Toluene neurotoxicity

Antti-Poika M, Juntunen J, Matikainen E, et al Occupational exposure to toluene neurotoxic effects with special emphasis on drinking habits. Int Arch Occup Environ Health 56 31-40, 1985... 

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. 

Takeuchi Y, Hisanaga N, Ono Y, et al. 1993. Modification of metabolism and neurotoxicity of hexane by co-exposure of toluene. Int Arch of Occup Environ Health 65(1) S227-S230. 

Three cases of polyneuropathy occurred in shoe factory workers exposed to combined MEK and acetone vapors, as well as MEK and toluene vapors at concentrations below 200 ppm/ Skin absorption also occurred. Although not highly neurotoxic itself, MEK may potentiate substances known to cause neuropathy... 

Paints often contain solvents such as toluene, xylene, halogenated aromatic hydrocarbons, and methylene chloride, as well as heavy metals in their pigments including chromium yellow, lemon yellow (barium chromate), vermilion red (cadmium and mercuric sulfides), and flake white (lead). Both acute and chronic exposures to toluene and xylene are associated with neurotoxicity and can also damage the liver and kidneys. 

See also Benzene Neurotoxicity Petroleum Hydrocarbons Poiiution, Air Indoor Toluene. 

Hydrocarbon fuels are complex mixtures of more than 250 different molecular species. Compounds contained in such fuels include benzene, toluene, xylene, various alkyl benzenes, naphthalene, hexanes, heptanes, octanes, and higher molecular weight alkanes, all of which are neurotoxic. Fuel additives further complicate the mixtures. Acute and chronic exposures to low levels of hydrocarbon fuels, including gasoline, kerosene, diesel fuel, and jet fuel result in neurotoxic and neurobehavioral effects that are at times seemingly different from those anticipated from exposure to the individual chemicalsJ105l... 

The histology technicians were regularly exposed to mixtures of formaldehyde toluene, and xylene and less frequently to ethanol, chloroform, and methyl methacrylate. All exposures were at levels below TLVs for the individual chemicals and below levels at which the neurotoxic effects that were observed are expected. All the mixtures to which the histology technicians were exposed contained at least one lipophile and one hydrophile. 

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. 

While individual VOCs like benzene and toluene have been linked with acute myeloid leukaemia and neurotoxicity, respectively [ 111,112], epidemiological studies of the health effects of indoor VOCs have related TVOC rather than individual VOC levels to exposure. The outcomes of such studies have been mixed [113]. In some cases,positive associations between SBS,building-related illness or multiple chemical sensitivity syndromes and TVOC levels were observed... 

Class II solvents Solvents to be limited. These include non-genotoxic animal carcinogens or possible causative agents (e.g., acetonitrile, cyclohexane, toluene, methanol and N,N-dimethylacetamide) of irreversible toxicity such as neurotoxicity... 

The most important neurotoxic aromatic hydrocarbons are benzene and its derivatives. The numerous derivatives of benzene include ni-trobenzenes, toluene, xylene, aniline, creosote, phenols, salicylates, tannic acid, sulfa drugs, dinitrobenzenes, diphenyl, formaldehyde, and tetryl, a booster for high explosives (A.B. Baker and Tichy 1953). Yearly production of benzene in 1976 amounted to 11 billion pounds, and 2 million workers held occupations with potential benzene exposure (Lilis 1992). 

Hersh R Abuse of ethyl chloride. Am J Psychiatry 148 270-271,1991 Heuser G, Mena I, Goldstein J, et al Neurospect findings in patients (PTS) exposed to neurotoxic chemicals (abstract). Clin Nucl Med 18 923, 1993 Hirai H, Ikeuchi Y [MRI of chronic toluene intoxication] (English abstract). Rinsho Shinkeigaku 33 552-555, 1993... 

