Studies of Toluene's Effects - vertigo, seizures, ataxia, stupor, and coma.

Toluene abuse can harm the nervous system and body, yet scientists know relatively little about its specific actions.

REPEATED TOLUENE EXPOSURE DEPRESSES BRAIN ACTIVITY

source in part by: NIDA  & MEDSCAPE

Researchers used microPET imaging to compare brain activity of a rat before and after chronic toluene exposure. Yellow indicates high activity. Three weeks after the last exposure, the brain showed recovery, but activity in the auditory cortex and some other areas remained depressed throughout the 2-month study.

TOLUENE DEPRESSES BRAIN METABOLISM

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, frac-fluid 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,

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]

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