Carmustine

Modify Date: 2024-01-02 13:27:02

Carmustine Structure
Carmustine structure
Common Name Carmustine
CAS Number 154-93-8 Molecular Weight 214.050
Density 1.5±0.1 g/cm3 Boiling Point 404ºC
Molecular Formula C5H9Cl2N3O2 Melting Point 30 °C(lit.)
MSDS USA Flash Point N/A
Symbol GHS06 GHS08
GHS06, GHS08
Signal Word Danger

 Use of Carmustine


Carmustine is an antitumor chemotherapeutic agent, which works by akylating DNA and RNA.

 Names

Name carmustine
Synonym More Synonyms

 Carmustine Biological Activity

Description Carmustine is an antitumor chemotherapeutic agent, which works by akylating DNA and RNA.
Related Catalog
Target

DNA Alkylator[1]

In Vitro Carmustine is an antitumor chemotherapeutic agent. Carmustine (8, 80, and 800 µM) decreases N-acetyltransferase (NAT) activities for 2-aminofluorene (AF) and p-aminobenzoic acid (PABA) in rat glial tumor cytosol and intact cells. In rat glial tumor cells, the DNA-AF adduct increases, and carmustine decreases the formation of DNA-AF adduct[1].
In Vivo Carmustine (BCNU; 25 mg/kg, i.p.) causes higher levels of the rhe ratio of liver weight to body weight and plasma conjugated bilirubin, and lower biliary flow, oxidised glutation levels (GSSG) and reduced glutation (GSH)/GSSG values compared with control rats[2].
Kinase Assay The determination of Acetyl-CoAdependent N-acetylation of 2-aminofluorene (AF) and p-aminobenzoic acid (PABA) are performed. Incubation mixtures in the assay system consists of a total volume of 90 μL: glial tumor cells cytosols, diluted as required, in 50 μL of lysis buffer (20 mM Tris/HCl, pH 7.5, 1 mM DTT and 1 mM EDTA), 20 μL of an Acetyl-CoA recycling mixture of 50 mM Tris-HCl (pH7.5), 0.2 mM EDTA, 2 mM DTT, 15 mM acetylcamitine, 2U/mL carnitine acetyltransferase, and AF or PABA at specific concentrations. The reactions are started by addition of 20 μL of Acetyl-CoA. The control reactions have 20 μL distilled water in place of Acetyl-CoA. For the single point activity measurements, the final concentration of AF or PABA is 0.1 mM and AcCoA is 0.5 mM. The reaction mixtures with or without specific concentrations of Carmustine and lomustine are incubated at 37°C for 10 min and stopped with 50 μL of 20% trichloroacetic acid for the PABA reactions, and 100 μL of acetonitrile for the AF reactions. All of the reactions (experiments and controls) are run in triplicate[1].
Animal Admin Rats[2] Individual rats are weighted prior to enter the study; their weights are recorded, and they are randomLy assigned to four groups. Group I (saline group); This group consists of 12 rats. These rats are injected with 2 mL/kg of saline intraperitoneally (IP) 48 h before the study, being included by the study 48 h later. Group II (corn oil group) consists of 15 rats. These rats are injected with 2 mL/kg of corn oil (vehicle) IP 48 h before the study. Group III (Carmustine group) consists of 16 rats. These rats are injected with 1 mL per day of saline IP, administered at the same hour of the day as a single-dose for 3 days. Twelve hours after the first dose of saline, corn oil 2 mL/kg + Carmustine 25 mg/kg IP are injected, and the rats are included in the study 48 h after the administration of corn oil + Carmustine. Group IV (trimetazidine group) consists of 12 rats. These rats are injected with 2.5 mg/kg per day of trimetazidine (TMZ) IP, administered at the same hour of the day as a single-dose for 3 days. 12 h after the first dose of TMZ, corn oil 2 mL/kg + Carmustine 25 mg/kg IP are injected, and the rats are included in the study 48 h after the administration of corn oil + Carmustine[2].
References

[1]. Hung CF. Effects of carmustine and lomustine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in rat glial tumor cells. Neurochem Res. 2000 Jun;25(6):845-51.

[2]. Demir A, et al. The effect of trimetazidine on intrahepatic cholestasis caused by carmustine in rats. Hepatol Res. 2001 May 1;20(1):133-143.

 Chemical & Physical Properties

Density 1.5±0.1 g/cm3
Boiling Point 404ºC
Melting Point 30 °C(lit.)
Molecular Formula C5H9Cl2N3O2
Molecular Weight 214.050
Exact Mass 213.007187
PSA 61.77000
LogP 1.30
Index of Refraction 1.549
Water Solubility <0.1 g/100 mL at 18 ºC

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
YS2625000
CHEMICAL NAME :
Urea, 1,3-bis(2-chloroethyl)-1-nitroso-
CAS REGISTRY NUMBER :
154-93-8
LAST UPDATED :
199612
DATA ITEMS CITED :
98
MOLECULAR FORMULA :
C5-H9-Cl2-N3-O2
MOLECULAR WEIGHT :
214.07
WISWESSER LINE NOTATION :
ONN2GVM2G

