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October 8, 1999 Reformulated
Gasoline: A Source of Illness Observations and Speculations by Also by Peter M. Joseph: I believe there is a new illness in our region which is affecting thousands of people and is largely unknown and unrecognized by most patients and physicians.1 It is due to a sensitivity reaction to a chemical used in the new "reformulated" gasoline (RFG) whose sole purpose is, ironically, to improve our health. The chemical is methyl tertiary butyl ether (MTBE). Whether adding such oxygenated chemicals to gasoline really reduces vehicle emissions is now considered to be doubtful, consistent with earlier analyses2. A recent EPA committee recommending phasing out this additive, but did not specify a time schedule for doing so. In the meantime, people are suffering from its effects. This document is organized as follows:
SYMPTOMS: The symptoms can be roughly categorized as respiratory, neurological, or allergic. The respiratory symptoms could be more accurately described as "inflammatory", since they include inflammation of any of the mucous membranes in the upper respiratory track (URT), including rhinitis, pharyngitis, or bronchitis, as well as other membranes exposed to the air such as those in the sinuses, eye or ear. These symptoms are more similar to those of allergic reactions rather than of infection. More important, the time course is very different from URT infections, since the symptoms continue for an indefinite period of time, usually many weeks or months, but are often modulated by subtle changes in the weather conditions (see below). Antihistamines are usually not helpful, certainly not as much as they are in conventional seasonal allergies. Patients often report a feeling of severe malaise, described as "I just feel terrible". Perhaps the most important respiratory effect is exacerbation of asthma, the prevalence of which is definitely skyrocketing in those east coast cities with MTBE-RFG in use; these include Philadelphia3 with 29%, New York City4(22%), Hartford5(40%) and Stamford6(24%) Connecticut. Both New York City and Philadelphia have formed a special Asthma Task Force to try to understand this problem. There is much discussion today of rapid increases in asthma in children. However, there is both anecdotal and statistical evidence of an epidemic of adult onset asthma, as well. The neurological symptoms include headache, nausea, palpitations, anxiety, insomnia, and sometimes visual disturbances. One symptom I have found most troubling is a sense of lightheadedness, similar to ethanol intoxication. Some patients complain of lethargy. These can be modulated by weather conditions or be constant for many weeks. Heart palpitations in some susceptible individuals can lead to cardiac arrhythmia as documented on ECG. The allergic symptoms commonly are skin rash or tearing in the eyes. These are exacerbated by exposure to gasoline fumes or byproducts, such as by riding in cars in heavy traffic. Some people experience a hot flushed feeling in the skin of the head and neck. This can probably be attributed to exposure to methyl nitrite (see below). Very few people get all of these symptoms, more commonly only a few are seen. It is relatively common for one person to have either the respiratory or neurological symptoms, but not both. Some of these symptoms would normally be attributable to more conventional causes, such as emotional stress or viral infections. However, from the circumstances that induce the symptoms, as well as certain historical studies, one can conclude that MTBE is, directly or indirectly, the cause. AGGRAVATING CIRCUMSTANCES: The most unusual aspect of this problem, and the reason why thousands of people believe that it exists, are the very unusual circumstances that cause or aggravate the symptoms. One can distinguish three kinds of aggravating circumstances: (1) direct exposure to reformulated gasoline with 11% MTBE. An excellent review of this problem has been written by Mehlman7. (2) oral or inhalation exposure to MTBE as a pollutant in drinking water. Vojdani et al have published a study of a community of 350 people so affected8. (3) inhalation exposure to exhaust fumes from cars burning MTBE- RFG. While these symptoms will obviously get worse while riding in heavy traffic, effects are seen from the resulting pollution of the ambient community air. This implies symptoms not obviously associated with automobiles, such as in one's bedroom at night. People with this sensitivity find that they become asymptomatic when they avoid these exposures, such as by travelling to a region where MTBE-RFG is not used. Most of the material in this document will focus on this problem. I believe this problem is caused not by MTBE itself but by an unidentified exhaust product, probably methyl nitrite (MN). MN, which is CH3ONO, is easily destroyed by sunlight. This would explain a very unusual symptomatic feature, namely, many