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Toluene Toxicity
Introduction
Toluene is a simple benzene derivative also known as methylbenzene, phenylmethane, or toluol. Chronic low-level occupational or industrial exposure to toluene can cause toxicity. As a volatile solvent, misuse or abuse is common, resulting in an acute toxidrome. Toluene is an aromatic hydrocarbon with narcotic and neurotoxic effects and, like all inhalants, has the potential to induce addiction pathology.[1][2] The mechanism of action of toluene is not clearly understood, but toluene appears to affect a wide variety of voltage-gated and ligand-gated ion channels.[2]
Recent literature suggests that toluene profoundly modulates dopaminergic neuronal firing from the ventral tegmental area into the limbic and cortical structures, altering signaling-reward pathways.[3][4][5][6][7][8]
Most commonly, studies highlight the prevalence and toxicity associated with acute exposures. Toluene is perceived as safe amongst individuals who misuse solvents and is readily available in multiple formulations meant for household purposes. Therefore, acute toxicity is a common occurrence. While data regarding the precise frequency of toluene toxicity is limited, a single-center emergency department reported 20 acute toxicities within 2 years.[9] However, this may be an underestimation as toluene is ubiquitous in our society, and many individuals experiencing toxicity may not seek care or want to seek care.
Etiology
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Etiology
Toluene (C7H8) is a colorless aromatic hydrocarbon with a wide range of industrial utility. Toluene is used to manufacture plastics, nylon, and polyurethane and as a solvent in paints, inks, adhesives, fragrances, coatings, and cleaning agents. In veterinary medicine, toluene is used to remove ascarids and tapeworms. The United States military uses toluene to manufacture 2,4,6-Trinitrotoluene (TNT), a dangerously explosive nitroaromatic. Toluene is also an important petrochemical used to improve the octane rating of gasoline. [National Center for Biotechnology Information. PubChem Compound Summary for CID 1140, Toluene.]
Approximately 30 billion pounds or 13.6 million metric tons of toluene is produced yearly. Exposure limits have been established for manufacturing plants, construction sites, nail salons, printing establishments, maritime employment, and automobile repair facilities.
The Occupational Safety and Health Administration (OSHA) uses a reference concentration of 5 mg/m3. At this concentration, the acute minimal risk level is 2 ppm (exposure from 1 to 14 days), while the chronic minimal risk level is 1 ppm (greater than 365 days). The permissible exposure limit is 200 ppm for 8 hours, with an acceptable ceiling concentration of 300 ppm and an acceptable peak beyond the ceiling concentration of 500 ppm over 10 minutes. The National Institute for Occupational Safety and Health (NIOSH) recommends a more stringent standard of 100 ppm for 8 hours with an acceptable peak of 150 ppm over 15 minutes. (NIOSH. Toluene standards) Both organizations recommend the minimum use of personal protective equipment for chemical cartridge respirators with organic vapor cartridges, with additional recommendations based on time and concentration of exposure.
There is limited data on dermal exposure limits. However, multiple studies have reported defatting dermatitis, pruritus, and epidermal thickening with repeated exposures.[10][11] An estimated exposure concentration that resulted in dermatitis and pruritus was reported in female shoe workers as 65 ppm (15 ppm to 100 ppm) in winter to 100 ppm (10 ppm to 200 ppm) in summer over 40 months.[10][11]
Outside of occupational exposure, toluene can be found in the atmosphere, water sources, and soil. Domestic manufacturing and processing facilities release an estimated 22 million pounds (10,000 metric tons) of toluene into the atmosphere annually. Newly constructed buildings and areas of high gasoline emissions are noted in areas of heightened concentrations, eg, a new apartment has levels as high as 66.06 μg/m3. In comparison, the outdoor levels were 11.05 μg/m3. An estimated 54,000 pounds (245 metric tons) of toluene is released from industrial discharge and spill incidents into local water sources. Water sources neighboring hydraulic fracturing operations in Colorado had a mean sample concentration of 750 μg/L with a 95th percentile concentration of 1,900 μg/L. Approximately 1.3 million pounds (590 metric tons) of toluene are estimated to be released into the soil.
