Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.

B.M. de Rooij; J.N.M. Commandeur; O.R. Hommes; T. Aalbers; E.J. Groot; N.P.E. Vermeulen

doi:10.1021/tx970020n

Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.

B.M. de Rooij, J.N.M. Commandeur, O.R. Hommes, T. Aalbers, E.J. Groot, N.P.E. Vermeulen

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Abstract

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 metabolites, 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 (r

Original language	English
Pages (from-to)	111-118
Journal	Chemical Research in Toxicology
Volume	11
DOIs	https://doi.org/10.1021/tx970020n
Publication status	Published - 1998

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title = "Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.",

abstract = "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 metabolites, 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 (r",

author = "{de Rooij}, B.M. and J.N.M. Commandeur and O.R. Hommes and T. Aalbers and E.J. Groot and N.P.E. Vermeulen",

year = "1998",

doi = "10.1021/tx970020n",

language = "English",

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pages = "111--118",

journal = "Chemical Research in Toxicology",

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T1 - Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.

AU - de Rooij, B.M.

AU - Commandeur, J.N.M.

AU - Hommes, O.R.

AU - Aalbers, T.

AU - Groot, E.J.

AU - Vermeulen, N.P.E.

PY - 1998

Y1 - 1998

N2 - 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 metabolites, 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 (r

AB - 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 metabolites, 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 (r

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DO - 10.1021/tx970020n

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SN - 0893-228X

VL - 11

SP - 111

EP - 118

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

ER -

Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.

Abstract

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