Effect of acute exposure to toluene on cortical excitability, neuroplasticity, and motor learning in healthy humans.

Abstract

Toluene is a well-known neurotoxic organic solvent and a major component of many industrial and commercial products such as adhesives, paint thinners and gasoline. Many workers are regularly exposed to toluene in their working environment and occupational exposure limits (OELs) have been set to avoid adverse health effects. These OELs or short-term exposure limits vary from 14 to 300ppm across countries partly due to heterogeneity of the findings from animal and human studies about its neurotoxic effects and the evaluation of the adversity of the underlying mechanisms. Furthermore, its acute neurophysiological effects remain poorly understood in humans. The purpose of this study was to investigate the effects of acute exposure to toluene on cortical excitability, plasticity, and implicit motor learning in healthy volunteers. Seventeen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, short-latency intracortical inhibition and intracortical facilitation, and short-interval afferent inhibition before and after clean air or toluene (single peak of 200ppm) administration. Furthermore, we evaluated long-term potentiation-like neuroplasticity induced by anodal transcranial direct current stimulation (tDCS) over the motor cortex, and the participants conducted a motor sequence learning task, the serial reaction time task. Our findings revealed that toluene abolished the plasticity induced by anodal tDCS, attenuated intracortical facilitation, and increased inhibition in the short-latency afferent inhibition measure, while cortico-spinal excitability and intracortical inhibition were not affected. On the behavioural level, toluene did not alter performance of the motor learning task. These results suggest that toluene might act by modulating NMDA receptor activity, as well as cortical glutamatergic and cholinergic neurotransmission in the human brain. This study encourages further research to obtain more knowledge about mechanisms of action and effects of toluene on both naïve and chronically exposed populations.