APPLICATION OF NEUROBEHAVIORAL TOXICOLOGY METHODS TO THE MILITARY DEPLOYMENT TOXICOLOGY ASSESSMENT PROGRAM*

Abstract

The military Tri-Service (Army, Navy & Marines, Air Force) Deployment Toxicology Assessment Program (DTAP) represents a 30-year (1996–2026) planning effort to implement comprehensive systems for the protection of internationally deployed troops against toxicant exposures. A major objective of DTAP is the implementation of a global surveillance system to identify chemicals with the potential to reduce human performance capacity. Implementation requires prior development of complex human risk assessment models, known collectively as the Neurobehavioral Toxicity Evaluation Instrument (NTEI), based on mathematical interpolation of results from tissue-based and in vivo animal studies validated by human performance assessment research. The Neurobehavioral Toxicity Assessment Group (NTAG) at the Naval Health Research Center Detachment-Toxicology (NHRC-TD), Dayton, OH, and associated academic institutions are developing and cross-validating cellular-level (NTAS), laboratory small animal (NTAB), nonhuman primate (GASP), and human-based (GASH) toxicity assessment batteries. These batteries will be utilized to develop and evaluate mathematical predictors of human neurobehavioral toxicity, as a function of laboratory performance deficits predicted by quantitative structural analysis relationship (QSAR-like) properties of potential toxicants identified by international surveillance systems. Finally, physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PBPD) modeling of NTAS, NTAB, GASP, GASH data will support multi-organizational development and validation of the NTEI. The validated NTEI tool will represent a complex database management system, integrating global satellite surveillance input to provide real-time decision-making support for deployed military personnel.

Notes

* This research was funded by the Office of Naval Research (ONR) Work Unit 62233N.MM33130.008-1605. The opinions and assertions contained herein are those of the authors, and are not to be construed as those of the U.S. Navy or the military service at large. The experiments reported herein were conducted according to the principles set forth in The Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, DHHS (1996). Approved for public release; distribution is unlimited.