甲氨蝶呤_MSDS_作用_用途_甲氨蝶呤CAS号【59-05-2】

Methotrexate是一种叶酸拮抗剂,在体外试验中 IC50 为 78 nM。

甲氨蝶呤为抗叶酸类抗肿瘤药，对多种动物肿瘤有抑制作用。实验证明，此药通过对二氢叶酸还原酶的竞争性抑制而发挥作用。二氢叶酸还原酶是一个在DNA合成中重要的酶，特别是在叶酸变成四氢叶酸及脱氧尿嘧啶核苷甲基化而转变成胸腺嘧啶核苷的过程中是必不可少的。此药选择性地作用于DNA合成期(即S期)，属周期特异性药物。近来有人认为本品还有第二作用点，即G1/S转换期，它还能抑制白介素-2合成和抑制中性粒细胞的趋化性作用，故具有免疫抑制和抗炎作用。在大剂量时对非增殖细胞特别是肝细胞也有直接毒性作用，临床常用CF作为解毒剂。
甲氨蝶呤(简称MTX)的结构与叶酸近似，叶酸4位上羟基和10位NH的氢在MTX中分别为氨基和CH3。MTX与二氢叶酸还原酶结合，阻断叶酸和二氢叶酸还原为活化型的四氢叶酸，因而抑制细胞内的一碳转移，影响嘌呤新合成和脱氧尿嘧啶核苷酸转变为脱氧胸腺嘧啶核苷酸，使DNA和RNA合成受阻。MTX在血浆中浓度达10-8mol/L，能有效地阻断脱氧尿嘧啶核苷经由脱氧胸腺嘧啶核苷酸掺入DNA，而抑制嘌呤合成的浓度为10-7mol/L。MTX与二氢叶酸还原酶的结合是可逆的，但很牢固。二氢叶酸的量高于MTX1000倍时才能对抗MTX的结合。在体外，当MTX低于完全抑制DNA合成的浓度时，能诱导人体绒毛膜上皮癌细胞的分化，增加绒毛膜促性腺激素的产生。MTX为细胞周期特异性药物，主要作用于S期细胞，对G1期亦有一定作用，对G1/S有延缓作用。

[ 描述 ]:

Methotrexate是一种叶酸拮抗剂,在体外试验中 IC50 为 78 nM。

[ 相关类别 ]:

信号通路 >> 抗体- 药物偶联物 >> ADC细胞毒素

信号通路 >> 细胞周期/DNA损伤 >> 叶酸

研究领域 >> 癌症

[ 靶点 ]

Antifolate[1]

[体外研究]

甲氨喋呤(MTX)具有比氨蝶呤更可预测的毒性,已成为治疗儿童急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤的基石[1]。

[体内研究]

甲氨蝶呤(MTX)暴露可降低小鼠的胸腺和脾脏指数。甲氨蝶呤在剂量≥5mg/ kg时显着降低白细胞,胸腺和脾淋巴细胞。然而,治疗加对照组和模型组之间存在显着差异(p <0.01)。葡萄籽原花青素和西伯利亚人参刺五加苷的组合明显减少了甲氨蝶呤暴露对小鼠胸腺和脾脏指数的影响[2]。

[细胞实验]

使用96孔微量滴定板在生长抑制实验中研究每种细胞系。由于抗体是依赖于时间表的，因此初步实验旨在确定最长的暴露持续时间，其允许细胞的连续对数期生长而不改变培养基，同时保持SRB光密度和细胞数之间的线性关系。细胞铺板后24小时，将细胞系暴露于抗病毒载体120小时（每个实验重复三次）。为确保能够观察到完整的S形存活 - 浓度曲线，研究了以下药物浓度：甲氨蝶呤（0.002-5μM），AMT（0.0001-1μM），PXD（0.0003-10μM），TLX（0.0002-0.5） μM）。实验重复至少两次[1]。

[动物实验]

