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Methyl tert-butyl ether (MTBE) and its Effects on Humans and Animals
Tameka B. Dew, Tony Chung and Antonio F. Machado
Dept. of Environmental and Occupational Health, California State University, Northridge
ABSTRACT
MTBE METABOLISM AND METABOLITES
MTBE is an ether that is produced in large amounts in the United States. It is mainly
The mechanism for MTBE metabolism is important because MTBE and its metabolites may cause renal toxicity, cell proliferation, renal tumors,
exported to other countries as a fuel additive. MTBE is a concern because it is highly
liver tumors and testicular tumors.[1] Another reason it is important is because the metabolites can be used as a marker for exposure to MTBE.[1]
soluble, moves quickly into ground water and stays in the environment for long periods of Pathways for the degradation of MTBE is by CYP-450. Kinetic studies have shown that CYP-2A6 has a significant role in the metabolism of
time. Human and environmental exposures to MTBE are extensive; human health effects MTBE.[27]
are unknown but many studies on animals and microorganisms have been studied.
The main intermediate products in the metabolism of MTBE [27]:
Animals studies have shown shown the carcinogenicity and toxicity of MTBE but more ① Tert-butyl alcohol (TBA)
information is needed on the adverse effects on human health. This project will review
② Formaldehyde
the available information on the effects of MTBE and the potential effects of MTBE on ③ Tert-butoxy methanol
human health, fate and transport, remediation and regulations.
④ 2-methyl-2-hydroxy-1-propanol
⑤ 2-hydroxy isobutyric acid
⑥ Acetone
INTRODUCTION
⑦ Acetaldehyde
MTBE is used as a solvent and fuel additive that is added to unleaded gasoline to
increase the oxygen content and to decrease carbon monoxide emissions. MTBE is a
synthetic chemical made from isobutylene and methanol. MTBE is volatile and
lipophilic. It is a colorless flammable liquid that has a very high mobility in soil and is
FATE AND TRANSPORT
resistant to degradation. [19] The properties of MTBE is a greater problem when it
contaminates ground water because it resist biodegradation, moves rapidly through
① MTBE enters the environment during all phases of the
aquifers, and remains at high levels for longer periods of time. [10]
petroleum fuel cycle (auto emissions, evaporative
loss, gasoline stations, vehicle & storage tank
MTBE cancer bioassays have provide evidence of carcinogenicity in experimental
releases, pipeline leaks, accidental spills, and refinery
animals. Inhalation and oral study in male rats resulted in kidney and testicular tumors,
releases [19]
female rats resulted in leukemia and lymphoma. MTBE is not classifiable as to its
carcinogenicity to humans because there is no epidemiological evidence. The American
Conference of Governmental Industrial Hygienists (ACGIH) classify MTBE as a
Confirmed Animal Carcinogen with unknown relevance to Humans.[20] The U.S.
① The release of MTBE into the environment
Environmental Protection Agency (USEPA) has tentatively classified MTBE as a
contaminates air, soil and water [19]
possible human carcinogen.[24]
ECOTOXICOLOCIAL EFFECTS OF MTBE
Species
MTBE
Concentration
Effects
Zebra fish
(Danio Rerio) [23]
0.11 and 37 mg/L
• Increases vitellognin
synthesis in males.
• Lowers fish sperm motility.
Bacteria
(Streptomyces spp.) [7]
1/800
Minimum Inhibitory
Concentration (MIC)
• Suppresses the growth of
Streptomyces.
• Changes the balance of soil
micro flora.
2400 mg/L
Reduces growth and changes
algal community composition.
Algae [26]
(Navicula pelliculosa,
Synechococcus leopoliensis)
① MTBE is highly soluble so it moves rapidly through
soil and into ground water. [19]
① Contamination of water supply leads to exposure
when water is drunk. [12]
CHEMICAL STRUCTURE
MTBE travels easily in soil through which it migrates quickly to groundwater. It is highly
soluble in groundwater and biodegrades very slowly. In surface water MTBE volatilizes
easily and as a result it is usually detected at lower concentration than groundwater. The
physical and chemical properties of MTBE makes it likely to contaminate public drinking
water system.
Groundwater (2743 samples) [22]
Mean concentration range of MTBE
< 0.2 μg/l
4.9%
0.2 – 20 μg/l
0.4%
> 20 μg/l
 Inhalation is another MTBE exposure
route.[24]
REMEDIATION
HEALTH EFFECTS OF MTBE
REGULATION
There are various health complaints documented following MTBE exposure. In particular residents of Fairburn, Alaska reported
symptoms such as headaches, dizziness, nausea and respiratory irritation following an oxygenated fuel program using 15% volume
MTBE [20]. Currently, the are no definitive human health effects of MTBE but there are concerns regarding the carcinogenicity, the
cytotoxicity and the oxidative stress induced by MTBE in rodents. [8,12]
MTBE Induces Cytotoxicity and Oxidative Stress on
Carcinogenic Effects of MTBE in Rats
Spermatogenic and Sertoli cells in Male Rats
Agency
Type of Regulation
Regulation Levels
Date of
Effective
USEPA
Drinking Water Advisory
20-40 ppb
12/1997
Cancer bioassay in SragueDawley Rats
Cancer bioassay in Fischer
344 rats
ATSDR
Acute Inhalation Minimal Risk Level
Chronic Inhalation Minimal Risk Level
Acute Oral Minimal Risk Level
Intermediate Oral Minimal Risk Level
2.0 ppm
0.7 ppm
0.4 mg/kg/day
0.3 mg/kg/day
08/1996
8 week old rats were gavage with 0,
250 and 1000 mg/kg b.w. of MTBE
over 104 weeks until death at 166
weeks. [4]
Fischer 344 rats were exposed
to 3000 and 8000 ppm MTBE
via inhalation for 24 months.
