Agency for Toxic Substances and Disease Registry
Toluene Toxicity
Biological Fate

Biological Fate

• Systemic absorption of inhaled toluene is rapid.

Inhalation is the primary route of toluene exposure; however, toluene can be absorbed through ingestion and dermal contact. Peak blood concentrations occur 15 to 30 minutes after inhalation. The amount of toluene absorbed by inhalation depends on the respiratory minute volume; thus, exercise affects the absorption rate of toluene. At rest, the lungs absorb about 50% of an inhaled dose.

The rate of absorption after oral intake is slower than after inhalation. Nevertheless, gastrointestinal absorption is nearly complete, and blood toluene levels peak 1 to 2 hours after ingestion. Percutaneous absorption is slow through intact skin and rarely produces toxicity.

• Toluene is distributed to highly perfused and fatty tissues.

Toluene is lipophilic and has little water solubility. It is distributed quickly to highly perfused tissues such as brain, liver, and kidney. It passes readily through cellular membranes and accumulates primarily in adipose and other tissues with high fat content. In the body, the half-life of toluene ranges from several minutes in highly vascular organs to slightly over 1 hour in fatty tissue. Toluene's affinity for the lipid-rich structures of nervous tissue results in CNS toxic effects within minutes.

• The major toluene metabolite is hippuric acid, which is excreted in the urine.

About 80% of absorbed toluene is oxidized in the liver to benzoic acid, which is then conjugated with glycine to form hippuric acid or with glucuronic acid to form benzoyl glucuronate. A small amount of toluene undergoes aromatic ring oxidation to form ortho- and para-cresols. Most inhaled or ingested toluene is eliminated in urine within 12 hours after exposure; a small amount (up to 20%) is eliminated as free toluene in expired air. Less than 2% of total toluene metabolites are excreted in the bile.

Challenge

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