As children grow, they may show developmental delay, hyperactivity, and cerebellar dysfunction (63, 64). Data from 1994 disclosed that 19.9% of eighth graders reported that they had used inhalants, with 5.6% reporting use within the past 30 days (1). Author information: (1)Department of Occupational Health and Safety, Faculty of Public … This causes inflammation and injury to the sheath and ultimately to the nerve fibers that it surrounds. Despite the severe white matter damage and numerous PAS-positive macrophages, there was good Purkinje and granule cell neuronal preservation (D). Cyclohexane Inhalation Produces Long-Lasting Alterations in the Hippocampal Integrity and Reward-Seeking Behavior in the Adult Mouse. Patients with these polymorphisms may develop toxicity with a lower dose of a drug or toxin. Building on these observations, standardized neurobehavioral testing was undertaken in another cohort of toluene abusers and a characteristic clinical profile emerged (21). Princeton researchers — led by Jeffrey Schwartz, professor of chemistry, and Jean Schwarzbauer, the Eugene Higgins Professor of Molecular Biology — have developed a technique for adhering and aligning cells on a soft and flexible material, known as hydrogel, with the goal of creating … Chronic solvent-induced encephalopathy (CSE) is a condition induced by long-term exposure to organic solvents, often but not always in the workplace, that lead to a wide variety of persisting sensorimotor polyneuropathies and neurobehavioral deficits even after solvent exposure has been removed. This site needs JavaScript to work properly. The experimental findings of astrocytic activation in animal models are, however, of great interest in light of the considerable reactive astrocytosis that has been demonstrated in several human cases of toluene abuse, even in areas with seemingly intact myelin (Fig. These observations support the notion that myelin, which contains 70% lipid, is targeted for damage. CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Aim: Neuroprotective effects of ebselen against free radical damage have been studied extensively. The selective damage to white matter caused by chronic toluene abuse has offered an unprecedented opportunity for behavioral neurologists to study the specific effects of cerebral white matter disorders on behavior. Although toluene leukoencephalopathy is well documented in inhalant abusers, the potential of low-level occupational or household toluene exposure to cause brain damage is uncertain. 2C). Advanced neuroimaging techniques such as diffusion tensor imaging, magnetization transfer imaging, and magnetic resonance spectroscopy promise to improve the early recognition of leukoencephalopathy in individuals exposed to toluene when the potential for reversibility is maximal. Exposure to toluene can cause eye and nose irritation, tiredness, confusion, euphoria, dizziness, headache, dilated pupils, tears, anxiety, muscle fatigue, insomnia, nerve damage, inflammation of the skin, and liver and kidney damage. Toluene abuse and white matter: a model of toxic leukoencephalopathy. Peripheral neuropathy develops when nerves in the body's extremities, such as the hands, feet and arms, are damaged. More than 3 million tons of toluene are produced each year in the United States alone (6), and this solvent is found in many occupational settings and in numerous household products. For severe nerve damage, it will take quite a long time to heal and function normally. Even though most abusers start using inhalants at a young age, they often continue this form of substance abuse for many years. Despite these EM and biochemical similarities to ALD, Cases 1 and 2 showed several histological features distinctly different than ALD. The primary target of toluene is thought to be the CNS (6, 8), and both acute and chronic effects are recognized. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. The central nervous system and exposure to toluene: a risk characterization. 2F). AJNR Am J Neuroradiol. In the UK it's estimated almost 1 in 10 people aged 55 or over are affected by peripheral neuropathy. In recent years it has been recognized that disorders of the cortical gray matter (e.g. Epub 2018 Jul 26. The peripheral nervous system . nom grammaire . 2020 Oct 21;25(20):4866. doi: 10.3390/molecules25204866. MRS provides measures of brain metabolism (39), and can be used to quantitate the chemical environment of brain tissues in the brain without the need for cerebral biopsy. In an autopsy study of a patient who inhaled toluene … The myelin loss was milder, more uniform, and the borders between severely depleted and moderately demyelinated areas were ill defined; features identical to those seen in our original case (41). Neuropsychiatry Neuropsychol Behav Neurol. Your skin will also become numb. A second patient with a chronic encephalopathy due to gasoline sniffing reported in 1978 demonstrated cerebellar cortical atrophy (45). The extent of exposure has been shown to be one important determinant, as has been documented in MRI studies that