Bergamaschi E, Smargiassi A, Mutti A, et al Peripheral markers of catecholaminergic dysfunction and symptoms of neurotoxicity among styrene-exposed workers. Int Arch Occup Environ Health 69 209-214,1997 Challenor J, Wright D Aggression in boat builders a search for altered mood states in boat builders exposed to styrene. Occup Med (Lond) 50 185-192, 2000 Cherry N, Rodgers B, Venables H, et al Acute behavioural effects of styrene exposure a further analysis. British Journal of Industrial Medicine 38 346-350, 1981 Cherry N, Hutchins H, Pace T, et al Neurohehavioural effects of repeated occupational exposure to toluene and paint solvents. British Journal of Industrial Medicine 42 291-300, 1985... 

The alkylbenzenes (single-ring aromatic compounds with single or multiple aliphatic side chains) are constituents of JP-8. Toluene (methylbenzene) and mixed xylenes (o-, m-, andp-) are present in JP-8 and have been identified as potential neurotoxic chemicals after sufficiently high intentional, accidental, or occupational exposures (Gamberale and Hultengren 1972 Boor and Hurtig 1977 Klaucke et al. 1982 Hipolito 1980). 

Morata et al. (1995) reported metabolic and toxic interactions between toluene and several components of jet fuels. In rats exposed to toluene and hexane for 18 hr/day for 61 days, a synergistic reduction in auditory sensitivity occurred in the toluene-plus-hexane group that persisted for 365 days. Pryor and Rebert (1992) evaluated possible interactions between toluene and n-hexane exposures (individual vs. mixture protocols). Generally, the addition of toluene to the -hcxanc exposure reduced -hcxanc-induccd neuropathy. Perbellini et al. (1992) showed that inhibition of -hcxanc-induccd neuropathy by toluene was related to inhibition of -hcxanc metabolism to its neurotoxic metabolite, 2,5-hexanedione. -l lexanc and toluene use similar oxidative pathways for their primary metabolism. 

Male preteen children are most likely to experiment with solvent inhalation. Abuse of nitrous oxide is relatively common. Toxic inhalants such as heptane, hexane, methylethylketone, toluene, and trichloroethylene may result in central and peripheral neurotoxicity, liver and kidney damage, and pulmonary disease. Sudden death has occurred following inhalation of fluorocarbons. Industrial solvents rarely cause methemoglobinemia, but this (and headaches) may occur following excessive use of nitrites. The answer is (C). 

Exposure to styrene is the main occupational hygiene problem in reinforced plastics industry, where it is used as a crosslinking agent and solvent in unsaturated polyester resins. In addition, workers are exposed to acetone which is used as a clean-up solvent. Other solvents, such as methylene chloride, toluene, xylene, heptane (TLV 400 ppm, the Finnish OEL 300 ppm), methylcyclohexane (TLV and the Finnish OEL 400 ppm), and butyl acetate (TLV and the Finnish OEL 150 ppm) may also be used. Styrene is neurotoxic. Styrene is also a suspected carcinogen because it is metabolized via styrene-7,8-oxide. The TLV and the Finnish OEL of styrene is 20 ppm. Urinary mandelic acid concentration is the most common biological monitoring method for styrene. The ACGIH BEI is 800 mg/g creatinine and the FIOH BEI 3.2 mmol/1. 

Some published data are difficult to interpret. For example, 26 men were exposed in tanks and holds of two merchant vessels being painted (solvents) and sprayed with mala-thion 20% and pyrethrin 1.5%, with piperonyl butoxide in toluene. They showed losses of concentration, unawareness of danger and unconsciousness at toluene levels estimated as 10,000 to 12,000 ppm and up to 30,000 ppm below waist level. Additive effects of the neurotoxic insecticides were not discussed. 

Xylene toxicity has received less study than that of toluene, but appears considerable less which supports attributed the neurotoxicity to toluene of mixtures of xylene, benzene and toluene with straight chain hydrocarbons such as gasoline. 

---