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Toluene (methylbenzene, methylbenzol, phenylmethane, toluol) and xylene (dimethylbenzene, methyltoluene, and xylol) are common aromatic solvents found as additives in glues, inks, dyes, lacquers, varnishes, paints, paint removers, pesticides, cleaners, and de-greasers 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 intentionally abused by inhaling lacquer thinner, paints, glues, and other commercial products to induce a "sniffer's high."
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MECHANISM OF TOXICITY
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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.
Pulmonary aspiration may cause a hydrocarbon pneumonitis.
Chronic overexposure can lead to degenerative CNS disease as well as other target end-organ effects.
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 leading to predictable metabolites including hippuric acid (toluene) and methylhippuric acid (xylene). Cresols are a minor metabolite of toluene.
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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.
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.
Prolonged dermal exposure may cause chemical burns in additional to systemic absorption effects. Both toluene and xylene are well absorbed across the skin.
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CLINICAL PRESENTATION
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Toxicity may be the result of ingestion, pulmonary aspiration, skin absorption, or inhalation.
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Acute inhalation (or heavy skin absorption) can be irritating to the respiratory tract ...