The purpose of this hearing is to examine the impact of MTBE on our water supply which led to passage of Senate legislation this year. My bill (SB 1189) established a $5 million cleanup fund to help local communities while they go after responsible private parties, and requires official health taste and odor standards to be established during the next 12 months.

The scientific evidence points to MTBE as both a carcinogen and a neurotoxin.

On its carcinogenicity, I am submitting a paper by Dr. John Froines, chairman of the UCLA Department of Health Sciences. He describes MTBE as a "B2 probable carcinogen" based on a review of its structure activity, genotoxicity, case studies, epidemiology and animal studies. Based on carcinogenic effects in animal studies, he cites the Health Effects Institute report on oxygenates in gasoline, as follows:

"In assessing the overall significance of the cumulative data produced by the studies investigating MTBE and TBA in rodents, the most disconcerting aspect of the findings is that the two chemicals produce tumors at five different organ sites in two strains of two species. Considering that the mechanisms of action of these and other non-mutagenic rodent carcinogens are poorly understood, it would seem imprudent to dismiss these results as irrelevant to the human condition."

Dr. Froines calls for urgent further study "while doing everything we can to limit exposure to MTBE."

As to neurotoxicity, I am submitting testimony by Dr. Jorge Mancillas, formerly with UCLA and now a member of my Senate staff. He notes that in 1988, the Interagency Testing Committee (ITC) gave MTBE an "A" designation, which means there is "an unreasonable risk of neuroxicity for which there is substantial human exposure". Animal inhalation studies have shown MTBE's neurotoxic effects, specifically a depression of central nervous system activity. Dr. Mancillas goes into detail about the scientific controversies, concluding that "original studies indicating neurotoxic effects of MTBE have been misrepresented or ignored" by public agencies. For example, the Cal EPA claim in April 1997 that they were "unable to associate them (complaints) with MTBE exposure" was strongly objected to by the authors of those same studies.

More research is always helpful, but what should be condemned without reservation is the lack of conclusive evidence that MTBE was safe before it was introduced in California. Now our groundwater is at risk and the public rightly should be concerned with having to play the experimental role of guinea pigs.

The original point of my SB 1189 and Senator Mountjoy's SB 521 was to place the burden of proof on the state and industry to, show by a reasonable deadline, that MTBE was safe for the public or else phase it out.

That legislative intent was weakened during the legislative struggle. But the final passage of SB 1189 and SB 521 seem to have contributed to a basic rethinking by industry of the prudence of continuing to rely on MTBE.

Chevron and Tosco have made business decisions to consider alternatives to MTBE before waiting for further evidence or public outcry over its impact on groundwater.

In the meantime, we have a lot of groundwater to clean up. A Lawrence Livermore survey says there may be 9000 gas storage tanks in California where MTBE is leaking into groundwater.

We need double-walled storage tanks in this state and nation as soon as possible. But even that will not work to prevent airborne MTBE contamination of the soil and MTBE pollution of our lakes and reservoirs.

MTBE may not have a future at all. I believe that it is an unacceptable public health problem. Its future depends on the willingness of public officials to reconsider past judgments as well as the internal cost-benefit analysis of the oil industry.

How did this terrible situation arise? It is a question of governance and politics, not simply one of faulty science. I have two comments here:

First, we in the Legislature made an historic mistake in delegating to the Air Resources Board the issue of whether and which oxygenates to use in gasoline. This delegation was meant to "take the politics out" of the decision-making process, but in fact the politics simply went behind closed-doors into the dim lit world of professional lobbyists and their scientific mercenaries. We in the Legislature now must take steps to reclaim the issue and provide a credible public process to examine the alternatives.

Second, environmental organizations were blinded by a specialization between "air" and "land" experts that split air quality considerations from groundwater ones. As a result, many environmentalists joined in coalition with the oil industry to achieve the standards of the Clean Air Act, not realizing the adverse groundwater impacts nor becoming concerned that some in the industry had created a profitable subsidiary to produce and market MTBE.

So it is time to return to the origins of this debate: how the oil and automobile industries can become compatible with protecting our air and our water supplies.

