Oral toxicity of a tocotrienol preparation in rats.
H Nakamura, F Furukawa, A Nishikawa, M Miyauchi, H Y Son, T Imazawa, M Hirose, H Nakamura, F Furukawa, A Nishikawa, M Miyauchi, H.-Y Son, T Imazawa, M Hirose
Index: Food Chem. Toxicol. 39(8) , 799-805, (2001)
Full Text: HTML
Abstract
Tocotrienols are added as antioxidants to food. As there have been no reports of toxicological evaluation, a 13-week oral toxicity study was performed in Fischer 344 rats of both sexes at dose levels of 0 (group 1), 0.19 (group 2), 0.75 (group 3) and 3% (group 4) of a preparation in powdered diet. Suppression of body weight gain was observed in group 4 males. On hematological examination, significant decrease in mean corpuscular volume (MCV) was observed in all treated males. Platelets were significantly reduced in group 3 and 4 males. Hemoglobin concentration, MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were significantly decreased in group 3 and 4 females and hematocrit in group 4 females. On serum biochemical examination, increase in the albumin/globulin ratio (A/G) and alkaline phosphatase in all treated males, elevated alanine transaminase in group 4 of both sexes and increases in asparagine transaminase and gamma-glutamyl transaminase in group 4 females were observed. With regard to relative organ weights, liver weights in group 4 of both sexes and adrenal weights in all treated males demonstrated an increase, and ovary and uterus weights in group 4 females were reduced. Histopathologically, slight hepatocellular hypertrophy in group 3 and 4 males, and reduction of cytoplasmic vacuolation in the adrenal cortical region in group 4 males were observed. Because of pathological changes in male liver and hematological changes in females, the no-observed-adverse-effect level (NOAEL) was concluded to be 0.19% in the diet (120 mg/kg body weight/day for male rats and 130 mg/kg body weight/day for female rats). As a decrease in MCV, an increase in the A/G, elevation of alkaline phosphatase and increase in adrenal weight were observed in all treated males, a no-observed-effect level (NOEL) could not be determined in this examination.
Related Compounds
Related Articles:
Novel HPLC analysis of tocopherols, tocotrienols, and cholesterol in tissue.
1999-12-01
[Free Radic. Biol. Med. 27(11-12) , 1137-40, (1999)]
The tocopherol, tocotrienol, and vitamin E content of the average Finnish diet.
1991-01-01
[Int. J. Vitam. Nutr. Res. 61(1) , 27-32, (1991)]
Selective excretion of yolk-derived tocotrienols into the bile of the chick embryo.
1998-12-01
[Comp. Biochem. Physiol. B Biochem. Mol. Biol. 121(4) , 393-6, (1998)]
Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols.
1999-01-01
[Nutr. Cancer 33(1) , 26-32, (1999)]
2007-02-01
[J. Nutr. 137(2) , 345-50, (2007)]