A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats

Drug and Chemical Toxicology
S KarlssonG M Williams

Abstract

The carcinogenic potential of the nonsteroidal triphenylethylene antiestrogen toremifene (Fareston) was evaluated in a standard 104-week rat dietary carcinogenicity study. The doses were 0, 0.12, 1.2, 5.0 and 12 mg/kg/day and the number of animals 50/sex/dose group. The body weight gain and food consumption were monitored once weekly (study weeks 1-16) or once every four weeks thereafter (study weeks 17-104). Blood samples were taken at weeks 34, 52 and 104 and the plasma concentrations of toremifene, as well as the two main metabolites (deaminohydroxy)toremifene and N-demethyltoremifene, were measured. All doses of toremifene reduced food intake and body weight gain. Toremifene caused a significant reduction in mortality, which was mainly due to reduced incidences of pituitary tumors. This was evident in all dose groups. Drug-related decrease of mammary tumors in females (at all doses) and testicular tumors in male rats (doses > or = 1.2 mg/kg/day) were also evident. The incidence of the preneoplastic foci of basophilic hepatocytes were significantly decreased in treated female groups. Toremifene induced no preneoplastic or neoplastic lesions. Based on histopathology, no obvious toxicity could be observed. Drug-related changes...Continue Reading

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Citations

Aug 9, 2003·Expert Opinion on Drug Safety·Karen Brown
Mar 26, 2002·Climacteric : the Journal of the International Menopause Society·S L SilfenH U Bryant
Dec 5, 1998·Drug and Chemical Toxicology·G M WilliamsS Karlsson
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Eero PukkalaKaija Holli
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Apr 27, 2016·Critical Reviews in Toxicology·Jan Willem van der LaanMarkku Pasanen
Mar 19, 2002·The Breast Journal·Pirkko HirsimäkiEero Mäntylä
Aug 10, 2001·Journal of Hepatology·H A JärveläinenK O Lindros

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