Toluene central nervous system

Solvents acetone, methyl ethyl ketone (MEK), toluene, xylene, glycol, ethers, alcohol defats and dries skin some may be absorbed may carry other components through skin high volatility, exposure possible irritation central nervous system depression (e.g. dizziness, loss of coordination) low to high toxicity, longterm effects... 

Peripheral neuropathy has also occurred in humans as the result of solvent abuse of products containing -hexane (Altenkirch et al. 1977 Chang et al. 1998 Spencer et al. 1980). Clinical signs were very similar to those seen after occupational exposure however, signs of central nervous system toxicity may also be present due to other components in the inhaled mixtures, e.g., toluene (Spencer et al. 1980). 

In a study where both peripheral and central nervous system effects were measured in rats co-exposed to u-hexane and toluene (Pryor and Rebert 1992), toluene exposure at 1,400 ppm for 14 hours a day for 9 weeks prevented the peripheral neurotoxicity (decreased grip strength and nerve conduction velocities) caused by exposure to 4,000 ppm 77-hcxanc alone. There was no reciprocal action of 77-hexane on the motor syndrome (shortened and widened gait and widened landing foot splay) and hearing loss caused by toluene. Brainstem auditory response amplitudes were decreased by 77-hcxanc, co-exposure to toluene did not block this effect. 

Toxicology. p-tert-Butyl toluene is an irritant of the mucous membranes, a central nervous system depressant and may cause cardiovascular and hematologic disturbances chronic exposure in animals causes lung, brain, liver, and kidney damage. 

Toxicology. Toluene causes central nervous system depression. 

Toluene, also known as methylbenzene, is the simplest member of the series known as alkylbenzenes, where an alkyl group, e.g. CH3, is directly attached to the benzene ring. As the use of benzene as a nonpolar solvent has long been prohibited because of its adverse effect on the central nervous system (CNS) and on bone marrow, as well as its carcinogenic property, toluene has replaced benzene as a nonpolar solvent. Although it has a CNS depressant property like benzene, it does not cause leukaemia or aplastic anaemia. 

The exact mechanism of action of most volatile substances remains unknown. Altered function of ionotropic receptors and ion channels throughout the central nervous system has been demonstrated for a few. Nitrous oxide, for example, binds to NMDA receptors and fuel additives enhance GABAa receptor function. Most inhalants produce euphoria increased excitability of the VTA has been documented for toluene and may underlie its addiction risk. Other substances, such as amyl nitrite ("poppers"), primarily produce smooth muscle relaxation and enhance erection, but are not addictive. With chronic exposure to the aromatic hydrocarbons (eg, benzene, toluene), toxic effects can be observed in many organs, including white matter lesions in the central nervous system. Management of overdose remains supportive. 

Toluene (methylbenzene) does not possess the myelotoxic properties of benzene, nor has it been associated with leukemia. It is, however, a central nervous system depressant and a skin and eye irritant. It is also fetotoxic. See Table 56-1 for the TLVs. Exposure to 800 ppm can lead to severe fatigue and ataxia 10,000 ppm can produce rapid loss of consciousness. Chronic effects of long-term toluene exposure are unclear because human studies indicating behavioral effects usually concern exposures to several solvents. In limited occupational studies, however, metabolic interactions and modification of toluene s effects have not been observed in workers also exposed to other solvents. Less refined grades of toluene contain benzene. 

Xylene (dimethylbenzene) has been substituted for benzene in many solvent degreasing operations. Like toluene, the three xylenes do not possess the myelotoxic properties of benzene, nor have they been associated with leukemia. Xylene is a central nervous system depressant and a skin irritant. Less refined grades of xylene contain benzene. See Table 56-1 for the TLVs. 

Carpenter et al. (1988) carried out a nested case-control study of cancer of the central nervous system among workers at two nuclear facilities located in Tennessee (United States). They identified 89 cases (72 males and 17 females) who had died between 1943 and 1979. Four controls, living at the time the case was diagnosed, were matched to each case. Job history records were scrutinized by an industrial hygienist to assess potential exposure to each of 26 chemicals or chemical groups. Toluene, xylene (see this volume) and 2-butanone (methyl ethyl ketone) were evaluated as one chemical group the matched relative risk was 2.0 (95% confidence interval (Cl), 0.7-5.5 n = 28) in comparison with unexposed workers. Almost all cases had had low exposure, according to the classification used and there was no dose-response trend. The authors stated that the relative risks w ere adjusted for internal and external exposure to radiation. 

Toluene toxicity is most prominent in the central nervous system after acute and chronic exposure. Reproductive toxicity has been observed in exposed humans and rats. 

Cumene has a potent narcotic action characterized by a slow induction period. It is a depressant to the central nervous system. The long duration of its action indicates a possible slow rate of elimination, meaning that cumulative effects must be considered. Cumene is thought to have a greater acute toxicity than either benz or toluene (Ref 4) Cumene is used in org synthesis as a solvent, diluent, and as an additive to aviation gasoline... 

