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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.”

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  1. Mechanism of toxicity

    1. 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.

    2. Pulmonary aspiration may cause a hydrocarbon pneumonitis (See Hydrocarbons).

    3. Chronic abuse of toluene can cause diffuse CNS demyelination, renal tubular damage, and myopathy.

    4. 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.

  2. Toxic dose

    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. The Environmental Protection Agency (EPA) oral reference dose (RfD), or maximum acceptable oral dose, is 0.08 mg/kg/d.

    2. 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.

    3. 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.

  3. Clinical presentation. Toxicity may be the result of ingestion, pulmonary aspiration, or inhalation.

    1. Acute inhalation produces euphoria, dizziness, headache, nausea, and weakness. ...

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