AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Toluene (methylbenzene, toluol, phenylmethane) is an aromatic hydrocarbon (C₇H₈) commonly used as an industrial solvent for the manufacturing of paints, chemicals, pharmaceuticals, and rubber. It is identified as CAS#108-88-3 and United Nations Department of Transportation's number for toluene is UN#1294.

Toluene is found in gasoline, acrylic paints, varnishes, lacquers, paint thinners, adhesives, glues, rubber cement, airplane glue, and shoe polish. At room temperature, toluene is a colorless, sweet smelling, volatile liquid.

Toxicity can occur from accidental or deliberate inhalation of fumes, ingestion, or absorption through the skin. Toluene abuse or glue sniffing has become widespread, especially among children or adolescents, because it is readily available and inexpensive. Toluene is commonly abused by saturating or soaking a sock or rag with spray paint, placing it over the nose and mouth, and inhaling to get a sensation of euphoria, buzz, or high. Slang names for inhalation include huffing (ie, soaking a sock or rag) and bagging (ie, spraying paint into a plastic bag and inhaling). With bagging, exhaled air is rebreathed and resulting hypoxia and hypercapnia may add to the disorienting effects of the solvent.

The Occupational Safety and Health Administration (OSHA) has determined the acceptable level of occupational exposure to toluene for people in the workplace. Toluene levels of 100 ppm are considered safe for workers. Levels of 150 ppm are acceptable for short periods ( <8 h). Toluene levels of 2000 ppm are considered dangerous to life and health. However, some people may be more sensitive to the effects of inhaled solvents than others; occupational asthma has occurred in some workers exposed to toluene levels considered safe in the workplace. For such people, protective equipment should be used and provided by employers, even when toluene levels are in the acceptable range.

Workers with a history of asthma induced by solvent exposure should also be warned about and protected from short-term exposure to higher concentrations. The duration of the exposure, not just the level, may be significant as well. Recent animal studies have suggested that exposure to subtoxic toluene levels, as low as 40 ppm, for prolonged periods, 104 hours per week for 16 weeks, may cause neurotoxicity.

Pathophysiology

Acute intoxication from inhalation primarily affects the CNS, causing euphoria, dizziness, confusion, CNS depression, headache, vertigo, hallucinations, seizures, ataxia, tinnitus, optic neuropathy, peripheral neuropathy, stupor, and coma.

Toluene also may have direct negative effects on cardiac automaticity and conduction and may sensitize the myocardium to circulating catecholamines. Sudden death secondary to cardiac arrhythmias has been reported. Pulmonary effects include bronchospasm, asphyxia, and aspiration pneumonitis.

Long-term toluene exposure or abuse is devastating, affecting the CNS, GI system, liver, kidneys, skeletal muscle, blood, and skin. Chronic CNS sequelae include neuropsychosis, cerebral cortex atrophy, cerebellar degeneration and ataxia, optic and peripheral neuropathies, decreased cognitive ability, blindness, ototoxicity, and deafness.

GI symptoms from inhalation and ingestion may result in abdominal pain, nausea, vomiting, and hematemesis. Reported renal toxicity from toluene exposure includes renal tubular acidosis, hypokalemia, hypophosphatemia, hyperchloremia, azotemia, pyuria, hematuria, and proteinuria. Hepatotoxicity manifests with ascites, jaundice, hepatomegaly, and liver failure. With the widespread abuse of volatile substances in young people today, hepatitis secondary to toluene toxicity, not just infectious causes, should be considered in the differential diagnosis in young patients who present with concerning findings.

Hematological consequences of exposure may include lymphocytosis, macrocytosis, eosinophilia, hypochromia, and basophilic stippling. Cutaneous contact with skin may range in severity from dermatitis to extensive chemical burns with coagulation necrosis. Toluene affects skeletal muscle; rhabdomyolysis, myoglobinemia, and a severe muscle weakness similar to Guillain-Barré have been reported.In 2005, chronic exposure to toluene by inhalation was found to affect bone metabolism, contributing to bone resorption and inhibiting bone formation.

