Revisions to the FDA's Redbook guidelines for toxicity testing: neurotoxicity

In 1982, the Food and Drug Administration issued a publication, known as the Redbook, that described the current toxicological principles used for the safety assessment of regulated food and color additives. However, this document contained only minimum reference to neurotoxicity as a specific toxicological concern and only general mention of the types of data that should be collected to detect and assess adverse changes to the nervous system. The general nature of the toxicological information typically derived from studies based on the original Redbook has had only limited use as a guide for comprehensive assessment of neurotoxic hazard. This limitation is one of the issues being addressed in the current efforts to update the information provided in the Redbook. In the revised Redbook, neurotoxicity, encompassing adverse structural and functional changes to the nervous system, is explicitly identified as an important criterion in the assessment of food chemical safety. The proposed strategy for evaluating neurotoxic hazard has a tiered testing approach. Accordingly, testing would initially involve the identification of chemicals presumptively associated with neurotoxic effects. As appropriate, subsequent testing would be carried out to confirm and delineate the scope of the neurotoxicity, to determine the dose response kinetics, and to define the no-adverse-effect levels.