Aromatic (Benzene, Toluene) Toxicity


Article Author:
Christina Vitale


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Scott Gutovitz



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Updated:
1/20/2019 8:22:39 AM

Introduction

Hydrocarbons are organic compounds consisting of carbon and hydrogen atoms. 

There are three basic structural forms of hydrocarbons: 

  • Aliphatic: straight or branched chained carbon arrangements
  • Aromatic: carbons arranged in a ring
  • Halogenated: consisting of carbons, hydrogens and a halogen atom

Two aromatic hydrocarbons that are commonly abused for their euphoric effect include toluene (methylbenzene) and benzene. Toluene is a colorless, clear liquid that has a sweet, distinct smell. It is insoluble in water but soluble in nonpolar compounds. It is widely used as a raw material in the production of organic compounds such as benzene. Toluene and benzene can be found in products such as gasoline, nail polish, hair dye, acrylic spray paint, airplane glue, plastic cement, cleaning products, and paint thinners. Toluene and/or benzene exposure, whether environmental, accidental or intentional, can cause toxicity throughout the body, specifically affecting the pulmonary system, central and peripheral nervous system, gastrointestinal, cardiovascular, renal, hepatic, dermal, and hematological systems. The hallmark complications of toluene toxicity are renal tubular acidosis and hypokalemic paralysis. Benzene is known to cause hematological disorders. Rarely, both can result in death.[1]

Etiology

The effects of toluene and benzene toxicity is usually acquired through inhalation.

Inhalation occurs by three different methods[2]:

  • Huffing: the individual soaks a rag with a chemical and then places it over the mouth and nose.
  • Bagging: the individual puts the chemical in a bag and repeatedly inhales deeply from the bag.
  • Sniffing: the chemical is directly inhaled via the nostrils. 

Epidemiology

Toluene is the most widely abused inhaled volatile drug. Abusers who seek its euphoric effect are typically teenagers and younger adults. According to the Toxic Exposure Surveillance System of the American Association of Poison Control Systems, 54% of the abusers of inhaled volatile substances were teenagers age 13 to 19 years old, and 15% were children aged 6 to 12 years old. In addition, there is a higher incidence of volatile substance abuse in states with larger rural populations and in lower socioeconomic groups.[3]

Pathophysiology

The toxic potential of hydrocarbons depends on the following:

  • Physical Characteristics
    • Viscosity: thickness of a liquid. Fluids with low viscosity flow more easily.
    • Surface tension: the ability of liquid molecules to cohere to each other.
    • Volatility: the ability of a liquid or solid to vaporize.
  • Chemical Characteristics
    • Aliphatic
    • Aromatic
    • Halogenated
  • Presence of Toxic Additives
    • Pesticides
    • Heavy metals
  • Routes of Exposure
    • Inhalation
    • Ingestion
    • Topical
  • Concentration 
  • Dose

Toluene and benzene are highly volatile aromatic hydrocarbons with a usual route of exposure in the form of inhalation. Inhalation of an aromatic hydrocarbon can result in systemic absorption and the potential for significant toxicity.[4]

Pulmonary Toxicity

All hydrocarbons, including toluene and benzene, can cause chemical pneumonitis by direct contact with the pulmonary parenchyma and destroying alveolar and capillary membranes. This results in vascular permeability and edema.

Cardiac Toxicity

All hydrocarbons can cause life-threatening dysrhythmias, such as ventricular tachycardia and ventricular fibrillation.

Central Nervous System Toxicity

Toluene causes euphoria followed by depression.

Renal and Metabolic Toxicities

Toluene specifically causes renal tubular acidosis. The typical metabolic profile is a normal anion gap hyperchloremic acidosis with hypokalemia and a urine pH of 5.5. Toluene’s metabolites, hippuric acid and benzoic acid, are possibly the cause for an elevated anion gap metabolic acidosis. In addition, toluene also causes hypokalemia leading to muscle weakness and if low enough, muscle paralysis. Rhabdomyolysis is a common complication.[5]

Hematological Toxicities

Exposure to benzene is associated with an increased incidence of hematologic disorders, such as aplastic anemia, acute myelogenous leukemia, and multiple myeloma.[6]

Toxicokinetics

Toluene

Toluene is inhaled via the lungs and distributed widely throughout the body, specifically adipose tissue, brain, liver, and kidneys. The liver converts toluene into organic acids. Toluene is metabolized by the cytochrome P-450 system. The end products include benzoic acid and hippuric acid. Hippuric acid is excreted by the kidney. Some toluene is excreted unchanged in expired air and urine.[7]

Benzene

Benzene is absorbed in the body through inhalation, skin exposure, and ingestion. It is rapidly metabolized in the liver, becomes water soluble, and is excreted by the kidneys within 48 hours. Benzene itself is non-toxic, but its metabolites form in the liver, specifically benzoquinone and malonaldehyde, have bone marrow toxicity.[8]

History and Physical

History

While taking the history, try to obtain the following information:

  • To what drug or substance was the patient exposed?
  • Was it intentional or accidental exposure?
  • What was the route of exposure inhalation or ingestion?
  • How long ago did exposure occur?
  • How long was patient inhaling/ingesting the toxic substance?
  • Did patient use or was exposed to any other toxic substance?

