Heliotridine

155.197

155.19

UP6A16MHFO

43.7

-0.56 @ 25 deg C

1.29±0.1 g/cm3(Predicted)

58 °C

In water, 1X10+6 mg/L @ 25 deg C /Estimated/

1.5X10-5 mm Hg @ 25 deg C /Estimated/

SPECIFIC OPTICAL ROTATION: 124 DEG (ETHANOL, 1%)

Henry's Law constant = 4.1X10-11 atm-cu m/mol @ 25 °C /Estimated/

pKa= 9.01 +/- 0.05

Hydroxyl radical reaction rate constant = 1.2X10-10 cu cm/molec-sec @ 25 °C /Estimated/

MONOGRAPH ON THE PYRROLIZIDINE ALKALOIDS, INCLUDING HELIOTRIDINE.[BULL LB ET AL; THE PYRROLIZIDINE ALKALOIDS; WILEY PUBLISHING COMPANY, 1968]

LD50 Rat (male) ip 1200 mg/kg

HELIOTRIDINE IS THE AMINO ALCOHOL PRESENT IN A LARGE NUMBER OF PYRROLIZIDINE ALKALOIDS WIDELY DISTRIBUTED AMONG SEVERAL PLANT FAMILIES & CLASSES.

Heliotridine, the hydrolysis product from heliotrine and lasiocarpine, was excreted in the form of the N-oxide in larger quantities after the administration of each of these alkaloids /to rats/.|The pa /pyrrolizidine alkaloids/, like many other foreign substances, undergo metab changes in animal body by more than one pathway. ... The known metabolites represent products of n-oxidation and dehydrogenation of pyrrolizidine moiety, of o-demethylation of methoxy groups when these are present in acidic moiety, and products of hydrolysis of ester linkages. ... The part of the administered dose that is excreted in the urine as the unchanged parent alkaloid depends mainly on its basic properties and water solubility. Lasiocarpine is excreted in trace quantities.../and/ heliotridine, 40%...|Evidence from animal studies suggests that the hepatotoxicity is due to the formation of toxic pyrrolic metabolites by the mixed function oxidases of liver cells.|Levels of pyrrolic metabolites were measured in the livers of rats given some pyrrolizidine alkaloids and semisynthetic derivatives. ... Heliotridine-based alkaloids gave more pyrrole than similar retronecine esters, heliotridine ditiglate gave less pyrrole than retronecine ditiglate because the former was more open to hydrolytic attack.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/|Presentation depends on the active toxic agent. In most cases, vomiting, abdominal pain, and diarrhea occur within 60 to 90 minutes of significant ingestion. With some toxins, severe gastroenteritis may result in massive fluid and electrolyte loss. ... Maintain open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, arrhythmias, and hypotension if they occur. Replace fluid loss caused by gastroenteritis with intravenous crystalloid solutions. ... Administer activated charcoal if available ... Gastric emptying is not necessary if activated charcoal is given promptly. /Plants and Herbal Medicines: Group 1/

