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The Peroxidative Activation of Butylated Hydroxytoluene to BHT-Quinone Methide and Stilbenequinone

  • David C. Thompson
  • Young Nam Cha
  • Michael A. Trush
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

Butylated hydroxytoluene (BHT, 2,6-di-tert-butyl-4-methyl-phenol) is a commonly used antioxidant allowed in foods in amounts up to 0.02% of the weight of fat present. BHT helps prevent undesirable oxidation reactions from occurring by acting as a free radical scavenger. BHT is also used as a stabilizer in pesticides, gasolines and lubricants, soaps and cosmetics, and as an antiskinning agent in paints and inks (1). BHT has been shown to have a protective effect against the toxicity and carcinogenicity of a wide variety of chemicals (2). However, several recent animal studies have questioned the presumed safety of this antioxidant. For example, BHT has been shown to cause lung damage in mice (3,4), hemorrhagic death in rats (5) and can act as a tumor promoter in both mice and rats (6,7). One of the best characterized toxic effects of BHT is the destruction of type I alveolar and pulmonary endothelial cells (8) in the mouse lung. This lung damage is thought to arise from the biotransformation of BHT into BHT-quinone methide (2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone) (9,10), a highly reactive compound (see Figure 1). BHT has been demonstrated to be metabolized to BHT-quinone methide in vivo in the mouse (10) and rat (11). This reaction is presumably catalyzed by a cytochrome P-450 related enzyme (12,13). As a class of chemical compounds, quinone methides have been shown to react with cellular nucleophiles including amines, carbohydrates, alcohols, thiols, and olefins (14).

Keywords

Covalent Binding Butylate Hydroxy Toluene Microsomal Protein Butylate Hydroxyanisole Peroxidase Enzyme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • David C. Thompson
    • 1
  • Young Nam Cha
    • 2
  • Michael A. Trush
    • 1
  1. 1.Dept. Environmental Health SciencesJohns Hopkins University BaltimoreUSA
  2. 2.Dept. PharmacologyYonsei University College of MedicineSeoulKorea

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