An overview of the development, validation, and application of neurobehavioral and neuromolecular toxicity assessment batteries: potential applications to combustion toxicology

Abstract

Currently, there are few alternatives to the use of animals in toxicology for human risk assessment. Neurobehavioral toxicology is an emerging area in which complex performance capacity is evaluated during or following toxicological exposure. While a number of single tests and a few more complex neurobehavioral batteries exist, no fully validated and comprehensive neurobehavioral toxicity assessment battery has yet been 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 potential neurobehavioral toxicity of compounds of Navy interest, especially those found in combustion atmospheres. The NTAB is intended to identify specific areas of deficit (e.g. motivational, sensory, motor, and cognitive) from complex changes in performance induced by toxic exposures, as well as to provide a mechanism to evaluate recovery of neurobehavioral integrity. Portions of the NTAB have been successfully used to assess the risk of brief exposure to low concentrations of combustion gases, including smoke from electrical aircraft fires, ozone-depleting substances and their replacements, and the novel neuroconvulsant trimethylolpropane phosphate. The goal of the NMRI/TD Neurobehavioral Toxicology Group and the Tri-Service Toxicology Consortium's neurobehavioral toxicology program is the incorporation of more molecular techniques involving neurophysiology, neuropharmacology, in vivo electrochemistry, and real-time microdialysis for correlative use with the neurobehavioral battery in human risk assessment. This overview discusses the application of neurobehavioral and neuromolecular endpoint test batteries to combustion toxicology.