The current status of the GRAS evaluation program of flavoring substances operated by the Expert Panel of FEMA is discussed. The Panel maintains a rigorous rotating 10-year program of continuous review of scientific data related to the safety evaluation of flavoring substances. The Panel concluded a comprehensive review of the GRAS (GRASa) status of flavors in 1985 and began a second comprehensive review of the same substances and any recently GRAS materials in 1994. This second re-evaluation program of chemical groups of flavor ingredients, recognized as the GRAS reaffirmation (GRASr) program, is scheduled to be completed in 2005. The evaluation criteria used by the Panel during the GRASr program reflects the significant impact of advances in biochemistry, molecular biology and toxicology that have allowed for a more complete understanding of the molecular events associated with toxicity. The interpretation of novel data on the relationship of dose to metabolic fate, formation of protein and DNA adducts, enzyme induction, and the cascade of cellular events leading to toxicity provides a more comprehensive basis upon which to evaluate the safety of the intake of flavor ingredients under conditions of intended use. The interpretation of genotoxicity data is evaluated in the context of other data such as in vivo animal metabolism and lifetime animal feeding studies that are more closely related to actual human experience. Data are not viewed in isolation, but comprise one component that is factored into the Panel's overall safety assessment. The convergence of different methodologies that assess intake of flavoring substances provides a greater degree of confidence in the estimated intake of flavor ingredients. When these intakes are compared to dose levels that in some cases result in related chemical and biological effects and the subsequent toxicity, it is clear that exposure to these substances through flavor use presents no significant human health risk.