eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Toluene

Nathanael J McKeown, DO, Assistant Professor, Oregon Health and Science University; Medical Toxicologist, Oregon Poison Center; Attending Physician, Emergency Medicine, Portland Veteran Affairs Medical Center, Oregon Health and Science University

Updated: May 20, 2009

Introduction

Background

Toluene (methylbenzene, toluol, phenylmethane) is an aromatic hydrocarbon (C₇ H₈) commonly used as an industrial solvent for the manufacturing of paints, chemicals, pharmaceuticals, and rubber. It is identified as CAS#108-88-3, and the 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, and volatile liquid.

Toxicity can occur from unintentional or deliberate inhalation of fumes, ingestion, or transdermal absorption. 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 hypercarbia 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. The Permissible Exposure Limit (PEL) of 200 ppm is considered an acceptable level of exposure as a time-weighted average for an 8-hour workday.¹ Toluene levels of 500 ppm are considered immediately dangerous to life and health. 

Due to genetic polymorphisms, some people may be more sensitive to the effects of inhaled solvents than others.²  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 also contribute to asthma exacerbations, and should be monitored. 

Pathophysiology

Toluene is highly lipophilic, which accounts for its primary effects on the central nervous system (CNS). After crossing the blood-brain barrier, toluene, along with other volatile anesthetic agents, had been previously thought to inhibit neuronal transmission by causing a change in membrane or membrane protein conformation. Recent research has shown that interactions with several key brain neurotransmitters, mainly γ-aminobutyric acid_A (GABA), to a lessor degree glycine, and possibly dopamine, are responsible for the clinical effects seen.³ Postmortem studies along with magnetic resonance imaging (MRI) findings have shown diffuse white matter demyelination and gliosis (solvent vapor/toluene leukoencephalopathy), which is postulated to be the end product by which chronic toxicity occurs, although the exact mechanism by which this occurs remains unclear.⁴

Central nervous system

Acute intoxication from inhalation is characterized by rapid onset of CNS symptoms including euphoria, hallucinations, delusions, tinnitus, dizziness, confusion, headache, vertigo, seizures, ataxia, stupor, and coma.

Chronic CNS sequelae include neuropsychosis, cerebral and cerebellar degeneration with ataxia, seizures, choreoathetosis, optic and peripheral neuropathies, decreased cognitive ability, anosmia, optic atrophy, blindness, ototoxicity, and deafness.

Cardiopulmonary

Toluene has direct negative effects on cardiac automaticity and conduction and can sensitize the myocardium to circulating catecholamines. "Sudden sniffing death" secondary to cardiac arrhythmias has been reported. Pulmonary effects include bronchospasm, asphyxia, acute lung injury (ALI), and aspiration pneumonitis.

Gastrointestinal 

GI symptoms from inhalation and ingestion may result in abdominal pain, nausea, vomiting, and hematemesis. Hepatotoxicity manifests with ascites, jaundice, hepatomegaly, and liver failure. A rare form of hepatitis—hepatic reticuloendothelial failure (HREF)—has been reported with toluene exposure.⁵ With the widespread abuse of volatile substances in young adults today, hepatitis secondary to toluene toxicity, not just infectious causes, should be considered in the differential diagnosis in the younger patient population who present with concerning findings.

Renal and metabolic

Reported renal toxicity from toluene exposure includes renal tubular acidosis (RTA), hypokalemia, hypophosphatemia, hyperchloremia, azotemia, sterile pyuria, hematuria, and proteinuria.

Hematologic

Hematologic consequences of exposure may include lymphocytosis, macrocytosis, eosinophilia, hypochromia, and basophilic stippling, and in severe cases, aplastic anemia.  

Dermatologic

Cutaneous contact with skin may range in severity from dermatitis to extensive chemical burns with coagulation necrosis.

Musculoskeletal

Toluene can affect skeletal muscles directly, resulting in rhabdomyolysis and myoglobinemia. Profound hypokalemia due to RTA can produce severe muscle weakness mimicking Guillain-Barré syndrome. In animal studies, chronic inhalational exposure to toluene was found to affect bone metabolism, contributing to bone resorption and inhibition of bone formation.⁶

Frequency

United States

Solvents including glue are easily accessible and inexpensive, making them a frequently abused substance. Glue sniffing is most frequently observed in teenagers and young adults in lower economic groups. According to the National Survey on Drug Use and Health in 2007, approximately 775,000 people were new inhalant users.⁷ Almost 23.5 million people older than12 years reported trying an inhalant at least once. 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.

