AN OVERVIEW OF THE DEVELOPMENT, VALIDATION, AND APPLICATION OF NEUROBEHAVIORAL AND NEUROMOLECULAR TOXICITY ASSESSMENT BATTERIES - POTENTIALAPPLICATIONS TO COMBUSTION TOXICOLOGY

Currently, there are few alternatives to the use of animals in toxicol ogy for human risk assessment. Neurobehavioral toxicology is an emergi ng area in which complex performance capacity is evaluated during or f ollowing toxicological exposure. While a number of single tests and a few more complex neurobehavioral batteries exist, no fully validated a nd comprehensive neurobehavioral toxicity assessment battery has yet b een developed. The Neurobehavioral Toxicity Assessment Battery (NTAB) is a multi-test battery being developed by the Naval Medical Research Institute Detachment (Toxicology) (NMRI/TD) to categorize the potentia l neurobehavioral toxicity of compounds of Navy interest, especially t hose found in combustion atmospheres. The NTAB is intended to identify specific areas of deficit (e.g. motivational, sensory, motor, and cog nitive) from complex changes in performance induced by toxic exposures , as well as to provide a mechanism to evaluate recovery of neurobehav ioral integrity. Portions of the NTAB have been successfully used to a ssess the risk of brief exposure to low concentrations of combustion g ases, including smoke from electrical aircraft fires, ozone-depleting substances and their replacements, and the novel neuroconvulsant trime thylolpropane phosphate. The goal of the NMRI/TD Neurobehavioral Toxic ology Group and the Tri-Service Toxicology Consortium's neurobehaviora l toxicology program is the incorporation of more molecular techniques involving neurophysiology, neuropharmacology, in vivo electrochemistr y, and real-time microdialysis for correlative use with the neurobehav ioral battery in human risk assessment. This overview discusses the ap plication of neurobehavioral and neuromolecular endpoint test batterie s to combustion toxicology.