Journal of Medical Toxicology

, Volume 4, Issue 2, pp 115–126 | Cite as

Epidemiology, toxicokinetics, and health effects of methyltert-butyl ether (MTBE)

  • Scott PhillipsEmail author
  • Robert B. Palmer
  • Aaron Brody
Toxicology Reviews


This paper reviews the published information assessing the kinetics and potential for adverse health effects related to exposure to the fuel oxygenate, methyltert-butyl ether (MTBE). Data were obtained from previously published reports, using human data where possible. If human data were not available, animal studies were cited. The kinetic profile of MTBE in humans is similar for ingestion and inhalation. The concentrations of MTBE to which the general public is expected to be exposed are orders of magnitude below concentrations that have caused adverse health effects in animals. Controlled human studies have not replicated early epidemiology studies that suggested, but did not confirm, a possible association between MTBE exposure and nonspecific health complaints.


MTBE toxicokinetics epidemiology t-butanol metabolism oxygenate reformulated gasoline oxyfuel 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ahmed FE. Toxicology and human health effects following exposure to oxygenated or reformulated gasoline.Toxicol Lett 2001;123:89–113.PubMedCrossRefGoogle Scholar
  2. 2.
    Hutcheon DE, Arnold JD, ten Hove W, Boyle J III. Disposition, metabolism, and toxicity of methyl tertiary butyl ether, an oxygenate for reformulated gasoline.J Toxicol Environ Health 1996;47:453–464.PubMedCrossRefGoogle Scholar
  3. 3.
    McGregor D. Methyl tertiary-butyl ether: studies for potential human health hazards.Crit Rev Toxicol 2006;36:319–358.PubMedCrossRefGoogle Scholar
  4. 4.
    Stern BR, Kneiss JJ. Methyl tertiary-butyl ether (MTBE): use as an oxygenate in fuels.J Appl Toxicol 1997;17 Suppl 1:S1-S2.PubMedCrossRefGoogle Scholar
  5. 5.
    Mumtaz M, Wilbur S. In: Agency for Toxic Substances Disease Register, ed. Toxicological Profile for Methylt-Butyl Ether. Atlanta, GA: Centers for Disease Control;1996: 221.Google Scholar
  6. 6.
    Gibbons JH et al. Interagency assessment of oxygenated fuels. National Science and Technology Council. 1997.Google Scholar
  7. 7.
    Edison SA, Maier M, Kohler B, et al. Direct dissolution of gallstones with methyltert-butyl ether by endoscopic cannulation of the gallbladder.Am J Gastroenterol 1993;88:1242–1248.PubMedGoogle Scholar
  8. 8.
    Leuschner U, Hellstern A, Schmidt K, et al. Gallstone dissolution with methyltert-butyl ether in 120 patients—efficacy and safety.Dig Dis Sci 1991;36:193–199.PubMedCrossRefGoogle Scholar
  9. 9.
    Neoptolemos JP, Hall C, O’Connor HJ, Murray WR, Carr-Locke DL. Methyl-tert-butyl-ether for treating bile duct stones: the British experience.Br J Surg 1990;77:32–35.PubMedCrossRefGoogle Scholar
  10. 10.
    Pauletzki J, Holl J, Sackmann M, et al. Gallstone recurrence after direct contact dissolution with methyltert-butyl ether.Dig Dis Sci 1995;40:1775–1781.PubMedCrossRefGoogle Scholar
  11. 11.
    Soehendra N, Schulz H, Nam VC, et al. ESWL and gallstone dissolution with MTBE via a naso-vesicular catheter.Endoscopy 1990;22:176–179.PubMedCrossRefGoogle Scholar
  12. 12.