Chronic nonintentional exposure also occurs among people in the painting, gasoline, chemical, and rubber industries. The 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data Systems records only 1077 exposures to toluene and xylene combined.⁸ Of these, only 5 sustained major adverse outcomes, and 1 death was 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.⁹ In Brazil, 6.1% of the population older than 12 years report trying an inhalant at least once.¹⁰ 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.

In Singapore, toluene glue sniffing has reached epidemic proportions.¹¹ 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 2005, 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.¹²

In Australia, 22% of 12-year-olds reported lifetime use of inhalants, decreasing to 15% by age 15 and 11% by age 17.¹³

Mortality/Morbidity

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

Volatile substance abuse sensitizes the myocardium to circulating catecholamines. Sudden alarm, exercise, sexual activity, or any kind of startling (eg, parents, police) 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).

• In the 1960s, a total of 110 cases of sudden death from solvent abuse were reported in the United States. In a review of death records in Virginia from 1987-1996, 39 deaths related to solvent abuse were identified. Males accounted for 95% of cases with the majority (70%) of deaths occurring at age 22 or younger.¹⁴  One death was reported to be an occupational exposure. In Texas, a 10-year review of death certificates identified 144 people in whom inhalants were a contributing factor. The majority were male (92%), white (81%), with a mean age of 25.6 years.¹⁵
• In 1988, in the United Kingdom, 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.⁹
• 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.¹¹
• From 1983-1991, 4 deaths attributed to occupational exposures were reported in Singapore.¹¹
• In a 20-year retrospective review of autopsy cases in Australia, 0.2% were attributed to inhalant use, with the majority (92%) being male.¹⁶

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), epidemiologic studies more than 20 years ago showed more than 50% of chronic solvent abusers were females in their prime childbearing years.¹⁵ A more recent report in 2006 in Florida showed higher rates among females compared to males in high school for lifetime and current use.

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

History

Determining a history of toluene exposure or risk of exposure on admission is important, as well as the the route of exposure, whether inhalation, ingestion, or transdermal absorption. 

• 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 nonintentional acute or chronic exposure and may be at risk
• Hobbies or activities that lead to nonintentional 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 and acute lunge injury also may occur.
  • Cutaneous exposure may result in coagulation necrosis without copious skin irrigation.

Physical

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

Patients with chronic exposure may present with wide variety of complaints.

• General/vitals
  • Patients may be tachypneic, tachycardic, and hypoxic on initial evaluation.
  • Hypotension may be present.
  • Fever may be present, secondary to aspiration pneumonitis.
  • Sweet smelling odor: Hair, breath, and clothing may smell of solvent. Twenty percent of inhaled toluene is expired from the lungs unchanged.
  • Paint or oil stains may be seen on clothing.
• Head, eyes, ears, nose, and throat (HEENT)
  • "Huffer's eczema": Perioral defatting dermatitis secondary to contact of solvent vapors with skin may be noted.
  • Mucosal irritation (eg, burning mouth, eyes, throat)
  • Injected sclera
  • Nystagmus
• Neurologic
  • Decreased level of consciousness leading to coma
  • Dizziness and headaches
  • Confusion
  • Hallucinations
  • Amnesia
  • Seizure activity
  • Paresthesias (Toluene has anesthetic effects.)
  • Decreased deep tendon reflexes
  • Cerebellar signs  
    • Decreased motor coordination
    • Impaired fine motor movements
    • Ataxia
    • Balance problems
    • Anesthesia
• Pulmonary
  • Respiratory distress
  • Dyspnea
  • Chest pain (with aspiration)
  • Tachypnea
  • Cyanosis
  • Wheezing from bronchospasm
• Gastrointestinal
  • Nausea
  • Vomiting
  • Abdominal pain
  • Hematemesis
  • Jaundice
• Dermatologic
  • Itching or burns from skin contact
  • Glue sniffer's rash (see in HEENT)
• Musculoskeletal: Profound muscle weakness due to hypokalemia; muscle pain

Causes

• Inhalation of airborne toluene is the most common cause of exposure.
• Exposure can occur in several occupations including paint workers, dye makers, and workers in the chemical and petrochemical industry.
• Toluene toxicity can occur from the following:
  • Nonintentional 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

Differential Diagnoses

Workup

Laboratory Studies

• Arterial blood gas (ABG) measurements indicate acidosis, hypoxemia, and hypercarbia.
• Measure serum electrolytes and glucose levels.
  • 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 levels 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.
• Serum toluene concentrations are available only through specialized laboratories and are not available quickly enough to guide therapy.¹⁷
  • Blood toluene levels of 2.5 mg/L correlate with toxicity.
  • levels of 50 mg/L are probably fatal.
• Perform toxicological screens to test for alcohol, acetaminophen, 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 levels measure hepatotoxic effects, which may cause jaundice, hepatitis, and liver failure.
• A CBC with differential and peripheral blood smear test results may detect many hematologic effects. Patients need to be monitored for anemia, leucocytosis, and abnormalities of blood elements.

