Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, 44139, Dortmund, Germany.
Department of Toxicology, Networking Group: Neurotoxicology and Chemosensation, Leibniz Research Centre for Working Environment and Human Factors, 44139, Dortmund, Germany.
Arch Toxicol. 2018 Oct;92(10):3149-3162. doi: 10.1007/s00204-018-2277-x. Epub 2018 Aug 10.
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.
甲苯是一种众所周知的神经毒性有机溶剂，也是许多工业和商业产品的主要成分，如胶水、油漆稀释剂和汽油。许多工人在工作环境中经常接触甲苯，为避免产生不良健康影响，已经制定了职业接触限值 (OEL)。这些 OEL 或短期暴露限值因各国情况不同而有所差异，部分原因是动物和人体研究对其神经毒性作用的结果存在异质性，以及对潜在机制不良影响的评估存在差异。此外，其急性神经生理学效应在人类中仍知之甚少。本研究旨在调查健康志愿者急性接触甲苯对皮质兴奋性、可塑性和内隐运动学习的影响。17 名受试者接受了不同经颅磁刺激测量：运动阈值、短潜伏期皮质内抑制和皮质内易化，以及在吸入清洁空气或甲苯（单峰 200ppm）前后的短间隔传入抑制。此外，我们评估了经颅直流电刺激（tDCS）阳极刺激对运动皮质诱导的类似长时程增强的神经可塑性，以及参与者进行了运动序列学习任务，即序列反应时间任务。我们的研究结果表明，甲苯可消除阳极 tDCS 诱导的可塑性，减弱短潜伏期传入抑制测量中的皮质内易化，并增加抑制，而皮质脊髓兴奋性和皮质内抑制不受影响。在行为水平上，甲苯并未改变运动学习任务的表现。这些结果表明，甲苯可能通过调节 NMDA 受体活性，以及大脑中的皮质谷氨酸能和胆碱能神经传递来发挥作用。本研究鼓励进一步研究，以获得更多关于甲苯对未暴露和慢性暴露人群的作用机制和影响的知识。
