The United States Food and Drug Administration initially stated in 1976, and reiterated its position in 2006, that when inhaled, ozone is a toxic gas which has no demonstrated safe medical application, though their position statements primarily deal with its potential for causing inflammation and pulmonary edema in the lungs. They also emphasize that in order for ozone to be effective as a germicide, it must be present at concentrations far greater than can be safely tolerated by humans or other animals. More recent reviews have highlighted that different routes of administration may result in different therapeutic and side effect profiles, though a statistically robust meta-analysis of available research has not been performed to date.