Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice

Int J Toxicol. 2014 Nov-Dec;33(6):450-8. doi: 10.1177/1091581814554929. Epub 2014 Oct 28.

Abstract

The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs.

Keywords: delta-tocotrienol; gamma-tocotrienol; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Chromans / toxicity*
  • Dermatitis, Contact / etiology*
  • Dermatitis, Contact / pathology
  • Female
  • Irritants / toxicity*
  • Male
  • Mice
  • Skin / drug effects
  • Skin / pathology
  • Toxicity Tests, Acute
  • Vitamin E / analogs & derivatives*
  • Vitamin E / toxicity

Substances

  • Chromans
  • Irritants
  • Vitamin E
  • tocotrienol, delta
  • plastochromanol 8