Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. Dec 1993; 101(Suppl 6): 133–141.
PMCID: PMC1520019
Research Article

Neurotoxic effects of gasoline and gasoline constituents.

Abstract

This overview was developed as part of a symposium on noncancer end points of gasoline and key gasoline components. The specific components included are methyl tertiary butyl ether, ethyl tertiary butyl ether, tertiary amyl methyl ether, butadiene, benzene, xylene, toluene, methyl alcohol, and ethyl alcohol. The overview focuses on neurotoxic effects related to chronic low-level exposures. A few general conclusions and recommendations can be made based on the results of the studies to date. a) All the compounds reviewed are neuroactive and, as such, should be examined for their neurotoxicity. b) For most of the compounds, there is a substantial margin of safety between the current permissible exposure levels and levels that would be expected to cause overt signs of neurotoxicity in humans. This is not the case for xylene, toluene, and methanol, however, where neurologic effects are observed at or below the current Threshold Limit Value. c) For most of the compounds, the relationship between chronic low-level exposure and subtle neurotoxic effects has not been studied. Studies therefore should focus on examining the dose-response relationship between chronic low-level exposure and subtle changes in central nervous system function.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Fortenberry JD. Gasoline sniffing. Am J Med. 1985 Dec;79(6):740–744. [PubMed]
  • Kumar P, Gupta BN, Pandya KP, Clerk SH. Behavioral studies in petrol pump workers. Int Arch Occup Environ Health. 1988;61(1-2):35–38. [PubMed]
  • Schwartz E. Proportionate mortality ratio analysis of automobile mechanics and gasoline service station workers in New Hampshire. Am J Ind Med. 1987;12(1):91–99. [PubMed]
  • Pandya KP, Rao GS, Dhasmana A, Zaidi SH. Occupational exposure of petrol pump workers. Ann Occup Hyg. 1975 Dec;18(4):363–364. [PubMed]
  • Vyskocil A, Tusl M, Obrsál J, Zaydlar K. A subchronic inhalation study with unleaded petrol in rats. J Appl Toxicol. 1988 Aug;8(4):239–242. [PubMed]
  • Allen MJ, Borody TJ, Bugliosi TF, May GR, LaRusso NF, Thistle JL. Rapid dissolution of gallstones by methyl tert-butyl ether. Preliminary observations. N Engl J Med. 1985 Jan 24;312(4):217–220. [PubMed]
  • Conaway CC, Schroeder RE, Snyder NK. Teratology evaluation of methyl tertiary butyl ether in rats and mice. J Toxicol Environ Health. 1985;16(6):797–809. [PubMed]
  • Biles RW, Schroeder RE, Holdsworth CE. Methyl tertiary butyl ether inhalation in rats: a single generation reproduction study. Toxicol Ind Health. 1987 Dec;3(4):519–534. [PubMed]
  • Kreiling R, Laib RJ, Filser JG, Bolt HM. Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis. Arch Toxicol. 1987;61(1):7–11. [PubMed]
  • Dempster AM, Evans HL, Snyder CA. The temporal relationship between behavioral and hematological effects of inhaled benzene. Toxicol Appl Pharmacol. 1984 Oct;76(1):195–203. [PubMed]
  • Green JD, Leong BK, Laskin S. Inhaled benzene fetotoxicity in rats. Toxicol Appl Pharmacol. 1978 Oct;46(1):9–18. [PubMed]
  • Tilson HA, Squibb RE, Meyer OA, Sparber SB. Postnatal exposure to benzene alters the neurobehavioral functioning of rats when tested during adulthood. Neurobehav Toxicol. 1980 Summer;2(2):101–106. [PubMed]
  • Hsieh GC, Parker RD, Sharma RP. Subclinical effects of groundwater contaminants. II. Alteration of regional brain monoamine neurotransmitters by benzene in CD-1 mice. Arch Environ Contam Toxicol. 1988 Nov;17(6):799–805. [PubMed]
  • Carpenter CP, Kinkead ER, Geary DL, Jr, Sullivan LJ, King JM. Petroleum hydrocarbon toxicity studies. V. Animal and human response to vapors of mixed xylenes. Toxicol Appl Pharmacol. 1975 Sep;33(3):543–558. [PubMed]
