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Toxicity Effects

CAS Registry Number: 303-34-4

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 7-((2,3-Dihydroxy-2-(1-Methoxyethyl)-3-Methyl-1-Oxobutoxy)Methyl)-2-Butanoic Acid (9ci)

Human Toxicity Excerpts

  • ... LASIOCARPINE IS THE MAIN TOXIC ALKALOID OF HELIOTROPIUM LASIOCARPUM, REPORTS OF TOXICITY IN HUMANS DUE TO CONSUMPTION OF BREAD MADE FROM WHEAT, BARLEY OR MILLET CONTAMINATED WITH THE SEEDS OF THIS PLANT ARE RELEVANT. EPIDEMICS IN USSR AFFECTED GROUPS OF AGRICULTURAL WORKERS & THEIR FAMILIES IN SPECIFIC REGIONS ... .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 286 (1976)] **PEER REVIEWED**
  • ... SIGNS OF HELIOTROPE TOXICOSIS WERE HEPATOMEGALY, ASCITES & DISTURBANCES OF HEPATIC FUNCTION; HEPATOMEGALY OCCURRED IN ALL CASES, ASCITES IN 85% & JAUNDICE IN 2-3%. RECOVERY WAS COMPLETE IN 60% OF CASES ... WITH SLIGHT RESIDUAL HEPATOMEGALY IN 35%; IN 3% HEPATOMEGALY PERSISTED; & RECURRENT ASCITES WERE SEEN IN 2%.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 286 (1976)] **PEER REVIEWED**
  • AFTER TREATMENT WITH LASIOCARPINE, CULTURED HUMAN EMBRYO LIVER CELLS SHOWED MORPHOLOGICAL ALTERATIONS INDICATIVE OF: (1) NUCLEAR & NUCLEOLAR CHANGES, PROBABLY RELATED TO THE ALKYLATION OF DNA & ENSUING INHIBITION OF NUCLEIC ACID & PROTEIN SYNTHESIS; (2) INDUCTION OF POSSIBLE CHROMOSOMAL DAMAGE & MUTATION; (3) GENERALIZED REDUCTION OF THE METABOLIC ACTIVITY OF THE CELLS DUE TO MEMBRANE & MITOCHONDRIAL DAMAGE, & TO ALKYLATION & INACTIVATION OF CELL ENZYMES & PROTEINS; & (4) LONG-TERM INHIBITION OF MITOSIS LEADING TO FORMATION OF GIANT CELLS.[ARMSTRONG SJ, ZUCKERMAN AJ; BRIT J EXP PATHOL 53 (2): 145 (1972)] **PEER REVIEWED**
  • Consumption of bread contaminated by Heliotropium seeds caused an outbreak of hepatic veno-occlusive disease in Afghanistan which was twice as prevalent in males as females. ... The principal toxic alkaloids of Heliotropium are heliotrine and lasiocarpine; their N-oxides are even more potent. Drying and heating does not affect their toxicity.[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1295] **PEER REVIEWED**
  • IN CENTRAL ASIAN REPUBLICS OF USSR, CONTAMINATION OF CEREAL GRAIN FOR HUMAN CONSUMPTION BY SEEDS OF HELIOTROPIUM LASIOCARPUM OCCURRED AT LEAST UNTIL 1946. AT THAT TIME THE SEEDS WERE SHOWN TO BE THE CAUSE OF A DISEASE THEN KNOWN AS 'TOXIC HEPATITIS WITH ASCITES' BUT RE-NAMED 'HELIOTROPIC DYSTROPHY OF THE LIVER'.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 283 (1976)] **PEER REVIEWED**
