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

Details

• Personal Author:
  Cha YN ; Thompson DC ; Trush MA
• Description:
  Butylated hydroxy toluene (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. BHT has been shown to have a protective effect against the toxicity and carcinogenicity of a wide variety of chemicals. 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, hemorrhagic death in rats and can act as a tumor promoter in both mice and rats. One of the best characterized toxic effects of BHT is the destruction of type I alveolar and pulmonary endothelial cells in the mouse lung. This lung damage is thought to arise from the biotransformation of BHT into BHT-quinone methide (2,6-di-tert-butyl4-methylene-2,5-cyclohexadienone), a highly reactive compound (see Figure 1). BHT has been demonstrated to be metabolized to BHT-quinone methide in vivo in the mouse and rat. This reaction is presumably catalyzed by a cytochrome P-450 related enzyme. As a class of chemical compounds, quinone methides have been shown to react with cellular nucleophiles including amines, carbohydrates, alcohols, thiols, and ole fins. Peroxidase enzymes have recently been shown to catalyze the activation of a wide variety of xenobiotic compounds to reactive intermediates and these enzymes, particularly prostaglandin H synthase, have been suggested to play a role in the extrahepatic toxicity and carcinogenicity of several compounds. Since antioxidants are good electron donors we investigated whether BHT might be metabolically activated to BHT-quinone methide by peroxidase enzymes. This study reports on the metabolic activation of BHT by two peroxidase enzymes: horseradish peroxidase and prostaglandin H synthase. [Description provided by NIOSH]
• Subjects:
  Animals Enzymes Occupational Health Oxidants Safety Toxicology
• Keywords:
  Animal Studies Enzyme Activity Food Additives Oxidation Oxidative Processes Toxic Effects
• ISSN:
  0065-2598
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  301-309
• Volume:
  197
• NIOSHTIC Number:
  nn:20060365
• Citation:
  Adv Exp Med Biol 1986 Jan; 197:301-309
• Contact Point Address:
  David C. Thompson, Department Environmental Health Sciences, Johns Hopkins University Baltimore, MD 21205, USA
• CAS Registry Number:
  2,6-Di-tert-butyl-4-methylphenol (CAS RN 128-37-0)
• Editor(s):
  Kocsis JJ; Jollow DJ; Witmer CM; Nelson JO; Snyder R
• Federal Fiscal Year:
  1986
• Performing Organization:
  Johns Hopkins University, Baltimore, Maryland
• Peer Reviewed:
  True
• Start Date:
  19830701
• Source Full Name:
  Advances in Experimental Medicine and Biology
• End Date:
  19850630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7f7db8a015e744e42bf2cede03023c8144893e92e68611712aad3e778f1d3d550e71273a2c1ddead1951d5c28d24e5315142f4e3c8d7eb10d8764b3d30cca969
• Download URL:
  https://stacks.cdc.gov/view/cdc/224300/cdc_224300_DS1.pdf
• File Type:
  [PDF - 873.49 KB ]