  • Olson BA, Gamberale F, Iregren A. Coexposure to toluene and p-xylene in man: central nervous functions. Br J Ind Med. 1985 Feb;42(2):117–122. [PMC free article] [PubMed]
  • Savolainen K, Riihimäki V, Seppäläinen AM, Linnoila M. Effects of short-term m-xylene exposure and physical exercise on the central nervous system. Int Arch Occup Environ Health. 1980 Feb;45(2):105–121. [PubMed]
  • Gamberale F, Annwall G, Hultengren M. Exposure to xylene and ethylbenzene. III. Effects on central nervous functions. Scand J Work Environ Health. 1978 Sep;4(3):204–211. [PubMed]
  • Riihimäki V, Savolainen K. Human exposure to m-xylene. Kinetics and acute effects on the central nervous system. Ann Occup Hyg. 1980;23(4):411–422. [PubMed]
  • Bushnell PJ. Behavioral effects of acute p-xylene inhalation in rats: autoshaping, motor activity, and reversal learning. Neurotoxicol Teratol. 1988 Nov-Dec;10(6):569–577. [PubMed]
  • Andersson K, Fuxe K, Nilsen OG, Toftgård R, Eneroth P, Gustafsson JA. Production of discrete changes in dopamine and noradrenaline levels and turnover in various parts of the rat brain following exposure to xylene, ortho-, meta-, and para-xylene, and ethylbenzene. Toxicol Appl Pharmacol. 1981 Sep 30;60(3):535–548. [PubMed]
  • Honma T, Sudo A, Miyagawa M, Sato M, Hasegawa H. Significant changes in the amounts of neurotransmitter and related substances in rat brain induced by subacute exposure to low levels of toluene and xylene. Ind Health. 1983;21(3):143–151. [PubMed]
  • Savolainen H, Pfäffli P. Dose-dependent neurochemical changes during short-term inhalation exposure to m-xylene. Arch Toxicol. 1980 Jul;45(2):117–122. [PubMed]
  • Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol. 1986 Sep-Oct;1(5):309–334. [PubMed]
  • Frederick LJ, Schulte PA, Apol A. Investigation and control of occupational hazards associated with the use of spirit duplicators. Am Ind Hyg Assoc J. 1984 Jan;45(1):51–55. [PubMed]
  • Martin-Amat G, Tephly TR, McMartin KE, Makar AB, Hayreh MS, Hayreh SS, Baumbach G, Cancilla P. Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey. Arch Ophthalmol. 1977 Oct;95(10):1847–1850. [PubMed]
  • McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning. V. Role of formate metabolism in the monkey. J Pharmacol Exp Ther. 1977 Jun;201(3):564–572. [PubMed]
  • Makar AB, Tephly TR. Methanol poisoning in the folate-deficient rat. Nature. 1976 Jun 24;261(5562):715–716. [PubMed]
  • Makar AB, Tephly TR. Methanol poisoning VI: role of folic acid in the production of methanol poisoning in the rat. J Toxicol Environ Health. 1977 May;2(5):1201–1209. [PubMed]
  • Mohler FS, Gordon CJ. Effects of methanol on autonomic thermoregulation of rats at different ambient temperatures. Toxicol Lett. 1990 Jul;52(2):153–162. [PubMed]
  • Mohler FS, Gordon CJ. Thermoregulatory effects of methanol in Fischer and Long Evans rats. Neurotoxicol Teratol. 1990 Jan-Feb;12(1):41–45. [PubMed]
  • Wecker JR, Ison JR. Acute exposure to methyl or ethyl alcohol alters auditory function in the rat. Toxicol Appl Pharmacol. 1984 Jun 30;74(2):258–266. [PubMed]
  • Nelson BK, Brightwell WS, MacKenzie DR, Khan A, Burg JR, Weigel WW, Goad PT. Teratological assessment of methanol and ethanol at high inhalation levels in rats. Fundam Appl Toxicol. 1985 Aug;5(4):727–736. [PubMed]
  • Infurna R, Weiss B. Neonatal behavioral toxicity in rats following prenatal exposure to methanol. Teratology. 1986 Jun;33(3):259–265. [PubMed]
  • Jeganathan PS, Namasivayam A. Methanol induced biogenic amine changes in discrete areas of rat brain: role of simultaneous ethanol administration. Indian J Physiol Pharmacol. 1988 Jan-Mar;32(1):1–10. [PubMed]
