Inhalation pharmacokinetics of 1,2-dichloroethane after different dietary pretreatments of male Sprague-Dawley rats.
Igwe OJ; Hee SS; Wagner WD
Arch Toxicol 1986 Oct; 59(3):127-134
The effects of pretreatment of weanling male Sprague-Dawley-rats with phenobarbital (50066) (PB), butylated-hydroxyanisole (25013165) (BHA) or disulfiram (97778) (DSF) on the inhalation kinetics of 1,2- dichloroethane (107062) (EDC) were determined. Rats were pretreated with one of four diets: AIN'76 powdered diet alone (control), with DSF for 10 days, with BHA for 10 days, or with PB for 7 days. After pretreatment, rats (two at a time) were exposed to EDC in a closed recirculation system for 5 hours and decline in EDC concentration was recorded. The maximum rate of metabolism (Vmax) and the apparent inhalation Michaelis constant (Km) were estimated for each treatment group. K(m) and V(max) values for EDC were lowest after DSF pretreatment. Thermodynamic (Ostwald's) partition coefficients were determined for EDC, and indicated moderate stability of EDC in adipose tissues. The pharmacokinetic dose dependence of EDC metabolism was demonstrated in control and DSF, BHA, and PB pretreated rats. Results suggest that at low EDC concentration range, uptake and or transport to the metabolizing enzymes limit the rate of metabolism but not the substrate affinity to the enzymes. The influence of DSF, PB and BHA on the basic inhalational kinetic constants may be used to predict the time course of equilibration and metabolism of any EDC concentration. While pretreatment did not seem to affect whole body equilibration time (90 to 100 minutes in all cases), metabolic parameters for EDC were affected. DSF had the greatest effect. Results indicate that systemic metabolism is responsible for the vast majority of EDC vapor uptake from the exposure system.
NIOSH-Author; Laboratory-animals; Pharmacology; Exposure-chambers; Dietary-effects; Chlorinated-ethanes; Toxic-effects; Thiurams; Anisoles;
Author Keywords: Inhalation pharmacokinetics; Butylated hydroxyanisole; Tetraethylthiuram disulfide; Disulfiram; 1,2-Dichloroethane; Glutathione S-transferases; Cytochrome P450
Orisa J. Igwe. The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105, USA
50-06-6; 25013-16-5; 97-77-8; 107-06-2
Archives of Toxicology