  • Large acute doses over a number of days produce occlusion of hepatic venules and the clinical picture of Reye's syndrome characterized by vomiting, progressive hyperpnea, and encephalopathy. In pyrrolizidine poisoning, however, jaundice, ascites, hepatomegaly, hypoglycemia, and massive elevations of serum hepatic aminotransferase levels are much more prominent. In epidemic settings, the symptoms are more insidious and begin with anorexia, lassitude, and weight loss. Subsequently, ascites, edema, emaciation, firm hepatomegaly, and splenomegaly develop. Fever, jaundice, and bleeding are uncommon in this form. Prolonged pyrrolizidine alkaloid consumption also can cause pulmonary artery hypertension, leading to cor pulmonale and right ventricular hypertrophy.[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1295] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ... HIGH DOSES CAUSE RAPID DEATH /IN GUINEA-PIGS & MONKEYS/ WITHIN FEW HR, OFTEN WITH CONVULSIONS ... LOWER DOSES ... PRODUCE SEVERE HEMORRHAGIC NECROSIS OF LIVER, GI HEMORRHAGE ... CONGESTION & EDEMA OF LUNGS, CONGESTION OF ADRENALS & ... PYLORIC, DUODENAL & RECTAL ULCERATION. LEUCOCYTOSIS & ... HYPOPROTHROMBINEMIA ALSO OCCUR.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 284 (1976)] **PEER REVIEWED**
  • 25 INBRED MALE FISCHER 344 RATS WERE GIVEN IP INJECTIONS OF 7.8 MG/KG BODY WT OF LASIOCARPINE TWICE WEEKLY FOR 4 WK THEN ONCE/WK FOR 52 WK, WHEREUPON INJECTIONS WERE DISCONTINUED. 18 SURVIVED THE TIME OF THE APPEARANCE OF THE FIRST TUMOR (56 WEEKS), AND 16 DEVELOPED TUMORS 60 TO 76 WK AFTER THE BEGINNING OF THE EXPERIMENT. 10 RATS DEVELOPED HEPATOCELLULAR CARCINOMAS, 6 DEVELOPED WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMAS OF THE SKIN OF THE BACK, 5 DEVELOPED PULMONARY ADENOMAS, 2 DEVELOPED WELL DIFFERENTIATED ADENOCARCINOMAS OF THE SMALL INTESTINE, 1 DEVELOPED A CHOLANGIOCARCINOMA, 1 AND ADENOMYOMA OF THE ILEUM AND 1 AN INTERSTITIAL CELL TUMOR OF THE TESTES.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 283 (1976)] **PEER REVIEWED**
  • A BIOASSAY OF LASIOCARPINE FOR POSSIBLE CARCINOGENICITY WAS CONDUCTED BY ADMIN THE TEST CHEM IN THE DIET TO FISCHER 344 RATS. GROUPS OF 24 RATS OF EACH SEX WERE ADMIN LASIOCARPINE AT 7, 15, OR 30 PPM, FOR 104 WK. MATCHED CONTROLS CONSISTED OF GROUPS OF 24 UNTREATED RATS OF EACH SEX. THERE WAS A POS DOSE RELATED TREND IN THE INCIDENCE OF ANGIOSARCOMA OF THE LIVER. METASTATIC ANGIOSARCOMAS WERE PRESENT IN THE LUNGS FROM A FEW RATS IN ALL 3 TREATED GROUPS OF BOTH SEXES. THUS, UNDER THE CONDITIONS OF THIS BIOASSAY LASIOCARPINE WAS CARCINOGENIC FOR LIVER OF FISCHER 344 RATS.[DHEW/NCI; BIOASSAY OF LASIOCARPINE FOR POSSIBLE CARCINOGENICITY p.vii (1978) TECHNICAL RPT SERIES NO. 039 DHEW PUB NO. (NIH) 78-839] **PEER REVIEWED**
  • A SINGLE DOSE OF 80 MG OF LASIOCARPINE PER KG GIVEN TO WEANLING RATS, SPRAGUE-DAWLEY & WISTAR, 22 DAYS OLD VIA STOMACH TUBE PRODUCED A DELAYED PROGRESSIVE FORM OF SUBACUTE OR CHRONIC HEPATITIS CHARACTERIZED BY STRIKING ENLARGEMENT OF THE PARENCHYMAL CELLS, FOCAL NECROSIS, INFLAMMATION, NODULAR HYPERPLASIA, DUCTULAR PROLIFERATION, & FIBROSIS. 4 WK OLD RATS GIVEN 120 MG OF LASIOCARPINE PER KG EXHIBITED MEGALOCYTES BUT FAILED TO SHOW ANY OF THE OTHER FEATURES OF THE DELAYED LESION.[NOLAN JP ET AL; AM J PATHOL 49 (1): 129 (1966)] **PEER REVIEWED** PubMed Abstract Full text: PMC1916461
