Lasiocarpine

Lasiocarpine, a hepatotoxic pyrrolizidine alkaloid (PA), causes fatal liver veno-occlusive disease in vivo. Lasiocarpine is toxic only after its metabolic conversion to the toxic intermediate, including dehydrolasiocarpine and N-oxide[1].

Research Areas >> Cancer

Lasiocarpine is toxic only after its metabolic conversion to the toxic intermediate, known as dehydrolasiocarpine[1]. Dehydrolasiocarpine and other putative didehydropyrrolizidine alkaloids (the pyrrolic esters) are very reactive,they attack nucleophilic macromolecules such as DNA and proteins, eliciting severe toxicities, including liver veno-occlusive disease and tumors[1]. Lasiocarpine is mainly metabolized in vitro through five metabolic pathways, dehydrogenation, ester bond cleavage, demethylation[1].

[1]. Muluneh M Fashe, et al. Species-Specific Differences in the in Vitro Metabolism of Lasiocarpine. Chem Res Toxicol. 2015 Oct 19;28(10):2034-44.

MOLECULAR FORMULA :

C21-H33-N-O7

MOLECULAR WEIGHT :

411.55

WISWESSER LINE NOTATION :

T55 AN CUTJ D1OVXQXQ1&1&Y1&O1 FOVY1&U2

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 :

110 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 :

78 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 - rat

DOSE/DURATION :

88 mg/kg

TOXIC EFFECTS :

Liver - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

80 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 :

72 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 :

85 mg/kg

TOXIC EFFECTS :

Liver - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Liver - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold 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 - hamster

DOSE/DURATION :

67500 ug/kg

TOXIC EFFECTS :

Liver - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

255 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Liver - angiosarcoma

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

470 mg/kg/56W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

546 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Liver - angiosarcoma

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1310 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Liver - angiosarcoma

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

760 mg/kg/48W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Skin and Appendages - tumors

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Heritable translocation test

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Mutation test systems - not otherwise specified

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: 10,281,1976 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: 10,281,1976 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 CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 60,1171,1976