The role of enzyme induction on metabolite formation of bis(2-methoxyethyl) ether in the rat

Details

• Personal Author:
  Begley KB ; Cheever KL ; Richards, Donald E. ; Weigel WW
• Description:
  The effect of enzyme induction on the metabolism of bis(2- methoxyethyl)ether (111966) (diglyme) was studied in rats. Male Sprague-Dawley-rats were administered 5.1 millimoles per kilogram (mmol/kg) diglyme or 0.1 percent phenobarbital (PB) in their drinking water for 22 days. The effects on hexobarbital sleeping time were evaluated. Other rats were pretreated with 5.1mmol/kg labeled diglyme or 0.1 percent PB administered in their drinking water for 22 days, and then given a single oral dose of 5.1mmol/kg carbon-14 labeled diglyme. Urine samples were collected at 6 to 96 hours post dosing and analyzed for diglyme metabolites. PB and diglyme caused significant decreases in hexobarbital sleeping time, PB showing the greater effect. Pretreatment with PB or diglyme did not significantly affect cumulative excretion of carbon-14 activity. Cumulative excretion of methoxyacetic-acid (625456), a minor metabolite, was significantly increased by both phenobarbital and diglyme, phenobarbital showing the greater effect. The authors conclude that pretreating rats with diglyme or PB increases the extent of cleavage of the ether bond in diglyme, forming 2- methoxyethanol, a precursor of methoxyacetic-acid, a putative reproductive toxicant. The possibility of altered metabolism and toxicity resulting from a shift from a major to a minor pathway may be an important consideration when assessing the risk of occupational exposure to diglyme or similar aprotic glycol ethers. [Description provided by NIOSH]
• Subjects:
  Enzymes Glycols Laboratories Occupational Health Safety Solvents Urine
• Keywords:
  Biotransformation Enzyme-activity In-vivo-studies Laboratory-animals NIOSH-Author Organic-acids Organic-solvents Urinalysis
• ISSN:
  0748-2337
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  5
• Issue:
  3
• NIOSHTIC Number:
  nn:00188654
• Citation:
  Toxicol Ind Health 1989 May; 5(3):601-607
• CAS Registry Number:
  Diglyme (CAS RN 111-96-6) ; Methoxyacetic acid (CAS RN 625-45-6)
• Federal Fiscal Year:
  1989
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Industrial Health
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2a90a82da6e503ff217a90a0eace77bcb302b8554df38e50cc88f913091e26491626ff73333a0a901e066b0beff3bf01133a29971372f583361a67b4050758c5
• Download URL:
  https://stacks.cdc.gov/view/cdc/205773/cdc_205773_DS1.pdf
• File Type:
  [PDF - 589.05 KB ]