  • ADMIN INTRAGASTRICALLY TO PREGNANT RATS MAINTAINED ON CONTROL & ON LIPOTROPE-DEFICIENT DIETS DURING GESTATION. EFFECTS OF THE TOXIN ON THE MATERNAL LIVER WERE NOTED AS WELL AS THE TRANSPLACENTAL EFFECTS ON THE NEWBORN RAT AT BIRTH & SEVEN WK POSTPARTUM. LASIOCARPINE SULFATE WAS GIVEN IN DIVIDED DOSES OF 35 MG/KG EACH ON GESTATIONAL DAYS 13 & 17. THE LOW LIPOTROPE DIET ENHANCED THE EFFECTS OF LASIOCARPINE SULFATE ON BOTH MATERNAL & FETAL LIVER.[NEWBERNE PM; CANCER RES 28 (11): 2337 (1968)] **PEER REVIEWED**
  • CHRONIC TOXICITY /IN GUINEA-PIGS & MONKEYS/ GIVES RISE TO SMALL, NODULAR LIVERS, ... FOCAL HEPATIC NECROSIS & BILE-DUCT PROLIFERATION, ANEMIA, BILIRUBINEMIA, PERSISTENT HYPOPROTHROMBINEMIA, GI HEMORRHAGE, PULMONARY, PANCREATIC, SUBCUTANEOUS OR GENERALIZED EDEMA, SPLENIC ENLARGEMENT & DAMAGED KIDNEYS, THYMUS & PANCREAS.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 284 (1976)] **PEER REVIEWED**
  • HIGH DOSE ... CAUSES ... DROP IN THE ACTIVITY OF DNA-DEPENDENT RNA POLYMERASE OF RAT LIVER NUCLEI. HOWEVER, THE ALKALOID DOES NOT INHIBIT THE TRANSCRIPTION OF RAT LIVER DNA BY MICROCOCCUS LYSODEIKTICUS-RNA POLYMERASE ... SYNTHESIS OF DNA IN 24-HR REGENERATING LIVER IS ... INHIBITED TO 70-92% BY ADMIN ... 1-3 HR BEFORE ASSAY.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 286 (1976)] **PEER REVIEWED**
  • Heliotropium europaeum (wild heliotrope) contains the hepatotoxic pyrrolizidine alkaloids heliotrine and lasiocarpine and their N-oxides. These have a cumulative effect, and an animal may survive one season to succumb the next. They cause an atrophic hepatosis, with clinical signs of jaundice and hemoglobinuria. Death may be due to actual liver damage or to the upsetting of the copper storage mechanism which leads to a build-up of copper in the organ, resulting in the acute hemolytic crisis associated with chronic copper poisoning. Heliotropium europaeum intoxication has been recorded in cattle ... in Australia and calves in Israel ... and Australia ... . Pigs consuming home-mixed rations contaminated with Heliotropium europaeum seed have suffered fatal intoxication associated with pathological lesions characteristic of pyrrolizidine alkaloidosis ... . Low doses of heliotrine produced retarded growth, which did not appear to be due to hepatic dysfunction, in chickens ... . Heliotrine and lasiocarpine can produce ascites and degenerative lesions in the liver in chickens and ducks ... .[Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 236] **PEER REVIEWED**
  • INGESTION OF /HELIOTROPIUM EUROPAEUM BY SHEEP/ WHICH CONTAINS LASIOCARPINE & /ITS/ N-OXIDES ... EFFECT IS CUMULATIVE ... ATROPHIC HEPATOSIS, WITH ... SIGNS OF JAUNDICE & HEMOGLOBINURIA. DEATH DUE TO ACTUAL DAMAGE DONE TO LIVER, OR TO UPSETTING OF COPPER STORAGE MECHANISM ... RESULTING IN ACUTE HEMOLYTIC CRISIS ... .[Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 279] **PEER REVIEWED**
