塞替派_MSDS_用途_密度_塞替派CAS号【52-24-4】

Thio-TEPA 是一种 DNA 烷化剂 (DNA alkylator),具有抗肿瘤作用。

[ 描述 ]:

Thio-TEPA 是一种 DNA 烷化剂 (DNA alkylator),具有抗肿瘤作用。

[ 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]

Thio-TEPA在大鼠肝切片孵育中表现出烷化活性。 Thio-TEPA不影响大鼠肝切片的活力,并且在所有剂量分别为2,5,10mM时不会在切片中累积[1]。

[体内研究]

具有全身照射(TBI)的Thio-TEPA(20mg/kg,ip)在前10周期间增强供体型血液嵌合体,但是不显着高于单独的TBI组。仅Thio-TEPA可改善小鼠的短期和长期植入[2]。

[细胞实验]

通过测定细胞内钾（K +）渗漏来研究Thio-TEPA对切片活力的影响。细胞内K +通过火焰光度法测量，并且使用荧光测定法测量与DNA含量相关的表达。加入浓度为1,2,5和10mM的Thio-TEPA，并将切片温育6,12和24小时。将结果与无药物对照的值进行比较。在三个最高浓度下孵育3,6和9小时后测量培养基和切片中的Thio-TEPA。使用Krebs-HEPES缓冲液作为切片缓冲液，使用Waymouth的MB 752/1培养基补充10μg庆大霉素作为培养基[1]。

[动物实验]

小鼠[2]将19周龄，25至30g的雄性C57BL / 6JIco小鼠用作接受者。同基因C57BL / 6J-Gpi-1a / Gpi-1a（B6-Gpi-1a）和BALB.B10LiLa（Gpi-1a）小鼠分别用作同源和同种异体供体骨髓的来源。后一种组合是H-2相容的（均为H-2b），但在许多次要组织相容性基因座上不匹配。将Thio-TEPA溶解在PBS中并以20mg / kg的单次推注ip腹膜内注射。初步试验已经证实，当较高剂量导致致命的胃肠道毒性时，这近似于最大耐受剂量。将环磷酰胺（CY）溶解在PBS中，并以200mg / kg的单剂量腹膜内施用。使用137Csγ-照射单元以87cGy / min的剂量率向5Gy剂量递送全身照射。在Thio-TEPA处理后，将小鼠维持在新霉素（3.5g / L无菌饮用水）上2周，以通过肠毒性最小化内毒素血症的可能问题[2]。

[参考文献]

[1]. Hagen B, et al. Metabolism and alkylating activity of thio-TEPA in rat liver slice incubation. Cancer Chemother Pharmacol. 1991;28(6):441-7.

[2]. Down JD, et al. Thiotepa improves allogeneic bone marrow engraftment without enhancing stem cell depletion in irradiated mice. Bone Marrow Transplant. 1998 Feb;21(4):327-30.

[相关活性小分子]

[ 密度 ]:
1.5±0.1 g/cm3

[ 沸点 ]:
270.2±23.0 °C at 760 mmHg

[ 熔点 ]:
54-57 °C

[ 分子式 ]:
C₆H₁₂N₃PS

[ 分子量 ]:
189.218

[ 闪点 ]:
117.2±22.6 °C

[ 精确质量 ]:
189.048950

[ PSA ]:
50.93000

[ LogP ]:
0.52

[ 外观性状 ]:
白色晶体或粉末

[ 蒸汽压 ]:
0.0±0.6 mmHg at 25°C

[ 折射率 ]:
1.709

[ 储存条件 ]:
2-8°C

[ 稳定性 ]:
Stable. Incompatible with strong oxidizing agents.

