制备方法

苯甲醛经缩合、氧化得到联苯甲酰，然后与尿素重排、环合得到苯妥英钠。将水、尿素及联苯甲酰依次加入反应锅，搅拌加热至98℃，加入30%氢氧化钠，回流1.5h。加水及适量少性炭脱色，冷至26-28℃，过滤，滤液用5%左右盐酸酸化至pH=5-6，温度45-55℃，过滤，用水洗涤，得苯妥英。将苯妥英投入碱液中加热溶解，用氢氧化钠溶液调节pH至11-11.5，加活万籁 炭于75-80℃脱色半小时。压滤，冷至37-38℃，加入晶种放置结晶。冷至25℃过滤，结晶用蒸馏水洗涤，甩干，粉碎，于80℃左右干燥，得苯妥英钠。

合成制备方法

苯甲醛经缩合、氧化得到联苯甲酰，然后与尿素重排、环合得到苯妥英钠。将水、尿素及联苯甲酰依次加入反应锅，搅拌加热至98℃，加入30%氢氧化钠，回流1.5h。加水及适量少性炭脱色，冷至26-28℃，过滤，滤液用5%左右盐酸酸化至pH=5-6，温度45-55℃，过滤，用水洗涤，得苯妥英。将苯妥英投入碱液中加热溶解，用氢氧化钠溶液调节pH至11-11.5，加活万籁 炭于75-80℃脱色半小时。压滤，冷至37-38℃，加入晶种放置结晶。冷至25℃过滤，结晶用蒸馏水洗涤，甩干，粉碎，于80℃左右干燥，得苯妥英钠。

用途简介

抗癫痫药及抗心律失常药。对癫痫大发作疗效好，对精神运动性发作和局限性发作次之，对小发作不但无效，甚至能诱发。

用途

抗癫痫药及抗心律失常药。对癫痫大发作疗效好，对精神运动性发作和局限性发作次之，对小发作不但无效，甚至能诱发。

包装等级：

III

风险类别：

6.1(b)

海关代码：

2933990090

WGK_Germany：

3
德国有关水污染物质的分类清单

危险类别码：

R22;R43;R62;R63

安全说明：

S22-S36/37/39-S45

RTECS号：

MU1400000

安全标志：

S22:不要吸入粉尘。
S45:出现意外或者感到不适，立刻到医生那里寻求帮助（最好带去产品容器标签）。
:

危险标志：

Xn:Harmful;

CHEMICAL IDENTIFICATION

RTECS NUMBER :

MU1400000

CHEMICAL NAME :

Hydantoin, 5,5-diphenyl-, monosodium salt

CAS REGISTRY NUMBER :

630-93-3

LAST UPDATED :

199706

DATA ITEMS CITED :

60

MOLECULAR FORMULA :

C15-H11-N2-O2.Na

MOLECULAR WEIGHT :

274.27

WISWESSER LINE NOTATION :

T5MVMV EHJ ER& ER &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

70 mg/kg/17D-I

TOXIC EFFECTS :

Behavioral - anorexia (human) Gastrointestinal - nausea or vomiting Skin and Appendages - dermatitis, allergic (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

4 mg/kg/D

TOXIC EFFECTS :

Endocrine - other changes Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

78 mg/kg

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure) Blood - hemorrhage Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

647 mg/kg/21W-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, allergic (after systemic exposure)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

12571 ug/kg/25M-C

TOXIC EFFECTS :

Cardiac - pulse rate Cardiac - other changes Vascular - BP lowering not characterized in autonomic section

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

7143 ug/kg/14M-C

TOXIC EFFECTS :

Cardiac - other changes Lungs, Thorax, or Respiration - other changes Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

29 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 - rat

DOSE/DURATION :

1530 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 :

138 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 :

230 mg/kg

TOXIC EFFECTS :

Skin and Appendages - hair

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

90 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 - rat

DOSE/DURATION :

153 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

165 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 :

103 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 :

400 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 :

98 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 :

540 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 :

90 mg/kg

TOXIC EFFECTS :

Cardiac - other changes Lungs, Thorax, or Respiration - other changes Blood - hemorrhage

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

157 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 - guinea pig

DOSE/DURATION :

280 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 :

Rodent - guinea pig

DOSE/DURATION :

38600 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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1800 mg/kg/30D-I

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

150 mg/kg/3D-I

TOXIC EFFECTS :

Endocrine - changes in spleen weight Endocrine - changes in thymus weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 9-18 day(s) after conception

TOXIC EFFECTS :

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) Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3 gm/kg

SEX/DURATION :

female 9-13 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 - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

640 mg/kg

SEX/DURATION :

female 5-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - delayed effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1280 mg/kg

SEX/DURATION :

female 5-20 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 :

1200 mg/kg

SEX/DURATION :

female 7-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

650 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 7 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1300 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 7 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

130 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 7 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1500 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

600 mg/kg

SEX/DURATION :

female 12-16 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 :

Oral

DOSE :

780 mg/kg

SEX/DURATION :

female 1 week(s) pre-mating female 1-17 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 - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

480 mg/kg

SEX/DURATION :

female 1 week(s) pre-mating female 1-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

189 mg/kg

SEX/DURATION :

female 8-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

263 mg/kg

SEX/DURATION :

female 11-13 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 :

75 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) 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 :

130 mg/kg

SEX/DURATION :

female 12-13 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 - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

165 mg/kg

SEX/DURATION :

female 8-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

50 mg/kg

SEX/DURATION :

female 12 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 :

Subcutaneous

DOSE :

150 mg/kg

SEX/DURATION :

female 11-13 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 - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

150 mg/kg

SEX/DURATION :

female 11-13 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 :

360 mg/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

200 mg/kg

SEX/DURATION :

female 11-14 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 :

Oral

DOSE :

26 mg/kg

SEX/DURATION :

female 10-22 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 :

900 mg/kg

SEX/DURATION :

female 7-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - gastrointestinal system Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

300 mg/kg

SEX/DURATION :

female 7-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

900 mg/kg

SEX/DURATION :

female 7-18 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 :

1200 mg/kg

SEX/DURATION :

female 7-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

Micronucleus test

MUTATION DATA

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TEST SYSTEM :

Rodent - mouse Embryo

DOSE/DURATION :

200 mg/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 187,91,1987 *** 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: 66,175,1996 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: 13,201,1977 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: 66,175,1996 IARC Cancer Review:Group 2B 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: 66,175,1996 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4463 No. of Facilities: 244 (estimated) No. of Industries: 3 No. of Occupations: 9 No. of Employees: 11866 (estimated) No. of Female Employees: 9470 (estimated)

生态数据：

该物质对环境可能有危害，对水体应给予特别注意。

中国海关编码：2933990090

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

摘要/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%

计算化学数据

1、   疏水参数计算参考值（XlogP）：

2、   氢键供体数量：1

3、   氢键受体数量：3

4、   可旋转化学键数量：2

5、   拓扑分子极性表面积（TPSA）：47.2

6、   重原子数量：20

7、   表面电荷：0

8、   复杂度：356

9、   同位素原子数量：0

10、   确定原子立构中心数量：0

11、   不确定原子立构中心数量：0

12、   确定化学键立构中心数量：0

13、   不确定化学键立构中心数量：0

14、   共价键单元数量：1

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  5
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  5-二苯基乙内酰脲钠盐红外图谱(IR1)