  • Jeganathan PS, Namasivayam A. Brain biogenic amine levels after methanol administration: possible mechanism of action on central monoaminergic neurons in discrete areas of brain in Wistar rat. Indian J Physiol Pharmacol. 1989 Jul-Sep;33(3):151–156. [PubMed]
  • Jeganathan PS, Namasivayam A. Methanol-induced monoamine changes in hypothalamus and striatum of albino rats. Alcohol. 1989 Nov-Dec;6(6):451–454. [PubMed]
  • Smith MS. The neurological sequelae to toluene inhalation. J R Nav Med Serv. 1990 Summer;76(2):69–74. [PubMed]
  • Baelum J, Lundqvist GR, Mølhave L, Andersen NT. Human response to varying concentrations of toluene. Int Arch Occup Environ Health. 1990;62(1):65–71. [PubMed]
  • Echeverria D, Fine L, Langolf G, Schork A, Sampaio C. Acute neurobehavioural effects of toluene. Br J Ind Med. 1989 Jul;46(7):483–495. [PMC free article] [PubMed]
  • Antti-Poika M, Juntunen J, Matikainen E, Suoranta H, Hänninen H, Seppäläinen AM, Liira J. Occupational exposure to toluene: neurotoxic effects with special emphasis on drinking habits. Int Arch Occup Environ Health. 1985;56(1):31–40. [PubMed]
  • Foo SC, Jeyaratnam J, Koh D. Chronic neurobehavioural effects of toluene. Br J Ind Med. 1990 Jul;47(7):480–484. [PMC free article] [PubMed]
  • Juntunen J, Matikainen E, Antti-Poika M, Suoranta H, Valle M. Nervous system effects of long-term occupational exposure to toluene. Acta Neurol Scand. 1985 Nov;72(5):512–517. [PubMed]
  • Mørck HI, Winkel P, Gyntelberg F. Health effects of toluene exposure. Dan Med Bull. 1988 Apr;35(2):196–200. [PubMed]
  • Benignus VA. Neurobehavioral effects of toluene: a review. Neurobehav Toxicol Teratol. 1981 Winter;3(4):407–415. [PubMed]
  • Glowa JR. Some effects of sub-acute exposure to toluene on schedule-controlled behavior. Neurobehav Toxicol Teratol. 1981 Winter;3(4):463–465. [PubMed]
  • Hinman DJ. Biphasic dose-response relationship for effects of toluene inhalation on locomotor activity. Pharmacol Biochem Behav. 1987 Jan;26(1):65–69. [PubMed]
  • Kishi R, Harabuchi I, Ikeda T, Yokota H, Miyake H. Neurobehavioural effects and pharmacokinetics of toluene in rats and their relevance to man. Br J Ind Med. 1988 Jun;45(6):396–408. [PMC free article] [PubMed]
  • Taylor JD, Evans HL. Effects of toluene inhalation on behavior and expired carbon dioxide in macaque monkeys. Toxicol Appl Pharmacol. 1985 Sep 30;80(3):487–495. [PubMed]
  • Arito H, Tsuruta H, Nakagaki K. Acute effects of toluene on circadian rhythms of sleep-wakefulness and brain monoamine metabolism in rats. Toxicology. 1984 Dec;33(3-4):291–301. [PubMed]
  • Fuxe K, Andersson K, Nilsen OG, Toftgård R, Eneroth P, Gustafsson JA. Toluene and telencephalic dopamine: selective reduction of amine turnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene. Toxicol Lett. 1982 Jul;12(2-3):115–123. [PubMed]
  • Fuxe K, Martire M, von Euler G, Agnati LF, Hansson T, Andersson K, Gustafsson JA, Härfstrand A. Effects of subacute treatment with toluene on cerebrocortical alpha- and beta-adrenergic receptors in the rat. Evidence for an increased number and a reduced affinity of beta-adrenergic receptors. Acta Physiol Scand. 1987 Jun;130(2):307–311. [PubMed]
  • Dyer RS, Muller KE, Janssen R, Barton CN, Boyes WK, Benignus VA. Neurophysiological effects of 30 day chronic exposure to toluene in rats. Neurobehav Toxicol Teratol. 1984 Sep-Oct;6(5):363–368. [PubMed]
  • Himnan DJ. Tolerance and reverse tolerance to toluene inhalation: effects on open-field behavior. Pharmacol Biochem Behav. 1984 Oct;21(4):625–631. [PubMed]
  • Mattsson JL, Gorzinski SJ, Albee RR, Zimmer MA. Evoked potential changes from 13 weeks of simulated toluene abuse in rats. Pharmacol Biochem Behav. 1990 Jul;36(3):683–689. [PubMed]
