While a significant amount of toluene, 25%–40%, is exhaled unchanged via the lungs, a greater proportion is metabolised and excreted via other pathways.

The primary route of toluene metabolism is by hydroxylation to benzyl alcohol by members of the cytochrome P450 (CYP) superfamily.

[4] Often toluene exposure occurs in conjunction with benzene and since they are to some degree metabolised by the same enzymes, the relative concentrations will determine their rate of elimination.

Studies have shown that even a modest amount of acute ethanol consumption can significantly decrease the distribution or elimination of toluene from the blood resulting in increased tissue exposure.

[15] There is significant endogenous hippuric acid production by humans; which shows inter- and intra-individual variation influenced by factors such as diet, medical treatment, alcohol consumption, etc.

[15][16] It has been suggested that urinary hippuric acid, the traditional marker of toluene exposure is simply not sensitive enough to separate the exposed from the non-exposed.

[20][21] Serious adverse behavioural effects are often associated with chronic occupational exposure [22] and toluene abuse related to the deliberate inhalation of solvents.

[23] Long-term toluene exposure is often associated with effects such as: psychoorganic syndrome;[24] visual evoked potential (VEP) abnormality;[24] toxic polyneuropathy, cerebellar, cognitive, and pyramidal dysfunctions;[23][24] optic atrophy; hearing disorders[25][26] and brain lesions.

[23] The neurotoxic effects of long-term use (in particular repeated withdrawals) of toluene may cause postural tremors by downregulating GABA receptors within the cerebellar cortex.