Toxicologic studies on clomiphene

Abstract

The acute LD 50's for clomiphene citrate in rats were 530 and 5750 mg/kg for the intraperitoneal and oral routes, respectively. In rats given clomiphene citrate at dosages of 5, 15, and 40 mg/kg/day for 53 weeks, food consumption and rate of growth were depressed. Varying degrees of alopecia occurred, with the incidence related to dose and duration of drug administration. Subcapsular cataracts occurred in 4 of 29 rats (13.8%) receiving the highest level of drug (40 mg/kg/day), but not in those at lower levels. Gross and histopathologic changes in the reproductive organs and accessory glands were consistent with gonadotropin inhibition. These included varying degrees of atrophy with depressed function of secretory glands, and depression or inhibition of ovulation and spermatogenesis. Cystic dilatation of ovarian follicles also occurred in some treated females. No significant hematologic changes were found. In dogs given clomiphene citrate orally at levels of 5, 15, and 40 mg/kg/day for 53 weeks, gross and histopathologic changes consistent with gonadotropin inhibition were found. These included atrophy of the prostate gland and depression or inhibition of spermatogenesis and ovulation. Endometrial glands were consistently dilated. Average plasma cholesterol levels were depressed in dogs given 15 mg/kg/day or more, and desmosterol levels were elevated in dogs given 5 mg/kg/day or more. No other significant clinicopathologic alterations associated with the drug were demonstrated.