Senkirkine

365.42

365.42

DTXSID4021266

93.14000

0.94740

1.22g/cm3

198 °C

604.9ºC at 760 mmHg

319.6ºC

1.546

Readily soluble in ethyl acetate and chloroform; less soluble in water, ethanol, acetone and benzene

-20°C

3X10-14 mm Hg @ 25 °C /Estimated/

Specific optical rotation: -6.2 deg @ 15 dec C/D (in chloroform); max absorption: 215 nm (epsilon= 286)

Henry's Law constant = 1.6X10-13 atm-cu m/mol @ 25 °C /Estimated/

Readily hydrolyzed with alkali|Hydroxyl radical reaction rate constant = 2.2X10-10 cu cm/molec-sec @ 25 °C /Estimated/

III

6.1(b)

1544

3

22

Xn

Stable at room temp in closed containers.

P301 + P310

H301

A REVIEW WITH 36 REFERENCES ON THE HEALTH HAZARDS, INCLUDING CARCINOGENICITY, OF PYRROLIZIDINE ALKALOIDS (PA). PA HAVE BEEN CORRELATED WITH VENO-OCCLUSIVE DISEASE IN AFGHANISTAN & INDIA & WITH LIVER DISEASE IN MEXICAN-AMERICAN CHILDREN. VARIOUS PA, INCLUDING SENKIRKIN, HAVE CAUSED TUMORS, NEOPLASTIC LESIONS, OR CONGENITAL DEFECTS IN RATS. USE OF PA FOR MEDICINAL OR OTHER PURPOSES PRESENTS SERIOUS HEALTH HAZARDS.[SCHOENTAL R; HEALTH HAZARDS OF PYRROLIZIDINE ALKALOIDS: A SHORT REVIEW; TOXICOL LETT 10(4) 323 (1982)]|A REVIEW WITH 307 REFERENCES ON NATURAL CARCINOGENIC PRODUCTS OF PLANT ORGIN, INCLUDING THE PYRROLIZIDINE ALKALOID SENKIRKIN.[HIRONO I; NATURAL CARCINOGENIC PRODUCTS OF PLANT ORIGIN; CRIT REV TOXICOL 8(3) 235 (1981)]

LD50 Rat ip 220 mg/kg

...Occurs in several species of the tribe Senecioneae (family compositae) including Brachyglottis repanda; Petasites laevigatus (wild) Nardosmia laevigata (wild); Senecio kirkii; S kleinia; S remardii; S antieuphorbium (l), Parfugium japonicum, and Tussilago farfara. It also occurs in Crotalaria laburnifolia subspecies eldomas (family leguminosae).|Plant sources of hepato toxic pyrrolizidine alkaloids, including senkirkin.

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 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/|/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/

neosenkirkine

Senkirkine occurs in several species of the tribe Senecioneae (family Compositae) including Brachyglottis repanda Forst. et Forst. F.; Petasites laevigatus (Willd.) Reichenb. [Nardosmia laevigata (Wild.) DC.]; Senecio krikii Hook. f. ex Kirk; S. kleinia Sch. Bip.; S. renardii Winkl.; S. antieuphorbium (L.) Sch. Bip; Farfugium japonicum Kitam.; and Tussilago farfara. It also occurs in Crotalaria laburnifolia subsp. eldomae (family Leguminosae).

A method has been developed specifically for senkirkine in plant material, using a combination of gas chromatography and mass spectrometry. The limit of detection is approximately 5 mg/kg.|SEPARATION & DETERMINATION OF MACROCYCLIC PYRROLIZIDINE ALKALOIDS, INCLUDING SENKIRKIN, PRESENT IN PETASITES JAPONICUS BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY.|THE DETERMINATION OF PYRROLIZIDINE ALKALOIDS, INCLUDING SENKIRKIN, IN SEVERAL SENECIO SPECIES BY GAS CHROMATOGRAPHY. THE DETECTION LIMITS RANGED FROM 20 TO 150 NG.|THE DETERMINATION OF PYRROLIZIDINE ALKALOIDS, INCLUDING SENKIRKIN, IN GOATS MILK BY GAS CHROMATOGRAPHY. SENSITIVITY OF THE METHOD WAS ESTIMATED TO BE 0.1 PPM.|For more Analytic Laboratory Methods (Complete) data for SENKIRKINE (9 total), please visit the HSDB record page.

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