Toluene inhalation

Bredt DS, Snyder SEl Nitric oxide, a novel neuronal messenger. Neuron 8 3—11, 1992 Brouette T, Anton R Clinical review of inhalants. Am J Addict 10 79-94, 2001 Brown ES, Nejtek VA, Perantie DC, et al Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord4 406 11, 2002 Bushnell PJ, Evans EIL, Palmes ED Effects of toluene inhalation on carbon dioxide production and locomotor activity in mice. Fundam Appl Toxicol 5 971-977, 1983... 

Himnan DJ Tolerance and reverse tolerance to toluene inhalation effects on open-field behavior. Pharmacol Biochem Behav 21 625-631, 1984 Hinman DJ Biphasic dose-response relationship for effects of toluene inhalation on locomotor activity. Pharmacol Biochem Behav 26 65-69, 1987 Hormes JT, Filley CM, Rosenberg NL Neurologic sequelae of chronic solvent vapor abuse. Neurology 36 698—702, 1986... 

Knox JW, Nelson JR Permanent encephalopathy from toluene inhalation. N Engl J Med 275 1494-1496, 1966... 

Rea TM, Nash JF, Zabik JE, et al Effects of toluene inhalation on brain biogenic amines in the rat. Toxicology 31 143-1450, 1984 Rebert CS, Matteucci MJ, Pryor GT Acute electrophysiologic effects of inhaled toluene on adult male Long-Evans rats. Pharmacol Biochem Behav 33 157—165, 1989 Reynolds JEF Martindale The Extra Pharmacopoeia, 28th Edition. London, Pharmaceutical Press, 1982, pp 745-746... 

The analgesic drugs paracetamol and acetylsalicylic acid at normal clinical doses had no acute effect on toxicokinetics of toluene inhaled at 300 mg/m (Lbf el al., 1990b) similarly, neither carbohydrate diets nor the consumption of 47 g ethanol as wine on the evening before exposure to 200 mg/m- toluene for 2 h had any effect on toluene kinetics (Hjelm et al., 1994). 

Hypokalemia is a common accompaniment of the metabolic acidosis that toluene inhalation can cause (see below). However, severe hypokalemia has also been reported in the absence of acidosis (31). 

Carder JR, Fuerst RS. Myocardial infarction after toluene inhalation. Pediatr Emerg Care 1997 13(2) 117-9. 

In 2002, Madina Gerasimov and colleagues at the Brookhaven National Laboratory found that inhalation of a behaviorally relevant concentration of toluene (the amount a sniffer would use) caused an increase in dopamine release in the brains of freely moving rats. Toluene inhalation combined... 

Gerasimov, M.R., W.K. Schiffer, D. Marstellar, R. Ferrieri, D. Alexoff, and S.L. Dewey. Toluene Inhalation Produces Regional Specific Ghanges in Extracellular Dopamine. Drug and Alcohol Dependence 65 (2002) 243-251. 

Aromatic EC5-EC9 Exposures Associated with Health Effects - Benzene—Inhalation 6-2 Aromatic EC5-EC9 Exposures Associated with Health Effects - Toluene—Inhalation... 

Castilla-Serna L, Rodriguez-Perez, Osorio-Cruces F, et al. 1991. Effects of chronic toluene inhalation on avoidance conditioned behavior in rats. Arch Invest Med 22 295-301. 

King MD Neurological sequelae of toluene abuse. Hum Toxicol 1 281-287,1982 King MD, Day RE, Oliver JS, et al Solvent encephalopathy. BMJ 283 663-665, 1981 Knox WJ, Nelson JR Permanent encephalopathy from toluene inhalation. N Engl J Med 275 1494-1496, 1966... 

Other mixtures which may be employed are carbon tetrachloride (b.p. 77°) and toluene (b.p. 110-111°) chloroform (b.p. 61°) and toluene methyl alcohol (b.p. 65°) and water (b.p. 100°). The last example is of interest because almost pure methyl alcohol may be isolated no constant boiling point mixture (or azeotropic mixture) is formed (compare ethyl alcohol and water, Sections 1,4 and 1,5). Attention is directed to the poisonous character of methyl alcohol the vapour should therefore not be inhaled. 

