EPA’s assessment of tetrachloroethylene follows a traditional approach to developing cancer slope factors and hazard indexes that takes uncertainties into account qualitatively and via uncertainty factors. EPA states that it has introduced a new method for uncertainty analysis in the context of the dose-response assessments for tetrachloroethylene, but the only notable differences between its tetrachloroethylene assessment and those of other chemicals are the consideration of multiple end points and the limited use of bootstrap simulation for only a portion of uncertainties. EPA’s uncertainty analysis remained typically focused on individual sources of uncertainty, and the analysis was often qualitative without presenting a full range of the uncertainty. Without an in-depth illustration of the propagation and cumulative effect of the uncertainties on the final risk estimate, quantification of the overarching uncertainty surrounding the final risk assessment is not possible. The committee notes that the current state of practice in quantitative uncertainty analysis does not fully meet the spirit of principles, guidelines, and recommendations that have accrued in recent years.