NCTR’s Division of Neurotoxicology - Quick Facts

The overall goals of the Division of Neurotoxicology are to develop and validate quantitative biomarkers and precursor events of neurotoxicity and to use these to elucidate mechanisms of action. Attaining these goals will increase the certainty of the underlying assumptions made for human risk assessments for neurotoxicants. The strategy for achieving these goals has been to develop a multidisciplinary approach integrating neurochemical/neurobiological (including genomics and proteomics), neuropathological, neurophysiological, and behavioral assessments to determine adverse effects and explore mechanisms and modes of neurotoxic action. Unique features of the NCTR’s neurotoxicology research efforts are the capabilities to determine target-tissue chemical concentrations and cellular level interactions of neurotoxicants and to reduce the uncertainty associated with extrapolating findings across species by effectively using rodent and nonhuman primate animal models--as well as humans--whenever possible.

In the United States, brain-related disorders account for more hospitalizations than any other major disease group. One of four Americans will suffer a brain-related disorder during their lifetime and the estimated cost to the national economy for treatment, rehabilitation, and related consequences is in the neighborhood of half a trillion dollars annually. At no time in the past, however, have researchers been better poised to increase our understanding of brain-related disorders and reduce the risks associated with neurotoxic events.

According to a report from the Congressional Office of Technology Assessment, “Neurotoxicity: Identifying and Controlling Poisons of the Nervous System,” the known or suspected causes of brain-related disorders include exposures to chemicals such as therapeutic drugs, food additives, foods, cosmetic ingredients, pesticides, and naturally occurring substances. The number of potential neurotoxicants that require FDA regulation is estimated to be in the thousands and yet guidelines for neurotoxicity risk assessment remain vague and underdeveloped compared with those for cancer. Chemicals from the categories listed above are vital to the national economy and our quality of life. The challenge is to determine at what dose and under what conditions a specific chemical may produce nervous system-related toxicity. Over the last decade, increasing expertise, technologically advanced equipment, and improved facilities have been interwoven to pursue the overall goals of neurotoxicology research through three primary research areas. These focal areas were developed and based on prevailing scientific understanding and the importance of each area to regulatory concerns. They include mechanistically-based approaches for defining and understanding the potential of a broad range of drugs and other chemicals to produce neurotoxic effects during developmental, adult, or senescent life stages. These focal research areas are:

1. monoamine (dopamine and serotonin) neurotransmitter systems as targets for neurotoxicity;
2. mitochondrial dysfunction and oxidative stress as mechanisms of neurotoxicity; and
3. the NMDA receptor complex as a mediator of adult and developmental neurotoxicity.

An interdisciplinary approach, the use of multiple, established animal models and innovative biomarkers, and an in-depth working knowledge of and experience with mechanistically-based focal areas of researchenable the Division of Neurotoxicology to be responsive to FDA regulatory needs in a timely fashion. Several ongoing or planned studies, many in conjunction with other FDA centers, exemplify the application of the group’s approach to providing critical research information applicable to FDA’s regulatory concerns

Additional information about NCTR's Division of Neurotoxicology.