Riddelliine can be found as a contaminant in foods such as meat, grains, seeds, milk, herbal tea, and honey.
It emits toxic fumes of nitrogenoxide when heated to decomposition.Riddelliine is produced naturally by a variety of plants in the genus Senecio.
By hydrolyzing the rest of the riddelliic acid from the original molecule, the resulting dehydropyrrolizine (DHP) can bind to another DNA base, which introduces a covalent cross-linking.
[9] Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic pyrrolizidine alkaloids (PAs).
Human exposure to PAs occurs through consumption of herbal dietary supplements, including comfrey, and through contaminated livestock products (e.g., milk).
[13] In an in-vitro system, exposure to riddelliine caused sister chromatid exchange in human lymphocytes, DNA-protein cross linking in bovine kidney epithelial cells and gene mutations in bacteria.
[13] In mice, oral administration of riddelliine led to hemangiosarcomas in the liver in males and to broncho-alveolar adenomas and carcinomas in females.
One study observed the characteristic nucleobases transversion of G:C to T:A, in which T:A amounts were elevated from 9% in the control group to 17% in the riddelliine-treated rats.
These results suggest that the relatively high mutagenicity of riddelliine in rat liver endothelial cells may be partially responsible for the tumorigenic specificity of this agent.
[5] Clinical signs in poisoned animals include neurological, gastrointestinal (diarrhea), and hematologic (high blood ammonia, hemolysis) effects.
Molyneux et al. (1991) reported that calves fed Senecio riddellii, which contains only riddelliine and its N-oxide, for 20 days showed weight loss, signs of depression, reduced feed intake, ataxia of hind limbs, ascites, and edema before death.
[15] Microscopic examination revealed hepatocellular necrosis and collapse of lobules, increased numbers of fibroblasts and collagen, portal edema, anisokaryosis of hepatocyte nuclei with some cytomegaly, and bile duct proliferation.
[5] The first reported isolation of 'Riddelliine' was done by Richard H. F. Manske, a chemist at the National Research Laboratories in Ottawa, Ontario, Canada.