All over California we hear paid commercials proclaiming that "success is in the air". Why is the public being presented with this propaganda barrage? Why was $13 million just spent by industry to cast doubt on whether global warming is a real issue? Why has our government retreated from a commitment to tougher fuel efficiency standards and low-emission, zero-emission vehicles?

We are driving backwards from our environmental goals. It is projected that our nation's gasoline use is projected to increase by 33 percent in the next 12 years. Every gallon burned emits 2 pounds of carbon dioxide. Industry executives are reveling in our consumption of sport utility vehicles which, according to the New York Times, "will be the fastest-growing source of global warming gases in the United States over the next decade" and which are exempt from gas-guzzler and luxury vehicle taxes. At this rate we will never reach the Clinton Administration's already modest goal of reducing carbon emissions to 1990 levels by 2010. Reformulated gasoline is not the answer, it is only a transitional stop as we look for alternatives to greater dependence on fossil fuels.

Your hearing takes place at an important moment of reappraisal of MTBE, but also at an important global moment when the nations of the world are gathered in Kyoto to discuss global warming. The pollution of our democratic process is the challenge we must address in order to ensure a safe and sustainable resource base for the future. I urge you to take the lead in returning this country to a path of clean and efficient fuels and renewable energy resources.


I appreciate the opportunity to appear before you and testify on the matter of methyl tertiary butyl ether (MTBE), the gasoline additive designed to reduce carbon monoxide and toxic air contaminants in reformulated gasoline. My name is John R. Froines. I am Professor of Toxicology and Chair of the Department of Environmental Health Sciences at the UCLA School of Public Health. I direct the UCLA Center for Occupational and Environmental Health.

I serve on two State Committees with direct relevance to this testimony: the Carcinogen Identification Committee of the CAL/EPA Science Advisory Board and the Scientific Review Panel of the Air Resources Board. My own research focuses in part on mechanistic issues in chemical carcinogenesis and, in particular, on the carcinogenicity of arsenic and chromium. I co-direct the UCLA Pollution Prevention Education and Research Center, and pollution prevention is directly relevant to the issues before us today.

At the outset I want to list my conclusions relating to the use of MTBE as a fuel additive in California. I will then discuss some of the issues in greater detail.

1. It is highly laudable for the Legislature to be holding hearings to determine whether there are problems in the use of MTBE. Unfortunately, MTBE has been used in the U.S. since 1979 and there should have adequate discussion at the federal level of the possible risks associated with exposure to MTBE long before we reached the current widespread use of the chemical. In my view the California Legislature should establish legislation which requires a thorough review of the possible impact on public health from the introduction of new chemicals with potential for widespread use and possible exposure.

2. The use of MTBE is very wide and growing and becoming international. There were 27 companies producing 9.1 million pounds of MTBE in 1992 and 12. 3 billion pounds were produced in the U.S. in 1995. The widespread use affects the content of the debate since both government and industry now have a vested interest in the continued use of the product, thereby making an independent, scientifically neutral evaluation more difficult. This reemphasizes why we have to adequately assess chemicals for toxicity before their introduction.

3. While I would prefer us to be discussing electric vehicles or alternative (non- petroleum) fuels, the issue before us is the use of MTBE in reformulated gasoline. I consider reformulated gasoline to be a major advance in reducing ambient concentrations of toxic air contaminants. I support the use of reformulated gasoline while other alternatives are being developed. Reformulated gasoline has reduced the atmospheric concentrations of human carcinogens such as 1,3-butadiene and benzene.

4. The primary issue to consider here is whether MTBE should be the compound in reformulated fuel used for octane enhancement and reduction of carbon monoxide in the ambient environment? A corollary to that question is whether MTBE has been adequately tested for toxicity. The answer to this latter question is an unequivocal no, and this means the answer to the primary question is uncertain.

MTBE may turn out to be safe with little toxicity but we do not know that yet. The unanswered questions remain before us, and there is considerable uncertainty in the scientific information available to address issues of public health.

I hope that MTBE turns out to be perfectly safe; I have no prejudices about this issue. My concern is that we resolve the uncertainties before we proceed to impact the environment further.

