Agency for Toxic Substances and Disease Registry
Toluene Toxicity
Who is at Risk

Who is at Risk

Workers who manufacture or use toluene or toluene-containing products are at increased risk of exposure. An estimated 4 to 5 million workers are occupationally exposed to toluene. Workers at greatest risk for exposure include automobile mechanics; gasoline manufacturers, shippers, and retailers; dye and ink makers; and painters. Other workers who are potentially exposed to toluene include, but are not limited to, the following:

• Chronic, intentional toluene abuse can lead to serious adverse effects and death.

Many organic solvents, including toluene, have an addictive potential. Alcohol or opiates demonstrate a physiologic or biochemical addiction. Toluene is psychologically addictive. The adolescent population is most likely to intentionally abuse solvents, although the prevalence of this abuse is unknown. Solvent inhalation techniques are referred to as "bagging" or "huffing." Studies indicate that volatile-solvent sniffers are typically boys between the ages of 10 and 15 years of age who might concurrently use or later develop an alcohol, marijuana, or opiate habit. In general, solvent abuse tends to decrease with increasing age, but adults of both sexes might also abuse organic solvents.

• Concurrent use of alcohol or salicylates increases the risk of adverse effects from toluene exposure.

Because toluene is metabolized in the liver, liver disease can increase its
acute toxic effects. Concurrent use of alcohol, which competitively inhibits toluene metabolism, can also increase toluene's acute effects. In addition, experimental animal studies indicate that chronic exposure to toluene augments alcohol-induced fatty liver disease; thus, workers exposed to toluene who are chronic alcohol drinkers can have added risk due to their inability to detoxify alcohol.

Concurrent use of medication with toluene exposure can have an influence on toluene toxicity. Salicylates can competitively inhibit toluene metabolism; concurrent use of salicylates can reduce the clearance of both toluene and salicylates. Studies in humans indicate that the common analgesics, acetaminophen and aspirin, might inhibit toluene metabolism and influence toluene toxicity. CYP2E1 is involved in the initial step of the principal metabolic pathway for toluene and acetaminophen, and represents a potential site for a competitive metabolic interaction. Aspirin and one of the principal downstream metabolites of toluene, benzoyl coenzyme A, are conjugated with glycine. When glycine pools are depleted by competition for glycine by aspirin metabolism, toluene metabolism might be inhibited. In volunteers exposed for 4 hours to 300 mg/m³ toluene (80 parts per million [ppm]) with or without doses (1,000 mg/70 kg=14.3 mg/kg) of acetaminophen (paracetamol) or acetyl salicylic acid (aspirin), co-exposures with these analgesics increased the concentration of toluene in the blood compared with exposure to toluene alone. Acetaminophen co-exposure also significantly increased the area under the blood concentration versus time curve and the apparent blood clearance of toluene, consistent with an inhibition of toluene metabolism. These results are consistent with the hypothesis that high doses of aspirin might potentiate toluene effects on hearing by inhibiting toluene metabolism. This mechanism can be particularly important in workers exposed to toluene.

• Persons with cardiovascular, respiratory, and liver disease are at increased risk for toluene's adverse effects.

Like many organic solvents, toluene is a respiratory tract irritant, particularly at high airborne concentrations. Persons with underlying respiratory tract disorders, such as asthma and chronic obstructive pulmonary disease (COPD) or reactive airways dysfunction syndrome (RADS), can experience bronchospasm on exposure to any irritant, including toluene. Because toluene accumulates in adipose tissues, persons who are obese tend to retain more toluene than persons of normal weight, but the clinical significance of this is unknown.

Challenge

The patient's history is negative for asthma, chronic bronchitis, and allergic conditions. She has not been employed in any position entailing chemical exposure since the toluene diisocyanate exposure 2 years ago, but she has noticed mild, transient chest tightness and difficulty breathing when using self-service gasoline filling stations and when exposed to tobacco smoke.

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