As part of their product stewardship efforts and in preparation for the IARC review of gasoline and certain oxygenated components, Sustainable Fuels, ACFA and ACELA commissioned a review conducted by ToxStrategies, an independent scientific consultancy, of all studies available to identify data on how MTBE, ETBE and their common metabolite TBA behave as potential carcinogenic, genotoxic, and mutagenic substances. This review (Borghoff et al. 2025) was based on sound science and research, and conducted in line with the general principles and procedures for conducting cancer hazard evaluations, such as the Key Characteristics of Carcinogens (KCC) approach. The findings from this review result in :
• Inadequate evidence from a single human epidemiological study: this study is considered unreliable based on study design and lack of clarity in the relationship between exposure to ethers and tumor outcomes.
• Limited evidence on cancer studies performed on living organisms. High levels of ethers exposure provoked a low incidence of tumors in the liver of female mice and in the kidneys and brain of male rats. It is important to note that the way these tumors develop does not apply to humans.
• Limited evidence on mechanistic data (genotoxicity and other mechanistic data): no mechanistic data are available in humans. Overall evidence in relevant models indicates that ethers and TBA are not mutagenic or genotoxic, mainly due to inconsistent activity in all available data assessed (mechanistic studies of living organisms, human cell lines, and mammalian primary cells or cell lines).

Our review of the available data demonstrates that MTBE, ETBE and TBA are unlikely to be a carcinogenic hazard for humans based on the evidence gathered and assessed across human (inadequate evidence), living organism cancer studies (limited evidence), and mechanistic data (limited evidence).