nized as safe” (GRAS) by qualified experts in light of scientific procedures or, for substances used prior to 1958, in light of scientific procedures or experience based on common use in food. As discussed in the next section, FDA has in place a process for assessing the worthiness of claims of GRAS status.
FDA conducts safety assessments of new food additives under the principle of establishing a reasonable certainty of no harm by applying a decision framework. This framework uses a risk-assessment approach that includes the compilation of available data and information and the application of toxicological and other types of decision elements.
FDA then reviews the available toxicology studies. It has developed guidelines (Toxicological Principles for the Safety of Food Ingredients, commonly known as The Redbook [OFAS, 2003]) for interested parties to use when assembling the required data for submission of a food additive petition. The Redbook outlines the types of toxicological testing FDA normally expects to be provided in support of the food additive’s safety, based initially on the additive’s chemical structure and probable human exposure. (The Redbook provides guidance; it does not include requirements.) Using the information submitted, FDA assigns additives to initial “concern levels” (or “minimum testing levels”) of I, II, or III. In its data review, FDA applies toxicological decision elements to further refine the scope of needed toxicological data.
From the animal studies, FDA determines the highest level of intake associated with no adverse toxicological effect in the most sensitive, longest duration, most relevant animal study. This “highest no-effect level” is then divided by an “uncertainty factor” (or “safety factor”), often a factor of 100, to account for both intra- and interspecies variability. The resulting value is the acceptable daily intake (ADI) for the additive. The ADI is compared to the estimated daily intake to determine whether the proposed use of the additive is consistent with a reasonable certainty of no harm.
For some substances, the traditional risk assessment approach is not applicable. For example, an additive may be so toxicologically inactive that not enough of the additive can be orally ingested by the test animals to elicit a toxic response without perturbing normal nutrition. In such cases it is difficult to determine an ADI. FDA may then employ other types of decision elements. In these cases, increased emphasis may be placed on, for example, chemical identity information and structure-activity relationships; data on absorption, distribution, metabolism, and excretion; and human tolerance studies (to look at physiological and nutritional responses).
Once all the information has been evaluated, FDA concludes whether the proposed use of a food additive is consistent with a reasonable certainty of no harm and can be safely marketed. After a new food additive is on the market, FDA may monitor the substance for safety through examination of