  • In this study, acute and chronic responses of pancreatic hepatocytes induced in F-344 rats by copper depletion-repletion protocol to certain hepatocarcinogens were examined. Administration of a single dose of tannic acid (subcutaneous), aflatoxin B1 (gavage), or lasiocarpine (intraperitoneally) caused characteristic nucleolar segregation in parenchymal cells of liver as well as in pancreatic hepatocytes. Chronic dietary administration of 2-acetylaminofluorene (0.025%) for 12 to 32 wk led to the development of glutathione S-transferase-P-positive pancreatic hepatocytes in the pancreas. In addition, oval cell proliferation was observed in close association with pancreatic hepatocytes, but not in other areas of pancreas containing residual acinar cells. Oval cells in the pancreas and in the liver that developed in rats after chronic 2-acetylaminofluorene treatment and pancreatic duct cells stained positively with rat liver oval cell marker OV-6 antibodies by immunoperoxidase. These findings indicate that pancreatic hepatocytes respond to carcinogens in a fashion similar to parenchymal cells of liver.[Rao MS et al; Am J Pathol 139 (5): 1111-7 (1991)] **PEER REVIEWED** PubMed Abstract Full text: PMC1886328
  • LASIOCARPINE (80 MG/KG, IP) STRONGLY INHIBITED PROTEIN SYNTHESIS IN RAT LIVER WITHIN 15 MIN AFTER ADMIN, WHILE MAX INHIBITION OCCURRED AFTER 1-3 HR & A PROGRESSIVE RECOVERY OCCURRED THEREAFTER. IN LASIOCARPINE TREATED RATS, THE RELATIVE AMT OF LIVER POLYSOMES INCR WHEREAS RIBOSOMAL SUBUNITS & 80 S MONOMERS WERE MARKEDLY ENHANCED.[DEMARLE A, MOULE Y; INT J CANCER 8 (1): 86 (1971)] **PEER REVIEWED** PubMed Abstract
  • LASIOCARPINE (86 MG/KG, IP) CAUSED HIGH FREQUENCIES OF MICRONUCLEATED ERYTHROCYTES IN FETAL LIVER 20 HR AFTER INJECTION INTO PREGNANT MICE. ITS METABOLITES CROSS THE PLACENTA & ARE ACTIVATED BY FETAL LIVER CELLS.[STOYEL CJ, CLARK AM; MUTAT RES 74 (5): 393 (1980)] **PEER REVIEWED** PubMed Abstract
  • LASIOCARPINE 80 MG/KG INJECTED INTO RATS 1 OR 3 HR BEFORE KILLING INHIBITED THE LIVER NUCLEAR RNA SYNTHESIS 55.4 & 52.6%, RESPECTIVELY. WHEN GIVEN TO RATS WITH 24 HR REGENERATING LIVERS AT 1 & 3 HR BEFORE KLLING, LIVER NUCLEAR RNA SYNTHESIS WAS INHIBITED 52 & 97%, RESPECTIVELY, & DNA SYNTHESIS WAS INHIBITED 70 & 92.5%, RESPECTIVELY.[FRAYSSINET C, MOULE Y; NATURE (LONDON) 223 (5212): 1269 (1969)] **PEER REVIEWED**
  • LASIOCARPINE HAD AN ANTAGONISTIC POTENCY AGAINST RESPONSES TO BOTH ACETYLCHOLINE & HISTAMINE ON ISOLATED GUINEA PIG ILEUM PREPN. THE ALKALOID HAD NO APPRECIABLE ACTIVITY AS ANTAGONISTS OF HISTAMINE IN THE ISOLATED TOAD RECTUS ABDOMINIS PREPN. THESE RESULTS WERE DISCUSSED WITH RESPECT TO INTERACTIONS OF THE ALKALOID AT RECEPTOR SITES INVOLVED IN ANTICHOLINERGIC ACTIVITY AT THE MUSCARINIC RECEPTOR.[POMEROY AR, RAPER C; BRIT J PHARMACOL 41 (4): 680 (1971)] **PEER REVIEWED**
