3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

Endpoint summary

Additional information

After oral administration of DL-Alpha-Tocopheryl acetate (4 ml emulsion with 2 mg DL-Alpha-Tocopheryl acetate and 50 μC of d, l-α-tocopheryl-1’,2’-3H2-acetate) to rats.

DL-Alpha-Tocopheryl acetate is extensively metabolised by rat tissues.

The adrenals, ovaries, adipose tissue and heart appeared to extract vitamin E from the blood for up to 48 hours postabsorptively. The metabolite most abundantly occurring under these conditions was alpha-tocopheryl quinone. In the adrenal glands, however, the most highly labeled compound was unesterified tocopherol. The authors concluded that the adrenal tissue played a definite role in the metabolism of vitamin E. (Gallo-Torres, 1971). From these data on oral uptake, the oral absorption is set at 100% (regardless the vehicle).

Thirty minutes after intravenous administration of DL-Alpha-Tocopheryl acetate

(1 ml emulsion with 136 I. U. unlabeled DL-Alpha-Tocopheryl acetate and 25 μC of DL-Alpha-Tocopheryl-1’,2’-3H2-acetate) to rats, 96% of the chromatographed radioactivity was due to unchanged DL-Alpha-Tocopheryl acetate. Forty eight hours after injection, only 8% of the chromotographed radioactivity found in plasma corresponded to DL-Alpha-Tocopheryl acetate as such. At this period 16% was due to unesterified tocopherol and 64% to tocopheryl quinone. Most of the radioactivity accumulated in the liver. In the liver, DL-Alpha-Tocopheryl acetate, is rapidly and extensively hydrolysed: 48 hours after injection only 2.8% of the chromatographed radioactivity was due to the injected DL-Alpha-Tocopheryl acetate. Also the spleen and lung tissues metabolized DL-Alpha-Tocopheryl acetate extensively. Whereas the skeletal muscle, adipose tissue, small intestine, adrenals and ovaries showed a gradual increase in radioactivity in time, the uptake of the brain and pituitary was very slow compared to that of other organs. After i. v. administration only traces of DL-Alpha-Tocopheryl acetate in the small intestine were observed. The authors conclude that the intestine of the rat is able to hydrolyze DL-Alpha-Tocopheryl acetate almost completely (Gallo-Torres, 1971)

Dermal absorption

In an in vitro skin absorption test (similar to OECD 428, non-GLP) , it is concluded that Vitamin-E-Acetate-3H penetrates into and through intact and stripped pig skin (Csato and Klecak, 1995). The total skin penetration rates of Vitamin E acetate 3H from 3 alpha-hydroxy-acid creams were time-, formulation type- and skin condition-dependent, although not significantly different. The percutaneous absorption observed was in the range of 1.1 – 4.2 %, tested at 1h, 6h and 18h exposure with 3 different formulations (nominal dose 5%). The dermal absorption is set at 5%.