Is Urban Asthma Caused by Methyl Tertiary Butyl Ether ?

Is Urban Asthma Caused by Methyl Tertiary Butyl Ether ? – MTBE

Peter Joseph

SUBSEQUENT TO 1979, methyl tertiary butyl ether (MTBE) has been used in increasing amounts as an octane enhancer in U.S. gasoline. In 1992, the U.S. Environmental Protection Agency issued an initial, large-scale mandate that MTBE be used as an oxygenate in gasoline. This action, however, has been met with continued controversy.[1-3] Originally, MTBE was intended for reduction of carbon monoxide (CO) emissions from automobiles, and later it was used as a component of reformulated gasoline (RFG) in an attempt to reduce emissions of ozone precursors. However, in one report by the National Research Council,[4] investigators reported that its impact on CO is, at most, 0-10%, whereas in a more-recent report,[5] researchers concluded that use of oxygenate in RFG has negligible impact on ambient ozone concentrations.

Recently, use of MTBE in gasoline has come under intense attack because there is a continuing and widespread problem of contamination of underground water supplies.[6] Given this reason alone, it now seems likely that MTBE will be systematically phased out of the U.S. gas supply during a period of several years.

There remains extensive debate on the toxicology of MTBE in humans.[7] In certain animal experiments,[8] MTBE has been cited as carcinogenic, although it is arguable that the effect occurs only at much higher exposures than are likely with respect to occupational or aquatic exposures.[9] It is not, however, my intention to contribute to that debate herein.

For several years, I have been convinced that the use of MTBE in gasoline has contributed some unsuspected pollutant to the ambient air that has caused widespread public-health problems, especially in certain eastcoast U.S. cities in which its use as an oxygenate has been virtually mandatory. In this editorial, I wish to briefly describe the existing evidence that supports this view, as well as to outline several areas of research needed to confirm or refute the hypotheses involved.

The evidence for harmful effects from MTBE is both anecdotal and epidemiological. The epidemiological data for asthma is slowly becoming overwhelming, with explosive growth in certain eastcoast cities during the past few years. In 1997, I presented a paper[10] to the Air and Waste Management Association; the data were obtained from a group of eight clinics in Philadelphia, Pennsylvania, for the period 1993-1995. The data demonstrated increases–on the order of several tens of percentages–in not only asthma occurrences but also in several other conditions of respiratory and/or inflammatory natures. The percentage increases in those specific conditions were much larger than the total increase in visits to the clinics, and they had a high degree of statistical significance. Subsequent to 1997, there have been reports of truly astonishing prevalence rates for asthma among children in Philadelphia, Pennsylvania (28%),[11] Stamford, Connecticut (24%),[12] and Hartford, Connecticut (40%).[13] In the case of New York City, results were especially instructive, because in one survey of childhood asthma in the Bronx, there was only approximately 8% asthma prevalence in 1991,[14] whereas a study in the same borough in 1998 revealed a prevalence of 22%.[15] This discrepancy obviously indicates an increase of extraordinary rapidity during the period in which MTBE was used as an oxygenate. Very important, however, was the very different result obtained by the New York State Department of Health in 1997: there was only 7% asthma prevalence among adults statewide![16] Inasmuch as MTBE is not used as an oxygenate state-wide in New York, but, instead, is used only in the New York City and Long Island regions, these results suggest that the current asthma epidemic is very geographically selective. This conclusion argues against those who reject the MTBE-asthma link and who claim that “asthma is increasing everywhere”; it appears that asthma is not increasing at the same rate everywhere. In areas where MTBE-RFG is not used, the relatively slow increase in asthma could result from the gradual increase in the use of MTBE as an octane enhancer. We need a coordinated survey of different parts of the country, and asthma in regions with and without MTBE-RFG should be compared, and consistent selection and diagnostic criteria should be used.

In my previous publications, I have argued that the previous studies of health effects from MTBE were based on a major false assumption (i.e., only the toxicology of MTBE itself is relevant). I have argued[10] that the existing studies[16-19] are entirely consistent with harmful effects from an unknown exhaust product that enters the ambient air. This conclusion implies that such concerns about how much MTBE exposure occurs at gas pumps or from occupational exposure to gasoline are irrelevant to my point.

