Toxicity studies of intravenous vitamin E in newborn rabbits.
This study was designed to investigate the toxicity of intravenously administered alpha-tocopherol, alpha-tocopheryl acetate, and a polysorbate vehicle similar to that used in a commercial preparation of alpha-tocopheryl acetate intended for intravenous administration. Cesarean-delivered newborn rabbits fed intravenously were administered 100 mg of either alpha-tocopherol or alpha-tocopheryl acetate in a polysorbate vehicle, or the vehicle only, or no treatment for 6 or 7 days. Two intravenous diets were employed which differed in nutritional content and were termed low energy (LE) and high energy (HE). High concentrations of alpha-tocopherol were present in the tissues of all pups that received either treatment with alpha-tocopherol or alpha-tocopheryl acetate in the polysorbate vehicle, irrespective of the nutritional regimen. Pups in all treatment and control groups which received the LE diet had hepatic centrilobular degeneration, necrosis and pigment accumulation, which was attributed to malnutrition. No additional toxicities could be attributed to the vitamin E or polysorbate treatments. Administration of the HE diet eliminated the nutrition-related centrilobular degeneration, and revealed treatment-related liver changes. HE pups treated with alpha-tocopheryl acetate in the polysorbate vehicle had microscopic evidence of mild bile stasis and had elevated serum bilirubin. Minimal lipidosis or fatty change in the liver was observed only in alpha-tocopherol and alpha-tocopheryl acetate-treated pups. Lipidosis in the spleen was moderate in the alpha-tocopherol group and minimal in the alpha-tocopheryl acetate group. Lipidosis also occurred in the adrenal gland primarily in the alpha-tocopheryl acetate group.(ABSTRACT TRUNCATED AT 250 WORDS)
Rivera
A
A
Department of Pediatrics, University of Iowa, Iowa City.
Abdo
K M
KM
Bucher
J R
JR
Leininger
J R
JR
Montgomery
C A
CA
Roberts
R J
RJ
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood; D004798:Enzymes / Q000097:blood; D007275:Injections, Intravenous; D010289:Parenteral Nutrition, Total; D011136:Polysorbates / Q000378:metabolism; D011817:Rabbits; D014810:Vitamin E / Q000008:administration & dosage / Q000633:toxicity*
D004798:Enzymes; D011136:Polysorbates; D014810:Vitamin E; D001663:Bilirubin