Toxicity and carcinogenicity of riddelliine in rats and mice.
These investigations of riddelliine analyzed potential carcinogenesis and the utility of the female-rat/male-mouse design in bioassays and dose-response. Groups of 50 Fischer rats and B6C3F1 mice were gavage-administered riddelliine 5 days per week for 105 weeks. The dose levels for male rats were 0 or 1.0 mg/kg body weight; female rats 0, 0.01, 0.033, 0.1, 0.33, or 1.0 mg/kg; male mice 0, 0.1, 0.3, or 1.0, 3.0 mg/kg; and female mice 0 or 3.0 mg/kg. The dose groups were purposely designed to evaluate the dose-response relationship only in female rats and male mice. In rats, liver hemangiosarcoma, hepatocellular adenoma, and mononuclear cell leukemia were significantly increased in the 1.0 mg/kg male and female dose groups. Non-neoplastic lesions occurred in the liver and kidney of male and female rats. In mice, hemangiosarcomas increased significantly in the liver of males in the 3.0 mg/kg dose group. Alveolar/bronchiolar neoplasms in the 3.0 mg/kg dose group of female mice were significantly increased. Hepatocellular neoplasms were significantly decreased in the 1.0 mg/kg dose group of male and 3.0 mg/kg dose groups of male and female mice. Non-neoplastic lesions occurred in the liver and kidney of male and female, and lung and arteries of female mice. These studies demonstrate toxicity and carcinogenicity of riddelliine in rats and mice, and a dose-response relationship in female rats and male mice under the experimental conditions employed.
Chan
Po C
PC
Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-9998, USA. chanp@niehs.nih.gov
Haseman
Joseph K
JK
Prejean
J D
JD
Nyska
Abraham
A
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D005260:Female; D006394:Hemangiosarcoma / Q000139:chemically induced / Q000662:veterinary; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007938:Leukemia / Q000139:chemically induced / Q000662:veterinary; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000662:veterinary; D008297:Male; D051379:Mice; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D002273:Carcinogens; D011763:Pyrrolizidine Alkaloids; C013672:riddelliine