  • LASIOCARPINE TESTED FOR ITS EFFECTS ON CHINESE HAMSTER LUNG V79 CELLS PRODUCED CYTOPLASMIC VACUOLIZATION, & CAUSED CELLULAR & NUCLEAR ENLARGEMENT. CHROMOSOMAL ABERRATION WERE INDUCED IN CELLS TREATED. LASIOCARPINE INDUCED AN 8-AZAGUANINE-RESISTANT MUTATION IN V79 CELLS BY DIRECT TREATMENT FOR 48 HR. MUTATION WAS ALSO INDUCED BY TREATMENT FOR 1 HR IN THE PRESENCE OF RAT LIVER METABOLIC ACTIVATION SYSTEM.[TAKANASHI H ET AL; MUTAT RES 78 (1): 67 (1980)] **PEER REVIEWED** PubMed Abstract
  • LASIOCARPINE WAS EXAMINED FOR TUMOR-INHIBITING PROPERTIES AGAINST ADENOCARCINOMA 755, LYMPHOID LEUKEMIA L1210, & SARCOMA 180 IN MICE & WALKER 256 INTRAMUSCULAR OR SUBCUTANEOUS IN RATS & PLASMACYTOMA 1 IN HAMSTERS. LASIOCARPINE WAS HIGHLY ACTIVE AGAINST THE WALKER 256 INTRAMUSCULAR SYSTEM.[CULVENOR CC J; J PHARM SCI 57 (7): 1112 (1968)] **PEER REVIEWED** PubMed Abstract
  • LASIOCARPINE WAS EXAMINED IN THE RAT HEPATOCYTE PRIMARY CULTURE/DNA REPAIR TEST & COMPARED TO MUTAGENICITY IN A MODIFIED SALMONELLA/MICROSOME TEST. LASIOCARPINE WAS POS IN THE DNA-REPAIR TEST.[WILLIAMS GM ET AL; MUTAT RES 79 (1): 1 (1980)] **PEER REVIEWED** PubMed Abstract
  • LIVERS OF RAT FETUSES, WHOSE MOTHERS HAD RECEIVED LASIOCARPINE DURING PREGNANCY, SHOWED SINUSOIDAL DILATION & CONGESTION. ORAL DOSES GIVEN TO NEONATES PRODUCED RAPID & CHARACTERISTIC CHANGES IN THE LIVER, PREDOMINATELY MEGALOCYTOSIS.[BHATTACHARYYA K; J PATHOL BACTERIOL 90 (10): 151 (1965)] **PEER REVIEWED** PubMed Abstract
  • MALE RATS WERE MORE RESISTANT TO CHRONIC, LETHAL, HEPATIC LESIONS FORMED AFTER THE RECEIVED REPEATED LOCAL DOSES OF LASIOCARPINE THAN WERE FEMALE RATS. RESISTANCE TO LASIOCARPINE DECR WITH AGE.[JAGO MV; J PATHOL 105 (1): 1 (1971)] **PEER REVIEWED** PubMed Abstract
  • MUTAGENICITY OF LASIOCARPINE ON SALMONELLA TYPHIMURIUM WAS STUDIED USING AN IN VITRO METABOLIC ACTIVATION SYSTEM. MUTAGENESIS WAS DETECTED BY HAMSTER S9, BUT NOT WITH RAT S9.[MATSUSHIMA T ET AL; MICROSOMES DRUG OXID CHEM CARCINOG (INT SYMP MICROSOMES DRUG OXID 4TH, 1979) 2: 1093 (1980)] **PEER REVIEWED**
  • MUTAGENICITY OF LASIOCARPINE TO SALMONELLA TYPHIMURIUM TA 98, TA 100, TA 1535, TA 1537, TA 1538 & HIS G46 WAS DEMONSTRATED BY A MODIFIED AMES METHOD. PREINCUBATION WITH RAT OR HAMSTER LIVER S9 MIX & THE SALMONELLA TYPHIMURIUM TESTER STRAINS IN A LIQ MEDIUM WAS ESSENTIAL FOR THE DEMONSTRATION OF MUTAGENICITIES.[YAMANAKA H ET AL; MUTAT RES 68 (3): 211 (1979)] **PEER REVIEWED** PubMed Abstract
  • SUPPRESSION MUTATIONS OF SEVERAL TYPES HAVE BEEN INDUCED IN ASPERGILLUS NIDULANSFOLLOWING TREATMENT OF CONIDIA WITH 20 MM AQUEOUS SOLN OF LASIOCARPINE OF UNDEFINED PURITY.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 286 (1976)] **PEER REVIEWED**
