Circadian Variations of Acute Toxicity and Blood and Brain Concentrations of Inhaled Toluene in Rats

To investigate circadian variations in the acute toxicity of toluene, rats were exposed to it (2000 ppm or 4000 ppm) both in the dark (the animals' active phase) and the light (the inactive phase) for 4 hours. The performance decrements of rats were greater in the light phase than in the dark phase in all time zones of exposure to toluene. In the dark phase, the performance recovered almost to that pre-exposure, whereas a significant delay of recovery was noted in the light phase. The differences in the number of lever presses between exposure to 2000 ppm toluene and control (air) exposure were also greater in the light phase than in the dark phase. Significant differences according to the time of exposure were also found in toluene concentrations in blood and the brain. Both blood and brain concentrations in the light phase were higher than those in the dark phase at four hours after exposure to 2000 ppm toluene or at two hours after exposure to 4000 ppm toluene. These results suggest that there was a significant difference in circadian susceptibility after exposure to toluene, which might be caused by circadian differences in the pharmacokinetics of toluene in the light and dark phases.