Systematic Evaluation of the Evidence Base on Ethyl tert-Butyl Ether and tert-Butyl Alcohol for Carcinogenic Potential in Humans; Lack of Concern Based on Animal Cancer Studies and Mechanistic Data

Ethyl tertiary-butyl ether (ETBE) is a component of fuel and tert-butyl alcohol (TBA) is used as a solvent or manufacture agent for flotation agents and perfumes. TBA is also a primary metabolite of ETBE and methyl tert-butyl ether (MTBE). Exposure to either chemical has the potential to occur via all classical exposure routes: inhalation, oral and dermal. The objective of this assessment was to evaluate the human carcinogenic hazard of ETBE and TBA by assessing available human and animal cancer studies, as well as mechanistic data. A systematic literature search and review was conducted to identify relevant cancer studies and mechanistic data in exposed humans and in animal models. Mechanistic data were integrated and synthesized using key characteristics of carcinogens (KCCs). No human studies were identified for either ETBE or TBA while there were two ETBE and two TBA standard cancer bioassays in animal models. There was a low incidence of all tumors reported following exposure to ETBE (liver tumors) or TBA (kidney and thyroid tumors) at high exposure concentrations. ETBE and TBA lacked mutagenic and genotoxic activity. Together, these data support a non-genotoxic mechanism of tumor development that occurs at the highest ETBE/TBA exposure concentrations. Mechanistic evidence within the other KCCs was limited either due to a lack of data, or inconsistencies in activity across similar studies. This assessment supports an overall lack of concern for carcinogenic hazard of both ETBE and TBA in humans.