5. Should there be a moratorium on the use of MTBE during the evaluation of exposure, toxicity and other unanswered questions? With our current state of knowledge my answer is an equally unequivocal no. We don't want to increase the concentrations of butadiene and benzene by not using reformulated gasoline with MTBE, but we also should do everything we can to limit exposure to MTBE while unresolved issues of toxicity are being addressed.

6. Are the chronic animal bioassays that have been conducted to determine whether MTBE is a carcinogen relevant to humans or are they specific to the species tested, namely rats and mice? I consider the animal bioassays to be highly relevant and I agree with the sentiments of the Health Effects Institute (HEI) report on oxygenates added to gasoline which concluded:

"The mechanisms by which exposure to high concentrations of MTBE or TBA [(tertiary butyl alcohol) a metabolite and breakdown product of MTBE] causes tumor formation in different organ systems of mice and rats are not understood... In assessing the overall significance of the cumulative data produced by the studies investigating MTBE and TBA in rodents, the most disconcerting aspect of the findings is that the two chemicals produce tumors at five different organ sites in two strains of two species. Considering that the mechanisms of action of these and other non-mutagenic rodent carcinogens are poorly understood, it would seem imprudent to dismiss these results as irrelevant to the human condition."

7. What should we do to evaluate MTBE and how long will it take? In terms of chemical testing for toxicity, I believe there should be collaboration between scientists at the University of California, the Office of Environmental Health Hazard Assessment (OEHHA) and the National Institute of Environmental Health Sciences (NIEHS) to develop protocols to test MTBE. The units within the University of California should be those established by the University and the Legislature to address issues of chemical toxicity, namely, the Centers for Occupational and Environmental Health and the Toxic Substances Research and Teaching Program with input from other appropriate faculty.

8. Additional chronic animal bioassays may be required and they can take a considerable period of time. Determination if the use of genetically altered rodents (transgenics) could be used to limit the time would be a matter for consideration. However, the protocols developed for testing should be reviewed by committees with input from affected parties, because if transgenic mice were used, interested parties could challenge the results arguing the test animals were genetically altered and therefore not relevant to the human condition. The requirement for an agreed upon protocol is necessary before any toxicity testing is initiated.

MTBE Background

MTBE is a colorless organic ether used primarily as an octane booster in reformulated gasoline. It has a high vapor pressure. MTBE has high solubility in water; it is mobile and relatively resistant to biodegradation which creates the potential for chronic contamination of groundwater and surface water. MTBE travels through soil quickly and persists in the environment for long periods of time.

MTBE has significant taste and odor problems associated with its contamination of drinking water. The aroma has been reported to be similar to paint thinner or turpentine and can be detected as low as 13.5 to 45.4 ppb, lower than the levels considered unacceptable for health reasons.

Exposure to the public occurs via inhalation where MTBE arises from manufacture of the product, gasoline production, tailpipe emissions and evaporative emissions. Exposure can also occur from contaminated drinking water as we have seen in Santa Monica where levels have been reported as high as 610 ppb.

Carcinogenicity of MTBE

In this testimony I shall address the qualitative issue of whether MTBE should be considered a carcinogen and the level of evidence associated with the determination. I shall not consider quantitative risk assessment since I believe the qualitative issue remains fundamental to its use. I do not believe the issue should be whether to use oxygenated fuel with MTBE as the octane enhancer versus the use of non-reformulated gasoline containing other carcinogenic chemicals. I believe we should be conducting research to identify safe alternatives even while we investigate the toxicity and carcinogenicity of MTBE.

There are five approaches to the identification of a chemical as a carcinogen and more recently the use of mechanistic considerations to assess the relevance of some of these approaches has become important. The five sources of information are:

1. Structure-activity (Does the chemical structure suggest the chemical may be carcinogenic).

2. Genotoxicity (Does the chemical produce alterations in the genetic makeup of test systems)

3. Chronic animal bioassays

4. Epidemiologic evidence (human studies)

5. Case reports

All of these approaches have proved valuable as tools to determine the potential carcinogenicity of a particular compound. For example, vinyl chloride was first considered carcinogenic based on identification of workers with a rare liver cancer, angiosarcoma, at BF Goodrich in the early 1970s. Structure-activity considerations have proved valuable in predicting the carcinogenicity of compounds or their metabolites known to be electrophilic. The Ames assay for detecting mutagens (genotoxicity) has been an important source of information on potential carcinogens. Animal studies have been crucial in identifying human carcinogens and with the exception of arsenic every known human carcinongen is carcinogenic in animals. Human studies have been very important in the qualititative identification of carcinogens, for example, butadiene, chromium, and arsenic have been identified as a result of epidemiologic investigation.