There are additional groups that have provided recommendations on occupational exposure limits. The Lower Olefins and Aromatics (LOA) REACH Consortium recognizes 100 ppm over 15 minutes or 20 ppm over 8 hours before side effects occur.[12] Excessive amounts greater than 500 ppm are associated with a range of clinical presentations, from acute euphoric effects to organ failure and sudden death.[13][14][15][16]
Epidemiology
Toluene is the most commonly misused volatile solvent. The prevalence of toluene misuse and acute toxicity peaks at 12 to 14 years of age and significantly declines after age 18, perhaps reflecting a shift to other substances.[2][17][18] Reports of toluene misuse are significantly higher in boys and young men than in girls and young women.[19] The reported prevalence rate of toluene misuse amongst American 8th to 12th graders has been steady for the past 20 years at 10%; only marijuana has a higher reported usage rate in this age group.[17] Worldwide, the highest prevalence rates of toluene misuse are found in Brazil (16.5%) and Australia (10.3%), while Canada (3% to 5%) and Japan (1.2%) are among the countries with the lowest prevalence.[17][18][19] Communities that are disproportionately affected by toluene toxicity include indigenous groups located in America, Australia, and Canada, with rates ranging from 50% to 60%.[18]
Toluene is ubiquitous in general, maritime, construction, and petrochemical industries. The prevalence and exposure rates among industrial workers have yet to be established, as toluene is typically found. OSHA and NIOSH have identified groups at increased risk of toluene exposure, including workers near underground gasoline storage tanks, nail salon technicians, construction workers who use adhesives, solvents, and paints, and workers involved in gasoline production. (OSHA. Toluene Standards.)(NIOSH. Toluene standards.)
Pathophysiology
Toluene exposure may occur via inhalational, transdermal, or absorptive routes. Inhalational exposure, whether occupational, accidental, or intentional, is the most common. Acute toluene toxicity can result from ingestion, leading to gastrointestinal absorption.[9]
Toluene is rapidly absorbed from the lungs and gastrointestinal tract but absorbed at low concentrations following transdermal exposure. Toluene is lipophilic and readily crosses cell membranes, blood-brain, and placental barriers.[20] Following absorption, toluene is widely distributed in well-vascularized tissues, including the central and peripheral nervous systems, liver, kidneys, and bone marrow. Peak absorption following inhalation occurs within 15 to 30 minutes.[20] In a study of 6 healthy subjects exposed to toluene vapor for 4 hours, the concentrations of toluene in the brain and the blood were exponentially correlated to toluene in the air.[21]
The onset of an acute toxidrome may occur within seconds, and the concentration of toluene and length of exposure dictates the duration of adverse effects. The half-life of toluene is estimated to be 3 minutes in highly vascularized organs, 40 minutes in soft tissue, and more than 12 hours in adipose tissue.[20]
The metabolism of toluene predominately occurs via 2 pathways. Cytochrome P450 isozymes, predominately CYP2E1, catalyze methyl hydroxylation to form benzyl alcohol. Alcohol dehydrogenase and aldehyde dehydrogenase oxidize benzyl alcohol to yield benzoic acid. Conjugation with glycine forms hippuric acid, the major metabolite (95%), or glucuronic acid, forming benzyl glucuronide. The second major pathway begins with ring hydroxylation of toluene with similar P450 isozymes to yield epoxide intermediates, precursors to various aromatic configurations of cresol. Conjugation with sulfate or glucuronic acid yields a trace amount of metabolites.[2][20][22]
Most toluene is eliminated after 20 hours of exposure through urination as hippuric acid (31% to 80%) and other metabolites (3% to 4%), exhalation as intact toluene (7% to 14%), and bile (2%).[20]
Toluene toxicity leads to a range of acute and chronic effects that are attributed to its major metabolite, hippuric acid. The hallmark of toluene toxicity is type 1 renal tubular acidosis. Toluene is metabolized to hippuric acid by cytochrome p-450 enzymes, which deprotonates in plasma to hippurate, then ionically binds with ammonium, sodium, or potassium cations and is excreted in the urine.[9] Additionally, toxicity may be associated with hypokalemia, resulting in weakness, spasticity, cardiac arrhythmias, and other complications such as rhabdomyolysis.[9]
Neurologic features of toluene toxicity include early euphoria followed by emotional lability, dizziness, dysarthria, ataxia, and visual or auditory hallucinations. Known neuronal targets of toluene include N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA), and serotonin (5HT3).