The obvious weak link in this theory is the lack of hard data that identify this toxic byproduct. In a recent publication,[20] I argued that methyl nitrite ([CH.sub.3]ONO, or MeONO) is a plausible candidate. The detailed chemistry of its possible production in the combustion of MTBE-RFG is described in the publication available from the Air and Waste Management Association.[20]

I emphasize that MeONO is already known as an extremely toxic chemical; the lethal concentration to 50% ([LC.sub.50]) for a 4-hr exposure to rats is only 160 ppm, and death results from massive pulmonary hemorrhage.[21] The [LC.sub.50] described is only 1% of the corresponding value for benzene and 0.5% of the value for MTBE. Furthermore, there are published reports of accidental occupational exposure to humans that resulted in emergency hospitalization for methemoglobinemia.[22] There are no published studies of long-term, low-level exposure in animals or humans.

There are several areas of research that one could pursue to confirm or reject this hypothesis. Obviously, the possible emission of MeONO from MTBE exhaust requires study, as does its concentration in the ambient air in cities in which MTBE is used heavily as an oxygenate. If MeONO is found, further toxicology studies would be warranted, including long-term exposure studies with animals. In that case, the choice of species would be critical. To verify a possible impact on asthma, one must study a species that gets spontaneous asthma (rats and mice do not). Statistical data from the University of Pennsylvania School of Veterinary Medicine[10] indicate that asthma in Philadelphia house cats also increased in parallel with asthma in humans during the period 1992-1995; it would appear, therefore, that cats would be an ideal choice for study.

A very attractive feature of the MeONO hypothesis is the fact that the compound is destroyed rapidly by sunlight (mean life = 10-15 min).[23] This feature provides the first plausible explanation for the so-called cloudy-day effect, in which sensitive individuals experience discomfort in regions with MTBE-RFG exposure only at night or on cloudy days.[24] The effect does not result from lower air pressure, because the symptoms also disappear during rainstorms. I know of no other plausible explanation for these extensive and consistent anecdotal reports.

Even if the MeONO hypothesis is incorrect, we must nonetheless determine empirically if the addition of MTBE to gasoline makes the exhaust stream more or less healthy for humans. There have been no studies of health effects from actual MTBE-RFG exhaust. What is needed is a controlled study of human exposure to engine exhaust–in which sensitive individuals are used (e.g., asthmatics, individuals with allergies)–and in which fuels with and without MTBE are compared.

Additional epidemiological studies are also needed. Whereas it is not difficult for one to obtain data on hospitalizations for various conditions, most of the reported symptoms rarely lead to hospitalization. Therefore, some source of widespread data about physician office visits is needed–data that are not obtained easily in the United States. One possibility would be for us to study office visits of the elderly, given that most are covered by Medicare insurance, and data are available from the Health Care Financing Administration (HCFA). It is noteworthy that anecdotal and statistical data in Philadelphia indicate a large increase in adult onset asthma; the effects, therefore, are by no means limited to children.

If these needed research studies are not done, we may find ourselves banning MTBE for the wrong reason. This situation could easily lead us to create yet another epidemic from the use of another gasoline additive, the health impact of which would also not be understood. For example, I would expect that any ether in gasoline would produce some kind of organic nitrite, with effects that mirror those of MeONO. It is imperative that funding agencies recognize the urgency of this research.


[1.] Middaugh JP. Reacting to gasoline additives. Science 1994; 263: 1545.

[2.] Mehlman M. Pollution by gasoline containing hazardous methyl tertiary butyl ether (MTBE). Arch Environ Health 1998; 53: 245-46.

[3.] Mehlman M. Dangerous and cancer-causing properties of products and chemicals in the oil-refining and petrochemical industries. XXV. J Clin Technol, Environ Toxicol, Occup Med 1998; 7:65-87.