In addition to the traditional approaches the International Agency for Research on Cancer (IARC) and the U.S. EPA now make use of other information on the mechanism of cancer associated with the carcinogenesis of a particular substance. Mechanistic considerations have been important in the classification of a number of chemicals by IARC and EPA is beginning to use this type of information in their determinations. However, a cautionary note is required since we know limited knowledge about the true mechanisms of cancer induction from chemicals. It is important not assume the validity of mechanistic arguments without careful testing of the inherent assumptions underlying the hypothesis. We do not want to rush to judgement on a substance which may have significant public health implications as a result of its use in commerce and the environment.


1. Structure-activity. Structure activity considerations would result in the carcinogen, formaldehyde, being considered a likely product of biotransformation and degradation, but overall MTBE would not have been predicted to be a carcinogen. Formaldehyde and tertiary butyl alcohol are products of metabolism and degradation.

2. Genotoxicity. MTBE is not considered genotoxic, although there is some limited evidence in one assay, which has been associated with the genotoxicity of formaldehyde. Investigators at USC have reported MTBE is positive in the Ames Assay using TA 102, an infrequently used tester strain. These results require firrther investigation to validate. Formaldehyde is genotoxic.

3. Case studies There are no case studies suggesting specific cancers have arisen from MTBE.

4. Epidemiology There are no studies on the carcinogenicity of MTBE in humans, and the limited timeframe of MTBE use would inhibit epidemiologic investigation.

5. Animal studies MTBE, TBA, and formaldehyde have all been found to be carcinogenic in animal studies. Chronic animal bioassays of MTBE have resulted in the identification of lymphomas and leukemias, kidney, testes and liver cancers. Thyroid and kidney tumors derived from the degradation product TBA and nasal cancers have been found in rats exposed to formaldehyde by inhalation.

MTBE is metabolized to tertiary butyl alcohol (TBA) and formaldehyde. Formaldehyde is considered a known human carcinogen and is regulated as such by the Occupational Safety and Health Administration (OSHA). Formaldehyde is a product of atmospheric degradation of MTBE where it would be of more concern than via ingestion in drinking water because of its metabolism. TBA is further metabolized to other products whose toxicity has not been well investigated. The information on metabolism remains somewhat limited.

These data taken together would suggest MTBE should be considered either a probable or possible carcinogen. EPA defines a probable carcinogen as an agent where the epidemiologic evidence is either "limited" or where there is "inadequate evidence" and where there is "sufficient evidence" in animal studies. An agent would be a B1 carcinogen if the epidemiologic evidence is limited and B2 if the evidence is inadequate. In my view MTBE should be considered a B2 probable carcinogen until further testing resolves the issue further.

The Health Effects Institute and Office of Science and Technology reports on MTBE both consider carcinogenic potency and U.S. EPA has developed a risk assessment. While it may be useful to review the risk assessment values I believe it is premature to make policy decisions based on those risk assessment values until further confirmation of the animal bioassays and resolution of mechanistic issues is completed.

Uncertainties associated with the Animal bioassays

There are a number of uncertainties associated with the animal studies which require further investigation.

1. The doses of MTBE were very high which may have caused toxicity and in some cases did cause early mortality in the treated animals. Is MTBE a carcinogen at the lower exposure levels found in the environment? This requires further investigation of the mechanism of carcinogenicity of MTBE.

2. There is evidence that tumors in male rats may be species specific and therefore not relevant to assessment of human risk. The renal tumors may be secondary to alpha-2-micro-globulin nephropathy that is specific to male rats. However, serious questions have been raised about whether this proposed mechanism is a response to exposure or whether it constitutes an adequate explanation for the renal tumors. Based on our understanding of the mechanism of renal tumor formation we cannot disregard these tumors as being species specific at this point.