- NMDA: non-competitively inhibits NMDA receptors, leading to an influx of chlorine through the cellular membrane, neuronal hyperpolarization, inhibition of nerve impulse propagation, and central nervous system depression.[23][20][24][25][20]
- GABA: enhances GABA receptor function, increasing pyramidal neurons' inhibitory tone. This is especially true within the hippocampus, and chronic exposure leads to decreased cognition and learning disabilities.[25][3][26][3]
- 5HT3: reversible, concentration-dependent potentiation of serotonin-3A is seen with toluene exposure, which is further attributed to signaling alterations consistent with addiction.[27][25][27]
- nAchR: inhibits[25][23]
Chronic exposure, including occupational or repeat misuse, may cause permanent effects such as cognitive impairment and behavior irregularities from changes in neuronal spasticity and signaling pathways listed above.[3] Defatting has been reported from multiple sources, which can lead to dermatitis on the distal upper extremities, mouth, and nose.[28][29] This same defatting has been seen in neurologic complications attributed to toluene, termed “toluene leukoencephalopathy,” in which autopsy reports demonstrated atrophy and mottling of white matter as though the lipid-based myelin was dissolved away.[30] Similar to the features found in an individual with fetal alcohol syndrome, fetal solvent syndrome has been described in children born to women with chronic toluene misuse.[15][31]
Histopathology
The histological features of toluene toxicity are primarily studied in mice and rat lungs, brains, and kidneys. Toluene-treated mouse lung demonstrated irregular cellular architecture with compaction of the interalveolar septum, alveolar septa thickening, deposition of fibrous node-like structures, and hyperplasia.[32] Mice exposed to toluene had increased expression of glial fibrillary acidic protein and astrogliosis in the hippocampus, cortex, and cerebellum.[33] Rat kidneys were noted to have massive tubular degeneration, glomerular disorganization with shrinkage, congestion, and tubular cell vacuolization.[34]
History and Physical
During history intake, special consideration should be given to potential exposure sources (eg, occupation, travel, or home renovations), and if explicitly stated by the patient, the characteristics of the exposure (eg, product inhaled, the evolution of symptoms, chronicity, and concomitant substance misuse).
A physical examination should involve all systems as no set of findings exists that are specific to toluene toxicity nor dichotomize acute versus chronic exposure.[2] There is a progression of stages after acute exposure to toluene described by multiple studies: euphoria followed by excitability, disinhibition, and impulsive behaviors.[18][35][36][37]
Major clinical presentations by the system include:
- Neurologic: Headache, slurred speech, diplopia, mood lability, loss of motor control, illusions, hallucinations, dizziness, and nausea. Progression of toxicity can lead to obtundation characterized by seizures, coma, and death. Chronic users can have cognitive impairment, encephalopathy, and changed social behaviors.[38]
- Cardiac: Arrhythmias that can be initially identified by palpation or auscultation via alteration in the strength or rate of cardiac activity.[39]
- Pulmonary: Persistent cough and respiratory distress with breath sounds that can either be clear or have adventitious sounds such as rhonchi or wheezing.[2]
- Renal: Pyuria, dysuria, and hematuria.[40]
- Integumentary: Areas notable for defatting dermatitis, irritation, and pruritus, especially on the distal upper extremities, mouth, and nose.
Evaluation
Initial evaluation should address airway compromise, respiratory distress, and circulatory collapse. Vital signs, including temperature, cardiac evaluation with an electrocardiogram, pulmonary evaluation with chest radiography and ultrasound, and serology or urine studies revealing end-organ dysfunction or electrolyte abnormalities must assess a broad differential diagnosis. Focal neurological deficits may warrant imaging studies.