show a correlation between duration of toluene abuse and the severity of the white matter abnormalities (22, 24). In severe cases, an infection can spread to the bone or lead to tissue death. Toluene exposure can cause eye and nose irritation, fatigue, confusion, dizziness, enlarged pupils, anxiety, muscle fatigue, insomnia, nerve damage, skin inflammation, even liver and kidney damage. The brain from both patients showed cerebral atrophy, with weights of 1,100 and 980 grams, respectively. Most of the available toxicity studies relate to exposure via inhalation. Oligodendrocytes were reduced in number but there was only a mild gliotic reaction. The symptoms depend on which nerves are affected. Neuropathological examination shows cerebral and especially cerebellar myelin loss, perivascular macrophages stuffed with coarse or linear PAS-positive debris, and trilaminar inclusions by EM. High glucose levels causes chemical changes in nerves, if glucose levels remain high over a long period of time, … At autopsy the brain showed cerebral and cerebellar atrophy and severe thinning of the corpus callosum. 1B). Arch Neurol 31:160-167, 1974 Toluene Optic Neuropathy James R. Keane, M D Cerebellar damage associated with exposure to toluene (methyl benzene) has been discussed in this journal by Boor and Hurtig [I]. Rosenberg NL, Kleinschmidt-DeMasters BK, Davis KA, Dreisbach JN, Hormes JT, Filley CM. SYX00254 ; Aldrich CPR; Sigma-Aldrich pricing. Peripheral nerves were also affected. Nerve damage of this type has been found to MRI demonstrates cerebral and cerebellar atrophy, and the severity of cognitive dysfunction correlates with the degree of cerebral white matter hyperintensity on T2-weighted images. D: Axial T2-weighted image demonstrating severe, diffuse cerebral white matter hyperintensity and marked ventricular enlargement. Obtundation may also lead to suffocation, hypothermia due to exposure, or fatal motor vehicle accidents. Use of Biodegradable, Chitosan-Based Nanoparticles in the Treatment of Alzheimer's Disease. As with DTI, it is anticipated that MTI will prove useful in quantitating white matter damage in areas of NAWM. 2A), and the cerebellar white matter (Fig. Epub 2013 Apr 15. Our previous clinical and MRI studies support the idea that in the early years of even heavy toluene abuse, relatively little white matter damage can be detected by MRI scans even though it is likely that myelinotoxic injury is already occurring. Recovery from an injured or damaged nerve may take long time, but again it depends on the degree or severity of the nerve injury. Concomitant use of several different chemicals of abuse could also potentiate the myelin damage from toluene, a possibility discussed by Kornfeld et al (43). Our original autopsy case presents the milder end of the spectrum; although myelin pallor was best seen in the cerebellum, as illustrated in our original paper (41), in the cerebral white matter illustrated here (G) the myelin loss was more subtle and associated with only scattered PAS-positive macrophages, seen here near a small blood vessel. cranial nerve dysfunction as the most disabling aspect of. DTI has been used to detect microstructural lesions of white matter in stroke, leukoaraiosis, traumatic brain injury, neoplasms, and MS (33, 34), even in areas that appear to be normal on conventional MRI—the so-called “normal-appearing white matter” (NAWM; 35). On light microscopy of Case 1, Luxol fast blue-periodic acid-Schiff (LFB-PAS) staining showed severe myelin loss especially around blood vessels. Most inhaled toluene is metabolized in the liver by conversion to benzoic acid by two enzymes, alcohol dehydrogenase and aldehyde dehydrogenase (6). Toluene and other inhalants are a particular problem with minors because these drugs are widely and easily accessible, legal, and inexpensive. While a spectrum of neurobehavioral deficits and white matter damage on MRI can be seen in patients with chronic toluene abuse, severely affected individuals with toluene leukoencephalopathy serve as an excellent example of white matter dementia (7, 10, 25, 26). The health impacts of lead exposure in children include anemia, behavioral disorders, low IQ, reading and learning disabilities, and nerve damage. A Wearable and Wireless Gas-Sensing System Using Flexible Polymer/Multi-Walled Carbon Nanotube Composite Films. The level of exposure also depends on the dose, duration, and work done [6]. