Mode of action

The brain is the main target organ in toluene toxicity (Benignus, 1981b), but the mechanism of action is not known. Toluene has high lipid solubility and distributes in brain lipids. The toluene concentration in fatty tissue may be 80 times that in blood, however, accumulation in fatty tissue is slow due to poor blood supply. Nervous tissue is well supplied with blood and as a result toluene may accumulate and the concentration may be relatively high causing neurological effects (Cohr and Stokholm, 1979).

It has been suggested that the neurological changes seen on MRI scans of chronic toluene abusers (loss of grey and white matter differentiation, increased periventricular white matter signal intensity, diffuse cerebellar, cerebral and brainstem atrophy) may be due to increased water content of white matter or toluene induced metabolic changes in myelin (Rosenberg et al., 1988).

Electrolyte imbalance (usually associated with renal tubular acidosis) may cause ECG changes. Tachyarrhythmias are believed to be due to sensitisation of the myocardium to the potential arrhythmogenic effects of endogenous catecholamines.

The mechanism of toluene induced renal tubular acidosis seen with chronic toluene abuse has not been fully elucidated. The impaired ability to sustain a steep pH gradient in the collecting tubule, with normal or enhanced kidney bicarbonate reabsorption capacity, is evidence of distal renal tubular acidosis. There is also impairment of proximal nephron transport giving rise to aminoaciduria, hypophosphataemia, hyponatraemia, hypokalaemia and hypocalcaemia. The metabolite hippuric acid plays an important role in metabolic acidosis (Carlisle et al., 1991). The loss of sodium ions leads to extracellular fluid volume contraction and a decrease in the glomerular filtration rate. This may result in a high anion gap due to accumulation of hippuric acid and other anions (Carlisle et al., 1991). Distal renal tubular dysfunction may be due to decreased conductance of hydrogen ions through the active transport pathway resulting in distal acidification (Batlle et al., 1988).

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