Hydrocarbon toxicity is difficult to identify, which is more complicated as no laboratory study is available to confirm exposure.[36] While gas chromatography can identify volatile substances, this is not feasible for emergent assessment. Hippuric acid levels in urine greater than 3 g per gram of creatinine are 98.1% sensitive and 100% specific for toluene toxicity, and urine hippuric acid is the preferred way to monitor for exposure in high-risk occupations.[41]
Additional findings that may be present in the setting of toluene toxicity include hypokalemia (with associated electrocardiogram changes), low bicarbonate, elevated creatinine phosphokinase, and hematuria.[42][43][44]
Treatment / Management
Treatment of toluene toxicity focuses on airway management, correcting metabolic acidosis and electrolyte abnormalities, and counseling the patient on the dangers of toluene exposure. Patients should be hospitalized for laboratory monitoring until such derangements are addressed.
Specific management of toluene toxicity is limited to small clinical trials and case studies. Of note, there have been data to suggest the administration of acetaminophen and aspirin as they may inhibit toluene metabolism (CYP2E1 as the site of competitive metabolic interaction), limiting the acute production of hippuric acid.[21] In a study with 40 subjects, psychosis or behavioral changes were reduced by treatment with carbamazepine and haloperidol by 50%.[38] Aggressive fluid management is helpful as toluene metabolites are water soluble and renally excreted.[45] Patients presenting in extremis due to toluene toxicity have benefited from extracorporeal membrane oxygenation.[46](B3)
Neither gastric lavage nor activated charcoal administration is recommended due to aspiration risk and limited gastrointestinal absorption.[47][48] All cases should be reported to the local poison control center for further guidance.(B3)
Differential Diagnosis
The differential diagnosis for toluene toxicity is broad, as its presenting symptoms are nonspecific. The main features of toluene toxicity include altered mental status, pneumonitis, and metabolic acidosis. While this list is not exhaustive, an accurate history is critical.
- Substance misuse (barbiturates, benzodiazepines, opioids)
- Medication overdose (lithium, diuretics)
- Carbon monoxide exposure
- Benzene inhalation
- Acute respiratory distress syndrome
- Suicide
- Traumatic brain disorders
- Toxic encephalopathy
- Primary aldosteronism
- Thyrotoxicosis
- Licorice with glycyrrhizin-induced pseudo-aldosteronism
- Neurovascular or neuromuscular disorders
- Pneumonia
- Neoplasms
Prognosis
Toluene toxicity has a proposed mortality rate of 15%.[9] While extremely high, there are limited studies that record either morbidity or mortality. Acute exposure, if the patient is diagnosed and treated promptly, has minimal lasting complications. However, signs of altered mental status, severe metabolic acidosis, and concomitant hypokalemia are associated with poor outcomes.
Complications from chronic use include tremors, peripheral neuropathy, cerebellar dysfunction, mood changes, chronic encephalopathy, gait disturbance, dementia, and spasticity.[38] There is conflicting evidence regarding whether or not these complications are reversible.[49][50] Significant improvement has been associated with abstinence, younger age, lower level of exposure, and initial symptoms at presentation.[51] Patients with encephalopathy have the worst rates of recovery.[38]
Complications
Toluene toxicity can cause dangerous pulmonary, cardiac, and renal side effects, including acute respiratory distress syndrome, deadly cardiac arrhythmias, and renal failure. Complications regarding patients who are pregnant are not elucidated; however, reproductive and teratogenic risks have been described.[31][52]
Deterrence and Patient Education
Neither toluene toxicity nor inhalant dependence and misuse are discussed in the general population, which could be, in part, due to the lack of literature on the subject. A Cochrane review in 2010 assessed randomized-control trials and controlled clinical trials for the treatment of inhalant dependence and misuse but determined no studies met the inclusion criteria.[53] A 2012 systematic review for volatile substance misuse failed to identify effective therapeutic interventions.[54] One trial identified a significant decrease in inhalant misuse after 1 year of cognitive behavioral therapy intervention.[55] Additional studies must be completed that can strategize effective deterrence and provide information for patient education.
Enhancing Healthcare Team Outcomes
Toxicities of any drug necessitate management by an interprofessional team of healthcare professionals. In addition to physicians, the role of pharmacists, social workers, case managers, and nurses cannot be overstated. Constant monitoring, education, and continued care after hospital discharge sometimes lead to improved patient outcomes and cessation of misuse behavior. All patients should be counseled on the recommended toluene exposure levels deemed safe, determined by their safety organization or safety manager. Finally, parents should be thoroughly educated on the variety of commercial products susceptible to toluene misuse, leading to toxicity.
