The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats.
The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.
Dallas
C E
CE
Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602.
Ramanathan
R
R
Muralidhara
S
S
Gallo
J M
JM
Bruckner
J V
JV
D000280:Administration, Inhalation; D000818:Animals; D001944:Breath Tests; D006843:Hydrocarbons, Chlorinated / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014240:Trichloroethanes / Q000493:pharmacokinetics* / Q000633:toxicity
D006843:Hydrocarbons, Chlorinated; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane