COMPARISONS BETWEEN OPERANT RESPONSE AND 1,1,1-TRICHLOROETHANE TOXICOKINETICS IN MOUSE-BLOOD AND BRAIN

The effect of 1,1,1-trichloroethane (TRI) inhalation on operant respon se was evaluated in relation to the concentration of TRI in blood and brain tissue in mice during exposure. Male CD-1 mice were trained to l ever-press for an evaporated milk reinforcer on a variable interval (V I 60) schedule for 2 h. Trained mice were then exposed to either 3500 or 5000 ppm TRI for 100 min, and the changes in the schedule-controlle d performance were measured. Additional groups of mice were exposed un der the same conditions as those used in the behavioral study and sacr ificed at various times during exposure, and the blood and brain sampl es were collected and subsequently analyzed for TRI content by headspa ce gas chromatography. Uptake of TRI into blood and brain was rapid, w ith near steady-state levels reached after approximately 40-60 min of exposure. Inhalation of 5000 ppm, but not 3500 ppm TRI was seen to cau se inhibition of operant response, starting similar to 30 min followin g the initiation of inhalation exposure and beginning to recover after 80 min of exposure. The threshold concentrations for the maximal beha vioral inhibition were similar to 110 mu g/g and 130 mu g/ml in mouse brain and blood, respectively. It appears that in addition to TRI conc entrations in blood and brain tissue, the time it takes to reach the a pparent threshold TRI concentration was also a determinant for the ons et of TRI neurobehavioral depression.