Minimal tolerance to the effects of 1,1,1-trichloroethane on fixed-ratio responding in mice

Most laboratory animal studies of the behavioral or neurophysiological effects of repeated exposures to volatile organic solvents find little evidence for substantial tolerance. This study examined the development of tolerance to the effects of 1,1,1-trichloroethane (1,1,1-TCE) on fixed-ratio responding in four mice. The subjects were exposed to 6000 ppm solvent vapor for 20 min of the daily 45-min operant sessions. Once a week, a series of four concentrations (1000-8000 ppm) were substituted for the daily exposure in order to obtain a cumulative concentration-effect curve. This proved to be a rapid and reliable method with which to ascertain the effects of 1,1,1-TCE over a range of concentrations. During the 15 days of 20-min exposure, the subjects showed a slight but significant increase in both response rates during exposure and in the rate of recovery following exposure. Maximal changes in these measures were evident in the first 7 days, with no further decreased sensitivity over the final 8 days of exposure. The concentration-effect curves determined during and after the daily exposures showed no significant shifts in either direction from the initial curve. Thus, while some alteration in the daily acute effects was noted, this tolerance was not of large magnitude and could not be detected as a change in the concentration-effect curve.