Linked Life Data

9511902

Source:http://linkedlifedata.com/resource/pubmed/id/9511902

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-4-17
pubmed:abstractText
The urinary excretion of metabolites of phenyl glycidyl ether (PGE) and o-cresyl glycidyl ether (o-CGE) was investigated in rats. Urine was collected, in fractions, from rats intraperitoneally administered PGE or o-CGE in doses ranging from 0.033 to 1.0 mmol/kg. The metabolites were extracted from acidified urine with ethyl acetate or diethyl ether, and their identity was elucidated by GC/MS analysis. The epoxide of PGE can be inactivated by glutathione (GSH) conjugation or epoxide hydrolysis. After further metabolism, these routes lead to the urinary excretion of phenyl glycidyl ether mercapturic acid (PGEMA) and 3-(phenyloxy)lactic acid (POLA). The excretion of PGEMA and POLA was described before and is confirmed in this study. Additionally, a new metabolite was identified as N-acetyl-O-phenylserine (NAPS), which is proposed to be formed from POLA by subsequent oxidation, transamination, and N-acetylation. For PGEMA a linear dose-excretion relationship was found (r2 = 0.988), and the percentage of the dose excreted declined from 27% to 10% with increasing PGE dose. For NAPS also a linear dose-excretion relationship was found (r2 = 0.985), and NAPS accounted for 27% of the PGE dose. The excretion of PGEMA and NAPS was rather fast: 93% and 75%, respectively, of the respective total cumulative amounts excreted was already collected within 6 h after administration. The urinary metabolite profile of o-CGE was not investigated in rats before. Three urinary metabolites of o-CGE were identified, namely, 3-(o-cresyloxy)lactic acid (COLA), o-cresyl glycidyl ether mercapturic acid (o-CGEMA), and N-acetyl-O-(o-cresyl)serine (NACS), showing that the metabolite profiles of PGE and o-CGE are comparable. Up to a o-CGE dose of 0.333 mmol/kg, the excretion of o-CGEMA was linear (r2 = 0.997), while above this dose the excretion did not increase anymore. The percentage of the o-CGE dose excreted as o-CGEMA declined from 31% to 11% with increasing dose. Again 93% of the total cumulative amount of o-CGEMA excreted was collected within 6 h after administration of o-CGE. Analytical methods were developed for the quantitative determination of mercapturic acid metabolites of PGE and o-CGE. These methods were sufficiently sensitive for their determination in urine of rats administered PGE or o-CGE in the dose range applied. It is anticipated that the analytical methods developed are also sufficiently sensitive to investigate excretion of the mercapturic acid metabolites in humans occupationally exposed to low air concentrations (<6 mg/m3 of air, 8h-TWA) of PGE or o-CGE.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
111-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.
pubmed:affiliation
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't