/DURATION : female 13-18 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 : Unscheduled DNA synthesis TYPE OF TEST : Mutation test systems - not otherwise specified MUTATION DATA TEST SYSTEM : Rodent - rat DOSE/DURATION : 7600 mg/kg/30D (Continuous) REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 202,1080,1964 *** REVIEWS *** TOXICOLOGY REVIEW BCSTB5 Biochemical Society Transactions. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1973- Volume(issue)/page/year: 2,695,1974 TOXICOLOGY REVIEW PLMJAP Pahlavi Medical Journal. (Shiraz, Iran) V.1-9, 1970-78. Volume(issue)/page/year: 6,160,1975 TOXICOLOGY REVIEW AUHPAI Australian Journal of Hospital Pharmacy. (B.R. Miller, POB 125, Heidelberg, Vic., Australia) V.1- 1971- Volume(issue)/page/year: 4(1),5,1974 TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 2,365,1973 TOXICOLOGY REVIEW INTEAG Internist. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1960- Volume(issue)/page/year: 15,7,1974 TOXICOLOGY REVIEW CLPTAT Clinical Pharmacology and Therapeutics (St. Louis). (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1960- Volume(issue)/page/year: 5,480,1964 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 TOXICOLOGY REVIEW ATXKA8 Archiv fuer Toxikologie. (Berlin, Fed. Rep. Ger.) V.15-31, 1954-74. For publisher information, see ARTODN. Volume(issue)/page/year: 28,135,1971 TOXICOLOGY REVIEW NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 267,1238,1962 TOXICOLOGY REVIEW NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 267,1184,1962 TOXICOLOGY REVIEW LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,45,1962 TOXICOLOGY REVIEW BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,646,1962 TOXICOLOGY REVIEW LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,303,1962

安全

• 符号: GHS07, GHS08
• 信号词: Danger
• 危害声明: H302-H360D
• 警示性声明: P201-P280-P301 + P312 + P330-P308 + P313
• 个人防护装备: Eyeshields;Faceshields;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): R46;R61;R21;R25;R62
• 安全声明 (欧洲): S53-S22-S26-S36/37/39-S45
• 危险品运输编码: UN 2811 6.1/PG 3
• WGK德国: 3
• RTECS号: TI4375000
• 包装等级: III
• 危险类别: 6.1(b)
• 海关编码: 2925190090

合成路线

上下游产品

上游产品  9
3343-28-0 7607-72-9 85-44-9 56-85-9
131-11-3 88-95-9 3343-29-1 671787-01-2
340-90-9
下游产品  5
2614-06-4 841-67-8 145945-21-7 26581-81-7
220460-55-9

海关

海关编码	2925190090
中文概述	2925190090 其他酰亚胺及其衍生物盐. 增值税率:17.0% 退税率:9.0% 监管条件:无 最惠国关税:6.5% 普通关税:30.0%
申报要素	品名, 成分含量, 用途
Summary	2925190090 other imides and their derivatives; salts thereof VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%