3. It is not apparent what weight should be given to mouse liver tumors. Mouse liver tumors may result from different mechanistic pathways than human cancers and their relevance to assessing human risk has been questioned. At this stage, however, we cannot assume the liver cancers have no human significance based on mechanistic considerations.

4. A series of issues have been raised about the findings of leukemias and lymphomas in the gavage study of Maltoni. A review of his pathology slides would assist clarification of the questions, but the findings represent very important conclusions until proven otherwise.

Overall, the chronic animal bioassays remain important findings, but further followup studies are required. The HEI report gives the most detailed recommendations for further investigations and they are provided as appendices to this testimony. The recommendations indicate the wide range of health related questions that remain to be addressed. This recommended research will not be completed by 1998-1999, although considerable information could be developed by 1999 if we begin immediately. The State will need to coordinate its activities with U.S. EPA and NIEHS. In my view it is essential for NIEHS to be involved in all health related research. NIEHS should conduct research in contrast to the EPA approach which requires testing done by affected industry. Industry should be asked to contribute to the costs of the research, but independent academic and NIEHS researchers must conduct the studies.

During the time the health and exposure related studies are being conducted there should be an equally energetic investigation of non-toxic substitutes for MTBE.

The Tables included with this testimony are taken from the Health Effects Institute report entitled "The Potential Health Effects of Oxygenates added to Gasoline, A Review of the Current Literature". This was a special report of the Institute's Oxygenates Evaluation Committee.

Dr. Jorge R. Mancillas
May 12, 1997
Testimony before the California State Senate Environmental Quality Committee
Bill under consideration: SB 1189


The decision as to the fate of MTBE has serious economic and public health ramifications. The argument that phasing out MTBE as an additive in oxygenated fuels would have serious economic consequences is based on the fact that-large amounts of MTBE are used in California and throughout the country. It is this widespread Use, however, that provides the risk of exposure to a population of over 100 million Americans and requires that any potential or established risk to public health be taken with the outmost seriousness. Similarly, one can not make the argument that sufficient amounts of MTBE are being used widely enough to pose a risk to human health without acknowledging that any decision as to its future use must take in consideration its economic consequences.

The best way to arrive at a policy decision regarding the future of MTBE as a gasoline additive is to rely strictly on solid science and careful and well-supported analysis of economic impact Policy is best when based on fact, not fear, communication and cooperation, rather than cohersion.

The goal should be to protect the health of our citizens, the integrity of our natural environment, and the solvency of the economic institutions that provide an adequate supply of fuels. Enlightened policy does not require that any of those objectives be brushed aside. Any proposals should include measures to insure prevention of harm to human health and thoughtful consideration of how to best handle the economic and environmental consequences of any changes in current policy.

This testimony is intended to underscore tile urgency of dealing with the potential risks to public health posed by the use of MTBE as an additive in oxygenated fuels. Concern during policy discussions has centered on risks of carcinogenicity, based on evidence in the peer-reviewed literature of MTBE's carcinogenic potential with chronic exposure to high enough doses in animal studies. Claims have also been made of associations with other pathological conditions which may merit further investigation.

My testimony, however, focuses on the primary effect of MTBE on the human body: alteration of nervous system function.. The view that the use of MTBE poses a significant risk of neurotoxic effects and that this is an immediate public health concern is based on:

 the fact that MTBE is a neuroactive substance (section I of this written testimony)

 known plausible cellular mechanisms by which it disrupts normal function (section 2)

 animal studies which document its neurotoxicity (section 4a) and

 human epidemiological studies which document observed adverse effects symptomatic of nervous system disruption after exposure to MTBE (section 4b)


MTBE (Methyl Tertiary Butyl Ether) is an ether. Ethers are neuroactive.

Ethers were first isolated over 150 years ago and became of interest because of their ability to produce anesthetic effects in humans. Ether was first used as an anesthetic by dentist William Horton in Boston in 1846. It has been replaced as an anesthetic because the chemical characteristics that make some ethers useful as a gasoline additive, their flammability, created fire risks.

