CAS 148-82-3|melphalan

Introduction：Basic information about CAS 148-82-3|melphalan, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. melphalan BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles161
8. Synonyms

Common Name	melphalan
CAS Number	148-82-3	Molecular Weight	305.200
Density	1.3±0.1 g/cm3	Boiling Point	473.1±45.0 °C at 760 mmHg
Molecular Formula	C₁₃H₁₈Cl₂N₂O₂	Melting Point	~180 °C
MSDS	ChineseUSA	Flash Point	239.9±28.7 °C
Symbol	GHS06, GHS08	Signal Word	Danger

Names

Name	melphalan
Synonym	More Synonyms

melphalan BiologicalActivity

Description	Melphalan is an effective DNA alkylating agent, with potent antitumor activity.
Related Catalog	Signaling Pathways >>Cell Cycle/DNA Damage >>DNA Alkylator/CrosslinkerResearch Areas >>Cancer
Target	DNA Alkylator/Crosslinker[1]
In Vitro	Melphalan is a DNA alkylating agent, used for multiple myeloma[1]. Melphalan-DNA adducts can be visualised in both cultured cells and solid tumour tissue[3].
In Vivo	Melphalan (12 mg/kg, i.p.) increases pharmacological activity with heat in SD rats[2].
Cell Assay	Melphalan cytotoxicity is determined by an MTT assay. The cells are seeded at 1000 cells per well in a 96-well microtitre plate in 100 μL culture medium to obtain approximately 4000 cells per well after 2 days at 37°C, 5% CO2. Then, the cells are washed and exposed to 0, 10, 25, 50, 100, 250 or 500 μM melphalan for 1 h at 37°C, 5% CO2. To control for cytotoxicity from hydrochloric acid, the solvent for melphalan, cells are also exposed to hydrochloric acid at a concentration adjusted to the highest concentration of melphalan (500 μM). After treatment the cells are washed twice with culture medium and 100 μL fresh culture medium is added. The day after exposure to melphalan another 100 μL fresh culture medium is added. After an additional 2 days the culture medium is removed and 200 μL fresh culture medium is added. At day 4 after treatment the culture medium is removed and cells are incubated for 4 h with 100 μL fresh culture medium and 10 μL MTT-labelling agent. Subsequently, 100 μL solubilisation solution (10% (v/v) in 0.01 M HCl) is added. After incubation overnight the absorbance at 590 nm is measured by a microtitre-plate reader[3].
Animal Admin	Rats[2] Twenty rats are randomized into two groups according to the intraperitoneal temperature. The normothermic (NT) group receives intraperitoneal chemotherapy with intraperitoneal temperatures maintained between 32.5 and 34.5°C, and the hyperthermic (HT) group receives intraperitoneal chemotherapy with intraperitoneal temperatures maintained between 41.5 and 42.5°C. Melphalan at a dose of 12 mg/kg is diluted in 150 mL 0.9% NaCl solution immediately before administration. A closed perfusion system is utilized. The perfusate is heated in a tube coil in a thermostatically regulated water bath and infused into the peritoneal cavity with a roller pump at a rate of 80 mL/min for 90 min. Rhythmic massage of the abdomen is used to facilitate uniform heat distribution within the peritoneal cavity. When the proper temperature for the experiment is reached inside the peritoneal cavity, melphalan is added to the perfusate in the reservoir. For each animal, 0.5 mL peritoneal fluid and 0.5 mL blood are collected at 5, 15, 30, 60, and 90 min after the initiation of chemotherapy. The venous catheter is flushed with 0.2 mL of heparinized saline after each blood sampling. At the end of the procedure the rats are killed and tissues samples are taken[2].
References	[1]. BLUMBERG BS, et al. AN ALKYLATING AGENT FOR MULTIPLE MYELOMA: MELPHALAN. JAMA. 1965 Feb 15;191:547-9. [2]. Glehen O, et al. Hyperthermia modifies pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rat model. Cancer Chemother Pharmacol. 2004 Jul;54(1):79-84. [3]. Rothbarth J, et al. Immunohistochemical detection of melphalan-DNA adducts in colon cancer cells in vitro and human colorectal liver tumours in vivo. Biochem Pharmacol. 2004 May 1;67(9):1771-8.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	473.1±45.0 °C at 760 mmHg
Melting Point	~180 °C
Molecular Formula	C₁₃H₁₈Cl₂N₂O₂
Molecular Weight	305.200
Flash Point	239.9±28.7 °C
Exact Mass	304.074524
PSA	66.56000
LogP	1.79
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.597
InChIKey	SGDBTWWWUNNDEQ-LBPRGKRZSA-N
SMILES	NC(Cc1ccc(N(CCCl)CCCl)cc1)C(=O)O
Storage condition	-20?C Freezer
Water Solubility	95% ethanol and 1 drop 6 N HCl: 0.05 g/mL, clear \| <0.1 g/100 mL at 22 ºC

