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Title: A Liquid Chromatography-Mass Spectrometric Method to Evaluate the Distribution Kinetics of 1,2-Diethylbenzene and its Metabolite, 1,2-Diacetylbenzene in the F344 Male Rat

Abstract

Diethylbenzene (DEB) is a moderately volatile, colorless liquid found in gasoline, kerosene, and fuel oils. Exposure to DEB has been shown to produce peripheral neuropathy in rats, and the ortho isomer of DEB (1,2-DEB) is generally believed to be the isomer responsible. 1,2-DEB is assumed to be metabolized primarily by direct oxidation of the ethyl side chain to form two enantiomers of 1-(2-ethylphenol) ethanol and their glucuroconjugates, which are the main 1,2-DEB metabolites, and 1,2-diacetylbenzene (1,2-DAB), a minor metabolite. The metabolite 1,2-DAB appears to be a chromogenic neurotoxin. A liquid chromatographic-mass spectrometric (LC-MS) method using Atmospheric Pressure Photoionization (APPI) for quantifying 1,2-DEB and 1,2-DAB in blood, urine and brain tissues from animals treated with an intraperitoneal injection of 1,2-DEB was developed. Calibration curves were prepared using matrix-specific standards with concentrations ranging from 0.068 to 402 µM. Results indicate that the concentration of 1,2-DEB in blood peaked at 2 hr post intraperitoneal injection and rapidly declined thereafter. In contrast, 1,2-DAB levels in blood were fairly constant up to 24 hr post injection. Urine concentrations of 1,2-DEB were highest at the first collection interval (0-12 hr post injection), and dropped rapidly thereafter; concentrations at 24 hr were similar to concentrations observed atmore » 48 hr post exposure. Urine concentrations of 1,2-DAB, however, showed the reverse, with peak concentrations observed at 24 hr post injection and only a slight decrease in concentration by 48 hr.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
899147
Report Number(s):
PNNL-SA-48094
400412000; TRN: US200706%%511
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Toxicology and Environmental Health, 70(1):67-72
Country of Publication:
United States
Language:
English
Subject:
02 PETROLEUM; ANIMALS; ATMOSPHERIC PRESSURE; BLOOD; BRAIN; CALIBRATION; ETHANOL; FUEL OILS; GASOLINE; INTRAPERITONEAL INJECTION; ISOMERS; KEROSENE; KINETICS; MALES; METABOLITES; OXIDATION; PHOTOIONIZATION; URINE

Citation Formats

Thrall, Karla D., Gies, Richard A., Cartmell, Allison M., Wu, Hong, Soelberg, Jolen J., and Klein, Joel A. A Liquid Chromatography-Mass Spectrometric Method to Evaluate the Distribution Kinetics of 1,2-Diethylbenzene and its Metabolite, 1,2-Diacetylbenzene in the F344 Male Rat. United States: N. p., 2007. Web. doi:10.1080/15287390600751173.
Thrall, Karla D., Gies, Richard A., Cartmell, Allison M., Wu, Hong, Soelberg, Jolen J., & Klein, Joel A. A Liquid Chromatography-Mass Spectrometric Method to Evaluate the Distribution Kinetics of 1,2-Diethylbenzene and its Metabolite, 1,2-Diacetylbenzene in the F344 Male Rat. United States. doi:10.1080/15287390600751173.
Thrall, Karla D., Gies, Richard A., Cartmell, Allison M., Wu, Hong, Soelberg, Jolen J., and Klein, Joel A. Mon . "A Liquid Chromatography-Mass Spectrometric Method to Evaluate the Distribution Kinetics of 1,2-Diethylbenzene and its Metabolite, 1,2-Diacetylbenzene in the F344 Male Rat". United States. doi:10.1080/15287390600751173.
@article{osti_899147,
title = {A Liquid Chromatography-Mass Spectrometric Method to Evaluate the Distribution Kinetics of 1,2-Diethylbenzene and its Metabolite, 1,2-Diacetylbenzene in the F344 Male Rat},
author = {Thrall, Karla D. and Gies, Richard A. and Cartmell, Allison M. and Wu, Hong and Soelberg, Jolen J. and Klein, Joel A.},
abstractNote = {Diethylbenzene (DEB) is a moderately volatile, colorless liquid found in gasoline, kerosene, and fuel oils. Exposure to DEB has been shown to produce peripheral neuropathy in rats, and the ortho isomer of DEB (1,2-DEB) is generally believed to be the isomer responsible. 1,2-DEB is assumed to be metabolized primarily by direct oxidation of the ethyl side chain to form two enantiomers of 1-(2-ethylphenol) ethanol and their glucuroconjugates, which are the main 1,2-DEB metabolites, and 1,2-diacetylbenzene (1,2-DAB), a minor metabolite. The metabolite 1,2-DAB appears to be a chromogenic neurotoxin. A liquid chromatographic-mass spectrometric (LC-MS) method using Atmospheric Pressure Photoionization (APPI) for quantifying 1,2-DEB and 1,2-DAB in blood, urine and brain tissues from animals treated with an intraperitoneal injection of 1,2-DEB was developed. Calibration curves were prepared using matrix-specific standards with concentrations ranging from 0.068 to 402 µM. Results indicate that the concentration of 1,2-DEB in blood peaked at 2 hr post intraperitoneal injection and rapidly declined thereafter. In contrast, 1,2-DAB levels in blood were fairly constant up to 24 hr post injection. Urine concentrations of 1,2-DEB were highest at the first collection interval (0-12 hr post injection), and dropped rapidly thereafter; concentrations at 24 hr were similar to concentrations observed at 48 hr post exposure. Urine concentrations of 1,2-DAB, however, showed the reverse, with peak concentrations observed at 24 hr post injection and only a slight decrease in concentration by 48 hr.},
doi = {10.1080/15287390600751173},
journal = {Journal of Toxicology and Environmental Health, 70(1):67-72},
number = ,
volume = ,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}