  • Senecio Alkaloids. These natural products, consisting mainly of monocrotaline, lasiocarpine, heliotrine, and the basic skeleton retronecine, are complex, aliphatic, hydroxylated fatty acid esters used extensively as teas or as drugs in some civilizations ... . They have a distinct effect on the liver, namely hepatomegalocytosis, following prolonged administration of these agents. ... They exert a pronounced antimitotic effect, but some of these alkaloids have a carcinogenic effect in rats. The intake of such alkaloids in some areas of the world, perhaps together with mycotoxins and in the presence of viral agents such as hepatitis B, may contribute to the liver cancer prevalent in these areas.[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 184] **PEER REVIEWED**
  • The specificity of a cytochrome involved in the oxidation of debrisoquine toward various monooxygenase substrates was investigated to provide a biochemical basis for risk assessment. Debrisoquine is the prototype of the largest group of drugs showing genetic polymorphism of oxidation and the most striking variations among the individual rates of metabolism. Polyclonal antibodies raised toward a debrisoquine 4-hydroxylating cytochrome p450 species purified from rat liver were used to determine which monooxygenase reactions were linked to debrisoquine hydroxylation in human liver. Anti p450-UT-A did not inhibit the oxidation of any of a group of potential carcinogens, toxicants and model substrates, but was inhibitory for the hydroxylation of debrisoquine, bufuralol, lasiocarpine and monocrotaline. These results indicated a definite substrate specificity for the human liver cytochrome p450-dbrisoquine. Studies using space filling models suggested that the structures of all drugs whose metabolism is associated to debrisoquine fit a common structural element. All debrisoquine related drugs possessed a basic nitrogen atom. Each structure can be fit to a model where the site of hydroxylation is at a distance of about 5 angstroms from the basic nitrogen atom. Compounds whose metabolism was not inhibited by anti-p450-UT-H were devoid of one or both structural features. The authors suggest that the individual who is a poor metabolizer of debrisoquine and related drugs is not necessarily at a higher risk to the toxic effects of industrial chemicals than is the extensive metabolizer phenotype.[Wolff T et al; Arch Toxicol 60 (1-3): 89-90 (1987)] **PEER REVIEWED** PubMed Abstract