Frequency

United States

Glue is accessible and inexpensive; thus, glue sniffing is becoming widespread. Most frequently, glue sniffing is observed in teenagers and young adults in lower economic groups. An estimated 3-4% of American teenagers engage in sniffing on a regular basis and 7-12% of high school students have tried sniffing at least once. Incidence in young people is rising. Chronic nonintentional exposure also occurs among people in the painting, gasoline, chemical, and rubber industries. The 1998 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System records only 2312 exposures to toluene and xylene combined. Of these, only 15 sustained major adverse outcomes, and no deaths were reported. This report severely underestimates the abuse of this agent.

International

Solvent abuse is a popular practice around the world. In the United Kingdom, 3.5-10% of children younger than 13 years have abused volatile substances, and 0.5-1% are long-term users. In Singapore, toluene glue sniffing has reached epidemic proportions. In 1980, 24 cases of solvent abuse were reported. By 1984, this number had increased to 763. From 1987-1991, 1781 glue sniffers were identified.

In 2004, it was reported that street children in India were abusing typewriter eraser fluid, which contains toluene; the patients cited easy access, affordability, and a regular "high" as reasons for usage. In low-income families in Sao Paulo, Brazil, 24% of children had inhaled a volatile substance at some time and 4.9% had inhaled within the last month.

Petrol (containing 13% toluene) sniffing has been reported among Native Americans in Canada and Aborigines in Australia. In Japan, studies have shown an increased likelihood of illicit drug use including toluene abuse, amongst children with the tendencies of attention deficit/hyperactivity disorder.

Mortality/Morbidity

Sudden death is the most serious risk from inhalation of toluene or other volatile substances. Although trauma, aspiration, and asphyxia from plastic bag use are contributing factors to mortality from solvent abuse, 4 direct modes of toxicity leading to death from toluene and other inhaled substances are anoxia, respiratory depression, vagal stimulation, and, most importantly, cardiac arrhythmias.

Volatile substance abuse sensitizes the myocardium to circulating catecholamines. Sudden alarm, exercise, and sexual activity may induce arrhythmias. In many cases of death associated with solvent abuse, fright and running were the immediate antemortem events.

Prolonged exposure to toluene by inhalation is associated with CNS, heart, liver, kidney, and lung damage. Other sequelae include muscle weakness, nasal ulcerations, recurrent epistaxis, chronic rhinitis, neuropsychiatric abnormalities, GI symptoms, and peripheral neuropathies (see Pathophysiology).

Fifty percent of chronic solvent abusers are women in their prime childbearing years. With exposure, toluene crosses the placenta and additional morbidity arises from children born with abnormalities similar to fetal-alcohol syndrome (FAS).

Exposure to toluene may be harmful during childhood development as well. Some research in young rats age 5 days to 8 weeks, has shown that p-nitrotoluene has an adverse affect on the developing brain inducing hyperactivity.

• In the 1960s, a total of 110 cases of sudden death from solvent abuse were reported in the US. In 1988, in the UK, 133 deaths were reported in people aged 11-76 years and from varying social backgrounds; 72% of these deaths occurred in adolescents, and 90% of deaths occurred in males.
• In Singapore, from 1983-1991, 33 people were found to have toluene in their blood postmortem; 22 were known glue sniffers; 11 were suspected of solvent abuse; 6.1% of deaths were from acute toluene poisoning; and 87.9% were associated with falling, drowning, or jumping, which suggests a correlation between the intoxicating effect of toluene and the high incidence of traumatic death of its users.
• From 1983-1991, 4 deaths attributed to occupational exposures were reported in Singapore.

Race

No scientific data indicate that outcomes of toluene exposure are based on race.

Sex

Although typically thought of as an activity of young males (most mortalities occur in young males), more than 50% of chronic solvent abusers are females in their prime childbearing years.

Age

Toluene inhalation is found in people of all ages.

• Most acute cases occur in young males aged 11-19 years who participate in glue sniffing as a group activity.
• Cases have been reported in people aged in their 50s and 60s.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Determining a history of toluene exposure or risk of exposure on admission is important; determining whether exposure was by inhalation, ingestion, or skin absorption is important. Determining if the patient has a history of toluene diisocyanate (TDI)–induced asthma from work-related exposure is also important. One recent study found that doxycycline, in patients with a history of toluene-induced occupational asthma, may reduce airway inflammation and hyperresponsiveness.

