International scientific committees, regional scientific committees such as those of the European Union, and national regulatory agencies generally use the uncertainly factor approach for establishing acceptable or tolerable intakes of substances that exhibit thresholds of toxicity. No observed adverse effect levels (NOAELs) are identified in the critical studies to which appropriate uncertainly factors are applied to allocate acceptable daily intake (ADI). This paper discusses the different steps of the risk assessment process considered for decades worldwide a pragmatic approach to allocate safe doses, yet in need of improvements during the extrapolation phase which could increase the confidence level of the work performed by risk assessors.