Oral toxicity of a tocotrienol preparation in rats.
Nakamura H, Furukawa F, Nishikawa A, Miyauchi M, Son HY, Imazawa T, Hirose M.
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga,
Setagaya-ku, 158-8501, Tokyo, Japan.
"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
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