• History of huffing or bagging before presentation or history of previous abuse of inhalants
• History of other drugs that may be in the patient's system, including alcohol (ETOH), cocaine, and marijuana
• • Toluene intoxication has a similar presentation to alcohol intoxication.
  • Alcohol inhibits the metabolism of toluene and raises the concentration of toluene in the blood 2-fold.
  • Cocaine, or any sympathomimetic use, may increase risks of fatal arrhythmias.
• History of workers' occupations (eg, painters, chemists, textile workers, gasoline refinery workers, rubber industry workers) to assess whether workers may have had accidental acute or chronic exposure and may be at risk
• Hobbies or activities that lead to accidental or intentional exposure
• • Model airplane glues and rubber cements are sources of toluene.
  • Varnishes may affect people refinishing wooden furniture.
• Toxicities and risks that vary with routes of exposure
• • Ingestion may cause hematemesis and abdominal pain.
  • Inhalation is a risk for airway compromise secondary to aspiration and induction of bronchospasm; subsequent hypoxemia from chemical pneumonitis also may occur.
  • Cutaneous exposure may result in coagulation necrosis without copious skin irrigation in the ED or at the scene.

Physical

Physical examination is an important aid in confirming a suspected diagnosis of toluene poisoning. Patients with acute toluene poisoning may present with a variety of symptoms depending on duration, route of exposure, and level of toluene in the air or liquid. Patients with chronic exposure may present with different complaints.

• Glue sniffer's rash: Perioral dermatitis secondary to contact of solvent vapors with skin causes a defatting dermatitis.
• Sweet smelling odor: Hair, breath, and clothing may smell of solvent. Twenty percent of inhaled toluene is expired from the lungs unchanged.
• Decreased level of consciousness leading to coma
• Neurologic
• • Dizziness and headaches
  • Confusion
  • Euphoria
  • Hallucinations
  • Amnesia
  • Seizure activity
• Respiratory distress
• • Shortness of breath
  • Chest pain (with aspiration)
  • Tachypnea
  • Hypoxia
  • Hypercapnia
  • Cyanosis
  • Wheezing from bronchospasm
• Mucosal irritation (eg, burning mouth, eyes, and throat)
• Gastrointestinal
• • Nausea
  • Vomiting
  • Abdominal pain
  • Hematemesis
• Hematuria
• Hypotension
• Itching or burns from skin contact
• Jaundice
• Cerebellar signs
• • Decreased motor coordination
  • Fine motor movements
  • Ataxia
  • Balance problems
  • Anesthesia

• Tinnitus, blurry vision, and/or epistaxis
• Paresthesias (Toluene has anesthetic effects.)
• Muscle weakness, muscle pain
• Decreased deep tendon reflexes
• Tachycardia
• Bradycardia
• Fever secondary to aspiration pneumonitis

Causes

• Toluene toxicity can occur from the following:
• • Accidental or deliberate inhalation of fumes
  • Ingestion
  • Absorption through the skin
• Toluene is found in the following:
• • Gasoline
  • Acrylic paints
  • Varnishes
  • Lacquers
  • Paint thinners
  • Adhesives
  • Glues
  • Rubber cement
  • Airplane glue
  • Shoe polish
  • Typewriter erasing fluid

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Arterial blood gases (ABGs) indicate acidosis, hypoxemia, and hypercarbia.
• Measure serum electrolytes and glucose.
• • Toluene exposure may cause hypokalemia, hyperchloremia, metabolic acidosis, hypocalcemia, and hypophosphatemia.
  • Hypoglycemia must be ruled out as a cause of decreased mental status.
• Blood urea nitrogen (BUN) and creatinine are necessary to monitor kidney function because toluene can cause renal failure.
• Obtain urine or serum creatinine kinase (CK) and myoglobin measurements to test for rhabdomyolysis from toluene-induced muscle damage, which may contribute to renal failure.
• Measure serum hippuric acid level.
• • Hippuric acid is the major metabolite from toluene breakdown by the cytochrome P-450 system in the liver.
  • In addition, a hippurate-creatinine ratio higher than 1:1 indicates recent exposure to the solvent, which has a half-life of 2-3 hours in the body.
• Measure serum toluene levels.
• • Blood toluene levels of 2.5 mcg/mL correlate with this illness.
  • Levels of 50 mcg/mL are probably fatal.
• Perform toxicological screens to test for alcohol, cocaine, and salicylates levels.
• • Alcohol can cause similar mental status changes to toluene and can increase serum toluene levels and decrease its metabolism.
  • Salicylates may cause metabolic acidosis.
  • Cocaine may worsen cardiac arrhythmias.
• Liver enzymes and bilirubin test hepatotoxic effects, which may cause jaundice, hepatitis, and liver failure.
• A CBC with differential and peripheral blood smear tests for many hematologic effects. Patients need to be monitored for anemias, leucocytosis, and abnormalities of blood elements.
• A chest x-ray (CXR) may show aspiration pneumonitis.
• In patients with chronic exposure to toluene, a CT scan of the head may show cerebral cortex and cerebellar atrophy.
• An MRI may reveal cerebral cortex, cerebellar, and brain stem atrophy. Increased periventricular white matter and loss of differentiation of gray and white matter also may be observed.
• Technetium 99 radionucleotide scan of the liver may show a rare form of hepatotoxicity secondary to toluene exposure. In hepatic reticuloendothelial failure (HREF), a decreased uptake of the radionucleotide suggesting impaired liver function occurs.