小鼠[2]在甲氨蝶呤暴露前一周施用生物活性植物化学物质的组合。治疗组I：小鼠给予来自西伯利亚人参的绿茶多酚和刺五加苷的组合（0.2mL / 10g，每天一次），持续15天，并且单次剂量的甲氨蝶呤（2mg / kg，ip每天一次）是在第8天添加。治疗组II：给小鼠提供来自西伯利亚人参的葡萄籽原花色素和刺五加苷的组合15天，并且在第8天以类似方式给予甲氨蝶呤。模型组：动物接受蒸馏水代替生物活性植物化学物质组合15天，并且在第8天将相同的甲氨蝶呤方案应用于该组。对照组：给小鼠15天蒸馏水，第8天以类似方式给予生理盐水代替甲氨蝶呤。最后一次给药后12小时，通过颈椎脱臼使动物安乐死。

[参考文献]

[1]. Norris RE, et al. Clinical potency of methotrexate, aminopterin, talotrexin and pemetrexed in childhood leukemias. Cancer Chemother Pharmacol. 2010 May;65(6):1125-30.

[2]. Gu S, et al. Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals. PeerJ. 2016 May 11;4:e1983.

[相关活性小分子]

[ 密度 ]:
1.4080

[ 沸点 ]:
561.26°C

[ 熔点 ]:
195°C

[ 分子式 ]:
C₂₀H₂₂N₈O₅

[ 分子量 ]:
454.439

[ 闪点 ]:
11℃

[ 精确质量 ]:
454.171326

[ PSA ]:
210.54000

[ LogP ]:
-0.24

[ 外观性状 ]:
黄色结晶粉末

[ 折射率 ]:
1.6910

[ 储存条件 ]:
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

[ 稳定性 ]:
Stable, but light sensitive and hygroscopic. Incompatible with strong acids, strong oxidizing agents. Store at -15C or below.

[ 水溶解性 ]:
Insoluble. <0.1 g/100 mL at 19 ºC

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MA1225000

CHEMICAL NAME :: Glutamic acid, N-(p-(((2,4-diamino-6-pteridinyl)methyl)methylamino)b enzoyl)-, L-

CAS REGISTRY NUMBER :: 59-05-2

LAST UPDATED :: 199806

DATA ITEMS CITED :: 143

MOLECULAR FORMULA :: C20-H22-N8-O5

MOLECULAR WEIGHT :: 454.50

WISWESSER LINE NOTATION :: T66 BN DN GN JNJ CZ EZ H1N1&R DVMYVQ2VQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Non-standard exposure

ROUTE OF EXPOSURE :: Administration into the eye

SPECIES OBSERVED :: Human

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 4286 ug/kg/2.7Y-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - fibrosis, focal (pneumoconiosis) Lungs, Thorax, or Respiration - respiratory obstruction Blood - aplastic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 2 mg/kg/17W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Blood - leukopenia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 643 ug/kg/6W-I

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 43 mg/kg/5Y

TOXIC EFFECTS :: Liver - liver function tests impaired Liver - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 2 mg/kg/12D

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - cough Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 800 ug/kg/4D-I

TOXIC EFFECTS :: Blood - leukopenia Blood - thrombocytopenia Blood - oxidant related (GPD deficient) anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 740 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 100 mg/kg/4H

TOXIC EFFECTS :: Blood - thrombocytopenia Blood - other changes Biochemical - Metabolism (Intermediary) - effect on inflammation or mediation of inflammation

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 4650 ug/kg/4W-I

TOXIC EFFECTS :: Liver - fatty liver degeneration Liver - liver function tests impaired

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Human

DOSE/DURATION :: 200 mg/kg/5Y

TOXIC EFFECTS :: Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 7143 ug/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Blood - changes in leukocyte (WBC) count Blood - changes in platelet count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 2600 ug/kg

TOXIC EFFECTS :: Brain and Coverings - changes in cerebral spinal fluid Lungs, Thorax, or Respiration - fibrosis, focal (pneumoconiosis) Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 150 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraspinal

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 36 mg/kg/15D

TOXIC EFFECTS :: Spinal Cord - other degenerative changes Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 135 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 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 :: 58 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 :: 14 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 :: Intramuscular

SPECIES OBSERVED :: Human

DOSE/DURATION :: 35 mg/kg/28W

TOXIC EFFECTS :: Vascular - BP lowering not characterized in autonomic section 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 - mouse

DOSE/DURATION :: 146 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 - mouse

DOSE/DURATION :: 50 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 :: 250 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 - mouse