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. After inhalation, toluene is rapidly absorbed through the lungs and then widely distributed throughout the body (8). Grossly, there was thinning of the corpus callosum but no discernible white matter discoloration or cavitation. Parkinson disease), and the cerebral white matter each manifest a distinctive constellation of cognitive and emotional disturbances. Patients with sufficiently severe cerebral white matter pathology can be expected to develop deficits in sustained attention, memory retrieval, visuospatial skills, frontal lobe function, and psychiatric status; in contrast, language, procedural memory, and extrapyramidal function are usually preserved (10, 26). It is also found in fuels. The myelin loss was near-total in the cerebellum, except for relative sparing of the hilum and fleece of the dentate nucleus, findings identical to those described in Case 1 of Kornfeld et al (43) (Fig. These results suggested a primary impact on sustained attention, speed of information processing and visuospatial skills, combined with relative sparing of language (23), a pattern consistent with previous neurobehavioral observations in toluene abuse (21). A serious health concern is that toluene may have an effect on your nervous system (brain and nerves). Electron microscopy on Cases 1 and 2 revealed that the macrophages containing coarse PAS-positive granules were packed with clusters of trilaminar inclusions, similar to those seen in adrenoleukodystrophy (ALD) (43). Inhalants produce potent psychoactive effects that have been described as causing a euphoric state similar to that seen with inebriation from ethanol (1). 2H). Exposure to inhalants occurs primarily via pulmonary absorption, and significantly less absorption takes place through the skin or gastrointestinal tract (1). People “huff” or “sniff” paint, paint thinner, or glue in order … His autopsy findings, coupled with MRI data, were the first to confirm that the brunt of the toxic damage from toluene is directed toward the CNS white matter. Nerve damage can make you lose feeling in your feet, so even minor cuts can turn into sores or ulcers without your realizing it. Toluene is also used in the production of polymers used to make nylon, plastic soda bottles, and polyurethanes and for pharmaceuticals, dyes, cosmetic nail products, and the synthesis of organic chemicals. Inhalants, along with alcohol and marijuana, may serve as the initial substances of abuse for young people (3). In this regard, it is noteworthy that of these four recent well-studied patients (41, 43, Case 2 1995 Diagnostic Slide Session of AANP), the two with the most severe myelin and axonal loss were both said to have a history of “paint and glue sniffing” (Case 1 of Kornfeld and colleagues, and the case of Dr. Halliday). The … Over time, nerve damage can also occur in the fingers and hands. Since results of laboratory tests are usually not rapidly available, diagnosis of acute toxicity is usually made based on the clinical history, coupled with the onset of a constellation of neurological symptoms and signs consistent with inebriation (1). Neurotoxicology. Thus the correlation between the effects of a given inhalant such as toluene and its clinical and neuroradiological findings can be difficult in some patients. Even in areas with ostensibly intact myelin there was reactive gliosis (H, GFAP immunohistochemistry, cerebral white matter) and collections of perivascular macrophages (I, LFB-PAS, pons), changes that may foreshadow detectable myelin loss. Although many questions about the toxic effects of inhalants in general are unresolved, the nervous system is clearly vulnerable to toxicity from these substances (4). The idea that toluene may be most damaging when myelin is being formed is corroborated by animal studies demonstrating that rats show a permanent reduction in forebrain myelination after prenatal toluene exposure (50). Search for other works by this author on: Correspondence to: B. K. Kleinschmidt-DeMasters, MD, UCHSC B-216, 4200 East Ninth Avenue, Denver, CO 80262. As mentioned, this solvent, like many others, is highly lipophilic , and in laboratory animals toluene is preferentially distributed in lipid-rich regions of the brain . An area of uncertainty in the study of toluene leukoencephalopathy is the threshold of toluene exposure that is necessary to induce damage to the brain white matter. The patient reported by Escobar et al also showed severe myelin, axon, and neuronal loss, and was acknowledged to abuse both “thinner” and “glue;” the authors acknowledged that he was therefore exposed to both toluene and n-hexane (40). Good animal models of toluene abuse embryopathy have been developed (50, 67). Over time, nerve damage can also occur in the fingers and hands. 1988 Jun;23(6):611-4. doi: 10.1002/ana.410230614. This may in part be due to the fact that brain damage from chronic toluene abuse is probably under-recognized by pathologists. In addition, peripheral nerve dysfunction has been reported, but the peripheral neuropathies may have been due to impurities, such as n-hexane, in the toluene. Animal studies suggest that astrocytes are activated by toluene, paralleling the reactive gliosis seen in human cases with lesser degrees of myelin damage. She was a known substance abuser and had been described as often being intoxicated and “smelling of glue.” Neither detailed neurological examinations nor neuroimaging were performed in life and she died by hanging. There will be partial or complete recovery of the nerve and Wallerian degeneration occurs distal to the injury site. COVID-19 is an emerging, rapidly evolving situation. Peripheral neuropathy may be caused by a number of