Influence of exposure route and oral dosage regimen on 1, 1-dichloroethylene toxicokinetics and target organ toxicity

The Journal of Pharmacology and Experimental Therapeutics
J V BrucknerC E Dallas

Abstract

The objective of this investigation was to elucidate the effects of route of exposure and oral dosage regimen on the toxicokinetics (TK) of 1,1-dichloroethylene (DCE). Fasted male Sprague-Dawley rats that inhaled 100 or 300 ppm for 2 h absorbed total systemic doses of (10 or 30 mg/kg DCE, respectively. Other groups of rats received 10 or 30 mg/kg DCE by intravenous injection, bolus gavage (by mouth), or gastric infusion (g.i.) over a 2-h period. Serial microblood samples were taken from the cannulated, unanesthetized animals and analyzed for DCE content by gas chromatography to obtain concentration versus time profiles. Inhalation resulted in substantially higher peak blood concentrations and area under blood-concentration time curves (AUC(0)(2)) than did gastric infusion of the same dose over the same time frame at each dosage level, although inhalation (AUC(0)(infinity)) values were only modestly higher. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltranspeptidase (GGT) activities were monitored as indices of kidney injury in the high-dose groups. NAG and GGT excretion were much more pronounced after inhalation than gastric infusion. Administration of DCE by gavage also produced much higher Cmax and AUC(0)(2...Continue Reading

References

Jan 1, 1978·Journal of Toxicology and Environmental Health·C C LeeJ S Woods
May 1, 1989·Toxicology and Applied Pharmacology·C E DallasJ V Bruckner
Jan 1, 1986·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J F QuastJ M Norris
Nov 1, 1986·Environmental Health Perspectives·J E KlaunigM A Pereira
Dec 1, 1985·Toxicology Letters·N M Jackson, R B Conolly
Aug 1, 1985·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·T A JorgensonM Robinson
Apr 1, 1969·Experimental and Molecular Pathology·K S Rao, R O Recknagel
Jan 1, 1983·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J F QuastJ M Norris
Feb 1, 1981·Toxicology and Applied Pharmacology·P ChiecoE S Reynolds
Apr 14, 1995·Chemico-biological Interactions·T F DowsleyJ L Bolton
Jan 1, 1996·Archives of Toxicology. Supplement. = Archiv Für Toxikologie. Supplement·W Dekant
Aug 1, 1996·Toxicology and Applied Pharmacology·K M LeeJ M Gallo
Jan 1, 1996·Environmental Health Perspectives·C P Weisel, W K Jo
Mar 31, 2000·Toxicology and Applied Pharmacology·K M LeeJ V Bruckner
Dec 2, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·J C CoffinM A Pereira
Feb 27, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·B S CummingsL H Lash
Mar 29, 2001·Drug Metabolism Reviews·P G Forkert
Dec 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Erik J MartinPoh-Gek Forkert
May 5, 2004·The Journal of Pharmacology and Experimental Therapeutics·Andrea C SimmondsPoh-Gek Forkert
Apr 4, 2006·Environmental Health Perspectives·Sydney M GordonPhilip C Singer
Feb 3, 2007·Environmental Science & Technology·Michael J MoranPaul J Squillace
Jul 8, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Y LiuJ V Bruckner
May 1, 2008·Environmental Toxicology and Pharmacology·Hana R PohlChristopher T De Rosa

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