Exposure to MTBE and Acute Human Health Effects: A Critical Literature Review

Whether use of oxygen-rich gasoline additives to reduce air pollution is a cause of acute adverse health effects is an ongoing concern in the United States. Attention has focused in particular on use of methyl tert-butyl ether (MTBE, CAS #1634-04-4) and, despite considerable published research, debate persists regarding its potential for adverse health effects. To better understand the debate, we critically reviewed published and unpublished reports to assess whether differences in methodological approach or quality could explain the variable results reported. We considered studies on acute human health effects of inhalation exposure to MTBE either alone or in gasoline (19 reports) as well as clinical use of parenteral MTBE to dissolve cholesterol gall stones (12 reports). Each study was reviewed from three perspectives (epidemiology, industrial hygiene, and, clinical diagnostics), judged satisfactory, limited adequacy, or unsatisfactory for each criterion, and grouped into one of three categories from most to least adequate in overall methodology. The studies judged most adequate on individual criteria and those with highest overall adequacy found no significant association between MTBE exposure and symptoms. We propose that the persistent debate has been fueled by the findings of methodologically weak hypothesis-generating studies.