Effects Diseases In humans, acute hepatic veno-occlusive disease was observed after the consumption of a herbal preparation containing riddelliine. Genotoxicity 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. Carcinogenicity There are no data on the carcinogenicity of riddelliine to humans, but based on experimental animal studies, riddelliine is classified as a Group 2B compound, which means that it is possibly carcinogenic to humans. Effects on animals Riddelliine is toxic to animals, with ingestion being the most common method of exposure. In particular, riddelliine has a carcinogenic effect on rats and mice. In rats, oral administration of riddelliine led to an increase in hemangiosarcomas in the liver, cellular carcinomas and/or adenomas in the liver and mononuclear cell leukemia. In mice, oral administration of riddelliine led to hemangiosarcomas in the liver in males and to broncho-alveolar adenomas and carcinomas in females. Furthermore, during a 5 and 30 day study, where the rats and mice were force-fed riddelliine, there was unscheduled DNA synthesis in the cultured hepatocytes in male as well as female rats and mice. Riddelliine has also been known to disturb the estrus cycle in rodents. Riddelliine has also been observed to increase mutations in endothelial cells in the liver of rats. 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. In contrast, G:C→A:T transition, the major mutation in control rats that made up 54% of all mutations, was reduced to 40% of mutations in riddelliine-treated rats within the same study. 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. Toxicity has also been observed in bacteria, particular the Salmonella bacteria S. Typhimurium. When exposed to Riddelliine, the bacterial cell contains many mutations within the genetic strains. Clinical signs in poisoned animals include neurological, gastrointestinal (diarrhea), and hematologic (high blood ammonia, hemolysis) effects. Ascites is often observed. 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. Microscopic examination revealed hepatocellular necrosis and collapse of lobules, increased