Archives of Toxicology

, Volume 92, Issue 10, pp 3149–3162 | Cite as

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

  • Fatemeh Yavari
  • Christoph van Thriel
  • Michael A. Nitsche
  • Min-Fang KuoEmail author
Organ Toxicity and Mechanisms


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 300 ppm 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 200 ppm) 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.


Toluene Neuroplasticity Cognitive functions Motor learning Transcranial direct current stimulation Transcranial magnetic stimulation 



This research was funded by Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.

Compliance with ethical standards

Conflict of interest

M. A. Nitsche is a member of Advisory Board of Neuroelectrics. None of the remaining authors has potential conflicts of interest to be disclosed.

Supplementary material

204_2018_2277_MOESM1_ESM.pdf (1.1 mb)
Supplemental Fig. 1 Breathing and heart rates were recorded during two 35 minutes blocks in each session. Each block consisted of seven interleaved 5-minutes resting and cycling blocks. Blocks 2, 4, and 6 are related to cycling, and blocks 1, 3, 5, and 7 are rest periods. Data are shown as Mean ± SEM. Both heart and breathing rates increased during cycling. A significant interaction was observed between toluene and block for HR, which could be caused by increased arousal of the toluene-naïve participants in the first block. No other significant effect of toluene was observed (HR: Heart rate, BR: Breathing rate) (PDF 1095 KB)
204_2018_2277_MOESM2_ESM.docx (36 kb)
Supplementary material 2 (DOCX 36 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Fatemeh Yavari
    • 1
  • Christoph van Thriel
    • 2
  • Michael A. Nitsche
    • 1
    • 3
  • Min-Fang Kuo
    • 1
    Email author
  1. 1.Department of Psychology and NeurosciencesLeibniz Research Centre for Working Environment and Human FactorsDortmundGermany
  2. 2.Department of Toxicology, Networking Group: Neurotoxicology and ChemosensationLeibniz Research Centre for Working Environment and Human FactorsDortmundGermany
  3. 3.University Medical Hospital BergmannsheilBochumGermany

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