GENOTOXICITY TESTING OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN THE SALMONELLA MICROSUSPENSION ASSAY AND MOUSE BONE-MARROW MICRONUCLEUS TEST

Methyl tertiary-butyl ether (MTBE) is an oxygenated fuel additive that is present in gasoline at levels up to 15% by volume. Since the 1990 Clean Air Act amendments require the use of oxygenated gasoline in 39 areas of the USA, the use of MTBE is projected to continue to dramatic ally increase. As the use of MTBE increases, the potential for environ mental release of MTBE from gasoline stations and automobiles will als o increase. Despite its growing use as a fuel additive and its potenti al for increased exposure to the public, few genotoxicity data on MTBE have been published in the peer-reviewed literature, In the present s tudy, we tested the potential genotoxicity of MTBE in two short-term t est systems, an in vitro Salmonella microsuspension assay and an in vi vo mouse bone marrow micronucleus test. For the microsuspension assay, MTBE was tested at 7 dose levels of 30 to 7400 mu g/tube in tester st rains TA98, TA100, TA104, and TA1535, with and without the addition of metabolic enzymes (S9) at 4 concentrations (0, 300, 600, and 1200 mu g S9/ml final concentration). A closed system was used to minimize los s of MTBE. The response was not significant. However, a high degree of toxicity was observed at the highest doses in all tester strains. MTB E was also tested for clastogenicity in the mouse bone marrow micronuc leus test using both male and female Swiss-Webster mice. Mice were adm inistered single intraperitoneal injections of MTBE in olive oil at 5 doses ranging from 0.25 to 1.75 g/kg. Then were no significant increas es in micronucleus formation at any dose of MTBE when compared with th e negative control animals receiving only olive oil. MTBE was not posi tive when tested for point mutations and clastogenicity, using respect ively, a Salmonella microsuspension assay and the mouse bone marrow mi cronucleus test. (C) 1998 Elsevier Science B.V.