Some science behind the scenes

Toluene

Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is widely used as an industrial  solvent , able to dissolve paints, paint thinners, silicone sealants, many chemical reactants, rubber, printing ink, adhesives (glues), lacquers, leather tanners, and disinfectants.. It is also used as a cement for fine polystyrene kits (by dissolving and then fusing surfaces) as it can be applied very precisely by brush and contains none of the bulk of an adhesive.

It has also been  used as an octane booster in gasoline fuels used in internal combustion engines. Toluene at 86% by volume fueled all the turbo Formula 1 teams in the 1980s.  Finally it has also been used in the process of removing the cocaine from coca leaves in the production of Coca-Cola syrup.

The name toluene was derived from the older name toluol, which refers to tolu balsam, an aromatic extract from the tropical Colombian tree Myroxylon balsamum, from which it was first isolated. It was originally named by Jöns Jakob Berzelius.

Toluene occurs naturally at low levels in crude oil and is usually produced in the processes of making gasoline or making coke from coal.

Toluene can be used to break open red blood cells in order to extract hemoglobin in biochemistry experiments, which should tell you something of its effects when it gets into the body

Effects if inhaled

The background papers that support the following summary are provided in the next section. Toluene is known to cause

  • lung damage
  • sleep apnea
  • high blood pressure or low blood pressure
  • dementia   
  • leukoencephalopathy
  • Lactic acidosis  - a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate.   The condition typically occurs when cells receive too little oxygen (hypoxia).  Elevated lactate is indicative of tissue hypoxia, hypoperfusion, and possible damage
  • Nausea and Vomiting
  • Hyperventilation
  • Abdominal pain
  • Lethargy
  • Anxiety
  • Severe anaemia
  • Irregular heart rate and tachycardia
  • death

Background papers supporting findings

AJNR Am J Neuroradiol. 2002 Aug;23(7):1173-9. - Cranial MR findings in chronic tolueneabuse by inhalation - Aydin K Sencer S, Demir T, Ogel K Tunaci A Minareci O;  Department of Radiology, Istanbul University Medical School, Capa Hospital, Turkey.

BACKGROUND AND PURPOSE:
Chronic abuse of toluene by inhalation causes variable white matter changes and thalamic hypointensity on T2-weighted MR images. The purpose of our study was to assess cranial MR findings in a large series of patients who chronically abuse toluene-containing solvents to investigate the factors causing the qualitative variability of white matter changes and thalamic hypointensity.

METHODS:
We studied the neurologic signs, symptoms, and cranial MR findings in 41 patients who chronically abused thinner, a toluene-containing solvent. We classified white matter changes as diffuse or restricted. We tested the associations of the development of white matter lesions and thalamic hypointensity with patient age at onset of abuse and duration of abuse.

RESULTS:
MR images revealed white matter lesions in 46% of the patients, atrophic dilatation of ventricles and sulci in 27%, and thalamic hypointensity in 20%. White matter changes were restricted in 53% and diffuse in 47%. The development of white matter changes and thalamic hypointensity were significantly associated with duration of abuse longer than 4 years (P <.05 and P <.01, respectively).

CONCLUSION:
White matter changes seem to start in the deep periventricular white matter, and they spread into peripheral white matter, causing the loss of gray matter-white matter differentiation with continued toluene abuse. The deposition of iron due to demyelination and axonal loss is the most probable mechanism for the thalamic hypointensity found in solvent abusers.

Comment in
AJNR Am J Neuroradiol. 2002 Aug;23(7):1072-3.
PMID: 12169477

AJNR Am J Neuroradiol 1993 Sep-Oct;14(5):1195-9.- MR imaging of "spray heads": toluene abuse via aerosol paint inhalation - Xiong L, Matthes JD, Li J, Jinkins JR.

Neuroradiology Section, University of Texas Health Science Center at San Antonio 78284-7800.

PURPOSE:
Three male patients with a history of spray-paint inhalation are presented.

METHODS:
Spin-echo MR was used to evaluate the central nervous system changes secondary to toluene inhalation delivered via spray-paint fumes.

