Retronecine

Very sol in water, alc; sol in acetone; slightly sol in ether

In water, 8X10+5 mg/L @ 25 °C /Estimated/

Danger

H300+H310+H330 (100%): Fatal if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Retronecine is classified as a pyrrolizidine alkaloid (PA). Unsaturated pyrrolizidine alkaloids are hepatotoxic, that is, damaging to the liver. PAs also cause hepatic veno-occlusive disease and liver cancer. PAs are tumorigenic. Disease associated with consumption of PAs is known as pyrrolizidine alkaloidosis. (Wikipedia)

/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/

Steric hindrance around the ester groups was the major factor inhibiting hydrolysis of pyrrolizidine alkaloids. Enzymic hydrolysis of retronecine di-isovalerate occurred primarily at the allylic 9-ester group. The results supported the view that a factor contributing to the lower hepatotoxicity of semisynthetic retronecine diesters compared with some natural pyrrolizidine alkaloids, is their greater susceptibility to detoxication by hydrolysis.

Levels of pyrrolic metabolites were measured in the livers of rats given some pyrrolizidine alkaloids and semisynthetic derivatives. Structural and chemical features favoring the formation of such metabolites were defined. The most important of these were steric hindrance or chemical properties giving resistance to ester hydrolysis; lipophilic character, allowing access to hepatic microsomal enzymes; a conformation favoring microsomal oxidation of the pyrroline ring in preference to n-oxidation.

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.

Lactating rats dosed with (3)H-retronecine excreted within 3 hr approx 0.08% of the applied radioactivity in the milk mainly as yet not identified water soluble retronecine-derived metabolites and approx 0.02% as unchanged pyrrolizidine alkaloids (pas). Highest tissue levels of pas and metabolites, 6 hr after admin were found in liver and lungs.

Some of the Senecio species in which it occurs have been used as medicinal herbs; e.g., S. discolor (S.W.) DC. was used against coughs, colds, fevers and indigestion in Jamaica; S. bupleuroides DC. was reported to be an ingredient in an African remedy for chest troubles; and S. vulgaris was used in Europe for dysmenorrhea and amenorrhea and in the USA as a diaphoretic, diuretic, tonic and emmenagogue.

Retronecine is a pyrrolizidine alkaloid found in a variety of plants in the genera Senecio and Crotalaria, and the family Boraginaceae.