    Uchida N, Nakatsu T, Hirabayashi S, et al. Direct dissolution of gallstones with methyl tert-butyl ether (MTBE) via endoscopic transpapillary catheterization in the gallbladder (ETCG).J Gastroenterol 1994;29:486–494.PubMedCrossRefGoogle Scholar
  13. 13.
    Williams HJ Jr, Bender CE, LeRoy AJ. Dissolution of cholesterol gallstones using methyltert-butyl ether.Cardiovasc Intervent Radiol 1990;13:272–277.PubMedCrossRefGoogle Scholar
  14. 14.
    Brown SL. Atmospheric and potable water exposures to methyltert-butyl ether (MTBE).Regul Toxicol Pharmacol 1997;25:256–276.PubMedCrossRefGoogle Scholar
  15. 15.
    Drinking Water Advisory. Consumer Acceptability Advice and Health Effects Analysis on Methyl tertiary-Butyl Ether. US Environmental Protection Agency;1997.Google Scholar
  16. 16.
    Moran MJ, Zogorski JS, Squillace PJ. MTBE and gasoline hydrocarbons in ground water of the United States.Ground Water 2005;43:615–627.PubMedCrossRefGoogle Scholar
  17. 17.
    Williams PR, Benton L, Sheehan PJ. The risk of MTBE relative to other VOCs in public drinking water in California.Risk Anal 2004;24:621–634.PubMedCrossRefGoogle Scholar
  18. 18.
    Moolenaar RL, Hefflin BJ, Ashley DL, Middaugh JP, Etzel RA. Methyl tertiary butyl ether in human blood after exposure to oxygenated fuel in Fairbanks, Alaska.Arch Environ Health 1994;49:402–409.PubMedGoogle Scholar
  19. 19.
    Nihlen A, Sumner SC, Lof A, Johanson G. 13C(2)-Labeled methyl tert-butyl ether: toxicokinetics and characterization of urinary metabolites in humans.Chem Res Toxicol 1999;12:822–830.PubMedCrossRefGoogle Scholar
  20. 20.
    White MC, Johnson CA, Ashley DL, Buchta TM, Pelletier DJ. Exposure to methyl tertiary-butyl ether from oxygenated gasoline in Stamford, Connecticut.Arch Environ Health 1995;50:183–189.PubMedGoogle Scholar
  21. 21.
    Mannino DM, Schreiber J, Aldous K, Ashley D, Moolenaar R, Almaguer D. Human exposure to volatile organic compounds: a comparison of organic vapor monitoring badge levels with blood levels.Int Arch Occup Environ Health.1995;67:59–64.PubMedCrossRefGoogle Scholar
  22. 22.
    Saarinen L, Hakkola M, Pekari K, Lappalainen K, Aitio A. Exposure of gasoline road-tanker drivers to methyltert-butyl ether and methyltert-amyl ether.Int Arch Occup Environ Health 1998;71:143–147.PubMedCrossRefGoogle Scholar
  23. 23.
    Amberg A, Rosner E, Dekant W. Biotransformation and kinetics of excretion of methyl-tert-butyl ether in rats and humans.Toxicol Sci 1999;51:1–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Amberg A, Rosner E, Dekant W. Toxicokinetics of methyl tert-butyl ether and its metabolites in humans after oral exposure.Toxicol Sci 2001;61:62–67.PubMedCrossRefGoogle Scholar
  25. 25.
    Buckley TJ, Prah JD, Ashley D, Zweidinger RA, Wallace LA. Body burden measurements and models to assess inhalation exposure to methyl tertiary butyl ether (MTBE).J Air Waste Manag Assoc 1997;47:739–752.PubMedGoogle Scholar
  26. 26.
    Nihlen A, Walinder R, Lof A, Johanson G. Experimental exposure to methyl tertiary-butyl ether. II. Acute effects in humans.Toxicol Appl Pharmacol 1998;148:281–287.PubMedCrossRefGoogle Scholar
  27. 27.