RESULTS:
The remarkable findings included the loss of cerebral and cerebellar gray-white matter discrimination, scattered multifocal deep white matter lesions, and gross generalized atrophy of the cerebrum, the cerebellum, and the corpus callosum.

CONCLUSION:
Although the observed changes are nonspecific, combined with a positive history the diagnosis of inhalation toluene abuse can be made on the basis of consistent MR findings.

PMID: 8237703

Complications of chronic glue (toluene) abuse in adolescents.
Devathasan G, Low D, Teoh PC, Wan SH, Wong PK.

Recently there has been an alarming increase in the number of schoolchildren sniffing glue (toluene). The medical complications seen in 18 boys, aged 14 to 18 years, include:

  • physical and mental dependence
  • pulmonary hypertension with cor pulmonale
  • restrictive lung defect
  • encephalopathy
  • peripheral neuropathy and high frequency, continuous discharges (neuromyotonia) on electromyogram.

Glue sniffing took place in small groups and abusers sniffed directly from cans containing glue. Lower socio-economic status, overcrowding, lack of attention by working parents, school failure and easy availability of the glue were commonly cited associated factors.

Handb Clin Neurol. 2012;103:201-13;  Toxic agents causing cerebellar ataxias - Manto M.
Unité d'Etude du Mouvement, FNRS Neurologie, ULB Erasme, Brussels, Belgium.

The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of:

  • drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors),
  • drug abuse and addiction (such as cocaine, heroin, phencyclidine),
  • and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives).

Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening.

2012 Elsevier B.V. All rights reserved.

PMID: 21827890

Ind Health. 2001 Jul;39(3):231-4.
Toluene
alters mu-opioid receptor expression in the rat brainstem.
Saracibar G  Hernandez ML, Echevarria E, Barbero I, Gutierrez A, Casis O.
Department of Physiology, School of Pharmacy, University of the Basque Country, Vitoria, Spain.

Toluene is an ototoxic organic solvent widely used in industry and could be a cause of sleep apnea. Acute toluene administration in rats induces an increase in the number of neural cells immunostained for mu-opioid receptors in several brainstem nuclei, such as the inferior colliculus, dorsal and lateral periaqueductal gray and dorsal raphe, without changes in the superior colliculus and the interpeduncular and lateral reticular nuclei. These data suggest that mu-opioid receptors could be involved in toluene-induced neurotoxic effects on the physiological regulation of breathing during sleep, and auditive function.

PMID: 11499998`

J Neuropathol Exp Neurol 2004 Jan;63(1):1-12.

The effects of toluene on the central nervous system - Filley CM, Halliday W, Kleinschmidt-DeMasters BK;   Department of Neurology, University of Colorado School of Medicine, Denver, Colorado 80262, USA.

In recent decades the organic solvent toluene (methylbenzene) has emerged as one of the best-studied neurotoxins. Long-term and intense exposure to toluene vapors in humans who abuse spray paint and related substances has led to the recognition that toluene has a severe impact on central nervous system myelin. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. In this paper, we consider the impact of toluene abuse on our society, describe the specific neurobehavioral deficits in toluene leukoencephalopathy, review the spectrum of neuroimaging findings in patients with this disorder, summarize the teratogenic effects of toluene in both humans and animal models, and offer possible explanations for the range of neuropathological damage seen in brains of individuals who chronically abuse toluene.

PMID: 14748556

Saudi J Anaesth. 2011 Jan;5(1):73-5.
Reported survival with severe mixed acidosis and hyperlactemia after
toluene poisoning.
Omar AS, Rahman MU, Abuhasna S.
Department of Critical Care Medicine, Tawam Hospital/ John Hopkins Medicine, Al Ain, UAE.

Lactic acidosis is a recognized complication of the inhalant abuse such as toluene, especially in patients with renal insufficiency. We report a case of severe metabolic acidosis and hyperlactemia due to toluene sniffing. The favorable outcome, despite extremely poor clinical symptoms, signs, laboratory and radiological findings, was unexpected. Specific aspects of the clinical course are addressed. Toluene sniffing should be considered in evaluating sever metabolic acidosis. Favorable outcome could be achieved with early diagnosis and proper interventions.

PMID: 21655021

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