This assessment is the first phase of a comprehensive evaluation of oxygenated fuels now being conducted under the coordination of the National Science and Technology Council's Committee on Environmental and Natural Resources (CENR). The present document does not address the potential health benefits of the oxygenated gasoline program, nor does it compare risks of oxygenated gasoline to the risks of conventional gasoline. The assessment focuses on exposures to oxygenates and oxygenated gasoline which occur through inhalation; other routes of exposure not addressed here, such as through contaminated groundwater, may also be an issue, but are being considered in the next phase.
Methyl tertiary butyl ether (MTBE) has become the most widely used motor vehicle fuel oxygenate in the U.S., though in some areas, ethanol is the dominant oxygenate used for motor vehicle fuel. Typically, MTBE-oxygenated gasoline in the winter oxygenate program contains approximately 15% MTBE by volume. The Clean Air Act requires at least a 2.7% oxygen content for gasoline sold in CO nonattainment areas, and 15% MTBE achieves this requirement. This assessment focuses primarily on MTBE. Emphasis on MTBE reflects its widespread use, but does not imply that this is the only oxygenate of concern. Because of limitations of available data, this assessment does not address to the same degree other oxygenates, such as ethanol, ethyl tertiary butyl ether (ETBE), tertiary amyl methyl ether (TAME), tertiary amyl ethyl ether (TAEE), and diisopropyl ether (DIPE). Ethanol is an exception for which the data base is extensive, but it pertains primarily to ethanol ingestion, not inhalation exposure to an ethanol/gasoline blend.
The second phase of this assessment process will evaluate the scientific literature related to the potential health risks associated with MTBE and other fuel oxygenates in gasoline relative to conventional gasoline. It will also assess risks associated with groundwater contamination, changes in air quality, benefits associated with reduced emissions or improved air quality, and engine performance and fuel economy. The second phase is anticipated to be completed by mid-1996.
This document was prepared by scientists from three federal agencies (the Centers for Disease Control and Prevention (CDC), the National Institute of Environmental Health Sciences (NIEHS), and the Environmental Protection Agency (EPA)), under the guidance of an Interagency Oxygenated Fuels Assessment Steering Committee. The initial assessment and its peer review were completed in an intensive effort over a two-month period. The final draft then underwent a second round of external peer review.
The three controlled human-exposure studies of MTBE among healthy human volunteers provide a consistent picture: exposure to pure MTBE in air at concentrations as high as 50 ppm under laboratory conditions did not cause increased symptoms or any notable measurable responses. (In oxygenated gasoline, however, MTBE is present as part of a complex gasoline mixture, and this mixture has not been tested under controlled exposure conditions.) These findings also do not rule out the possibility that a subpopulation of people in the general population may be especially sensitive to MTBE alone or in gasoline, or that effects might be associated with exposure to evaporative or combustion emissions from oxygenated gasoline or with some other factor that has not yet been characterized. Studies in animals have not provided evidence of overt neurotoxicity due to MTBE exposure at air concentrations from 100 ppm to 3000 ppm MTBE, but neuroactive properties are displayed at higher concentrations.
With regard to human exposures to MTBE, the assessment concludes that data are too limited for a quantitative estimate of the full range of exposures to MTBE among the general population. Less information is available on exposures to oxygenates other than MTBE. The limited data available on air quality and micro environments (e.g., at gasoline pumps, inside cars, in personal garages) were used to estimate reasonable worst-case (high-end) potential exposures on the basis of certain assumed activity patterns and approximate micro-environmental concentrations.
Studies of MTBE metabolism in experimental animals demonstrated that the metabolism and elimination of MTBE and its metabolites proceeded rapidly regardless of the route of administration. Among humans, clearance of most of the internal dose of MTBE is rapid, but a small fraction is slowly eliminated from the body.
The available scientific evidence regarding human exposure to oxygenated gasoline and acute health symptoms was considered insufficient to develop estimates of exposure-related effects.
Considering the magnitude and duration of exposures in the animal studies and the association of developmental effects with maternal toxicity, it is concluded that MTBE is not expected to pose a reproductive or developmental health hazard under the intermittent, low-level exposures experienced by humans. The EPA reference concentration for other chronic noncancer health effects for MTBE (0.83 ppm) is higher than the reasonable worst-case annual average daily exposure estimate (0.019 ppm).
While there are no studies on the carcinogenicity of MTBE in humans, MTBE should be regarded as posing a potential carcinogenic risk to humans based on animal cancer data. Experimental studies in rats and mice indicate that MTBE is carcinogenic at multiple sites after oral or inhalation exposure. The primary metabolites of MTBE, tertiary butyl alcohol (TBA) and formaldehyde, are also carcinogenic in animals. No studies have been reported on the carcinogenicity of ETBE or TAME.
Based on the animal carcinogenicity data, estimates of human cancer risk for lifetime exposure to MTBE (70 years) were calculated, recognizing that there are large uncertainties in the distribution of exposures to MTBE in the population and in the estimates of human cancer potency. To deal with these uncertainties several assumptions were made in order to estimate potential low dose responses in humans. Thus, depending on the validity of the assumptions used in making these estimates, the actual cancer risks could even be nearly zero.
It is not known whether the cancer risk of oxygenated gasoline containing MTBE is significantly different from the cancer risk of conventional gasoline. The estimated upper bound cancer unit risks of MTBE are similar to or slightly lower than those of fully vaporized conventional gasoline, which has been listed by EPA as a probable human carcinogen based on animal carcinogenicity data. However, because of a lack of health data on the nonoxygenated gasoline vapors to which humans are actually exposed, it is not possible to have a reasonably good estimate of population cancer risk to conventional gasoline. The estimated upper bound cancer unit risk of MTBE (i.e., cancer potency) is approximately an order of magnitude lower than that of benzene, a constituent of gasoline that is classified as a known human carcinogen, and more than 100 times less than that of 1,3-butadiene, a carcinogenic emission product of incomplete fuel combustion. The comparative risk among oxygenated and nonoxygenated gasoline types has not been established.
The data were generally inadequate to evaluate the health risks of oxygenates other than MTBE, a factor which makes other oxygenates and gasoline mixtures to which they are added all the more important to investigate further.