Toxicokinetics and bioavailability of oral and intravenous 1,1-dichloroethylene.
Although aliphatic halocarbons have been identified as contaminants of drinking water supplies, little definitive information is available on their gastrointestinal (G.I) 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 (t1/2) or in any other pharmacokinetic parameter. Total body clearance, t1/2, 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 t1/2 of 1,1-DCE in orally dosed rats was somewhat longer than in their iv counterparts. The t1/2 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.
Putcha
L
L
Bruckner
J V
JV
D'Souza
R
R
Desai
F
F
Feldman
S
S
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001682:Biological Availability; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D004986:Ether; D005215:Fasting; D006207:Half-Life; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D004986:Ether; C029297:vinylidene chloride