different medical conditions, such as diabetes and cancer. In the 1980s, more comprehensive studies of selective toluene abusers appeared. In 1961, Grabski documented chronic cerebellar degeneration in a person who sniffed toluene for an extended period, and this individual was the first published case documenting persistent neurotoxicity from toluene (13). The spectrum of leukoencephalopathy in toluene abuse as demonstrated by brain MRI. These individuals displayed a pattern of neurobehavioral deficits consisting of inattention, apathy, memory dysfunction, visuospatial impairment, and preserved language (21). Extent of myelin and axonal loss in patients is highly variable, possibly due to extent of exposure, age of onset of toluene abuse, coexistent abuse of other substances, or polymorphisms in the gene encoding the enzyme aldehyde dehydrogenase. 2B). 2019 Dec;179(Pt B):108834. doi: 10.1016/j.envres.2019.108834. Of all the inhalants, the greatest incidence of abuse of a single substance is found with toluene, prompting many human and animals studies on the specific effects of this compound. The highly lipophilic nature of toluene explains its rapid concentration in the lipid-rich central nervous system (CNS; 1). Long term exposure to low levels of toluene has been speculated to cause neurobehavioral dysfunction, but the threshold of exposure above which leukoencephalopathy occurs is debated. Complications list for Occupational liver damage -- Toluene: The list of complications that have been mentioned in various sources for Occupational liver damage -- Toluene includes: Liver failure. MRI also reveals a predilection for damage to the corpus callosum (Fig. This is the largest nerve in the human body that extends from the lower back through the hips and the buttocks and down each leg. Long-term toluene abuse has led to neuropsychiatric and neurobehavioral disorders, which in many cases, but not all, were reversible. Your skin will also become numb. USA.gov. Coronal brain sections from the autopsy case presented by Dr. William Halliday represent the severe end of the spectrum of white matter damage due to toluene abuse, but nevertheless show rather subtle, ill-defined, patchy discoloration of the white matter of the occipital lobe (A), with more obvious involvement of the cerebellar hemisphere (B). Our original autopsied case was a relatively pure chronic toluene abuser who had sniffed paint on a daily basis for many years up until the time of death (41). For someone whose livelihood relies on their voice, the situation was confronting. Perhaps the most significant toxic effect of chronic exposure to inhalants is widespread and long-lasting damage to the brain and other parts of the nervous system. Physical Hazards: Flammable Potential Health Effects Inhalation: Irritation, nausea, headache, drowsiness, dizziness, disorientation, sleep disturbances, loss of coordination, dilated pupils, kidney damage and liver damage Skin Contact: Irritation 65 First Street Troy, NY 12180 Phone: 518.273.6266 www.evidentthermo.com PbS Core EviDots in Toluene MSDS June … methylbenzene . Caldemeyer KS Pascuzzi RM Moran CG Smith RS. Case 2 differed from Case 1 in that PAS-positive macrophages were considerably fewer, the myelin loss significantly less, and the gliosis was several times more intense than in Case 1. Symptoms present similar to those resulting from vestibular and cochlear damage, including tinnitus, ringing of the ears, difficulty walking, deafness, and balance and orientation issues. Nervous system effects can be temporary, such as headaches, dizziness, or unconsciousness. Biochemical analyses also showed increases in very long chain fatty acids in brain, further mimicking ALD. Comparison to adrenoleukodystrophy, Pathology of lacquer thinner induced neuropathy, Acute and chronic progressive encephalopathy due to gasoline sniffing, Degeneration in central and peripheral nervous systems produced by pure n-hexane: An experimental study, Toluene abuse embryopathy: Longitudinal neurodevelopmental effects of prenatal exposure to toluene in rats, Central nervous system distribution of inhaled toluene, Toluene-induced oxidative stress in several brain regions and other organs, Effects of toluene and its metabolites on cerebral reactive oxygen species generation, Neuronal loss in hippocampus in rats exposed to toluene, Toluene inhalation induces glial cell line-derived neurotrophic factor, transforming growth factor and tumor necrosis factor in rat cerebellum, Toluene inhibits synaptic transmission without causing gross morphological disturbances, Toluene at environmentally relevant low levels disrupts differentiation of astrocyte precursor cells, Astrocytes as targets for CNS effects of organic solvents, Effect of toluene on astrocytes and neurotrophic factor in rat brain, Developmental neurotoxicity: Do similar phenotypes indicate a common mode of action? Toluene leukoencephalopathy has become a prototypical example of white matter dementia, and, more generally, underscores the importance of cerebral white matter in neurobehavioral