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Metabolism of diglyme by rat hepatocytes and human microsomes.

Authors
Toraason-M; Richards-DE; Tirmenstein-MA
Source
Occup Hyg 1996 Jan; 2(1-6):33-43
Link
NIOSHTIC No.
00234461
Abstract
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.
Keywords
NIOSH-Author; Ethers; Reproductive-hazards; Occupational-hazards; Laboratory-animals; Pregnancy; Prenatal-exposure; Glycols; Ethylenes; Cytotoxicity
CODEN
OCHYE9
CAS No.
111-96-6; 625-45-6; 109-86-4
Publication Date
19960101
Document Type
Journal Article
Fiscal Year
1996
NTIS Accession No.
NTIS Price
Issue of Publication
1-6
ISSN
1061-0251
NIOSH Division
DBBS
Source Name
Occupational Hygiene
State
OH
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