The principal effect of toluene exposure is CNS depression.
Toluene produces reversible effects on the liver, kidneys, and nervous system; the nervous system appears to be most sensitive to its effects. The physiologic effects of toluene depend on the concentration and length of exposure. Most data concerning toluene’s effects on human health come from studies of workers with chronic exposure to toluene or from intentional solvent abusers who inhale high levels of toluene for self-intoxication. The applicability of these data to relatively low-level exposure in the environmental setting, however, is unknown.
Toluene’s anesthetic action can result in rapid CNS depression and narcosis at high concentrations. Volatilization after ingestion and hypoxia after aspiration can contribute to CNS toxicity, and aromatic impurities in commercial toluene-containing products can have added neurotoxic effects.
At low concentrations, toluene produces disturbances in basal ganglia dopaminergic mechanisms in experimental animals. Human exposure to 100 ppm of toluene (the permissible exposure level in the workplace) causes substantial complaints about poor air quality, altered temperature and noise perception, increased irritation of the nose and lower airways, and feelings of intoxication. Chronically exposed workers have scored lower on some tests of cognitive performance than did unexposed controls.
Several studies have examined the neuropsychiatric effects of acute exposure to toluene vapors. Cerebellar and CNS integrative dysfunction predominate. In addition, peripheral nerve dysfunction has been reported, but the peripheral neuropathies might have been due to impurities, such as n-hexane, in the toluene. Long-term toluene abuse has led to neuropsychiatric and neurobehavioral disorders, which in many cases, but not all, were reversible. Some chronic toluene abusers have developed structural CNS damage. Magnetic-resonance imaging (MRI) and brainstem auditory-evoked response evaluation of the brains of chronic toluene abusers show permanent changes in brain structure that correlated with the degree of brain dysfunction. MRI results revealed loss of gray-white matter contrast, diffuse supratentorial white matter high-signal lesions, and low signal in the basal ganglia and midbrain. in the brains of neuropsychologically impaired toluene abusers.
Toluene acts initially as a respiratory tract irritant. Several mechanisms precede respiratory decompensation: replacement of alveolar air by vaporized hydrocarbon, ventilation-perfusion dysfunction caused by bronchospasm, formation of a hyaline membrane, and solubilization of the lipid surfactant layer. As severity of exposure increases, respiratory depression leading to death can result. Pulmonary aspiration of gastric contents that might occur during altered consciousness can lead to chemical pneumonitis.
Cardiac dysrhythmias are postulated to be a leading cause of death after intentional toluene abuse.
Toluene appears to lower the threshold of myocardial susceptibility to the dysrhythmogenic effects of catecholamines. Sudden death among volatile-solvent abusers has often been preceded by strenuous physical activity and is believed to result from lethal, nonperfusing cardiac dysrhythmias. In cases of severe poisoning, cardiac dysrhythmias can also occur secondary to hypoxia and acidosis caused by CNS-mediated hypoventilation.
Toluene does not cause the severe blood dyscrasias associated with
benzene exposure.
Toluene does not cause the hematopoietic effects noted with chronic benzene exposure. Early studies suggesting such effects were performed using toluene that was contaminated with benzene. Modern distillation methods prevent significant benzene contamination of toluene.
Metabolic acidosis can occur in persons who abuse volatile organic solvents, including toluene.
Metabolic acidosis, hypokalemia, hematuria, proteinuria, distal renal-tubular acidosis, and pyuria have been reported in chronic volatile-solvent abusers, although these effects have usually been reversible. Accumulation of hippuric acid and other organic acid by-products of toluene metabolism is thought to be responsible for the elevated anion-gap metabolic acidosis that occurs with toluene abuse. Elevated urinary concentration of retinol-binding protein has been correlated with toluene exposure in a dose-dependent manner, which suggests that early renal-tubular effects might occur in abusers. Hepatotoxicity has been reported in glue sniffers, but studies in chronically exposed workers show no or minimal hepatic damage.
The role of toluene in developmental toxicity is uncertain.
Toluene has been implicated in adverse developmental effects that have occurred in offspring of chronic toluene abusers. Children chronically exposed in utero from high-dose maternal solvent abuse throughout pregnancy have demonstrated microcephaly, CNS dysfunction, attention deficits and hyperactivity, developmental delay, minor craniofacial and limb anomalies, and variable growth deficiency. Severe neonatal acidosis has also been noted, possibly secondary to maternal renal-tubular acidosis. However, these case reports must be regarded with caution because most results to date have been confounded by probable exposure to alcohol or other organic solvents during pregnancy. In addition, the small number of exposed persons and the lack of precise exposure data limit the conclusions that can be drawn.
Although epidemiologic studies of workers exposed to multiple organic solvents have found greater risks of death from numerous cancers compared to the general nonexposed population, no evidence exists showing that toluene alone causes cancer. Animal studies have not suggested that toluene is carcinogenic.
In high concentrations, toluene exerts an irritant action on the eyes, skin, and mucous membranes. Direct dermal exposure defats the skin, leading to dryness, fissuring, and possible secondary infection. A few cases of contact urticaria have been described after occupational exposure to a solvent mixture containing toluene, but it is not clear that toluene was the responsible agent.