Solvents, such as chlorinated hydrocarbons, toluene, benzene, and xylene, can cause a feeling of euphoria, but they can be deadly toxins. Small, daily doses may cause dizziness, mental confusion, and fatigue high doses will cause permanent damage to the central nervous system. Lead, mercury, and manganese ion poisoning will alter and destroy central and peripheral nerve function and cause personality changes. 

Toluene 110 Yes Yes nausea headache mild anemia central nervous system damage (less toxic than benzene)... 

Xylenes and ethylbenzene (Figure 13.7) are common gasoline constituents, industrial solvents, and reagents, so human exposure to these materials is common. The absorption (primarily through inhalation), metabolism, and effects of these solvents are generally similar to those of toluene. Effects are largely on the central nervous system. Effects of xylenes and ethylbenzene on organs other than the central nervous system appear to be limited. 

The aromatic hydrocarbons, such as xylene and toluene, exhibit their toxic effects on the central nervous system. 

Filley CM, Halliday W, Kleinschmidt-DeMasters BK. The effects of toluene on the central nervous system. J Neuropathol Exp Neurol 2004 63(1) 1-12. 

Although the exact biochemical mechanism of toxicity has not been identified for toluene, it is known that the primary toxic effect of toluene is dysfunction of the brain and central nervous system (CNS-nar-cosis). The main function of neurons is to conduct electrochemical signals to one, several, or thousands of other cells. The normal physiology of these neurons is, in turn, largely dependent on the integrity of the cell membrane, which polarizes and depolarizes during the transmission of these signals. Thus, the most probable mechanism of toxicity is the unique... 

All the BTEXs cause neurological effects. Neurological effects are the basis for MRLs for both acute and chronic exposures to toluene and mixed xylenes, and for intermediate exposures to benzene neurological effects are not as sensitive for ethylbenzene. The neurological effects consist primarily of central nervous system depression. Toluene s neurotoxicity also includes ototoxicity. Evidence of hearing loss has been seen in both occupationally exposed humans and in animals. There is limited evidence that chronic inhalation exposure to benzene may affect the peripheral nervous system this evidence is from a single study of occupationally exposed humans who also had aplastic anemia. 

Data for the oral route of exposure are less extensive. The BTEXs cause neurological effects, generally central nervous system depression, by the oral route. This is a sensitive effect for toluene and / -xylene, for which it is the basis of acute and/or intermediate MRLs. Renal and hepatic effects are also seen with oral exposure to these compounds. Renal effects are the basis for the intermediate MRL for mixed xylenes and hepatic effects are the basis for the intermediate MRL for m-xylene. The hepatic effects tend to be mild, including increased liver weight and cytochromes P-450 and b5 contents. Benzene causes hematological effects by the oral route that are similar to those seen from inhalation exposure. 

Central nervous system (CNS) depression caused by acute inhalation exposure to volatile aliphatic and aromatic petroleum hydrocarbons is generally thought to occur when the lipophilic parent hydrocarbon dissolves in nerve cell membranes and disrupts the function of membrane proteins by disrupting their lipid environment or by directly altering protein conformation. Oxidative metabolism of CNS-depressing hydrocarbons reduces their lipophilicity and represents a process that counteracts CNS-depression toxicity. More detailed information on this mechanism of toxicity can be found in ATSDR profiles on toluene (ATSDR 1994), ethylbenzene (ATSDR 1999a), and xylene (ATSDR 1995d). 

Factors that inhibit or alter the activity of the mixed function oxidase enzymes may increase the risk from exposure to the indicator compounds in the aromatic EC5-EC9 fraction (the BTEXs), the aromatic EC>16-EC35 fraction (the carcinogenic PAHs in this fraction) and a constituent of the aliphatic I < C5IiCH fraction (//-hexane). For example, concurrent alcohol consumption may increase the risk of central nervous system depression from the BTEXs, ototoxicity from toluene, and hematotoxicity from benzene. Acetone exposure may increase the risk of peripheral neuropathy of n-hexane. People who take haloperidol, acetaminophen, or aspirin, or who have a nutritionally inadequate diet, may also be more susceptible to the toxicity of these agents. ATSDR (1995f) noted that a substantial percentage of children consume less than the recommended dietary allowances of certain nutrients. 

Eller N, Netterstrom B, Laursen P Risk of chronic effects on the central nervous system at low toluene exposure. Occup Med 49 389-395, 1999 Foo SC, Jeyaratnam J, Koh D Chronic neurobehavioral effects of toluene. British Journal of Industrial Medicine 47 480-484, 1990 Foo SC, Ngim CH, Salleh I, et al Neurobehavioral effects in occupational chemical exposure. Environ Res 60 267-273, 1993... 

Lazar RB, Sam UH, Melen O, et al Multifocal central nervous system damage caused by toluene abuse. Neurology 33 1337-1340,1983 Lewis JD, Moritz D, Mellis LP Long-term toluene abuse. Am J Psychiatry 138 368-370, 1981... 

Rosenberg NL, Kleinschmidt-Demasters BK, Davis KA, etal Toluene abuse causes diffuse central nervous system white matter changes. Ann Neurol 23 611-614, 1988a... 

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