Metabolism of diglyme by rat hepatocytes and human microsomes.

Details

• Personal Author:
  Richards, Donald E. ; Tirmenstein MA ; Toraason M
• Description:
  An overview of previously reported research utilizing in-vivo and in- vitro models to assess the metabolism of bis(2-methoxyethyl)ether (111966) (diglyme) was presented. Diglyme was linked to increased rates of miscarriages in women employed in the computer chip industry. Diglyme toxicity was attributed to its metabolite methoxyacetic-acid (625456) through cleavage of the interior ether bond of diglyme to form 2-methoxyethanol (109864) (ME). The bond cleavage was mediated by certain cytochrome-P450 isozymes. Diglyme metabolism in Sprague-Dawley-rats, rat hepatocytes, and human and rat hepatic microsomes confirmed that ME formation accounted for the toxicity of diglyme. Diglyme metabolites in urine and hepatocytes were qualitatively similar. The cleavage of diglyme to ME was comparable in microsomes from rats and humans, with human microsomes being more efficient at cleaving diglyme than rat microsomes. The involvement of CYP2E1-P450 isozyme in converting diglyme to ME in rats and humans was strongly implicated in in-vitro models. Pretreatment of rats with diglyme enhanced the formation of ME. The authors conclude that chronic exposure to diglyme may increase the cleavage of diglyme to ME in exposed workers. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Ether Ethylenes Glycols Laboratories Occupational Exposure Occupational Health Pregnancy Safety Urogenital Diseases Urogenital System

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• Keywords:
  NIOSH-Author; Ethers; Reproductive-hazards; Occupational-hazards; Laboratory-animals; Pregnancy; Prenatal-exposure; Glycols; Ethylenes; Cytotoxicity
• ISSN:
  1061-0251
• 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
• Pages in Document:
  33-43
• Volume:
  2
• NIOSHTIC Number:
  nn:00234461
• Citation:
  Occup Hyg 1996 Jan; 2(1-6):33-43
• CAS Registry Number:
  2-Methoxyethanol (CAS RN 109-86-4) ; Diglyme (CAS RN 111-96-6) ; Methoxyacetic acid (CAS RN 625-45-6)
• Federal Fiscal Year:
  1996
• Peer Reviewed:
  False
• Source Full Name:
  Occupational Hygiene
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/243521/cdc_243521_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]