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Source (1,2,3,5)
Toluene is a clear, colorless, flammable liquid with a sweet, pungent odor. It occurs naturally in crude oil and in the tolu tree. Toluene is a solvent that can be found in paints, lacquers, thinners, cleaning agents, adhesives, fingernail polish, rubber, and dyes. The manufacturing process of other chemicals, nylon, and plastics may also involve toluene. To improve octane ratings of gasoline, toluene is added along with benzene and xylene.
Toluene exposure can include:
- Inhalation, ingestion, or dermal exposures
- Breathing contaminated workplace air or automobile exhaust
- Working with gasoline, paint, lacquer, or dyes
- Living near hazardous waste sites
- Individuals who intentionally smoke or inhale products containing toluene to get high. Toluene is the most frequently abused inhaled volatile drug.
Toluene does not stay in the environment long due to evaporation in the air and degradation by bacteria, but may be introduced when:
- Products containing toluene are used and enter the air
- Solvents and petroleum products are spilled or leak into surface and ground water
- Toluene-containing products are disposed in landfills and enter soil or water nearby
Toxicokinetics and Biotransformation (1,4)
Toluene is readily absorbed from both the respiratory tract when inhaled and the gastrointestinal tract when ingested. This solvent can be detected in arterial blood within 10 seconds following exposure in the air and within 15 to 30 minutes in the gastrointestinal tract. Toluene rapidly accumulates in the brain due to its high rate of perfusion and lipid content. Toluene is first transformed to benzyl alcohol by cytochrome P450 enzymes in the liver. Benzyl alcohol is then metabolized to benzaldehyde and benzoic acid by ADH and ALDH. Following this transformation, liver enzymes activate benzoic acid forming a coenzyme A benzoic acid derivative. When it reacts with glycine, this derivative forms hippuric acid. About 60-70% of toluene absorbed from the lungs in excreted in urine as hippuric acid within 12 hours of exposure. A small portion may also be exhaled unchanged. The image below shows the biotransformation from toluene to hippuric acid.
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Mechanism of Action (1)
The mechanism of action for toluene toxicity is not completely known. One possible mechanism is the Meyer-Overton theory which involves the partitioning of lipophilic parent compounds into membrane lipids. Solvents in cholesterol-filled interstices between phospholipids and sphingolipids change membrane fluidity, and this may affect intercellular communication and normal ion movement. Another potential mechanism is that toluene partitions into hydrophobic areas of proteins, and this interaction alters membrane-bound enzyme activity and receptor specificity. The mechanism of chronic toluene toxicity is not known, but seems to concentrate in areas of the brain with the highest myelin content.
Target organs (1,5)
The central nervous system (especially the brain) is the primary target organ in both acute and chronic exposures. The below image depicts what occurs after toluene concentrates in the brain. Toluene rapidly accumulates in the brain due to its high rate of perfusion and high lipid content. Other tissues with high lipid content such as adipose tissue also tend to accumulate toluene. It is also possible that the heart, kidney, and liver may also be targets.
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Biomarkers (2,5)
Toluene and its metabolites can be measured in blood and urine to determine if exposure to toluene has occurred. Toluene leaves the body rapidly, so tests must be done within 12 hours of exposure.
Signs and symptoms of toxicity (2,4,5)
Acute exposure at low to moderate levels include:
-
- Tiredness
- Confusion
- Headache
- Weakness
- Dizziness
- Euphoria
- Drunken-type actions
- Memory loss
- Nausea
- Vomiting (with blood if ingested)
- Loss of appetite
- Chest tightness
- Eye irritation from vapor exposure
- Skin irritation from dermal contact
Acute exposure at high levels include:
-
- Blurred vision
- Tremors
- Shallow, rapid breathing
- Brain ventricular irregularities
- Cardiac arrhythmias
- Paralysis
- Unconsciousness
- Convulsions
Chronic daily inhalation exposure in the workplace may cause:
-
- Hearing loss
- Color vision loss
- Nystagmus (involuntary eye movement)
- Impaired speech
- Ataxia
- Tremors
- Permanent brain damage (cerebral atrophy)
- Respiratory tract irritation, pulmonary lesions
Treatments (3,6)
- Remove the individual from the exposure area.