people become symptomatic only at night or on dark cloudy days when the sun is not shining. This implies of course, that they are unlikely to exhibit the symptoms during a routine clinical examination, unless it is done at night or on a dark cloudy day without rain. HISTORY: When MTBE was added to gasoline in Fairbanks, Alaska, in the winter of 1992, many people (estimated to be 10% of the population) complained of the above symptoms. The symptoms were associated with gasoline fumes and/or exhaust in that they got worse when people drove in traffic and better in their homes out of town. The CDC did a thorough investigation, including measuring blood levels of MTBE and its metabolite TBA.9 The governor of Alaska demanded that MTBE be removed and the symptoms complaints promptly subsided. The same scenario was repeated at the same time in Missoula, Montana with the same result, except that the CDC was not involved. The CDC did another driver survey study in Stamford Connecticut in March 1993 and found people reporting the same symptoms as in Fairbanks, Alaska10. They concluded that "Persons with high blood concentrations of MTBE reported a high prevalence of one or more of the key symptoms ... that had been previously associated with MTBE exposure in Fairbanks, Alaska. This association appears to be specific to these symptoms." A study of New Jersey garage workers in 1993 compared northern and southern workers who had high and low MTBE exposure, respectively and claimed to find no difference. However, their group of northern workers who pump gasoline more than 5 hours per day did show a statistically significant (P=0.03) increase in MTBE symptoms. Some people interpret that study as negative because in a specially selected subgroup of only 11 individuals no increase in MTBE-type symptoms was found. That obviously does not rule out a possible sensitive subgroup on the order of a few percent. Since then, spontaneous citizen protest groups have arisen in Maine, Pennsylvania, New Jersey, Connecticut, Colorado, Texas, Wisconsin and especially California. In January, 1995, ABC Television ran a 15 minute documentary explaining the history of this problem. In New Jersey, the citizens' group "Oxybusters" has collected about 15,000 petition signatures against MTBE. The California Oxybusters has collected over 100,000 signatures against MTBE. This lead to the legislature ordering a formal study by the University of California (http://tsrtp.ucdavis.edu/mtberpt/homepage.html), which concluded that: (1) MTBE is not needed to reduce air pollution (2) MTBE is polluting thousands of underground water wells. (3) MTBE could be causing asthma, but more research is needed. MTBE has been used as a gasoline additive since approximately 1979. However, it was used solely to increase the octane of some brands of premium gasoline and the amount used in any region was at least an order of magnitude less than today. In November 1992, certain cities were required to have 15% MTBE (or its equivalent) in all gasoline for the winter months only. (The regions affected were the cities from Washington to New York City on the east coast, and all of California.) Starting in January 1995, a different gasoline formulation containing 11% MTBE was required, in a larger number of urban areas, in most cases 12 months per year. (This last point is important, because many people mistakenly believe that it is used only during the winter months.) The actual usage pattern is very dependent on where you are: consult your state environmental department, or ask me via email. I personally developed severe neurological symptoms in the winter of 1992-93, and was then diagnosed as being highly atopic. I suffered from various of these symptoms in synchrony with the MTBE seasonal usage. I was started on immunotherapy in September 1993, and by January 1997 had been essentially cured of this sensitivity problem. Further details are available upon request. It was from careful observation of the pattern of circumstances of my own symptoms, as well as by conversations with over 200 other people, that many of the conclusions in this document were reached. METABOLIC BYPRODUCTS AND IN VIVO EFFECTS: It is known that the main metabolic products of MTBE are formaldehyde (F) and tertiary butyl alcohol (TBA). This conversion is rather fast, half life of about one hour. F is known to be both toxic and a potent sensitizer. TBA is not as well known, but there is a report of allergy11 which suggests that it also can sensitize. There have been a few acute (one hour) exposure studies with human volunteers using pure MTBE; these were all done with healthy young adults and no effects were seen. These studies obviously do not address the problems synergistic interaction with other chemicals in gasoline, or sensitive subpopulations, or especially of contaminants or exhaust products other than MTBE. There have been no controlled studies of the effect of MTBE-RFG exhaust on sensitive