L-Glutamicacid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]- cas no:59-05-2

NameL-Glutamicacid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-
CAS59-05-2
SynonymsGlutamicacid, N-[p-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-, L-(+)-(8CI);(+)-Amethopterin;Amethopterin;Amethopterine;Antifolan;CL 14377;EMT 25299;Emtexate;Emthexate PF;L-Amethopterin;L-Methotrexate;Ledertrexate;Metatrexan;Mexate;N-[p-[[2,4-Diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-(+)-glutamicacid;NSC 740;R 9985;Rheumatrex;Trexall;
EINECS(EC#)200-413-8
Molecular FormulaC₂₀H₂₂N₈O₅
Molecular Weight454.44

Appearanceyellow crystalline powder
storage temp?20°C

Hazardclass6.1(b)

Hazard T:Toxic
Risk R61;R25;R36/38
Safety

A human poison by intraspinal route. Poison experimentally by ingestion, intravenous, subcutaneous, and intraperitoneal routes. Human teratogenic effects by ingestion: developmental abnormalities of the craniofacial area and the musculoskeletal system. Human systemic effects by multiple routes: thrombocytopenia (decrease in the number of blood platelets), bone marrow changes, other blood changes, cerebral spinal fluid effects, eye effects, blood pressure lowering, cough, dyspnea, fibrosis (pneumoconiosis), cyanosis, gastrointestinal effects, fatty liver degeneration, hepatitis, impairment of liver function tests, other liver changes, fever, effects on inflammation or mediation of inflammation, leukopenia. Human mutation data reported. Experimental reproductive effects. A human eye irritant. Questionable human carcinogen producing leukemia, Hodgkin's disease, and skin tumors. An FDA proprietary drug. A chemotherapeutic agent. When heated to decomposition it emits toxic fumes including NOx.
Hazard Codes:?T
Risk Statements: 61-25-36/38-46?
R61: May cause harm to the unborn child.?
R25: Toxic if swallowed.?
R36/38: Irritating to eyes and skin.?
R46: May cause heritable genetic damage.
Safety Statements: 53-26-36/37-45-36/37/39
S53: Avoid exposure - obtain special instructions before use.?
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.?
S36/37: Wear suitable protective clothing and gloves.?
S45: In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)?
S36/37/39: Wear suitable protective clothing, gloves and eye/face protection.
RIDADR: UN 2811 6.1/PG 3
WGK Germany: 3
RTECS: MA1225000
F: 3-8-10
HazardClass: 6.1(b)
PackingGroup: III

