Crotaline

Names

[ CAS No. ]:
315-22-0

[ Name ]:
Crotaline

[Synonym ]:
Monocrotaline/crotaline
Monccrotalire
Bulbus Lilii
CROTALINE
(13a,14a)-14,19-Dihydro-12,13-dihydroxy-20-norcrotolanan-11,15-dione
Monocrotaline
2H-[1,6]Dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3H)-dione, 4,5,8,10,12,13,13a,13b-octahydro-4,5-dihydroxy-3,4,5-trimethyl-, (3R,4R,5R,13aR,13bR)-
(3R,4R,5R,13aR,13bR)-4,5-Dihydroxy-3,4,5-trimethyl-4,5,8,10,12,13,13a,13b-octahydro-2H-[1,6]dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3H)-dione
MONOCRATALINE
MFCD00084656
A 6080
MONOCROTALIN
CROTALIN
Crotaline,Monocrotaline

Biological Activity

[Description]:

Monocrotaline is an pyrrolizidine alkaloid extracted from the seeds of the Crotalaria spectabilis plant to induce pulmonary hypertension in rodents.

[Related Catalog]:

Signaling Pathways >> Others >> Others

Natural Products >> Others

Research Areas >> Metabolic Disease

[In Vitro]

Monocrotaline (MCT) is an 11-membered macrocyclic pyrrolizidine alkaloid (PA) derived from the seeds of the Crotalaria spectabilis plant[1]. Monocrotaline a natural ligand exhibits dose-dependent cytotoxicity with potent antineoplastic activity. The in vitro cytotoxicity of monocrotaline is proved at IC50 24.966 µg/mL and genotoxicity at 2 X IC50 against HepG2 cells[2].

[In Vivo]

MCT causes a pulmonary vascular syndrome in rats characterized by proliferative pulmonary vasculitis, pulmonary hypertension (PH), and cor pulmonale[3]. Among preclinical models of pulmonary arterial hypertension (PAH), monocrotaline animal model offers the advantage of mimic several key aspects of human PAH, including vascular remodeling, proliferation of smooth muscle cells, endothelial dysfunction, upregulation of inflammatory cytokines, and right ventricle failure, requiring a single drug injection[4]. Changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis are observed with the injection of monocrotaline[5].

[Animal admin]

Rats: A total of 20 male Sprague Dawley rats (SD; 220-270g) are used in this study (n=10 per group). Control group received vehicle for monocrotaline (MCT). Pre-pulmonary hypertension (PH) group received a single injection of MCT (60 mg/kg i.p.) to induce and are sacrificed after 14 days[5].

[References]

[1]. Gomez-Arroyo JG, et al. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol. 2012 Feb 15;302(4):L363-9.

[2]. Kusuma SS, et al. Antineoplastic activity of monocrotaline against hepatocellular carcinoma. Anticancer Agents Med Chem. 2014;14(9):1237-48.

[3]. Wilson DW, et, al. Mechanisms and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol. 1992;22(5-6):307-25.

[4]. Nogueira-Ferreira R, et al. Exploring the monocrotaline animal model for the study of pulmonary arterial hypertension: A network approach. Pulm Pharmacol Ther. 2015 Dec;35:8-16.

[5]. Rafikova O,et al. Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed RatLung. PLoS One. 2016 Mar 3;11(3):e0150480.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
537.3±50.0 °C at 760 mmHg

[ Melting Point ]:
204ºC (dec.)(lit.)

[ Molecular Formula ]:
C₁₆H₂₃NO₆

[ Molecular Weight ]:
325.357

[ Flash Point ]:
278.7±30.1 °C

[ Exact Mass ]:
325.152527

[ PSA ]:
96.30000

[ LogP ]:
-0.37

[ Vapour Pressure ]:
0.0±3.2 mmHg at 25°C

[ Index of Refraction ]:
1.586

[ Storage condition ]:
2~8°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QB3140000

CHEMICAL NAME :: Monocrotaline

CAS REGISTRY NUMBER :: 315-22-0

BEILSTEIN REFERENCE NO. :: 0048732

LAST UPDATED :: 199612

DATA ITEMS CITED :: 44

MOLECULAR FORMULA :: C16-H23-N-O6

MOLECULAR WEIGHT :: 325.40

WISWESSER LINE NOTATION :: T55 AN CUTJ FQ D1OV1- ET5OVTJ C1 D1 EQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 66 mg/kg

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

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 130 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Liver - other changes

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 60 mg/kg

TOXIC EFFECTS :: 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 :: 92 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 :: 60 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 :: 259 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 :: 261 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 :: Unreported

SPECIES OBSERVED :: Mammal - species unspecified

DOSE/DURATION :: 60 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 :: 61600 ug/kg/28D-C

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - changes in lung weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other oxidoreductases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18 mg/kg/10D-C

TOXIC EFFECTS :: Cardiac - changes in heart weight Lungs, Thorax, or Respiration - changes in lung weight 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 :: 75600 ug/kg/3W-C

TOXIC EFFECTS :: Vascular - BP elevation not characterized in autonomic section Lungs, Thorax, or Respiration - changes in lung weight Cardiac - changes in heart weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 288 mg/kg/48W-I

TOXIC EFFECTS :: Vascular - thrombosis distant from injection site Blood - hemorrhage Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1050 mg/kg/14D-I

TOXIC EFFECTS :: Liver - changes in liver weight Endocrine - changes in spleen weight Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 130 mg/kg/1Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Heritable translocation test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Mammal - species unspecified Leukocyte

DOSE/DURATION :: 25 umol/L

REFERENCE :: CYTBAI Cytobios. (Faculty Press, 88 Regent St., Cambridge, UK) V.1- 1969- Volume(issue)/page/year: 14,151,1975 *** 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: 10,291,1976 IARC Cancer Review:Human No Adequate Data 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: 10,291,1976 IARC Cancer Review:Group 2B IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987 TOXICOLOGY REVIEW FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 35,89,1976 TOXICOLOGY REVIEW CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 60,1171,1976

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H351

[ Precautionary Statements ]:
P281-P301 + P310

[ 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: Toxic;

[ Risk Phrases ]:
R25

[ Safety Phrases ]:
36/37/39-45

[ RIDADR ]:
UN 1544 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
QB3140000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
29399990

Precursor & DownStream

Precursor

DownStream

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