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Human - child
DOSE/DURATION :
78 mg/kg/52W-I
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - other changes Gastrointestinal - nausea or vomiting Blood - changes in bone marrow (not otherwise specified)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Human
DOSE/DURATION :
125 mg/kg
TOXIC EFFECTS :
Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Human
DOSE/DURATION :
6 mg/kg
TOXIC EFFECTS :
Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Parenteral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
1566 mg/kg
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - fibrosis (interstitial) 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 - rat
DOSE/DURATION :
20 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 :
17420 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 :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
83200 ug/kg
TOXIC EFFECTS :
Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
13800 ug/kg
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - chronic pulmonary edema Gastrointestinal - ulceration or bleeding from stomach Blood - changes in bone marrow (not otherwise specified)
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
79600 ug/kg
TOXIC EFFECTS :
Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
19 mg/kg
TOXIC EFFECTS :
Gastrointestinal - hypermotility, diarrhea Liver - jaundice, other or unclassified Kidney, Ureter, Bladder - urine volume increased
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
21260 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 :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
24 mg/kg
TOXIC EFFECTS :
Gastrointestinal - hypermotility, diarrhea Liver - jaundice, other or unclassified Kidney, Ureter, Bladder - urine volume increased
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
45 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 :
Intramuscular
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
86300 ug/kg
TOXIC EFFECTS :
Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Unreported
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
42 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 :
Oral
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
5 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 :
2 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 :
Primate - monkey
DOSE/DURATION :
10 mg/kg
TOXIC EFFECTS :
Gastrointestinal - other changes Blood - leukopenia Blood - other changes
TYPE OF TEST :
LD10 - Lethal Dose
ROUTE OF EXPOSURE :
Parenteral
SPECIES OBSERVED :
Rodent - hamster
DOSE/DURATION :
18 mg/kg
TOXIC EFFECTS :
Tumorigenic - active as anti-cancer agent
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
15 mg/kg/7W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
16 mg/kg/60W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Administration onto the skin
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
276 mg/kg/23W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Skin and Appendages - hair Skin and Appendages - tumors
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
98 mg/kg/26W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors
TYPE OF TEST :
TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
26 mg/kg/60W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors
TYPE OF TEST :
TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
45 mg/kg/60W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors
TYPE OF TEST :
TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
51 mg/kg/24W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Gastrointestinal - tumors
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
8 mg/kg
SEX/DURATION :
female 6-9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
8 mg/kg
SEX/DURATION :
female 6-9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
9 mg/kg
SEX/DURATION :
male 9 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) 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 :
4 mg/kg
SEX/DURATION :
female 6-9 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 :
11 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 :
40 mg/kg
SEX/DURATION :
female 12 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 :
Intravenous
DOSE :
6500 ug/kg
SEX/DURATION :
female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
TYPE OF TEST :
Sex chromosome loss and nondisjunction
TYPE OF TEST :
DNA damage
TYPE OF TEST :
Micronucleus test
TYPE OF TEST :
DNA damage
TYPE OF TEST :
DNA inhibition
TYPE OF TEST :
Cytogenetic analysis
TYPE OF TEST :
Sister chromatid exchange
TYPE OF TEST :
Sister chromatid exchange
TYPE OF TEST :
Sperm Morphology
TYPE OF TEST :
DNA inhibition

MUTATION DATA

TYPE OF TEST :
DNA damage
TEST SYSTEM :
Mammal - species unspecified Lymphocyte
DOSE/DURATION :
10 mmol/L
REFERENCE :
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 44,1887,1984 *** 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: 26,79,1981 IARC Cancer Review:Human Limited 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: 26,79,1981 IARC Cancer Review:Group 2A IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,150,1987 TOXICOLOGY REVIEW NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB282-265 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3594 No. of Facilities: 373 (estimated) No. of Industries: 1 No. of Occupations: 7 No. of Employees: 14122 (estimated) No. of Female Employees: 10338 (estimated)

 Safety Information

Symbol GHS06 GHS08
GHS06, GHS08
Signal Word Danger
Hazard Statements H300-H350-H360
Precautionary Statements P201-P264-P301 + P310-P308 + P313
Personal Protective Equipment 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
Hazard Codes T+:Verytoxic;
Risk Phrases R45;R46;R60;R61;R28
Safety Phrases S53-S22-S36/37/39-S45
RIDADR 3249
WGK Germany 3
RTECS YS2625000
Packaging Group II
Hazard Class 6.1(a)
HS Code 2924199090

 Customs

HS Code 2924199090
Summary 2924199090. other acyclic amides (including acyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

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 Synonyms

1,3-bis(2-Chlorethyl)-1-nitrosourea
Bicnu
Becenun
Carmustine
BCNU
EINECS 205-838-2
Urea, N,N'-bis(2-chloroethyl)-N-nitroso-
MFCD00057706
1,3-Bis(2-chloroethyl)-1-nitrosourea
Carustine
1,3-Bis(2-chloroethyl)-1-nitrosourea BCNU
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