Toluene (methylbenzene, methylbenzol, phenylmethane, toluol) and xylene (dimethylbenzene, methyltoluene, and xylol) are common aromatic solvents used in laboratories and found as additives in glues, inks, dyes, lacquers, varnishes, paints, paint removers, pesticides, cleaners, and degreasers and as inherent constituents of gasoline. Xylene occurs in three isomers (meta-, ortho-, and para-), and commercial grade xylene contains a mixture of these, with the meta-isomer predominant. Toluene and xylene are both 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 is sometimes used recreationally by inhaling lacquer thinner, paints, glues, and other commercial products to induce a “sniffer's high.”

Is based on a history of exposure and typical CNS manifestations, such as euphoria or “drunkenness” followed by excitability, disinhibition, and various sensory and motor abnormalities. After acute ingestion, pulmonary aspiration is suggested by coughing, choking, tachypnea, or wheezing and is confirmed by chest radiography. Chronic past toxicity may be more difficult to establish beyond an exposure history and consistent end-organ effects without another likely cause.

1. 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 monitor exposure. Urine levels may correlate poorly with systemic effects.
2. Other useful laboratory studies may include CBC, electrolytes including phosphorous, glucose, BUN, creatinine, liver aminotransferases, creatine kinase (CK), blood gas analysis (to assess acidosis), and urinalysis. Chest radiographs and oxygenation assessment are recommended for severe inhalation or if pulmonary aspiration is suspected.

1. Toluene and xylene cause generalized CNS depression. Like other aromatic hydrocarbons, they may sensitize the myocardium to the arrhythmogenic effects of catecholamines. They are mild mucous membrane irritants that can affect the eyes and the respiratory and GI tracts.
2. Pulmonary aspiration may cause a hydrocarbon pneumonitis.
3. Chronic overexposure can lead to degenerative CNS disease as well as other target end-organ effects.
4. Kinetics. Symptoms of CNS toxicity are apparent rapidly after inhalation of high concentrations and 30-60 minutes after ingestion. Pulmonary effects may not appear for up to 6 hours after exposure. Toluene and xylene are each metabolized by multiple hepatic cytochrome P450 enzymes (mainly CYP2E1) leading to predictable metabolites including hippuric acid (toluene) and methylhippuric acid (xylene). Cresols are a minor metabolite of toluene.

1. 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.
2. Inhalation. The recommended workplace limits for toluene are 20 ppm (ACGIH TLV-TWA, with a “skin” notation for absorption), 10 ppm (California OSHA PEL-TWA, also “skin”) and 200 ppm (Federal OSHA PEL-TWA) and for xylene 100 ppm (ACGIH TLV-TWA and California and Federal OSHA PELs). The air levels considered immediately dangerous to life or health (IDLH, NIOSH) are 500 ppm for toluene and 900 ppm for xylene. Death has been reported after exposure to toluene at 1,800-2,000 ppm for 1 hour. The EPA reference concentration (RfC) is 5 mg/m³ for toluene and 0.1 mg/m³ for xylene, which is an estimate of the air level for the general population (including sensitive subgroups) that is likely to be without risk for deleterious effects over lifetime exposure.
3. Prolonged dermal exposure may cause chemical burns in additional to systemic absorption effects. Both toluene and xylene are well absorbed across the skin.

Toxicity may be the result of ingestion, pulmonary aspiration, skin absorption, or inhalation.

1. Acute inhalation (or heavy skin absorption) can be irritating to the respiratory tract and produce euphoria, dizziness, headache, nausea, and weakness. Exposure to high concentrations may cause delirium, coma, seizures, pulmonary edema, respiratory arrest, although most victims regain consciousness rapidly after they are removed from exposure. Prolonged QT, ST segment elevation, and dysrhythmias may result from cardiac sensitization. Massive exposures can cause pulmonary edema and ventilatory failure.
2. Chronic inhalation of toluene may cause permanent CNS impairment, including tremors; ataxia; brainstem, cerebellar, and cerebral atrophy; and cognitive and neurobehavioral abnormalities (including psychotic features). Other neurotoxic end-organ adverse effects of toluene include hearing and color vision impairment. Renal tubular acidosis type 1 (RTA-1) is another important manifestation of chronic toluene or subacute toxicity and can lead to severe electrolyte abnormalities and rhabdomyolysis. Chronic xylene exposure also has CNS neurotoxic potential as well as potential adverse renal, hepatic, and bone marrow effects.
3. 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.
4. Reproductive effects. Toluene is an established experimental and human reproductive hazard. Although reproductive toxicity from xylene is less firmly established, both solvents cross the placenta and are excreted in breast milk.

1. Emergency and supportive measures
   1. Inhalational exposure. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen and monitor oxygenation.
      1. If the patient is coughing or dyspneic, consider aspiration pneumonia. Treat for hydrocarbon pneumonia.
      2. If the patient remains asymptomatic after a 6-hour observation, chemical pneumonia is unlikely, and further observation or chest radiography should not be required.
   2. Treat coma, arrhythmias and bronchospasm if they occur. Caution: Epinephrine and other sympathomimetic amines may provoke or aggravate cardiac arrhythmias. Tachyarrhythmias may be treated with propranolol, 1-2 mg IV, or esmolol, 0.025-0.1 mg/kg/min IV.
2. Specific drugs and antidotes. There is no specific antidote.
3. Decontamination. Patients exposed only to solvent vapor who have no skin or eye irritation do not need decontamination. Clothing or skin contaminated with liquid can potentially expose response personnel by direct contact or through off-gassing vapor.
   1. Inhalation. Remove the victim from exposure and give supplemental oxygen if available.
   2. Skin and eyes. Remove contaminated clothing and wash exposed skin with soap and water. Flush exposed or irritated eyes with plain water or saline.
   3. Ingestion. Consider activated charcoal orally if conditions are appropriate (see Table I-37,), or removal via nasogastric tube if a very large, recent ingestion.
4. Enhanced elimination. There is no role for enhanced elimination.