function. Sciatic Nerve Conditions . Environ Res. The process can result in multiple areas of scarring (sclerosis). Chronic near lifetime toluene exposure in rodents does not replicate solvent abuse leukoencephalopathy in humans. Alzheimer disease), the subcortical gray matter (e.g. Prior to the lead phase-out in gasoline, the total amount of lead used in gasoline was over 200,000 tons per year. In contrast, Case 2 of Kornfeld et al (43) and our original case (41) were both described as “paint sniffers” only and showed significantly less myelin loss. Complementary to the human clinical data, several animal studies have verified that toluene targets the central, not peripheral, nervous system. Christopher M. Filley, MD, William Halliday, MD, B. K. Kleinschmidt-Demasters, MD, The Effects of Toluene on the Central Nervous System, Journal of Neuropathology & Experimental Neurology, Volume 63, Issue 1, January 2004, Pages 1–12, https://doi.org/10.1093/jnen/63.1.1. Disorders of the muscles, cardiovascular effects, renal tubular damage, and sudden death have occurred in chronic abusers of toluene. Deficits in executive function and working memory were the most prominent abnormalities in the solvent abusers, and again language was spared (24), paralleling results of previous investigations (21–23). To reduce and even eliminate toluene toxins in chemical component could be using detoxification by foods. 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. 1C and 1D courtesy of James N. Dreisbach, MD). Toluene is a used as paint, lacquer thinner, or a dyeing agent. Perhaps the most significant toxic effect of chronic exposure to inhalants is widespread and long-lasting damage to the brain and other parts of the nervous system. Toluene-4-sulfonic acid tetrahydro-furan-3-ylmethyl ester. The medical treatments to heal nerve damage should be taken under the guidance of an experienced doctor. He occasionally used a rag. Toluene abuse causes diffuse central nervous system white matter changes. Toluene inhalation in rats also causes the induction of basic fibroblastic growth factor, glial cell-line derived neurotrophic factor, transforming growth factor beta 1, and tumor necrosis factor-alpha (55, 59). Animal and human research shows that most inhalants are extremely toxic. Damaged nerves can send your bladder faulty messages, so you feel like you have to pee a lot or have trouble making it to the restroom in time. It usually starts in the nerves farthest from the brain and spinal cord -- like those in the feet and hands. The combination of this pulse and an imaging sequence allows the derivation of a figure known as the magnetization transfer ratio (MTR), the most commonly used MTI parameter (36). If the damage is severe, paralysis may result; this paralysis is rarely permanent but recovery is slow. Two different studies in rats exposed to toluene by inhalation or by oral dosing showed that toluene concentrations were highest in brainstem areas (medulla, pons) with high lipid content (42, 51), and lowest in the cerebral cortex and hippocampus, where less myelin is found (42), underscoring the lipophilic distribution of toluene (1).  |  The chronic encephalopathy associated with long-term toluene abuse is particularly important because it appears to be a permanent and disabling disorder related to white matter damage in the brain. In 1980, Escobar et al (40) described an autopsy case of a 27-year-old man who had abused several solvents, including glue, which also may contain n-hexane or other solvents known to cause both central and distal axonal degeneration (46, 47). A comparison of fetal alcohol syndrome, toluene embryopathy, and maternal phenylketonuria, Toluene embryopathy: Clinical delineation and developmental follow-up, Toluene embryopathy: Delineation of the phenotype and comparison with fetal alcohol syndrome, Solvent abuse in pregnancy: A perinatal perspective, Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex. See also the symptoms of Occupational liver damage -- Toluene and Occupational liver damage -- Toluene: Introduction. Toluene generates reactive oxygen species (ROS) and the toxic effects relating to these reactants. Medical personnel do not regularly see many chronic toluene abusers and most abusers are notoriously poor historians, due in part to their encephalopathy. . The advent of MRI offered an enormous advantage in the investigation of toluene leukoencephalopathy because of its excellent sensitivity to changes in the cerebral white matter. We would therefore concur with the comment of Gotohda et al that “astrocytes may play a role in the neurophysiological changes observed in toluene intoxication” (59). Moreover, nerve growth factor (NGF), tumor necrosis fa … The acute phase effects of toluene on the brain have been investigated in this study using rabbit brain via histopathological, immunohistochemical, and biochemical methods. In the white matter, a low MTR indicates damage to myelin and axons from a wide variety of disorders, including MS (37) and ischemia (38). 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