    Prah J, Ashley D, Blount B, et al. Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.Toxicol Sci 2004;77:195–205.PubMedCrossRefGoogle Scholar
  28. 28.
    Benson JM, Barr EB, Krone JR. MTBE inhaled alone and in combination with gasoline vapor: uptake, distribution, metabolism, and excretion in rats.Res Rep Health Eff Inst 2001;73-94; discussion 95–109.Google Scholar
  29. 29.
    Hong JY, Yang CS, Lee M, et al. Role of cytochromes P450 in the metabolism of methyl tert-butyl ether in human livers.Arch Toxicol 1997;71:266–269.PubMedCrossRefGoogle Scholar
  30. 30.
    Licata AC, Dekant W, Smith CE, Borghoff SJ. A physiologically based pharmacokinetic model for methyltert-butyl ether in humans: implementing sensitivity and variability analyses.Toxicol Sci 2001;62:191–204.PubMedCrossRefGoogle Scholar
  31. 31.
    Cain WS, Leaderer BP, Ginsberg GL, et al. Acute exposure to low-level methyl tertiary-butyl ether (MTBE): Human reactions and pharmacokinetic response.Inhal Toxicol 1996;8:21–48.CrossRefGoogle Scholar
  32. 32.
    Fiedler N, Mohr S, Kelly-McNeil K. Response of sensitive groups to methyl tertiary-butyl ether (MTBE). Conference on MTBE and Other Oxygenates: A Research Update.1993. Google Scholar
  33. 33.
    Hong JY, Wang YY, Bondoc FY, et al. Metabolism of methyl tert-butyl ether and other gasoline ethers by human liver microsomes and heterologously expressed human cytochromes P450: identification of CYP2A6 as a major catalyst.Toxicol Appl Pharmacol 1999;160:43–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Beller HR, Middaugh JP. Potential illness due to exposure to oxygenated fuels: Fairbanks, Alaska. Conference on MTBE and Other Oxygenates: A Research Update.1992. Google Scholar
  35. 35.
    Chandler B, Middaugh JP. Potential illness due to exposure to oxygenated fuels: Anchorage, Alaska. Conference on MTBE and Other Oxygenates: A Research Update. Falls Church, Virginia, July 26–28,1993. Google Scholar
  36. 36.
    Mohr S, Fiedler N, Weisel C, Kelly-McNeil K. Health effects of MTBE among New Jersey garage workers.Inhal Toxicol 1994;6:553–562.CrossRefGoogle Scholar
  37. 37.
    Anderson HA, Hanrahan L, Goldring J, Delaney B. An investigation of health concerns attributed to reformulated gasoline use in southeastern Wisconsin. Wisconsin Department of Health and Social Services, Bureau of Public Health, Section of Environmental Epidemiology and Prevention;1995. Google Scholar
  38. 38.
    Clayton GD, Clayton FE. Patty’s Industrial Hygiene and Toxicology. ed. New York: John Wiley & Sons;1981–1982.Google Scholar
  39. 39.
    Daughtrey WC, Gill MW, Pritts IM, Douglas JF, Kneiss JJ, Andrews LS. Neurotoxicological evaluation of methyl tertiarybutyl ether in rats.J Appl Toxicol 1997;17 Suppl 1:S57-S64.PubMedCrossRefGoogle Scholar
  40. 40.
    Lington AW, Dodd DE, Ridlon SA, Douglas JF, Kneiss JJ, Andrews LS. Evaluation of 13-week inhalation toxicity study on methyl t-butyl ether (MTBE) in Fischer 344 rats.J Appl Toxicol 1997;17 Suppl 1:S37-S44.PubMedCrossRefGoogle Scholar
  41. 41.
    Belpoggi F, Soffritti M, Filippini F, Maltoni C. Results of long-term experimental studies on the carcinogenicity of methyl tert-butyl ether.Ann N Y Acad Sci 1997;837:77–95.PubMedCrossRefGoogle Scholar
  42. 42.
