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Evaluation of the Carcinogenic Potential of Clofibrate in the Neonatal MouseGlaxoSmithKline, Safety Assessment, Ware, United Kingdom
GlaxoSmithKline, Safety Assessment, Research Triangle Park, North Carolina, USA
Jane Allen Consulting, Inc, Raleigh, North Carolina, USA
Forest Laboratories Inc., Bioanalytical and Drug Metabolism Department, Farmingdale, New York, USA
DerConsulting, Raleigh, North Carolina, USA
GlaxoSmithKline, Safety Assessment, Research Triangle Park, North Carolina, USA Correspondence: Address correspondence to Sarah R. Nesfield, Park Road, Ware, Hertfordshire, SG12 0DP, United Kingdom. E-mail:sarah.r.nesfield{at}gsk.com
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)
Key Words: Carcinogenicity • CD-1 • Clofibrate • Diethylnitrosamine • Mice • Neonatal
International Journal of Toxicology, Vol. 24, No. 5,
341-348 (2005) This article has been cited by other articles:
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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, diethyl-nitrosamine (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. 