/HUMAN EXPOSURE STUDIES/ The largest outbreak reported to date occurred in the Gulran district of Herat Province in northwest Afghanistan, close to the border of the USSR. ...The outbreak, was estimated to have affected a population of approximately 35,000 in 98 villages. Examination of 7,200 inhabitants of the affected villages showed evidence of disease in 22.6%, which was more serious in 15%. Thus, it was estimated that approximately 8,000 subjects suffered from the disease including 5,000 who were seriously affected. All age groups were affected, but 46% of subjects were below 14 years of age. However, no sign of disease was found in children below 2 years of age. A detailed report concerning the pathological material obtained from 14 liver biopsies and 8 autopsies was made... /although/ the time interval between the onset of symptoms and the biopsy/autopsy was not indicated. Pathological findings were characteristic, ranging from acute disease with characteristic veno-occlusion to non-portal cirrhosis, which was observed in 5 of the above 22 cases. The outbreak was ascribed to massive contamination of wheat, the staple food crop, following 2 years of drought, with the seeds of Heliotropium popovii H. Riedl subsp. gillianum H. Riedl, which had been growing profusely among the wheat crop. The seeds contained pyrrolizidine alkaloids at concentrations reported by 2 laboratories to be 7.2 and 13.2-14.9 g/kg, identified mainly as the N-oxide of heliotrine (74%)..., and one or two other compounds similar in character to lasiocarpine. Samples of wheat from several villages contained an average of 40 seeds/kg, i.e., 0.03% by weight. It was estimated that an adult consumed at least 700 g flour/day, containing approximately 2 mg alkaloid (based on a mean of the seed analyses). /Pyrrolizidine alkaloids/|/HUMAN EXPOSURE STUDIES/ The two main sources of pyrrolizidine alkaloid poisoning reported in human beings are the consumption of cereal grain contaminated by weeds containing the alkaloids and the use of alkaloid-containing herbs for medicinal and dietary purposes. ...Three of the largest outbreaks of the disease have been reported from South Asia, two from the same site in central India and one from North-West Afghanistan. The first Indian outbreak... occurred in a group of 5 tribal villages in central India in 1972-73. ...Out of a total population of 2,060 in these villages, 71 households with 366 members were investigated. Among these, 39 cases had developed and 19 had died before commencement of the investigations. The incidence rate was 1.1% and the case fatality rate was 50%. All cases occurred among 20 households. In many households, several members were affected. In one household, 4 out of 5 cases died. ...The etiological factor of this outbreak was not established, though dietary contamination with pyrrolizidine alkaloids was considered. A second outbreak occurred at the same site in 1975... . A total population of 486 was affected, 67 cases were reported, of whom 28 (46%) had died. There was a strong family history... . In a later survey, 108 patients were studied and the mortality rate was estimated to be 63%. This time the etiological factor was identified as the plant Crotalaria nana Burm, which had been growing in the fields of millet (Panicum miliare), their staple food crop. The seeds of this plant became mixed with the cereal grain during harvesting. The toxic seeds contained pyrrolizidine alkaloids that were identified as a macrocyclic ester closely similar to monocrotaline. The total alkaloid content was estimated to be 5.3 g/kg of seed, expressed as monocrotaline. The levels of contamination of the millet with seeds were reported to be 0-3.4 g/kg in the unaffected and 0-19 g/kg in the affected households... . /Pyrrolizidine alkaloids/|/SIGNS AND SYMPTOMS/ About 30 pyrrolizidine alkaloids have been found to be hepatotoxic, mostly in rodents, and circumstantial evidence suggests that some are hepatotoxic to man. Evidence from animal studies suggests that the hepatotoxicity is due to the formation of toxic pyrrolic metabolites by the mixed function oxidases of liver cells. The initial product formed from alkaloids that are esters of heliotridine or retronecine is very probably the dehydroalkaloid. The dehydroalkaloids are highly reactive alkylating agents. This exposure may arise by the intentional use of certain herbs as remedies /SRP: Folk remedy/ for ailments or as food, or unintentionally, by the contamination of food crops by alkaloid-containing plants.

heliotridine

THE ANALYSIS OF PLANT MATERIAL FOR PYRROLIZIDINE ALKALOIDS IS BASED ON A GENERAL PROCEDURE FOR EXTRACTION OF THE TERTIARY BASE ALKALOIDS BEFORE AND AFTER REDUCTION OF THE ALKALOID N-OXIDES WHICH ARE ALSO USUALLY PRESENT. THE DIFFERENCE IN THE TWO RESULTS IS AN APPROXIMATE MEASURE OF THE N-OXIDE CONTENT OF THE PLANT MATERIAL. THE LEVELS OF BOTH TERTIARY BASE AND N-OXIDE FORMS OF THE ALKALOID ARE RELEVANT TO AN EVALUATION OF THE TOXICITY OF THE PLANT MATERIAL. THE INDIVIDUAL BASES ARE SEPARATED AND ESTIMATED BY PARTITION CHROMATOGRAPHY OR THIN-LAYER, PAPER OR GAS CHROMATOGRAPHY. /PYRROLIZIDINE ALKALOIDS/|PYRROLIZIDINE ALKALOIDS, UNSATURATED AT THE 1,2 POSITION, WERE DETECTED FOLLOWING TLC DIRECT OXIDATION TO PYRROLES BY USING O-CHLORANIL, FOLLOWED BY SPRAYING WITH EHRLICH'S REAGENT. N-OXIDES WERE DETECTED BY SPRAYING WITH AC20 FOLLOWED BY EHRLICH'S REAGENT. /PYRROLIZIDINE ALKALOIDS/|Underivatized pyrrolizidine alkaloids ... from natural sources (plants and insects) have been analysed by capillary gas chromatography-mass spectrometry. Thin-layer chromatography (TLC) and nuclear magnetic resonance (NMR) spectroscopy have also been used to detect pyrrolizidine alkaloids in plant extracts. /Pyrrolizidine Alkaloids/

Pyrrolizidine alkaloids may be estimated in animal tissues and fluids by removing protein, chromatographing on Florisil and estimating colorimetrically with methyl orange. /Pyrrolizidine Alkaloids/