Α-Tocopheryl acetate

Use in cosmetics

α-Tocopheryl acetate is often used in dermatological products such as skin creams. It is not oxidized and can penetrate through the skin to the living cells, where about 5% is converted to free tocopherol. Claims are made for beneficial antioxidant effects. α-Tocopheryl acetate is used as an alternative to tocopherol itself because the phenolic hydroxyl group is blocked, providing a less acidic product with a longer shelf life. It is believed that the acetate is slowly hydrolyzed after it is absorbed into the skin, regenerating tocopherol and providing protection against the sun's ultraviolet rays. Tocopheryl acetate was first synthesized in 1963 by workers at Hoffmann-La Roche.

Although there is widespread use of tocopheryl acetate as a topical medication, with claims for improved wound healing and reduced scar tissue, reviews have repeatedly concluded that there is insufficient evidence to support these claims. There are reports of vitamin E-induced allergic contact dermatitis from use of vitamin E derivatives such as tocopheryl linoleate and tocopherol acetate in skin care products. Incidence is low despite widespread use.

Misuse

Ingredient in vape liquids

On September 5, 2019, the United States Food and Drug Administration (US FDA) announced that 10 out of 18, or 56% of the samples of vape liquids sent in by states, linked to the then recent vaping-related lung disease outbreak in the United States, tested positive for vitamin E acetate which had been used as a thickening agent by illicit THC vape cartridge manufacturers. On November 8, 2019, the Centers for Disease Control and Prevention (CDC) identified vitamin E acetate as a very strong culprit of concern in the vaping-related illnesses, but has not ruled out other chemicals or toxicants as possible causes. Research suggests when vitamin E acetate is inhaled, it may interfere with normal lung functioning. A 2020 study found that vaporizing vitamin E acetate produced carcinogenic alkenes and benzene, but also exceptionally toxic ketene gas, which may be a contributing factor to the pulmonary injuries.

Chemistry

At room temperature, α-tocopheryl acetate is a fat-soluble liquid. It has 3 chiral centers and thus 8 stereoisomers. It is made by esterifying α-tocopherol with acetic acid. 2R,4R,8R-isomer, also known as RRR-α-tocopheryl acetate, is the most common isomer used for various purposes. This is because α-tocopherol occurs in nature primarily as RRR-α-tocopherol.

α-Tocopheryl acetate does not boil at atmospheric pressure and begins to degrade at 240 °C.

α-Tocopheryl acetate is hydrolyzed to α-tocopherol and acetic acid under suitable conditions or when ingested by people.

References

References

1. (June 2020). "Culprit or correlate? An application of the Bradford Hill criteria to Vitamin E acetate". Archives of Toxicology.
2. (February 23, 2015). "Linus Pauling Institute Research Report: All About E".
3. (1995). "Hydrolysis of RRR-alpha-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat)". J Photochem Photobiol B.
4. (1963). "Über die Chemie des Vitamins E. 3. Mitteilung. Die Totalsynthese von (2''R'', 4''′R'', 8''′R'')- und (2''S'', 4''′R'', 8''′R'')-α-Tocopherol". Helvetica Chimica Acta.
5. (2004). "Topical alpha-tocopherol acetate in the bulk phase: eight years of experience in skin treatment". Ann. N. Y. Acad. Sci..
6. (2015). "A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring". Arch. Dermatol. Res..
7. (2016). "The Role of Topical Vitamin E in Scar Management: A Systematic Review". Aesthet Surg J.
8. (2010). "Vitamin E and allergic contact dermatitis". Dermatitis.
9. Sun, Lena. (September 6, 2019). "Contaminant found in marijuana vaping products linked to deadly lung illnesses, tests show". Washington Post.
10. (September 10, 2019). "Three Companies Subpoenaed in Weed Vape Illness Investigation".
11. (November 8, 2019). "Outbreak of Lung Injury Associated with E-Cigarette Use, or Vaping". [[Centers for Disease Control and Prevention]].
12. (March 24, 2020). "Potential for release of pulmonary toxic ketene from vaping pyrolysis of vitamin E acetate". Proceedings of the National Academy of Sciences of the United States of America.
13. (2016). "Safety assessment of the substance α-tocopherol acetate for use in food contact materials". EFSA Journal.
14. (1996). "The Merck index". Merck.