Imaging Studies

• A chest radiograph may show aspiration pneumonitis or acute lung injury.
• In patients with chronic exposure to toluene, a CT scan of the head may show cerebral cortex and cerebellar atrophy with brainstem atrophy in severe cases.
• An MRI may reveal cerebral cortex, cerebellar, and brainstem atrophy with sulcal widening and ventricular dilation. Increased periventricular white matter and loss of differentiation of gray and white matter may also be observed.
• Technetium Tc 99m 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.⁵

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

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 a 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 the 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 the 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 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, hypoxia, and hypercarbia.
• 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.
• Propranolol and esmolol have both been used successfully in treatment of ventricular dysrhythmias from inhalant abuse.
• 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, if necessary, to maintain blood pressure. Use IV fluid boluses with normal saline or lactated Ringer solution at 20 mL/kg to maintain blood pressure and to ensure adequate urinary output.
• Careful use of vasopressors to support blood pressure can be considered, sympathomimetic agents may increase risk of developing dysrhythmias and should be used with caution.
• Replete potassium, calcium, and phosphorus 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.
• Facilitate gastric decontamination with nasogastric (NG) tube gastric lavage for patients who are symptomatic following ingestion of toluene.

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

No specific antidotal drug therapy for toluene poisoning exists. Toluene is not significantly adsorbed by activated charcoal.

Presently, inhaled beta-agonists and steroid therapy should be considered first-line agents for patients presenting with asthma and respiratory symptoms.

Cardiovascular Agent

These agents may be used to convert an inhalant-induced dysrhythmia.

Esmolol

Ultra–short-acting agent that selectively blocks beta1-receptors with little or no effect on beta2-receptor types. Particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Shown to reduce episodes of chest pain and clinical cardiac events compared to placebo. Can be discontinued abruptly if necessary. Useful in patients at risk for experiencing complications from beta-blockade; particularly those with reactive airway disease, mild-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

Dosing

Adult

Loading dose: 250-500 mcg/kg/min IV for 1 min followed by a 4-min maintenance infusion of 50 mcg/kg/min
If adequate therapeutic effect not observed within 5 min, repeat loading dose and follow with maintenance infusion using increments of 50 mcg/kg/min (for 4 min); sequence may be repeated up to 4 times if needed
As the desired heart rate is approached, omit loading infusion and reduce incremental dose of maintenance infusion from 50 mcg/kg/min to 25 mcg/kg/min or lower; interval between titration steps may be increased from 5-10 min if needed

Pediatric

Not established; suggested dose is 100-500 mcg/kg administered IV over 1 min

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of esmolol, possibly resulting in decreased pharmacologic effect; cardiotoxicity of esmolol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity of esmolol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when medication is abruptly withdrawn; withdraw drug slowly and monitor patient closely

Propranolol

Class II antiarrhythmic, nonselective, beta-adrenergic, receptor blocker with membrane-stabilizing activity that decreases automaticity of contractions.

Effective for treating aggression resulting from head injury. They also are used for reducing restlessness and disinhibition. Treatment for persistent agitation and aggression in organic brain syndromes.

Dosing

Adult

1-3 mg (under careful monitoring) IV; not to exceed 1 mg/min to avoid lowering blood pressure and causing cardiac standstill

Allow time for drug to reach site of action (particularly if slow circulation); administer second dose after 2 min prn; thereafter, do not give additional drug in <4 h

Do not continue doses after desired alteration in rate or rhythm achieved; switch to PO ASAP; 10-30 mg tid/qid (usual)

Pediatric

2-4 mg/kg/d PO divided bid (ie, 1-2 mg/kg bid)
IV use is not recommended; however, for arrhythmias, a dose of 0.01-0.1 mg/kg, not to exceed 1 mg/dose by slow push, has been recommended; change to PO ASAP

Interactions

Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease propranolol effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity of propranolol; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase with propranolol

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely

Alkalinizing agents

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

Sodium bicarbonate (Neut)

Neutralizes hydrogen ion concentrations and raises blood and urinary pH. Drip can be prepared with 2-3 ampules of bicarbonate in 1 L of D5W, run at 50-200 mL/h, with pH followed to maintain range of 7.45-7.55; alternatively, monitor patient and administer boluses of bicarbonate prn if QRS widening and block resolves with initial treatment

Dosing

Adult

1-2 mEq/kg IV push, initial

Pediatric

1 mEq/kg slow IV push

Interactions

Urinary alkalinization induced by increased sodium bicarbonate concentrations may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines, pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Can cause alkalosis, decreased plasma potassium, hypocalcemia, and hypernatremia; caution in electrolyte imbalances such as CHF, cirrhosis, edema, corticosteroid use, or renal failure; when administering, avoid extravasation because can cause tissue necrosis

Follow-up

Further Inpatient Care

• Consider admitting patients with toluene exposure or abuse for observation and treatment if they have electrolyte abnormalities, cardiovascular problems, hypoxia, seizures, rhabdomyolysis, or persistent mental status changes.
• 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 (asymptomatic, back to baseline) 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.

