Toxicokinetics and Bioavailability of Oral and Intravenous 1, 1 -Dichloroethylene

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. Althoughaliphatic halocarbons have been identified as contaminants ofdrinking water supplies, little definitive information is availableon 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 chemicalfollowing 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 poto fasted and nonfasted male Sprague—Dawley rats. Serialblood samples were taken from the tail artery of the lightlyetherized animals for up to 490 min after dosing. 1,1-DCE concentrationsin the whole blood were determined by gas chromatographic head-spaceanalysis. Evaluation of the iv data revealed that disappearanceof 1,1-DCE from the systemic circulation followed a triexponentialpattern. Light ether anesthesia did not appear to alter thepharmacokinetics of iv-injected 1,1-DCE. There was no differencebetween 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 distributionin the central compartment did show increases with increasingdose in these animals. Oral dosing experiments revealed that1,1-DCE was absorbed very rapidly and completely from the G.I.tract. Peak blood levels were reached 2 to 8 min following oraladministration of 1,1-DCE as an aqueous suspension. The t of1,1-DCE in orally dosed rats was somewhat longer than in theiriv counterparts The t values for nonfasted, orally dosed ratswere longer than for their fasted counterparts, suggesting delayedabsorption due to the presence of food in the G.I. tract. Bioavailabilityof 1,1-DCE, as determined by comparing areas under blood concentrationversus time curves (AUCs), was equivalent in animals given thesame dose of 1,1-DCE iv and po. AUCs increased with increasingdose in iv and po groups, but the increases were not proportionalto dose.