[ 水溶解性 ]:
19 G/100 ML (25 ºC)

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SZ2975000

CHEMICAL NAME :: Phosphine sulfide, tris(1-aziridinyl)-

CAS REGISTRY NUMBER :: 52-24-4

BEILSTEIN REFERENCE NO. :: 0145978

LAST UPDATED :: 199612

DATA ITEMS CITED :: 116

MOLECULAR FORMULA :: C6-H12-N3-P-S

MOLECULAR WEIGHT :: 189.24

WISWESSER LINE NOTATION :: T3NTJ APS&- AT3NTJ&- AT3NTJ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Standard Draize test

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Human

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 631 ug/kg

TOXIC EFFECTS :: Peripheral Nerve and Sensation - paresthesis Blood - changes in bone marrow (not otherwise specified)

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 8 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 :: 9400 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 :: Intraarterial

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 8750 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 :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 38 mg/kg

TOXIC EFFECTS :: Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - somnolence (general depressed activity) Behavioral - ataxia

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 11 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 :: 16500 ug/kg

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), zonal Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - changes in spleen

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 14500 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 :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 11500 ug/kg

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

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 760 ug/kg

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

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 1500 ug/kg

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

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 5500 ug/kg

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), zonal Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - changes in spleen

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Bird - quail

DOSE/DURATION :: 237 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 :: Bird - wild bird species

DOSE/DURATION :: 5620 ug/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 :: Parenteral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 33 mg/kg/3Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 17 mg/kg/56W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 218 mg/kg/1Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Ear) - effect, not otherwise specified Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 52 mg/kg/1Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 10 gm/kg/17W-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 47 mg/kg/8W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 360 mg/kg/1Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia Blood - lymphoma, including Hodgkin's disease

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 218 mg/kg/1Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Ear) - effect, not otherwise specified Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

TOXIC EFFECTS :: 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 :: Intraperitoneal

DOSE :: 5 mg/kg

SEX/DURATION :: female 12 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 Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 7500 ug/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 :: 2500 ug/kg

SEX/DURATION :: female 12 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 :: Intraperitoneal

DOSE :: 500 ug/kg

SEX/DURATION :: female 13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intratesticular

DOSE :: 8 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 25 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

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 :: Intraperitoneal

DOSE :: 625 ug/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 10 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 :: 1250 ug/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) 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 :: 5 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 7500 ug/kg

SEX/DURATION :: female 7 day(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 3 mg/kg

SEX/DURATION :: female 10 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 :: 5 mg/kg

SEX/DURATION :: male 5 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 :: 1 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intratesticular

DOSE :: 16 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Dominant lethal test

TYPE OF TEST :: Dominant lethal test

TYPE OF TEST :: Sperm Morphology

TYPE OF TEST :: Heritable translocation test

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - rabbit Kidney

DOSE/DURATION :: 15 mg/L

REFERENCE :: ECREAL Experimental Cell Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.10- 1950- Volume(issue)/page/year: 36,92,1964 *** 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: 9,85,1975 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: 50,123,1990 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: 50,123,1990 IARC Cancer Review:Human Inadequate 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: 9,85,1975 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: 50,123,1990 TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW ANPIAM Arquivos de Neuro-Psiquiatria. (Caixa Postal 30.657, 01051 Sao Paulo, Brazil) V.1- 1943- Volume(issue)/page/year: 5,447,1965 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: 2,159,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4618 No. of Facilities: 142 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 11452 (estimated) No. of Female Employees: 8724 (estimated)

[ 符号 ]:

GHS06, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H300-H350

[ 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) ]:
R28;R45;R46

[ 安全声明 (欧洲) ]:
53-22-26-36/37/39-45-36/37-28

[ 危险品运输编码 ]:
UN 2811 6.1/PG 2

[ WGK德国 ]:
3

[ RTECS号 ]:
SZ2975000

[ 包装等级 ]:
II

[ 危险类别 ]:
6.1(a)

[ 海关编码 ]:
2933990090

详细合成路线

塞替派上游产品

塞替派下游产品

将乙撑亚胺、三乙胺和无水苯冷却至 0 ℃ 以下，搅拌下滴加硫氯化磷和苯的溶液，温度控制在 5 ℃ 以下，加毕，室温下搅拌2-3h，过滤。滤饼为三乙胺盐酸盐，用无水苯洗涤。洗、滤液合并，减压蒸去苯，残液加石油醚析出结晶，冷却过滤。结晶用石油醚重结晶，得成品塞替派。收率79.4%。

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮杂原子的杂环化合物. 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:20.0%

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[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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