Inpatient & Outpatient Medications

• 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

Complications of toluene toxicity are listed below:

• CNS complications
  • Neuropsychosis
  • Cerebellar ataxia
  • Cognitive impairment, dementia
  • Tremors
  • Neuropathies
  • Blindness
  • Deafness
• Sudden death resulting from cardiac arrhythmias
• Respiratory depression, hypoxia, bronchospasm, acute lunge injury, and aspiration pneumonitis
• Hepatotoxicity
  • Hepatic reticuloendothelial failure (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 poor 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

Medicolegal Pitfalls

• Underestimating the clinical course
• Inadequate period of observation or monitoring
• Failure to consider toluene poisoning as a diagnosis in patients with altered mental status and profound hypokalemia (Presentation is similar to that of alcohol intoxication.)

Special Concerns

• Pregnancy: Toluene easily crosses the placenta and has been shown to cause a syndrome of birth defects similar to fetal alcohol syndrome (FAS). Defects include the following:
  • Microcephaly (67%)
  • Premature birth (39%)
  • Intrauterine growth restriction (54%)
  • Developmental delay (80%)
  • Craniofacial abnormalities (83%)
  • Renal anomalies (26%)
  • Other minor anomalies (89%)
• Geriatrics - Toluene must be considered as a possible cause for mental status changes or confusion.

References

1. United States Department of Labor. Occupational Safety and Health Administration. Safety and Health topics: Toluene. Last revised March 17, 2004. Available at: http://www.osha.gov/dts/chemicalsampling/data/CH_272200.html.

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3. Long, Heather. Inhalants. In: Goldfrank's Toxicologic Emergencies. 8^th ed. New York: McGraw-Hill; 2006:1192-1201.

4. Rosenberg NL, Kleinschmidt-DeMasters BK, Davis KA, Dreisbach JN, Hormes JT, Filley CM. Toluene abuse causes diffuse central nervous system white matter changes. Ann Neurol. Jun 1988;23(6):611-4. [Medline].

5. Shiomi S, Kuroki T, Kuroda T, et al. Absence of hepatic uptake of Tc-99m phytate in a man with chronic toluene hepatotoxicity. Clin Nucl Med. Aug 1993;18(8):655-6. [Medline].

6. Atay AA, Kismet E, Turkbay T, Kocaoglu M, Demirkaya E, Sarici SU, et al. Bone mass toxicity associated with inhalation exposure to toluene. Biol Trace Elem Res. Summer 2005;105(1-3):197-203. [Medline].

7. United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration, Office of Applied Studies. 2007 National Survey on Drug Use and Health: National Survey. Sept 2008. Available at: http://oas.samhsa.gov/nsduh/2k7nsduh/2k7Results.pdf.

8. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].

9. Flanagan RJ, Ruprah M, Meredith TJ, Ramsey JD. An introduction to the clinical toxicology of volatile substances. Drug Saf. Sep-Oct 1990;5(5):359-83. [Medline].

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Keywords

toluene poisoning, toluene toxicity, toluene intoxication, toluene exposure, toluene ingestion, toluene inhalation, toluene solvent, chemical toxicity, causes, symptoms, treatment, methylbenzene, toluol, phenylmethane, huffing, bagging, TDI, toluene diisocyanate, p-nitrotoluene, p- nitrotoluene, toluene-induced asthma, toluene-induced occupational asthma, gasoline, acrylic paints, varnishes, lacquers, paint thinners, adhesives, glues, rubber cement, airplane glue, shoe polish

Contributor Information and Disclosures

Author

Nathanael J McKeown, DO, Assistant Professor, Oregon Health and Science University; Medical Toxicologist, Oregon Poison Center; Attending Physician, Emergency Medicine, Portland Veteran Affairs Medical Center, Oregon Health and Science University
Nathanael J McKeown, DO is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Debra Slapper, MD, Consulting Staff, Department of Emergency Medicine, St Anthony's Hospital
Debra Slapper, MD is a member of the following medical societies: American Academy of Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Chair, Department of Emergency Medicine, Director of Medical Toxicology - Allegheny General Hospital, Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Kevin A Martin, MD, to the development and writing of this article.

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