References
Fishbein L. An overview of environmental and toxicological aspects of aromatic hydrocarbons. II. Toluene. The Science of the total environment. 1985 Apr:42(3):267-88 [PubMed PMID: 3890176]
Level 3 (low-level) evidenceCruz SL, Rivera-García MT, Woodward JJ. Review of toluene action: clinical evidence, animal studies and molecular targets. Journal of drug and alcohol research. 2014:3():. pii: 235840. Epub [PubMed PMID: 25360325]
Level 3 (low-level) evidenceWoodward JJ, Beckley J. Effects of the abused inhalant toluene on the mesolimbic dopamine system. Journal of drug and alcohol research. 2014:3():. pii: 235838. Epub [PubMed PMID: 25360326]
Kondo H, Huang J, Ichihara G, Kamijima M, Saito I, Shibata E, Ono Y, Hisanaga N, Takeuchi Y, Nakahara D. Toluene induces behavioral activation without affecting striatal dopamine metabolism in the rat: behavioral and microdialysis studies. Pharmacology, biochemistry, and behavior. 1995 May:51(1):97-101 [PubMed PMID: 7617740]
Level 3 (low-level) evidenceRiegel AC, French ED. Acute toluene induces biphasic changes in rat spontaneous locomotor activity which are blocked by remoxipride. Pharmacology, biochemistry, and behavior. 1999 Mar:62(3):399-402 [PubMed PMID: 10080229]
Level 3 (low-level) evidenceFunada M, Sato M, Makino Y, Wada K. Evaluation of rewarding effect of toluene by the conditioned place preference procedure in mice. Brain research. Brain research protocols. 2002 Aug:10(1):47-54 [PubMed PMID: 12379437]
Level 3 (low-level) evidenceLee DE, Gerasimov MR, Schiffer WK, Gifford AN. Concentration-dependent conditioned place preference to inhaled toluene vapors in rats. Drug and alcohol dependence. 2006 Oct 15:85(1):87-90 [PubMed PMID: 16675162]
Level 3 (low-level) evidenceBowen SE, Wiley JL, Balster RL. The effects of abused inhalants on mouse behavior in an elevated plus-maze. European journal of pharmacology. 1996 Sep 26:312(2):131-6 [PubMed PMID: 8894586]
Level 3 (low-level) evidenceCamara-Lemarroy CR, Rodríguez-Gutiérrez R, Monreal-Robles R, González-González JG. Acute toluene intoxication--clinical presentation, management and prognosis: a prospective observational study. BMC emergency medicine. 2015 Aug 18:15():19. doi: 10.1186/s12873-015-0039-0. Epub 2015 Aug 18 [PubMed PMID: 26282250]
Level 2 (mid-level) evidenceWinchester RV, Madjar VM. Solvent effects on workers in the paint, adhesive and printing industries. The Annals of occupational hygiene. 1986:30(3):307-17 [PubMed PMID: 3777750]
WOLF MA, ROWE VK, MCCOLLISTER DD, HOLLINGSWORTH RL, OYEN F. Toxicological studies of certain alkylated benzenes and benzene; experiments on laboratory animals. A.M.A. archives of industrial health. 1956 Oct:14(4):387-98 [PubMed PMID: 13361560]
Level 3 (low-level) evidenceRooseboom M, Kocabas NA, North C, Radcliffe RJ, Segal L. Recommendation for an occupational exposure limit for toluene. Regulatory toxicology and pharmacology : RTP. 2023 Jun:141():105387. doi: 10.1016/j.yrtph.2023.105387. Epub 2023 May 9 [PubMed PMID: 37169161]
Bowen SE, Daniel J, Balster RL. Deaths associated with inhalant abuse in Virginia from 1987 to 1996. Drug and alcohol dependence. 1999 Feb 1:53(3):239-45 [PubMed PMID: 10080050]
Level 2 (mid-level) evidenceBass M. Sudden sniffing death. JAMA. 1970 Jun 22:212(12):2075-9 [PubMed PMID: 5467774]
