The changing role of animal toxicology in support of regulatory decisions.

The Clean Air Act is the basic U.S. Federal law for controlling air pollution. Under Sections 108 and 109, primary (health) national ambient air quality standards (NAAQS) can be set for pollutants which are ubiquitous in the ambient air. The standard-setting process includes a comprehensive summary of scientific information on effects and controls in criteria and control techniques, and the selection of an appropriate standard which, in the judgment of the Administrator, protects the health of normal and susceptible subpopulations with an adequate margin of safety. Determining the adequacy of existing NAAQS or establishing new standards requires that the scientific information base be evaluated to assess pollutant effects on public health. Improvements in this process can be accomplished not only through new health effects research, but also through improved use of currently available data. The commonality joining these two efforts is in the area of extrapolation modeling, which is the topic of this paper. Extrapolation modeling involves determining the effective dose delivered to the target organ of several species and the sensitivity of the target organ to that dose so that effective pollutant concentrations can be estimated across species. This in turn allows greater utilization of the results from animals in making judgments about the effects in man from exposure to a given pollutant.