Toluene, also known as methylbenzene or phenylmethane is a clear, water-insoluble liquid with the typical smell of paint thinners, reminiscent of the sweet smell of the related compound benzene. It is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent.
The name toluene was derived from the older name toluol that refers to tolu balsam, an aromatic extract from the tropical American tree Myroxylon balsamum, from which it was first isolated. It was originally named by Jöns Jakob Berzelius.
Catalytic hydrogenation of toluene to methylcyclohexane requires a high pressure of hydrogen to go to completion, because of the stability of the aromatic system.
Inhalation of toluene fumes can be intoxicating, but in larger doses nausea-inducing. Chronic or frequent inhalation of toluene over long time periods leads to irreversible brain damage. Toluene may enter the human system not only through vapour inhalation from the liquid evaporation, but also following soil contamination events, where human contact with soil, ingestion of contaminated groundwater or soil vapour off-gassing can occur.
The toxicity of toluene can be explained mostly by its metabolism. As toluene has very low water solubility, it cannot exit the body via the normal routes (urine, feces, or sweat). It must be metabolized in order to be excreted. The methyl group of toluene is more easily oxidized by cytochrome P450 than the benzene ring. Therefore, in the metabolism of toluene, 95% is oxidized to become benzyl alcohol. The toxic metabolites are created by the remaining 5% that are ring oxidized to epoxides. Most of the epoxides become glutathione conjugated. However, the remainder will severely damage cells.
The metabolism of toluene
Toluene is mainly excreted as benzoic acid and hippuric acid, both formed by further metabolic oxidation of benzyl alcohol.
Toluene causes postural tremors by increasing extracellular concentrations of γ-aminobutyric acid (GABA) within the cerebellar cortex.4 Treatment with GABA agonists such as, benzodiazepines provide some relief from toluene induced tremor and ataxia.4 An alternative to drug treatment is vim thalamotomy.4 The tremors associated with toluene misuse do not seem to be a transient symptom, but an irreversible and progressive symptom which continues after solvent abuse has been discontinued.4There is some evidence that low level toluene exposure may cause disruption in the differentiation of astrocyte precursor cells.6 This does not appear to be a major hazard to adults; however, exposure of pregnant women to toluene during critical stages of fetal development could cause serious disruption to neuronal development.6
# B. S. Furnell et al., Vogel's Textbook of Practical Organic Chemistry, 5th edition, Longman/Wiley, New York, 1989. # (a) L. G. Wade, Organic Chemistry, 5th ed., p. 871, Prentice Hall, Upper Saddle RIver, New Jersey, 2003. # J. March, Advanced Organic Chemistry, 4th ed., p. 723, Wiley, New York, 1992.# Miyagi, Y., Shima, F., Ishido, K. et al. Tremor induced by toluene misuse successfully treated by a Vim thalamotomy. Journal of Neurology Neurosurgery and Psychiatry 66(6):794-6, (1999).# Urban, P., Lukáš, E., Pelclová, D. et al. Neurological and Neurophysiological Follow-up on Workers With Severe Chronic Exposure to Toluene. Neurotoxicity P25:s130, (2003).# Yamaguchi, H., Kidachi, Y. and Ryoyama, K. Toluene at Environmentally Relevant Low Levels Disrupts Differentiation of Astrocyte Precursor Cells. Archives of Environmental Health 57(3):232-8, (2002).