[5]
ACGIH
Threshold Limit Value
Time weighed average
100 ppm 8-10hr
California
Secondary MCL
EPA complete Ban
5.0 ppb
01/07/1999
12/31/2003
Result
Significantly higher incidence
of renal and Leydig cell
adenomas were reported in
male rats.
No more than trace
amounts (0.5% by
vol.) MTBE.
5/11/2000
2/28/2001
Results
Higher incidence of Leydig
interstitial cell tumors of the testes
in male rats and increase
lymphomas and leukemia in female
rats.
Iowa,
EPA Partial Ban
South Dakota
 High concentrations of MTBE in gasoline
contaminates soil, surface water, and ground
water by point sources of oxygenated
gasoline.[24]
1. Granular activated carbon (GAC) is the most popular adsorbent
used to remove MTBE from contaminated water and has been
proven as a successful MTBE remover. [16]
2. Carbonaceous resins of Ambersorb 563 and 572 has high
adsorption capacity for MTBE in water. [16]
3. Zeolite with appropriate pore size as adsorbent removal.
4. Nafion as a solid catalyst for the MTBE removal from aqueous
solutions. [20]
5. Removal of MTBE by the PAM-zeolite composite. [15]
6. Native microbial bioremediation. [15]
7. Ultraviolet-Base Ozone and Hydrogen Peroxide. [29]
LEVELS IN ENVIRONMENT
94.7%
 In the United States, almost all MTBE is used
as a fuel oxygenate in gasoline. [24]
• MTBE induces oxidative stress on spermatogenic cells
and Sertoli cells of the testis of rodents. Notably, testicular
cell membrane are vulnerable to oxidative stress because
they are high in polyunsaturated fatty acids that are
susceptible to lipid peroxidation. [17]
• In addition there was significant increase of the enzyme
oxoguanine DNA glycosylase (Ogg1), which repairs DNA
impaired by oxidative stress. Suggesting that Sertoli cells
of the testis were damaged at the DNA levels following
exposure to MTBE. [17]
• MTBE impedes testicular cell function and therefore is
likely hinder spermatogenesis or may even lead to cell
death. [17]
There are also notable changes to liver, thyroids and adrenals of
rodents administered MTBE in published studies. [8,12]
Study on Hsp60, a stress protein in human nasal
septa cell
Minnesota,
EPA complete ban
2000
To ascertain Hsp60 expression as a biomarker for MTBE
EFFECTS ON REPRODUCTIVE SYSTEM
Nebraska and
exposure, human nasal septum cells were exposed to
OF MALE RATS
Colorado
MTBE concentrations ranging from 0 to 1000μg/l. Notably,
Many in vitro and in vivo studies have shown the carcinogenicity and the concentrations used in the study correspond to the blood
MTBE contamination of Santa Monica, Ca. Charnock well field
• In 1995 the city of Santa Monica detected MTBE concentrations that peaked at 610μg/L in their toxicity of MTBE. Subacute exposure of MTBE studies have also levels measured in residents of US regions that had health
demonstrated how MTBE has a significant adverse effect on the complaints following MTBE exposure. Also the levels of
water wells. [14]
reproductive system of male Sprague Dawley rats. [18]
• It was found that MTBE leaked from underground storage tank at nearby gasoline stations.
MTBE used in study were relevant to those measured in
• This resulted in loss of approximately 6 million gallon per day of groundwater supply.
ground water samples. [6]
• Consequently the city of Santa Monica filed a lawsuits against several oil companies and Effects observed
① Increase in abnormal sperm
currently there are ongoing remediation. [9]
② Irregular and disordered arrangement of the seminiferous epithelium Results
③ Change in levels of testosterone (T)
CONCLUSION
There was a 2-fold increase in the expression of stress
④ Change in luteinizing hormone (LH)
protein Hsp60 in human nasal septum cells after MTBE
Based on findings of the animal studies and the physiochemical properties of MTBE the EPA ⑤ Change in follicle stimulating hormone (FSH)
exposure. [6]
should reconsider a safer fuel additive than MTBE. The current EPA drinking water advisory of ⑥ Decrease levels of mRNA
20-40 ppb is based on taste and odor is more concerned with the aesthetics of drinking water for ⑦ Decrease levels of androgen binding proteins (ABP)
The findings of the present study suggest that MTBE
consumer consumption. To increase the margin of safety for the public further epidemiology
induces stress on the human respiratory system. [6]
studies should be conducted on MTBE.
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4. Belpoggi, F. , Soffritti, M. , & Maltoni, C. (1995). Methyl-tertiary-butyl ether (mtbe)--a gasoline additive--causes testicular and lymphohaematopoietic cancers in rats. Toxicology and Industrial Health, 11(2), 119-149.
5. Bird, M.G., Burleigh-Flayer, H.D., Chun, J.S., Douglas, J.F., Kneiss, J.J., Andrews, L.S., 1997. Oncogenicity studies of inhaled methyl tertiary-butyl ether (MTBE) in CD-1 mice and F-344 rats. J. Appl. Toxicol. 17 (Suppl.1),S45–55.
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