The organs first and most abundantly perfused with MTBE once it reaches the bloodstream after penetrating the body either through inhalation, ingestion or dermal absorption are the brain, kidney, and liver. The first biological target of MTBE and the organ most sensitive to its actions is the nervous system.


Cell membranes are lipid bilayers. MTBE, because of its solubility in lipids, alters membrane fluidity, potentially affecting all cells in the body. Nerve cells are more sensitive to agents which disrupt membrane integrity because their function is performed by membrane-bound molecules:

Transmission of information by nerve cells is accomplished through: a) generation of electrical impulses (action potentials) by changing conductances of ion channels (which are proteins extending through their membranes); b) through secretion of neurotransmitters at the end of nerve fibers (another process which depends on cell membrane integrity); and c) through responsiveness to neurotransmitters by receptor molecules inserted in the membranes of their dendrites.

The question then is, if MTBE is neuroactive, is there a significant risk of neurotoxic effects for humans at current levels of exposure?


In March 1988, the Interagency Testing Committee (ITC), after review of a number of substances which included MTBE, gave MTBE an MAN finding. An MAN finding was assigned to substances which present an unreasonable risk of neurotoxicity and for which there is substantial human exposure.

The MAN finding on MTBE required conducting a core test battery for neurotoxicity, including a functional observational battery, motor activity tests, and neuropathological evaluations after acute and subchronic exposure.

The ITC is a muItidisciplinary advisory panel composed of one member of EPA, OSHA, Council on Environmental Quality, NIOSH, NIEH, NCI, NSF and the Department of Commerce. It issued 24 reports to EPA between 1977 and 1989, proposing 100 chemicals for inclusion in the priority list testing under section 4 of TSCA. Its finding on MTBE came before it was used as a gasoline additive as extensively as it is now and before its use became controversial.

After negotiations with industry, EPA (Office of Toxic Substances) issued a consent decree (March 1988, Federal Register, volume 53 - 10391) mandating neurotoxicity evaluation. Industry proposed testing to be performed by the Bushy Run Research Center, owned by Union Carbide. Tests were completed and a report written in September 1989 (Report 52-533, September 19, 1989). The results indicate MTBE has neurotoxic effects.



The Bushy Run Research Center studies, conducted on rats exposed to 4 concentrations through inhalation (0, 8900, 4,000 and 8,000 ppm) showed that MTBE caused depression of Central Nervous System activity which was more apparent at higher doses.

Amongst the effects observed after acute exposure were:


 duck walk gait

 labored respiration

 decreased muscle tone

 decreased body temperature

 decreased treadmill performance

 decreased hind-limb grip strength

 increased hind-limb splay, piloerection and lacrimation

 increased mean latency to rotate on an inclined screen

In the studies after sub-chronic exposure:

 Effects similar to those caused by acute exposure were observed although the authors questioned their toxicological significance.

 Significant changes in body temperature, motor activity and fore limb strength were observed.

 Absolute brain weight was lower in animals exposed to 8,000 ppm. Unfortunately, the authors did not examine or report what specific cell populations in the central nervous system account for the brain weight loss.

Given the results of animal studies, does MTBE pose a risk of neurotoxicity in humans at the exposure levels resulting from its use as a gasoline additive?


In response to the 1990 amendments to the Clean air Act, Alaska converted to the use of oxygenated fuel containing 15% by volume MTBE in mid-October 1992. MTBE had not previously been added to gasoline in Alaska either as an octane enhancer or as an oxygenate.

Within the first 3 weeks of November 1992, reports of headaches, dizziness and nausea poured into a local telephone hotline.

In response to the complaints, a study was conducted by the Alaska Department of Health and Social Services and the Centers for Disease Control in December 1992, and January and February 1993.

Workers who were exposed in the workplace and commuters subjected to nonoccupational exposure were evaluated while MTBE was in use and after use of oxygenated fuels was suspended in Alaska.

 Air concentrations of MTBE were monitored.

 Blood levels of MTBE in the subjects was measured.


 In areas where MTBE was added to gasoline, MTBE was detectable in the blood of occupationally exposed persons and the general public.