Other Tests

• ECG is an essential test because toluene-induced arrhythmias, including ventricular fibrillation, often are responsible for the sudden death associated with poisoning.
• Cardiac monitoring of patients should be continuous during observation so that any dysrhythmias may be detected promptly.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Administer supportive care including supplemental oxygen as soon as possible at the scene. If a patient is not breathing, administer ventilatory support with bag valve mask. Avoid mouth-to-mouth breathing because 20% of toluene is expired unchanged and the rescuer may be overcome by direct inhalation of fumes.

• Upon discovery of the patient, remove patient's clothing because the clothes may have additional solvent on them, which is harmful to the patient and rescue workers. Examine the skin for burns so that irrigation, if needed, can begin immediately.
• Remove the patient from area of contamination because toxic fumes may overcome rescue workers.
• Immediate irrigation of the skin, eyes, and mucous membranes at the scene greatly reduces skin damage (eg, coagulation necrosis from prolonged contact).

Emergency Department Care

Treatment is supportive, and often the patient's airway is not in jeopardy.

• Administer supplemental oxygen.
• Make certain that intubation equipment is available, if needed, at the bedside. Consider intubation in patients with increasing respiratory distress, decreased level of consciousness, inability to protect their own airway, predicted worsening clinical course, and risk of aspiration from ingestion.
• Observe patients for tachypnea and obtain ABGs to monitor for signs of metabolic acidosis.
• Follow advanced cardiac life support (ACLS) protocols for patients with arrhythmias, if needed. Central line placement may be necessary for patients requiring ACLS or defibrillation following ventricular fibrillation or significant hypotension.
• Cardioversion of dysrhythmias induced by toluene exposure may be necessary.
• Establish intravenous access for administration of fluids or medicines with 2 large bore peripheral IV sites, or obtain central venous access, if needed.
• Use fluid boluses, dopamine, or epinephrine, if necessary, to maintain blood pressure. Use IV fluid boluses with normal saline or lactated Ringer solution at 20 cc/kg to maintain blood pressure and to ensure adequate urinary output.
• Replete potassium, calcium, and phosphorous losses caused by effects of toluene, if necessary. Use sodium bicarbonate in cases of severe acidosis.
• Do not assume that adequate irrigation of contaminated skin was achieved in the field. Copiously irrigate wounds to reduce potential burn damage and coagulation necrosis.
• Monitor urinary output and kidney functions to avoid acute renal failure from myoglobinemia secondary to rhabdomyolysis. Fluid boluses can help.
• Facilitate gastric decontamination with nasogastric (NG) tube gastric lavage for patients who are symptomatic following ingestion of toluene.
• Consider doxycycline if the patient has a history of (TDI) toluene-induced occupational asthma if the patient is not allergic to doxycycline.