Health and Safety Factors. Animal-feeding studies of DMPPO itself have shown it to be nontoxic on ingestion. The solvents, catalyst, and monomers that are used to prepare the polymers, however, should be handled with caution. Eor example, for the preparation of DMPPO, the amines used as part of the catalyst are flammable toxic on ingestion, absorption, and inhalation and are also severe skin and respiratory irritants (see Amines). Toluene, a solvent for DMPPO, is not a highly toxic material in inhalation testing the TLV (71) is set at 375 mg/m, and the lowest toxic concentration is reported to be 100—200 ppm (72). Toxicity of 2,6-dimethylphenol is typical of alkylphenols (qv), eg, for mice, the acute dermal toxicity is LD q, 4000 mg/kg, whereas the acute oral toxicity is LD q, 980 mg/kg (73). The Noryl blends of DMPPO and polystyrene have PDA approval for reuse food apphcations. 

Like many organic solvents, including hexane, heptane, ben2ene, xylene, toluene, gasoline, and particularly some of the other chlorinated and fluorinated solvents, methylene chloride may cause cardiac arrhythmias in the presence of elevated epinephrine when inhaled at concentrations as high as 20,000 ppm (36). 

Benzene, which has been used as a solvent successfully and extensively in the past for reactions and purification by chromatography and crystallisation is now considered a very dangerous substance so it hasto be used with extreme care. We emphasise that an alternative solvent system to benzene (e.g. toluene, toluene-petroleum ether, or a petroleum ether to name a few) should be used first. However, if no other solvent system can be found then all operations involving benzene have to be performed in an efficient fumehood and precautions must be taken to avoid inhalation and contact with skin and eyes. Whenever benzene is mentioned in the text an asterisk e.g. C Hg or benzene, is inserted to remind the user that special precaution should be adopted. 

Benzene is a flammable liquid and its vapors are toxic and explosive. Low concentrations are dangerous on continued inhalation because benzene affects the blood forming function of the bone marrow and it is a cancirogen. Dermatitis may result from repeated skin contact. Alkyl derivatives such as toluene and xylenes are far less toxic and are, therefore, much safer than benzene for use in solvents. Some of the symptoms of benzene poisoning are dizziness, constriction of the chest, and tightening of the leg muscles. 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

The nicotinic acetylcholine (nACh) receptor also displays sensitivity to inhalants (Bale et al. 2002). To varying degrees, toluene appeared to antagonize the function of nACh receptors that comprise different subunits. At concentrations of 50 pM to 10 mM, toluene produced a reversible, concentration-dependent inhibition of acetylcholine-induced current in Xenopus oocytes expressing various nicotinic receptor subtypes, with the ol — 2 d ct3—P2 subunit combinations being more sensitive to inhibition than other receptor... 

Similar to alcohol (Lovinger and White 1991) and volatile anesthetics (Machu and Harris 1994), trichoroethane, trichloroethylene, and toluene enhance 5-HT3 receptor function. All three inhalants significantly and reversibly potentiated, in a dose-dependent manner, 5-HT-activated currents, mediated by mouse 5-HT3 receptors expressed in Xenopus oocytes. Another feature common to these drugs is that the acute use of inhalants, as well as alcohol and volatile anesthetics, can produce nausea and vomiting (Meredith et al. 1989). It is believed that 5-HT3 receptors located in the area postrema mediate this action of alcohol and the volatile anesthetics (Aapro 1991). 

Studies of the intoxicating effects of toluene showed that the inhalation of its vapor at a concentration of 200 ppm was associated with the development of mild-to-moderate intoxication, characterized by sedation, paresthesias, and hyporeflexia. Toluene vapor concentrations of 600-800 ppm induced a confusional state, whereas greater concentrations produced an intense euphoria (Benignus 1981 Press and Done 1967). In humans, plasma concentrations of toluene of 10-100 pM have been reported to be intoxicating these concentrations are close to the intoxicating concentrations of alcohol and in-halational anesthetics (Miller 1985). 

Inhalant intoxication dehrium can occur as a consequence of disturbances in dopaminergic, glutamatergic, and GABAergic neu to transmission secondary to acute, high-level exposure to psychoactive ingredients in solvents such as toluene, trichloroethane, and trichloroethylene. Systemic effects of solvent inhalation such as cerebral hypoxia and/or metabolic acidosis may also be involved (Rosenberg 1982). Under these circumstances, inhalant intoxication dehrium develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. Usually, the delirium resolves as the intoxication ends or within a few hours after cessation of use. 

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