卡莫司汀_MSDS_用途_密度_卡莫司汀CAS号【154-93-8】

Carmustine 是一种抗肿瘤化疗剂,为 DNA 和 RNA 的烷化剂 (alkylator)。

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[ 描述 ]:

Carmustine 是一种抗肿瘤化疗剂,为 DNA 和 RNA 的烷化剂 (alkylator)。

[ 相关类别 ]:

信号通路 >> 细胞周期/DNA损伤 >> DNA烷基化剂/交联剂

研究领域 >> 癌症

[ 靶点 ]

DNA Alkylator[1]

[体外研究]

卡莫司汀是一种抗肿瘤化疗剂。卡莫司汀(8,80和800μM)降低大鼠胶质瘤细胞和完整细胞中2-氨基芴(AF)和对氨基苯甲酸(PABA)的N-乙酰转移酶(NAT)活性。在大鼠胶质瘤细胞中,DNA-AF加合物增加,而卡莫司汀减少DNA-AF加合物的形成[1]。

[体内研究]

卡莫司汀(BCNU; 25 mg/kg,ip)引起肝脏重量与体重和血浆结合胆红素的比值水平较高,胆汁流量,氧化损伤水平(GSSG)和谷蛋白降低(GSH)/ GSSG值比较与对照大鼠[2]。

[激酶实验]

进行2-氨基芴（AF）和对氨基苯甲酸（PABA）的乙酰-CoA依赖性N-乙酰化的测定。测定系统中的孵育混合物由总体积为90μL的胶原肿瘤细胞胞浆组成，根据需要稀释于50μL裂解缓冲液（20 mM Tris / HCl，pH 7.5,1 mM DTT和1 mM EDTA）中，20 μL的50mM Tris-HCl（pH7.5），0.2mM EDTA，2mM DTT，15mM乙酰肉碱，2U / mL肉毒碱乙酰转移酶和特定浓度的AF或PABA的乙酰辅酶A再循环混合物。通过添加20μL乙酰-CoA开始反应。对照反应用20μL蒸馏水代替乙酰-CoA。对于单点活性测量，AF或PABA的最终浓度为0.1mM，AcCoA为0.5mM。将具有或不具有特定浓度的卡莫司汀和洛莫司汀的反应混合物在37℃下孵育10分钟，并用50μL的20％三氯乙酸进行PABA反应，并用100μL的乙腈进行AF反应。所有反应（实验和对照）一式三份进行[1]。

[动物实验]

大鼠[2]在进入研究之前对个体大鼠进行加权;记录它们的权重，并将它们随机分配给四组。第一组（生理盐水组）;该组由12只大鼠组成。在研究前48小时，对这些大鼠腹膜内（IP）注射2mL / kg盐水，48小时后进行研究。 II组（玉米油组）由15只大鼠组成。在研究前48小时向这些大鼠注射2mL / kg玉米油（载体）IP。 III组（卡莫司汀组）由16只大鼠组成。这些大鼠每天注射1mL盐水IP，在一天的同一时间以单剂量给药3天。在第一剂盐水后12小时，注射玉米油2mL / kg +卡莫司汀25mg / kg IP，并且在施用玉米油+卡莫司汀后48小时将大鼠包括在研究中。第IV组（曲美他嗪组）由12只大鼠组成。这些大鼠每天注射2.5mg / kg曲美他嗪（TMZ）IP，在一天的同一时间以单剂量给药3天。在第一剂TMZ后12小时，注射玉米油2mL / kg +卡莫司汀25mg / kg IP，并且在施用玉米油+卡莫司汀后48小时将大鼠包括在研究中[2]。

[参考文献]

[1]. Hung CF. Effects of carmustine and lomustine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in rat glial tumor cells. Neurochem Res. 2000 Jun;25(6):845-51.

[2]. Demir A, et al. The effect of trimetazidine on intrahepatic cholestasis caused by carmustine in rats. Hepatol Res. 2001 May 1;20(1):133-143.

[相关活性小分子]

[ 密度 ]:
1.5±0.1 g/cm3

[ 沸点 ]:
404ºC

[ 熔点 ]:
30 °C(lit.)

