Jul 6, 2000

Repeated dose (28 days) oral toxicity study of flutamide in rats, based on the draft protocol for the 'Enhanced OECD Test Guideline 407' for screening for endocrine-disrupting chemicals

Archives of Toxicology
K ToyodaMasao Hirose

Abstract

In association with the international validation project to establish a test protocol for the 'Enhanced OECD Test Guideline 407', we performed a preliminary 28-day, repeated-dose toxicity study of flutamide, a non-steroidal androgen antagonist, and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine-disrupting chemicals (EDCs). Seven-week-old CD(SD)IGS rats were divided into four groups, each consisting of 10 males and 10 females, and administered flutamide once daily by oral gavage at doses of 0 (control), 0.25, 1 and 4 mg/kg body weight/day. Male rats were killed 1 day after the 28th administration. Female rats were killed on the day they entered the diestrus stage in the estrous cycle following the last treatment. Male rats receiving flutamide at dose levels of 1 and 4 mg/kg showed lobular atrophy of the mammary gland and a decrease in epididymal weight. In addition, 4 mg/kg flutamide-treated males exhibited raised serum testosterone and estradiol levels and decreased weight of the accessory sex glands. In females, a slight prolongation of the estrous cycle was also observed in the 4 mg/kg flutamide-treated group. No dose-related changes could be detected by haematology, seru...Continue Reading

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Mentioned in this Paper

Serum Hormone Levels (Lab Test)
Hematology (Discipline)
Mammary Gland
Epididymis
Hematology Procedure
Toxicity Tests
Hormone Antagonists
Antagonist Muscle Action
Estradiol Measurement
Weighing Patient

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