SENECIO SPECIES AND RIDDELLIINE
RIDDELLIINE (Group
2B)
For definition of Groups, see Preamble Evaluation.
VOL.: 82 (2002) (p. 153)
CAS No.:
5. Summary of Data Reported and Evaluation
5.1 Exposure data
Riddelliine is a pyrrolizidine alkaloid that is found in Senecio riddellii and other Senecio species, including S. longilobus, which is used as a herbal remedy in the south-western USA.
5.2 Human carcinogenicity data
No data on the carcinogenicity of riddelliine to humans were available to the Working Group.
5.3 Animal carcinogenicity data
In mice, oral administration of riddelliine induced hepatic haemangiosarcomas in males and bronchiolo-alveolar adenomas and carcinomas in females. In rats, oral administration of riddelliine increased the incidence of hepatic haemangiosarcomas, hepatocellular carcinomas and/or adenomas and mononuclear cell leukaemia in both males and females. In a short-term study, a few rats developed hepatocellular adenomas after 13 weeks of oral administration.
5.4 Other relevant data
Riddelliine and its N-oxide are absorbed from the gastrointestinal tract. Riddelliine is metabolized to riddelliine N-oxide and dehydroretronecine in rat liver microsomes.
A herbal preparation made from Senecia longilobus, of which riddelliine is a constituent, causes hepatic veno-occlusive disease in humans. Intoxication of calves with either S. riddellii or one of its two main pyrrolizidine alkaloid constituents, riddelliine N-oxide, led to the typical signs and symptoms of seneciosis. A similar toxicity profile was induced by riddelliine in rodents.
Riddelliine disturbs the estrus cycle in rodents. It causes developmental toxicity in the absence of marked toxicity in rodents.
DNA adducts of dehydroretronecine are found in rat liver following oral administration of riddelliine. Dehydroretronecine is genotoxic in a number of in-vitro systems. It induced sister chromatid exchange in human lymphocytes, DNA-protein cross-links in bovine kidney epithelial cells in vitro and gene mutations in bacteria.
5.5 Evaluation
There are no data on the carcinogenicity of riddelliine to humans.
There is sufficient evidence in experimental animals for the carcinogenicity of riddelliine.
Overall evaluation
Riddelliine is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 10 (1976); Suppl. 7 (1987) (p. 71)
Synonyms
Last updated: 4 December 2002
See Also:
Toxicological Abbreviations