    Bird MG, Burleigh-Flayer HD, Chun JS, Douglas JF, Kneiss JJ, Andrews LS. Oncogenicity studies of inhaled methyl tertiary-butyl ether (MTBE) in CD-1 mice and F-344 rats.J Appl Toxicol 1997;17 Suppl 1:S45-S55.PubMedCrossRefGoogle Scholar
  43. 43.
    Kado NY, Kuzmicky PA, Loarca-Pina G, Moiz Mumtaz M. Genotoxicity testing of methyl tertiary-butyl ether (MTBE) in the Salmonella microsuspension assay and mouse bone marrow micronucleus test.Mutat Res 1998;412:131–138.PubMedGoogle Scholar
  44. 44.
    Borghoff SJ, Williams HJ. Species specific tumor responses following exposure to methyl tert-butyl ether. Chemical Industry Institute of Toxicology Activities.2000;20.Google Scholar
  45. 45.
    Williams TM, Cattley RC, Borghoff SJ. Alterations in endocrine responses in male Sprague-Dawley rats following oral administration of methyltert-butyl ether.Toxicol Sci 2000;54:168–176.PubMedCrossRefGoogle Scholar
  46. 46.
    Billitti JE, Faulkner BC, Wilson BW. Absence of acute testicular toxicity of methyl-tert butyl ether and breakdown products in mice.Bull Environ Contam Toxicol 2005;75: 228–235.PubMedCrossRefGoogle Scholar
  47. 47.
    Biles RW, Schroeder RE, Holdsworth CE. Methyl tertiary butyl ether inhalation in rats: a single generation reproduction study.Toxicol Ind Health 1987;3:519–534.PubMedGoogle Scholar
  48. 48.
    Bevan C, Neeper-Bradley TL, Tyl RW, et al. Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) in rats.J Appl Toxicol 1997;17 Suppl 1:S13-S19.PubMedCrossRefGoogle Scholar
  49. 49.
    Conaway CC, Schroeder RE, Snyder NK. Teratology evaluation of methyl tertiary butyl ether in rats and mice.J Toxicol Environ Health 1985;16:797–809.PubMedCrossRefGoogle Scholar
  50. 50.
    Bevan C, Tyl RW, Neeper-Bradley TL, et al. Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by inhalation in mice and rabbits.J Appl Toxicol 1997;17 Suppl 1:S21-S29.PubMedCrossRefGoogle Scholar
  51. 51.
    Gerrity T, Prah J, Devlin R, et al. Acute responses of healthy human subjects to MTBE exposure. Conference on MTBE and Other Oxygenates: A Research Update.1993; 172–210.Google Scholar
  52. 52.
    Fiedler N, Kelly-McNeil K, Mohr S, et al. Controlled human exposure to methyl tertiary butyl ether in gasoline: symptoms, psychophysiologic and neurobehavioral responses of self-reported sensitive persons.Environ Health Perspect 2000;108:753–763.PubMedCrossRefGoogle Scholar
  53. 53.
    Prah JD, Goldstein GM, Devlin R, et al. Sensory symptomatic, inflammatory and ocular responses to, and the metabolism of, methyl tertiary-butyl ether in a controlled human exposure experiment.Inhal Toxicol 1994;6:521–538.CrossRefGoogle Scholar

Copyright information

© American College of Medical Toxicology 2008

Authors and Affiliations

  • Scott Phillips
    • 1
    Email author
  • Robert B. Palmer
    • 2
  • Aaron Brody
    • 3
  1. 1.Division of Clinical Pharmacology & ToxicologyUniversity of Colorado Health Sciences Center, Rocky Mountain Poison & Drug CenterDenver
  2. 2.Department of Surgery, Division of Emergency Medicine, Toxicology SectionUniversity of Colorado School of Medicine, Rocky Mountain Poison and Drug CenterDenver
  3. 3.Hadassah-Hebrew University HospitalJerusalemIsrael

Personalised recommendations