Bowen SE. Two serious and challenging medical complications associated with volatile substance misuse: sudden sniffing death and fetal solvent syndrome. Substance use & misuse. 2011:46 Suppl 1():68-72. doi: 10.3109/10826084.2011.580220. Epub [PubMed PMID: 21609149]
Hobara T, Okuda M, Gotoh M, Oki K, Segawa H, Kunitsugu I. Estimation of the lethal toluene concentration from the accidental death of painting workers. Industrial health. 2000 Apr:38(2):228-31 [PubMed PMID: 10812847]
Level 3 (low-level) evidenceBeckley JT, Woodward JJ. Volatile solvents as drugs of abuse: focus on the cortico-mesolimbic circuitry. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2013 Dec:38(13):2555-67. doi: 10.1038/npp.2013.206. Epub 2013 Aug 19 [PubMed PMID: 23954847]
Level 3 (low-level) evidenceCairney S, Maruff P, Burns C, Currie B. The neurobehavioural consequences of petrol (gasoline) sniffing. Neuroscience and biobehavioral reviews. 2002 Jan:26(1):81-9 [PubMed PMID: 11835986]
Level 3 (low-level) evidenceHynes-Dowell M, Mateu-Gelabert P, Barros HM, Delva J. Volatile substance misuse among high school students in South America. Substance use & misuse. 2011:46 Suppl 1(0 1):27-34. doi: 10.3109/10826084.2011.580192. Epub [PubMed PMID: 21609142]
Level 2 (mid-level) evidenceLima AR. Toluene: correlation between occupational exposure limits and biological exposure indices. Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT. 2022 Oct-Dec:20(4):633-641. doi: 10.47626/1679-4435-2022-715. Epub 2023 Feb 13 [PubMed PMID: 37101451]
Löf A, Hansen SH, Näslund P, Steiner E, Wallén M, Hjelm EW. Relationship between uptake and elimination of toluene and debrisoquin hydroxylation polymorphism. Clinical pharmacology and therapeutics. 1990 Mar:47(3):412-7 [PubMed PMID: 2311341]
Cosnier F, Brochard C, Burgart M, Cossec B. Mercapturic acids derived from toluene in rat urine samples: identification and measurement by gas chromatography-tandem mass spectrometry. Analytical and bioanalytical chemistry. 2012 Oct:404(6-7):1907-17. doi: 10.1007/s00216-012-6262-6. Epub 2012 Jul 25 [PubMed PMID: 22829455]
Level 3 (low-level) evidenceBale AS, Smothers CT, Woodward JJ. Inhibition of neuronal nicotinic acetylcholine receptors by the abused solvent, toluene. British journal of pharmacology. 2002 Oct:137(3):375-83 [PubMed PMID: 12237258]
Level 3 (low-level) evidenceCruz SL, Mirshahi T, Thomas B, Balster RL, Woodward JJ. Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed in Xenopus oocytes. The Journal of pharmacology and experimental therapeutics. 1998 Jul:286(1):334-40 [PubMed PMID: 9655877]
Level 3 (low-level) evidenceBeckley JT, Woodward JJ. The abused inhalant toluene differentially modulates excitatory and inhibitory synaptic transmission in deep-layer neurons of the medial prefrontal cortex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2011 Jun:36(7):1531-42. doi: 10.1038/npp.2011.38. Epub 2011 Mar 23 [PubMed PMID: 21430649]
Level 3 (low-level) evidenceBeckstead MJ, Weiner JL, Eger EI 2nd, Gong DH, Mihic SJ. Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse. Molecular pharmacology. 2000 Jun:57(6):1199-205 [PubMed PMID: 10825391]
Level 3 (low-level) evidenceLopreato GF, Phelan R, Borghese CM, Beckstead MJ, Mihic SJ. Inhaled drugs of abuse enhance serotonin-3 receptor function. Drug and alcohol dependence. 2003 May 1:70(1):11-5 [PubMed PMID: 12681521]
Level 3 (low-level) evidenceYakes B, Kelsey KT, Seitz T, Hashimoto D, Feldman HA, Christiani DC. Occupational skin disease in newspaper pressroom workers. Journal of occupational medicine. : official publication of the Industrial Medical Association. 1991 Jun:33(6):711-7 [PubMed PMID: 1830898]