Consultations

• Consult the regional poison control center or local medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine) for additional information and patient care recommendations.
• Pursue pulmonary consultation for patients with respiratory compromise or complications from aspiration.
• Consult cardiology department personnel for patients with ventricular dysrhythmias or cardiac arrest.
• Consult with ear, nose, and throat (ENT) and/or plastic surgery specialists if significant burns or irritation of the mucous membranes are present on the face or significant dermal burns are observed on the rest of the body.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No specific drug therapy for toluene poisoning exists. Toluene is not significantly adsorbed by activated charcoal. One recent study using mice found that in patients with a history of toluene-induced occupational asthma doxycycline may reduce airway inflammation and hyperresponsiveness. However, further studies are needed. Presently, inhaled beta-agonists and steroid therapy should be considered first-line agents for patients presenting with asthma and respiratory symptoms. However, in the future, further studies may find doxycycline to provide some benefit in the appropriate patient population.

Drug Category: Cardiovascular agents

Dopamine and epinephrine may be used to maintain blood pressure. These agents augment coronary and cerebral blood flow during states of low blood flow. Sodium bicarbonate is used in cases of severe acidosis.

Drug Category: Alkalinizing agents

These agents may be used to raise blood and urinary pH.

Drug Category: Antibiotics

These agents may inhibit enzymes involved in the inflammatory process.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients with toluene exposure or abuse for observation and treatment if they have electrolyte abnormalities, cardiovascular problems, pulmonary problems, seizures, rhabdomyolysis, or persistent mental status changes.
• • Sudden death has been reported in these patients within 3 days.
  • Patients with continuing respiratory, cardiac, and renal problems may need to be admitted to the critical care unit.

Further Outpatient Care

• Workers with occupational exposures and patients who are not chronic abusers, without laboratory abnormalities, and who demonstrate improved mental status may be discharged from the ED after 4-6 hours of observation.
• • Arrange for follow-up care with the primary care physician within 1-3 days.
  • Advise patients and families to return to the ED if changes in mental status, decreased urine output, abdominal pain, muscle pain or weakness, shortness of breath, chest pain, or choking sensation occurs.
  • Arrange substance abuse counseling for abusers, although recidivism is extremely high.
• Refer long-term abusers with no laboratory abnormalities and improved mental status to a drug rehabilitation program.

In/Out Patient Meds

• No specific medication is warranted for further treatment of patients.

Transfer

• Transfer patients to a facility with critical care if they require critical care monitoring and are admitted to a hospital without sufficient ICU facilities.

Deterrence/Prevention

• Advise workers with occupational exposure not to work in poorly ventilated enclosed rooms.
• Inform chronic glue sniffers of the long-term sequelae and consequences associated with abuse.

Complications

• CNS complications
• • Neuropsychosis
  • Cerebellar ataxia
  • Cognitive impairment
  • Tremors
  • Neuropathies
  • Blindness
  • Deafness
• Sudden death resulting from cardiac arrhythmias and myocardial infarction (MI)
• Respiratory depression, emphysema, and aspiration pneumonitis
• Hepatotoxicity
• • HREF
  • Ascites
  • Jaundice
  • Liver failure
• Renal tubular acidosis, renal stones, hematuria, proteinuria, electrolyte disturbances, and acute renal failure
• Abdominal pain, hematemesis, and vomiting
• Muscle pain and weakness, rhabdomyolysis, and myoglobinemia
• Contact dermatitis (defatting hydrocarbon dermatitis), chemical burns, and coagulation necrosis
• Epistaxis, nasal ulcerations, and chronic rhinitis

Prognosis

• Prognosis is good if patients receive appropriate counseling and follow-up and are compliant with recommendations.
• Prognosis is dismal in patients who continue to abuse toluene.

Patient Education

• Inform patients of the consequences of toluene abuse.
• Advise patients of opportunities for counseling, therapy, and detoxification.
• For excellent patient education resources, visit eMedicine's Substance Abuse Center. Also, see eMedicine's patient education article Substance Abuse.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Underestimating the clinical course
• Inadequate period of observation or monitoring
• Failure to consider toluene poisoning as a diagnosis (Presentation is similar to alcohol intoxication.)

Special Concerns

• Pregnancy: More than 50% of chronic solvent abusers are women in their prime childbearing years. Toluene easily crosses the placenta and causes a syndrome of birth defects similar to FAS. Defects include the following:
• • Microcephaly (67%)
  • Premature birth (39%)
  • Intrauterine growth restriction (54%)
  • Developmental delay (80%)
  • Craniofacial abnormalities (83%)
• Pediatrics: Toluene has been implicated in MI in children.
• Geriatrics - Toluene must be considered as a possible cause for mental status changes or confusion.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: May 30, 2006