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AY3675000

CHEMICAL NAME :: Alanine, 3-(p-(bis(2-chloroethyl)amino)phenyl)-, L-

CAS REGISTRY NUMBER :: 148-82-3

BEILSTEIN REFERENCE NO. :: 2816456

LAST UPDATED :: 199712

DATA ITEMS CITED :: 95

MOLECULAR FORMULA :: C13-H18-Cl2-N2-O2

MOLECULAR WEIGHT :: 305.23

WISWESSER LINE NOTATION :: QVYZ1R DN2G2G -L

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Rinsed with water

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rabbit

TYPE OF TEST :: Standard Draize test

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rabbit

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 700 mg/kg/7D

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 1200 ug/kg/5D-I

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 4500 mg/kg

TOXIC EFFECTS :: Behavioral - anorexia (human) Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 8140 mg/kg

TOXIC EFFECTS :: Behavioral - anorexia (human) Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - infant

DOSE/DURATION :: 28 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis Blood - thrombocytopenia

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 11200 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4484 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 :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4100 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 :: Intracerebral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 200 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD10 - Lethal Dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 32 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 :: 20800 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Blood - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Rodent - mouse

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 :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 29600 ug/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 :: 3 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14 mg/kg/7D-I

TOXIC EFFECTS :: Endocrine - changes in spleen weight Immunological Including Allergic - decrease in humoral immune response Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 80 ug/kg/D-C

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 57 ug/kg/D-C

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 26 mg/kg/2Y-C

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 70 mg/kg/26W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Tumorigenic - tumors at site of application

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 58 mg/kg/9W-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

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

TOXIC EFFECTS :: Tumorigenic - Carcinogenic 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 15 mg/kg/6W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 66 mg/kg/4Y-I

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 34 mg/kg/2Y-I

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 12 mg/kg/3Y-I

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 23 mg/kg/2Y-I

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 17 mg/kg/4Y-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3750 ug/kg

SEX/DURATION :: female 25 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 8800 ug/kg

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

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - other effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5946 ug/kg

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

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Unscheduled DNA synthesis

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Dominant lethal test

TYPE OF TEST :: Heritable translocation test

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 2500 nmol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 368,235,1996 *** REVIEWS *** IARC Cancer Review:Human Sufficient Evidence IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,239,1987 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: 9,167,1975 IARC Cancer Review:Group 1 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,239,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4742 No. of Facilities: 140 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 2418 (estimated) No. of Female Employees: 974 (estimated)

Safety Information

Symbol	GHS06, GHS08
Signal Word	Danger
Hazard Statements	H300-H310-H330-H350-H361
Precautionary Statements	P201-P260-P264-P280-P284-P302 + P350
Personal Protective Equipment	Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges
Hazard Codes	T+:Verytoxic;
Risk Phrases	R45;R46;R26/27/28;R63
Safety Phrases	S53-S22-S36/37/39-S45
RIDADR	UN 2811 6.1/PG 2
WGK Germany	3
RTECS	AY3675000
Packaging Group	II
Hazard Class	6.1(a)
HS Code	2922499990

Customs

HS Code	2922499990
Summary	HS:2922499990 other amino-acids, other than those containing more than one kind of oxygen function, and their esters; salts thereof VAT:17.0% Tax rebate rate:9.0% Supervision conditions:AB(certificate of inspection for goods inward,certificate of inspection for goods outward) MFN tariff:6.5% General tariff:30.0%

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Synonyms

4-[Bis(2-chloroethyl)amino]-L-phenylalanine

L-3-[p-[Bis(2-chloroethyl)amino]phenyl]alanine

melphalan

L-Phenylalanine, 4-(bis(2-chloroethyl)amino)-

2-Amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoic acid

MFCD00057717

Alanine, 3-(p-(bis(2-chloroethyl)amino)phenyl)-, L-

(2S)-2-amino-3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid

L-Phenylalanine, 4-[bis(2-chloroethyl)amino]-

Sarcoclorin

3025 C.B.

L-Phenylalanine mustard

EINECS 205-726-3

p-Di(2-chloroethyl)amino-L-phenylalanine

3-(4-bis(2-chloroethyl)aminophenyl)-L-alanine

3-[p-[Bis(2-chloroethyl)amino]phenyl]-L-alanine

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