 Persons exposed to and with higher blood levels of MTBE more frequently reported headaches, eye irritation, nausea, dizziness, burning of the nose and throat, coughing, spaciness or disorientation, and vomiting, compared to those with lower blood levels of MTBE.

 Exposure to gasoline without MTBE did not result in increased symptoms.


Use of oxygenated fuels with MTBE was suspended in Alaska.

Alaska has been able to comply with the requirements of the Clean Air Act. Measures other than the use of reformulated gasoline, including comprehensive inspection and maintenance program resulted in a dramatic improvement in air quality and allowed for an immediate suspension of the use of MTBE while alternatives were sought. Ethanol was later introduced as a replacement for MTBE in Anchorage.


Complaints indicative of adverse health effects similar to those reported in Alaska have been reported in Montana, New Jersey, Wisconsin, Maine, Connecticut, Pennsylvania, Texas and Colorado.

In April 1993, the Centers for Disease Control conducted studies in Stamford Connecticut similar to those in Alaska with the cooperation of the Connecticut Health Department. Again, the subjects with the highest blood MTBE levels had a higher incidence of symptoms of disruption of nervous system function.

A study conducted in Albany, New York yielded negative results. Comparisons may be misleading, however, because the blood levels of MTBE were significantly much lower than in Alaska and Connecticut (levels for gasoline station attendants, for example, were 15.19 micrograms per liter in Stamford vs. 0.42 micrograms per liter in Albany). A study comparing selected populations of southern and northern New Jersey did not include analysis of blood samples and its results are therefore more difficult to interpret.


The results of the Alaska studies have been misrepresented by CAL EPA in its April 1997 report (p. 9) when stating that they "were unable to associate them [complaints] with MTBE exposure." The authors of the studies strongly object to that characterization. Reviews by Federal agencies have tried to downplay the results.

Similarly, a November 1993 review by the ORD of the US-EPA misrepresents the Stamford CDC studies by creating categories of subjects which dilute the results. Whereas the relevant correlation to examine is that between blood levels and symptoms of adverse effects, they compare the median of one or another occupational category, diluting the strength of the correlation between MTBE blood levels and health effects. That and other reviews give equal or more weight to negative results in Albany than to those obtained in Alaska and Stamford, with complete disregard to the clear differences in blood levels.

Whatever the intent is, one should be cautious and not rely on "reviews" and "assessments" of the literature but consult the original studies, with a definite preference for studies the results of which have been published in peer-reviewed journals. The only reliable measure of exposure is a quantitative and pharmacokinetic analysis of blood levels, with measurement of symptoms at relevant time points in relation to changes in blood levels. Guesses about exposures based on measurement of air levels are misleading and at best dilute the results.

If the results of the studies mentioned in 4a and 4b are indicative of neurotoxic effects of MTBE, why is there such little public awareness and reporting of adverse health effects?


One of the major problems in establishing the risk of neurotoxicity for a human population is that irreversible neurotoxic effects are often not detected, nor accurately diagnosed. Even in the case of reversible, acute effects, the association of overt symptoms with exposure to the causative agent is rarely established. Usually, no one is looking for them and neither the public nor most doctors are trained to identify, recognize and interpret symptoms of neurotoxicity.

Damage to the nervous system is more commonly expressed as loss of nerve cells, or impaired peripheral nerves, as opposed to visible abnormal growth as it is the case with cancer. Loss of neural tissue does not cause detectable biochemical changes that can serve as indicators.

Doctors are not taught in medical school to look for neurotoxic effects. When patients complain doctors rarely conduct assays for the presence of neurotoxic substances in blood samples. It is also extremely rare, for example, for a doctor to have the equipment to measure speed of conduction of peripheral nerves.

Nervous tissue is the most delicate, vulnerable and irreparable of all tissues. While other tissues can regenerate, a lost nerve cell is lost forever. Nerve cells can not divide. They are not replaced. Thus, damage to the nervous system is irreparable and cumulative.

Often, as attested by even serious debilitating diseases, like Parkinson's disease or Alzheimer's disease, neuropathies do not present an immediate risk of death. Yet they harm the most essential, intimate human organ, that associated with all uniquely human qualities: the brain.

