(1S,7aR)-2,3,5,7a-テトラヒドロ-1-ヒドロキシ-1H-ピロリザイン-7-メタノール

0.000015 [mmHg]

1.5X10-5 mm Hg @ 25 °C /Estimated/

Intraperitoneal LD50 (rat) = 1500 mg/kg; [RTECS] An outbreak of thousands of cases of liver disease was reported in Afghanistan after the seeds of the plant (Heliotropium popovii H. Riedl subsp. gillianum H. Riedl) contaminated the wheat crop; Emergency treatment: Plants- pyrrolizidine alkaloids; [HSDB] Over 6000 plants produce pyyrolizidine alkaloids, some of which are toxic. This is probably the most common plant toxin, and it affects livestock, wildlife, and humans. [Haddad, p. 494] Mechanism of toxicity is the metabolic conversion into pyrroles that act as alkylating agents. Hepatic disease leads to cirrhosis and possibly increased risk for hepatic carcinoma. Most poisoning cases have resulted from contamination of food grain with the seeds containing the alkaloid or from medicinal herbs. An estimated 20% of patients die, 50% recover completely, and 30% develop chronic hepatic veno-occlusive disease. [Goldfrank, p. 647, 1546]

/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/

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.

An amino alcohol found in many pyrrolizidine alkaloids in several families of plants; [HSDB]

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.