title: A liquid chromatographic-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 microM. Results indicate that the concentration of 1,2-DEB in blood peaked at 2 h post intraperitoneal injection and rapidly declined thereafter. In contrast, 1,2-DAB levels in blood were fairly constant up to 24 h postinjection. Urine concentrations of 1,2-DEB were highest at the first collection interval (0-12 h postinjection), and dropped rapidly thereafter; concentrations at 24 h were similar to concentrations observed at 48 h postexposure. Urine concentrations of 1,2-DAB, however, showed the reverse, with peak concentrations observed at 24 h postinjection and only a slight decrease in concentration by 48 h.
authors.affiliation: Center for Biological Monitoring and Modeling, Health Effects and Risk Sciences Division, Battelle, Pacific Northwest Division, Richland, Washington 99352, USA. karla.thrall@pnl.gov
authors.forename: Karla D
authors.initials: KD
authors.lastname: Thrall
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gies
authors.forename: Allison M
authors.initials: AM
authors.lastname: Cartmell
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Jolen J
authors.initials: JJ
authors.lastname: Soelberg
authors.forename: Joel A
authors.initials: JA
authors.lastname: Klein
mesh_terms: D000098:Acetophenones / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D001555:Benzene Derivatives / Q000032:analysis / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000032:analysis / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000098:Acetophenones; D001555:Benzene Derivatives; D004785:Environmental Pollutants; C064750:1,2-diethylbenzene; C048792:1,2-diacetylbenzene