Thirteen-week toxicity study of d-alpha-tocopheryl acetate (vitamin E) in Fischer 344 rats

A 13-wk study was conducted by administering d-alpha-tocopheryl acetate (vitamin E) in corn oil by gavage to groups of ten male and ten female Fischer 344 rats at doses of 0, 125, 500 or 2000 mg/kg body weight daily for 13 wk. The dose of corn oil given was 3.5 ml/kg. Additional groups of ten males and ten females were included and served as untreated controls. Deaths occurred only in males at 2000 mg/kg. Vitamin E dosing had no effect on body weight or food consumption. The liver-to-body weight ratio of females at 2000 mg/kg was significantly increased. In males, high levels of vitamin E (2000 mg/kg) caused prolongation of both prothrombin and activated partial thromboplastin (APTT) times, reticulocytosis and a decrease in haematocrit values and haemoglobin concentrations. APTT was also lengthened in females at this dose level. High levels (2000 mg/kg) caused haemorrhagic diathesis in both males and females and increased medullary erythropoiesis in the spleen of one male. Vitamin E at all doses tested caused interstitial inflammation and adenomatous hyperplasia of the lung. The above findings indicate that vitamin E administration in excessive amounts is potentially toxic.