  • Pryor GT. A toluene-induced motor syndrome in rats resembling that seen in some human solvent abusers. Neurotoxicol Teratol. 1991 Jul-Aug;13(4):387–400. [PubMed]
  • Arito H, Tsuruta H, Nakagaki K, Tanaka S. Partial insomnia, hyperactivity and hyperdipsia induced by repeated administration of toluene in rats: their relation to brain monoamine metabolism. Toxicology. 1985 Oct;37(1-2):99–110. [PubMed]
  • Bjornaes S, Naalsund LU. Biochemical changes in different brain areas after toluene inhalation. Toxicology. 1988 May;49(2-3):367–374. [PubMed]
  • Kostas J, Hotchin J. Behavioral effects of low-level perinatal exposure to toluene in mice. Neurobehav Toxicol Teratol. 1981 Winter;3(4):467–469. [PubMed]
  • Charness ME, Simon RP, Greenberg DA. Ethanol and the nervous system. N Engl J Med. 1989 Aug 17;321(7):442–454. [PubMed]
  • Freund G. Chronic central nervous system toxicity of alcohol. Annu Rev Pharmacol. 1973;13:217–227. [PubMed]
  • Pratt OE, Rooprai HK, Shaw GK, Thomson AD. The genesis of alcoholic brain tissue injury. Alcohol Alcohol. 1990;25(2-3):217–230. [PubMed]
  • Shoemaker WJ. The neurotoxicity of alcohols. Neurobehav Toxicol Teratol. 1981 Winter;3(4):431–436. [PubMed]
  • LESTER D, GREENBERG LA. The inhalation of ethyl alcohol by man. I. Industrial hygiene and medicolegal aspects. II. Individuals treated with tetraethylthiuram disulfide. Q J Stud Alcohol. 1951 Jun;12(2):168–178. [PubMed]
  • Ferko AP, Bobyock E. Induction of physical dependence in rats by ethanol inhalation without the use of pyrazole. Toxicol Appl Pharmacol. 1977 May;40(2):269–276. [PubMed]
  • Goldstein DB, Pal N. Alcohol dependence produced in mice by inhalation of ethanol: grading the withdrawal reaction. Science. 1971 Apr 16;172(3980):288–290. [PubMed]
  • Nelson BK, Brightwell WS, MacKenzie DR, Khan A, Burg JR, Weigel WW, Goad PT. Teratological assessment of methanol and ethanol at high inhalation levels in rats. Fundam Appl Toxicol. 1985 Aug;5(4):727–736. [PubMed]
  • Rogers J, Wiener SG, Bloom FE. Long-term ethanol administration methods for rats: advantages of inhalation over intubation or liquid diets. Behav Neural Biol. 1979 Dec;27(4):466–486. [PubMed]
  • Conry J. Neuropsychological deficits in fetal alcohol syndrome and fetal alcohol effects. Alcohol Clin Exp Res. 1990 Oct;14(5):650–655. [PubMed]
  • Nanson JL, Hiscock M. Attention deficits in children exposed to alcohol prenatally. Alcohol Clin Exp Res. 1990 Oct;14(5):656–661. [PubMed]
  • Streissguth AP, Barr HM, Sampson PD. Moderate prenatal alcohol exposure: effects on child IQ and learning problems at age 7 1/2 years. Alcohol Clin Exp Res. 1990 Oct;14(5):662–669. [PubMed]
  • West JR, Goodlett CR, Brandt JP. New approaches to research on the long-term consequences of prenatal exposure to alcohol. Alcohol Clin Exp Res. 1990 Oct;14(5):684–689. [PubMed]
  • Riley EP. The long-term behavioral effects of prenatal alcohol exposure in rats. Alcohol Clin Exp Res. 1990 Oct;14(5):670–673. [PubMed]
  • Hunt WA. The effect of ethanol on GABAergic transmission. Neurosci Biobehav Rev. 1983 Spring;7(1):87–95. [PubMed]
  • Sytinsky IA, Guzikov BM, Gomanko MV, Eremin VP, Konovalova NN. The gamma-aminobutyric acid (GABA) system in brain during acute and chronic ethanol intoxication. J Neurochem. 1975 Jul;25(1):43–48. [PubMed]
  • Muller P, Britton RS, Seeman P. The effects of long-term ethanol on brain receptors for dopamine, acetylcholine, serotonin and noradrenaline. Eur J Pharmacol. 1980 Jul 11;65(1):31–37. [PubMed]
  • Clarren SK, Astley SJ, Bowden DM, Lai H, Milam AH, Rudeen PK, Shoemaker WJ. Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation. Alcohol Clin Exp Res. 1990 Oct;14(5):674–683. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...