[4.] National Academy Press. Toxicological and Performance Aspects of Oxygenated Motor Vehicle Fuels. Washington, DC: National Academy Press, 1996; pp 75-115.

[5.] Ozone-Forming Potential of Reformulated Gasoline. Washington, DC: National Academy Press, 1999; pp 1-212.

[6.] Andrews C. MTBE–a long-term threat to ground-water quality. Ground Water 1998; 36:705-06.

[7.] Mehlman M. Human health effects from exposure to gasoline containing methyl-tert-butyl ether. Eur J Oncol 1998; 3:171-89.

[8.] Belpoggi F, Soffritti M, Maltoni C. Methyl-tertiary butyl ether (MTBE): a gasoline additive causes testicular and lymphohaemotopoietic cancers in rats. Toxicol Ind Health 1995; 11:119-49.

[9.] Caprino L, Giuseppina IT. Potential health effects of gasoline and its constituents: a review of current literature (1990-1997) on toxicological data. Environ Health Perspect 1998; 106:115-25.

[10.] Joseph PM. Changes in disease rates in Philadelphia following the introduction of oxygenated gasoline. Annual Meeting Paper 97-TA34.02, June 10, 1997. Pittsburgh, PA: Air and Waste Management Association, 1997; pp 1-15.

[11.] Mangione S, Papastamelos C, Elia J, et al. Asthma prevalence and absenteeism among innercity school children: a survey of two Philadelphia Middle Schools. Am J Respir Crit Care Med 1997; 155:1-1.

[12.] McBride AD. Outcome of Asthma Survey of Kindergartners Entering the Public School System in 1996. Stamford, CT: Stamford Department of Health, 1996; pp 1-1.

[13.] Hathaway W. Asthma: An Epidemic among Hartford’s Children. In: Hartford Courant. Hartford, CT: June 22, 1999; p A1.

[14.] Crain EF, Weiss KB, Biijur PE, et al. An estimate of the prevalence of asthma and wheezing among inner-city children. Pediatrics 1994; 94:356-62.

[15.] Leighton J, Matte T, Findley S, et al. Asthma Prevalence among school children in a Bronx community. Asthma Conference, February 9, 1999. Atlanta, GA: Centers for Disease Control and Prevention, 1999; p 26.

[16.] Luttinger D. Use of the behavioral risk factor surveillance system (BRFSS) for assessing information about adult asthma in New York State. Asthma Conference, February 9, 1999. Atlanta, GA: Centers for Disease Control and Prevention, p 34.

[17.] Belier M, Schloss M, Middaugh J. Evaluation of health effects from exposure to oxygenated fuel in Fairbanks, Alaska. State Alaska Bull 1992; 26:1-1.

[18.] Anderson HA, Hanrahan L, Goldring J, et al. An Investigation of Health Concerns Attributed to Reformulated Gasoline Use in Southeastern Wisconsin. Madison, WI: Wisconsin Department of Health, 1995; pp 1-97.

[19.] Mohr SN, Fiedler N, Weisel C, et al. Health effects of MTBE among New Jersey Garage Workers. Inhal Toxicol 1994; 6: 553-62.

[20.] Joseph PM. New Hypotheses for MTBE Combustion Products. Annual Meeting Paper 99-885, June 22, 1999. Pittsburgh, PA: Air Waste Management Association, 1999; pp 1-10.

[21.] Klonne DR, Ulrich CE, Weissman J, et al. Acute inhalation toxicity of aliphatic (C1-C5) nitrites in rats. Fund Appl Toxicol 1987; 8:101-06.

[22.] Wax PM, Hoffman RS. Methemoglobinemia: an occupational hazard of phenylpropanolamine production. Clin Toxicol 1994; 32:299-303.

[23.] Seinfeld JH, Pandis SN. Atmospheric Chemistry and Physics. New York: John Wiley, 1998; p 314.

[24.] Joseph PM. Letter to the editor. Arch Environ Health 1995; 50:395-96.

Dr. Peter Joseph Department of Radiology University of Pennsylvania Philadelphia, Pennsylvania

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