Hansbrough JF, Zapata-Sirvent R, Dominic W, Sullivan J, Boswick J, Wang XW. Hydrocarbon contact injuries. The Journal of trauma. 1985 Mar:25(3):250-2 [PubMed PMID: 3981678]
Level 3 (low-level) evidenceKornfeld M, Moser AB, Moser HW, Kleinschmidt-DeMasters B, Nolte K, Phelps A. Solvent vapor abuse leukoencephalopathy. Comparison to adrenoleukodystrophy. Journal of neuropathology and experimental neurology. 1994 Jul:53(4):389-98 [PubMed PMID: 8021713]
Level 3 (low-level) evidenceHannigan JH, Bowen SE. Reproductive toxicology and teratology of abused toluene. Systems biology in reproductive medicine. 2010 Apr:56(2):184-200. doi: 10.3109/19396360903377195. Epub [PubMed PMID: 20377315]
Level 3 (low-level) evidenceSvenson DW, Davidson CJ, Thakur C, Bowen SE. Acute exposure to abuse-like concentrations of toluene induces inflammation in mouse lungs and brain. Journal of applied toxicology : JAT. 2022 Jul:42(7):1168-1177. doi: 10.1002/jat.4285. Epub 2022 Jan 26 [PubMed PMID: 34993988]
Baydas G, Reiter RJ, Nedzvetskii VS, Yaşar A, Tuzcu M, Ozveren F, Canatan H. Melatonin protects the central nervous system of rats against toluene-containing thinner intoxication by reducing reactive gliosis. Toxicology letters. 2003 Feb 3:137(3):169-74 [PubMed PMID: 12523959]
Level 3 (low-level) evidenceAbouee-Mehrizi A, Rasoulzadeh Y, Mesgari-Abbasi M, Mehdipour A, Ebrahimi-Kalan A. Nephrotoxic effects caused by co-exposure to noise and toluene in New Zealand white rabbits: A biochemical and histopathological study. Life sciences. 2020 Oct 15:259():118254. doi: 10.1016/j.lfs.2020.118254. Epub 2020 Aug 12 [PubMed PMID: 32800833]
Kurtzman TL, Otsuka KN, Wahl RA. Inhalant abuse by adolescents. The Journal of adolescent health : official publication of the Society for Adolescent Medicine. 2001 Mar:28(3):170-80 [PubMed PMID: 11226839]
Williams JF, Storck M, American Academy of Pediatrics Committee on Substance Abuse, American Academy of Pediatrics Committee on Native American Child Health. Inhalant abuse. Pediatrics. 2007 May:119(5):1009-17 [PubMed PMID: 17473104]
Howard MO, Bowen SE, Garland EL, Perron BE, Vaughn MG. Inhalant use and inhalant use disorders in the United States. Addiction science & clinical practice. 2011 Jul:6(1):18-31 [PubMed PMID: 22003419]
Level 2 (mid-level) evidenceTormoehlen LM, Tekulve KJ, Nañagas KA. Hydrocarbon toxicity: A review. Clinical toxicology (Philadelphia, Pa.). 2014 Jun:52(5):479-89. doi: 10.3109/15563650.2014.923904. Epub [PubMed PMID: 24911841]
Level 3 (low-level) evidenceShepherd RT. Mechanism of sudden death associated with volatile substance abuse. Human toxicology. 1989 Jul:8(4):287-91 [PubMed PMID: 2777268]
Olgar S, Oktem F, Dindar A, Kilbas A, Turkoglu UD, Cetin H, Altuntas I, Yilmaz R, Uz E, Ertugrul T, Omeroglu R, Aydogan U. Volatile solvent abuse caused glomerulopathy and tubulopathy in street children. Human & experimental toxicology. 2008 Jun:27(6):477-83. doi: 10.1177/0960327108092292. Epub [PubMed PMID: 18784200]
Thiesen FV, Noto AR, Barros HM. Laboratory diagnosis of toluene-based inhalants abuse. Clinical toxicology (Philadelphia, Pa.). 2007 Jun-Aug:45(5):557-62 [PubMed PMID: 17503266]
Streicher HZ, Gabow PA, Moss AH, Kono D, Kaehny WD. Syndromes of toluene sniffing in adults. Annals of internal medicine. 1981 Jun:94(6):758-62 [PubMed PMID: 7235417]
