Studies on the mechanism of enhancement of butylated hydroxytoluene-induced mouse lung toxicity by butylated hydroxyanisole.

Details

• Personal Author:
  Thompson DC ; Trush MA
• Description:
  Mechanisms by which butylated-hydroxyanisole (25013165) (BHA) enhances the lung toxicity induced by butylated-hydroxytoluene (128370) (BHT) were examined in CD1-mice. In glutathione depleted lung slices BHA enhanced covalent binding of BHT to protein by 360 percent. Although BHT at 175mg/kg intraperitoneally (ip) had no effect on lung to body weight ratios (LBR), BHA at 250mg/kg or diethyl-maleate (141059) (DEM) at 1mg/kg given subcutaneously 30 minutes prior to BHT at that dose significantly increased the LBR. Neither 250mg/kg BHA nor 1500mg/kg BHA had an effect on lung glutathione levels 4 hours after treatment. The covalent binding of BHT to mouse lung microsomes in the presence of hydrogen-peroxide (H2O2) was increased by the addition of BHA to the reaction media. Other peroxides also increased the binding of BHT to lung microsomes. In lung and liver microsomes, NADPH oxidation and H2O2 formation significantly increased in the presence of BHA. A scheme of the possible mechanisms of BHA enhancement of BHT was included. The authors conclude that BHA may enhance the toxicity of BHT by facilitating the activation of BHT. [Description provided by NIOSH]
• Subjects:
  Antioxidants Food Additives Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Food-additives In-vitro-studies In-vivo-studies Laboratory-animals Liver-microsomal-metabolism Liver-microsomes Lung-cells NIOSH-Grant NIOSH-Publication Synergism
• ISSN:
  0041-008X
• 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:
  122-131
• Volume:
  96
• Issue:
  1
• NIOSHTIC Number:
  nn:00184500
• Citation:
  Toxicol Appl Pharmacol 1988 Oct; 96(1):122-131
• CAS Registry Number:
  2,6-Di-tert-butyl-4-methylphenol (CAS RN 128-37-0) ; Diethyl maleate (CAS RN 141-05-9) ; tert-Butylhydroxyanisole (CAS RN 25013-16-5)
• Federal Fiscal Year:
  1989
• NORA Priority Area:
  Pulmonary System Disorders
• Performing Organization:
  Johns Hopkins University
• Peer Reviewed:
  True
• Start Date:
  19830701
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  19851231
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f8e3108e46d989af67b1cb52137f244fbc8a0838e7d37434ba3025396aac7659473f437d5c6fa96407c21b9f78b0b931311f89504b2042fc53d4c3a61035fc1d
• Download URL:
  https://stacks.cdc.gov/view/cdc/185682/cdc_185682_DS1.pdf
• File Type:
  [PDF - 832.71 KB ]