- Flush with water for at least 15 minutes if exposed to eyes or skin. Following thorough irrigation, eye or skin ointment treatments may be applied to treat symptoms. If skin is severely burned, surgical removal may be required.
- Give milk if toluene has been ingested. Do not induce vomiting. Gastric lavage may be used to eliminate substance from the stomach
- Symptomatic treatment to address seizures, abnormal heart rate, and breathing support if necessary
- Administer IV fluids to correct electrolyte and acid base alterations (potassium replacement, hydration)
- If exposure is intentional, patient education, therapy, rehabilitation, and follow-up should be a focus.
Carcinogenicity (2,4)
Toluene is generally considered non-carcinogenic. It has not shown mutagenicity or carcinogenicity in humans or laboratory animals.
Genetic susceptibility or heritable traits (3)
Women have been found to be at an increased risk for toluene-induced arrhythmias such as QT prolongation and Torsades de Pointes.
Historical or unique exposures (7,8)
Gasoline and chemical spills are unfortunately very common due to leaks in pipelines and barge crashes. There are many instances where toluene has been leaked into the environment and have lead to potential exposures to the general population. As discussed earlier, once toluene reaches the air, it generally evaporates or is degraded but small amounts may remain in waterways and soil. One of the largest toluene leaks occurred in Fremont, Ohio in 1988. Approximately 100,000 gallons of toluene leaked from a pipeline and contaminated 14 miles of the Sandusky River. About 500 people were evacuated from the area due to the fumes. At least two emergency response workers were treated for toluene exposure, one from inhalation and the second from direct contact with contaminated water after falling through the icy river.
The majority of toluene exposures occur in the workplace due to accidents. A search of the OSHA website for accidental cases using the keyword toluene results in 100 cases. Several of the cases resulted in death due to inhalation of large amounts of toluene when enclosed in a small area or from explosions caused by the very flammable liquid. Details of each of these cases can be found here.
References
- Bruckner JV, Anand S, Warren D. Toxic Effects of Solvents and Vapors. In: Klaassen CD. eds. Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition. McGraw-Hill; Accessed June 24, 2020. https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=958§ionid=53483749
- Agency for Toxic Substances and Disease Registry: Division of Toxicology and Human Health Sciences. Toluene-ToxFAQs. Accessed June 24, 2020. Available from: https://www.atsdr.cdc.gov/toxfaqs/tfacts56.pdf
- Camara-Lemarroy CR, Rodriguez-Gutierrez R, Monreal0-Robles R, and Gonzaelz-Gonzalez JG. Acute toluene intoxication – clinical presentation, management and prognosis: a prospective observational study. BMC Emergency Medicine. 2015; 15: 19.
- Von Burg R. Toxicology Update: Toluene. Journal of Applied Toxicology. March 1993; 13(6): 441-446.
- U.S. Environmental Protection Agency. Toluene. Accessed July 5, 2020. Available from: https://www.epa.gov/sites/production/files/2016-09/documents/toluene.pdf
- Purohit MP. First Aid for Toluene Poisoning. Dove Med. Accessed July 6, 2020. Available from: https://www.dovemed.com/healthy-living/first-aid/first-aid-toluene-poisoning/
- Weiss M. Hundreds Evacuated in Pipeline Leak. The Associated Press. 18 February 1988. Available from: https://apnews.com/923440fa513b8ecf61fffff5ff07f358
- United States Department of Labor: Occupational Safety and Health Administration. Accident search results for toluene. Available from: https://www.osha.gov/pls/imis/accidentsearch.search?sic=&sicgroup=&naics=&acc_description=&acc_abstract=&acc_keyword=%22Toluene%22&inspnr=&fatal=&officetype=&office=&startmonth=&startday=&startyear=&endmonth=&endday=&endyear=&keyword_list=on&p_start=&p_finish=0&p_sort=&p_desc=DESC&p_direction=Next&p_show=20