Biomonitoring Summary

Methyl tert-butyl ether (MTBE)

CAS No. 1634-04-4

General Information

Methyl tert-butyl ether (MTBE) was added to reformulated gasoline to boost octane and to reduce carbon monoxide exhaust emissions in high smog areas of the United States in the1980s. Because of concerns for groundwater contamination and water quality, MTBE was banned or its usage was limited in several states. Ethanol has replaced MTBE as an additive to reformulated gasoline (U.S. DOE, 2003 and 2006; U.S. EPA, 2000). MTBE contamination of groundwater has been more common in urban areas (Squillace et al., 2004) and in areas near leaking underground storage tanks (Rowe et al., 2007). MTBE also has been detected in ambient air near blending facilities, in cities where MTBE is used in reformulated gasoline, and in the breathing zone during consumer refueling at service stations (IPCS, 1998). MBTE is also used in small amounts as a laboratory solvent and as a pharmaceutical agent (ATSDR, 1996).

The general population is exposed to MBTE primarily by inhalation of contaminated air. Contaminated water is a less common source though exposure can occur by ingestion or inhalation of vaporized MTBE from water (IPCS, 1998). Workplace exposure to MTBE may occur in the production, transportation, and use of petrochemicals. MTBE is well absorbed after inhalational, oral, or dermal exposure and is rapidly cleared from the blood with an estimated half-life of several hours (Dekant et al., 2001). Most MTBE absorbed by the body is metabolized by the liver and then eliminated in urine, primarily as 2-hydroxyisobutyrate with tert-butyl alcohol and 2-methyl-1,2-propanediol as minor urinary metabolites (Amberg et al., 1999; Amberg et al., 2001). Depending upon the dose, more than one third of inhaled MTBE may be excreted in exhaled air (ATSDR, 1996; Nihlen et al., 1998).

Human health effects from MTBE at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Following the introduction of MTBE reformulated gasoline, complaints of respiratory tract irritation, headache, nausea, and dizziness prompted several population surveys, epidemiologic studies, and experimental human volunteer studies that provided little evidence of an association between MTBE exposure and health complaints (ATSDR, 1996). Based upon high dose animal studies, MTBE has been considered to be a skin and eye irritant (IPCS, 1998). Animal studies of carcinogenicity have been inconclusive (ATSDR, 1996). MTBE does not appear to be a reproductive or developmental in animal studies (IPCS, 1998). Methyl tert-butyl ether is unclassifiable as a human carcinogen by IARC. The U.S. EPA has established standards and guidelines for MTBE in water and air, and ACGIH has adopted guidelines for workplace air exposure. Information about external exposure (ie., environmental levels) and health effects is available from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Levels of MTBE in blood reflect recent exposure. In the NHANES 2001-2002, 2003-2004 and 2005-2006 subsamples, MTBE was detectable in most of the population; geometric means have decreased over time, from 16.4 to 6.16 pg/mL for the total population. In a subsample of adults in NHANES 1999-2000, Lin et al. (2008) found geometric mean blood levels of MTBE to be 17 and 15 pg/mL in smokers and non-smokers, respectively. In a small study of U.S. automobile drivers when MTBE was used as a fuel additive, blood levels were about 100 times higher than those in the NHANES subsamples (White et al., 1995). Commuters in urban areas with high vehicular traffic had median blood MTBE blood levels that were more than tenfold higher than those in the U.S. general population (Lemire et al., 2004). Workers exposed to oxygenated gasoline fumes and vehicle exhaust had levels that were by 10 to 100 times higher than general population levels (Mannino et al., 1995; Moolenaar et al., 1994; Romieu et al., 1999; White et al., 1995), depending in part on the concentration of MTBE in the gasoline.

Finding a measurable amount of MTBE in blood does not imply that the level of MTBE causes an adverse health effect. Biomonitoring studies of blood MTBE can provide physicians and public health officials with reference values so that they can determine whether or not people have been exposed to higher levels of MTBE than levels found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for methyl tert-butyl ether. 1996 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=228&tid;=41. 8/3/12

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):1-8.

Amberg A, Rosner E, Dekant W. Toxicokinetics of methyl tert-butyl ether and its metabolites in humans after oral exposure. Toxicol Sci 2001;61(1):62-67.

Dekant W, Bernauer U, Rosner E, Amberg A. Biotransformation of MTBE, ETBE, and TAME after inhalation or ingestion in rats and humans. Res Rep Health Eff Inst 2001;102:29-71.

International Programme on Chemical Safety (IPCS). Environmental Health Criteria 206. Methyl Tertiary-Butyl Ether. Geneva, Switzerland.1998 [online]. Available at URL: http://www.inchem.org/documents/ehc/ehc/ehc206.htm. 8/3/12

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, Meneses-Gonzalez F, Hernandez-Avila M. Environmental exposure of commuters in Mexico City to volatile organic compounds as assessed by blood concentrations, 1998. Salud Publica Mex 2004;46:32-38.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels of volatile organic compounds in air and blood from the general population. J Expo Sci Environ Epidemiol 2008;18(4):421-429.

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(1):59-64.

Moolenaar RL, Heffline BJ, Ashley DL, Middaugh JP, Etzel RA. Methyl tertiary butly ether in human blood after exposure to oxygenated fuel in Fairbanks, Alaska. Arch Environ Health 1994;49(5):402-409.

Nihlen A, Lof A, Johanson G. Experimental exposure to methyl tertiary-butyl ether. I. Toxicokinetics in humans. Toxicol Appl Pharmacol 1998;148:274-280.

Romieu I, Ramirez M, Meneses F, Ashley D, Lemire S, Colome S, et al. Environmental exposure to volatile organic compounds among workers in Mexico City as assessed by personal monitors and blood concentrations. Environ Health Perspect 1999;107(7):511-515.

Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. Occurrence and potential human-health relevance of volatile organic compounds in drinking water from domestic wells in the United States. Environ Health Perspect 2007;115(11):1539-1546.

Squillace PJ, Moran MJ, Price CV. VOCs in shallow groundwater in new residential/commercial areas of the United States. Environ Sci Technol 2004;38(20):5327-5338.

United States Environmental Protection Agency (U.S. EPA). Advance notice of proposed rulemaking to control MTBE in gasoline. Regulatory Announcement. Office of Transportation and Air Quality. Federal Register: March 24, 2000 (Volume 65, Number 58) [online]. Available at URL: https://www.epa.gov/EPA-TOX/2000/March/Day-24/t7323.htm. 8/3/12

United States Department of Energy (U.S. DOE). Status and impact of state MTBE ban. 2003 [online]. Available at URL: https://www.eia.doe.gov/oiaf/servicerpt/mtbeban/. 8/3/12

United States Department of Energy (U.S. DOE). Eliminating MTBE in gasoline in 2006. 2006 [online]. Available at URL: https://www.eia.doe.gov/pub/oil_gas/petroleum/feature_articles/2006/mtbe2006/mtbe2006.pdf. 8/3/12

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(3):183-189.