CAS 480-54-6|isatidine

Introduction：Basic information about CAS 480-54-6|isatidine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. isatidine BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Articles28
7. Synonyms

Common Name	isatidine
CAS Number	480-54-6	Molecular Weight	351.394
Density	1.3±0.1 g/cm3	Boiling Point	583.2±50.0 °C at 760 mmHg
Molecular Formula	C₁₈H₂₅NO₆	Melting Point	208-211ºC(lit.)
MSDS	ChineseUSA	Flash Point	306.5±30.1 °C
Symbol	GHS06	Signal Word	Danger

Names

Name	retrorsine
Synonym	More Synonyms

isatidine BiologicalActivity

Description	Retrorsine is a naturally occurring toxic pyrrolizidine alkaloid. Retrorsine can bind with DNA and inhibits the proliferative capacity of hepatocytes[1][2].
Related Catalog	Research Areas >>OthersSignaling Pathways >>Others >>Others
In Vitro	Retrorsine (60-240 μM; 24 hours) significantly reduces HSEC-CYP3A4 cells viability, depletes GSH, and increases formation of pyrrole-protein adducts[3]. Cell Viability Assay[3] Cell Line: HSEC-CYP3A4 cells Concentration: 60 μM, 120 μM , 240 μM Incubation Time: 24 hours Result: Significantly decreased cell viability.
In Vivo	Retrorsine (30 mg/kg; i.p.; twice) impairs liver regeneration in the PBL model not only by an S or G2/M phase block, but also by a block located before the G1/S transition of the cell cycle[1]. Animal Model: Male Wistar rats (180±20 g), portal branch ligation (PBL) model[1] Dosage: 30 mg/kg Administration: Intraperitoneal injection, twice, separated by 2-week interval Result: Strongly impaired the liver weight gain, protein and DNA synthesis as well as induction of cell cycle related proteins in the regenerating lobes after PBL.
References	[1]. F J Cubero, et al. Hepatic proliferation in Gunn rats transplanted with hepatocytes: effect of retrorsine and tri-iodothyronine. Cell Prolif. 2005 Jun;38(3):137-46. [2]. F J Cubero, et al. Hepatic proliferation in Gunn rats transplanted with hepatocytes: effect of retrorsine and tri-iodothyronine. Cell Prolif. 2005 Jun;38(3):137-46. [3]. Yao Lu, et al. Establishment of a novel CYP3A4-transduced human hepatic sinusoidal endothelial cell model and its application in screening hepatotoxicity of pyrrolizidine alkaloids. J Environ Sci Health C Toxicol Carcinog. 2020;38(2):169-185.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	583.2±50.0 °C at 760 mmHg
Melting Point	208-211ºC(lit.)
Molecular Formula	C₁₈H₂₅NO₆
Molecular Weight	351.394
Flash Point	306.5±30.1 °C
Exact Mass	351.168182
PSA	96.30000
LogP	-0.14
Vapour Pressure	0.0±3.7 mmHg at 25°C
Index of Refraction	1.590
InChIKey	BCJMNZRQJAVDLD-CQRYIUNCSA-N
SMILES	CC=C1CC(C)C(O)(CO)C(=O)OCC2=CCN3CCC(OC1=O)C23

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VH7525000

CHEMICAL NAME :: Retrorsine

CAS REGISTRY NUMBER :: 480-54-6

LAST UPDATED :: 199512

DATA ITEMS CITED :: 22

MOLECULAR FORMULA :: C18-H25-N-O6

MOLECULAR WEIGHT :: 351.44

WISWESSER LINE NOTATION :: T55-12- 1A Q EN IOVY OVO BUTJ KU2 M1 NQ N1Q

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 :: 34 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 :: 34 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Liver - other changes 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 :: 38 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Liver - hepatitis (hepatocellular necrosis), diffuse Blood - lymphoma, including Hodgkin's disease

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

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 35 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 :: 65 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 :: 59 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Liver - hepatitis (hepatocellular necrosis), diffuse Blood - lymphoma, including Hodgkin's disease

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 46 mg/kg

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), zonal Liver - other changes Blood - macrocytosis

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - species unspecified

DOSE/DURATION :: 33 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 175 mg/kg/5D-I

TOXIC EFFECTS :: Liver - other changes Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 560 mg/kg/62W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Liver - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 150 mg/kg/22W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 68 mg/kg/43W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors Kidney, Ureter, Bladder - Kidney tumors

TYPE OF TEST :: Sex chromosome loss and nondisjunction

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Rodent - hamster Lung

DOSE/DURATION :: 3160 nmol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 282,169,1992 *** REVIEWS *** IARC Cancer Review:Animal 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: 10,303,1976 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: 10,303,1976 IARC Cancer Review:Group 3 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 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
Signal Word	Danger
Hazard Statements	H300
Precautionary Statements	P264-P301 + P310
Personal Protective Equipment	Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges
Hazard Codes	T
Risk Phrases	25
Safety Phrases	S22;S45;S36/S37/S39
RIDADR	UN 1544
RTECS	VH7525000
Packaging Group	II
Hazard Class	6.1(a)

Articles28

Diversity of pyrrolizidine alkaloids in native and invasive Senecio pterophorus (Asteraceae): implications for toxicity.

Phytochemistry 108 , 137-46, (2014)

Changes in plant chemical defenses after invasion could have consequences on the invaded ecosystems by modifying the interactions between plants and herbivores and facilitating invasion success. Howev...

Involvement of organic cation transporter 1 and CYP3A4 in retrorsine-induced toxicity.

Toxicology 322 , 34-42, (2014)

Retrorsine (RTS) is a hepatotoxic pyrrolizidine alkaloid present in plants of the Senecio genus. The present study is aimed at clarifying the role of organic cation transporters (OCTs) in the liver di...

Are effects of common ragwort in the Ames test caused by pyrrolizidine alkaloids?

Mutat. Res. 778 , 1-10, (2015)

It has previously been demonstrated by others that acetone extracts of Senecio jacobaea (syn. Jacobaea vulgaris, common or tansy ragwort) test positive in the Salmonella/microsome mutagenicity test (A...

Synonyms

(15Z)-12,18-Dihydroxysenecionan-11,16-dione

[1,6]Dioxacyclododecino[2,3,4-gh]pyrrolizine-2,7-dione, 3-ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6-(hydroxymethyl)-5-methyl-, (3Z,5R,6S,14aR,14bR)-

isatidine

trans-15-Ethylidene-12b-hydroxy-12a-hydroxymethyl-13b-methylsenec-1-enine

b-Longilobine

12,18-dihydroxy-senecionane-11,16-dione

12,18-Dihydroxysenecionan-11,16-dione

β-Longilobine

cis-Retronecic acid ester of retronecine

Retrorsin

(3Z,5R,6S,14aR,14bR)-3-Ethylidene-6-hydroxy-6-(hydroxymethyl)-5-methyl-3,4,5,6,9,11,13,14,14a,14b-decahydro[1,6]dioxacyclododecino[2,3,4-gh]pyrrolizine-2,7-dione

MFCD00013331

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