Patel R, Benjamin J Jr. Renal disease associated with toluene inhalation. Journal of toxicology. Clinical toxicology. 1986:24(3):213-23 [PubMed PMID: 3014162]
Level 3 (low-level) evidenceGarland EL, Howard MO. Phenomenology of adolescent inhalant intoxication. Experimental and clinical psychopharmacology. 2010 Dec:18(6):498-509. doi: 10.1037/a0021737. Epub [PubMed PMID: 21186924]
Kopec KT, Brent J, Banner W, Ruha AM, Leikin JB. Management of cardiac dysrhythmias following hydrocarbon abuse: clinical toxicology teaching case from NACCT acute and intensive care symposium. Clinical toxicology (Philadelphia, Pa.). 2014 Feb:52(2):141-5. doi: 10.3109/15563650.2014.882001. Epub 2014 Jan 30 [PubMed PMID: 24476044]
Level 3 (low-level) evidenceColombier S, Prêtre R, Iafrate M, Niclauss L. Double-stage venous cannulation combined with Avalon® cannula for potential prolongation of respiratory ECMO in end-stage pulmonary disease. Perfusion. 2016 Oct:31(7):593-7. doi: 10.1177/0267659116641483. Epub 2016 Mar 25 [PubMed PMID: 27015915]
Dice WH, Ward G, Kelley J, Kilpatrick WR. Pulmonary toxicity following gastrointestinal ingestion of kerosene. Annals of emergency medicine. 1982 Mar:11(3):138-42 [PubMed PMID: 7065488]
Level 3 (low-level) evidenceKhanna P, Devgan SC, Arora VK, Shah A. Hydrocarbon pneumonitis following diesel siphonage. The Indian journal of chest diseases & allied sciences. 2004 Apr-Jun:46(2):129-32 [PubMed PMID: 15072330]
Level 3 (low-level) evidenceLubman DI, Yücel M, Lawrence AJ. Inhalant abuse among adolescents: neurobiological considerations. British journal of pharmacology. 2008 May:154(2):316-26. doi: 10.1038/bjp.2008.76. Epub 2008 Mar 10 [PubMed PMID: 18332858]
Level 3 (low-level) evidenceDingwall KM, Cairney S. Recovery from central nervous system changes following volatile substance misuse. Substance use & misuse. 2011:46 Suppl 1():73-83. doi: 10.3109/10826084.2011.580221. Epub [PubMed PMID: 21609150]
van Valen E, Wekking E, van der Laan G, Sprangers M, van Dijk F. The course of chronic solvent induced encephalopathy: a systematic review. Neurotoxicology. 2009 Nov:30(6):1172-86. doi: 10.1016/j.neuro.2009.06.002. Epub 2009 Jun 16 [PubMed PMID: 19538991]
Level 2 (mid-level) evidenceHamid OIA, Domouky AM, El-Fakharany YM. Molecular evidence of the amelioration of toluene induced encephalopathy by human breast milk mesenchymal stem cells. Scientific reports. 2022 Jun 2:12(1):9194. doi: 10.1038/s41598-022-13173-6. Epub 2022 Jun 2 [PubMed PMID: 35654991]
Konghom S, Verachai V, Srisurapanont M, Suwanmajo S, Ranuwattananon A, Kimsongneun N, Uttawichai K. Treatment for inhalant dependence and abuse. The Cochrane database of systematic reviews. 2010 Dec 8:(12):CD007537. doi: 10.1002/14651858.CD007537.pub2. Epub 2010 Dec 8 [PubMed PMID: 21154379]
Level 1 (high-level) evidenceMacLean S, Cameron J, Harney A, Lee NK. Psychosocial therapeutic interventions for volatile substance use: a systematic review. Addiction (Abingdon, England). 2012 Feb:107(2):278-88. doi: 10.1111/j.1360-0443.2011.03650.x. Epub [PubMed PMID: 22248138]
Level 2 (mid-level) evidenceÖgel K, Coskun S. Cognitive behavioral therapy-based brief intervention for volatile substance misusers during adolescence: a follow-up study. Substance use & misuse. 2011:46 Suppl 1():128-33. doi: 10.3109/10826084.2011.580233. Epub [PubMed PMID: 21609157]
Level 1 (high-level) evidence