The safety assessment of food additives and of flavoring agents resembles in a general fashion methods used for the safety assessment of chemical products. There are, however, specificities in the area of food safety. During the last 40 years, the assessment of food additives has employed some of the most advanced methodology to evaluate the risk resulting from the presence of xenobiotic compounds in food. Even if the general methodology of toxicological assessment has been widely studied, this methodology is not without failings and could be improved.