© 1986 Oxford University Press
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Toxicokinetics and Bioavailability of Oral and Intravenous 1, 1 -Dichloroethylene1,2
Department of Pharmacology and Toxicology, University of Georgia Athens, Georgia 30602 *Department of Pharmaceutics, College of Pharmacy, University of Houston Houston, Texas 77030
Toxicokinetics and Bioavailability of Oral and Intravenous 1,1-Dichloroethylene. PUTCHA, L., BRUCKNER, J. V., D'SOUZA, R., DESAI, F., AND FELDMAN, S. (1986). Fundam. Appl. Toxicol. 6, 240–250. Although aliphatic halocarbons have been identified as contaminants of drinking water supplies, little definitive information is available on their gastrointestinal (G.1) absorption and toxicokinetics. Therefore, a study of a representative halocarbon, 1,1-dichloroethylene (1,1-DCE), was undertaken to contrast the kinetics of the chemical following iv injection with that following oral administration. Four dosage-levels of 1,1-DCE (10, 25, 50, and 100 mg/kg BW) in 50% aqueous polyethylene glycol 400 were given iv and po to fasted and nonfasted male Sprague—Dawley rats. Serial blood samples were taken from the tail artery of the lightly etherized animals for up to 490 min after dosing. 1,1-DCE concentrations in the whole blood were determined by gas chromatographic head-space analysis. Evaluation of the iv data revealed that disappearance of 1,1-DCE from the systemic circulation followed a triexponential pattern. Light ether anesthesia did not appear to alter the pharmacokinetics of iv-injected 1,1-DCE. There was no difference between nonfasted and fasted iv rats in biological half-life (t
) or in any other pharmacokinetic parameter. Total body clearance, t apparent volume of distribution and volume of distribution in the central compartment did show increases with increasing dose in these animals. Oral dosing experiments revealed that 1,1-DCE was absorbed very rapidly and completely from the G.I. tract. Peak blood levels were reached 2 to 8 min following oral administration of 1,1-DCE as an aqueous suspension. The t of 1,1-DCE in orally dosed rats was somewhat longer than in their iv counterparts The t values for nonfasted, orally dosed rats were longer than for their fasted counterparts, suggesting delayed absorption due to the presence of food in the G.I. tract. Bioavailability of 1,1-DCE, as determined by comparing areas under blood concentration versus time curves (AUCs), was equivalent in animals given the same dose of 1,1-DCE iv and po. AUCs increased with increasing dose in iv and po groups, but the increases were not proportional to dose.