individuals, other than anecdotal reports from myself and a few others. These experiences indicate that the exhaust from gasoline with MTBE is far more harmful than that without MTBE. The interested physician might try to breath the exhaust from his own car, after allowing it to run in a garage for a few minutes first thing in the morning! Methyl nitrite (MN) is known to be extremely toxic. The LC50 for a four hour exposure to rats is only 170 ppm, which is one hundred times smaller than that for benzene. There is a published report12 of two accidental exposures which resulted in hospitalization for methemoglobinemia. However, it is likely that chronic exposure may result in more subtle effects. Analogous organic nitrites, such as amyl nitrite, are well known as drugs of abuse due to neurological effects.13,14 TREATMENT: The question of what the practicing physician can do is difficult. Since the very existence of the disease is controversial, there are no established treatment guidelines. Antihistamines are usually not helpful. In cases of extreme skin rash, treatment with high doses of oral prednisone for several weeks was necessary. There is a blood test that may be useful for some patients. Vojdani et al 15 have developed a test that demonstrates the existence of antibodies to the MTBE molecule. This test is commercially available (Immunosciences Lab, Inc. Beverly Hills,CA). Interestingly, the test will cross react with certain other molecules which contain the methoxy group, so that a cross reaction with Methyl nitrite is possible. (This has not been studied). However, it must be emphasized that many people become "sensitized" to the MTBE, MN, or other byproducts in some way that does not appear to involve immunoglobins. This may be an example of a neurological sensitization, which can lead to neurogenic inflammation16. Some people go on to develop major respiratory problems similar to, or possibly including, asthma, which require inhaled steroids for management. In some cases the physicians diagnose only "dyspnea" since spirometry tests for asthma are interpreted as negative. There is growing anecdotal evidence for a huge increase in the number of children diagnosed with attention deficit disorder (ADD) in the Philadelphia area. Since many of the neurological symptoms experienced by myself and other adults are very similar (lighheadedness, difficulty in concentrating, etc.), it is not unreasonable to attribute this diagnosed condition in children to some component of MTBE-induced air pollution. Since the use of Ritalin in children with ADD is controversial, the physician might want to suggest a temporary change of geographic location to determine if the child's symptoms are related to local MTBE usage. MTBE should have a high index of suspicion for automobile or gasoline workers with these symptoms. Mehlman17 found that a large percentage of workers in oil refinery plants using MTBE developed the symptoms discussed here. People whose homes have attached garages may get sick from the fumes from their cars kept there. For those who suffer from the pollution of ambient air (and not just from gasoline fumes), the best solution is to move to another region of the country. A less drastic treatment is to purchase an air filtering machine capable of removing the relevant toxins from the home environment. From my experience, it is essential that the machine contain both activated carbon as well as potassium permangenate. The KMnO4 is intended to oxidize formaldehyde, but it has been found useful (even essential) for the nighttime pollutant, which is probably methyl nitrite. To the best of my knowledge, such a machine is not sold in stores in the USA and must be ordered by mail. Contact me for details. I encourage any physicians who are interested to contact me for more detailed information. I can be reached at the Hospital of the University of Pennsylvania, telephone number 215-662-6679. email: joseph@rad.upenn.edu APPENDIX: Exhaust from MTBE-RFG The published studies 18,19 look only for a preselected list of pure hydrocarbons, plus a handful of aldehydes. These studies invariably list a few percent "unidentified hydrocarbons". In some cases the quantity of "unidentified hydrocarbons" increased when MTBE was added to the fuel.18 This is extremely important because proponents of MTBE talk as if it were proven that adding MTBE to gasoline can only decrease all possible exhaust products (except for formaldehyde, acknowledged to be increased with MTBE). Many individuals have noticed a foul odor coming from cars burning MTBE-RFG under certain conditions, such as acceleration during cloudy days. From subjective experiments in my own garage, comparing exhaust from MTBE versus ethanol RFG, I can say that there is some extremely foul and irritating substance produced from MTBE fuel that is not found with ethanol fuel. Furthermore, my symptoms did increase while breathing air in the environment with the MTBE-RFG. REFERENCES |