Toluene (methylbenzene, methylbenzol, phenylmethane, toluol) and xylene (dimethylbenzene, methyltoluene, and xylol) are common aromatic solvents found in glues, inks, dyes, lacquers, varnishes, paints, paint removers, pesticides, cleaners, and degreasers. The largest source of exposure is in the production and use of gasoline. Toluene and xylene are clear, colorless liquids with a sweet, pungent odor that is detectable at low air concentrations. They are less dense than water and highly volatile, readily producing flammable and toxic concentrations at room temperature. The vapor is heavier than air and may accumulate in low-lying areas. Toluene frequently is intentionally abused by inhaling lacquer thinner and paints (particularly spray paints) to induce a “sniffer's high.”
Mechanism of toxicity
Toluene and xylene cause generalized CNS depression. Like other aromatic hydrocarbons, they may sensitize the myocardium to the arrythmogenic effects of catecholamines. They are mild mucous membrane irritants that affect the eyes and the respiratory and GI tracts.
Pulmonary aspiration may cause a hydrocarbon pneumonitis (See Hydrocarbons).
Chronic abuse of toluene can cause diffuse CNS demyelination, renal tubular damage, and myopathy.
Kinetics. Symptoms of CNS toxicity are apparent immediately after inhalation of high concentrations and 30–60 minutes after ingestion. Pulmonary effects may not appear for up to 6 hours after exposure. Toluene is metabolized by alcohol dehydrogenase and by several cytochrome P-450 isoenzymes to benzyl alcohol (CYP2E1), p-cresol (CYP2E1, CYP2B6, CYP1A2), and o-cresol (CYP1A2). The presence of ethanol can inhibit toluene metabolism and prolong systemic toxicity.
Ingestion. As little as 15–20 mL of toluene is reported to cause serious toxicity. A 60-mL dose was fatal in a male adult, with death occurring within 30 minutes. The Environmental Protection Agency (EPA) oral reference dose (RfD), or maximum acceptable oral dose, is 0.08 mg/kg/d.
Inhalation. The recommended workplace limits are 50 ppm (ACGIH TLV-TWA) and 200 ppm (OSHA PEL) for toluene and 100 ppm (ACGIH TLV-TWA and OSHA PEL) for xylene, with a “skin” notation indicating the potential for appreciable skin absorption. The OSHA and ACGIH limits are based on the risk for irritant, narcotic, and chronic effects associated with exposure, and the NIOSH limit is based on the potential to cause CNS depression and respiratory irritation. The air levels considered immediately dangerous to life or health (IDLH) are 500 ppm for toluene and 900 ppm for xylene. Death has been reported after exposure to toluene at 1800–2000 ppm for 1 hour. The EPA reference concentration (RfC) is 5 mg/m3 based on neurologic effects in occupationally exposed workers. An RfC is an estimate of a continuous inhalation exposure concentration to people (including sensitive subgroups) that is likely to be without risk for deleterious effects during a lifetime.
Prolonged dermal exposure may cause chemical burns. Both toluene and xylene are well absorbed across the skin. The eye irritation threshold for xylene is 200 ppm.
Clinical presentation. Toxicity may be the result of ingestion, pulmonary aspiration, or inhalation.
Acute inhalation produces euphoria, dizziness, headache, nausea, and weakness. Exposure to high concentrations may rapidly cause delirium, coma, pulmonary edema, respiratory arrest, and death, although most victims regain consciousness rapidly after they are removed from exposure. Arrhythmias may result from cardiac sensitization. Acute exposure to vapors can irritate the mucous membranes of the respiratory tract, leading to reactive airway dysfunction syndrome (RADS). Massive exposures can cause pulmonary edema and respiratory arrest.
Chronic inhalation may cause permanent CNS impairment, including tremors; ataxia; brainstem, cerebellar, and cerebral atrophy; and cognitive and neurobehavioral abnormalities. Myopathy, hypokalemia, electrolyte and acid-base imbalance, renal tubular acidosis, and hepatitis are also common. Workers repeatedly exposed to toluene at 200–500 ppm have reported loss of coordination, impaired memory, and anorexia.
Ingestion of toluene or xylene may cause vomiting and diarrhea. If pulmonary aspiration occurs, chemical pneumonitis may result. Systemic absorption may lead to CNS depression.
Reproductive effects. Toluene at high levels is a reproductive hazard in humans and animals, but this effect has not been observed with low, chronic exposures. Both solvents cross the placenta and are excreted in breast milk. Microcephaly, developmental delay, and craniofacial and limb anomalies have been reported in women who regularly abused toluene recreationally while pregnant.
Diagnosis is based on a history of exposure and typical manifestations of acute CNS effects, such as euphoria and “drunkenness.” After acute ingestion, pulmonary aspiration is suggested by coughing, choking, tachypnea, or wheezing and is confirmed by chest radiography.
Specific levels. In acute symptomatic exposures, toluene or xylene may be detectable in blood drawn with a gas-tight syringe, but usually only for a few hours. The metabolites hippuric acid, o-cresol (toluene), and methylhippuric acid (xylene) are excreted in the urine and can be used to document exposure, but urine levels do not correlate with systemic effects.
Other useful laboratory studies include CBC, electrolytes, glucose, BUN, creatinine, liver aminotransferases, creatine kinase (CK), and urinalysis. Chest radiographs and pulse oximetry (or arterial blood gas measurements) are recommended for severe inhalation or if pulmonary aspiration is suspected.
Emergency and supportive measures
Inhalational exposure. Maintain an open airway and assist ventilation if necessary (See Airway and Breathing). Administer supplemental oxygen and monitor oxygenation.
If the patient is coughing or dyspneic, consider aspiration pneumonia. Treat for hydrocarbon pneumonia (See Hydrocarbons).
If the patient remains asymptomatic after a 6-hour observation, chemical pneumonia is unlikely, and further observation or chest radiography is not needed.
Treat coma (See Coma and stupor), arrhythmias (See Ventricular dysrhythmias), and bronchospasm (See Hypoxia) if they occur. Caution: Epinephrine and other sympathomimetic amines may provoke or aggravate cardiac arrhythmias. Tachyarrhythmias may be treated with
(See Propranolol), 1–2 mg IV, or
(See Esmolol), 0.025–0.1 mg/kg/min IV.
Specific drugs and antidotes. There is no specific antidote.
Decontamination. Patients exposed only to solvent vapor who have no skin or eye irritation do not need decontamination. However, victims whose clothing or skin is contaminated with liquid can secondarily contaminate response personnel by direct contact or through off-gassing vapor.
Log In to View More
If you don't have a subscription, please view our individual subscription options
below to find out how you can gain access to this content.
Want access to your institution's subscription?
Sign in to your MyAccess Account while you are actively authenticated on this website
via your institution (you will be able to tell by looking in the top right corner
of any page – if you see your institution’s name, you are authenticated). You will
then be able to access your institute’s content/subscription for 90 days from any
location, after which you must repeat this process for continued access.
If your institution subscribes to this resource, and you don't have a MyAccess account,
please contact your library's reference desk for information on how to gain access
to this resource from off-campus.
AccessMedicine Full Site: One-Year Subscription
Connect to the full suite of AccessMedicine content and resources including more than 250 examination and procedural videos, patient safety modules, an extensive drug database, Q&A, Case Files, and more.
Pay Per View: Timed Access to all of AccessMedicine
48 Hour Subscription
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.