HS Code 29335995

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
child	TDLo	intravenous	100mg/kg/4H (100mg/kg)	BLOOD: THROMBOCYTOPENIA BLOOD: OTHER CHANGES	Cancer Vol. 33, Pg. 1151, 1974.
child	TDLo	oral	2mg/kg/12D (2mg/kg)	LUNGS, THORAX, OR RESPIRATION: COUGH LUNGS, THORAX, OR RESPIRATION: DYSPNEA	JAMA, Journal of the American Medical Association. Vol. 209, Pg. 1861, 1969.
human	TDLo	intramuscular	35mg/kg/28W (35mg/kg)	VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION LUNGS, THORAX, OR RESPIRATION: DYSPNEA LUNGS, THORAX, OR RESPIRATION: CYANOSIS	British Medical Journal. Vol. 2, Pg. 156, 1970.
human	TDLo	intramuscular	200mg/kg/5Y (200mg/kg)	LIVER: "HEPATITIS, FIBROUS (CIRRHOSIS, POST-NECROTIC SCARRING)"	Archives of Dermatology. Vol. 100, Pg. 531, 1969.
human	TDLo	intravenous	4650ug/kg/4W- (4.65mg/kg)	LIVER: FATTY LIVER DEGERATION LIVER: LIVER FUNCTION TESTS IMPAIRED	Proceedings of the American Association for Cancer Research. Vol. 5, Pg. 26, 1964.
human	TDLo	intravenous	7143ug/kg (7.143mg/kg)	GASTROINTESTINAL: NAUSEA OR VOMITING BLOOD: CHANGES IN PLATELET COUNT BLOOD: CHANGES IN LEUCOCYTE (WBC) COUNT	Zhongguo Yaoxue Zazhi. Chinese Pharmacuetical Journal. Vol. 27, Pg. 673, 1992.
human	TDLo	oral	43mg/kg/5Y (43mg/kg)	LIVER: LIVER FUNCTION TESTS IMPAIRED LIVER: OTHER CHANGES	Archives of Dermatology. Vol. 100, Pg. 523, 1969.
man	TDLo	intramuscular	214ug/kg/12D- (0.214mg/kg)	SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE"	Clinical and Experimental Rheumatology. Vol. 14, Pg. 450, 1996.
man	TDLo	intravenous	740mg/kg (740mg/kg)	GASTROINTESTINAL: OTHER CHANGES	Archives of Internal Medicine. Vol. 136, Pg. 1321, 1976.
man	TDLo	oral	643ug/kg/6W-I (0.643mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Journal of Rheumatology. Vol. 14, Pg. 74, 1987.
man	TDLo	oral	4286ug/kg/2.7 (4.286mg/kg)	LUNGS, THORAX, OR RESPIRATION: "FIBROSIS, FOCAL (PNEUMOCONIOSIS)" LUNGS, THORAX, OR RESPIRATION: RESPIRATORY OBSTRUCTION BLOOD: APLASTIC ANEMIA	Clinical Rheumatology. Vol. 12, Pg. 535, 1993.
mouse	LD50	intraperitoneal	50mg/kg (50mg/kg)	?	Anatomical Record. Vol. 178, Pg. 465, 1974.
mouse	LD50	intravenous	65mg/kg (65mg/kg)	?	Drugs in Japan Vol. 6, Pg. 841, 1982.
mouse	LD50	oral	146mg/kg (146mg/kg)	?	Drugs in Japan Vol. 6, Pg. 841, 1982.
mouse	LD50	subcutaneous	250mg/kg (250mg/kg)	?	National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. Vol. JAN1986,
mouse	LD50	unreported	69mg/kg (69mg/kg)	?	Cancer Research. Vol. 46, Pg. 2703, 1986. Link to PubMed
rat	LD50	intraperitoneal	6mg/kg (6mg/kg)	?	Drugs in Japan Vol. 6, Pg. 841, 1982.
rat	LD50	intravenous	14mg/kg (14mg/kg)	?	Arzneimittel-Forschung. Drug Research. Vol. 20, Pg. 1467, 1970. Link to PubMed
rat	LD50	oral	135mg/kg (135mg/kg)	?	Drugs in Japan Vol. 6, Pg. 841, 1982.
rat	LD50	subcutaneous	58mg/kg (58mg/kg)	?	Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 23, Pg. 93, 1992.
rat	LD50	unreported	133ug/kg (0.133mg/kg)	?	United States Patent Document. Vol. #4746662,
women	LDLo	intraspinal	36mg/kg/15D (36mg/kg)	SPINAL CORD: OTHER DEGENERATIVE CHANGES GASTROINTESTINAL: NAUSEA OR VOMITING	New England Journal of Medicine. Vol. 289, Pg. 770, 1973.
women	TDLo	oral	800ug/kg/4D-I (0.8mg/kg)	BLOOD: LEUKOPENIA BLOOD: THROMBOCYTOPENIA BLOOD: OXIDANT RELATED (GPD DEFICIENT) ANEMIA	Medical Journal of Australia. Vol. 155, Pg. 493, 1991.
women	TDLo	oral	2mg/kg/17W-I (2mg/kg)	LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES BLOOD: LEUKOPENIA	Journal of Rheumatology. Vol. 14, Pg. 74, 1987.
women	TDLo	parenteral	2600ug/kg (2.6mg/kg)	BRAIN AND COVERINGS: CHANGES IN CEREBRAL SPINAL FLUID LUNGS, THORAX, OR RESPIRATION: "FIBROSIS, FOCAL (PNEUMOCONIOSIS)" LUNGS, THORAX, OR RESPIRATION: DYSPNEA	Cancer Vol. 38, Pg. 1529, 1976.
women	TDLo	unreported	11400ug/kg/44 (11.4mg/kg)	LUNGS, THORAX, OR RESPIRATION: "FIBROSIS, FOCAL (PNEUMOCONIOSIS)"	Clinical and Experimental Rheumatology. Vol. 15, Pg. 583, 1997.
women	TDLo	unreported	150mg/kg (150mg/kg)	SENSE ORGANS AND SPECIAL SENSES: OTHER: EYE	Cancer Vol. 48, Pg. 2158, 1981.