The impact on an individual's quality of life when an impairment is sustained in memory, intelligence or motor skills is incalculable. The cumulative effect for society of diminished intellectual capacity (analytical abilities, information processing abilities, memory, intelligence) at the level of a population is hard to assess. The devastating emotional impact is clear for those with relatives or friends suffering from neurological diseases.

As long as systematic, comprehensive epidemiological studies are not conducted with human populations currently exposed to inhalation or ingestion of MTBE in the air or contaminated water, uncertainty will remain about the possibility of neurotoxic effects for the general population or for specially vulnerable sub-populations.

At best, a massive experiment is being conducted and no one is collecting the data. At worst, significant neurological damage is being sustained by segment of the population with unknown and possibly immeasurable consequences.



Gasoline contains other components long recognized as hazardous for human health. Therefore, people will tend to exercise some degree of caution when handling reformulated gasoline. The discovery of MTBE contamination in wells, however, raises additional concerns. When leakage from underground tanks or pipes occurs, MTBE diffuses faster and farther than other gasoline components and it stays in the environment longer. Its solubility in water and its high partition coefficient with soil allows it to diffuse faster than other components of gasoline and its rate of degradation is slower, especially when not vulnerable to photolysis. People may be exposed to MTBE without their knowledge. Exposure to low levels of MTBE by ingestion increases the exposure burden already present through inhalation.


The two main products of MTBE degradation are toxic. As MTBE degrades and ceases to directly pose a risk it creates substances, formaldehyde and TBA (TERTIARY BUTYL ALCOHOL), which pose well documented risks to human health.

The enzyme that catalyzes MTBE in the human body saturates. Therefore larger doses or prolonged exposure does not only have a cumulative effect but exposure to additional MTBE poses a larger risk.


The safest course of action would be to responsibly phase out MTBE and replace it with a safer alternative. If this alternative is chosen, sufficient time should be allowed for an orderly and cost- effective transition to alternatives which would accomplish the same fuel-efficiency and clean-air goals.

While MTBE use in reformulated fuels is phased out, as long as any significant amounts remain in the environment (i.e., in contaminated wells) or if MTBE continues to be used as a gasoline additive, minimum protective measures should include:

1. Strict monitoring of levels of MTBE and its degradation products - in particular TBA and formaldehyde - in the air and water.

2. Thorough monitoring of MTBE and TBA blood levels when there is likelihood of exposure.

3. Require industry to effectively inform residents or workers in areas where MTBE is present of what are the symptoms associated with MTBE exposure. Provide hot-line to take in reports.

4. Serious epidemiological investigation of complaints of adverse health effects.


(Complete list available on request)

1. EPA Testing Consent Order on Methyl Tertiary Butyl Ether and response to the Interagency Testing Committee (1988), Federal Register 53(62) 10391-10394

2. Gill, M.W. (1989) "Methyl Tertiary Butyl Ether "Single exposure vapor inhalation neurotoxicity study in rats", Bushy Run Research Center Report 52-533

3. Daughtrey, W.C., Gill, M.W., Pritts, I.M., Douglas, J.F., Kneiss, J.J. and Andrews, L.S. (1997), "Neurotoxicological evaluation of Methyl Tertiary Butyl Ether in rats", Journal of applied toxicology, In Press (manuscript available upon request)

4. Burbacher, T.M. (1993), "Neurotoxic effects of gasoline and gasoline constituents", Environmental Health Perspectives 101 (s6): 133-141

5. Moolenar, R.L., Hefflin, B.J., Ashley, D.L. Middaugh, J.P. , and Ezel, R.A. (1994), "Metyl Tertiary Butyl Ether in human blood after exposure to oxygenated fuels in Fairbanks, Alaska", Archives of Environmental Health, 49: 402-409

6. "An investigation of exposure to Methyl Tertiary Butyl Ether in oxygenated fuels in Fairbanks, Alaska", September 14, 1993, National Center for Environmental health, Centers for Disease Control and Prevention

7. Middaugh, J.P. (1994), "Reacting to gasoline additives", Science 263:1545

8. "Neurotoxicity: identifying and controlling poisons of the nervous system", Office of Technology Assessment, Congress of the U.S., April 1990.