Physical Exam for Hydrocarbon Exposure[4]

After exposure to hydrocarbons, any of the following can be present: 

Pulmonary

  • Tachypnea
  • Grunting
  • Wheezing
  • Retractions

Cardiac

  • Ventricular arrhythmias

Central nervous system

  • Slurred speech
  • Ataxia
  • Lethargy
  • Coma

Gastrointestinal

  • Nausea
  • Vomiting
  • Abdominal pain 

Specific for toluene

  • Headache
  • Dizziness
  • Confusion
  • Muscle weakness and paralysis

Specific for benzene

  • Lethargy
  • Shortness of breath

Evaluation

There are no specific hydrocarbon tests in standard use when evaluating suspected hydrocarbon intoxication.[4]

When evaluating these patients, initial actions include:

  • Cardiac monitor
  • Pulse oximetry
  • ECG

Laboratory tests include:

  • Complete blood count
  • Complete metabolic panel
  • Arterial blood gas
  • Creatine kinase

Radiographic tests include:

  • Chest x-ray. However, Note that the initial radiograph in a symptomatic patient may be deceptively clear. Radiographic changes usually occur in 2 to 6 hours and are almost always present by 24 hours. The most common radiographic finding is bilateral infiltrates at the bases with multi-lobar involvement.

Treatment / Management

There is no specific antidote for toluene or benzene toxicity.[9][4][10]

When treating these patients, the following actions should be taken:

  • Contact poison control
  • Secure airway
  • Provide supplemental oxygen, if wheezing
  • Administer B2-agonists, if wheezing
  • Ventilatory support
  • Treat hypotension with aggressive IV crystalloid fluid
  • Treat hydrocarbon induced dysrhythmias with propranolol, esmolol, or lidocaine
  • No benefit to gastric lavage or activated charcoal
  • Correct electrolyte abnormalities
  • Administer blood products as needed

Pearls and Other Issues

Contact a medical toxicologist or regional poison control center for all symptomatic and asymptomatic exposures to aromatic hydrocarbons or hydrocarbons with toxic additives.[4]

Further observation or hospitalization is required for patients with symptomatic hydrocarbon exposure.

For toluene, the patient should be admitted to correct renal tubular acidosis, hypokalemia, and/or rhabdomyolysis.

For benzene, consult hematologist/oncologist for further evaluation of hematological abnormality. 

Pearls:

  • The hallmarks of acute toluene toxicity include renal tubular acidosis and hypokalemic paralysis.
  • Benzene toxicity can cause hematological disorders such as aplastic anemia, acute myelogenous leukemia, and multiple myeloma.

Enhancing Healthcare Team Outcomes

The management of toluene toxicity is by a multidisciplinary team that consists of an emergency department physician, internist, hematologist, toxicologist, and poison control. These patients may develop multiorgan failure and rapid management is vital. The care of these patients is supportive with hydration, blood transfusion and reversal of any electrolyte imbalance. The prognosis of these patients is guarded; in the long term exposure to these aromatic compounds increases the risk of certain leukemias and multiple myeloma. (Level V)

 

 


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Aromatic (Benzene, Toluene) Toxicity - Questions

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A 17-year-old male who presents to the emergency department with a chief complaint of dizziness and severe muscle cramping. Patient states he was in his basement decorating posters with spray paint when he felt symptoms. The patient may have toluene toxicity. What would the arterial blood gas show for a patient with toluene toxicity?



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A 17-year-old male who presents to the emergency department with a chief complaint of dizziness and severe muscle cramping. The patient states he was sniffing glue before onset of symptoms. The patient may have toluene toxicity. Which of the following is the best explanation for the patient’s muscle weakness?



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A patient was recently diagnosed with acute myelogenous leukemia. What is the structural form of the hydrocarbon that causes hematological disorders?



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A 17-year-old male who presents to the emergency department with a chief complaint of a headache, dizziness, confusion and muscle cramping. Patient states he is addicted to huffing gasoline. His arterial blood gas shows metabolic acidosis. Which of the following hydrocarbons is responsible for his symptoms and how does it cause metabolic acidosis?



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A 17-year-old who presents to the emergency department with her parents after inhaling four acrylic paint cans. Which of the following is associated with acute toluene toxicity?



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Aromatic (Benzene, Toluene) Toxicity - References

References

Ford JB,Sutter ME,Owen KP,Albertson TE, Volatile substance misuse: an updated review of toxicity and treatment. Clinical reviews in allergy     [PubMed]
Flanagan RJ,Fisher DS, Volatile substance abuse and crime: data from U.K. press cuttings 1996-2007. Medicine, science, and the law. 2008 Oct     [PubMed]
Spiller H,Lorenz DJ, Trends in volatile substance abuse. Journal of addictive diseases. 2009     [PubMed]
Tormoehlen LM,Tekulve KJ,Nañagas KA, Hydrocarbon toxicity: A review. Clinical toxicology (Philadelphia, Pa.). 2014 Jun     [PubMed]
Dickson RP,Luks AM, Toluene toxicity as a cause of elevated anion gap metabolic acidosis. Respiratory care. 2009 Aug     [PubMed]
Rinsky RA,Smith AB,Hornung R,Filloon TG,Young RJ,Okun AH,Landrigan PJ, Benzene and leukemia. An epidemiologic risk assessment. The New England journal of medicine. 1987 Apr 23     [PubMed]
Decharat S, Hippuric Acid levels in paint workers at steel furniture manufacturers in Thailand. Safety and health at work. 2014 Dec     [PubMed]
Arnold SM,Angerer J,Boogaard PJ,Hughes MF,O'Lone RB,Robison SH,Schnatter AR, The use of biomonitoring data in exposure and human health risk assessment: benzene case study. Critical reviews in toxicology. 2013 Feb     [PubMed]
Lifshitz M,Sofer S,Gorodischer R, Hydrocarbon poisoning in children: a 5-year retrospective study. Wilderness     [PubMed]
Khanna P,Devgan SC,Arora VK,Shah A, Hydrocarbon pneumonitis following diesel siphonage. The Indian journal of chest diseases     [PubMed]

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