Development of Tier I Neurobehavioral Testing Capabilities for Incorporation into Pivotal Rodent Safety Assessment Studies

Abstract

A functional observational battery and an automated test of motor activity have been developed in this laboratory in response to present and future needs for routine assessment of behavioral function in acute and repeated dose rodent safety assessment studies. Data have been collected for untreated 42–49-day-old animals of both sexes in order to gain information on normal ranges of responses in animals of this age as well as to determine the relative variability of the various test measures. Data will continue to be added to this database, both for animals of this age range and for other age ranges. A validation strategy has been outlined that emphasizes the characterization of behavioral profiles of both pharmacologic agents and chemically related neurotoxins, as well as the importance of determining how well these results translate to those observed in humans exposed to the same test agents. The logistical and economic factors associated with neurobehavioral testing and the importance of intralaboratory standardization are discussed in detail. Both controllable and difficult to control environmental and experimental variables that can affect the outcome of a behavioral study are identified. The problems associated with neurobehavioral data interpretation and the importance of a multisystem approach to interpreting functional changes in the context of toxicology studies are discussed.

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