[ 分子式 ]:
C₅H₉Cl₂N₃O₂

[ 分子量 ]:
214.050

[ 精确质量 ]:
213.007187

[ PSA ]:
61.77000

[ LogP ]:
1.30

[ 外观性状 ]:
橙色-黄色固体

[ 折射率 ]:
1.549

[ 储存条件 ]:
库房通风低温干燥,与食品原料分开存放

[ 水溶解性 ]:
<0.1 g/100 mL at 18 ºC

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YS2625000

CHEMICAL NAME :: Urea, 1,3-bis(2-chloroethyl)-1-nitroso-

CAS REGISTRY NUMBER :: 154-93-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 98

MOLECULAR FORMULA :: C5-H9-Cl2-N3-O2

MOLECULAR WEIGHT :: 214.07

WISWESSER LINE NOTATION :: ONN2GVM2G

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 78 mg/kg/52W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Gastrointestinal - nausea or vomiting Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 125 mg/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 6 mg/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 1566 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - fibrosis (interstitial) Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 20 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 :: 17420 ug/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 :: 83200 ug/kg

TOXIC EFFECTS :: Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 13800 ug/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - chronic pulmonary edema Gastrointestinal - ulceration or bleeding from stomach Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 79600 ug/kg

TOXIC EFFECTS :: Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 19 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Liver - jaundice, other or unclassified Kidney, Ureter, Bladder - urine volume increased

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 21260 ug/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 :: 24 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Liver - jaundice, other or unclassified Kidney, Ureter, Bladder - urine volume increased

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 45 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 :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 86300 ug/kg

TOXIC EFFECTS :: Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 42 mg/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 :: 5 mg/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 :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2 mg/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 :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes Blood - leukopenia Blood - other changes

TYPE OF TEST :: LD10 - Lethal Dose

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 18 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15 mg/kg/7W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16 mg/kg/60W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 276 mg/kg/23W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Skin and Appendages - hair Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 98 mg/kg/26W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 26 mg/kg/60W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 45 mg/kg/60W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 51 mg/kg/24W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 8 mg/kg

SEX/DURATION :: female 6-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 8 mg/kg

SEX/DURATION :: female 6-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 9 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) 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 :: Intraperitoneal

DOSE :: 4 mg/kg

SEX/DURATION :: female 6-9 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 :: Intraperitoneal

DOSE :: 11 mg/kg

SEX/DURATION :: male 1 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 :: Intraperitoneal

DOSE :: 40 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 6500 ug/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Sperm Morphology

TYPE OF TEST :: DNA inhibition

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 10 mmol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 44,1887,1984 *** REVIEWS *** IARC Cancer Review:Animal 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: 26,79,1981 IARC Cancer Review:Human 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: 26,79,1981 IARC Cancer Review:Group 2A IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,150,1987 TOXICOLOGY REVIEW NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB282-265 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3594 No. of Facilities: 373 (estimated) No. of Industries: 1 No. of Occupations: 7 No. of Employees: 14122 (estimated) No. of Female Employees: 10338 (estimated)

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[ 符号 ]:

GHS06, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H300-H350-H360

[ 警示性声明 ]:
P201-P264-P301 + P310-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+:Verytoxic;

[ 风险声明 (欧洲) ]:
R45;R46;R60;R61;R28

[ 安全声明 (欧洲) ]:
S53-S22-S36/37/39-S45

[ 危险品运输编码 ]:
3249

[ WGK德国 ]:
3

[ RTECS号 ]:
YS2625000

[ 包装等级 ]:
II

[ 危险类别 ]:
6.1(a)

[ 海关编码 ]:
2924199090

详细合成路线

卡莫司汀上游产品

卡莫司汀下游产品

该品有三条合成路线：（1）以乙烯亚胺为原料，经与光气缩合生成双（β-氯乙基）脲，再经亚硝化制得卡氮芥；（2）以脲为原料，经缩合、开环、氯化、亚硝化而得；（3）以乙醇胺为原料，经与方法（2）相似的步骤得到卡氮芥。第一种方法只需两步操作就可得到产品，但使用的原料乙烯亚胺及光气均为极毒品，劳动保护和生产设备要求很高。第二种方法原料易得，操作也较方便。

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[ 海关编码 ]: 2924199090

[ 中文概述 ]:
2924199090. 其他无环酰胺（包括无环氨基甲酸酯)(包括其衍生物及盐）. 增值税率:17.0%. 退税率:13.0%. 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, 包装

[ Summary ]:
2924199090. other acyclic amides (including acyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

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