The underlying mechanisms of toluene-induced neurotoxicity in the human brain: physiological and cognitive perspectives

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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 with the potential risk to develop work-related diseases due to long-term exposure. Occupational exposure limits (OELs) have been set, ranging from 14-300ppm across countries, to avoid adverse health effects. The wide range of these safety limits is partially due to poor understanding of the underlying pathophysiological effects in humans. We have recently demonstrated the neurophysiological impact of acute toluene exposure via non-invasive brain stimulation techniques in healthy participants, and found important effects on neuroplasticity, and cortical excitability under exposures permitted by the German OEL. In this proposal, we aim to extend the knowledge about the action of toluene to the population with occupational long-term exposure with or without clinical symptoms. Three groups of participants (healthy controls without exposure, chronically exposed without symptoms, and chronically exposed with symptoms) will be recruited, and will be explored and compared with respect to both, cognitive and neurophysiological parameters. Additionally, the effects of acute exposure to toluene will be explored in the two groups without symptoms. We are expecting that in the study without acute toluene-exposition, the chronically exposed groups show cognitive, and physiological deficits, as compared to the healthy non-exposed group, and that this effect is more prominent in the group which developed symptoms. We expect furthermore that acute toluene exposition has more prominent effects on these parameters in the chronically exposed group without clinical symptoms, as compared to the not chronical exposed healthy control group. The results of this project will provide more profound insight into the mechanisms, and conditions, of the action of toluene in humans especially with respect to the transition from acute to chronic neurotoxic effects of this organic solvent.