Food and Drug Administration Proposed Guidelines for Neurotoxicological Testing of Food Chemicals

The fact that some chemicals may adversely affect the nervous system is certainly not a new concept in regulatory toxicology. In 1982, the FDA issued testing guidelines for the safety evaluation of proposed direct food and color additives which included the assessment of nervous system toxicity as part of the general toxicological profile. However, these guidelines provide only broad and nonspecific recommendations as to how this assessment may best be carried out. The information derived from toxicity screening studies conducted according to these guidelines enable little more than the detection of clearly evident adult nervous system toxicity associated with general neuropathology and overt neurological dysfunction. Little consistent or systematically documented information is typically developed about other equally important types of neurotoxic effects including, for example, behavioral dysfunction and developmental neurotoxicity. Concerns about these more subtle types of neurotoxic effects have become a prominent public health issue and have resulted in demands for an increasing level of assurance that efforts are being made to minimize even further the risks of neurotoxicity from human exposure to chemical substances. In an effort to address these concerns, the FDA is including specific attention to neurotoxicity in a proposed revision of its toxicity testing guidelines for food additives. These proposed guidelines focus on a more careful evaluation of structural and functional measures of neurotoxicity as a routine component of safety assessment. This focus will enable the development of the type of information needed for a more effective assessment of the full spectrum of neurotoxic hazards. The revised guidelines for neurotoxicity testing will be discussed in terms of the FDA's overall approach to safety assessment.