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- Title
Evaluation of the carcinogenic potential of clofibrate in the neonatal mouse.
- Authors
Nesfield, Sarah R; Williams, Thomas C; Hoivik, Debie J; Miller, Richard T; Allen, Jane S; Selinger, Krzysztof; Rickert, Douglas; Santostefano, Michael J
- Abstract
This study was conducted in support of the International Life Sciences Institute (ILSI) alternative carcinogenicity models initiative to evaluate the carcinogenic potential of clofibrate, a nongenotoxic peroxisome proliferator-activated receptor (PPAR) alpha agonist, following oral administration to neonatal mice. Male and female neonatal CD-1 mice were dosed with clofibrate at doses of 100, 250, and 500 mg/kg or with the positive control, diethylnitrosamine (DEN), at 2 mg/kg by oral gavage on days 9 and 16 post birth and observed for approximately 1 year for the development of tumors. Plasma levels of clofibric acid after the second administration increased with dose, but were not dose proportional. Clofibrate administered by gavage on litter days 9 and 16 to neonatal mice at doses of 100, 250, or 500 mg/kg did not produce a carcinogenic effect. The positive control DEN did produce tumors in the liver and lung (single and multiple adenomas and carcinomas) and harderian gland (adenoma) of both sexes. Non-neoplastic lesions related to DEN treatment were confined to myocardial degeneration/fibrosis and testicular interstitial hyperplasia in males, and to glomerulonephrosis and gastritis in both sexes.
- Publication
International journal of toxicology, 2005, Vol 24, Issue 5, p341
- ISSN
1091-5818
- Publication type
Journal Article
- DOI
10.1080/10915810500210401