In the United States, the Food and Drug Administration (FDA) regulates the safe use of food ingredients, including food additives. Food additives are subject to FDA premarket review and approval, a process conducted by FDA scientists to evaluate the additive's safety for the intended conditions of use. Typically, an acceptable daily intake level is established by toxicologists based on the highest no observable adverse effect level for the most sensitive noncancer toxicity end point determined from a pivotal nonclinical study with application of an appropriate safety factor. Utilizing other information, including the additive's use and exposure levels, a safety determination (reasonable certainty of no harm) is made. During ongoing safety assessments, pathologists are often consulted by toxicologists for case-specific reasons, which may include verifying that an observed pathological effect is treatment related and adverse, confirming the determination of the pivotal study, endorsing a mode of action, or evaluating the human relevance of a toxicological effect found in experimental animals. Last year, the FDA took regulatory action to no longer allow the use of the food additive myrcene, a synthetic flavoring agent, based on results from National Toxicology Program carcinogenicity studies. The cancer and noncancer end points from the rat studies are discussed.
Keywords: food additive; myrcene; pathology; regulatory review; toxicology.