International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 73 (1999) (p. 339)

Chem. Abstr. Serv. Reg. No.: 1634-04-4
Chem. Abstr. Name: 2-Methoxy-2-methyl-propane

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Methyl tert-butyl ether is a volatile synthetic chemical that has been used widely since the 1980s in proportions up to 15% as a component of gasolines for its octane-enhancing and air pollution-reducing properties. Exposure to methyl tert-butyl ether may occur through inhalation and skin contact during its production, formulation, distribution and use, either as methyl tert-butyl ether or in gasoline. In the petroleum industry, the average exposure is generally below 5 ppm (20 mg/m3), although higher exposure occurs during some operations. In service stations where fuels containing > 10% methyl tert-butyl ether are delivered, the average concentration to which attendants are exposed is about 0.5 ppm (2 mg/m3). The ambient air concentrations in regions where methyl tert-butyl ether-rich gasoline is used are usually 15 ppb (420 m g/m3), while in other regions they are below 1 ppb (4 m g/m3). During self-service refuelling, individuals may be exposed to levels up to 10 ppm (40 mg/m3) or more for a few minutes. Methyl tert-butyl ether has been detected in a small percentage of drinking-water samples in the United States.

5.2 Human carcinogenicity data

Although methyl tert-butyl ether has been in commercial use for gasoline blending since the 1970s, no analytical epidemiological studies have addressed a possible association of methyl tert-butyl ether with human cancer.

5.3 Animal carcinogenicity data

Methyl tert-butyl ether was tested for carcinogenicity in a non-standard protocol in rats by gavage. The incidences of Leydig-cell tumours of the testis in males and of lymphomas and leukaemias combined in females were increased. Methyl tert-butyl ether was tested by inhalation in one experiment in mice and in one experiment in rats. It increased the incidence of hepatocellular adenomas in female mice and that of renal tubular tumours in male rats in a non-dose-related manner.

tert-Butyl alcohol, a metabolite of methyl tert-butyl ether, marginally increased the incidence of follicular-cell adenomas of the thyroid in female mice.

5.4 Other relevant data

Methyl tert-butyl ether is metabolized in humans and rodents to tert-butyl alcohol. In both species, methyl tert-butyl ether is cleared from blood rapidly whereas tert-butyl alcohol accumulates and is cleared at a slower rate than the parent compound. In rats exposed to methyl tert-butyl ether, the metabolites identified in urine include tert-butyl alcohol, its sulfate and glucuronide conjugates, 2-methyl-1,2-propanediol and 2-hydroxyisobutyrate.

No significant acute effects on human health were seen after exposure of volunteers by inhalation to methyl tert-butyl ether itself or of service-station attendants to gasoline.

In male rats, methyl tert-butyl ether-induced kidney lesions were associated with a 2u-globulin nephropathy, a male rat-specific response. Exposure of female mice to 8000 ppm methyl tert-butyl ether in air was mitogenic to the liver and caused changes in oestrogen-regulated tissues.

Methyl tert-butyl ether did not induce developmental toxicity in rats or rabbits exposed via inhalation to concentrations that affected maternal food consumption. In one study in mice, increased incidences of postimplantation loss and cleft palate were seen at doses that also induced hypoactivity, ataxia and reduced food consumption in the dams. Another study in mice, conducted at lower doses that were less toxic to dams, did not provide evidence of developmental toxicity.

No data were available on the genetic and related effects of methyl tert-butyl ether in humans. The few available data indicate that methyl tert-butyl ether is not genotoxic in experimental systems.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of methyl tert-butyl ether.

There is limited evidence in experimental animals for the carcinogenicity of methyl tert-butyl ether.

Overall evaluation

Methyl tert-butyl ether is not classifiable as to its carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.


Last updated: 30 September 1999

    See Also:
       Toxicological Abbreviations
       Methyl tert-butyl ether (ICSC)