Hemorrhagic toxicity of d-alpha-tocopherol in the rat.

When male Sprague-Dawley rats were administered d-alpha-tocopherol and butylated hydroxytoluene in the diet or intraperitoneally for 7 days, prolongations of prothrombin time and partial thromboplastin time were observed in those given both chemicals by both routes in a dose-dependent manner. However, intraperitoneal d-alpha-tocopherol was less toxic and the prothrombin and partial thromboplastin time indices were approx. 70% and approx. 60% in rats given 2.91 mmol/kg body weight daily. Rats given d-alpha-tocopherol in the diet at a daily dose of 2.31 mmol/kg body weight were approx. 13% and approx. 16% of the control, and in those dietary groups severe hemorrhages in epididymis and other organs were also observed. Plasma concentrations of total tocopherols were more increased by the dietary than the intraperitoneal route. These results suggest that the great difference in the hemorrhagic effect of d-alpha-tocopherol between dietary and intraperitoneal route administration may largely be due to the differing absorption rates of the drug by these two means.