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Metabolism of bis(2-methoxyethyl)ether by rat and human liver microsomes.

Authors
Tirmenstein-MA
Source
Toxicologist 1992 Feb; 12(1):59
NIOSHTIC No.
20037030
Abstract
Bis(2-methoxyethyl)ether (diglyme) is a member of the glycol ether class of chemicals. These compounds are widely used as industrial solvents. Previous studies have shown that diglyme is metabolized in vivo by cleavage of the central ether linkage to 2-methoxyethanol (2-ME). 2-MB exposure has been associated with teratogenesis, immunotoxicity, testicular atrophy and hemopoietic toxicity in experimental animals. The present study was designed to assess the effects of various cytochrome P-450 inducers on diglyme metabolism and to compare human and rat liver metabolism of diglyme. Rat liver microsomes exhibited NADPH-dependent metabolism of diglyme to 2-ME, 2-(2-methoxyethoxy)ethanol and an unidentified metabolite. These products were also detected in incubations with NADPH and human liver microsomes although there were quantitative differences in the amounts of each metabolite formed between human and rat microsomes. Induction of rat microsomal enzymes with phenobarbital or ethanol increased the conversion of diglyme to methoxyethanol by a factor of 5.6 and 4.2 fold respectively over controls. However, B-naphthoflavone induction did not significantly increase diglyme cleavage to 2-ME. Pretreatment of rats with 0.6% diglyme in drinking water for 4 days significantly increased cytochrome P-450 and P-450 reductase levels in liver microsomes. In addition, there was an increase in P-450 associated enzyme activities (ethoxycoumarin deethylase and aniline hydroxylase activities) following the diglyme pretreatment. Microsomes from rats pretreated with diglyme exhibited a 2.4 fold increase in rates of diglyme cleavage as compared to controls. These results indicate that induction of rats with specific P-450 inducers can increase the formation of 2-ME from diglyme by rat liver microsomes. Also, diglyme pretreatment induced cytochrome P-450 levels in rat liver microsomes and apparently increased the activity of those P-450 isozymes associated with the cleavage of diglyme to 2-ME.
Keywords
Metabolic-activation; Metabolic-rate; Metabolic-study; Metabolism; Chemical-reactions; Laboratory-testing; Solvents; Glycols; In-vivo-study; Laboratory-animals; Animal-studies; Animals
CAS No.
111-96-6; 109-86-4; 111-77-3
Publication Date
19920201
Document Type
Abstract
Fiscal Year
1992
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0731-9193
NIOSH Division
DBBS
Source Name
The Toxicologist. Society of Toxicology 31st Annual Meeting, February 23-27,1992, Seattle, Washingtion
State
OH; FL
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