  • The use of a fluorescent stain containing Hoechst 33258 and pyronin Y in the fetal mouse transplacental micronucleus assay allows classification of erythrocytes into three subpopulations on the basis of RNA staining, and permits micronuclei to be scored in all three subpopulations. The youngest erythrocytes stain uniformly positive for RNA. In older erythrocytes RNA aggregates to give the cells a stippled appearance and ultimately disappears, leaving cells which do not stain positively for RNA. Frequencies of micronucleated uniform erythrocytes and stippled erythrocytes were determined at 30 and 48 hr following a single dose of methyl methanesulfonate, benzo[a]pyrene, lasiocarpine, monocrotaline or heliotrine. With each agent and dose tested, the frequency of micronuclei increased first in the younger uniform erythrocytes and later in stippled erythrocytes. The use of the Hoechst/pyronin staining procedure, which permits DNA to be distinguished from RNA, minimizes the potential for mis-scoring RNA artifacts as micronuclei and also increases the efficiency of the assay by permitting two age populations of erythrocytes to be scored in each sample.[MacGregor JT et al; Mutagenesis 4 (3): 190-9 (1989)] **PEER REVIEWED** PubMed Abstract

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rat intraperitoneal 78 mg/kg[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 1685] **PEER REVIEWED**
  • LD50 Rat oral 150 mg/kg[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 1685] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • LASROCARPINE (RANDOMLY LABELLED, 44% IN THE AMINO ALCOHOL) WAS ADMIN IP TO RATS (TOTAL DOSE, 5 MG) DISTRIBUTION OF LABEL AFTER 4 HR WAS AS FOLLOWS: CARCASS, 6.4%; INTESTINES, 8.6%; TESTES, 0.1%; LUNG, 0.05%; KIDNEY, 0.26%; HEART, 0.05%; SPLEEN, 0.01%; BRAIN, 0.03%; URINE, 27.2%; LIVER, 2.8%, EXPIRED CO2, 9.3% FRACTIONATION OF LIVER RESULTED IN 1.73% IN A TRICHLOROACETIC ACID EXTRACT, 0.6% IN PROTEIN, 0.48% IN LIPID & 0.005% IN NUCLEIC ACIDS.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 285 (1976)] **PEER REVIEWED**

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Metabolism/Metabolites

  • HUMAN EMBRYONIC LIVER SLICES CONVERTED THE PYRROLIZIDINE ALKALOID LASIOCARPINE INTO PYRROLES, AS INDICATED BY A POS EHRLICH COLOR REACTION, WHEREAS LUNG TISSUE DID NOT.[ARMSTRONG SJ, ZUCKERMAN AJ; NATURE (LONDON) 228 (5271): 569 (1970)] **PEER REVIEWED**
  • IN URINE ... OBTAINED 16 HR AFTER INJECTION ... TO RATS ... UNCHANGED LASIOCARPINE (1-1.5% OF DOSE), HELIOTRIDINE (1.5-3%), HELIOTRIDINE N-OXIDE (6%) & TRACES OF BASES WITH CHROMATOGRAPHIC PROPERTIES OF EUROPINE & 7-ANGELYHELIOTRIDINE (EXPECTED PRODUCTS OF PARTIAL HYDROLYSIS). ... METABOLITES IN 24-HR URINE SAMPLE ... 8.5% OF ADMIN LASIOCARPINE.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 286 (1976)] **PEER REVIEWED**
  • STUDIES WITH LASIOCARPINE HAVE CONFIRMED THE FORMATION OF PYRROLIC METABOLITES BY THE MIXED-FUNCTION OXIDASE SYSTEM OF THE MICROSOMAL FRACTION OF RAT LIVER. DEHYDROHELIOTRIDINE HAS BEEN ISOLATED & IDENTIFIED AS A PRODUCT OF MICROSOMAL OXIDATION OF LASIOCARPINE.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V10 285 (1976)] **PEER REVIEWED**

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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