Biphasic dose-response relationship for effects of toluene inhalation on locomotor activity

To investigate the effects of inhalation of toluene on spontaneous locomotor activity, rats were exposed to graded concentrations of toluene and locomotor activity was measured continuously before, during and after exposure. This study used a randomized, cross-over, graded-dose experimental design, with sham-exposure as the control. The locomotor activity pattern during toluene exposure depended upon the toluene concentration in the air. At the lowest effective concentration (5000 ppm) locomotor activity increased monophasically during exposure, and decreased monophasically during recovery. At higher concentrations (10,000-15,000 ppm) locomotor activity initially increased in a concentration-dependent manner. With continued exposure to the higher concentrations, locomotor activity decreased and eventually ceased at the highest concentration. Recovery from exposure to high concentrations of toluene was also biphasic. These results demonstrate that the behavioral responses to extremely high concentrations of toluene are characterized by biphasic actions as demonstrated both by analysis of concentration-response and time-action characteristics. Exposure to concentrations of toluene similar to those used in this study occurs during organic solvent abuse and glue sniffing in humans.