DOSE/DURATION :: 65 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 :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 69 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 :: 5600 ug/kg/4W-C

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - hepatitis (hepatocellular necrosis), zonal Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4200 ug/kg/6W-C

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), zonal

TYPE OF TEST :: TCLo - Lowest published toxic concentration

ROUTE OF EXPOSURE :: Inhalation

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 41 mg/m3/2W-C

TOXIC EFFECTS :: 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 :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 71500 ug/kg/5D-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - thrombocytopenia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 7 mg/kg/12W-C

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 125 mg/kg/6Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 51 mg/kg/4Y-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 210 mg/kg/50W-C

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Endocrine - adrenal cortex tumors Blood - lymphoma, including Hodgkin's disease

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 139 mg/kg/55W-C

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 55 mg/kg/78W-C

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 74 mg/kg/48W-I

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 8260 ug/kg/44W-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 250 ug/kg

SEX/DURATION :: female 9 week(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 200 ug/kg

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

SEX/DURATION :: female 14-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 200 ug/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) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 300 ug/kg

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

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 300 ug/kg

SEX/DURATION :: female 11 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 :: 100 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 :: Unreported

DOSE :: 500 ug/kg

SEX/DURATION :: female 9 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 :: 25 mg/kg

SEX/DURATION :: female 8-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 50 mg/kg

SEX/DURATION :: female 9 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 :: Intraperitoneal

DOSE :: 200 mg/kg

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

TOXIC EFFECTS :: Reproductive - Maternal Effects - oogenesis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 10 mg/kg

SEX/DURATION :: female 11 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 :: 25 mg/kg

SEX/DURATION :: female 11 day(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 260 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 :: 20 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 50 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 1 mg/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 :: Oral

DOSE :: 2 mg/kg

SEX/DURATION :: female 11-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2 mg/kg

SEX/DURATION :: female 17-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 600 ug/kg

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

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 600 ug/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 :: Intravenous

DOSE :: 9600 ug/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)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 9600 ug/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Dominant lethal test

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Mammal - species unspecified Cells - not otherwise specified

DOSE/DURATION :: 1 mmol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 120,139,1983 *** REVIEWS *** IARC Cancer Review:Animal 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: 26,267,1981 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: 26,267,1981 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,241,1987 TOXICOLOGY REVIEW NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 291,75,1974 TOXICOLOGY REVIEW PLMJAP Pahlavi Medical Journal. (Shiraz, Iran) V.1-9, 1970-78. Volume(issue)/page/year: 6,160,1975 TOXICOLOGY REVIEW MIMDAL Minnesota Medicine. (Minnesota Medical Assoc., 2221 University Ave., SE, Suite 400, Minneapolis, MN 55414) V.1- 1918- Volume(issue)/page/year: 57,19,1974 TOXICOLOGY REVIEW JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 172,1765,1960 TOXICOLOGY REVIEW THORA7 Thorax. (British Medical Assoc., BMA House, Travistock Square, London WC1H 9JR, UK) V.1- 1946- Volume(issue)/page/year: 27,636,1972 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 TOXICOLOGY REVIEW MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 2,1076,1971 TOXICOLOGY REVIEW MEDIAV Medicine. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1922- Volume(issue)/page/year: 55,371,1976 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3716 No. of Facilities: 529 (estimated) No. of Industries: 2 No. of Occupations: 24 No. of Employees: 17193 (estimated) No. of Female Employees: 9496 (estimated)

[ 符号 ]:

GHS06, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H315-H319-H340-H360

[ 警示性声明 ]:
P201-P280-P301 + P310 + P330-P305 + P351 + P338-P308 + P313-P337 + P313

[ 危害码 (欧洲) ]:
T:Toxic

[ 风险声明 (欧洲) ]:
R61;R25;R36/38

[ 安全声明 (欧洲) ]:
S53-S26-S36/37-S45

[ 危险品运输编码 ]:
UN 2811 6.1/PG 3

[ WGK德国 ]:
3

[ RTECS号 ]:
MA1225000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2933990090

详细合成路线

甲氨蝶呤上游产品

甲氨蝶呤下游产品

由2，4，5，6-四氨基嘧啶与二溴丙醛环合后，再与对甲氨基苯甲酰谷氨酸缩合而得。

[ 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%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ 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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